The pivotal role of offloading in the management of neuropathic foot ulceration.

PubMed

Wu, Stephanie C; Crews, Ryan T; Armstrong, David G

2005-12-01

Lower extremity amputations among persons with diabetes are generally preceded by neuropathic foot ulcerations. Healing of diabetic ulcerations in a timely manner is of central importance in any plan for amputation prevention. With sufficient vascular supply, appropriate débridement, and infection control, the primary mode of healing a diabetic neuropathic foot ulcer is pressure dispersion. The total contact cast has been deemed by many to be the gold standard in offloading; however, modification of a standard removable cast walker to ensure patient compliance may be as efficacious in healing diabetic foot ulcers as the total contact cast. Combining an effective, easy to use offloading device that ensures patient compliance with advanced wound healing modalities may form a formidable team in healing ulcers and potentially averting lower limb amputations.

Assessment of decisions in the treatment of Helicobacter pylori-related duodenal ulcer: a cost-effectiveness study.

PubMed

Chen, S Y; Wang, J Y; Chen, J; Zhang, X D; Zhang, S S

1999-10-01

Many treatment trials for Helicobacter pylori have been reported but few have evaluated treatment in terms of both cost and effectiveness. It is important to find a therapy with a high eradication rate and low cost, especially in China. The aim of the study is to assess the efficiency of therapy for duodenal ulcers, including ulcer healing, H. pylori eradication and ulcer recurrence. Ninety-six consecutive patients with duodenal ulcers and H. pylori infection were randomly allocated into two groups: AMT group (amoxycillin + metronidazole + tagamet); OA group (omeprazole + amoxycillin). Side-effects were recorded during the treatment period. Endoscopic examinations were repeated at the 7th or 8th week to assess ulcer healing. Patients were followed up for 6 months and repeat endoscopy was performed. Ulcer healing rate, H. pylori eradication rate and ulcer recurrence rate were compared. All costs were recorded and a cost-effectiveness analysis was conducted. In the AMT and OA groups, the ulcer healing rate was 83.7 and 93.5%, respectively (P = 0.27). The eradication rate of H. pylori was 65.1 and 69.6%, respectively and was significantly higher in patients with an ulcer diameter < or = 1 cm compared with those with an ulcer diameter > 1 cm, irrespective of treatment group. There was no difference in recurrence rate, duration of pain or the time lost because of the disease. Moderate or severe side-effects were found in 8.9% in AMT group and 6.5% in OA group. The cost of treatment for ulcer healing, H. pylori eradication and reduction in ulcer recurrence were all lower in the AMT group than in the OA group. Sensitivity analysis supported the result that AMT was more cost effective than OA. The AMT therapy was more effective and less costly than the OA therapy, especially in patients with H. pylori-related duodenal ulcers < 1 cm diameter.

Effect of antisecretory agents and vagotomy on healing of chronic cysteamine-induced duodenal ulcers in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulsen, S.S.; Raaberg, L.; Therkelsen, K.

1986-07-01

Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphologymore » of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.« less

Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the recurrence of gastric ulcer after healing by drug treatment in rats.

PubMed

Ajioka, H; Miyake, H; Matsuura, N

2000-08-01

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days' administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy. Copyright 2000 S. Karger AG, Basel

Therapeutic effect of D-002 (abexol) on gastric ulcer induced experimentally in rats.

PubMed

Molina, Vivian; Carbajal, Daisy; Arruzazabala, Lourdes; Más, Rosa

2005-01-01

D-002 is a mixture of higher aliphatic primary alcohols isolated from beeswax, wherein triacontanol is the most abundant alcohol, with antioxidant and anti-ulcer properties. Since compounds with cytoprotective and antioxidant effects can improve healing of gastroduodenal ulcer induced by noxious agents, this work investigated the healing effect of D- 002 on acute and chronic gastric ulcers induced with indomethacin and acetic acid, respectively, in rats. Acute gastric ulcer was induced with single oral doses of indomethacin (20 mg/kg). Treatments with D-002 at 50, 100, and 200 mg/kg or vehicle were administered 3 hours after ulcer induction. Three hours later, rats were sacrificed, and the stomach was removed for quantifying the lesions. Chronic gastric ulcer was induced by 50 microL of 80% acetic acid application on the anterior serosal surface of the glandular stomach during 20 seconds. Twenty-four hours later D-002 at 50, 100, and 200 mg/kg or vehicle was administered for 5 days. At the end of the treatment, animals were fasted for 24 hours and sacrificed, the stomachs were removed, and the lesions were quantified. D-002 orally administered at 100 and 200 mg/kg acutely significantly healed gastric ulcers induced with indomethacin by 39% and 56% compared with positive controls, respectively. Also, D-002 at 200 mg/kg, but not at 50 or 100 mg/kg, administered orally for 5 days after ulcer induction exerted a significant healing effect (65.8% inhibition) in gastric ulcers induced with acetic acid. In conclusion, this work demonstrated that D-002 administered after ulcer induction induced effective healing of acute and chronic gastric ulcers provoked by, respectively, indomethacin and acetic acid.

Topical Administration of Pirfenidone Increases Healing of Chronic Diabetic Foot Ulcers: A Randomized Crossover Study

PubMed Central

Janka-Zires, Marcela; Uribe-Wiechers, Ana Cecilia; Juárez-Comboni, Sonia Citlali; López-Gutiérrez, Joel; Escobar-Jiménez, Jarod Jazek; Gómez-Pérez, Francisco J.

2016-01-01

Only 30 percent of chronic diabetic foot ulcers heal after 20 weeks of standard treatment. Pirfenidone is a drug with biological, anti-inflammatory, and antifibrotic effects. The aim of this study was to evaluate the effect of topical pirfenidone added to conventional treatment in noninfected chronic diabetic foot ulcers. This was a randomized crossover study. Group 1 received topical pirfenidone plus conventional treatment for 8 weeks; after this period, they were switched to receive conventional treatment only for 8 more weeks. In group 2, the order of the treatments was the opposite. The end points were complete ulcer healing and size reduction. Final data were obtained from 35 ulcers in 24 patients. Fifty-two percent of ulcers treated with pirfenidone healed before 8 weeks versus 14.3% treated with conventional treatment only (P = 0.025). Between 8 and 16 weeks, 30.8% ulcers that received pirfenidone healed versus 0% with conventional treatment (P = 0.081). By week 8, the reduction in ulcer size was 100% [73–100] with pirfenidone versus 57.5% with conventional treatment [28.9–74] (P = 0.011). By week 16, the reduction was 93% [42.7–100] with pirfenidone and 21.8% [8–77.5] with conventional treatment (P = 0.050). The addition of topical pirfenidone to conventional treatment significantly improves the healing of chronic diabetic noninfected foot ulcers. PMID:27478849

Topical Administration of Pirfenidone Increases Healing of Chronic Diabetic Foot Ulcers: A Randomized Crossover Study.

PubMed

Janka-Zires, Marcela; Almeda-Valdes, Paloma; Uribe-Wiechers, Ana Cecilia; Juárez-Comboni, Sonia Citlali; López-Gutiérrez, Joel; Escobar-Jiménez, Jarod Jazek; Gómez-Pérez, Francisco J

2016-01-01

Only 30 percent of chronic diabetic foot ulcers heal after 20 weeks of standard treatment. Pirfenidone is a drug with biological, anti-inflammatory, and antifibrotic effects. The aim of this study was to evaluate the effect of topical pirfenidone added to conventional treatment in noninfected chronic diabetic foot ulcers. This was a randomized crossover study. Group 1 received topical pirfenidone plus conventional treatment for 8 weeks; after this period, they were switched to receive conventional treatment only for 8 more weeks. In group 2, the order of the treatments was the opposite. The end points were complete ulcer healing and size reduction. Final data were obtained from 35 ulcers in 24 patients. Fifty-two percent of ulcers treated with pirfenidone healed before 8 weeks versus 14.3% treated with conventional treatment only (P = 0.025). Between 8 and 16 weeks, 30.8% ulcers that received pirfenidone healed versus 0% with conventional treatment (P = 0.081). By week 8, the reduction in ulcer size was 100% [73-100] with pirfenidone versus 57.5% with conventional treatment [28.9-74] (P = 0.011). By week 16, the reduction was 93% [42.7-100] with pirfenidone and 21.8% [8-77.5] with conventional treatment (P = 0.050). The addition of topical pirfenidone to conventional treatment significantly improves the healing of chronic diabetic noninfected foot ulcers.

Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.

PubMed

Skorjanec, S; Kokot, A; Drmic, D; Radic, B; Sever, M; Klicek, R; Kolenc, D; Zenko, A; Lovric Bencic, M; Belosic Halle, Z; Situm, A; Zivanovic Posilovic, G; Masnec, S; Suran, J; Aralica, G; Seiwerth, S; Sikiric, P

2015-08-01

While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthase-inhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 μg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4(th) day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7(th) day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4(th) day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21(st) day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing, nitric oxide-system involvement, should illustrate further wound healing therapy to heal duodenal ulcers.

Antacids and peptic ulcer--a reappraisal.

PubMed Central

Morris, T; Rhodes, J

1979-01-01

Antacids can reduce gastroduodenal acidity for long periods if taken in substantial quantities after food. Their healing effect on gastric ulcer is minimal, if present at all, and easily overwhelmed by the benefit obtained from admission to hospital. Intensive antacid therapy appears effective in healing duodenal ulcer and preventing haemorrhage from stress ulcer, and is comparable in these respects with cimetidine but with a higher incidence of side-effects. Clinical impression strongly suggests that antacids relieve pain in peptic ulcer but objective confirmation is lacking. PMID:38192

Evaluating the effect of the new incentive system for high-risk pressure ulcer patients on wound healing and cost-effectiveness: a cohort study.

PubMed

Sanada, Hiromi; Nakagami, Gojiro; Mizokami, Yuko; Minami, Yukiko; Yamamoto, Aya; Oe, Makoto; Kaitani, Toshiko; Iizaka, Shinji

2010-03-01

To evaluate the effectiveness and cost-effectiveness of new incentive system for pressure ulcer management, which focused on skilled nurse staffing in terms of rate of healing and medical costs. A prospective cohort study included two types of groups: 39 institutions, which introduced the new incentive system, and 20 non-introduced groups (control). Sixty-seven patients suffering from severe pressure ulcers in the introduced group and 38 patients in the non-introduced group were included. Wound healing and medical costs were monitored weekly for three weeks by their skilled nurses in charge. Healing status and related medical costs. The introduced group showed significantly higher rate of healing compared with the control group at each weekly assessment. Multiple regression analysis revealed that the introduction of the new incentive system was independently associated with the faster healing rate (beta=3.44, P<.001). The budget impact analysis demonstrated that introducing this system could reduce cost of treating severe pressure ulcers by 1.776 billion yen per year. The new incentive system for the management of pressure ulcers, which focused on staffing with skilled nurses can improve healing rate with reduced medical cost. Copyright 2009 Elsevier Ltd. All rights reserved.

Comparison of the efficacy of rabeprazole 10 mg and omeprazole 20 mg for the healing rapidity of peptic ulcer diseases.

PubMed

Ji, Sangwon; Kim, Hyun Soo; Kim, Jae Woo; Jee, Myeong Kwan; Park, Kwang Wha; Uh, Young; Lee, Dong Ki; Song, Jae Suk; Baik, Soon Koo; Kwon, Sang Ok

2006-09-01

Rabeprazole has been known to inhibit H(+)/K(+)-ATPase more rapidly than omeprazole, the prototype proton pump inhibitor (PPI). The aim of this study was to demonstrate equivalence between low-dose rabeprazole 10 mg and omeprazole 20 mg for the healing rapidity of active peptic ulcer and for improvement of symptoms. Also, the effect of CYP2C19 genotypes on ulcer healing rapidity was investigated. A total of 112 patients with active peptic ulcer were randomized to receive either rabeprazole 10 mg q.d. or omeprazole 20 mg q.d. for 6 weeks. The remaining ratios (%) and complete healing of the ulcer were determined by endoscopy at 1 week and 6 weeks of treatment. The severity of ulcer pain was also investigated during treatment. CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The remaining ratio of peptic ulcers after 1 week and the complete healing rate after 6 weeks in the rabeprazole versus omeprazole group were 45.5% versus 50.3% (P = 0.475) and 80.6% versus 87.0% (P = 0.423), respectively. CYP2C19 genotypes had no effect on the remaining ratio of peptic ulcers after 1 week and the healing rate of peptic ulcers after 6 weeks in both groups. The proportions of patients with symptom improvement or resolution were comparable between the two groups. Low-dose rabeprazole 10 mg has a similar efficacy for the healing rapidity of active peptic ulcer disease and symptom improvement compared with standard-dose omeprazole 20 mg.

High-Mobility Group Box 1 Inhibits Gastric Ulcer Healing through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products

PubMed Central

Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Ohkawa, Fumikazu; Takeda, Shogo; Higashimori, Akira; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Takeuchi, Koji; Arakawa, Tetsuo

2013-01-01

High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR) 2, TLR4, and receptor for advanced glycation end products (RAGE), leading to tissue injury. Although HMGB1’s ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1’s effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO) activity, and the expression of tumor necrosis factor α (TNFα) mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO) mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses. PMID:24244627

High-mobility group box 1 inhibits gastric ulcer healing through Toll-like receptor 4 and receptor for advanced glycation end products.

PubMed

Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Ohkawa, Fumikazu; Takeda, Shogo; Higashimori, Akira; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Takeuchi, Koji; Arakawa, Tetsuo

2013-01-01

High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR) 2, TLR4, and receptor for advanced glycation end products (RAGE), leading to tissue injury. Although HMGB1's ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1's effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO) activity, and the expression of tumor necrosis factor α (TNFα) mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO) mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses.

Effects of administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer.

PubMed

Myung, Yu Sik; Hong, Su Jin; Han, Jae Pil; Park, Kyung Woo; Ko, Bong Min; Lee, Moon Sung

2017-01-01

In ulcerative early gastric cancer, improvement and exacerbation of ulceration repeat as a malignant cycle. Moreover, early gastric cancer combined with ulcer is associated with a low curative resection rate and high risk of adverse events. The aim of this study was to investigate the ulcer healing rate and clinical outcomes with the administration of a proton pump inhibitor before endoscopic submucosal dissection for differentiated early gastric cancer with ulcer. A total of 136 patients with differentiated early gastric cancer with ulcer who met the expanded indications for endoscopic submucosal dissection were reviewed between June 2005 and June 2014. Eighty-one patients were given PPI before endoscopic submucosal dissection and 55 patients were not given PPI. The complete ulcer healing rate was significantly different between the two groups (59.3 % vs. 23.6 %, P < 0.001). The procedure time was 38.1 ± 35.7 and 50.8 ± 50.2 min (P = 0.047). However, no significant differences were detected in the en bloc resection rate, complete resection rate, and adverse events including bleeding and perforation. Multivariate analysis showed that administration of PPI (OR = 10.83, P < 0.001) and mucosal invasion (OR = 24.43, P < 0.001) were independent factors that predicted complete healing of ulceration. The calculated accuracy for whether complete healing of the ulcer after PPI administration can differentiate mucosal from submucosal invasion was 75.3 %. Administration of PPI before ESD in differentiated EGC meeting the expanded criteria is effective to heal the ulcer lesion and reduce the mean procedure time. Complete healing of the ulcer after PPI administration suggests mucosal cancer.

Effectivity of artrihpi irrigation for diabetic ulcer healing: A randomized controlled trial

NASA Astrophysics Data System (ADS)

Gayatri, Dewi; Asmorohadi, Aries; Dahlia, Debie

2018-02-01

The healing process of diabetic ulcer is often impeded by inflammation, infection, and decreased immune state. High pressure irrigation (10-15 psi) may be used to control the infection level. This research was designed to identify the effectiveness of artrihpi irrigation device towards diabetic ulcers in public hospitals in the Central Java. This research is a randomized control trial with cross over design. Sixty four subjects were selected using block randomization technique, and were divided into control and intervention group. The intervention was given in 6 days along with wound healing evaluation in every 3 days. The results demonstrated that there was a significant difference decrease scoring healing after treatment, even though the difference scoring healing between both groups was not statistically significant. However, it means difference was found that in the intervention artrihpi the wound healing was better than the spuit. These results illustrates the artrihpi may be solution of using high pressure irrigation to help healing process diabetic ulcers.

ECAMulticapa: Effectiveness of double-layered compression therapy for healing venous ulcers in primary care: a Study Protocol.

PubMed

Folguera-Álvarez, Carmen; Garrido-Elustondo, Sofia; Verdú-Soriano, José; García-García-Alcalá, Diana; Sánchez-Hernández, Mónica; Torres-de Castro, Oscar German; Barceló-Fidalgo, Maria Luisa; Martínez-González, Olga; Ardiaca-Burgués, Lidia; Solano-Villarrubia, Carmen; Lebracón-Cortés, Pilar Raquel; Molins-Santos, Carmen; Fresno-Flores, Mar; Cánovas-Lago, Maria Carmen; Benito-Herranz, Luisa Fernanda; García-Sánchez, Maria Teresa; Castillo-Pla, Olga; Morcillo-San Juan, María Sol; Ayuso-de la Torre, Maria Begoña; Burgos-Quintana, Pilar; López-Torres-Escudero, Ana; Ballesteros-García, Gema; García-Cabeza, Piedad; de Francisco-Casado, Maria Ángeles; Rico-Blázquez, Milagros

2016-01-01

Chronic venous insufficiency, in its final stage can cause venous ulcers. Venous ulcers have a prevalence of 0.5 % to 0.8 % in the general population, and increases starting at 60 years of age. This condition often causes increased dependency in affected individuals, as well as a perceived reduced quality of life and family overload. Local Treating chronic venous ulcers has 2 components: topically healing the ulcer and controlling the venous insufficiency. There is evidence that compressive therapy favours the healing process of venous ulcers. The studies we have found suggest that the use of multilayer bandage systems is more effective than the use of bandages with a single component, these are mostly using in Spain. Multilayer compression bandages with 2 layers are equally effective in the healing process of chronic venous ulcers as 4-layer bandages and are better tolerated and preferenced by patients. More studies are needed to specifically compare the 2-layer bandages systems in the settings where these patients are usually treated. Randomised, controlled, parallel, multicentre clinical trial, with 12 weeks of follow-up and blind evaluation of the response variable. The objective is to assess the efficacy of multilayer compression bandages (2 layers) compared with crepe bandages, based on the incidence of healed venous ulcers in individuals treated in primary care nursing consultations, at 12 weeks of follow-up. The study will include 216 individuals (108 per branch) with venous ulcers treated in primary care nursing consultations. The primary endpoint is complete healing at 12 weeks of follow-up. The secondary endpoints are the degree of healing (Resvech.2), quality of life (CCVUQ-e), adverse reactions related to the healing process. Prognosis and demographic variables are also recorder. Effectiveness analysis using Kaplan-Meier curves, a log-rank test and a Cox regression analysis. The analysis was performed by intention to treat. The study results can contribute to improving the care and quality of life of patients with venous ulcers, decreasing healing times and healthcare expenditure and contributing to the consistent treatment of these lesions. This study has been recorded in the Clinical Trials.gov site with the code NCT02364921. 17 February 2015.

Effects of artemisinin, with or without lumefantrine and amodiaquine on gastric ulcer healing in rat.

PubMed

Ajeigbe, Kazeem O; Emikpe, Benjamin O; Olaleye, Samuel Babafemi

2018-04-27

Antimalarial drugs have been shown to predispose the stomach to ulceration in rats. However, their role in the modulation of gastric ulcer healing is not known. The aim of the present study is to investigate the effect of artemisinin-based combination therapies on ulcer healing. Gastric kissing ulcers were induced in 40 male albino rats (150-180 g) using 0.2 mL 50% acetic acid. One day after the ulcer induction, experimental rats were divided into four groups and treated once daily orally for 3 days as follows: (1) normal saline, (2) artemether-lumefantrine (2/12 mg/kg), (3) artesunate-amodiaquine (4/10 mg/kg), and (4) artesunate (2 mg/kg) only. A fifth group of 10 rats served as overall control with no ulcer induced and no treatment given. Ulcer healing was determined on days 4 and 7 post induction using ulcer score and planimetry. Artesunate decreased ulcer severity by 12.5% and 52.0% on days 4 and 7, respectively. Significant increases in severity were observed in rats treated with artemether-lumefantrine (25.0% and 40.0%) and artesunate-amodiaquine (50.0% and 95.0%). Lipid peroxidation was decreased by artesunate by day 7 (27%; p<0.05) but increased in artemether-lumefantrine and artesunate-amodiaquine administered rats (63.6% and 55%; p<0.05). The activity of superoxide dismutase was reduced by artesunate-amodiaquine on day 7 (22%; p<0.05) but no effect in the artemether-lumefantrine treatment. Neutrophil infiltration, total leukocyte count, neutrophil-lymphocyte ratio, and C-reactive protein values were significantly increased in the artemether-lumefantrine and artesunate-amodiaquine treated groups when compared with the untreated ulcer control group (p<0.05). These variables were all reduced by artesunate (p<0.05). This study revealed that although artesunate may be beneficial in gastric ulcer healing, its combination with either lumefantrine or amodiaquine may delay healing of gastric mucosal injury.

Essential oil of Cymbopogon citratus (lemongrass) and geraniol, but not citral, promote gastric healing activity in mice.

PubMed

Venzon, Larissa; Mariano, Luísa Nathália Bolda; Somensi, Lincon Bordignon; Boeing, Thaise; de Souza, Priscila; Wagner, Theodoro Marcel; Andrade, Sérgio Faloni de; Nesello, Luciane Angela Nottar; da Silva, Luísa Mota

2018-02-01

Cymbopogon citratus, popularly known as lemongrass, is used for the treatment of gastric, nervous and hypertensive disorders, in addition to its use in the food and pharmaceutical industries. This study evaluated the gastroprotective and gastric healing effect of essential oil of C. citratus (EOCC), citral and geraniol at doses of 1-100 mg/kg (p.o) on acute ethanol-induced ulcer and chronic acetic acid-induced ulcer. Histological and histochemical evaluation was also performed, as well as the in vitro evaluation of the effects of these phytochemicals on H + /K + -ATPase activity. In the ethanol-induced gastric ulcer, the minimum effective oral dose of EOCC, citral and geraniol were 10, 100 and 3 mg/kg, reducing the ulcer area by 51.67%, 96.57% and 55.74%, respectively, compared to vehicle group (25.82 ± 3.59 mm 2 ). Moreover, EOCC (10 mg/kg, p.o) and geraniol (3 mg/kg), but not citral (100 mg/kg), accelerated the gastric healing process by 34.52 and 80.57%, compared to acetic-acid ulcerated group treated with vehicle (36.04 ± 1.03 mm 2 ). These healing effects were confirmed histologically by the contraction of the ulcer base and by the enhancement on mucin staining in slices of ulcer site from mice treated with EOCC or geraniol. Interestingly, EOCC and citral at 100 μg/ml inhibited the H + / K + -ATPase activity by 28.26% and 44.36%, whereas geraniol did not change this parameter. Together, these findings confirm the gastroprotective and healing gastric ulcer effects of essential oil from aerial parts of C. citratus and added the information that geraniol, but not citral, promotes healing effects on installed ulcers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of systemic insulin treatment on diabetic wound healing.

PubMed

Vatankhah, Nasibeh; Jahangiri, Younes; Landry, Gregory J; Moneta, Gregory L; Azarbal, Amir F

2017-04-01

This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow-up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1-90.1 years) and 58 cases (68.2%) were males. Twenty-four cases reached a complete healing (healing rate: 22.4%). The median follow-up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7-21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random-effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x-ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates. © 2017 by the Wound Healing Society.

The Role of Pressure Offloading on Diabetic Foot Ulcer Healing and Prevention of Recurrence.

PubMed

Bus, Sicco A

2016-09-01

An increased plantar pressure is a causative factor in the development of plantar foot ulcers in people with diabetes mellitus, and ulcers are a precursor of lower extremity amputation. In this article, the evidence is reviewed that relieving areas of increased plantar pressure (ie, offloading) can heal plantar foot ulcers and prevent their recurrence. Noninfected, nonischemic neuropathic plantar forefoot ulcers should heal in 6 to 8 weeks with adequate offloading. Recent meta-analyses and systematic reviews show that nonremovable knee-high devices are most effective. This is probably because they eliminate the problem of nonadherence with the use of a removable device. Studies show a large discrepancy between evidence-based recommendations on offloading and what is used in clinical practice. Many clinics continue to use methods that are less effective or have not been proven to be effective, while ignoring evidence-based methods. Strategies are proposed to address this issue, notably the adoption and implementation of recent international guidelines by professional societies and a stronger focus of clinicians on expedited healing. For the prevention of plantar foot ulcer recurrence in high-risk patients, 2 recent trials have shown that the incidence of recurrence can be significantly reduced with custom-made footwear that has a demonstrated pressure-relieving effect through guidance by plantar pressure measurements, under the condition that the footwear is worn. This review helps to inform clinicians about effective offloading treatment for healing plantar foot ulcers and preventing their recurrence.

Novel submicronized rebamipide liquid with moderate viscosity: significant effects on oral mucositis in animal models.

PubMed

Nakashima, Takako; Sako, Nobutomo; Matsuda, Takakuni; Uematsu, Naoya; Sakurai, Kazushi; Ishida, Tatsuhiro

2014-01-01

This study aimed at developing a novel rebamipide liquid for an effective treatment of oral mucositis. The healing effects of a variety of liquids comprising submicronized rebamipide crystals were investigated using a rat cauterization-induced oral ulcer model. Whereas 2% rebamipide liquid comprising micro-crystals did not exhibit significant curative effect, 2% rebamipide liquids comprising submicronized crystals with moderate viscosities exhibited healing effects following intra-oral administration. The 2% and 4% optimized rebamipide liquids showed significant healing effects in the rat oral ulcer model (p<0.01). In addition, in the rat radiation-induced glossitis model, whereby the injury was caused to the tongue by exposing only around the rat's snout to a 15 Gy of X-irradiation, the 2% optimized rebamipide liquid significantly reduced the percent area of ulcerated injury (p<0.05). In conclusion, the submicronized rebamipide liquid with moderate viscosity following intra-oral administration showed better both healing effect in the rat oral ulcer model and preventive effect in the rat irradiation-induced glossitis model.

The Probiotic Mixture VSL#3 Accelerates Gastric Ulcer Healing by Stimulating Vascular Endothelial Growth Factor

PubMed Central

Dharmani, Poonam; De Simone, Claudio; Chadee, Kris

2013-01-01

Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6×109 bacteria) or high (1.2×1010 bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF. PMID:23484048

Does topical wound oxygen (TWO2) offer an improved outcome over conventional compression dressings (CCD) in the management of refractory venous ulcers (RVU)? A parallel observational comparative study.

PubMed

Tawfick, W; Sultan, S

2009-07-01

Topical wound oxygen (TWO(2)) may help wound healing in the management of refractory venous ulcers (RVU). The aim of this study was to measure the effect of TWO(2) on wound healing using the primary end-point of the proportion of ulcers healed at 12 weeks. Secondary end-points were time to full healing, percentage of reduction in ulcer size, pain reduction, recurrence rates and Quality-Adjusted Time Spent Without Symptoms of disease and Toxicity of Treatment (Q-TWiST). A parallel observational comparative study. Patients with CEAP C(6,s) RVU, assessed by duplex ultrasonography, were managed with either TWO(2) (n=46) or conventional compression dressings (CCD) (n=37) for 12 weeks or till full healing. Patients were followed up at 3 monthly intervals. At 12 weeks, 80% of TWO(2) managed ulcers were completely healed, compared to 35% of CCD ulcers (p<0.0001). Median time to full healing was 45 days in TWO(2) patients and 182 days in CCD patients (p<0.0001). The pain score threshold in TWO(2) managed patients improved from 8 to 3 by 13 days. After 12-month follow-up, 5 of the 13 healed CCD ulcers showed signs of recurrence compared to none of the 37 TWO(2) healed ulcers. TWO(2) patients experienced a significantly improved Q-TWiST. TWO(2) reduces recurrence rates, alleviates pain and improves the Q-TWiST. We believe it is a valuable tool in the armamentarium of management of RVU.

Effects of Topic Simvastatin for the Treatment of Chronic Vascular Cutaneous Ulcers: A Pilot Study.

PubMed

Raposio, Edoardo; Libondi, Guido; Bertozzi, Nicolò; Grignaffini, Eugenio; Grieco, Michele P

2015-12-01

Recent research suggests that statins might be useful in the process of wound healing, playing a positive immune-modulatory role, improving microvascular function and reducing oxidative stress. The aim of this pilot study was to evaluate the efficacy of topic application of Simvastatin-based cream in the treatment of chronic vascular cutaneous ulcers, comparing this type of treatment to a collagen-based dressing, proven to be effective for ulcer treatment. A total of 20 ulcers were studied in 2 Groups of randomly-chosen patients for a period of one month. In the first Group a 0.5% Simvastatin-based cream was topically administered, while the second Group (control) was treated with an absorbable type I bovine collagen-based medication. Each week, wound healing progress was observed in both Groups, and the ulcers photographed. Wound healing rate was calculated by considering the absolute change in area and by the formula "healing ratio (%) = [(Area 0 - Area t4 )/Area 0 ] × 100," both sets of data being related to the days comprised in the study in order to calculate healing rate per day. Statistical analysis was performed by Student t test. Study endpoint equaling the time-course changes of ulcer areas. At the end of the study, when considering absolute change in area, the experimental Group appeared to heal better and faster than the control Group although differences between the Groups were not statistically significant. Conversely, rates of wound healing in the experimental and control Groups were 46.88% and 64% respectively, revealing statistically significant differences. ( P < 0.05). In conclusion, topic application of a simvastatin-based cream proved to be well- tolerated but not effective in the management of vascular leg ulcers in a 4 week-period.

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people.

PubMed

Ford, Alexander C; Gurusamy, Kurinchi Selvan; Delaney, Brendan; Forman, David; Moayyedi, Paul

2016-04-19

Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.

Efficacy and safety of proton pump inhibitors (PPIs) plus rebamipide for endoscopic submucosal dissection-induced ulcers: a meta-analysis.

PubMed

Wang, Jun; Guo, Xufeng; Ye, Chuncui; Yu, Shijie; Zhang, Jixiang; Song, Jia; Cao, Zhuo; Wang, Jing; Liu, Min; Dong, Weiguo

2014-01-01

To compare the efficacy of proton pump inhibitors (PPIs) with rebamipide versus PPIs alone for the treatment of ulcers after endoscopic submucosal dissection (ESD). PubMed, Web of Science, Medline, Embase, the Cochrane Central Register of Controlled Trials and China Naitonal Knowledge Infrastructure were searched up to the end of October 2013 in order to identify all randomized controlled trials reporting the effects of PPIs plus rebamipide on healing ulcers after ESD. The outcome measurement was complete ulcer healing. A total of six studies involving 724 patients were included. The pooled data suggested a significantly higher rate of ulcer healing after endoscopic therapy among patients treated with PPIs plus rebamipide than among those treated with PPIs alone [odds ratio (OR)=2.40, 95% confidence interval (CI): 1.68-3.44]. The subgroup analysis showed PPI plus rebamipide therapy to be more effective in healing ESD-induced ulcers than treatment with PPIs alone after both four (OR=2.22, 95%CI: 1.53-3.24) and eight weeks of treatment (OR=3.19, 95%CI: 1.22-8.31). In addition, the combination therapy was found to be significantly more effective than the use of PPIs alone for all ESD ulcers greater than 20 mm in size (OR=4.77, 95%CI: 2.22-10.26). There were no significant differences between the treatment groups with regard to ulcer location (low, middle or upper stomach) or the presence of absence of H. pylori infection. No serious adverse events were observed in either group. The results of this meta-analysis suggest that treatment with PPIs plus rebamipide is superior to PPI monotherapy for healing ESD-induced ulcers over four weeks, particularly large ulcers. However, more well-designed trials are needed to confirm these findings.

Retrospective comparison of diabetic foot ulcer and venous stasis ulcer healing outcome between a dermal repair scaffold (PriMatrix) and a bilayered living cell therapy (Apligraf).

PubMed

Karr, Jeffrey C

2011-03-01

The goal of this study was to review clinical experience in treating diabetic and venous stasis wounds with Apligraf or PriMatrix. A total of 40 diabetic foot ulcers and 28 venous stasis ulcers were treated with either PriMatrix or Apligraf for number of days open and for number of days for complete healing between the 2 treatments. Although both treatments were highly effective, the study results of 68 ulcers in 48 patients demonstrated that patients treated with PriMatrix healed faster than patients treated with Apligraf despite larger wound sizes.

Therapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole.

PubMed

Skorjanec, Sandra; Dolovski, Zdravko; Kocman, Ivan; Brcic, Luka; Blagaic Boban, Alenka; Batelja, Lovorka; Coric, Marjana; Sever, Marko; Klicek, Robert; Berkopic, Lidija; Radic, Bozo; Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Cesarec, Vedran; Tonkic, Ante; Zoricic, Ivan; Mise, Stjepan; Staresinic, Mario; Ivica, Mihovil; Lovric Bencic, Martina; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2009-01-01

This study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers. The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 microg/kg) (12 ml/rat/day) or intraperitoneally (10 microg/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)]. Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine). We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.

[Research progress of dipeptidyl peptidase 4 inhibitors on healing of chronic diabetic foot ulcers].

PubMed

Gao, Yunyi; Liang, Yujie; Ran, Xingwu

2018-05-01

To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. DPP-4 inhibitors can accelerated the ulcer healing. The mechanisms probably include inhibiting the expression of the matrix metalloproteinase (MMP) and restoring the balance of the wound MMP and the tissue inhibitors of MMP; promoting recruitment of endothelial progenitor cells and augmenting angiogenesis; optimizing extracellular matrix construction and the immune response to persistent hypoxia in chronic diabetes wounds, and so on. At present, clinical researches show that DPP-4 inhibitors may be considered as an adjuvant treatment for chronic diabetic foot ulcers. DPP-4 inhibitors show promise in the local wound healing of chronic diabetic foot ulcers. However, more strictly designed, adequately powered, long-term follow-up, and high-quality randomized control trials are needed to further verify their efficacy and safety for chronic diabetic foot ulcers.

Diabetes - foot ulcers

MedlinePlus

... produce chemicals that help the ulcer heal. Taking Pressure off Your Foot Ulcer Foot ulcers are partly caused by too much ... ulcer has healed. These devices will take the pressure off of the ulcer area. This will help speed healing. Be sure ...

[Influence of honey, royal jelly and propolis on accelerating acetate healing of experimental gastric ulcers in rats].

PubMed

Belostotskiĭ, N I; Kas'ianenko, V I; Dubtsova, E A; Lazebnik, L B

2009-01-01

This study examines gastric acetic ulcer healing in the rat after administration of honey, royal jelly and propolis into the stomach. Chronic gastric ulcers were induced in male Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach on 60 sec. Bee-keeping products were administrated into the stomach from 2nd to 7th day after acetic ulcer induction. On 7th day animals were killed, and ulcer area was measured in mm2. In gastric juice pH and activity of pepsin were measured. The healing of acetic ulcers is accelerated with the administration of honey, royal jelly or propolis during six days. The largest healing effect was demonstrated with propolis and royal jelly, smaller one with the honey. It was revealed decrease of stomach acid secretion in the rats, which have received bee-keeping products versus the rats of control group.

Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats

PubMed Central

Chen, Yen-Cheng; Ho, Ching-Chun; Yi, Chih-Hsun; Liu, Xiu-Zhu; Cheng, Tzu-Ting

2017-01-01

Background Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. Methods and results Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area. Conclusion Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes. PMID:29095895

Efficacy and safety evaluation of systemic extremely low frequency magnetic fields used in the healing of diabetic foot ulcers--phase II data.

PubMed

Cañedo-Dorantes, Luis; Soenksen, Luis R; García-Sánchez, Clara; Trejo-Núñez, Daphny; Pérez-Chávez, Fernando; Guerrero, Arturo; Cardona-Vicario, Melisa; García-Lara, Carlos; Collí-Magaña, Dianelly; Serrano-Luna, Gregorio; Angeles Chimal, José S; Cabrera, Guillermo

2015-08-01

Cellular and animal models investigating extremely low frequency magnetic fields (ELF-MF) have reported promotion of leukocyte-endothelial interactions, angiogenesis, myofibroblast and keratinocyte proliferation, improvement of peripheral neuropathy and diabetic wound healing. In humans, it has also been reported that systemic exposure to ELF-MF stimulates peripheral blood mononuclear cells, promoting angiogenesis and healing of chronic leg ulcers. The aim of the study was to investigate the effect of exposing different blood volumes to specific ELF-MFs (120 Hz sinusoidal waves of 0.4-0.9 mT RMS) to induce healing of diabetic foot ulcers (DFUs). Twenty six diabetic patients with non-responsive DFUs were divided into two exposure groups to receive treatment and record healing time. The forearm group, exposed to ELF-MF 2 h/day, twice weekly (3.6 l of blood/session); and the thorax group, exposed 25 min/day, 2 times/week (162.5 l of blood/session). Treatment period was 100 days or upon complete healing. Ulcer recurrences and adverse effects were investigated during short-term (<1 year) and long-term (3.4-7.8 years) follow-up. Mean healing time was 61.48 ± 33.08 days in the forearm group and 62.56 ± 29.33 days for the thorax group. No adverse effects or ulcer recurrences in the original ulcer site were reported during treatment, the short-term follow-up period or the long-term follow-up period in both groups. Healing time was independent of the amount of blood exposed to ELF-MF used in this trial. ELF-MFs are effective and safe and could be applied to non-healing DFUs in conjunction with other preventive interventions to reduce DFUs complications. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Epidermal growth factor (EGF) in the gastroprotective and ulcer healing actions of colloidal bismuth subcitrate (De-Nol) in rats.

PubMed Central

Konturek, S J; Dembinski, A; Warzecha, Z; Bielanski, W; Brzozowski, T; Drozdowicz, D

1988-01-01

Colloidal bismuth subcitrate (CBS; De-Nol) exhibits gastroprotective properties in experimental animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether epidermal growth factor (EGF), which also has gastroprotective and ulcer healing properties, contributes to the action of De-Nol on the stomach in rats. It was found that De-Nol protects the gastric mucosa against ethanol damage and that this is accompanied by increased mucosal generation of prostaglandins (PG). Removal of the endogenous source of EGF (sialoadenectomy) did not significantly decrease the protective and PG stimulating effects of De-Nol. Pretreatment with exogenous EGF partially protected the stomach against ethanol injury, but did not influence the protective action of De-Nol in sialoadenectomised animals. De-Nol, like EGF given orally, enhanced the healing of chronic gastric and duodenal ulcers induced by serosal acetic acid. De-Nol was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer area. Thus the peptide is available locally in high concentrations to accelerate the re-epithelialisation and tissue repair of the ulcerated mucosa. These ulcer healing effects of De-Nol were reduced by sialoadenectomy and restored in part by oral administration of EGF. We conclude that salivary glands in rats are not essential for the gastroprotection induced by De-Nol, but seem to play an important role in the ulcer healing action of this drug possibly via an EGF mediated mechanism. PMID:3260885

Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.

PubMed

Armstrong, David G; Lavery, Lawrence A; Wu, Stephanie; Boulton, Andrew J M

2005-03-01

The purpose of this study was to evaluate the effectiveness of a removable cast walker (RCW) and an "instant" total contact cast (iTCC) in healing neuropathic diabetic foot ulcerations. We randomly assigned 50 patients with University of Texas grade 1A diabetic foot ulcerations into one of two off-loading treatment groups: an RCW or the same RCW wrapped with a cohesive bandage (iTCC) so patients could not easily remove the device. Subjects were evaluated weekly for 12 weeks or until wound healing. An intent-to-treat analysis showed that a higher proportion of patients had ulcers that were healed at 12 weeks in the iTCC group than in the RCW group (82.6 vs. 51.9%, P = 0.02, odds ratio 1.8 [95% CI 1.1-2.9]). Of the patients with ulcers that healed, those treated with an iTCC healed significantly sooner (41.6 +/- 18.7 vs. 58.0 +/- 15.2 days, P = 0.02). Modification of a standard RCW to increase patient adherence to pressure off-loading may increase both the proportion of ulcers that heal and the rate of healing of diabetic neuropathic wounds.

Chemical structure of bismuth compounds determines their gastric ulcer healing efficacy and anti-Helicobacter pylori activity.

PubMed

Sandha, G S; LeBlanc, R; Van Zanten, S J; Sitland, T D; Agocs, L; Burford, N; Best, L; Mahoney, D; Hoffman, P; Leddin, D J

1998-12-01

The recognition of the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has led to renewed interest in bismuth pharmacology since bismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precise chemical structure of current bismuth compounds is not known. This has hindered the development of new and potentially more efficacious formulations. We have created two new compounds, 2-chloro-1,3-dithia-2-bismolane (CDTB) and 1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), with known structure. In a rat model of gastric ulceration, BTBT was comparable to, and CDTB was significantly less effective than colloidal bismuth subcitrate in healing cryoprobe-induced ulcers. However, both BTBT and CDTB inhibited H. pylori growth in vitro at concentrations <1/10 that of colloidal bismuth subcitrate. The effects on ulcer healing are not mediated by suppression of acid secretion, pepsin inhibition, or prostaglandin production. Since all treated animals received the same amount of elemental bismuth, it appears that the efficacy of bismuth compounds varies with compound structure and is not simply dependent on the delivery of bismuth ion. Because the structure of the novel compounds is known, our understanding of the relationship of bismuth compound structure and to biologic activity will increase. In the future it may be possible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healing effects.

Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial.

PubMed

Li, Lan; Chen, Dawei; Wang, Chun; Yuan, Nanbing; Wang, Yan; He, Liping; Yang, Yanzhi; Chen, Lihong; Liu, Guanjian; Li, Xiujun; Ran, Xingwu

2015-01-01

The purpose of the study is to examine the safety and effectiveness of topical autologous platelet-rich gel (APG) application on facilitating the healing of diabetic chronic refractory cutaneous ulcers. The study was designed as a prospective, randomized controlled trial between January 1, 2007 and December 31, 2011. Eligible inpatients at the Diabetic Foot Care Center of West China Hospital, Sichuan University (China) were randomly prescribed with a 12-week standard treatment of ulcers (the control group) or standard treatment plus topical application APG (the APG group). The wound healing grades (primary endpoint), time to complete healing, and healing velocity within 12 weeks were monitored as short-term effectiveness measurements, while side effects were documented safety endpoints. The rates of survival and recurrence within the follow up were recorded as long-term effectiveness endpoints. Analysis on total diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers (DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was statistically more effective than standard treatment (p < 0.05 in both total DUs and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%) in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58 (69.0%) and 37/55 (67.3%) in the control group from intent to treat population. The Kaplan-Meier time-to-healing were significantly different between the two groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were identified after topical APG application. The long-term survival and recurrence rates were comparative between groups (p > 0.05). This study shows that topical APG application plus standard treatment is safe and quite effective on diabetic chronic refractory cutaneous ulcers, compared with standard treatment. © 2015 by the Wound Healing Society.

VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers.

PubMed

Iglesias, C; Nelson, E A; Cullum, N A; Torgerson, D J

2004-07-01

To compare the clinical and cost-effectiveness of two different compression bandages for the healing of venous leg ulcers. A pragmatic, randomised controlled trial with an economic evaluation. Community, district nurse-led services; community leg ulcer clinics; hospital leg ulcer clinics with community outreach. A range of urban and rural settings in England and Scotland. Patients with a venous leg ulcer of at least 1-week's duration, at least 1 cm in length or width and an ankle:brachial pressure index of at least 0.8. The four-layer bandage (4LB) (which is multilayer elastic compression) compared with the short-stretch bandage (SSB) (multilayer, inelastic compression). The primary end-point was complete healing of all the ulcers on the trial leg. Secondary outcomes were the proportion of patients healed at 12 and 24 weeks, rate of recurrence, costs of leg ulcer treatment and quality of life. Between April 1999 and December 2000 the trial recruited 387 people aged from 23 to 97 years at trial entry. The majority of patients in this trial (82%; 316/387) had a reference ulcer of area

Cost-effectiveness of nutritional intervention on healing of pressure ulcers.

PubMed

Hisashige, Akinori; Ohura, Takehiko

2012-12-01

Pressure ulcers not only affect quality of life among the elderly, but also bring a large economic burden. There is limited evidence available for the effectiveness of nutritional interventions for treatment of pressure ulcers. In Japan, recently, a 60-patient randomized controlled trial of nutritional intervention on pressure ulcers demonstrated improvement in healing of pressure ulcers, compared with conventional management. To evaluate value for money of nutritional intervention on healing of pressure ulcers, cost-effective analysis was carried out using these trial results. The analysis was carried out from a societal perspective. As effectiveness measures, pressure ulcer days (PUDs) and quality-adjusted life years (QALYs) were estimated. Prevalence of pressure ulcers was estimated by the Kaplan-Meier method. Utility score for pressure ulcers is derived from a cross-sectional survey among health professionals related to pressure ulcers. Costs (e.g., nutritional interventions and management of pressure ulcers) were estimated from trial data during observation and follow-up. Stochastic and qualitative sensitivity analyses were performed to examine the robustness of results. For observation (12 weeks) and follow-up (12-week observation plus 4-week follow-up), nutritional intervention reduced PUDs by 9.6 and 16.2 per person, and gained 0.226 × 10(-2) QALYs and 0.382 × 10(-2) QALYs per person, respectively. In addition, costs were reduced by $542 and $881 per person, respectively. This means nutritional intervention is dominant (cost savings and greater effectiveness). The sensitivity analyses showed the robustness of these results. Economic evaluation of nutritional intervention on healing pressure ulcers from a small randomized controlled trial showed that this intervention is cost saving with health improvement. Further studies are required to determine whether this is a cost-effective intervention for widespread use. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Inhibition of nocturnal acidity is important but not essential for duodenal ulcer healing.

PubMed Central

Bianchi Porro, G; Parente, F; Sangaletti, O

1990-01-01

We have determined the relative importance of day and night time gastric acid inhibition for duodenal ulcer healing by comparing the anti-ulcer efficacy of a single morning with that of a single bedtime dose of ranitidine. One hundred and thirty patients with active duodenal ulcer were randomly assigned to a double-blind therapy with ranitidine 300 mg at 8 am or the same dose at 10 pm for up to eight weeks. The antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring in 18 of these patients. At four weeks ulcers had healed in 41/61 (67%) of patients taking the morning dose and in 47/63 (75%) of those receiving the nocturnal dose (95% CI for the difference -0.09 +0.25; p ns). At eight weeks, the corresponding healing rates were 82% and 85.5%, respectively (95% CI for the difference -0.11 +0.17; p ns). Both treatments were significantly superior to placebo in raising 24 h intragastric pH, although the effects of the morning dose were of shorter duration than those of the nocturnal dose. These findings suggest that suppression of nocturnal acidity is important but not essential to promote healing of duodenal ulcers; a prolonged period of acid inhibition during the day (as obtained with a single large morning dose of H2-blockers) may be equally effective. PMID:2186980

The efficacy of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) and a mixture of topical hAMMSC-CM + vitamin C and hAMMSC-CM + vitamin E on chronic plantar ulcers in leprosy:a randomized control trial.

PubMed

Prakoeswa, C R S; Natallya, F R; Harnindya, D; Thohiroh, A; Oktaviyanti, R N; Pratiwi, K D; Rubianti, M A; Yogatri, B; Primasari, P I; Herwanto, N; Alinda, M D; Kusumaputra, B H; Astari, L; Listiawan, M Y; Agusni, I; Rantam, F A

2018-05-10

Healing of chronic plantar ulcers in leprosy (CPUL) typically takes a long time due to impaired neurological function, thereby reducing the levels of growth factors and cytokines. Cytokines can be found in metabolite products from amniotic membrane stem cells. Chronic ulcers are frequently characterized by high levels of reactive oxygen species. Vitamin E (α-tocopherol) is widely used in skin lesions, owing to its antioxidant and anti-inflammatory properties. Vitamin C also has antioxidant, anti-inflammatory, and collagen synthesis properties which are useful in wound healing. Herein, we compared the effects of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) alone and with vitamins C and E on healing of CPUL. In this randomized controlled trial, topical agents were applied every 3 days for up to 8 weeks. Ulcer size, side-effects, and possible complications were monitored weekly. Healing percentage increased each week in all groups. Mean difference in ulcer size was highest in the hAMMSC-CM + vitamin E group, implying better progress of wound healing. There were no side-effects or complications. hAMMSC-CM + vitamin E is best for healing of CPUL.

[Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized].

PubMed

Glinski, W; Chodynicka, B; Roszkiewicz, J; Bogdanowski, T; Lecewicz-Torun, B; Kaszuba, A; Bowszyc, J; Nowak, A; Wnorowski, J; Wasik, F; Glinska-Ferenz, M; Blaszczyk, M; Strzyga, P; Pachocki, R

2001-04-01

To determine the increase in healing rate of venous ulcer in patients receiving a micronised purified flavonoid fraction (MPFF) as supplementation to standard local care. A randomised, open, controlled, multicentre study. Departments of Dermatology and University Outpatients Clinics. One hundred and forty patients with chronic venous insufficiency and venous ulcers. PATIENTS received standard compressive therapy plus external treatment alone or 2 tablets of MPFF daily in addition to the above treatment for 24 weeks. Healing of ulcers and their reduction in size after 24 weeks of treatment. The percentage of patients whose ulcers healed completely was found to be markedly higher in those receiving MPFF in addition to standard external and compressive treatment than in those treated with conventional therapy alone (46.5% vs 27.5%; p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of patients in the MPFF group and in 50% of patients in the control group, whereas ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients (p<0.05), respectively. The mean reduction in ulcer size was also found to be greater in patients treated with MPFF (80%) than in the control group (65%) (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group was 1026.2 compared with 1871.8 in the control group. These results indicate that MPFF significantly improves the cure rate in patients with chronic venous insufficiency.

Racial and ethnic disparities in the healing of pressure ulcers present at nursing home admission.

PubMed

Bliss, Donna Z; Gurvich, Olga; Savik, Kay; Eberly, Lynn E; Harms, Susan; Mueller, Christine; Garrard, Judith; Cunanan, Kristen; Wiltzen, Kjerstie

2017-09-01

Pressure ulcers increase the risk of costly hospitalization and mortality of nursing home residents, so timely healing is important. Disparities in healthcare have been identified in the nursing home population but little is known about disparities in the healing of pressure ulcers. To assess racial and ethnic disparities in the healing of pressure ulcers present at nursing home admission. Multi-levels predictors, at the individual resident, nursing home, and community/Census tract level, were examined in three large data sets. Minimum Data Set records of older individuals admitted to one of 439 nursing homes of a national, for-profit chain over three years with a stages 2-4 pressure ulcer (n=10,861) were searched to the 90-day assessment for the first record showing pressure ulcer healing. Predictors of pressure ulcer healing were analyzed for White admissions first using logistic regression. The Peters-Belson method was used to assess racial or ethnic disparities among minority group admissions. A significantly smaller proportion of Black nursing home admissions had their pressure ulcer heal than expected had they been part of the White group. There were no disparities in pressure ulcer healing disadvantaging other minority groups. Significant predictors of a nonhealing of pressure ulcer were greater deficits in activities of daily living and pressure ulcer severity. Reducing disparities in pressure ulcer healing is needed for Blacks admitted to nursing homes. Knowledge of disparities in pressure ulcer healing can direct interventions aiming to achieve equity in healthcare for a growing number of minority nursing home admissions. Copyright © 2017 Elsevier B.V. All rights reserved.

Autoradiographic study on healing process of cysteamine-induced duodenal ulcer in rat. Possible importance of Brunner's glands in ulcer healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuse, Y.; Tsuchihashi, Y.; Sugihara, H.

1988-09-01

The healing process of cysteamine-induced duodenal ulcer was studied by (/sup 3/H)thymidine autoradiography. After the development of ulcer in the duodenum, cell proliferation was markedly activated not only in the crypts but also in the Brunner's glands near the ulcer. In the initial stages of ulcer healing, they both contributed to form the surface covering regenerating epithelium. Granulation tissue also proliferated at the base of the ulcer. In later stages of ulcer healing, new crypts were formed in the floor of the ulcer. New villi regenerated from these crypts and Brunner's glands regenerated by proliferation in situ. The ulcer basemore » then was completely covered with new villi and granulation tissue was replaced by dense fibrous connective tissue. The present study suggested that the Brunner's glands, together with the crypts of Lieberkuehn, play an important role in the healing process of cysteamine-induced duodenal ulcer.« less

Bio-sheet graft therapy for artificial gastric ulcer after endoscopic submucosal dissection: an animal feasibility study.

PubMed

Kwon, Chang-Il; Kim, Gwangil; Ko, Kwang Hyun; Jung, Yunho; Chung, Il-Kwun; Jeong, Seok; Lee, Don Haeng; Hong, Sung Pyo; Hahm, Ki Baik

2015-04-01

Various bio-sheet grafts have been attempted either to accelerate healing of artificial ulcers or to prevent adverse events after endoscopic submucosal dissection (ESD), but neither prospective nor mechanistic studies were available. To evaluate the substantial effect of a bio-sheet graft on artificial ulcer healing and its feasibility as an endoscopic treatment modality. Preclinical, in vivo animal experiment and proof-of-concept study. Animal laboratory. Three mini-pigs, Sus scrofa, mean age 14 months. Multiple ulcers sized 2.5 cm in diameter were generated by ESD in 3 mini-pigs and were assigned randomly into the following 3 groups; control group, bio-sheet group, or combination (bio-sheet plus drug) group. Bio-sheet grafts or bio-sheet plus drug combinations were applied on the artificial ulcers immediately after the ESD. Feasibility and efficacy of endoscopic bio-sheet graft therapy for the management of artificial ulcers and the evaluation of healing conditions based on histology changes in the remaining gastric bed tissues harvested from the stomachs. Thirty-three ESD specimens were obtained. On an image analysis of the ratio of healed area in the remaining gastric bed tissue compared with the matched dissected gastric mucosa, the control group showed the most significant improvement in healing activity among the 3 groups (P < .05), whereas the severity of inflammation in the remaining ulcer tissue was significantly attenuated in bio-sheet and combination groups (P < .05). Animal model. Although the bio-sheet grafts provided physical protection from gastric acid attack as reflected in the attenuated inflammation on the ulcer beds, unexpected delayed ulcer healing was noted in the bio-sheet graft group because of its physical hindrance of the healing process. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

PubMed

Tanigawa, T; Ahluwalia, A; Watanabe, T; Arakawa, T; Tarnawski, A S

2015-08-01

A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100β protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing locally administered exogenous nerve growth factor is retained in gastric tissue and is taken up by endothelial, neural, muscle and epithelial cells. This is likely the basis for the therapeutic action of locally administered nerve growth factor and its stimulation of angiogenesis, tissue regeneration and gastric ulcer healing.

Topical phenytoin for treating pressure ulcers.

PubMed

Hao, Xiang Yong; Li, Hong Ling; Su, He; Cai, Hui; Guo, Tian Kang; Liu, Ruifeng; Jiang, Lei; Shen, Yan Fei

2017-02-22

Pressure ulcers are common in clinical practice and pose a significant health problem worldwide. Apart from causing suffering to patients, they also result in longer hospital stays and increase the cost of health care. A variety of methods are used for treating pressure ulcers, including pressure relief, patient repositioning, biophysical strategies, nutritional supplementation, debridement, topical negative pressure, and local treatments including dressings, ointments and creams such as bacitracin, silver sulphadiazine, neomycin, and phenytoin. Phenytoin is a drug more commonly used in the treatment of epilepsy, but may play an important role in accelerating ulcer healing. To assess the effects of topical phenytoin on the rate of healing of pressure ulcers of any grade, in any care setting. In September 2016, we searched the following electronic databases to identify relevant randomized clinical trials: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid Embase; and EBSCO CINAHL Plus. We handsearched conference proceedings from the European Pressure Ulcer Advisory Panel, European Wound Management Association and the Tissue Viability Society for all available years. We searched the references of the retrieved trials to identify further relevant trials. We also searched clinical trials registries to identify ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting. We included all randomized controlled trials (RCTs) addressing the effects (both benefits and harms) of topical phenytoin on the healing of pressure ulcers of any grade compared with placebo or alternative treatments or no therapy, irrespective of blinding, language, and publication status. Two review authors independently selected studies, extracted information on participants, interventions, methods and results and assessed risk of bias using Cochrane methodological procedures. For dichotomous variables, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables, we calculated the mean difference with 95% CI. We rated the quality of the evidence by using Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE). Three small RCTs met our inclusion criteria and included a total of 148 participants. These compared three treatments with topical phenytoin: hydrocolloid dressings, triple antibiotic ointment and simple dressings. In the three RCTs, 79% of participants had grade II ulcers, and 21% of participants had grade I ulcers; no participants had grade III or IV ulcers. Two RCTs had a high risk of bias overall and the other RCT was at unclear risk of bias due to poor reporting. Two RCTs had three intervention arms and the other had two intervention arms.Two studies compared topical phenytoin with hydrocolloid dressing (84 participants analysed). The available data suggest that hydrocolloid dressings may improve ulcer healing compared to topical phenytoin (39.3% ulcers healed for phenytoin versus 71.4% ulcers healed for hydrocolloid dressings (RR 0.55, 95% CI 0.33 to 0.92; 56 participants, 1 study; low quality evidence). We downgraded the evidence twice: once due to serious limitations (high risk of bias) and once due to the small sample size and small number of events. Two studies compared topical phenytoin with simple dressings (81 participants analysed). From the available data, we are uncertain whether topical phenytoin improves ulcer healing compared to simple dressings (39.3% ulcers healed for phenytoin versus 29.6% ulcers healed for the simple dressing (RR 1.33, 95% CI 0.63 to 2.78; 55 participants, 1 study; very low quality evidence). This evidence was downgraded once due to serious limitations (high risk of bias) and twice due to the low number of outcome events and resulting wide CI which included the possibility of both increased healing and reduced healing. We therefore considered it to be insufficient to determine the effect of topical phenytoin on ulcer healing. One study compared topical phenytoin with triple antibiotic ointment, however, none of the outcomes of interest to this review were reported. No adverse drug reactions or interactions were detected in any of the three RCTs. Minimal pain was reported in all groups in one trial that compared topical phenytoin with hydrocolloid dressings and triple antibiotic ointment. This review has considered the available evidence and the result shows that it is uncertain whether topical phenytoin improves ulcer healing for patients with grade I and II pressure ulcers. No adverse events were reported from three small trials and minimal pain was reported in one trial. Therefore, further rigorous, adequately powered RCTs examining the effects of topical phenytoin for treating pressure ulcers, and to report on adverse events, quality of life and costs are necessary.

Comparison Between a New, Two-component Compression System With Zinc Paste Bandages for Leg Ulcer Healing: A Prospective, Multicenter, Randomized, Controlled Trial Monitoring Sub-bandage Pressures.

PubMed

Mosti, Giovanni; Crespi, Aldo; Mattaliano, Vincenzo

2011-05-01

Compression therapy is standard treatment for venous leg ulcers. The authors prefer multi-layer, multi-component, stiff, high-pressure bandages to treat venous leg ulcers. The Unna boot (UB) is an example of this type of bandage. The aim of this study was to compare the effectiveness and tolerability of UB to a new, two-component bandage. One hundred (100) patients with venous ulcers were randomized into two groups: group A (n = 50) received UB and group B (n = 50) 3M™ Coban™ 2 Layer Compression System (C2L). All patients were followed weekly for 3 months and then monthly until complete healing was achieved. The primary outcomes were: ulcer healing or surface reduction; pain; and exudate control. The secondary outcomes were: ease of application and removal of the bandage, pressure exerted in the supine and standing position after application and before removal, and bandage comfort. C2L was associated with 100% ulcer healing; 47 out of 50 cases healed within the first 3 months after application of the bandage. Compared with the UB, there was no statistically significant difference. In both groups the effect of compression on pain and overall well being was excellent; pain decreased by 50% within 1-2 weeks and remained low throughout the duration of treatment and overall well being improved significantly. There was no significant difference between the two systems concerning level of comfort. C2L proved to be effective in treating venous ulcers due to its stiffness and pressure. Its effectiveness was similar to UB, which is often considered the gold-standard compression device for venous ulcers. This fact, in combination with high tolerability and ease of application and removal, make this new bandage particularly suitable for the treatment of venous leg ulcers. .

To evaluate the safety and efficiency of low level laser therapy (LLLT) in treating decubitus ulcers: a review

NASA Astrophysics Data System (ADS)

Ahmed, Ambereen

2015-03-01

Introduction: Pressure sores (decubitus ulcer) are a serious problem in health care management, especially for middleaged to older people who are bed-ridden. Although preventative measures are used, the condition remains common and development of novel, improved treatment methods are desirable. This article reviews the application of laser-based methods, previously shown to be effective in accelerating wound-healing in animal models and in the treatment of decubitus ulcers in humans. Methods: About 23 scientific articles on the effect of low level laser therapy (LLLT) on wound healing in animals and humans from 2000-2014 were reviewed. Additionally, results of several randomized controlled trials (RCTs) were reviewed, and compared with other treatment methods available. Results: Whilst carefully controlled, laboratory-based animal studies indicated that LLLT can reduce healing time for several types of injuries, however similar studies in humans failed to demonstrate consistent beneficial effects in the clinical setting. An acceleration of decubitus ulcer healing has been occasionally found, although limited to certain wavelengths and sometimes only in combination with other types of therapies. Indeed, some of the clinical articles indicated that certain laser wavelengths can have detrimental effects on time of healing. Conclusions: To date, there remains no convincing evidence that LLLT has consistent medical benefit in treating decubitus ulcers. Caution should be applied when considering LLLT since only certain wavelengths utilized have shown beneficial effects. It is concluded that, more RCTs are needed since, there is no clinical justification for LLLT, alone or in combination with other methods, in treating decubitus ulcers.

A prospective study evaluating the Pressure Ulcer Scale for Healing (PUSH Tool) to assess stage II, stage III, and stage IV pressure ulcers.

PubMed

Günes, Ulkü Yapucu

2009-05-01

Many valid and reliable tools and techniques are available for wound measurement. However, few prospective clinical studies assessing these instruments have been conducted. A prospective, methodological study was conducted between September 2006 and November 2007 to evaluate use of the Pressure Ulcer Scale for Healing (PUSH) version 3 in patients with one or more pressure ulcer. A convenience sample of 72 persons (mean age 66.9 +/- 12.8 years) with 86 pressure ulcers (49% Stage II, 47% Stage III, and 4% Stage IV) was recruited and assessed weekly until healing, transfer, patient death, or end of study for a maximum of 8 weeks. Most ulcers (77%) were in the sacral area and 56% had been present for 1 month or longer. Repeated measures analysis revealed that PUSH total scores decreased significantly (P < 0.001) over the 8-week study, with significant differences in PUSH total scores between healed and unhealed ulcers each week, starting on week 1. The total PUSH score as well as the length x width item in the tool accurately differentiated between healed and nonhealed ulcers. Although the PUSH tool is practical, easy-to-use, and generally sensitive to change, some modifications would improve its value--ie, a wound size/depth subscale. Additional studies to help clinicians more accurately evaluate the effectiveness of their interventions, including studies to determine whether wound measurements alone may suffice to monitor healing, are needed.

Moist exposed burn ointment for treating pressure ulcers: A multicenter randomized controlled trial.

PubMed

Li, Wei; Ma, Yubo; Yang, Qi; Pan, Yu; Meng, Qinggang

2017-07-01

Pressure ulcers often seriously affect the quality of life of patients. Moist Exposed Burn Ointment (MEBO) has been developed to treat patients with pressure ulcers. The present study aimed to evaluate the efficacy and safety of MEBO in the treatment of pressure ulcers in Chinese patients. Seventy-two patients with pressure ulcers were randomly assigned to 2 groups who received a placebo or MEBO for 2 months. The primary outcomes included the wound surface area (WSA) and pressure ulcer scale for healing (PUSH) tool. The secondary outcomes included a visual analog scale (VAS), questionnaire of ulcer status, and adverse effects. Sixty-seven patients completed the study. After 2 months of treatment, the difference of mean change from the baseline was greater for MEBO (vs placebo) for WSA mean (SD) -6.0 (-8.8, -3.3), PUSH Tool -2.6 (-4.7, -1.5), and VAS score -2.9 (-4.4, -1.7). On the basis of the questionnaire, the pressure ulcers were "completely healed" (50.0% vs 16.7%) (P < .05) in patients after 2 months of treatment with MEBO versus placebo. No major adverse effects were found in the 2 groups. We showed that MEBO is effective and well tolerated for improving wound healing in Chinese patients with pressure ulcers.

Anti-ulcer and wound healing activities of Sida corymbosa in rats.

PubMed

John-Africa, Lucy Binda; Yahaya, Tijani Adeniyi; Isimi, Christianah Yetunde

2014-01-01

There are strong beliefs in the efficacy of traditional medical systems worldwide. Many herbs have been acclaimed to possess antiulcer effects and could be unexplored sources of new lead compounds. Sida corymbosa R. E. Fries (Malvaceae) is used in Northern Nigeria to treat ulcers and wounds. This work aimed to investigate the usefulness of Sida corymbosa in treatments of stomach ulcers and wounds in traditional medicine. Effect of the aqueous extract was determined on gastric ulceration, rate of wound healing and inflammation using ethanol-induced and diclofenac-induced ulceration, wound excision model and albumin-induced inflammation respectively in rats. The study demonstrated the anti-ulcer activity of Sida corymbosa as the extract (250, 500 and 1000 mg/kg) showed a dose-dependent, significant (P<0.05) reduction of ulcer indices against gastric ulcers induced by both ethanol and diclofenac. Topical application of a formulation prepared with the extract of Sida corymbosa on surgically created incisions produced an increase in the rate of healing of the wounds. The extract of Sida corymbosa exhibited a significant (P < 0.05), dose-related decrease in inflammation induced by fresh egg albumin. This study showed that Sida corymbosa has constituents with the ability to reduce the severity of haemorrhagic gastric lesions, promote wound healing and reduce inflammation. These actions may be attributed to any one of the active constituents or as a result of synergistic effects of these phytoconstituents. This study validates the use of the plant in traditional medicine for the treatment of stomach ulcers and wounds.

Cost consequences due to reduced ulcer healing times - analyses based on the Swedish Registry of Ulcer Treatment.

PubMed

Öien, Rut F; Forssell, Henrik; Ragnarson Tennvall, Gunnel

2016-10-01

Resource use and costs for topical treatment of hard-to-heal ulcers based on data from the Swedish Registry of Ulcer Treatment (RUT) were analysed in patients recorded in RUT as having healed between 2009 and 2012, in order to estimate potential cost savings from reductions in frequency of dressing changes and healing times. RUT is used to capture areas of improvement in ulcer care and to enable structured wound management by registering patients with hard-to-heal leg, foot and pressure ulcers. Patients included in the registry are treated in primary care, community care, private care, and inpatient hospital care. Cost calculations were based on resource use data on healing time and frequency of dressing changes in Swedish patients with hard-to-heal ulcers who healed between 2009 and 2012. Per-patient treatment costs decreased from SEK38 223 in 2009 to SEK20 496 in 2012, mainly because of shorter healing times. Frequency of dressing changes was essentially the same during these years, varying from 1·4 to 1·6 per week. The total healing time was reduced by 38%. Treatment costs for the management of hard-to-heal ulcers can be reduced with well-developed treatment strategies resulting in shortened healing times as shown in RUT. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Grafting with Cryopreserved Amniotic Membrane versus Conservative Wound Care in Treatment of Pressure Ulcers: A Randomized Clinical Trial

PubMed Central

Dehghani, Mehdi; Azarpira, Negar; Mohammad Karimi, Vahid; Mossayebi, Hamid; Esfandiari, Elaheh

2017-01-01

Objective: To compare the healing process of pressure ulcers treated with cryopreserved human amniotic membrane allograft and routine pressure ulcer care in our hospital. Methods: From January 2012 to December 2013, in a prospective randomized clinical trial (IRCT201612041335N2), 24 patients with second and third stage of pressure ulcers were enrolled in this study. All patients needed split-thickness skin grafts for pressure ulcer-wound coverage. Selected patients had symmetric ulcers on both upper and lower extremities. The patients were randomly divided into two groups: amnion and control. In the amnion group, the ulcer was covered with cryopreserved amniotic membrane and in the control group it was treated with local Dilantin powder application. The duration and success rate of complete healing was compared between the two groups. Results: The study group was composed of 24 pressure ulcers in 24 patients (19 males and 5 females) with a mean age of 44±12.70 years. The demographic characteristics, ulcer area, and underlying diseases were similar in both groups. The early sign of response, such as decrease in wound discharge, was detected 12-14 days after biological dressing. Complete pressure ulcer healing occurred only in the amnion group (p< 0.001). Partial healing was significantly higher in the amnion group (p< 0.03). Healing time in this group was faster than that the control group (20 days versus 54 days). No major complication was recorded with amniotic membrane dressing Conclusion: Cryopreserved amniotic membrane is an effective biologic dressing that promotes re-epithelialization in pressure ulcers PMID:29177171

Therapeutic effectiveness of a Calendula officinalis extract in venous leg ulcer healing.

PubMed

Buzzi, M; de Freitas, F; de Barros Winter, M

2016-12-02

Non-healing venous leg ulcers (VLUs) have a significant effect on patients' quality of life and substantially increase expenditures in health-care systems. The aim of this study was to evaluate the clinical efficacy of the Calendula officinalis extract, Plenusdermax, in the treatment of VLUs. Patients treated with Calendula officinalis extract (n=38) and control patients (n=19) were evaluated every two weeks for 30 weeks or until their ulcers healed. Assessments included determination of the wound area by planimetry, infection control, and evaluation of the clinical aspects of the wounds. The percentage of healing velocity per week (%HVw), taking the initial area at baseline into account, was also determined. The proportion of the treatment patients achieving complete epithelialisation was 72 % and 32 % in the treatment and control groups, respectively. The average healing time was approximately 12 weeks in the treatment group and 25 % in control patients. Patients with ulcers treated with Calendula officinalis extract had a significant 4-fold increase in percentage healing velocity per week, 7.4 %, compared with 1.7 % in the control group. No adverse events were observed during the Calendula officinalis extract treatment. Our findings indicate that Calendula officinalis extract is an effective treatment for VLUs. The authors have no conflict of interest.

Risk factors of delayed ulcer healing after gastric endoscopic submucosal dissection.

PubMed

Lim, Joo Hyun; Kim, Sang Gyun; Choi, Jeongmin; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2015-12-01

Although post-endoscopic submucosal dissection (ESD) iatrogenic ulcer is known to heal faster than peptic ulcer, some iatrogenic ulcers show delayed healing. The aim of this study was to clarify risk factors of delayed ulcer healing after gastric ESD. We retrospectively reviewed medical records of all patients who had ESD for gastric neoplasms (866 adenomas and 814 early gastric cancers) between January 2005 and February 2011. Of 1680 subjects, 95 had delayed ulcer healing in 3-month follow-up. Multivariate analysis showed that diabetes (OR 1.743; 95% CI 1.017-2.989, p = 0.043), coagulation abnormality (OR 3.195; 95% CI 1.535-6.650, p = 0.002), specimen size greater than 4 cm (OR 2.999; 95% CI 1.603-5.611, p = 0.001), and electrocoagulation (OR 7.149; 95% CI 1.738-29.411, p = 0.006) were revealed to be independent risk factors of delayed ulcer healing. Meanwhile, persistent Helicobacter pylori infection was not related to the delayed ulcer healing. Large iatrogenic ulcer by ESD with massive hemostasis, especially in patients with diabetes mellitus or coagulation abnormalities, tends to take more than 3 months to heal. For such cases, initial dosage increment of PPI or addition of other anti-ulcer agents after ESD may be beneficial.

The Healing Effect of Low-Temperature Atmospheric-Pressure Plasma in Pressure Ulcer: A Randomized Controlled Trial.

PubMed

Chuangsuwanich, Apirag; Assadamongkol, Tananchai; Boonyawan, Dheerawan

2016-12-01

Pressure ulcers are difficult to treat. Recent reports of low-temperature atmospheric-pressure plasma (LTAPP) indicated its safe and effectiveness in chronic wound care management. It has been shown both in vitro and vivo studies that LTAPP not only helps facilitate wound healing but also has antimicrobial efficacy due to its composition of ion and electron, free radicals, and ultraviolet ray. We studied the beneficial effect of LTAPP specifically on pressure ulcers. In a prospective randomized study, 50 patients with pressure ulcers were divided into 2 groups: Control group received standard wound care and the study group was treated with LTAPP once every week for 8 consecutive weeks in addition to standard wound care. We found that the group treated with LTAPP had significantly better PUSH (Pressure Ulcer Scale for Healing) scores and exudate amount after 1 week of treatment. There was also a reduction in bacterial load after 1 treatment regardless of the species of bacteria identified.

Treatment of chronic non-healing ulcers using autologous platelet rich plasma: a case series.

PubMed

Suthar, Manish; Gupta, Saniya; Bukhari, Suhail; Ponemone, Venkatesh

2017-02-27

Non-healing ulcers are a major health problem worldwide and have great impact at personal, professional and social levels, with high cost in terms of human and material resources. Recalcitrant non-healing ulcers are inevitable and detrimental to the lower limb and are a major cause of non-traumatic lower limb amputations. Application of autologous Platelet Rich Plasma (PRP) has been a major breakthrough for the treatment of non-healing and diabetic foot ulcers, as it is an easy and cost-effective method, and provides the necessary growth factors that enhance tissue healing. PRP is a conglomeration of thrombocytes, cytokines and various growth factors which are secreted by α-granules of platelets that augment the rate of natural healing process with decrease in time. The purpose of this case series was to evaluate the safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers on the lower extremity. Autologous PRP was prepared from whole blood utilizing a rapid, intraoperative point-of-care system that works on the principle of density gradient centrifugation. Twenty Four (24) patients with non-healing ulcers of different etiologies, who met the inclusion criteria, were treated with single dose of subcutaneous PRP injections along with topical application of PRP gel under compassionate use. The mean age of the treated patients was 62.5 ± 13.53 years and they were followed-up for a period of 24 weeks. All the patients showed signs of wound healing with reduction in wound size, and the mean time duration to ulcer healing was 8.2 weeks. Also, an average five fold increase in the platelet concentrate was observed in the final PRP product obtained using the rapid point-of-care device, and the average platelet dose administered to the patients was 70.10 × 10 8 . This case series has demonstrated the potential safety and efficacy of autologous platelet rich plasma for the treatment of chronic non-healing ulcers. NCT03026855 , Registered 4 January 2017 'Retrospectively'.

Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency.

PubMed

del Río Solá, Ma Lourdes; Antonio, Jose; Fajardo, González; Vaquero Puerta, Carlos

2012-07-01

To determine the effect of aspirin on ulcer healing rate in patients with chronic venous insufficiency, and to establish prognostic factors that influence ulcer evolution. Between 2001 and 2005, 78 patients with ulcerated lesions of diameter >2 cm and associated with chronic venous insufficiency were evaluated in our hospital. Of these, 51 patients (22 men, 29 women) with mean age of 60 years (range: 36-86) were included in a prospective randomized trial with a parallel control group. The treatment group received 300 mg of aspirin and the control group received no drug treatment; in both groups, healing was associated with standard compression therapy. During follow-up, held weekly in a blinded fashion, there was ulcer healing as well as cases of recurrence. Results were analyzed by intention-to-treat approach. Cure rate was estimated using Kaplan-Meier survival analysis, and the influence of prognostic factors was analyzed by applying the Cox proportional hazards model. In the presence of gradual compression therapy, healing occurred more rapidly in patients receiving aspirin versus the control subjects (12 weeks in the treated group vs. 22 weeks in the control group), with a 46% reduction in healing time. The main prognostic factor was estimated initial area of injury (P = 0.032). Age, sex, systemic therapy, and infection showed little relevance to evolution. The administration of aspirin daily dose of 300 mg shortens the healing time of ulcerated lesions in the chronic venous insufficiency (CVI). The main prognostic factor for healing of venous ulcerated lesions is the initial surface area of the ulcer. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Topical oxygen therapy promotes the healing of chronic diabetic foot ulcers: a pilot study.

PubMed

Hayes, P D; Alzuhir, N; Curran, G; Loftus, I M

2017-11-02

Interventions that can heal or reduce diabetic foot ulcer (DFU) size may reduce the incidence of infection and amputation, and reduce associated social and economic costs. Many chronic wounds exhibit a degree of hypoxia and this leads to a reduction in healing processes including cell division and differentiation, angiogenesis, infection prevention, and collagen production. The aim of this pilot study was to assess the effects of a device supplying continuous oxygen ambulatory therapy on healing in chronic DFUs. Patients with chronic DFUs from two tertiary referral hospitals in the UK received treatment with the device. Data were prospectively obtained on wound size using standardised digital images measured by a clinician blinded to the study. Data on device satisfaction and pain were also obtained. We recruited 10 patients, with a mean ulcer duration of 43 weeks (median: 43 weeks) before treatment. By week eight, mean ulcer size had decreased by 51% (median: 53%). Seven of the 10 ulcers were in a healing trajectory, one ulcer present for 56 weeks healed completely, a two-year old ulcer was reduced by more than 50%, and a third, present for 88 weeks, was down to 10% of its original size by the end of the eight-week study. There was also a non-significant trend towards reduction in pain and the device was extremely well tolerated. The ambulatory topical oxygen delivery device showed a significant beneficial effect on wound size. This poses practical advantages over currently existing oxygen-based wound therapies such as hyperbaric oxygen therapy due to its continuous oxygen delivery, ease of use, safety and lower cost. The results of this study warrant further review of the device in comparison to standard wound therapies.

Honey for wound healing, ulcers, and burns; data supporting its use in clinical practice.

PubMed

Al-Waili, Noori; Salom, Khelod; Al-Ghamdi, Ahmad A

2011-04-05

The widespread existence of unhealed wounds, ulcers, and burns has a great impact on public health and economy. Many interventions, including new medications and technologies, are being used to help achieve significant wound healing and to eliminate infections. Therefore, to find an intervention that has both therapeutic effect on the healing process and the ability to kill microbes is of great value. Honey is a natural product that has been recently introduced in modern medical practice. Honey's antibacterial properties and its effects on wound healing have been thoroughly investigated. Laboratory studies and clinical trials have shown that honey is an effective broad-spectrum antibacterial agent. This paper reviews data that support the effectiveness of natural honey in wound healing and its ability to sterilize infected wounds. Studies on the therapeutic effects of honey collected in different geographical areas on skin wounds, skin and gastric ulcers, and burns are reviewed and mechanisms of action are discussed. (Ulcers and burns are included as an example of challenging wounds.) The data show that the wound healing properties of honey include stimulation of tissue growth, enhanced epithelialization, and minimized scar formation. These effects are ascribed to honey's acidity, hydrogen peroxide content, osmotic effect, nutritional and antioxidant contents, stimulation of immunity, and to unidentified compounds. Prostaglandins and nitric oxide play a major role in inflammation, microbial killing, and the healing process. Honey was found to lower prostaglandin levels and elevate nitric oxide end products. These properties might help to explain some biological and therapeutic properties of honey, particularly as an antibacterial agent or wound healer. The data presented here demonstrate that honeys from different geographical areas have considerable therapeutic effects on chronic wounds, ulcers, and burns. The results encourage the use of honey in clinical practice as a natural and safe wound healer.

A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control.

PubMed

Shannon, Ronald; Nelson, Andrea

2017-08-01

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score-matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi-layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow-up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ 2 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model.

PubMed

O'Loughlin, Aonghus; Kulkarni, Mangesh; Vaughan, Erin E; Creane, Michael; Liew, Aaron; Dockery, Peter; Pandit, Abhay; O'Brien, Timothy

2013-01-01

Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non-healing diabetic foot ulcers in humans.

Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review.

PubMed

Bus, S A; van Deursen, R W; Armstrong, D G; Lewis, J E A; Caravaggi, C F; Cavanagh, P R

2016-01-01

Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment. We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006. We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches. Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of Jianweiyuyang granule on gastric ulcer recurrence and expression of VEGF mRNA in the healing process of gastric ulcer in rats.

PubMed

Dai, Xing-Ping; Li, Jia-Bang; Liu, Zhao-Qian; Ding, Xiang; Huang, Cheng-Hui; Zhou, Bing

2005-09-21

To investigate the effect of Jianweiyuyang (JWYY) granule on gastric ulcer recurrence and its mechanism in the treatment of gastric ulcer in rats. Gastric ulcer in rats was induced according to Okeba's method with minor modification and the recurrence model was induced by IL-1beta. The expression of vascular endothelial growth factor mRNA (VEGF mRNA) was examined by reverse transcription polymerase chain reaction in gastric ulcer and microvessel density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. MVD was higher in the JWYY treatment group (14.0+/-2.62) compared with the normal, model and ranitidine treatment groups (2.2+/-0.84, 8.8+/-0.97, 10.4+/-0.97) in rats (P<0.01). The expression level of VEGF mRNA in gastric tissues during the healing process of JWYY treatment group rats significantly increased compared with other groups (normal group: 0.190+/-0.019, model group: 0.642+/-0.034, ranitidine group: 0.790+/-0.037, P<0.01). JWYY granules can stimulate angiogenesis and enhance the expression of VEGF mRNA in gastric ulcer rats. This might be the mechanism for JWYY accelerating the ulcer healing, and preventing the recurrence of gastric ulcer.

Healing and Antisecretory Effects of Aqueous Extract of Eremomastax speciosa (Acanthaceae) on Unhealed Gastric Ulcers

PubMed Central

Amang, A. P.; Mezui, C.; Siwe, G. T.; Emakoua, J.; Mbah, G.; Nkwengoua, E. Z.; Enow-Orock, G. E.

2017-01-01

Objective This work investigated the healing and antisecretory effects of the aqueous extract of Eremomastax speciosa on “unhealed gastric ulcers” associated with gastric acid hypersecretion. Materials and Methods “Unhealed gastric ulcers” were induced using indomethacin following the establishment of acetic-acid-induced chronic gastric ulcers. The extract (200 and 400 mg/kg, per os) was administered concomitantly with indomethacin (1 mg/kg, subcutaneously). The effects of the extract on both basal and histamine-stimulated gastric acid secretion were determined. Mucus secretion and oxidative stress parameters were measured, and histological assessment of ulcer healing was carried out. Results The extract significantly promoted the healing process in rats subjected to “unhealed gastric ulcers” (82.4–88.5% healing rates). Treatment with the extract significantly reduced the basal (25.95–49.51% reduction rates) and histamine-stimulated (24.25–47.41%) acid secretions. The healing effect of the extract was associated with a significant (p < 0.05) increase of mucus secretion and concentrations of antioxidant enzymes compared with the controls. The extract at the highest dose showed normalization of the mucosa, without glandular destruction and with the disappearance of fibrosis and lymphocyte infiltration. Conclusion The abilities of the extract to increase mucus secretion, to reinforce antioxidant status, and to inhibit acid secretion would be some of the mechanisms by which this extract would accelerate the healing process in “unhealed gastric ulcers.” PMID:29234676

Glyprolines exert protective and repair-promoting effects in the rat stomach: potential role of the cytokine GRO/CINC-1.

PubMed

Bakaeva, Z V; Sangadzhieva, A D; Tani, S; Myasoedov, N F; Andreeva, L A; Torshin, V I; Wallace, J L; Tanaka, T

2016-04-01

Glyprolines have been reported to exert protective effects in the stomach. In this study, we examined the potential effects of intranasal administration of Pro-Gly-Pro (PGP) and N-acetyl-Pro-Gly-Pro (AcPGP) on experimental gastric ulcer formation and healing. We also studied gastric release of the cytokine GRO/CINC-1, and its potential role in ulcer development and healing. Gastric ulcers were induced in rats by applying acetic acid to the serosa of the stomach. PGP and AcPGP were then administered at a dose of 3.7 μmol/kg once daily on either days 1 - 3 (ulcer formation) or days 4 - 6 (ulcer healing). Measurement of ulcer area and histological examination of gastric tissue were carried out on days 4 and 7 after application of acetic acid. In vitro studies involved addition of the glyprolines to cultured rat gastric epithelial cells with or without lipopolysaccharide. Reverse transcription PCR, real-time PCR and ELISA were used for cytokine analysis. PGP and AcPGP significantly reduced ulcer areas on the 4(th) day and accelerated the healing on the 7(th) day compared with the control. After acetic acid-induced ulceration, the expression of GRO/CINC-1 mRNA in gastric tissue was increased 9-fold versus the sham-operated group. Treatment with PGP or AcPGP both significantly suppressed the expression of GRO/CINC-1 mRNA in gastric tissue. However, the glyprolines did not alter LPS-induced mRNA expression or release of GRO/CINC-1 from cultured rat gastric epithelial cells, even though those cells were harvested from rats subjected to the ulcer-induction procedure. The results of this study show that intranasal administration of PGP and AcPGP significantly increased resistance against acetic acid-induced ulceration and accelerated healing in the rats. These effects may be due, at least in part, to their ability to reduce the acetic acid-induced GRO/CINC-1 expression and production in gastric tissue.

The use of low output laser therapy to accelerate healing of diabetic foot ulcers: a randomized prospective controlled trial

NASA Astrophysics Data System (ADS)

Naidu, S. V. L. G.; Subapriya, S.; Yeoh, C. N.; Soosai, S.; Shalini, V.; Harwant, S.

2005-11-01

The aim of this study was to assess the effects of low output laser therapy as an adjuvant treatment in grade 1 diabetic foot ulcers. Methods: Sixteen patients were randomly divided equally into two groups. Group A had daily dressing only, while group B had low output laser therapy instituted five days a week in addition to daily dressing. Serial measurement of the ulcer was done weekly using digital photography and analyzed. Results: The rate of healing in group A was 10.42 mm2/week, and in group B was 66.14mm2/week. The difference in the rate of healing was statistically significant, p<0.05. Conclusion: Laser therapy as an adjuvant treatment accelerates diabetic ulcer healing by six times in a six week period.

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration

PubMed Central

XU, XIAOPING; LI, XIAOHUA; ZHANG, LEI; LIU, ZHAOHUI; PAN, YUAN; CHEN, DONG; BIN, DONGHUA; DENG, QUN; SUN, YU; HOFFMAN, M. ROBERT; YANG, ZHIJIAN; YUAN, HONG

2017-01-01

Background/Aim: Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. Materials and Methods: A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E2 (PGE2) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Results: Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. Conclusion: CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE2 and IL-8 may be involved in the mechanism of enhanced wound-healing. PMID:28652418

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration.

PubMed

Xu, Xiaoping; Li, Xiaohua; Zhang, Lei; Liu, Zhaohui; Pan, Yuan; Chen, Dong; Bin, Donghua; Deng, Qun; Sun, Y U; Hoffman, Robert M; Yang, Zhijian; Yuan, Hong

2017-01-01

Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E 2 (PGE 2 ) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE 2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE 2 and IL-8 may be involved in the mechanism of enhanced wound-healing. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Pressure ulcer treatment strategies: a systematic comparative effectiveness review.

PubMed

Smith, M E Beth; Totten, Annette; Hickam, David H; Fu, Rongwei; Wasson, Ngoc; Rahman, Basmah; Motu'apuaka, Makalapua; Saha, Somnath

2013-07-02

Pressure ulcers affect as many as 3 million Americans and are major sources of morbidity, mortality, and health care costs. To summarize evidence comparing the effectiveness and safety of treatment strategies for adults with pressure ulcers. MEDLINE, EMBASE, CINAHL, Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database for English- or foreign-language studies; reference lists; gray literature; and individual product packets from manufacturers (January 1985 to October 2012). Randomized trials and comparative observational studies of treatments for pressure ulcers in adults and noncomparative intervention series (n > 50) for surgical interventions and evaluation of harms. Data were extracted and evaluated for accuracy of the extraction, quality of included studies, and strength of evidence. 174 studies met inclusion criteria and 92 evaluated complete wound healing. In comparison with standard care, placebo, or sham interventions, moderate-strength evidence showed that air-fluidized beds (5 studies [n = 908]; high consistency), protein-containing nutritional supplements (12 studies [n = 562]; high consistency), radiant heat dressings (4 studies [n = 160]; moderate consistency), and electrical stimulation (9 studies [n = 397]; moderate consistency) improved healing of pressure ulcers. Low-strength evidence showed that alternating-pressure surfaces, hydrocolloid dressings, platelet-derived growth factor, and light therapy improved healing of pressure ulcers. The evidence about harms was limited. Applicability of results is limited by study quality, heterogeneity in methods and outcomes, and inadequate duration to assess complete wound healing. Moderate-strength evidence shows that healing of pressure ulcers in adults is improved with the use of air-fluidized beds, protein supplementation, radiant heat dressings, and electrical stimulation.

Coping style and depression influence the healing of diabetic foot ulcers: observational and mechanistic evidence.

PubMed

Vedhara, K; Miles, J N V; Wetherell, M A; Dawe, K; Searle, A; Tallon, D; Cullum, N; Day, A; Dayan, C; Drake, N; Price, P; Tarlton, J; Weinman, J; Campbell, R

2010-08-01

Experimental evidence suggests that the healing of diabetic foot ulcers is affected by psychosocial factors such as distress. We examined this proposal in a prospective study, in which we considered the role of psychological distress and coping style in the healing of diabetic foot ulcers over a 24 week period. We also explored the role of salivary cortisol and matrix metalloproteinases (MMPs) as potential mechanisms. For this prospective observational study we recruited 93 (68 men; mean age 60 years) patients with neuropathic or neuroischaemic diabetic foot ulcers from specialist podiatry clinics in secondary care. Clinical and demographic determinants of healing, psychological distress, coping, salivary cortisol and both MMP2 and MMP9 were assessed at baseline. Ulcers were assessed at baseline and at 6, 12 and 24 weeks post-baseline. The primary outcome was ulcer status at 24 weeks, i.e. healed vs not healed. After controlling for clinical and demographic determinants of healing, ulcer healing at 24 weeks was predicted by confrontation coping, but not by depression or anxiety. Patients with unhealed ulcers exhibited greater confrontation coping (model including depression: OR 0.809, 95% CI 0.704-0.929, p = 0.003; model including anxiety: OR 0.810, 95% CI 0.704-0.930, p = 0.003). However, change in ulcer size over the observation period was associated with depression only (p = 0.04, d = 0.31). Healed ulcers by 24 weeks were also associated with lower evening cortisol, higher precursor MMP2 and a greater cortisol awakening response. Confrontation coping and depression predict ulcer healing. Our preliminary enquiry into biological mechanisms suggests that cortisol and precursor MMP2 may underlie these relationships.

The value of debridement and Vacuum-Assisted Closure (V.A.C.) Therapy in diabetic foot ulcers.

PubMed

Eneroth, Magnus; van Houtum, William H

2008-01-01

Treatment of diabetic foot ulcers includes a number of different regimes such as glycaemic control, re-vascularization, surgical, local wound treatment, offloading and other non-surgical treatments. Although considered the standard of care, the scientific evidence behind the various debridements used is scarce. This presentation will focus on debridement and V.A.C. Therapy, two treatments widely used in patients with diabetes and foot ulcers. A review of existing literature on these treatments in diabetic foot ulcers, with focus on description of the various types of debridements used, the principles behind negative pressure wound therapy (NPWT) using the V.A.C. Therapy system and level of evidence. Five randomized controlled trials (RCT) of debridement were identified; three assessed the effectiveness of a hydrogel as a debridement method, one evaluated surgical debridement and one evaluated larval therapy. Pooling the three hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or standard care in healing diabetic foot ulcers. Surgical debridement and larval therapy showed no significant benefit. Other debridement methods such as enzyme preparations or polysaccharide beads have not been evaluated in RCTs of people with diabetes. More than 300 articles have been published on negative pressure wound therapy, including several small RCTs and a larger multi-centre RCT of diabetic foot ulcers. Negative pressure wound therapy seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care. Although debridement of the ulcer is considered a prerequisite for healing of diabetic foot ulcers, the grade of evidence is quite low. This may be due to a lack of studies rather than lack of effect. Negative pressure wound therapy seems to be safe and effective in the treatment of some diabetic foot ulcers, although there is still only one well-performed trial that evaluates the effect.

A Case-Control Study of Esomeprazole Plus Rebamipide vs. Omeprazole Plus Rebamipide on Post-ESD Gastric Ulcers.

PubMed

Bunno, Maki; Gouda, Kyosuke; Yamahara, Kunihiro; Kawaguchi, Masanori

2013-01-01

Endoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. There is no report about the efficacy of post-ESD gastric ulcers by esomeprazole. We examined retrospectively the efficacy of a combination therapy of esomeprazole plus rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing comparing with omeprazole plus rebamipide. We reviewed the medical records of patients who underwent ESD for gastric neoplasia. We conducted a case-control study to compare the healing rates within 4 weeks effected by esomeprazole plus rebamipide (group E) and omeprazole plus rebamipide (group O). The sizes of the artificial ulcers were divided into normal-sized or large-sized. The baseline characteristics did not differ significantly between the two groups except age and sex. Stage S1 disease was observed in 27.6% and 38.7% of patients after 4 weeks of treatment in the group E and O, respectively. In large-sized artificial ulcers, the healing rate of stage S1 in group E is significantly higher than that in group O in 4 weeks.(25% VS 0%:P = 0.02). The safety and efficacy profiles of esomeprazole plus rebamipide and omeprazole and rebamipide are similar for the treatment of ESD-induced ulcers. In large-sized ulcers, esomeprazole plus rebamipide promotes ulcer healing.

Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway

PubMed Central

Chatterjee, Ananya; Chatterjee, Sirshendu; Biswas, Angshuman; Bhattacharya, Sayanti; Chattopadhyay, Subrata; Bandyopadhyay, Sandip K.

2012-01-01

The healing activity of gallic acid enriched ethanolic extract (GAE) of Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose) administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO) activity and inducible nitric oxide synthase (i-NOS) expression. Proangiogenic parameters such as the levels of prostaglandin (PG) E2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL). Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE2 synthesis and augmenting e-NOS/i-NOS ratio. PMID:22966242

VenUS IV (Venous leg Ulcer Study IV) - compression hosiery compared with compression bandaging in the treatment of venous leg ulcers: a randomised controlled trial, mixed-treatment comparison and decision-analytic model.

PubMed

Ashby, Rebecca L; Gabe, Rhian; Ali, Shehzad; Saramago, Pedro; Chuang, Ling-Hsiang; Adderley, Una; Bland, J Martin; Cullum, Nicky A; Dumville, Jo C; Iglesias, Cynthia P; Kang'ombe, Arthur R; Soares, Marta O; Stubbs, Nikki C; Torgerson, David J

2014-09-01

Compression is an effective and recommended treatment for venous leg ulcers. Although the four-layer bandage (4LB) is regarded as the gold standard compression system, it is recognised that the amount of compression delivered might be compromised by poor application technique. Also the bulky nature of the bandages might reduce ankle or leg mobility and make the wearing of shoes difficult. Two-layer compression hosiery systems are now available for the treatment of venous leg ulcers. Two-layer hosiery (HH) may be advantageous, as it has reduced bulk, which might enhance ankle or leg mobility and patient adherence. Some patients can also remove and reapply two-layer hosiery, which may encourage self-management and could reduce costs. However, little robust evidence exists about the effectiveness of two-layer hosiery for ulcer healing and no previous trials have compared two-layer hosiery delivering 'high' compression with the 4LB. Part I To compare the clinical effectiveness and cost-effectiveness of HH and 4LB in terms of time to complete healing of venous leg ulcers. Part II To synthesise the relative effectiveness evidence (for ulcer healing) of high-compression treatments for venous leg ulcers using a mixed-treatment comparison (MTC). Part III To construct a decision-analytic model to assess the cost-effectiveness of high-compression treatments for venous leg ulcers. Part I A multicentred, pragmatic, two-arm, parallel, open randomised controlled trial (RCT) with an economic evaluation. Part II MTC using all relevant RCT data - including Venous leg Ulcer Study IV (VenUS IV). Part III A decision-analytic Markov model. Part I Community nurse teams or services, general practitioner practices, leg ulcer clinics, tissue viability clinics or services and wound clinics within England and Northern Ireland. Part I Patients aged ≥ 18 years with a venous leg ulcer, who were willing and able to tolerate high compression. Part I Participants in the intervention group received HH. The control group received the 4LB, which was applied according to standard practice. Both treatments are designed to deliver 40 mmHg of compression at the ankle. Part II and III All relevant high-compression treatments including HH, the 4LB and the two-layer bandage (2LB). Part I The primary outcome measure was time to healing of the reference ulcer (blinded assessment). Part II Time to ulcer healing. Part III Quality-adjusted life-years (QALYs) and costs. Part I A total of 457 participants were recruited. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.79 to 1.25; p = 0.96]. Time to ulcer recurrence was significantly shorter in the 4LB group (HR = 0.56, 95% CI 0.33 to 0.94; p = 0.026). In terms of cost-effectiveness, using QALYs as the measure of benefit, HH had a > 95% probability of being the most cost-effective treatment based on the within-trial analysis. Part II The MTC suggests that the 2LB has the highest probability of ulcer healing compared with other high-compression treatments. However, this evidence is categorised as low to very low quality. Part III Results suggested that the 2LB had the highest probability of being the most cost-effective high-compression treatment for venous leg ulcers. Trial data from VenUS IV found no evidence of a difference in venous ulcer healing between HH and the 4LB. HH may reduce ulcer recurrence rates compared with the 4LB and be a cost-effective treatment. When all available high-compression treatments were considered, the 2LB had the highest probability of being clinically effective and cost-effective. However, the underpinning evidence was sparse and more research is needed. Further research should thus focus on establishing, in a high-quality trial, the effectiveness of this compression system in particular. Current Controlled Trials ISRCTN49373072. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 57. See the NIHR Journals Library website for further project information.

Therapeutic effect of exogenous ghrelin in the healing of gingival ulcers is mediated by the release of endogenous growth hormone and insulin-like growth factor-1.

PubMed

Cieszkowski, J; Warzecha, Z; Ceranowicz, P; Ceranowicz, D; Kusnierz-Cabala, B; Pedziwiatr, M; Dembinski, M; Ambrozy, T; Kaczmarzyk, T; Pihut, M; Wieckiewicz, M; Olszanecki, R; Dembinski, A

2017-08-01

Ghrelin, an acylated 28-amino acid polypeptide, was primary isolated from the stomach, and the stomach is a main source of circulating ghrelin. Ghrelin strongly and dose-dependently stimulates release of growth hormone from the anterior pituitary, as well as increases food intake and fat deposition. Previous studies showed that ghrelin exhibits protective and therapeutic effect in different parts of the gastrointestinal system, including the oral cavity. The aim of present study was to examine the role of growth hormone and insulin-like growth factor-1 (IGF-1) in the healing of gingival ulcers. Studies were performed on rats with the intact pituitary gland and hypophysectomized rats. In anesthetized rats, chronic ulcers of the gum were induced by acetic acid. Rats were treated intraperitoneally twice a day with saline or ghrelin (4, 8 or 16 nmol/kg/dose) for six days. In pituitary-intact rats, administration of ghrelin significantly increased serum concentration of growth hormone and IGF-1 and this effect was associated with a significant increase in the healing rate of gingival ulcers. Moreover, treatment with ghrelin increased mucosal blood flow and DNA synthesis in the gum, while a local inflammation was decreased what was observed as a reduction in mucosal concentration of pro-inflammatory interleukin-1β. Hypophysectomy decreased serum level of growth hormone below a detection limit; whereas serum concentration of IGF-1 was reduced by 90%. On the other hand, removal of the pituitary gland was without any significant effect on the healing rate of gingival ulcers or on the ulcer-induced increase in DNA synthesis and concentration of pro-inflammatory interleukin-1β in gingival mucosa. Administration of ghrelin failed to affect serum level of growth hormone and IGF-1 in hypophysectomized rats, and was without any effect on the healing rate of gingival ulcers, mucosal blood flow, DNA synthesis or concentration of interleukin-1β in gingival mucosa. Neither induction of gingival ulcers nor hypophysectomy nor administration of ghrelin significantly affected serum concentration of pro-inflammatory interleukin-1β. We concluded that endogenous growth hormone and IGF-1 were involved in the therapeutic effect of exogenous ghrelin in the healing of gingival mucosa damage.

Honey as a topical treatment for wounds.

PubMed

Jull, Andrew B; Rodgers, Anthony; Walker, Natalie

2008-10-08

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (burns, lacerations and other traumatic wounds) and chronic wounds (venous ulcers, arterial ulcers, diabetic ulcers, pressure ulcers, infected surgical wounds). We searched the Cochrane Wounds Group Specialised Register (May 2008), CENTRAL (May 2008) and several other electronic databases (May 2008). Bibliographies were searched and manufacturers of dressing products were contacted for unpublished trials. Randomised and quasi randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised using a data extraction sheet by one author and independently verified by a second author. 19 trials (n=2554) were identified that met the inclusion criteria. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and nine trials evaluated the effect the honey in burns. In chronic wounds two trials evaluated the effect of honey in venous leg ulcers and one trial in pressure ulcers, infected post-operative wounds, and Fournier's gangrene respectively. Two trials recruited people with mixed groups of chronic or acute wounds. The poor quality of most of the trial reports means the results should be interpreted with caution, except in venous leg ulcers. In acute wounds, honey may reduce time to healing compared with some conventional dressings in partial thickness burns (WMD -4.68 days, 95%CI -4.28 to -5.09 days). All the included burns trials have originated from a single centre, which may have impact on replicability. In chronic wounds, honey in addition to compression bandaging does not significantly increase healing in venous leg ulcers (RR 1.15, 95%CI 0.96 to 1.38). There is insufficient evidence to determine the effect of honey compared with other treatments for burns or in other acute or chronic wound types. Honey may improve healing times in mild to moderate superficial and partial thickness burns compared with some conventional dressings. Honey dressings as an adjuvant to compression do not significantly increase leg ulcer healing at 12 weeks. There is insufficient evidence to guide clinical practice in other areas.

A retrospective study using the pressure ulcer scale for healing (PUSH) tool to examine factors affecting stage II pressure ulcer healing in a Korean acute care hospital.

PubMed

Park, Kyung Hee

2014-09-01

Stage II pressure ulcers (PUs) should be managed promptly and appropriately in order to prevent complications. To identify the factors affecting Stage II PU healing and optimize care, the electronic medical records of patients with a Stage II PU in an acute care hospital were examined. Patient and ulcer characteristics as well as nutritional assessment variables were retrieved, and ulcer variables were used to calculate Pressure Ulcer Scale for Healing (PUSH) scores. The effect of all variables on healing status (healed versus nonhealed) and change in PUSH score for healing rate were compared. Records of 309 Stage II PUs from 155 patients (mean age 61.2 ± 15.2 [range 5-89] years, 182 [58.9%] male) were retrieved and analyzed. Of those, 221 healed and 88 were documented as not healed at the end of the study. The variables that were significantly different between patients with PUs that did and did not heal were: major diagnosis (P = 0.001), peripheral arterial disease (P = 0.007), smoking (P = 0.048), serum albumin ( <2.5 g/dL) (P = 0.002), antidepressant use (P = 0.035), vitamin use (P = 0.006), history of surgery (P <0.001), PU size (P = 0.003), Malnutrition Universal Screening Tool (MUST) score (P = 0.020), Braden scale score (P = 0.003), and mean arterial pressure (MAP, mm Hg) (P = 0.026). The Cox proportional hazard model showed a significant positive difference in PUSH score change -indicative of healing - when pressure-redistribution surfaces were used (P <0.001, HR = 2.317), PU size was small (≤3.0 cm2, P = 0.006, HR = 1.670), MAP (within a range of 52-112 mm Hg) was higher P = 0.010, HR = 1.016), and patients were provided multivitamins (P = 0.037, HR=1.431). The results of this study suggest strategies for healing Stage II PUs in the acute care setting should include early recognition of lower-stage PUs, the provision of static pressure-redistribution surfaces and multivitamins, and maintaining higher MAP may facilitate healing and prevent deterioration. Further prospective research is warranted to verify the effect of these interventions.

Aspirin in venous leg ulcer study (ASPiVLU): study protocol for a randomised controlled trial.

PubMed

Weller, Carolina D; Barker, Anna; Darby, Ian; Haines, Terrence; Underwood, Martin; Ward, Stephanie; Aldons, Pat; Dapiran, Elizabeth; Madan, Jason J; Loveland, Paula; Sinha, Sankar; Vicaretti, Mauro; Wolfe, Rory; Woodward, Michael; McNeil, John

2016-04-11

Venous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing. This randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks. The ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018. Australian New Zealand Clinical Trials Registry, ACTRN12614000293662.

A prospective, randomised comparative study of weekly versus biweekly application of dehydrated human amnion/chorion membrane allograft in the management of diabetic foot ulcers

PubMed Central

Zelen, Charles M; Serena, Thomas E; Snyder, Robert J

2014-01-01

The aim of this study is to determine if weekly application of dehydrated human amnion/chorion membrane allograft reduce time to heal more effectively than biweekly application for treatment of diabetic foot ulcers. This was an institutional review board-approved, registered, prospective, randomised, comparative, non-blinded, single-centre clinical trial. Patients with non-infected ulcers of ≥ 4 weeks duration were included for the study. They were randomised to receive weekly or biweekly application of allograft in addition to a non-adherent, moist dressing with compressive wrapping. All wounds were offloaded. The primary study outcome was mean time to healing. Overall, during the 12-week study period, 92·5% (37/40) ulcers completely healed. Mean time to complete healing was 4·1 ± 2·9 versus 2·4 ± 1·8 weeks (P = 0·039) in the biweekly versus weekly groups, respectively. Complete healing occurred in 50% versus 90% by 4 weeks in the biweekly and weekly groups, respectively (P = 0·014). Number of grafts applied to healed wounds was similar at 2·4 ± 1·5 and 2·3 ± 1·8 for biweekly versus weekly groups, respectively (P = 0·841). These results validate previous studies showing that the allograft is an effective treatment for diabetic ulcers and show that wounds treated with weekly application heal more rapidly than with biweekly application. More rapid healing may decrease clinical operational costs and prevent long-term medical complications. PMID:24618401

Evaluation of the internal and external responsiveness of the Pressure Ulcer Scale for Healing (PUSH) tool for assessing acute and chronic wounds.

PubMed

Choi, Edmond P H; Chin, Weng Yee; Wan, Eric Y F; Lam, Cindy L K

2016-05-01

To examine the internal and external responsiveness of the Pressure Ulcer Scale for Healing (PUSH) tool for assessing the healing progress in acute and chronic wounds. It is important to establish the responsiveness of instruments used in conducting wound care assessments to ensure that they are able to capture changes in wound healing accurately over time. Prospective longitudinal observational study. The key study instrument was the PUSH tool. Internal responsiveness was assessed using paired t-testing and effect size statistics. External responsiveness was assessed using multiple linear regression. All new patients with at least one eligible acute or chronic wound, enrolled in the Nurse and Allied Health Clinic-Wound Care programme between 1 December 2012 - 31 March 2013 were included for analysis (N = 541). Overall, the PUSH tool was able to detect statistically significant changes in wound healing between baseline and discharge. The effect size statistics were large. The internal responsiveness of the PUSH tool was confirmed in patients with a variety of different wound types including venous ulcers, pressure ulcers, neuropathic ulcers, burns and scalds, skin tears, surgical wounds and traumatic wounds. After controlling for age, gender and wound type, subjects in the 'wound improved but not healed' group had a smaller change in PUSH scores than those in the 'wound healed' group. Subjects in the 'wound static or worsened' group had the smallest change in PUSH scores. The external responsiveness was confirmed. The internal and external responsiveness of the PUSH tool confirmed that it can be used to track the healing progress of both acute and chronic wounds. © 2016 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

Transcutaneous oxygen pressure measurement in diabetic foot ulcers: mean values and cut-point for wound healing.

PubMed

Yang, Chuan; Weng, Huan; Chen, Lihong; Yang, Haiyun; Luo, Guangming; Mai, Lifang; Jin, Guoshu; Yan, Li

2013-01-01

The purpose of this study was to investigate mean values and cut-point of transcutaneous oxygen pressure (TcPO2) measurement in patients with diabetic foot ulcers. Prospective, descriptive study. Sixty-one patients with diabetes mellitus and foot ulcers comprised the sample. The research setting was Sun Yat-sen Memorial Hospital of SunYat-sen University, Guangzhou, China. Participants underwent transcutaneous oxygen (TcPO2) measurement at the dorsum of foot. Patients were classified into 3 groups according to clinical outcomes: (1) ulcers healed with intact skin group, (2) ulcer improved, and (3) ulcer failed to improve. TcPO2 was assessed and cut-points for predicting diabetic foot ulcer healing were calculated. Thirty-six patients healed with intact skin, 8 experienced improvement, and 17 showed no improvement. Mean TcPO2 levels were significantly higher (P< .001) in healed ulcers with intact skin (32 ± 10 mmHg) when compared to the improvement group (30 ± 7 mmHg) and the nonhealing group (15 ± 12 mmHg). All patients with TcPO2≤ 10 mmHg failed to heal or experienced deterioration in their foot ulcers. In contrast, all patients with TcPO2≥ 40 mmHg achieved wound closure. Measurement of TcPO2 in the supine position revealed a cut-point value of 25 mmHg as the best threshold for predicting diabetic foot ulcer healing; the area under the curve using this cut-point was 0.838 (95% confidence interval = 0.700-0.976). The sensitivity, specificity, positive predictive value, and negative predictive value for TxPO2 were 88.6%, 82.4%, 90.7%, and 72.2%, respectively. TcPO2≥ 40 mmHg was associated with diabetic foot ulcer healing, but a TcPO2≤ 10 mmHg was associated with failure of wound healing. We found that a cut-point of 25 mmHg was most predictive of diabetic foot ulcer healing.

The role of nerve growth factor in the prophylaxis and treatment of diabetic foot ulcers

PubMed Central

Tiaka, Elisavet K; Papanas, Nikolaos; Manolakis, Anastassios C; Maltezos, Efstratios

2011-01-01

Diabetic foot ulcers are still particularly difficult to heal. Therefore, preventing and therapeutic adjuncts are increasingly being explored. Nerve growth factor (NGF) is a promising agent exhibiting beneficial actions on both diabetic peripheral neuropathy, one of the main causes of foot ulcers, and on ulcer healing. Indeed, preclinical research in animal models of diabetes has revealed the trophic effect of NGF on small C-fibres, while phase 2 human trials have provided evidence for a favourable effect on sensory neuropathy. However, the results of a phase 3 trial were moderate and, therefore, not enough to encourage widespread use of NGF in the treatment of diabetic neuropathy. Available literature on the role of NGF on diabetic wound healing is sparse but encouraging. Exogenous supplementation of NGF or the use of alternative techniques to increase its endogenous expression could emerge as a protective and therapeutic modality for diabetic foot ulcers in addition to standard treatment and other growth factors. The present review provides an outlook on the role of NGF in the prophylaxis and treatment of diabetic foot ulcers. PMID:22928161

A systematic review of maggot debridement therapy for chronically infected wounds and ulcers.

PubMed

Sun, Xinjuan; Jiang, Kechun; Chen, Jingan; Wu, Liang; Lu, Hui; Wang, Aiping; Wang, Jianming

2014-08-01

This study aimed to systematically evaluate maggot debridement therapy (MDT) in the treatment of chronically infected wounds and ulcers. We performed a meta-analysis referring to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We searched for published articles in the following databases: PubMed, Web of Science, Embase, Wanfang (Chinese), and the China National Knowledge Infrastructure (CNKI). The latest search was updated on March 14, 2014. For dichotomous outcomes, the effects of MDT were expressed as the relative risk (RR) and 95% confidence interval (CI). For continuous outcomes with different measurement scales, we calculated the standardized mean difference (SMD). The pooled effects were estimated using a fixed effect model or random effect model based on the heterogeneity test. Subgroup analyses were performed according to the types of wounds or ulcers. MDT had a significantly increased positive effect on wound healing compared with conventional therapies, with a pooled RR of 1.80 (95% CI 1.24-2.60). The subgroup analysis revealed that the combined RRs were 1.79 (95% CI 0.95-3.38) for patients with diabetic foot ulcers (DFU) and 1.70 (95% CI 1.28-2.27) for patients with other types of ulcers. The time to healing of the ulcers was significantly shorter among patients treated with MDT, with a pooled SMD of -0.95 (95% CI -1.24, -0.65). For patients with DFU, the SMD was -0.79 (95% CI -1.18, -0.41), and for patients with other types of ulcers, the SMD was -1.16 (95% CI -1.63, -0.69). MDT not only shortened the healing time but also improved the healing rate of chronic ulcers. Therefore, MDT may be a feasible alternative in the treatment of chronic ulcers. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Compressed air massage hastens healing of the diabetic foot.

PubMed

Mars, M; Desai, Y; Gregory, M A

2008-02-01

The management of diabetic foot ulcers remains a problem. A treatment modality that uses compressed air massage has been developed as a supplement to standard surgical and medical treatment. Compressed air massage is thought to improve local tissue oxygenation around ulcers. The aim of this study was to determine whether the addition of compressed air massage influences the rate of healing of diabetic ulcers. Sixty consecutive patients with diabetes, admitted to one hospital for urgent surgical management of diabetic foot ulcers, were randomized into two groups. Both groups received standard medical and surgical management of their diabetes and ulcer. In addition, one group received 15-20 min of compressed air massage, at 1 bar pressure, daily, for 5 days a week, to the foot and the tissue around the ulcer. Healing time was calculated as the time from admission to the time of re-epithelialization. Fifty-seven patients completed the trial; 28 received compressed air massage. There was no difference in the mean age, Wagner score, ulcer size, pulse status, or peripheral sensation in the two groups. The time to healing in the compressed air massage group was significantly reduced: 58.1 +/- 22.3 days (95% confidence interval: 49.5-66.6) versus 82.7 +/- 30.7 days (95% confidence interval: 70.0-94.3) (P = 0.001). No adverse effects in response to compressed air massage were noted. The addition of compressed air massage to standard medical and surgical management of diabetic ulcers appears to enhance ulcer healing. Further studies with this new treatment modality are warranted.

A comparison of healing rates on two pressure-relieving systems.

PubMed

Russell, L; Reynolds, T; Carr, J; Evans, A; Holmes, M

The authors have previously reported the preliminary results of a randomized-controlled trial comparing the relative efficacy of two pressure-relieving systems: Huntleigh Nimbus 3 and Aura Cushion, and Pegasus Cairwave Therapy System and ProActive Seating Cushion (Russell et al, 2000). Although both the mattresses and cushions were effective treatments for pressure ulcers, the Huntleigh equipment was demonstrated to be statistically more effective for heel ulcers, but no differences were demonstrated for sacral ulcers. This article gives a more detailed analysis of the 141 patients assessed using computerized-image analysis of the digital images of sacral ulcers captured during the trial and specifically discusses the healing rates and other patient characteristics. Ninety-eight per cent of ulcers examined were deemed superficial (Torrance grade 2a, 2b, 3). Precision of image analysis assessed by within- and between-batch coefficients of variation was excellent: calibration CV 0.93-1.84%; area CV 4.61-5.72%. The healing rates on the two mattresses were not shown to be statistically different from each other.

Severity and duration of diabetic foot ulcer (DFU) before seeking care as predictors of healing time: A retrospective cohort study

PubMed Central

Iversen, Marjolein M.; Igland, Jannicke; Østbye, Truls; Graue, Marit; Skeie, Svein; Wu, Bei; Rokne, Berit

2017-01-01

Objectives To investigate whether A) duration of ulcer before start of treatment in specialist health care, and B) severity of ulcer according to University of Texas classification system (UT) at start of treatment (baseline), are independent predictors of healing time. Methods This retrospective cohort study, based on electronic medical record data, included 105 patients from two outpatient clinics in Western Norway with a new diabetic foot ulcer during 2009–2011. The associations of duration of ulcer and ulcer severity with healing time were assessed using cumulative incidence curves and subdistribution hazard ratio estimated using competing risk regression with adjustment for potential confounders. Results Of the 105 participants, 45.7% achieved ulcer healing, 36.2% underwent amputations, 9.5% died before ulcer healing and 8.5% were lost to follow-up. Patients who were referred to specialist health care by a general practitioner ≥ 52 days after ulcer onset had a 58% (SHR 0.42, CI 0.18–0.98) decreased healing rate compared to patients who were referred earlier, in the adjusted model. High severity (grade 2/3, stage C/D) according to the UT classification system was associated with a decreased healing rate compared to low severity (grade1, stage A/B or grade 2, stage A) with SHR (95% CI) equal to 0.14 (0.05–0.43) after adjustment for referral time and other potential confounders. Conclusion Early detection and referral by both the patient and general practitioner are crucial for optimal foot ulcer healing. Ulcer grade and severity are also important predictors for healing time, and early screening to assess the severity and initiation of prompt treatment is important. PMID:28498862

Influence of defunctionalization and mechanical forces on intestinal epithelial wound healing

PubMed Central

Kovalenko, Pavlo L.; Flanigan, Thomas L.; Chaturvedi, Lakshmi

2012-01-01

The influence on mucosal healing of luminal nutrient flow and the forces it creates are poorly understood. We hypothesized that altered deformation and extracellular pressure mediate, in part, the effects of defunctionalization on mucosal healing. We created patent or partially obstructing defunctionalizing jejunal Roux-en-Y anastomoses in rats to investigate mucosal healing in the absence or presence of luminal nutrient flow and measured luminal pressures to document partial obstruction. We used serosal acetic acid to induce ulcers in the proximal, distal, and defunctionalized intestinal segments. After 3 days, we assessed ulcer area, proliferation, and phosphorylated ERK. In vitro, we measured proliferation and migration in Caco-2 and IEC-6 intestinal epithelial cells subjected to cyclic strain, increased extracellular pressure, or strain and pressure together. Defunctionalization of intestine without obstruction reduced phosphorylated ERK, slowed ulcer healing, and inhibited mucosal proliferation. This outcome was blocked by PD-98059. Partial obstruction delayed ulcer healing but stimulated proliferation independently of ERK. In vitro, strain increased Caco-2 and IEC-6 proliferation and reduced migration across collagen but reduced proliferation and increased migration across fibronectin. In contrast, increased pressure and the combination of pressure and strain increased proliferation and reduced migration independently of substrate. PD-98059 reduced basal migration but increased migration under pressure. These results suggest that loss of the repetitive distension may decrease mucosal healing in defunctionalized bowel, while increased luminal pressure above anastomoses or in spastic bowel disease could further inhibit mucosal healing, despite peristaltic repetitive strain. ERK may mediate the effects of repetitive deformation but not the effects of pressure. PMID:22997197

Maggot therapy for chronic ulcer: a retrospective cohort and a meta-analysis.

PubMed

Wilasrusmee, Chumpon; Marjareonrungrung, Mongkol; Eamkong, Suwannee; Attia, John; Poprom, Napaphat; Jirasisrithum, Sopon; Thakkinstian, Ammarin

2014-07-01

Maggot wound therapy (MWT) has been used in various wounds including diabetic foot ulcers, venous leg ulcers, pressure ulcers, and acute surgical wounds. However, the efficacy of MWT therapy has been controversial. We therefore conducted a cohort study and a meta-analysis to assess MWT effects. A retrospective cohort study was performed in diabetic foot ulcer (DFU) patients who were treated with MWT or conventional wound therapy (CWT) in Thailand. The Kaplan-Meier curve was applied to estimate the healing probability. A meta-analysis was performed to pool our study with four previous cohort studies identified from Medline and Scopus. The estimated incidence of wound healing was 5.7/100 (95% CI: 4.49, 7.32) patients-week, and the median time to healing was 14 weeks. The hazard ratio (HR) of wound healing was 7.87 times significantly higher in the MWT than the CWT (p < 0.001) after adjusting for duration and size of ulcers, ankle brachial index (ABI), and glycated hemoglobin (HbA1c). Meta-analysis was applied and suggested that the treatment effects were moderately heterogeneous {Chi-square = 6.18 [degrees of freedom (d.f.) = 4]; p = 0.186; I(2) = 35.2%}, with the pooled risk ratio (RR) of 1.77 [95% confidence intervals (CI) = 1.01, 3.11], i.e., the chance of wound healing was 20% significantly higher with MWT than CWT. The average costs of treatment in patients with DFU were lower in the MWT group than in the CWT group, with medians of US$292.82 and US$490, respectively. Our evidence suggests that MWT is significantly better for wound healing and more cost-effective than CWT. An updated meta-analysis or large scale randomized controlled trial (RCT) is required to confirm this effect. Copyright © 2013. Published by Elsevier B.V.

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers.

PubMed

Takayama, Masaki; Matsui, Shigenaga; Kawasaki, Masanori; Asakuma, Yutaka; Sakurai, Toshiharu; Kashida, Hiroshi; Kudo, Masatoshi

2013-09-14

To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

A Chinese 2-herb formula (NF3) promotes hindlimb ischemia-induced neovascularization and wound healing of diabetic rats.

PubMed

Tam, Jacqueline Chor-Wing; Ko, Chun-Hay; Lau, Kit-Man; To, Ming-Ho; Kwok, Hin-Fai; Chan, Yuet-Wa; Siu, Wing-Sum; Etienne-Selloum, Nelly; Lau, Ching-Po; Chan, Wai-Yee; Leung, Ping-Chung; Fung, Kwok-Pui; Schini-Kerth, Valérie B; Lau, Clara Bik-San

2014-01-01

Diabetic foot ulcer is closely associated with peripheral vascular disease. Enhancement of tissue oxidative stress, reduction of nitric oxide (NO) and angiogenic growth factors, and abnormal matrix metalloproteinase (MMP) activity are pathophysiological factors in post-ischemic neovascularization and diabetic wound healing. Our previous study demonstrated that the Chinese 2-herb formula, NF3, showed significant wound healing effects on diabetic foot ulcer rats. A novel rat diabetic foot ulcer with hindlimb ischemia model was established in order to strengthen our claims on the diabetic wound healing and post-ischemic neovascularization effects of NF3. Our results demonstrate that NF3 can significantly reduce the wound area of the diabetic foot ulcer rat with hindlimb ischemia by 21.6% (p<0.05) compared with the control group. In addition, flow cytometric analysis revealed that NF3 could boost circulating EPC levels for local wound vessel incorporation. Immunohistochemical analysis showed that NF3 could significantly augment blood vessel density, VEGF and eNOS expression, and attenuate tissue oxidative stress of ischemic muscles (p<0.001). NF3 significantly stimulated MMP activity involved in angiogenesis. Our study shows, for the first time, the beneficial effects of NF3 in wound healing and post-ischemic neovascularization in diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

A shift in priority in diabetic foot care and research: 75% of foot ulcers are preventable.

PubMed

Bus, Sicco A; van Netten, Jaap J

2016-01-01

Diabetic foot ulceration poses a heavy burden on the patient and the healthcare system, but prevention thereof receives little attention. For every euro spent on ulcer prevention, ten are spent on ulcer healing, and for every randomized controlled trial conducted on prevention, ten are conducted on healing. In this article, we argue that a shift in priorities is needed. For the prevention of a first foot ulcer, we need more insight into the effect of interventions and practices already applied globally in many settings. This requires systematic recording of interventions and outcomes, and well-designed randomized controlled trials that include analysis of cost-effectiveness. After healing of a foot ulcer, the risk of recurrence is high. For the prevention of a recurrent foot ulcer, home monitoring of foot temperature, pressure-relieving therapeutic footwear, and certain surgical interventions prove to be effective. The median effect size found in a total of 23 studies on these interventions is large, over 60%, and further increases when patients are adherent to treatment. These interventions should be investigated for efficacy as a state-of-the-art integrated foot care approach, where attempts are made to assure treatment adherence. Effect sizes of 75-80% may be expected. If such state-of-the-art integrated foot care is implemented, the majority of problems with foot ulcer recurrence in diabetes can be resolved. It is therefore time to act and to set a new target in diabetic foot care. This target is to reduce foot ulcer incidence with at least 75%. Copyright © 2016 John Wiley & Sons, Ltd.

Effectiveness of acupuncture, special dressings and simple, low-adherence dressings for healing venous leg ulcers in primary healthcare: study protocol for a cluster-randomized open-labeled trial

PubMed Central

Vas, Jorge; Modesto, Manuela; Mendez, Camila; Perea-Milla, Emilio; Aguilar, Inmaculada; Carrasco-Lozano, Jesus Manuel; Faus, Vicente; Martos, Francisco

2008-01-01

Background Venous leg ulcers constitute a chronic recurring complaint that affects 1.0–1.3% of the adult population at some time in life, and which corresponds to approximately 75% of all chronic ulcers of the leg. Multilayer compression bandaging is, at present, the only treatment that has been proved to be effective in treating this type of ulcer. There is no consensus, however, about the dressings that may be applied, beneath the compression, to promote the healing of this type of ulcer, as there does not seem to be any added benefit from using special dressings rather than simple, low-adherence ones. As well as analgesia, acupuncture provokes peripheral vasodilation, in skin and muscles – which has been demonstrated both experimentally and in clinical practice – probably due to the axon reflex, among other mechanisms. The aim of the present study is to measure the effectiveness and cost of compression treatment for venous leg ulcers combined with special dressings, in comparison with low-adherence ones and acupuncture. Methods/design Cluster-randomized open-labeled trial, at 15 primary healthcare clinics in the Sevilla-Sur Healthcare District, with a control group treated with compression bandaging and low-adherence dressings; the experiment will consist, on the one hand, of the compression treatment applied in combination with special dressings (Treatment 1), and on the other, the compression treatment applied in association with low-adherence dressings, together with acupuncture (Treatment 2). Discussion The results will be measured and recorded in terms of the median time elapsed until complete healing of the ulcer, and the rate of complete healing at 3 months after beginning the treatment. An economic analysis will also be made. This study, carried out in the context of real clinical practice, will provide information for decision-taking concerning the effectiveness of special dressings. Moreover, for the first time a high-quality study will evaluate the effectiveness of acupuncture in the process of healing venous leg ulcers. Trial registration Current Controlled Trials ISRCTN26438275. PMID:18547419

Cost-effectiveness of wound management in France: pressure ulcers and venous leg ulcers.

PubMed

Meaume, S; Gemmen, E

2002-06-01

This study set out to define realistic protocols of care for the treatment of chronic venous leg ulcers and pressure ulcers in France and, by developing cost-effectiveness models, to compare the different protocols of care for the two ulcer groups, enabling a calculation of direct medical costs per ulcer healed in a typical French health insurance plan. Clinical outcomes and some treatment patterns were obtained from published literature. Validations of different treatment patterns were developed using an expert consensus panel similar to the Delphi approach. Costs were calculated based on national averages and estimates from the UK and Germany. The models were used to measure costs per healed ulcer over a 12-week period. For both the pressure ulcer and venous leg ulcer models, three protocols of care were identified. For pressure ulcers and venous leg ulcers, the hydrocolloid DuoDERM (ConvaTec, also known as Granuflex in the UK and Varihesive in Germany) was most cost-effective in France. The combination of published data and expert consensus opinion is a valid technique, and in this case suggests that treating pressure ulcers and venous leg ulcers with hydrocolloid dressings is more cost-effective than treating them with saline gauze, in spite of the lower unit cost of the latter.

Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study.

PubMed

Naganuma, Makoto; Aoyama, Nobuo; Tada, Tomohiro; Kobayashi, Kiyonori; Hirai, Fumihito; Watanabe, Kenji; Watanabe, Mamoru; Hibi, Toshifumi

2018-04-01

Budesonide foam is used for the topical treatment of distal ulcerative colitis. This phase III study was performed to confirm mucosal healing and other therapeutic effects of twice-daily budesonide 2-mg foam in patients with mild-to-moderate ulcerative colitis including left-sided colitis and pancolitis. This was a multicenter, randomized, placebo-controlled, double-blind trial. A total of 126 patients with mild-to-moderate ulcerative colitis with active inflammation in the distal colon were randomized to two groups receiving twice-daily budesonide 2 mg/25 ml foam or placebo foam. The primary endpoint was the percentage of complete mucosal healing of distal lesions (endoscopic subscore of 0) at week 6. Some patients continued the treatment through week 12. Drug efficacy and safety were evaluated. The percentages of both complete mucosal healing of distal lesions and clinical remission were significantly improved in the budesonide as compared with the placebo group (p = 0.0003 and p = 0.0035). Subgroup analysis showed similar efficacy of budesonide foam for complete mucosal healing of distal lesions and clinical remission regardless of disease type. The clinical remission percentage tended to be higher in patients achieving complete mucosal healing of distal lesions than in other patients. There were no safety concerns with budesonide foam. This study confirmed for the first time complete mucosal healing with twice-daily budesonide 2-mg foam in mild-to-moderate ulcerative colitis with distal active inflammation. The results also indicated that complete mucosal healing of distal lesions by budesonide foam promotes clinical remission of ulcerative colitis. Clinical trial registration no.: Japic CTI-142704.

Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy.

PubMed

Daróczy, Judit

2006-01-01

The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema. To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers. 63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection. Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%). Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas).

Increased healing in diabetic toe ulcers in a multidisciplinary foot clinic-An observational cohort study.

PubMed

Almdal, T; Nielsen, A Anker; Nielsen, K E; Jørgensen, M E; Rasmussen, A; Hangaard, S; Siersma, V; Holstein, P E

2015-12-01

To study toe ulcer healing in patients with diabetic foot ulcers attending a multidisciplinary foot clinic over a 10 years period. The study was retrospective, consecutive and observational during 2001 through 2011. The patients were treated according to the International Consensus on the Diabetic Foot. During the period the chiropodist staffing in the foot clinic was doubled; new offloading material and orthopedic foot corrections for recalcitrant ulcers were introduced. Healing was investigated in toe ulcers in Cox regression models. 2634 patients developed foot ulcers, of which 1461 developed toe ulcers; in 790 patients these were neuropathic, in 551 they were neuro-ischemic and in 120 they were critically ischemic. One-year healing rates increased in the period 2001-2011 from 75% to 91% for neuropathic toe ulcers and from 72% to 80% for neuro-ischemic toe ulcers, while no changes was observed for ischemic toe ulcers. Adjusted for changes in the patient population, the overall rate of healing for neuropathic and neuro-ischemic toe ulcers almost doubled (HR=1.95 [95% CI: 1.36-2.80]). The results show that the healing of toe ulcers improved. This outcome could not be explained by changes in the patient characteristics, but coincided with a number of improvements in organization and therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of low-strength compression stockings with bandages for the treatment of recalcitrant venous ulcers.

PubMed

Brizzio, Eugenio; Amsler, Felix; Lun, Bertrand; Blättler, Werner

2010-02-01

To compare the proportion and rate of healing, pain, and quality of life of low-strength medical compression stockings (MCS) with traditional bandages applied for the treatment of recalcitrant venous leg ulcers. A single-center, randomized, open-label study was performed with consecutive patients. Sigvaris prototype MCS providing 15 mm Hg-25 mm Hg at the ankle were compared with multi-layer short-stretch bandages. In both groups, pads were placed above incompetent perforating veins in the ulcer area. The initial static pressure between the dressing-covered ulcer and the pad was 29 mm Hg and 49 mm Hg with MCS and bandages, respectively. Dynamic pressure measurements showed no difference. Compression was maintained day and night and changed every week. The primary endpoint was healing within 90 days. Secondary endpoints were healing within 180 days, time to healing, pain (weekly Likert scales), and monthly quality of life (ChronIc Venous Insufficiency Quality of Life [CIVIQ] questionnaire). Of 74 patients screened, 60 fulfilled the selection criteria and 55 completed the study; 28 in the MCS and 27 in the bandage group. Ulcers were recurrent (48%), long lasting (mean, 27 months), and large (mean, 13 cm2). All but one patient had deep venous reflux and/or incompetent perforating veins in addition to trunk varices. Characteristics of patients and ulcers were evenly distributed (exception: more edema in the MCS group; P = .019). Healing within 90 days was observed in 36% with MCS and in 48% with bandages (P = .350). Healing within 180 days was documented in 50% with MCS and in 67% with bandages (P = .210). Time to healing was identical. Pain scored 44 and 46 initially (on a scale in which 100 referred to maximum and 0 to no pain) and decreased within the first week to 20 and 28 in the MCS and bandage groups, respectively (P < .001 vs .010). Quality of life showed no difference between the treatment groups. In both groups, pain at 90 days had decreased by half, independent of completion of healing. Physical, social, and psychic impairment improved significantly in patients with healed ulcers only. Our study illustrates the difficulty of bringing large and long-standing venous ulcers to heal. The effect of compression with MCS was not different from that of compression with bandages. Both treatments alleviated pain promptly. Quality of life was improved only in patients whose ulcers had healed. Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Pentoxifylline for treating venous leg ulcers.

PubMed

Jull, A; Arroll, B; Parag, V; Waters, J

2007-07-18

Healing of venous leg ulcers is improved by the use of compression bandaging but some venous ulcers remain unhealed, and some people are unsuitable for compression therapy. Pentoxifylline, a drug which helps blood flow, has been used to treat venous leg ulcers. An earlier version of this review included 9 randomised controlled trials, but more research has been since been conducted and an updated review is required. To assess the effects of pentoxifylline (oxpentifylline or Trental 400) for treating venous leg ulcers, compared with placebo, or other therapies, in the presence or absence of compression therapy. For this second update we searched the Cochrane Wounds Group Specialised Register, CENTRAL, MEDLINE, EMBASE and Cinahl (date of last search was February 2007), and reference lists of relevant articles. Randomised trials comparing pentoxifylline with placebo or other therapy in the presence or absence of compression, in people with venous leg ulcers. Details from eligible trials were extracted and summarised by one author using a coding sheet. Data extraction was independently verified by one other author. Twelve trials involving 864 participants were included. The quality of trials was variable. Eleven trials compared pentoxifylline with placebo or no treatment; in seven of these trials patients received compression therapy. In one trial pentoxifylline was compared with defibrotide in patients who also received compression. Combining 11 trials that compared pentoxifylline with placebo or no treatment (with or without compression) demonstrated that pentoxifylline is more effective than placebo in terms of complete ulcer healing or significant improvement (RR 1.70, 95% CI 1.30 to 2.24). Significant heterogeneity was associated with differences in sample populations (hard-to-heal samples compared with "normal" healing samples). Pentoxifylline plus compression is more effective than placebo plus compression (RR 1.56, 95% CI 1.14 to 2.13). Pentoxifylline in the absence of compression appears to be more effective than placebo or no treatment (RR 2.25, 95% CI 1.49 to 3.39). A comparison between pentoxifylline and defibrotide found no statistically significant difference in healing rates. More adverse effects were reported in people receiving pentoxifylline (RR 1.56, 95% CI 1.10 to 2.22). Nearly three-quarters (72%) of the reported adverse effects were gastrointestinal. Pentoxifylline is an effective adjunct to compression bandaging for treating venous ulcers and may be effective in the absence of compression. The majority of adverse effects were gastrointestinal disturbances.

A prospective randomised trial of four-layer versus short stretch compression bandages for the treatment of venous leg ulcers.

PubMed Central

Scriven, J. M.; Taylor, L. E.; Wood, A. J.; Bell, P. R.; Naylor, A. R.; London, N. J.

1998-01-01

This trial was undertaken to examine the safety and efficacy of four-layer compared with short stretch compression bandages for the treatment of venous leg ulcers within the confines of a prospective, randomised, ethically approved trial. Fifty-three patients were recruited from a dedicated venous ulcer assessment clinic and their individual ulcerated limbs were randomised to receive either a four-layer bandage (FLB)(n = 32) or a short stretch bandage (SSB)(n = 32). The endpoint was a completely healed ulcer. However, if after 12 weeks of compression therapy no healing had been achieved, that limb was withdrawn from the study and deemed to have failed to heal with the prescribed bandage. Leg volume was measured using the multiple disc model at the first bandaging visit, 4 weeks later, and on ulcer healing. Complications arising during the study were recorded. Data from all limbs were analysed on an intention to treat basis; thus the three limbs not completing the protocol were included in the analysis. Of the 53 patients, 50 completed the protocol. At 1 year the healing rate was FLB 55% and SSB 57% (chi 2 = 0.0, df = 1, P = 1.0). Limbs in the FLB arm of the study sustained one minor complication, whereas SSB limbs sustained four significant complications. Leg volumes reduced significantly after 4 weeks of compression, but subsequent volume changes were insignificant. Ulcer healing rates were not influenced by the presence of deep venous reflux, post-thrombotic deep vein changes nor by ulcer duration. Although larger ulcers took longer to heal, the overall healing rates for large (> 10 cm2) and small (10 cm2 or less) ulcers were comparable. Four-layer and short stretch bandages were equally efficacious in healing venous ulcers independent of pattern of venous reflux, ulcer area or duration. FLB limbs sustained fewer complications than SSB. PMID:9682649

Stress, Illness Perceptions, Behaviors, and Healing in Venous Leg Ulcers: Findings From a Prospective Observational Study.

PubMed

Walburn, Jessica; Weinman, John; Norton, Sam; Hankins, Matthew; Dawe, Karen; Banjoko, Bolatito; Vedhara, Kavita

2017-06-01

The aim of the study was to investigate the impact of stress, illness perceptions, and behaviors on healing of venous leg ulcers. A prospective observational study of 63 individuals for 24 weeks investigated possible psychosocial predictors of healing. There were two indices of healing: rate of change in ulcer area and number of weeks to heal. Psychological variables were assessed at baseline using self-report measures (Perceived Stress Scale, Hospital Anxiety and Depression Scale, Revised Illness Perception Questionnaire, adapted Summary of Diabetes Self-Care Activities, Adherence Questionnaire, and Short-Form Health Survey). Controlling for sociodemographic and clinical variables, for the 24 weeks, a slower rate of change in ulcer area was predicted by greater stress (standardized β = -0.61, p = .008), depression (standardized β = -0.51, p = .039), and holding negative perceptions or beliefs about the ulcer (standardized β = -1.4, p = .045). By 24 weeks, 69% of ulcers had closed. A more negative emotional response to the ulcer at baseline (i.e., emotional representation of the ulcer) was associated with a greater number of weeks to heal (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.41-0.95, p = .028). Higher educational attainment (HR = 3.22, 95% CI = 1.37-7.55, p = .007) and better adherence to compression bandaging (HR = 1.41, 95% CI = 1.06-1.88, p = .019) were associated with fewer weeks to heal. No other psychosocial variable (stress, perceptions about the ulcer, health behaviors) predicted weeks to heal. Alongside ulcer-related predictors, psychological and sociodemographic factors were associated with healing. Future research should explore mediating mechanisms underlying these associations and develop interventions to target these variables.

Stress, Illness Perceptions, Behaviors, and Healing in Venous Leg Ulcers: Findings From a Prospective Observational Study

PubMed Central

Walburn, Jessica; Weinman, John; Norton, Sam; Hankins, Matthew; Dawe, Karen; Banjoko, Bolatito; Vedhara, Kavita

2017-01-01

ABSTRACT Objective The aim of the study was to investigate the impact of stress, illness perceptions, and behaviors on healing of venous leg ulcers. Methods A prospective observational study of 63 individuals for 24 weeks investigated possible psychosocial predictors of healing. There were two indices of healing: rate of change in ulcer area and number of weeks to heal. Psychological variables were assessed at baseline using self-report measures (Perceived Stress Scale, Hospital Anxiety and Depression Scale, Revised Illness Perception Questionnaire, adapted Summary of Diabetes Self-Care Activities, Adherence Questionnaire, and Short-Form Health Survey). Results Controlling for sociodemographic and clinical variables, for the 24 weeks, a slower rate of change in ulcer area was predicted by greater stress (standardized β = −0.61, p = .008), depression (standardized β = −0.51, p = .039), and holding negative perceptions or beliefs about the ulcer (standardized β = −1.4, p = .045). By 24 weeks, 69% of ulcers had closed. A more negative emotional response to the ulcer at baseline (i.e., emotional representation of the ulcer) was associated with a greater number of weeks to heal (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.41-0.95, p = .028). Higher educational attainment (HR = 3.22, 95% CI = 1.37–7.55, p = .007) and better adherence to compression bandaging (HR = 1.41, 95% CI = 1.06–1.88, p = .019) were associated with fewer weeks to heal. No other psychosocial variable (stress, perceptions about the ulcer, health behaviors) predicted weeks to heal. Conclusions Alongside ulcer-related predictors, psychological and sociodemographic factors were associated with healing. Future research should explore mediating mechanisms underlying these associations and develop interventions to target these variables. PMID:27941577

Efficacy of Rhizophora mangle aqueous bark extract (RMABE) in the treatment of aphthous ulcers: a pilot study.

PubMed

de Armas, Elizabeth; Sarracent, Yamina; Marrero, Eva; Fernández, Octavio; Branford-White, Christopher

2005-11-01

Rhizophora mangle aqueous bark extract (RMABE) (CIKRON-H), has been used as antiseptic and skin wound healing promoter. The present study was a randomised, single-blinded, placebo control trial conducted to asses the efficacy of RMABE in treating oral aphthous ulcers. Patients (n = 32) with aphthous ulcers were randomised to received placebo solution or RMABE topically, once a day, from Monday to Friday, until they healed. The efficacy of the treatment was evaluated by physician clinical observations (time to heal, change in condition), the quality of the patient's life and the tolerability through recording adverse effects. No demographic differences were noted between the two groups at base-line. Seven days after treatment, 12 of the 17 patients in the RMABE group (71%) were completely healed of their aphthous ulcers, with repaired mucosa and no symptoms of ulcers, compared with one in 15 patients in the placebo group (7%) (p < 0.0001). The time taken for the signs and symptoms of ulcers to diminish was also higher in the placebo than in RMABE-treatment group (erythema: placebo 10.54 +/- 1.24, RMABE 4.94 +/- 0.72 days, p = 0.0003; ardour: placebo 7.00 +/- 0.76, RMABE 2.93 +/- 0.49 days, p = 0.0001; and pain: placebo 7.43 +/- 1.21, RMABE 2.92 +/- 0.23 days, p = 0.0011). No subject showed any sign of adverse effects. These observations demonstrate that the R. mangle aqueous bark extract reduced the time to repair mucosal tissue, erythema, ardour and pain persistence. There was no evidence any adverse effects. This is the first time that the R. mangle extract has been reported to have mouth mucosa healing properties.

A pilot study on the effects of a polyherbal formulation cream on diabetic foot ulcers

PubMed Central

Viswanathan, Vijay; Kesavan, Rajesh; Kavitha, K.V.; Kumpatla, Satyavani

2011-01-01

Background & objectives: Diabetic foot ulcers are the most common cause of non-traumatic lower extremity amputations in developing countries. The aim of this pilot study was to evaluate the safety of using a polyherbal formulation in healing diabetic foot ulcers in comparison with standard silver sulphadiazine cream among patients with type 2 diabetes. Methods: A total of 40 (M:F=29:14) consecutive type 2 diabetes patients with foot ulcers were enrolled in this study. They were randomly assigned to two groups of 20 each; Group 1 was treated with polyherbal formulation and group 2 with silver sulphadiazine cream. All the patients were followed up for a period of 5 months. The baseline ulcer size was noted and photograph of the wound was taken at the baseline and at each follow up visit. Number of days taken for healing of the wound was recorded. Results: The mean age of patients, duration of diabetes and HbA1c% were similar in both the study groups. The mean length and width of the ulcers was also similar in both the groups at baseline visit. There was a significant decrease in the size of the wound (length and width) in both the study groups (P<0.001). The mean time taken for the healing of the ulcer was around 43 days in both groups. Interpretation & conclusions: Diabetic wound cream prepared by using polyherbal formulation was found to be effective as well as safe in healing diabetic foot ulcers like the standard silver sulphadiazine cream. PMID:21911968

Use of an autologous leucocyte and platelet-rich fibrin patch on hard-to-heal DFUs: a pilot study.

PubMed

Löndahl, M; Tarnow, L; Karlsmark, T; Lundquist, R; Nielsen, A M; Michelsen, M; Nilsson, A; Zakrzewski, M; Jörgensen, B

2015-04-01

Leucopatch is a leukocyte and platelet-rich fibrin patch that provides concentrated blood cells and signal substances to the surface of an ulcer. It is produced by centrifugation of the patient's own venous blood. The aim of this pilot multicentre cohort study was to evaluate effects of the leucocyte patch in patients with hard-to-heal diabetic foot ulcers (DFUs). Non-ischaemic Wagner grade 1 or 2 DFUs with a duration of more than 6 weeks and a maximal area of 10cm² were included. Patients with >40% ulcer area change during a two-week run-in period were excluded. The treatment was applied once a week for up to 19 treatments or until the foot ulcer was completely epithelialised. The primary endpoint was healing within 20 weeks. Of the 60 patients who gave consent 16 were excluded during run-in period, 44 patients initiated study treatment and 39 were included in the per-protocol analysis. Complete epithelisation was achieved in 34% (per-protocol analysis 36%) at 12 weeks and 52% (59%) at 20 weeks. In patients with ulcer duration less than 6 months, 73% of ulcers healed within 20 weeks. Patients with healed ulcers had larger ulcer area reduction during the first two treatment weeks compared to non-healers. Adverse events were mild and rare. The leucocyte patch is well-tolerated, easy to use and has potential in the armamentarium of the DFU treatment, provided this outcome is confirmed in an appropriately powered randomised clinical trial.

Piper umbellatum L.: A medicinal plant with gastric-ulcer protective and ulcer healing effects in experimental rodent models.

PubMed

da Silva Junior, Iberê Ferreira; Balogun, Sikiru Olaitan; de Oliveira, Ruberlei Godinho; Damazo, Amílcar Sabino; Martins, Domingos Tabajara de Oliveira

2016-11-04

Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti-ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed. The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA + and vacA + strain. The probable mechanism of action of HEPu was evaluated by determining gastric secretory parameters, antioxidant enzyme (catalase), non-protein sulfhydryl (glutathione) and malondialdehyde levels in gastric tissue, including pro-inflammatory (IL-1β, TNF-a, IL -17, RANTES, IFN-γ and MIP-2) and anti-inflammatory (IL-10) cytokines. HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti-inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity. The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is independent of anti-H. pylori activity, with substances probably responsible for the pharmacological activity being flavonoids, quercetin and rutin. These results support the popular use of P. umbellatum leaves in the treatment of peptic ulcers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Skin graft

MedlinePlus

... that need skin grafts to heal Venous ulcers, pressure ulcers , or diabetic ulcers that do not heal Very ... graft; Full thickness skin graft Patient Instructions Preventing pressure ulcers Surgical wound care - open Images Skin graft Skin ...

High probability of healing without amputation of plantar forefoot ulcers in patients with diabetes.

PubMed

Örneholm, Hedvig; Apelqvist, Jan; Larsson, Jan; Eneroth, Magnus

2015-01-01

Diabetic foot ulcer is an important entity which in many cases is the first serious complication in diabetes. Although a plantar forefoot location is common, there are few studies on larger cohorts and in such studies there is often a combination of various types of ulcer and ulcer locations. The purpose of this study is to discern the outcome of plantar forefoot ulcers and their specific characteristics in a large cohort. All patients (n = 770), presenting with a plantar forefoot ulcer at a multidisciplinary diabetes foot clinic from January 1, 1983 to December 31, 2012 were considered for the study. Seven hundred one patients (median age 67 [22-95]) fulfilled the inclusion criteria and were followed according to a preset protocol until final outcome (healing or death). Severe peripheral vascular disease was present in 26% of the patients and 14% had evidence of deep infection upon arrival at the foot clinic. Fifty-five percent (385/701) of the patients healed without foot surgery, 25% (173/701) healed after major debridement, 9% (60/701) healed after minor or major amputation and 12% (83/701) died unhealed. Median healing time was 17 weeks. An ulcer classified as Wagner grade 1 or 2 at inclusion and independent living were factors associated with a higher healing rate. Seventy-nine percent of 701 patients with diabetes and a plantar forefoot ulcer treated at a multidisciplinary diabetes foot clinic healed without amputation. For one third some form of foot surgery was needed to achieve healing. © 2015 by the Wound Healing Society.

Evaluation of the Efficacy of Highly Hydrophilic Polyurethane Foam Dressing in Treating a Diabetic Foot Ulcer.

PubMed

Jung, Jae-A; Yoo, Ki-Hyun; Han, Seung-Kyu; Dhong, Eun-Sang; Kim, Woo-Kyung

2016-12-01

To demonstrate the efficacy of a highly hydrophilic polyurethane foam dressing in the treatment of diabetic ulcers. Diabetic foot ulcers often pose a difficult treatment problem. Polyurethane foam dressings have been used worldwide to accelerate wound healing, but only a few clinical studies demonstrate the effect of foam dressing on the healing of diabetic ulcers. Medical records of 1342 patients with diabetic ulcers who were admitted and treated at the authors' institution were reviewed. A total of 208 patients met the study's inclusion criteria. Of these 208 patients, 137 were treated with a highly hydrophilic polyurethane foam dressing, and 71 were treated with saline gauze (control group). Except for the application of polyurethane foam dressing, the treatment method was identical for patients in both groups. The wound healing outcomes of the 2 groups were compared. Complete wound healing occurred in 87 patients (63.5%) in the polyurethane foam dressing group and in 28 patients (39.4%) in the control group within 12 weeks (P < .05, X test). The mean percentage of wound area reduction in both groups was statistically significant (P < .05, Mann-Whitney U test). The mean time required for complete closure in patients who achieved complete healing within 12 weeks was 6.2 (SD, 3.4) weeks and 7.3 (SD, 2.6) weeks in the polyurethane foam dressing and control groups, respectively (P < .05, Mann-Whitney U test). These results indicate that the highly hydrophilic polyurethane foam dressing may provide an effective treatment strategy for diabetic foot ulcers.

Laboratory and clinical data on wound healing by low-power laser from the Medical Institute of Vilafortuny, Spain

NASA Astrophysics Data System (ADS)

Trelles, Mario A.; Mayayo, E.; Resa, A. M.; Rigau, Josepa; Calvo, G.

1991-05-01

Low power laser has been claimed, both at laboratory and for clinical treatment to activate wound healing. Chronic ulcers respond very positively to laser treatment when particular rules of irradiation are take into account. The multiple etiology of chronic ulcers is not conductive to treatment selection, including laser treatment, if the associated illness is not taken into consideration. For more than 14 years our clinical experience have been significantly positive using lasers in the treatment of chronic ulcers. Our causistic, based on 242 cases treated from 1975 through 1983, has kept in many cases very close follow-up for an extended time periods of up to six years after healing. By controlling photographically and microscopically a chronic venous ulcer submitted to low density laser irradiation, as well as by studying the process of reparation of experimental ulcers and burns, produce on laboratory animal, the healing effects of laser radiation can be followed. Statistically, it is possible to estimate that low intensity laser irradiation produces faster reparation of damage tissue.

Polysaccharide of Black cumin (Nigella sativa) modulates molecular signaling cascade of gastric ulcer pathogenesis.

PubMed

Manjegowda, Srikanta Belagihalli; Rajagopal, Harsha Mysore; Dharmesh, Shylaja Mallaiah

2017-08-01

Gastric ulcer is a multi-step disease and healing requires a complex process including repair and re-architecture of gastric mucosa with the involvement of molecular events. Current study was designed to understand the gastric ulcer healing mechanism of rhamnogalacturonan-I type pectic polysaccharide of black cumin (BCPP) utilizing acetic acid induced gastric ulcers in rats. BCPP fed groups at 200mg/kg b.w. for 10days showed up to 85% healing of gastric ulcers with modulation of key molecular events involved in ulcer healing process such as increase in gastric mucin content, cyclooxygenase-2 (Cox-2) and prostaglandin E 2 (PGE 2 ). The increase in extracellular signal-regulated kinase-2 (ERK-2) indicated that, BCPP could induce PGE-2 synthesis by increasing ERK-2 mediated COX-2 activity. Increase in matrix metalloproteinase-2 (MMP-2) and decrease in MMP-9 levels in BCPP treated groups indicated differential regulation of MMP-2 and 9, an essential event required for gastric mucosal re-modulation. BCPP containing bound phenolics (26mg/g) might have also played a role in increasing speed and quality of ulcer healing by inhibiting H + , K + -ATPase and decreasing free radical mediated oxidation and cellular damages. Overall, studies showed that the polysaccharide can mediate ulcer healing by modulating signaling pathways involved in either ulcer aggravation or healing process. Copyright © 2017. Published by Elsevier B.V.

Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair.

PubMed

Xia, Dong-Lin; Chen, Yan-Pei; Wang, Yu-Fei; Li, Xiao-Dong; Bao, Ning; He, Hong; Gu, Hai-Ying

2016-11-01

Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers. The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated. The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation. Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors' study suggests a novel strategy for ulcer healing.

The influence of a change in medicare reimbursement on the effectiveness of stage III or greater decubitus ulcer home health nursing care.

PubMed

Eaton, Melody K

2005-02-01

This study was designed to describe and evaluate the influence of a change in a Medicare reimbursement on the effectiveness of home health nursing care for stage III or greater decubitus ulcer patients. This health policy originated from the Balanced Budget Act (BBA) of 1997 and took its full effect with initiation of the Prospective Payment System (PPS) on October 1, 2000. A quantitative quasi-experimental design used OASIS data from the state of Virginia to evaluate 555 stage III or greater decubitus ulcer patients, age 65 or older. Comparisons were investigated between pre-PPS, 2000, and post-PPS, 2001, outcomes related to reported ulcer healing, lengths of stay, and discharge disposition. Results demonstrated significant differences for the outcomes studied. In addition, sanitation, ulcer healing, and discharge disposition were linked as predictors for length of stay. Results demonstrated that PPS has affected nursing care effectiveness for stage III or greater decubitus ulcer home health patients.

Management of Chronic Pressure Ulcers

PubMed Central

2009-01-01

Executive Summary In April 2008, the Medical Advisory Secretariat began an evidence-based review of the literature concerning pressure ulcers. Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/tech/tech_mn.html to review these titles that are currently available within the Pressure Ulcers series. Pressure ulcer prevention: an evidence based analysis The cost-effectiveness of prevention strategies for pressure ulcers in long-term care homes in Ontario: projections of the Ontario Pressure Ulcer Model (field evaluation) Management of chronic pressure ulcers: an evidence-based analysis Objective The Medical Advisory Secretariat (MAS) conducted a systematic review on interventions used to treat pressure ulcers in order to answer the following questions: Do currently available interventions for the treatment of pressure ulcers increase the healing rate of pressure ulcers compared with standard care, a placebo, or other similar interventions? Within each category of intervention, which one is most effective in promoting the healing of existing pressure ulcers? Background A pressure ulcer is a localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in conjunction with shear and/or friction. Many areas of the body, especially the sacrum and the heel, are prone to the development of pressure ulcers. People with impaired mobility (e.g., stroke or spinal cord injury patients) are most vulnerable to pressure ulcers. Other factors that predispose people to pressure ulcer formation are poor nutrition, poor sensation, urinary and fecal incontinence, and poor overall physical and mental health. The prevalence of pressure ulcers in Ontario has been estimated to range from a median of 22.1% in community settings to a median of 29.9% in nonacute care facilities. Pressure ulcers have been shown to increase the risk of mortality among geriatric patients by as much as 400%, to increase the frequency and duration of hospitalization, and to decrease the quality of life of affected patients. The cost of treating pressure ulcers has been estimated at approximately $9,000 (Cdn) per patient per month in the community setting. Considering the high prevalence of pressure ulcers in the Ontario health care system, the total cost of treating pressure ulcers is substantial. Technology Wounds normally heal in 3 phases (inflammatory phase, a proliferative phase of new tissue and matrix formation, and a remodelling phase). However, pressure ulcers often fail to progress past the inflammatory stage. Current practice for treating pressure ulcers includes treating the underlying causes, debridement to remove necrotic tissues and contaminated tissues, dressings to provide a moist wound environment and to manage exudates, devices and frequent turning of patients to provide pressure relief, topical applications of biologic agents, and nutritional support to correct nutritional deficiencies. A variety of adjunctive physical therapies are also in use. Method Health technology assessment databases and medical databases were searched from 1996 (Medline), 1980 (EMBASE), and 1982 (CINAHL) systematically up to March 2008 to identify randomized controlled trials (RCTs) on the following treatments of pressure ulcers: cleansing, debridement, dressings, biological therapies, pressure-relieving devices, physical therapies, nutritional therapies, and multidisciplinary wound care teams. Full literature search strategies are reported in appendix 1. English-language studies in previous systematic reviews and studies published since the last systematic review were included if they had more than 10 subjects, were randomized, and provided objective outcome measures on the healing of pressure ulcers. In the absence of RCTs, studies of the highest level of evidence available were included. Studies on wounds other than pressure ulcers and on surgical treatment of pressure ulcers were excluded. A total of 18 systematic reviews, 104 RCTs, and 4 observational studies were included in this review. Data were extracted from studies using standardized forms. The quality of individual studies was assessed based on adequacy of randomization, concealment of treatment allocation, comparability of groups, blinded assessment, and intention-to-treat analysis. Meta-analysis to estimate the relative risk (RR) or weighted mean difference (WMD) for measures of healing was performed when appropriate. A descriptive synthesis was provided where pooled analysis was not appropriate or not feasible. The quality of the overall evidence on each intervention was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) criteria. Findings Findings from the analysis of the included studies are summarized below: Cleansing There is no good trial evidence to support the use of any particular wound cleansing solution or technique for pressure ulcers. Debridement There was no evidence that debridement using collagenase, dextranomer, cadexomer iodine, or maggots significantly improved complete healing compared with placebo. There were no statistically significant differences between enzymatic or mechanical debridement agents with the following exceptions: Papain urea resulted in better debridement than collagenase. Calcium alginate resulted in a greater reduction in ulcer size compared to dextranomer. Adding streptokinase/streptodornase to hydrogel resulted in faster debridement. Maggot debridement resulted in more complete debridement than conventional treatment. There is limited evidence on the healing effects of debridement devices. Dressings Hydrocolloid dressing was associated with almost three-times more complete healing compared with saline gauze. There is evidence that hydrogel and hydropolymer may be associated with 50% to 70% more complete healing of pressure ulcers than hydrocolloid dressing. No statistically significant differences in complete healing were detected among other modern dressings. There is evidence that polyurethane foam dressings and hydrocellular dressings are more absorbent and easier to remove than hydrocolloid dressings in ulcers with moderate to high exudates. In deeper ulcers (stage III and IV), the use of alginate with hydrocolloid resulted in significantly greater reduction in the size of the ulcers compared to hydrocolloid alone. Studies on sustained silver-releasing dressing demonstrated a tendency for reducing the risk of infection and promoting faster healing, but the sample sizes were too small for statistical analysis or for drawing conclusions. Biological Therapies The efficacy of platelet-derived growth factors (PDGFs), fibroblast growth factor, and granulocyte-macrophage colony stimulating factor in improving complete healing of chronic pressure ulcers has not been established. Presently only Regranex, a recombinant PDGF, has been approved by Health Canada and only for treatment of diabetic ulcers in the lower extremities. A March 2008 US Food and Drug Administration (FDA) communication reported increased deaths from cancers in people given three or more prescriptions for Regranex. Limited low-quality evidence on skin matrix and engineered skin equivalent suggests a potential role for these products in healing refractory advanced chronic pressure ulcers, but the evidence is insufficient to draw a conclusion. Adjunctive Physical Therapy There is evidence that electrical stimulation may result in a significantly greater reduction in the surface area and more complete healing of stage II to IV ulcers compared with sham therapy. No conclusion on the efficacy of electrotherapy can be drawn because of significant statistical heterogeneity, small sample sizes, and methodological flaws. The efficacy of other adjunctive physical therapies [electromagnetic therapy, low-level laser (LLL) therapy, ultrasound therapy, ultraviolet light therapy, and negative pressure therapy] in improving complete closure of pressure ulcers has not been established. Nutrition Therapy Supplementation with 15 grams of hydrolyzed protein 3 times daily did not affect complete healing but resulted in a 2-fold improvement in Pressure Ulcer Scale for Healing (PUSH) score compared with placebo. Supplementation with 200 mg of zinc three times per day did not have any significant impact on the healing of pressure ulcers compared with a placebo. Supplementation of 500 mg ascorbic acid twice daily was associated with a significantly greater decrease in the size of the ulcer compared with a placebo but did not have any significant impact on healing when compared with supplementation of 10 mg ascorbic acid three times daily. A very high protein tube feeding (25% of energy as protein) resulted in a greater reduction in ulcer area in institutionalized tube-fed patients compared with a high protein tube feeding (16% of energy as protein). Multinutrient supplements that contain zinc, arginine, and vitamin C were associated with a greater reduction in the area of the ulcers compared with standard hospital diet or to a standard supplement without zinc, arginine, or vitamin C. Firm conclusions cannot be drawn because of methodological flaws and small sample sizes. Multidisciplinary Wound Care Teams The only RCT suggests that multidisciplinary wound care teams may significantly improve healing in the acute care setting in 8 weeks and may significantly shorten the length of hospitalization. However, since only an abstract is available, study biases cannot be assessed and no conclusions can be drawn on the quality of this evidence. PMID:23074533

Management of chronic pressure ulcers: an evidence-based analysis.

PubMed

2009-01-01

In April 2008, the Medical Advisory Secretariat began an evidence-based review of the literature concerning pressure ulcers.Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/tech/tech_mn.html to review these titles that are currently available within the Pressure Ulcers series.PRESSURE ULCER PREVENTION: an evidence based analysisThe cost-effectiveness of prevention strategies for pressure ulcers in long-term care homes in Ontario: projections of the Ontario Pressure Ulcer Model (field evaluation)MANAGEMENT OF CHRONIC PRESSURE ULCERS: an evidence-based analysis The Medical Advisory Secretariat (MAS) conducted a systematic review on interventions used to treat pressure ulcers in order to answer the following questions: Do currently available interventions for the treatment of pressure ulcers increase the healing rate of pressure ulcers compared with standard care, a placebo, or other similar interventions?Within each category of intervention, which one is most effective in promoting the healing of existing pressure ulcers? A pressure ulcer is a localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in conjunction with shear and/or friction. Many areas of the body, especially the sacrum and the heel, are prone to the development of pressure ulcers. People with impaired mobility (e.g., stroke or spinal cord injury patients) are most vulnerable to pressure ulcers. Other factors that predispose people to pressure ulcer formation are poor nutrition, poor sensation, urinary and fecal incontinence, and poor overall physical and mental health. The prevalence of pressure ulcers in Ontario has been estimated to range from a median of 22.1% in community settings to a median of 29.9% in nonacute care facilities. Pressure ulcers have been shown to increase the risk of mortality among geriatric patients by as much as 400%, to increase the frequency and duration of hospitalization, and to decrease the quality of life of affected patients. The cost of treating pressure ulcers has been estimated at approximately $9,000 (Cdn) per patient per month in the community setting. Considering the high prevalence of pressure ulcers in the Ontario health care system, the total cost of treating pressure ulcers is substantial. Wounds normally heal in 3 phases (inflammatory phase, a proliferative phase of new tissue and matrix formation, and a remodelling phase). However, pressure ulcers often fail to progress past the inflammatory stage. Current practice for treating pressure ulcers includes treating the underlying causes, debridement to remove necrotic tissues and contaminated tissues, dressings to provide a moist wound environment and to manage exudates, devices and frequent turning of patients to provide pressure relief, topical applications of biologic agents, and nutritional support to correct nutritional deficiencies. A variety of adjunctive physical therapies are also in use. Health technology assessment databases and medical databases were searched from 1996 (Medline), 1980 (EMBASE), and 1982 (CINAHL) systematically up to March 2008 to identify randomized controlled trials (RCTs) on the following treatments of pressure ulcers: cleansing, debridement, dressings, biological therapies, pressure-relieving devices, physical therapies, nutritional therapies, and multidisciplinary wound care teams. Full literature search strategies are reported in appendix 1. English-language studies in previous systematic reviews and studies published since the last systematic review were included if they had more than 10 subjects, were randomized, and provided objective outcome measures on the healing of pressure ulcers. In the absence of RCTs, studies of the highest level of evidence available were included. Studies on wounds other than pressure ulcers and on surgical treatment of pressure ulcers were excluded. A total of 18 systematic reviews, 104 RCTs, and 4 observational studies were included in this review. Data were extracted from studies using standardized forms. The quality of individual studies was assessed based on adequacy of randomization, concealment of treatment allocation, comparability of groups, blinded assessment, and intention-to-treat analysis. Meta-analysis to estimate the relative risk (RR) or weighted mean difference (WMD) for measures of healing was performed when appropriate. A descriptive synthesis was provided where pooled analysis was not appropriate or not feasible. The quality of the overall evidence on each intervention was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) criteria. Findings from the analysis of the included studies are summarized below: CLEANSING: There is no good trial evidence to support the use of any particular wound cleansing solution or technique for pressure ulcers. DEBRIDEMENT: There was no evidence that debridement using collagenase, dextranomer, cadexomer iodine, or maggots significantly improved complete healing compared with placebo.There were no statistically significant differences between enzymatic or mechanical debridement agents with the following exceptions:Papain urea resulted in better debridement than collagenase.Calcium alginate resulted in a greater reduction in ulcer size compared to dextranomer.Adding streptokinase/streptodornase to hydrogel resulted in faster debridement.Maggot debridement resulted in more complete debridement than conventional treatment.There is limited evidence on the healing effects of debridement devices. DRESSINGS: Hydrocolloid dressing was associated with almost three-times more complete healing compared with saline gauze. There is evidence that hydrogel and hydropolymer may be associated with 50% to 70% more complete healing of pressure ulcers than hydrocolloid dressing.No statistically significant differences in complete healing were detected among other modern dressings.There is evidence that polyurethane foam dressings and hydrocellular dressings are more absorbent and easier to remove than hydrocolloid dressings in ulcers with moderate to high exudates.In deeper ulcers (stage III and IV), the use of alginate with hydrocolloid resulted in significantly greater reduction in the size of the ulcers compared to hydrocolloid alone.Studies on sustained silver-releasing dressing demonstrated a tendency for reducing the risk of infection and promoting faster healing, but the sample sizes were too small for statistical analysis or for drawing conclusions. BIOLOGICAL THERAPIES: The efficacy of platelet-derived growth factors (PDGFs), fibroblast growth factor, and granulocyte-macrophage colony stimulating factor in improving complete healing of chronic pressure ulcers has not been established.Presently only Regranex, a recombinant PDGF, has been approved by Health Canada and only for treatment of diabetic ulcers in the lower extremities.A March 2008 US Food and Drug Administration (FDA) communication reported increased deaths from cancers in people given three or more prescriptions for Regranex.Limited low-quality evidence on skin matrix and engineered skin equivalent suggests a potential role for these products in healing refractory advanced chronic pressure ulcers, but the evidence is insufficient to draw a conclusion. ADJUNCTIVE PHYSICAL THERAPY: There is evidence that electrical stimulation may result in a significantly greater reduction in the surface area and more complete healing of stage II to IV ulcers compared with sham therapy. No conclusion on the efficacy of electrotherapy can be drawn because of significant statistical heterogeneity, small sample sizes, and methodological flaws.The efficacy of other adjunctive physical therapies [electromagnetic therapy, low-level laser (LLL) therapy, ultrasound therapy, ultraviolet light therapy, and negative pressure therapy] in improving complete closure of pressure ulcers has not been established. NUTRITION THERAPY: Supplementation with 15 grams of hydrolyzed protein 3 times daily did not affect complete healing but resulted in a 2-fold improvement in Pressure Ulcer Scale for Healing (PUSH) score compared with placebo.Supplementation with 200 mg of zinc three times per day did not have any significant impact on the healing of pressure ulcers compared with a placebo.Supplementation of 500 mg ascorbic acid twice daily was associated with a significantly greater decrease in the size of the ulcer compared with a placebo but did not have any significant impact on healing when compared with supplementation of 10 mg ascorbic acid three times daily.A very high protein tube feeding (25% of energy as protein) resulted in a greater reduction in ulcer area in institutionalized tube-fed patients compared with a high protein tube feeding (16% of energy as protein).Multinutrient supplements that contain zinc, arginine, and vitamin C were associated with a greater reduction in the area of the ulcers compared with standard hospital diet or to a standard supplement without zinc, arginine, or vitamin C.Firm conclusions cannot be drawn because of methodological flaws and small sample sizes. MULTIDISCIPLINARY WOUND CARE TEAMS: The only RCT suggests that multidisciplinary wound care teams may significantly improve healing in the acute care setting in 8 weeks and may significantly shorten the length of hospitalization. However, since only an abstract is available, study biases cannot be assessed and no conclusions can be drawn on the quality of this evidence.

Successful Use of Adalimumab for Treating Pyoderma Gangrenosum with Ulcerative Colitis under Corticosteroid-tapering Conditions.

PubMed

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Nagai, Kenta; Hayashi, Ryohei; Chayama, Kazuaki

2015-01-01

A 52-year-old woman with ulcerative colitis was admitted to our hospital for an ulcerative colitis flare-up under salazosulfapyridine therapy. The symptoms improved with high-dose corticosteroids. After prednisolone was tapered to 10 mg, the frequency of diarrhea increased. The diarrhea was accompanied by joint pain and a skin ulcer with abscess formation, which was diagnosed to be pyoderma gangrenosum. The patient was started on adalimumab. A positive response to the adalimumab therapy was observed after 2 weeks, during which time the ulcerative skin lesion healed completely, however, colonic mucosal healing was achieved at 2 months. Therefore, adalimumab appears to be an effective therapeutic option for patients with ulcerative colitis-associated pyoderma gangrenosum.

The efficacy and safety of natural honey on the healing of foot ulcers: a case series.

PubMed

Mohamed, Hashim; Salma, Mansour Abu; Al Lenjawi, Badriya; Abdi, Seham; Gouda, Zaghloul; Barakat, Nour; Elmahdi, Hisham; Abraham, Sisy; Hamza, Abdul Hakeem; Al Khozaei, Dhyiaa; Al Majid, Shawqia; Al Majid, Hanaa; Abdini, Johina; Al Jaber, Maryam; Al Masseh, Fareeda; Al Ali, Amal Abdulla

2015-04-01

This clinical observation investigated the efficacy, cost-effectiveness, and acceptability of natural honey on the healing of a variety of chronic foot ulcers at the primary care level. A total of 12 patients with foot ulcers utilizing natural honey as an effective alternative to more expensive, advanced wound products were followed. Cases were referred to Umgwailinah Primary Health Care Center, Doha, Qatar from different health centers and from Hamad General Hospital, Doha, Qatar. There were also self-referred cases. After rinsing the site with normal saline, natural honey was applied and the wound was covered by glycerin-impregnated gauze (Adaptic Non-Adhering Dressing, Systagenix, San Antonio, TX) to prevent the absorption of honey into the cotton gauze and away from the wound site. Patients were followed on a daily basis for an average of 4 weeks. All ulcers healed with no contractures or scars with a mean healing time of 3 weeks. There was a 75% reduction in the dressing budget of the health center and a high level of satisfaction among both health professionals and patients. Patients' pain levels were reduced significantly after using natural honey, as evidenced by the use of the Visual Analog Scale. The use of natural honey in the management of chronic foot ulcers proved to be efficacious, cost-effective, and acceptable by both clinicians and patients.

Cross-talk between hydrogen sulfide and carbon monoxide in the mechanism of experimental gastric ulcers healing, regulation of gastric blood flow and accompanying inflammation.

PubMed

Magierowski, Marcin; Magierowska, Katarzyna; Hubalewska-Mazgaj, Magdalena; Surmiak, Marcin; Sliwowski, Zbigniew; Wierdak, Mateusz; Kwiecien, Slawomir; Chmura, Anna; Brzozowski, Tomasz

2018-03-01

Hydrogen sulfide (H 2 S) and carbon monoxide (CO) exert gastroprotection against acute gastric lesions. We determined the cross-talk between H 2 S and CO in gastric ulcer healing process and regulation of gastric blood flow (GBF) at ulcer margin. Male Wistar rats with acetic acid-induced gastric ulcers were treated i.g. throughout 9 days with vehicle (control), NaHS (0.1-10 mg/kg) +/- zinc protoporphyrin (ZnPP, 10 mg/kg), d,l-propargylglycine (PAG, 30 mg/kg), CO-releasing CORM-2 (2.5 mg/kg) +/- PAG. GBF was assessed by laser flowmetry, ulcer area was determined by planimetry/histology. Gastric mucosal H 2 S production was analysed spectrophotometrically. Protein and/or mRNA expression at ulcer margin for vascular endothelial growth factor (VEGF)A, epidermal growth factor receptor (EGFr), cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), heme oxygenases (HOs), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α and hypoxia inducible factor (HIF)-1α were determined by real-time PCR or western blot. IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF plasma concentration was assessed using Luminex platform. NaHS dose-dependently decreased ulcer area and increased GBF but ZnPP attenuated these effects. PAG decreased H 2 S production but failed to affect CORM-2-mediated ulcer healing and vasodilation. NaHS increased Nrf-2, EGFr, VEGFA and decreased pro-inflammatory markers expression and IL-1β, IL-2, IL-13, TNF-α, GM-CSF plasma concentration. CORM-2 decreased IL-1β and GM-CSF plasma levels. We conclude that NaHS accelerates gastric ulcer healing increasing microcirculation and Nrf-2, EGFr, VEGFA expression. H 2 S-mediated ulcer healing involves endogenous CO activity while CO does not require H 2 S. NaHS decreases systemic inflammation more effectively than CORM-2. Copyright © 2017 Elsevier Inc. All rights reserved.

Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action

PubMed Central

Bhattacharya, S; Banerjee, D; Bauri, AK; Chattopadhyay, S; Bandyopadhyay, SK

2007-01-01

AIM: To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties. METHODS: Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 μg/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. RESULTS: Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 μg/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better. CONCLUSION: APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties. PMID:17659730

Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action.

PubMed

Bhattacharya, S; Banerjee, D; Bauri, A-K; Chattopadhyay, S; Bandyopadhyay, S-K

2007-07-21

To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties. Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 mug/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 mug/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better. APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

Novel mechanisms and signaling pathways of esophageal ulcer healing: the role of prostaglandin EP2 receptors, cAMP, and pCREB

PubMed Central

Ahluwalia, Amrita; Baatar, Dolgor; Jones, Michael K.

2014-01-01

Clinical studies indicate that prostaglandins of E class (PGEs) may promote healing of tissue injury e.g., gastroduodenal and dermal ulcers. However, the precise roles of PGEs, their E-prostanoid (EP) receptors, signaling pathways including cAMP and cAMP response element-binding protein (CREB), and their relation to VEGF and angiogenesis in the tissue injury healing process remain unknown, forming the rationale for this study. Using an esophageal ulcer model in rats, we demonstrated that esophageal mucosa expresses predominantly EP2 receptors and that esophageal ulceration triggers an increase in expression of the EP2 receptor, activation of CREB (the downstream target of the cAMP signaling), and enhanced VEGF gene expression. Treatment of rats with misoprostol, a PGE1 analog capable of activating EP receptors, enhanced phosphorylation of CREB, stimulated VEGF expression and angiogenesis, and accelerated esophageal ulcer healing. In cultured human esophageal epithelial (HET-1A) cells, misoprostol increased intracellular cAMP levels (by 163-fold), induced phosphorylation of CREB, and stimulated VEGF expression. A cAMP analog (Sp-cAMP) mimicked, whereas an inhibitor of cAMP-dependent protein kinase A (Rp-cAMP) blocked, these effects of misoprostol. These results indicate that the EP2/cAMP/protein kinase A pathway mediates the stimulatory effect of PGEs on angiogenesis essential for tissue injury healing via the induction of CREB activity and VEGF expression. PMID:25059824

The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers: A Multicenter, Randomized Trial

PubMed Central

Ghatnekar, Gautam S; Grek, Christina L; Armstrong, David G; Desai, Sanjay C; Gourdie, Robert G

2015-01-01

The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways. PMID:25072595

Evaluation of Honey as a Topical Therapy for Intraoral Wound Healing in Rats.

PubMed

Chamani, Goli; Zarei, Mohammad Reza; Mehrabani, Mitra; Mehdavinezhad, Ali; Vahabian, Mehrangiz; Ahmadi-Motamayel, Fatemah

2017-03-01

Honey is one of the oldest known medicines. Its medical and therapeutic importance has been recently rediscovered. Honey is an effective treatment for infected wounds and ulcers. The aim of this study was to determine the effect of honey as a topical therapy for intraoral wound healing in rats. Thirty-two male rats were divided into experimental and control groups (consisting of 16 rats, 4 animals in each group). A 2-mm mucosal defect was made to the depth of the periosteum using punch biopsy. Honey was applied to the wound every day, and the ulcer size was measured daily. On days 2, 4, 6, and 8, four rats were euthanized from each group (experimental and control groups), and tissues were histopathologically evaluated. Healing processes were studied as follows: the size of ulcer, inflammatory response, reepithelialization, and granulation tissue formation. The mean rank of wound size was significantly reduced in the honey group (2.50), as compared to the control group (6.50). Reepithelialization and granulation tissue formation mean rank were significantly higher in the honey group (6.50) than in the control group (2.50). Inflammation mean rank was statistically lower in the honey group (2.63) compared with the control group (6.38). Honey was shown to have a beneficial effect on the healing of oral ulcers in rats in this model. Further research may shed light on the effects of honey on different types of ulcers in humans.

Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy

PubMed Central

Nema, Hiroaki; Kato, Mototsugu

2010-01-01

AIM: To compare the therapeutic effects of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin. METHODS: Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI (lansoprazole 30 mg, n = 30) or H2RA (famotidine 40 mg or if famotidine had been administered before assignment, ranitidine 300 mg, n = 30). The therapeutic effects were evaluated by endoscopy after 8-wk treatment. The presence or absence of Helicobacter pylori (H. pylori) was determined by urea breath test before treatment. Abdominal symptoms were compared with the gastrointestinal symptom rating scale (GSRS) questionnaire before and after treatment. RESULTS: Twenty-six patients in the PPI group and 26 patients in the H2RA group, excluding dropouts, were analyzed. There were no significant differences in median age, sex, underlying disease, smoking status, H. pylori infection, prevalence of ulcers before treatment, and lesion site between the two groups. The therapeutic effects were endoscopically evaluated as healed in 23 patients (88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients (84.6%) and not healed in 4 patients in the H2RA group. Abdominal symptoms before treatment were uncommon in both groups; the GSRS scores were not significantly reduced after treatment as compared with before treatment. CONCLUSION: The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group, with no significant difference between the two groups. PMID:21072898

Caffeic acid phenethyl ester promotes wound healing of mice pressure ulcers affecting NF-κB and NOS2 and NRF2 expression.

PubMed

Romana-Souza, Bruna; Dos Santos, Jeanine Salles; Monte-Alto-Costa, Andréa

2018-06-01

In pressure ulcers, the synthesis of reactive oxygen species induced by ischemia and reperfusion leads to chronic inflammation and tissue damage, which impair the closure of these lesions. Caffeic acid phenethyl ester (CAPE), found in propolis, promotes cutaneous wound healing of acute lesions and severe burns. However, the effects of CAPE on wound healing of pressure ulcers have not been investigated. This study investigated the effects of CAPE administration in a murine model of pressure ulcers. To induce pressure ulcers, two cycles of ischemia and reperfusion by external application of two magnetic plates were performed in the skin dorsum of mice. After the last cycle, animals were treated daily with CAPE or vehicle until they were euthanized. The nitric oxide synthesis, lipid peroxidation, macrophage migration, protein nuclear factor kappa B and nitric-oxide synthase-2 expression were increased 3 days after ulceration but decreased 7 days later, in pressure ulcers of the CAPE group compared to that of the control group. CAPE reduced the protein expression of nuclear factor-erythroid2-related factor 2 in pressure ulcers 3 days after ulceration, but increased 7 days later. Myofibroblast density was increased in the CAPE group 7 days after ulceration, but reduced 12 days later when compared to control group. In addition, CAPE promoted collagen deposition, re-epithelialization and wound closure of mice pressure ulcers 12 days after ulceration. CAPE brings forward inflammatory response and oxidative damage involved in injury by ischemia and reperfusion, promoting dermal reconstruction and closure of pressure ulcers. Copyright © 2017. Published by Elsevier Inc.

A randomized clinical trial comparing hydrocolloid, phenytoin and simple dressings for the treatment of pressure ulcers [ISRCTN33429693

PubMed Central

Hollisaz, Mohammad Taghi; Khedmat, Hossein; Yari, Fatemeh

2004-01-01

Background Pressure sores are important and common complications of spinal cord injury. Many preventive and therapeutic approaches have been tried and new trials are evolving. One relatively recent method is application of a hydrocolloid dressing (HD). In this study we compared the therapeutic effects of HD on pressure ulcer healing with two other topical applications, phenytoin cream (PC) and simple dressing (SD). Methods Ninety-one stage I and stage II pressure ulcers of 83 paraplegic male victims of the Iran-Iraq war were randomly allocated to three treatment groups. Mean age and weight of the participants were 36.64 ± 6.04 years and 61.12 ± 5.08 kg, respectively. All the patients were managed in long term care units or in their homes for 8 weeks by a team of general practitioners and nurses, and the ulcer status was recorded as "Complete healing", "Partial healing", "Without improvement" and "Worsening". Results Complete healing of ulcers, regardless of location and stage, was better in the HD group than the PC [23/31(74.19%) vs 12/30(40%); difference: 34.19%, 95% CI = 10.85–57.52, (P < 0.01)] or the SD [23/31(74.19%) vs 8/30(26.66%); difference: 47.53%, 95% CI = 25.45–69.61, (P < 0.005)] groups. Complete healing of stage I ulcers in the HD group [11/13(85%)] was better than in the SD [5/11(45%); difference: 40%, 95% CI = 4.7–75.22, (P < 0.05)] or PC [2/9 (22%); difference: 63%, 95% CI = 29.69–96.3, (P < 0.005)] groups. Complete healing of stage II ulcer in the HD group [12/18 (67%)] was better than in the SD group [3/19(16%); difference: 51%, 95% CI = 23.73–78.26, (P < 0.005)], but not significantly different from the PC group [10/21 (48%); difference: 19%, 95% CI = -11.47–49.47, (P > 0.05)]. We performed a second analysis considering only one ulcer per patient (i.e. 83 ulcers in 83 patients). This "per patient" analysis showed that complete ulcer healing in the HD group was better than in the PC [20/28(71.4%) vs 11/28 (39.3%); difference: 32.1%, 95% CI = 7.4–56.7, (P < 0.01)] or SD [20/28(71.4%) vs 8/27 (29.6%); difference: 41.8%, 95% CI = 17.7–65.8, (P < 0.005)] groups. Conclusion We deduced that HD is the most effective method investigated for treating stage I and II pressure ulcers in young paraplegic men. PMID:15601464

Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: neuropathic, ischemic, and neuro-ischemic type.

PubMed

Yotsu, Rie Roselyne; Pham, Ngoc Minh; Oe, Makoto; Nagase, Takeshi; Sanada, Hiromi; Hara, Hisao; Fukuda, Shoji; Fujitani, Junko; Yamamoto-Honda, Ritsuko; Kajio, Hiroshi; Noda, Mitsuhiko; Tamaki, Takeshi

2014-01-01

To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time. Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan-Meier method. Healing time among the three types was compared using the log rank test. The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle-brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values. Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

PubMed Central

Takayama, Masaki; Matsui, Shigenaga; Kawasaki, Masanori; Asakuma, Yutaka; Sakurai, Toshiharu; Kashida, Hiroshi; Kudo, Masatoshi

2013-01-01

AIM: To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. METHODS: We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. RESULTS: No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. CONCLUSION: The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing. PMID:24039365

Opened Proton Pump Inhibitor Capsules Reduce Time to Healing Compared With Intact Capsules for Marginal Ulceration Following Roux-en-Y Gastric Bypass.

PubMed

Schulman, Allison R; Chan, Walter W; Devery, Aiofe; Ryan, Michele B; Thompson, Christopher C

2017-04-01

Marginal ulceration, or ulceration at the gastrojejunal anastomosis, is a common complication of Roux-en-Y gastric bypass (RYGB). Acidity likely contributes to the pathophysiology, and proton pump inhibitors (PPIs) frequently are prescribed for treatment. However, patients with gastric bypass only have a small gastric pouch and rapid small-bowel transit, which limits the opportunity for capsule breakdown and PPI absorption. Soluble PPIs (open capsules [OCs]) might be absorbed more easily than intact capsules (ICs). We compared time to ulcer healing, number of endoscopic procedures, and use of health care for patients with marginal ulceration who received PPIs in OC vs IC form. We performed a retrospective study of 164 patients diagnosed with marginal ulceration who underwent RYGB at the Brigham and Women's Hospital from 2000 through 2015. Patients received high-dose PPIs and underwent repeat endoscopy every 3 months until ulcer healing was confirmed. We used time-to-event analysis with a Cox proportional hazards model to evaluate the association between mode of PPI administration and time to ulcer healing, in addition to Cox multivariate regression analysis. Total charge (procedural and maintenance) was determined by comparison of categorized charges incurred from time of ulcer diagnosis to resolution. The primary outcome was time to healing of marginal ulceration in RYGB patients receiving high-dose PPIs in OC vs IC form. A total of 162 patients were included (115 received OC and 49 received IC). All patients were followed up until ulcer healing was confirmed. The median time to ulcer healing was 91.0 days for the OC group vs 342.0 days for the IC group (P < .001). OC was the only independent predictor of time to ulcer healing (P < .001) when we controlled for known risk factors. The number of endoscopic procedures (P = .02) and overall health care utilization (P = .05) were lower in the OC than the IC group. Patients with marginal ulceration after RYGB who receive OC PPIs have shorter ulcer healing times, fewer endoscopic procedures, and use less health care resources compared with patients who receive IC PPIs. Given these results and the high prevalence of marginal ulceration in this patient population, the use of OC PPIs is a low-risk, low-cost alternative that should be considered. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Mouririelliptica: validation of gastroprotective, healing and anti-Helicobacter pylori effects.

PubMed

Moleiro, Fábio Cruz; Andreo, Márcio Aparecido; Santos, Raquel de Cássia Dos; Moraes, Thiago de Mello; Rodrigues, Clenilson Martins; Carli, Camila Bernardes de Andrade; Lopes, Flávia Cristine Mascia; Pellizzon, Cláudia Helena; Carlos, Iracilda Zeppone; Bauab, Tais Maria; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

2009-06-25

Mouriri elliptica Martius (Melastomataceae) is species reputed in folk medicine to heal gastric ulcer and gastritis. Methanolic extract (ME) and ethyl acetate fraction (EAF) from leaves of Mouriri elliptica were evaluated for their gastroprotective, healing, immunological, toxicological and anti-Helicobacter pylori activities. The gastroprotective action of ME and EAF was evaluated in rodent experimental models and to elucidate mechanisms of action, the antisecretory action, involvements of NO, SH, PGE(2), anti-Helicobacter pylori action of ME was evaluated. We also used immunohistochemical (PCNA and COX-2) and immunomodulatory (murine peritoneal macrophages) assays to evaluate Mouriri elliptica effects. ME present gastroprotective action without antisecretory effect. Otherwise, ME showed anti-Helicobacter pylori action (MIC=0.025mug/mL) and was able to inhibit NO production by macrophages. This species also accelerate the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA), COX-2 and maintained basal PGE(2) level independent action of NSAID in gastric mucosa. The phytochemical investigation showed that this species possesses phenolic acid derivatives, acylglycoflavonoids and condensed tannins which probably influenced their pharmacological action. All these results suggest the efficacy and safety of Mouriri elliptica in combating and healing gastric ulcer.

The Effectiveness of Hypochlorous Acid Solution on Healing of Infected Diabetic Foot Ulcers

ERIC Educational Resources Information Center

Ragab, Islam I.; Kamal, Ahmed

2017-01-01

Wound cleansing remains a corner stone in the management of diabetic foot ulcer. Hydrogen Peroxide (H[subscript 2]O[subscript 2]) and Povidone Iodine are topical antimicrobial agents but known to be toxic to cells involved in the wound healing cascade. The biggest challenge for the physicians and nurses is searching for a safe, noncytotoxic and…

A Randomized, Controlled Clinical Trial of Honey-Impregnated Dressing for Treating Diabetic Foot Ulcer.

PubMed

Imran, Muhammad; Hussain, Muhammad Barkaat; Baig, Mukhtiar

2015-10-01

To investigate the effect of Beri-honey-impregnated dressing on diabetic foot ulcer and compare it with normal saline dressing. A randomized, controlled trial. Sughra Shafi Medical Complex, Narowal, Pakistan and Bhatti International Trust (BIT) Hospital, Affiliated with Central Park Medical College, Lahore, from February 2006 to February 2010. Patients with Wagner's grade 1 and 2 ulcers were enrolled. Those patients were divided in two groups; group A (n=179) treated with honey dressing and group B (n=169) treated with normal saline dressing. Outcome measures were calculated in terms of proportion of wounds completely healed (primary outcome), wound healing time, and deterioration of wounds. Patients were followed-up for a maximum of 120 days. One hundred and thirty six wounds (75.97%) out of 179 were completely healed with honey dressing and 97 (57.39%) out of 169 wtih saline dressing (p=0.001). The median wound healing time was 18.00 (6 - 120) days (Median with IQR) in group A and 29.00 (7 - 120) days (Median with IQR) in group B (p < 0.001). The present results showed that honey is an effective dressing agent instead of conventional dressings, in treating patients of diabetic foot ulcer.

Improvement of wound healing by water-filtered infrared-A (wIRA) in patients with chronic venous stasis ulcers of the lower legs including evaluation using infrared thermography.

PubMed

Mercer, James B; Nielsen, Stig Pors; Hoffmann, Gerd

2008-10-21

Water-filtered infrared-A (wIRA) is a special form of heat radiation with a high tissue-penetration and with a low thermal burden to the surface of the skin. wIRA is able to improve essential and energetically meaningful factors of wound healing by thermal and non-thermal effects. prospective study (primarily planned randomised, controlled, blinded, de facto with one exception only one cohort possible) using wIRA in the treatment of patients with recalcitrant chronic venous stasis ulcers of the lower legs with thermographic follow-up. 10 patients (5 males, 5 females, median age 62 years) with 11 recalcitrant chronic venous stasis ulcers of the lower legs were treated with water-filtered infrared-A and visible light irradiation (wIRA(+VIS), Hydrosun radiator type 501, 10 mm water cuvette, water-filtered spectrum 550-1400 nm) or visible light irradiation (VIS; only possible in one patient). The uncovered wounds of the patients were irradiated two to five times per week for 30 minutes at a standard distance of 25 cm (approximately 140 mW/cm(2) wIRA and approximately 45 mW/cm(2) VIS). Treatment continued for a period of up to 2 months (typically until closure or nearly closure of the ulcer). The main variable of interest was "percent change of ulcer size over time" including complete wound closure. Additional variables of interest were thermographic image analysis, patient's feeling of pain in the wound, amount of pain medication, assessment of the effect of the irradiation (by patient and by clinical investigator), assessment of feeling of the wound area (by patient), assessment of wound healing (by clinical investigator) and assessment of the cosmetic state (by patient and by clinical investigator). For these assessments visual analogue scales (VAS) were used. The study showed a complete or nearly complete healing of lower leg ulcers in 7 patients and a clear reduction of ulcer size in another 2 of 10 patients, a clear reduction of pain and pain medication consumption (e.g. from 15 to 0 pain tablets per day), and a normalization of the thermographic image (before the beginning of the therapy typically hyperthermic rim of the ulcer with relative hypothermic ulcer base, up to 4.5 degrees C temperature difference). In one patient the therapy of an ulcer of one leg was performed with the fully active radiator (wIRA(+VIS)), while the therapy of an ulcer of the other leg was made with a control group radiator (only VIS without wIRA), showing a clear difference in favour of the wIRA treatment. All mentioned VAS ratings improved remarkably during the period of irradiation treatment, representing an increased quality of life. Failures of complete or nearly complete wound healing were seen only in patients with arterial insufficiency, in smokers or in patients who did not have venous compression garment therapy. wIRA can alleviate pain considerably (with an impressive decrease of the consumption of analgesics) and accelerate wound healing or improve a stagnating wound healing process and diminish an elevated wound exudation and inflammation both in acute and in chronic wounds (in this study shown in chronic venous stasis ulcers of the lower legs) and in problem wounds including infected wounds. In chronic recalcitrant wounds complete healing is achieved, which was not reached before. Other studies have shown that even without a disturbance of wound healing an acute wound healing process can be improved (e.g. reduced pain) by wIRA. wIRA is a contact-free, easily used and pleasantly felt procedure without consumption of material with a good penetration effect, which is similar to solar heat radiation on the surface of the earth in moderate climatic zones. Wound healing and infection defence (e.g. granulocyte function including antibacterial oxygen radical formation of the granulocytes) are critically dependent on a sufficient energy supply (and on sufficient oxygen). The good clinical effect of wIRA on wounds and also on problem wounds and wound infections can be explained by the improvement of both the energy supply and the oxygen supply (e.g. for the granulocyte function). wIRA causes as a thermal effect in the tissue an improvement in three decisive factors: tissue oxygen partial pressure, tissue temperature and tissue blood flow. Besides this non-thermal effects of infrared-A by direct stimulation of cells and cellular structures with reactions of the cells have also been described. It is concluded that wIRA can be used to improve wound healing, to reduce pain, exudation, and inflammation and to increase quality of life.

Is ranitidine therapy sufficient for healing peptic ulcers associated with non-steroidal anti-inflammatory drug use?

PubMed Central

YEOMANS, N D; SVEDBERG, L-E; NAESDAL, J

2006-01-01

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of serious gastroduodenal events. To minimise these risks, patients often require concomitant acid-suppressive therapy. We conducted a literature review of clinical trials examining use of ranitidine 150 mg twice daily to heal gastroduodenal ulcers (GU) in NSAID recipients. Seven studies were identified. After 8 weeks’ treatment with ranitidine, GU healing rates ranged from 50% to 74% and rates of duodenal ulcer (DU) healing ranged from 81% to 84%. Ranitidine was more effective when NSAIDs were discontinued (healing rates reaching 95% and 100%, respectively). The ulcer healing rate with sucralfate was similar to that of ranitidine. However, proton pump inhibitor (PPI) therapy was associated with significantly greater rates of both GU and DU healing than ranitidine; 8-week GU rates were 92% and 88% with esomeprazole 40 mg and 20 mg, respectively (vs. 74% with ranitidine, p < 0.01). For omeprazole, 8-week healing rates were 87% with omeprazole 40 mg and 84% with omeprazole 20 mg (vs. 64% for ranitidine, p < 0.001), and for lansoprazole the corresponding values were 73–74% and 66–69% for the 30 mg and 15 mg doses, respectively (vs. 50–53% for ranitidine, p < 0.05). In the PPI study reporting DU healing the values were 92% for omeprazole 20 mg (vs. 81% for ranitidine, p < 0.05) and 88% for omeprazole 40 mg (p = 0.17 vs. ranitidine). NSAID-associated GU are more likely to heal when patients receive concomitant treatment with a PPI rather than ranitidine. PMID:17073837

Current Status and Future of Skin Substitutes for Chronic Wound Healing.

PubMed

Nicholas, Mathew N; Yeung, Jensen

Chronic wounds, including diabetic ulcers, pressure ulcers, venous ulcers, and arterial insufficiency ulcers, are both difficult and expensive to treat. Conventional wound care may sometimes lead to suboptimal wound healing and significant morbidity and mortality for patients. The use of skin substitutes provides an alternative therapy showing superior efficacy and, in some cases, similar cost-effectiveness compared to traditional treatments. This review discusses the different types of currently available commercial skin substitutes for use in chronic wounds as well as the paucity of strong evidence supporting their use. It then delves into the limitations of these skin substitutes and examines the most recent research targeting these limitations.

Selective plantar fascia release for nonhealing diabetic plantar ulcerations.

PubMed

Kim, J Young; Hwang, Seungkeun; Lee, Yoonjung

2012-07-18

Achilles tendon lengthening can decrease plantar pressures, leading to resolution of forefoot ulceration in patients with diabetes mellitus. However, this procedure has been reported to have a complication rate of 10% to 30% and can require a long period of postoperative immobilization. We have developed a new technique, selective plantar fascia release, as an alternative to Achilles tendon lengthening for managing these forefoot ulcers. We evaluated sixty patients with diabetes for a mean of 23.5 months after selective plantar fascia release for the treatment of nonhealing diabetic neuropathic ulcers in the forefoot. Preoperative and postoperative dorsiflexion range of motion of the affected metatarsophalangeal joint and wound-healing data were used to evaluate the effectiveness of the procedure and to determine the relationship between plantar fascia release and ulcer healing. Complications were recorded. Thirty-six (56%) of the ulcers healed within six weeks, including twenty-nine (60%) of the plantar toe ulcers and seven (44%) of the metatarsophalangeal joint ulcers. The mean range of motion of the affected metatarsophalangeal joint increased from 15.3° ± 7.8° to 30.6° ± 14.1° postoperatively (p < 0.05). All patients in whom the preoperative dorsiflexion of the affected metatarsophalangeal joint was between 5° and 30° and in whom the range of motion of that joint increased by ≥13° after the procedure experienced healing of the ulcer. No ulcer recurrence in the original location was identified during follow-up. No patients experienced any complications associated with the selective plantar fascia release. Our results suggest that selective plantar fascia release can lead to healing of neuropathic plantar forefoot ulcers in diabetic patients. Ulcers in patients in whom the preoperative dorsiflexion angle of the affected metatarsophalangeal joint is between 5° and 30° and in whom the increase in range of motion is ≥13° postoperatively have the greatest chance of being cured. Therapeutic level IV. See Instructions for Authors for a complete description of the levels of evidence.

Clinic-epidemiological evaluation of ulcers in patients with leprosy sequelae and the effect of low level laser therapy on wound healing: a randomized clinical trial

PubMed Central

2010-01-01

Background Mycobacterium leprae is the only pathogenic bacteria able to infect peripheral nerves. Neural impairment results in a set of sensitive, motor and autonomic disturbances, with ulcers originating primarily on the hands and feet. The study objectives were to analyze the clinic-epidemiological characteristics of patients attended at one specialized dressing service from a leprosy-endemic region of the Brazilian Amazon and to evaluate the effect of low level laser therapy (LLLT) on wound healing of these patients. Methods Clinic-epidemiological evaluation of patients with leprosy sequelae was performed at the reference unit in sanitary dermatology of the state of Pará in Brazil. We conducted anamnesis, identification of the regions affected by the lesions and measurement of ulcer depth and surface area. After that, we performed a randomized clinical trial. Fifty-one patients with ulcers related to leprosy were evaluated, twenty-five of them were randomly assigned to a low level laser therapy group or a control group. Patients were treated 3 times per week for 12 weeks. Outcome measures were ulcer surface area, ulcer depth and the pressure ulcer scale for healing score (PUSH). Results Ninety-seven ulcers were identified, with a mean (SD) duration of 97.6 (111.7) months, surface area of 7.3 (11.5) cm2, and depth of 6.0 (6.2) mm. Statistical analysis of the data determined that there were no significant differences in the variables analyzed before and after treatment with low level laser therapy. Conclusions Ulcers in patients with leprosy remain a major source of economic and social losses, even many years after they have been cured of M. leprae infection. Our results indicate that it is necessary to develop new and more effective therapeutic tools, as low level laser therapy did not demonstrate any additional benefits to ulcer healing with the parameters used in this study. Trial Registration The trial was registered at ClinicalTrials.gov as NCT00860717. PMID:20698989

A topical haemoglobin spray for oxygenating pressure ulcers: a pilot study.

PubMed

Tickle, Joy

2015-03-01

The effect of pressure ulcers on patient quality of life have been recognised as a real problem for many years, and the need for robust and effective management of pressure ulcers is now a prominent national health-care issue. Myriad different interventions exist for the treatment of pressure ulcers, including clinically effective dressings and pressure-relieving devices, yet many pressure ulcers still do not heal and often become a chronic wound. This is the second of a series of articles (Norris, 2014) discussing the clinical evaluation of a topical oxygen therapy in practice. It describes a small evaluation involving 18 patients with pressure ulcers. The study set out to determine the effect of a topical oxygen therapy on wound size. The therapy comprises a canister that sprays pure haemoglobin in a water solution into or onto the wound. The haemoglobin spray needs to be used at least once every 3 days, does not require training on its use and can be used in any care setting. Overall, results identified wound healing progression in all 18 wounds and wound size reduction in 17 of the 18 wounds.

Rhamnogalacturonan from Acmella oleracea (L.) R.K. Jansen: gastroprotective and ulcer healing properties in rats.

PubMed

Maria-Ferreira, Daniele; da Silva, Luisa Mota; Mendes, Daniel Augusto Gasparin Bueno; Cabrini, Daniela de Almeida; Nascimento, Adamara Machado; Iacomini, Marcello; Cipriani, Thales Ricardo; Santos, Adair Roberto Soares; Werner, Maria Fernanda de Paula; Baggio, Cristiane Hatsuko

2014-01-01

A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.

[Having trouble with pressure ulcers care?].

PubMed

Mizuno, Masako; Noda, Yasuhiro; Nohara, Yoko; Fujii, Keiko; Sato, Noriko; Renda, Akiyoshi; Yuasa, Takashi; Muramatsu, Shuichi; Furuta, Katsunori

2004-12-01

Since 1997, we, the community pharmacists, have established this society, Aichi Prefecture Society for the Study of Pressure Ulcers Care, in order to furnish drug information about pressure ulcers care. Moist atmosphere is required for the healing of pressure ulcers. The moist environment that could be regulated depends on the physicochemical property of ointment bases. Therefore, ointment should reasonably be chosen to adjust the moisture. Since 2000, we have been committed to providing pharmacists, who work on home care, with a booklet to instruct how to choose ointments for pressure ulcers treatment. In 2002, when the Aichi pharmaceutical association held a training conference held at various hospitals using the booklet as a teaching material, hospital pharmacists cooperated by making a field study trip to observe pressure ulcers treatments. Nowadays researchers at pharmaceutical colleges have also cooperated in studying the efficacy and economical effect of the method of blending different ointments to improve the healing process of pressure ulcers.

Treatment of 'cimetidine-resistant' chronic duodenal ulcers with ranitidine or cimetidine: a randomised multicentre study.

PubMed Central

Quatrini, M; Basilisco, G; Bianchi, P A

1984-01-01

Forty patients with endoscopically proven persistent duodenal ulcer who had been treated for six weeks with cimetidine (1 g/day) were randomly allocated to receive a further six weeks' treatment with cimetidine (1 g/day) or ranitidine (300 mg/day). Ulcers healed in 12 of 19 patients given cimetidine (63%) and in 13 of 21 given ranitidine (62%); two patients on cimetidine and two on ranitidine dropped out. In the unhealed ulcer group the ulcer size was reduced in most patients. There was no change in basal acid output, peak acid output, plasma gastrin and pepsinogen I levels after either treatment. Clinical data, gastric function tests, and endoscopic features did not predict ulcer healing. Both treatments were effective in the relief of pain: 72% of patients with unhealed ulcers were asymptomatic at the end of the trial. PMID:6090280

The use of hyperbaric oxygen therapy and LED therapy in diabetic foot

NASA Astrophysics Data System (ADS)

Marques, Cristiane R. S.; Martin, Airton A.; Lima, Carlos J.; Conrado, Luis A. L.; Silveira, Fabricio L.; Carvalho, Marcos V.

2004-07-01

Chronic foot ulcers are common ailments presented in diabetes, which offer severe complications and are often unresponsive to therapy. In this work it was evaluated the effects of adjunctive Hyperbaric Oxygen Therapy (HBO) treatment and LEDtherapy irradiation on ulcer healing (HBO) in addition to conventional treatment. In ulcers of diabetic foot these treatments lead to a reduction in the probability of amputation up to almost four times compared with patients not receiving such co-adjutant treatment. The LEDtherapy irradiation was given concurrently using an energy density of 4J/cm2 for 5 min. During the experiment nine patients with diabetic foot ulcers were submitted for HBO sessions with 2,5 ATM for two hours. The experiment demonstrated the effectiveness of HBO + LEDtherapy treatment by favoring the ulcer healing through an increased fibroblastic response, collagen synthesis and neo-vascularization of the ischaemia, as well as increases in the leukocytic bactericidal activity.

Hair-follicle Transplant Into Chronic Ulcers: A New Graft Concept.

PubMed

Martínez Martínez, M L; Escario Travesedo, E; Jiménez Acosta, F

Chronic venous leg ulcers are a major therapeutic challenge in clinical practice, and the search for new approaches to improve wound healing is essential. Many ulcers do not heal with traditional treatment using compression, debridement, and dressings. Skin-grafts variants, such as pinch grafts, punch grafts, split- or full-thickness skin grafts, and grafts derived from cells cultured in the laboratory, are among the most widely used options in ulcers that do not heal. In recent years, numerous studies have brought to our attention the important role of the hair follicle in the healing process of cutaneous wounds. Putting knowledge into practice, hair follicles from the scalp have been used in punch-type grafts transplanted to the base of chronic ulcers to stimulate healing. Results appear to be better than those with traditional hairless punch grafts, opening new lines of treatment for recalcitrant chronic venous ulcers. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of activation of 5'-adenosine monophosphate-activated protein kinase in gastric ulcer healing in diabetic rats.

PubMed

Baraka, Azza M; Deif, Maha M

2011-01-01

The potential utility of 5'-adenosine monophosphate-activated protein kinase (AMPK)-activating agents, such as metformin, in inducing angiogenesis, could be a promising approach to promote healing of gastric ulcers complicated by diabetes mellitus. The aim of the present study was to assess the effect of a drug that activates AMPK, namely metformin, in gastric ulcer healing in streptozotocin-induced diabetic rats. Forty male Wistar albino rats were made diabetic by intraperitoneal (i.p.) streptozotocin injection and 10 rats were injected i.p. by a single dose of physiological saline. Six weeks following streptozotocin or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into group 1 (nondiabetic control), group 2 (streptozotocin-injected rats), groups 3-5 (streptozotocin-injected rats treated with metformin or metformin and an inhibitor of AMPK, namely compound C or pioglitazone) for 7 days following acetic acid application. Administration of metformin, but not pioglitazone, resulted in a significant decrease in the gastric ulcer area, a significant increase in epithelial regeneration assessed histologically, a significant increase in the number of microvessels in the ulcer margin, a significant increase in gastric vascular endothelial growth factor concentration and gastric von Willebrand factor as well as a significant increase in gastric phospho-AMPK. Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK. Our results suggest the feasibility of a novel treatment strategy, namely drugs activating AMPK, for patients in whom impairment of ulcer healing constitutes a secondary complication of diabetes mellitus. Copyright © 2011 S. Karger AG, Basel.

Acellular fetal bovine dermal matrix for treatment of chronic ulcerations of the midfoot associated with Charcot neuroarthropathy.

PubMed

Kavros, Steven J

2012-08-01

Gross deformity of the foot in Charcot neuroarthropathy can lead to collapse and subsequent ulceration, infection, amputation, or premature death. This study evaluated healing of midfoot ulcerations of Charcot neuroarthropathy using PriMatrix, a novel acellular fetal bovine dermal matrix. In this retrospective analysis, 20 patients with ulcerations of the midfoot associated with Charcot neuroarthropathy were treated with either PriMatrix in addition to standard wound care (PriMatrix group,n = 12) or standard wound care alone (control group, n = 8). All patients had chronic, nonhealing foot ulcerations of at least 2250 mm(3) for a minimum of 30 days duration. All foot ulcerations were full thickness with subcutaneous involvement. Ankle brachial index ≥0.90 and/or transcutaneous oximetry (TcPo(2)) ≥40 mm Hg at the periulcer site was necessary for inclusion. Patients were excluded if they had acute or chronic osteomyelitis of the foot. Demography, risk factors, baseline severity of Charcot neuroarthropathy, and wound volume (control 4078 mm(3), PriMatrix 3737.5 mm(3), P = nonsignificant) were similar between treatment groups. Mean time to healing in the PriMatrix group (116 days, 95% CI = 109-123) was significantly shorter than in the control group (180 days, 95% confidence interval [CI] = 171-188); P < .0001. A significantly faster rate of healing was observed with PriMatrix (87.9 mm(3)/wk, 95% CI = 115.2% to 60.6%) compared with control (59.0 mm(3)/wk, 95% CI = 72.8% to 45.3%); P < .0001). The significantly faster rate of healing and steeper slope of volume reduction in the PriMatrix group warrants further investigation into its effects on healing of neuropathic ulcerations and potential limb salvage.

Clinical validity of the estimated energy requirement and the average protein requirement for nutritional status change and wound healing in older patients with pressure ulcers: A multicenter prospective cohort study.

PubMed

Iizaka, Shinji; Kaitani, Toshiko; Nakagami, Gojiro; Sugama, Junko; Sanada, Hiromi

2015-11-01

Adequate nutritional intake is essential for pressure ulcer healing. Recently, the estimated energy requirement (30 kcal/kg) and the average protein requirement (0.95 g/kg) necessary to maintain metabolic balance have been reported. The purpose was to evaluate the clinical validity of these requirements in older hospitalized patients with pressure ulcers by assessing nutritional status and wound healing. This multicenter prospective study carried out as a secondary analysis of a clinical trial included 194 patients with pressure ulcers aged ≥65 years from 29 institutions. Nutritional status including anthropometry and biochemical tests, and wound status by a structured severity tool, were evaluated over 3 weeks. Energy and protein intake were determined from medical records on a typical day and dichotomized by meeting the estimated average requirement. Longitudinal data were analyzed with a multivariate mixed-effects model. Meeting the energy requirement was associated with changes in weight (P < 0.001), arm muscle circumference (P = 0.003) and serum albumin level (P = 0.016). Meeting the protein requirement was associated with changes in weight (P < 0.001) and serum albumin level (P = 0.043). These markers decreased in patients who did not meet the requirement, but were stable or increased in those who did. Energy and protein intake were associated with wound healing for deep ulcers (P = 0.013 for both), improving exudates and necrotic tissue, but not for superficial ulcers. Estimated energy requirement and average protein requirement were clinically validated for prevention of nutritional decline and of impaired healing of deep pressure ulcers. © 2014 Japan Geriatrics Society.

Effectiveness of Removable Walker Cast Versus Nonremovable Fiberglass Off-Bearing Cast in the Healing of Diabetic Plantar Foot Ulcer

PubMed Central

Faglia, Ezio; Caravaggi, Carlo; Clerici, Giacomo; Sganzaroli, Adriana; Curci, Vincenzo; Vailati, Wanda; Simonetti, Daniele; Sommalvico, Francesco

2010-01-01

OBJECTIVE To evaluate the efficacy of a removable cast walker compared with that of a nonremovable fiberglass off-bearing cast in the treatment of diabetic plantar foot ulcer. RESEARCH DESIGN AND METHODS Forty-five adult diabetic patients with nonischemic, noninfected neuropathic plantar ulcer were randomly assigned for treatment with a nonremovable fiberglass off-bearing cast (total contact cast [TCC] group) or walker cast (Stabil-D group). Treatment duration was 90 days. Percent reduction in ulcer surface area and total healing rates were evaluated after treatment. RESULTS A total of 48 patients were screened; however, 2 patients in the TCC group and 1 patient in the Stabil-D group did not complete the study and were considered dropouts. There were no significant differences in demographic and clinic characteristics of the 45 patients completing the study. Ulcer surface decreased from 1.41 to 0.21 cm2 (P < 0.001) in the TCC group and from 2.18 to 0.45 cm2 (P < 0.001) in the Stabil-D group, with no significant differences between groups (P = 0.722). Seventeen patients (73.9%) in the TCC group and 16 patients (72.7%) in the Stabil-D group achieved healing (P = 0.794). Average healing time was 35.3 ± 3.1 and 39.7 ± 4.2 days in the TCC and Stabil-D group, respectively (P = 0.708). CONCLUSIONS The Stabil-D cast walker, although removable, was equivalent in efficacy to the TCC in terms of ulcer size reduction and total healing rate. The easier use of Stabil-D may help increase the use of off-loading devices in the management of plantar neuropathic diabetic foot ulcers. PMID:20357377

Effectiveness and tissue compatibility of a 12-week treatment of chronic venous leg ulcers with an octenidine based antiseptic--a randomized, double-blind controlled study.

PubMed

Vanscheidt, Wolfgang; Harding, Keith; Téot, Luc; Siebert, Jörg

2012-06-01

The aim of this study was to evaluate the cytotoxic effect of octenidine dihydrochloride/phenoxyethanol (OHP) found in vitro by conducting a randomized, double-blind controlled clinical study focusing on its safe and effective use in chronic venous leg ulcers. In total, 126 male and female patients were treated with either OHP (n = 60) or Ringer solution (n = 66). The treatment lasted over a period of maximum 12 weeks. For the assessment of the wound-healing process, clinical outcome parameters were employed, that is, time span until 100% epithelization, wound status and the wound surface area were analysed. Side effects were recorded during the study period. The median time to complete ulcer healing was comparable between the OHP and Ringer solution groups (92 versus 87 days; P = 0·952), without being influenced by wound size or duration of the target ulcer (P-values: 0·947/0·978). In patients treated with OHP, fewer adverse events (AEs) were observed compared with the Ringer group (17% versus 29% of patients reported 20 versus 38 AEs). OHP is well suitable for the treatment of chronic wounds without cytotoxic effects. Furthermore, OHP does not impair the wound healing in chronic venous ulcers. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

PubMed

Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

2017-11-24

Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Oral aspirin for treating venous leg ulcers.

PubMed

de Oliveira Carvalho, Paulo Eduardo; Magolbo, Natiara G; De Aquino, Rebeca F; Weller, Carolina D

2016-02-18

Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwide; prevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. In May 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for published or ongoing trials. There were no language or publication date restrictions. We included randomised controlled trials (RCTs) that compared oral aspirin with placebo or no drug intervention (in the presence or absence of compression therapy) for treating people with venous leg ulcers. Our main outcomes were time to complete ulcer healing, rate of change in the area of the ulcer, proportion of ulcers healed in the trial period, major bleeding, pain, mortality, adverse events and ulcer recurrence (time for recurrence and proportion of recurrence). Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial and assessed overall quality of evidence for the main outcomes in the 'Summary of findings' table. The electronic search located 62 studies. We included two RCTs of oral aspirin (300 mg/daily) given in addition to compression compared with compression and placebo, or compression alone. To date, the impact of aspirin on VLUs has been examined by only two randomised clinical trials, both with a small number of participants. The first RCT was conducted in the United Kingdom (n=20) and reported that daily administration of aspirin (300mg) in addition to compression bandages increased both the rate of healing, and the number of participants healed when compared to placebo in addition to compression bandaging over a four month period. Thirty-eight per cent of the participants given aspirin reported complete healing compared with 0% in the placebo group . Improvement (assessed by reduction in wound size) occurred in 52% of the participants taking aspirin compared with 26% in those taking placebo). The study identified potential benefits of taking aspirin as an adjunct to compression but the sample size was small, and neither the mechanism by which aspirin improved healing nor its effects on recurrence were investigated.In 2012 an RCT in Spain (n=51) compared daily administration of aspirin (300mg) in addition to compression bandages with compression alone over a five month period. There was little difference in complete healing rates between groups (21/28 aspirin and 17/23 compression bandages alone) but the average time to healing was shorter (12 weeks in the treated group vs 22 weeks in the compression only group) and the average time for recurrence was longer in the aspirin group (39 days: [SD 6.0] compared with 16.3 days [SD 7.5] in the compression only group). Although this trial provides some limited data about the potential use of aspirin therapy, the sample size (only 20 patients) was too small for us to draw meaningful conclusions. In addition, patients were only followed up for 4 months and no information on placebo was reported. Low quality evidence from two trials indicate that there is currently insufficient evidence for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. We downgraded the evidence to low quality due to potential selection bias and imprecision due to the small sample size. The small number of participants may have a hidden real benefit, or an increase in harm. Due to the lack of reliable evidence, we are unable to draw conclusions about the benefits and harms of oral daily aspirin as an adjunct to compression in VLU healing or recurrence. Further high quality studies are needed in this area.

Evaluation of the effectiveness and cost-effectiveness of lightweight fibreglass heel casts in the management of ulcers of the heel in diabetes: a randomised controlled trial.

PubMed Central

Jeffcoate, William; Game, Frances; Turtle-Savage, Vivienne; Musgrove, Alison; Price, Patricia; Tan, Wei; Bradshaw, Lucy; Montgomery, Alan; Fitzsimmons, Deborah; Farr, Angela; Winfield, Thomas; Phillips, Ceri

2017-01-01

BACKGROUND Ulcers of the foot in people with diabetes mellitus are slow to heal and result in considerable cost and patient suffering. The prognosis is worst for ulcers of the heel. OBJECTIVE To assess both the clinical effectiveness and the cost-effectiveness of lightweight fibreglass casts in the management of heel ulcers. DESIGN A pragmatic, multicentre, parallel, observer-blinded randomised controlled trial. A central randomisation centre used a computer-generated random number sequence to allocate participants to groups. SETTING Thirty-five specialist diabetic foot secondary care centres in the UK. Those recruited were aged ≥ 18 years and had diabetes mellitus complicated by ulcers of the heel of grades 2-4 on the National Pressure Ulcer Advisory Panel and European Pressure Ulcer Advisory Panel scale. PARTICIPANTS In total, 509 participants [68% male, 15% with type 1 diabetes mellitus, mean age 67.5 years (standard deviation 12.4 years)] were randomised 1 : 1 to the intervention (n = 256) or the control (n = 253) arm. The primary outcome data were available for 425 participants (212 from the intervention arm and 213 from the control arm) and exceeded the total required; attrition was 16.5%. The median ulcer area at baseline was 275 mm(2) [interquartile range (IQR) 104-683 mm(2)] in the intervention group and 206 mm(2) (IQR 77-649 mm(2)) in the control group. There were no differences between the two groups at baseline in any parameter, neither in relation to the participant nor in relation to their ulcer. INTERVENTIONS The intervention group received usual care supplemented by the addition of an individually moulded, lightweight, fibreglass heel cast. The control group received usual care alone. The intervention phase continued either until the participant's ulcer had healed (maintained for 28 days) or for 24 weeks, whichever occurred first. During this intervention phase, the participants were reviewed every 2 weeks, and the fibreglass casts were replaced when they were no longer usable. MAIN OUTCOME MEASURES The primary outcome measure was ulcer healing (confirmed by a blinded observer and maintained for 4 weeks) within 24 weeks. Other outcome measures included the time taken for the ulcer to heal, the percentage reduction in the cross-sectional area, the reduction in local pain, amputation, survival and health economic analysis. The study was powered to define a difference in healing of 15% (55% intervention vs. 40% control). RESULTS Forty-four per cent (n = 94) of the intervention group healed within 24 weeks, compared with 37% (n = 80) of the control participants (odds ratio 1.42, 95% confidence interval 0.95 to 2.14; p = 0.088), using an intention-to-treat analysis. No differences were observed between the two groups for any secondary outcome. LIMITATIONS Although the component items of care were standardised, because this was a pragmatic trial, usual care was not uniform. There was some evidence of a small excess of adverse events in the intervention group; however, non-blinded observers documented these events. There was no excess of adverse device effects. CONCLUSIONS There may be a small increase in healing with the use of a heel cast, but the estimate was not sufficiently precise to provide strong evidence of an effect. There was no evidence of any subgroup in which the intervention appeared to be particularly effective. A health economic analysis suggested that it is unlikely that the intervention represents good value for money. The provision of a lightweight heel cast may be of benefit to some individuals, but we have found no evidence to justify the routine adoption of this in clinical practice. FUTURE WORK It is unlikely that further study of this intervention will have an impact on usual clinical care, and so future efforts should be directed towards other interventions designed to improve the healing of ulcers in this population. TRIAL REGISTRATION Current Controlled Trials ISRCTN62524796. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 34. See the NIHR Journals Library website for further project information. PMID:28644115

Aspirin can elicit the recurrence of gastric ulcer induced with acetic acid in rats.

PubMed

Wang, Guo-Zhong; Huang, Guo-Ping; Yin, Guo-Li; Zhou, Gang; Guo, Chun-Juan; Xie, Chun-Gang; Jia, Bing-Bing; Wang, Jin-Fu

2007-01-01

This study was supported by grants of New Ideas Capability for Backbone Teachers in Universities of Heilongjiang and of Scientific Research foundation in Qiqihar Medical College. Ulcer recurrence and poor healing may be critically important to the development of serious gastrointestinal complications in patients with long-term non-steroid anti-inflammatory drugs (NSAIDs). The present study is to investigate the effects of aspirin on ulcer recurrence and healing quality and to explore the mechanism. Gastric ulcers were induced with acetic acid in rats; aspirin was administrated by gavage from day 25 to day 54 after ulcer induction. The gastric juice volume, pH, gastric mucus, gastric mucosal blood flow (GMBF) and prostaglandin E(2) (PGE(2)) were measured. The mRNA transcription of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were analyzed with RT-PCR and protein expression with Western blot. The gastric juice volume was significantly increased in aspirin group compared with those of fasting or saline control groups (P<0.01); while the pH, mucus, GMBF and PGE(2) were significantly decreased in aspirin treated rats compared with those of other two groups (P<0.01). COX-2, evaluated with mRNA and protein expression, was significantly augmented in aspirin group compared with others. The quality of ulcer healing (QOUH) in Aspirin group was poorer than that of fasting or saline control groups. Aspirin enhance the recurrence of gastric ulcer. The inhibition of cycloxygenase, mucus secretion and mucosal blood flow may be involved. Aspirin also impair the quality of ulcer healing.

Four layer bandage compared with short stretch bandage for venous leg ulcers: systematic review and meta-analysis of randomised controlled trials with data from individual patients

PubMed Central

Tierney, Jayne; Cullum, Nicky; Bland, J Martin; Franks, Peter J; Mole, Trevor; Scriven, Mark

2009-01-01

Objective To compare the effectiveness of two types of compression treatment (four layer bandage and short stretch bandage) in people with venous leg ulceration. Design Systematic review and meta-analysis of patient level data. Data sources Electronic databases (the Cochrane Central Register of Controlled Trials, the Cochrane Wounds Group Specialised Register, Medline, Embase, CINAHL, and National Research Register) and reference lists of retrieved articles searched to identify relevant trials and primary investigators. Primary investigators of eligible trials were invited to contribute raw data for re-analysis. Review methods Randomised controlled trials of four layer bandage compared with short stretch bandage in people with venous leg ulceration were eligible for inclusion. The primary outcome for the meta-analysis was time to healing. Cox proportional hazards models were run to compare the methods in terms of time to healing with adjustment for independent predictors of healing. Secondary outcomes included incidence and number of adverse events per patient. Results Seven eligible trials were identified (887 patients), and patient level data were retrieved for five (797 patients, 90% of known randomised patients). The four layer bandage was associated with significantly shorter time to healing: hazard ratio (95% confidence interval) from multifactorial model based on five trials was 1.31 (1.09 to 1.58), P=0.005. Larger ulcer area at baseline, more chronic ulceration, and previous ulceration were all independent predictors of delayed healing. Data from two trials showed no evidence of a difference in adverse event profiles between the two bandage types. Conclusions Venous leg ulcers in patients treated with four layer bandages heal faster, on average, than those of people treated with the short stretch bandage. Benefits were consistent across patients with differing prognostic profiles. PMID:19376798

Antibiotics and antiseptics for venous leg ulcers.

PubMed

O'Meara, Susan; Al-Kurdi, Deyaa; Ologun, Yemisi; Ovington, Liza G; Martyn-St James, Marrissa; Richardson, Rachel

2013-12-23

Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. Two main strategies are used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics. The objective of this review was to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers; review authors also examined the effects of these interventions on clinical infection, bacterial flora, bacterial resistance, ulcer recurrence, adverse effects, patient satisfaction, health-related quality of life and costs. In May 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 24 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4); Ovid MEDLINE (1948 to Week 3 May 2013); Ovid MEDLINE (In-Process & Other Non-indexed Citations, 22 May 2013); Ovid EMBASE (1980 to Week 20 2013); and EBSCO CINAHL (1982 to 17 May 2013). No language or publication date restrictions were applied. Randomised controlled trials (RCTs) recruiting people with venous leg ulceration, evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two review authors while working independently. Information on the characteristics of participants, interventions and outcomes was recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one review author and were checked by a second. Data were pooled when appropriate. Forty-five RCTs reporting 53 comparisons and recruiting a total of 4486 participants were included, Many RCTs were small, and most were at high or unclear risk of bias. Ulcer infection status at baseline and duration of follow-up varied across RCTs. Five RCTs reported eight comparisons of systemic antibiotics, and the remainder evaluated topical preparations: cadexomer iodine (11 RCTs reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antisepticsCadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care. At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.

Endomicroscopy for assessing mucosal healing in patients with ulcerative colitis.

PubMed

Gheorghe, Cristian; Cotruta, Bogdan; Iacob, Razvan; Becheanu, Gabriel; Dumbrava, Mona; Gheorghe, Liana

2011-12-01

The assessment of tissue healing has emerged as an important treatment goal in patients with inflammatory bowel disease. In patients with ulcerative colitis (UC), mucosal healing may represent the ultimate therapeutic goal due to the fact that the inflammation is limited to the mucosal layer. Mucosal and histological healing may indicate a subset of UC patients in long-term clinical, endoscopic and histological remission in whom immunomodulators, biologics, and even aminosalicylates may be withdrawn. Confocal laser endomicroscopy allows the assessment of residual cellular inflammation, crypt and vessel architecture distortion during ongoing endoscopy, and therefore permits a real-time evaluation of histological healing in patients with ulcerative proctitis. Images of conventional optical microscopy and confocal laser endomicroscopy in patients with ulcerative proctitis in remission are presented.

Expected outcomes from topical haemoglobin spray in non-healing and worsening venous leg ulcers.

PubMed

Arenberger, P; Elg, F; Petyt, J; Cutting, K

2015-05-01

To evaluate the effect of topical haemoglobin spray on treatment response and wound-closure rates in patients with chronic venous leg ulcers. A linear regression model was used to forecast healing outcomes over a 12-month period. Simulated data were taken from normal distributions based on post-hoc analysis of a 72-patient study in non-healing and worsening wounds (36 patients receiving standard care and 36 receiving standard care plus topical haemoglobin spray). Using a simulated 25,000 'patients' from each group, the proportion of wound closure over time was projected. Simulation results predicted a 55% wound closure rate at six months in the haemoglobin group, compared with 4% in the standard care group. Over a 12-month simulation period, a 43% overall reduction in wound burden was predicted. With the haemoglobin spray, 85% of wounds were expected to heal in 12 months, compared with 13% in the standard care group. Topical haemoglobin spray promises a more effective treatment for chronic venous leg ulcers than standard care alone in wounds that are non-healing or worsening. Further research is required to validate these predictions and to identify achievable outcomes in other chronic wound types.

Proper muscle layer damage affects ulcer healing after gastric endoscopic submucosal dissection.

PubMed

Horikawa, Yohei; Mimori, Nobuya; Mizutamari, Hiroya; Kato, Yuhei; Shimazu, Kazuhiro; Sawaguchi, Masayuki; Tawaraya, Shin; Igarashi, Kimihiro; Okubo, Syunji

2015-11-01

Endoscopic submucosal dissection (ESD) is the established therapy for superficial gastrointestinal neoplasms. However, management of the artificial ulcers associated with ESD has become important and the relationship between ulcer healing factors and treatment is still unclear. We aimed to evaluate ESD-related artificial ulcer reduction ratio at 4 weeks to assess factors associating with ulcer healing after ESD that may lead to optimal treatment. Between January 2009 and December 2013, a total of 375 lesions fulfilled the expanded criteria for ESD. We defined ulcer reduction rate <90% as (A) poor-healing group; and rate ≥90% as (B) well-healing group. After exclusion, 328 lesions were divided into two groups and analyzed. These two groups were compared based on clinicopathological/endoscopic features, concomitant drugs, and treatment. Ulcer reduction rate was significantly correlated with factors related to the ESD procedure (i.e. procedure time, submucosal fibrosis, and injury of the proper muscle layer, in univariate analysis. Multivariate logistic regression analysis showed that submucosal fibrosis (F2) (P = 0.03; OR, 16.46; 95% CI, 1.31-206.73) and injury of the proper muscle layer (P = 0.01; OR, 4.27; 95% CI, 2.04-8.92) were statistically significant predictors of delayed healing. This single-center retrospective study indicated that ESD-induced artificial ulcer healing was affected by submucosal fibrosis and injury of the proper muscle layer, which induced damage to the muscle layer. Therefore, the preferable pharmacotherapy can be determined on completion of the ESD procedure. © 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

Dressings and topical agents for arterial leg ulcers.

PubMed

Forster, Rachel; Pagnamenta, Fania

2015-06-29

It is estimated that people in industrialised countries have a 1% chance of suffering from a leg ulcer at some time in their life. The majority of leg ulcers are associated with circulation problems; poor blood return in the veins causes venous ulcers (around 70% of ulcers) and poor blood supply to the legs causes arterial ulcers (around 22% of ulcers). Treatment of arterial leg ulcers is directed towards correcting the poor arterial blood supply, for example by correcting arterial blockages (either surgically or pharmaceutically). If the blood supply has been restored, these arterial ulcers can heal following principles of good wound care. Dressings and topical agents make up a part of good wound care for arterial ulcers but there are many products available and it is unclear what impact these have on ulcer healing. This is an update of a review first published in 2003. To determine whether topical agents and wound dressings affect healing in arterial ulcers. To compare healing rates, patient-centred outcomes and costs between wound dressings and topical agents. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2014) and The Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library) (2014, Issue 10). Randomised controlled trials (RCTs), or controlled clinical trials (CCTs) evaluating dressings and topical agents in the treatment of arterial leg ulcers were eligible for inclusion. The participants had to have ulcers that were described as arterial, and the time to healing, proportion completely healed, or rate of reduction in ulcer area had to be reported. All wound dressings and topical agents were eligible for inclusion in this review. The two review authors independently extracted information on the participants' characteristics, the interventions, and outcomes using a standardised data extraction form. Disagreements between the review authors were resolved through discussion. One trial met the inclusion criteria, which was a small trial that compared 2% ketanserin ointment in polyethylene glycol (PEG) with vehicle alone (PEG) control, changed twice a day in 40 participants with arterial leg ulcers. The overall quality of the evidence was low with a single small included study which showed inadequate reporting of the results and had too short a follow-up time (eight weeks) to be able to capture sufficient healing events to allow comparisons to be made. In addition, the study was of low methodological quality. The majority of the 'risk of bias' domains received an 'unclear' risk rating as very little information was provided in the text on the methods of the study. The trial demonstrated increased wound healing in the ketanserin group, compared with the control group, but the trial was too small and had too short a follow-up period (eight weeks) to be able to determine whether there was any difference in healing rates. It should also be noted that ketanserin is not licensed in all countries for use in humans. There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers.

The Proteolytic Fraction from Latex of Vasconcellea cundinamarcensis (P1G10) Enhances Wound Healing of Diabetic Foot Ulcers: A Double-Blind Randomized Pilot Study.

PubMed

Tonaco, Luís A B; Gomes, Flavia L; Velasquez-Melendez, Gustavo; Lopes, Miriam T P; Salas, Carlos E

2018-04-01

The aim of the study was to investigate the role of the proteolytic fraction from Vasconcellea cundinamarcensis, designated as P1G10, on the healing of chronic foot ulcers in neuropathic patients with diabetes 2. Fifty patients were enrolled in a prospective, randomized, double-blind trial, to verify the efficacy and safety of a topical dressing formulated with 0.1% P1G10, intended for wound healing, versus a hydrogel (control) protocol. Upon completion of the intervention, the outcome evaluated the number of patients attaining full epithelization (100%), or at least 80% healing. Statistical analysis compared the data on each group for the significance of the differences. Collection of data was finished in week 16, and the results were analyzed by intention to treat. The results showed that, in the control group, 5 patients attained 100% ulcer healing, 3 patients ≥ 80% healing and 11 experienced ulcer changes ≤ 80%, and the remainder showed no changes or their wounds became worse. Meanwhile, in the P1G10 group, 11 patients experienced full healing, 4 had healing ≥ 80% and 5 had ulcer changes ≤ lower than 80%, and the remainder showed no changes or their wounds became worse. The healing incidence for the first endpoint (100% healing) showed that the P1G10 group was 2.95-fold more efficacious than the control group (CI 95%) and 2.52-fold (CI, 95%) higher than its control for the second endpoint (80% healing). These data support the hypothesis that topical application of the proteolytic fraction identified as P1G10 significantly enhances foot ulcer healing compared to hydrogel treatment.

Non-healing foot ulcers in diabetic patients: general and local interfering conditions and management options with advanced wound dressings.

PubMed

Uccioli, Luigi; Izzo, Valentina; Meloni, Marco; Vainieri, Erika; Ruotolo, Valeria; Giurato, Laura

2015-04-01

Medical knowledge about wound management has improved as recent studies have investigated the healing process and its biochemical background. Despite this, foot ulcers remain an important clinical problem, often resulting in costly, prolonged treatment. A non-healing ulcer is also a strong risk factor for major amputation. Many factors can interfere with wound healing, including the patient's general health status (i.e., nutritional condition indicated by albumin levels) or drugs such as steroids that can interfere with normal healing. Diabetic complications (i.e., renal insufficiency) may delay healing and account for higher amputation rates observed in diabetic patients under dialysis treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and infection) may significantly influence healing by interfering with the physiological healing cascade and adding local release of factors that may worsen the wound. The timely and well-orchestrated release of factors regulating the healing process, observed in acute wounds, is impaired in non-healing wounds that are blocked in a chronic inflammatory phase without progressing to healing. This chronic phase is characterised by elevated protease activity (EPA) of metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase) that interfere with collagen synthesis, as well as growth factor release and action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state of non-healing ulcers. The availability of wound dressings that modulate EPA has added new therapeutic options for treating non-healing ulcers. The literature confirms advantages obtained by reducing protease activity in the wound bed, with better outcomes achieved by using these dressings compared with traditional ones. New technologies also allow a physician to know the status of the wound bed environment, particularly EPA, in a clinical setting. These may be helpful in guiding a clinician's options in treating very difficult-to-heal ulcers.

Treatment of Diabetic Foot Ulcers through Systemic Effects of Extremely Low Frequency Electromagnetic Fields

NASA Astrophysics Data System (ADS)

Trejo-Núñez, A. D.; Pérez-Chávez, F.; García-Sánchez, C.; Serrano-Luna, G.; Cañendo-Dorantes, L.

2008-08-01

This study was designed to, investigate the healing effects of extremely low frequency electromagnetic fields (ELF-EMF) on diabetic foot ulcers and test two different exposure systems aimed at reducing the ELF-EMF exposure time of patients. In the first system the ELF-EMF were applied to the arm where only 3% of the total blood volume/min circulates at any given time. In the second system the ELF-EMF were applied to the thorax where more than 100% of the total blood volume/minute circulates at any given time. Twenty-six diabetic patients, with superficial neuropathic ulcers unresponsive to medical treatment were included in this preliminary report. In the first group (17 patients), the arm was exposed two hours twice a week to a extremely low frequency electromagnetic field of 0.45-0.9 mTrms, 120 Hz generated inside a solenoid coil of 10.1 cm by 20.5 cm long. In the second group the thorax of 7 patients was exposed 25 minutes twice a week to an electromagnetic field of 0.4-0.85 mTrms, 120 Hz generated in the center of a squared quasi-Helmholtz coil 52 cm by side. One patient was assigned to a placebo configuration of each exposure system with identical appearance as the active equipment but without magnetic field. Patients with deep ulcers, infected ulcers, cancer, or auto-immune disease were excluded. These preliminary results showed that the two exposure systems accelerate the healing process of neuropathic ulcers. Complete healing of the ulcer had a median duration of 90 days in both exposure systems. Therefore thorax exposure where more blood is exposed to ELF-EMF per unit of time was able to reduce 4.8 times the patient treatment time. In those patients assigned to the placebo equipment no healing effects were observed. This study will continue with a parallel, double blind placebo controlled protocol.

Anti-inflammatory and in-vitro antibacterial activities of Traditional Chinese Medicine Formula Qingdaisan.

PubMed

Zhao, Xinghua; He, Xin; Zhong, Xiuhui

2016-12-05

Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS. Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control. Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn't show any significant antibacterial activity in vitro. The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn't have antibacterial activity to selected strains in vitro.

Fibreglass Total Contact Casting, Removable Cast Walkers, and Irremovable Cast Walkers to Treat Diabetic Neuropathic Foot Ulcers: A Health Technology Assessment

PubMed Central

Costa, Vania; Tu, Hong Anh; Wells, David; Weir, Mark; Holubowich, Corinne; Walter, Melissa

2017-01-01

Background Diabetic neuropathic foot ulcers are a risk factor for lower leg amputation. Many experts recommend offloading with fibreglass total contact casting, removable cast walkers, and irremovable cast walkers as a way to treat these ulcers. Methods We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences for offloading devices. We performed a systematic literature search on August 17, 2016, to identify randomized controlled trials that compared fibreglass total contact casting, removable cast walkers, and irremovable cast walkers with other treatments (offloading or non-offloading) in patients with diabetic neuropathic foot ulcers. We developed a decision-analytic model to assess the cost-effectiveness of fibreglass total contact casting, removable cast walkers, and irremovable cast walkers, and we conducted a 5-year budget impact analysis. Finally, we interviewed people with diabetes who had lived experience with foot ulcers, asking them about the different offloading devices and the factors that influenced their treatment choices. Results We identified 13 randomized controlled trials. The evidence suggests that total contact casting, removable cast walkers, and irremovable cast walkers are beneficial in the treatment of neuropathic, noninfected foot ulcers in patients with diabetes but without severe peripheral arterial disease. Compared to removable cast walkers, ulcer healing was improved with total contact casting (moderate quality evidence; risk difference 0.17 [95% confidence interval 0.00–0.33]) and irremovable cast walkers (low quality evidence; risk difference 0.21 [95% confidence interval 0.01–0.40]). We found no difference in ulcer healing between total contact casting and irremovable cast walkers (low quality evidence; risk difference 0.02 [95% confidence interval −0.11–0.14]). The economic analysis showed that total contact casting and irremovable cast walkers were less expensive and led to more health outcome gains (e.g., ulcers healed and quality-adjusted life-years) than removable cast walkers. Irremovable cast walkers were as effective as total contact casting and were associated with lower costs. The 5-year budget impact of funding total contact casting, removable cast walkers, and irremovable cast walkers (device costs only at 100% access) would be $17 to $20 million per year. The patients we interviewed felt that wound healing was improved with total contact casting than with removable cast walkers, but that removable cast walkers were more convenient and came with a lower cost burden. They reported no experience or familiarity with irremovable cast walkers. Conclusions Ulcer healing improved with total contact casting, irremovable cast walkers, and removable cast walkers, but total contact casting and irremovable cast walkers had higher rates of ulcer healing than removable cast walkers. Increased access to offloading devices could result in cost savings for the health system because of fewer amputations. Patients with diabetic foot ulcers reported a preference for total contact casting over removable cast walkers, largely because they perceived wound healing to be improved with total contact casting. However, cost, comfort, and convenience are concerns for patients. PMID:28989556

Fibreglass Total Contact Casting, Removable Cast Walkers, and Irremovable Cast Walkers to Treat Diabetic Neuropathic Foot Ulcers: A Health Technology Assessment.

PubMed

2017-01-01

Diabetic neuropathic foot ulcers are a risk factor for lower leg amputation. Many experts recommend offloading with fibreglass total contact casting, removable cast walkers, and irremovable cast walkers as a way to treat these ulcers. We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, and patient preferences for offloading devices. We performed a systematic literature search on August 17, 2016, to identify randomized controlled trials that compared fibreglass total contact casting, removable cast walkers, and irremovable cast walkers with other treatments (offloading or non-offloading) in patients with diabetic neuropathic foot ulcers. We developed a decision-analytic model to assess the cost-effectiveness of fibreglass total contact casting, removable cast walkers, and irremovable cast walkers, and we conducted a 5-year budget impact analysis. Finally, we interviewed people with diabetes who had lived experience with foot ulcers, asking them about the different offloading devices and the factors that influenced their treatment choices. We identified 13 randomized controlled trials. The evidence suggests that total contact casting, removable cast walkers, and irremovable cast walkers are beneficial in the treatment of neuropathic, noninfected foot ulcers in patients with diabetes but without severe peripheral arterial disease. Compared to removable cast walkers, ulcer healing was improved with total contact casting (moderate quality evidence; risk difference 0.17 [95% confidence interval 0.00-0.33]) and irremovable cast walkers (low quality evidence; risk difference 0.21 [95% confidence interval 0.01-0.40]). We found no difference in ulcer healing between total contact casting and irremovable cast walkers (low quality evidence; risk difference 0.02 [95% confidence interval -0.11-0.14]). The economic analysis showed that total contact casting and irremovable cast walkers were less expensive and led to more health outcome gains (e.g., ulcers healed and quality-adjusted life-years) than removable cast walkers. Irremovable cast walkers were as effective as total contact casting and were associated with lower costs. The 5-year budget impact of funding total contact casting, removable cast walkers, and irremovable cast walkers (device costs only at 100% access) would be $17 to $20 million per year. The patients we interviewed felt that wound healing was improved with total contact casting than with removable cast walkers, but that removable cast walkers were more convenient and came with a lower cost burden. They reported no experience or familiarity with irremovable cast walkers. Ulcer healing improved with total contact casting, irremovable cast walkers, and removable cast walkers, but total contact casting and irremovable cast walkers had higher rates of ulcer healing than removable cast walkers. Increased access to offloading devices could result in cost savings for the health system because of fewer amputations. Patients with diabetic foot ulcers reported a preference for total contact casting over removable cast walkers, largely because they perceived wound healing to be improved with total contact casting. However, cost, comfort, and convenience are concerns for patients.

Cost-effective non-surgical treatment of chronic pressure ulcers in the community.

PubMed

Dale, Megan; Cox-Martin, Bill; Shaw, Paula; Carolan-Rees, Grace

2014-03-01

The Salisbury Pressure Ulcer Outreach Service successfully treats patients with chronic pressure ulcers that have not healed during routine community treatment. These patients have grade 4 pressure ulcers, involving extensive destruction, or damage to muscle and bone. A combination of scientific, seating and tissue viability expertise with a holistic approach results in non-surgical healing for 70% of patients. For those who still require surgery, outcomes are more successful with this approach, resulting in low recurrence rates. Prior to creation of the outreach service, patients were referred directly for surgical closure, resulting in high recurrence levels and long waiting lists. The authors compared costs of the Pressure Ulcer Outreach Service with the previous system of surgical closure. The model base case found that the Pressure Ulcer Outreach Service saved £8588 per patient, and that cost savings could be even greater if the outreach service was extended into preventative work.

Factors Affecting Wound Healing in Individuals With Pressure Ulcers: A Retrospective Study.

PubMed

Karahan, Azize; AAbbasoğlu, Aysel; Işık, Sevcan Avcı; Çevik, Banu; Saltan, Çiğdem; Elbaş, Nalan Özhan; Yalılı, Ayşe

2018-02-01

Owing to the number and severity of concomitant factors, pressure ulcers remain a significant problem. A retrospective study of data from adult patients with a pressure ulcer was conducted to identify factors that may affect their healing. Data from patients who were hospitalized between January 1, 2011, and December 31, 2015, in a private Turkish university hospital who had a Stage 2, Stage 3, Stage 4, or unstageable pressure ulcer that was assessed using the Bates-Jensen Wound Assessment Tool (BWAT) were abstracted. The following variables were examined: demographic characteristics (gender, age, hospital unit, duration of hospitalization), health status and disease data (vital signs, mobility, nutrition, diagnosis, chronic diseases, medication), laboratory values (albumin, hemoglobin, blood glucose), and pressure ulcer characteristics (stage, location, healing status, duration) and pressure ulcer risk status as determined by patient Braden Scale score. Seventy-eight (78) patient records were identified. Patient mean age was 70.8 ± 13.47 years, and length of hospitalization was on average 32.52 ± 27.2 days. Most ulcers (62; 79.5%) were Stage 2 and located in the sacral area (59; 75.6%). Thirty-four (34) patients (43.6%) were discharged and 44 (56.4%) died. At the time of discharge or death, 65.4% of the ulcers had not healed. Patients whose wounds were healed were significantly more likely to have higher hemoglobin and mean arterial pressure, better mobility, received oral nutrition, and discharged from the hospital than patients whose ulcers did not heal. The results suggest that these variables, including Braden Scale and BWAT scores, might be considered when developing a treatment plan of care. Additional studies examining risk factors for nonhealing pressure ulcers, including studies with large samples to facilitate multivariate analyses, are needed.

Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study.

PubMed

Yang, Rui-Qi; Mao, Hua; Huang, Li-Yun; Su, Pei-Zhu; Lu, Min

2017-02-21

To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group ( P < 0.05). There were significant differences ( P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group ( P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group ( P < 0.05). Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa.

Clinical and cost-effectiveness of compression hosiery versus compression bandages in treatment of venous leg ulcers (Venous leg Ulcer Study IV, VenUS IV): a randomised controlled trial.

PubMed

Ashby, Rebecca L; Gabe, Rhian; Ali, Shehzad; Adderley, Una; Bland, J Martin; Cullum, Nicky A; Dumville, Jo C; Iglesias, Cynthia P; Kang'ombe, Arthur R; Soares, Marta O; Stubbs, Nikki C; Torgerson, David J

2014-03-08

Drawbacks exist with the standard treatment (four-layer compression bandages) for venous leg ulcers. We have therefore compared the clinical effectiveness and cost-effectiveness of two-layer compression hosiery with the four-layer bandage for the treatment of such ulcers. We undertook this pragmatic, open, randomised controlled trial with two parallel groups in 34 centres in England and Northern Ireland. The centres were community nurse teams or services, family doctor practices, leg ulcer clinics, tissue viability clinics or services, and wound clinics. Participants were aged 18 years or older with a venous leg ulcer and an ankle brachial pressure index of at least 0·8, and were tolerant of high compression. We randomly allocated participants (1:1) to receive two-layer compression hosiery or a four-layer bandage, using a remote randomisation service and prevalidated computer randomisation program. Participants were stratified by ulcer duration and ulcer area with permuted blocks (block sizes four and six). The primary endpoint was time to ulcer healing, with a maximum follow-up of 12 months. Although participants and health-care providers were not masked to treatment allocation, the primary endpoint was measured by masked assessment of photographs. Primary analysis was intention to treat with Cox regression, with adjustment for ulcer area, ulcer duration, physical mobility, and centre. This trial is registered with the ISRCTN register, number ISRCTN49373072. We randomly allocated 457 participants to the two treatment groups: 230 to two-layer hosiery and 227 to the four-layer bandage, of whom 453 (230 hosiery and 223 bandage) contributed data for analysis. Median time to ulcer healing was 99 days (95% CI 84-126) in the hosiery group and 98 days (85-112) in the bandage group, and the proportion of ulcers healing was much the same in the two groups (70·9% hosiery and 70·4% bandage). More hosiery participants changed their allocated treatment (38·3% hosiery vs 27·0% bandage; p=0·02). 300 participants had 895 adverse events, of which 85 (9·5%) were classed as serious but unrelated to trial treatment. Two-layer compression hosiery is a viable alternative to the four-layer bandage-it is equally as effective at healing venous leg ulcers. However, a higher rate of treatment changes in participants in the hosiery group than in the bandage group suggests that hosiery might not be suitable for all patients. NIHR Health Technology Assessment programme (07/60/26). Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictive value of neutrophil-to-lymphocyte ratio in diabetic wound healing.

PubMed

Vatankhah, Nasibeh; Jahangiri, Younes; Landry, Gregory J; McLafferty, Robert B; Alkayed, Nabil J; Moneta, Gregory L; Azarbal, Amir F

2017-02-01

The neutrophil-to-lymphocyte ratio (NLR) has been used as a surrogate marker of systemic inflammation. We sought to investigate the association between NLR and wound healing in diabetic wounds. The outcomes of 120 diabetic foot ulcers in 101 patients referred from August 2011 to December 2014 were examined retrospectively. Demographic, patient-specific, and wound-specific variables as well as NLR at baseline visit were assessed. Outcomes were classified as ulcer healing, minor amputation, major amputation, and chronic ulcer. The subjects' mean age was 59.4 ± 13.0 years, and 67 (66%) were male. Final outcome was complete healing in 24 ulcers (20%), minor amputation in 58 (48%) and major amputation in 16 (13%), and 22 chronic ulcers (18%) at the last follow-up (median follow-up time, 6.8 months). In multivariate analysis, higher NLR (odds ratio, 13.61; P = .01) was associated with higher odds of nonhealing. NLR can predict odds of complete healing in diabetic foot ulcers independent of wound infection and other factors. Copyright © 2016 Society for Vascular Surgery. All rights reserved.

The clinical and cost effectiveness of bee honey dressing in the treatment of diabetic foot ulcers.

PubMed

Moghazy, A M; Shams, M E; Adly, O A; Abbas, A H; El-Badawy, M A; Elsakka, D M; Hassan, S A; Abdelmohsen, W S; Ali, O S; Mohamed, B A

2010-09-01

Honey is known, since antiquity, as an effective wound dressing. Emergence of resistant strains and the financial burden of modern dressings, have revived honey as cost-effective dressing particularly in developing countries. Its suitability for all stages of wound healing suggests its clinical effectiveness in diabetic foot wound infections. Thirty infected diabetic foot wounds were randomly selected from patients presenting to Surgery Department, Suez Canal University Hospital, Ismailia, Egypt. Honey dressing was applied to wounds for 3 months till healing, grafting or failure of treatment. Changes in grade and stage of wounds, using University of Texas Diabetic Wound Classification, as well as surface area were recorded weekly. Bacterial load was determined before and after honey dressing. Complete healing was significantly achieved in 43.3% of ulcers. Decrease in size and healthy granulation was significantly observed in another 43.3% of patients. Bacterial load of all ulcers was significantly reduced after the first week of honey dressing. Failure of treatment was observed in 6.7% of ulcers. This study proves that commercial clover honey is a clinical and cost-effective dressing for diabetic wound in developing countries. It is omnipresence and concordance with cultural beliefs makes it a typical environmentally based method for treating these conditions. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Improvement of wound healing by water-filtered infrared-A (wIRA) in patients with chronic venous stasis ulcers of the lower legs including evaluation using infrared thermography

PubMed Central

Mercer, James B.; Nielsen, Stig Pors; Hoffmann, Gerd

2008-01-01

Background: Water-filtered infrared-A (wIRA) is a special form of heat radiation with a high tissue-penetration and with a low thermal burden to the surface of the skin. wIRA is able to improve essential and energetically meaningful factors of wound healing by thermal and non-thermal effects. Aim of the study: prospective study (primarily planned randomised, controlled, blinded, de facto with one exception only one cohort possible) using wIRA in the treatment of patients with recalcitrant chronic venous stasis ulcers of the lower legs with thermographic follow-up. Methods: 10 patients (5 males, 5 females, median age 62 years) with 11 recalcitrant chronic venous stasis ulcers of the lower legs were treated with water-filtered infrared-A and visible light irradiation (wIRA(+VIS), Hydrosun® radiator type 501, 10 mm water cuvette, water-filtered spectrum 550–1400 nm) or visible light irradiation (VIS; only possible in one patient). The uncovered wounds of the patients were irradiated two to five times per week for 30 minutes at a standard distance of 25 cm (approximately 140 mW/cm2 wIRA and approximately 45 mW/cm2 VIS). Treatment continued for a period of up to 2 months (typically until closure or nearly closure of the ulcer). The main variable of interest was “percent change of ulcer size over time” including complete wound closure. Additional variables of interest were thermographic image analysis, patient’s feeling of pain in the wound, amount of pain medication, assessment of the effect of the irradiation (by patient and by clinical investigator), assessment of feeling of the wound area (by patient), assessment of wound healing (by clinical investigator) and assessment of the cosmetic state (by patient and by clinical investigator). For these assessments visual analogue scales (VAS) were used. Results: The study showed a complete or nearly complete healing of lower leg ulcers in 7 patients and a clear reduction of ulcer size in another 2 of 10 patients, a clear reduction of pain and pain medication consumption (e.g. from 15 to 0 pain tablets per day), and a normalization of the thermographic image (before the beginning of the therapy typically hyperthermic rim of the ulcer with relative hypothermic ulcer base, up to 4.5°C temperature difference). In one patient the therapy of an ulcer of one leg was performed with the fully active radiator (wIRA(+VIS)), while the therapy of an ulcer of the other leg was made with a control group radiator (only VIS without wIRA), showing a clear difference in favour of the wIRA treatment. All mentioned VAS ratings improved remarkably during the period of irradiation treatment, representing an increased quality of life. Failures of complete or nearly complete wound healing were seen only in patients with arterial insufficiency, in smokers or in patients who did not have venous compression garment therapy. Discussion and conclusions: wIRA can alleviate pain considerably (with an impressive decrease of the consumption of analgesics) and accelerate wound healing or improve a stagnating wound healing process and diminish an elevated wound exudation and inflammation both in acute and in chronic wounds (in this study shown in chronic venous stasis ulcers of the lower legs) and in problem wounds including infected wounds. In chronic recalcitrant wounds complete healing is achieved, which was not reached before. Other studies have shown that even without a disturbance of wound healing an acute wound healing process can be improved (e.g. reduced pain) by wIRA. wIRA is a contact-free, easily used and pleasantly felt procedure without consumption of material with a good penetration effect, which is similar to solar heat radiation on the surface of the earth in moderate climatic zones. Wound healing and infection defence (e.g. granulocyte function including antibacterial oxygen radical formation of the granulocytes) are critically dependent on a sufficient energy supply (and on sufficient oxygen). The good clinical effect of wIRA on wounds and also on problem wounds and wound infections can be explained by the improvement of both the energy supply and the oxygen supply (e.g. for the granulocyte function). wIRA causes as a thermal effect in the tissue an improvement in three decisive factors: tissue oxygen partial pressure, tissue temperature and tissue blood flow. Besides this non-thermal effects of infrared-A by direct stimulation of cells and cellular structures with reactions of the cells have also been described. It is concluded that wIRA can be used to improve wound healing, to reduce pain, exudation, and inflammation and to increase quality of life. PMID:19675738

A cost and clinical effectiveness analysis among moist wound healing dressings versus traditional methods in home care patients with pressure ulcers.

PubMed

Souliotis, Kyriakos; Kalemikerakis, Ioannis; Saridi, Maria; Papageorgiou, Manto; Kalokerinou, Athena

2016-05-01

The aim of the study was a cost and clinical effectiveness analysis between moist wound healing dressings and gauze in a homecare set up for the treatment of stage III and IV pressure ulcers up to complete healing. In addition, we assessed the overall economic burden on the Healthcare System. Treatment method for each patient was chosen randomly by using sealed opaque envelopes. The authors monitored the healing progress and recorded treatment costs without interfering with the treatment process. The healing progress was estimated by using surface measurement transparent films. To estimate treatment costs, the authors took into account labor costs, cost of dressings, as well the cost of other materials such as cleansing gauzes, normal saline, syringes, examination gloves, antiseptics and adhesive tape. The patient group under treatment with moist wound healing dressings consisted of 27 men and 20 women aged 75.1 ± 8,6 and had an average ulcer surface of 43.5 ± 30.70 cm(2) ; the patient group under treatment with gauze comprised 25 men and 23 women aged 77.02 ± 8.02 and had an average ulcer surface 41.52 ± 29.41 cm(2) (p = 0.25, 95% CI, Student's t test). The average healing time for the moist wound healing dressings group' was 85.56 ± 52.09 days, while 121.4 ± 52.21 days for the "gauze group" (p = 0.0001, 95% CI, Student's t test). The dressing change frequency per patient was reduced in the "moist wound healing dressings group," 49.5 ± 29.61, compared with a dressing change frequency per patient of 222.6 ± 101.86 for the "gauze group" (p = 0.0001, 95% CI, Student's t test). The use of moist wound healing dressings had a lower total treatment cost of 1,351 € per patient compared with, the use of gauzes (3,888 €). © 2016 by the Wound Healing Society.

A controlled, randomized, comparative study of a radiant heat bandage on the healing of stage 3-4 pressure ulcers: a pilot study.

PubMed

Thomas, David R; Diebold, Marilyn R; Eggemeyer, Linda M

2005-01-01

Pressure ulcers, like other chronic wounds, fail to proceed through an orderly and timely process to produce anatomical or functional integrity. Treatment of pressure ulcers is directed to improving host factors and providing an optimum wound environment. In addition to providing a moist wound environment, it has been theorized that preventing hypothermia in a wound and maintaining a normothermic state might improve wound healing. Forty-one subjects with a stage 3 or stage 4 truncal pressure ulcer >1.0 cm(2) were recruited from outpatient clinics, long-term care nursing homes, and a rehabilitation center. The experimental group was randomized to a radiant-heat dressing device and the control group was randomized to a hydrocolloid dressing, with or without a calcium alginate filler. Subjects were followed until healed or for 12 weeks. Eight subjects (57%) in the experimental group had complete healing of their pressure ulcer compared with 7 subjects (44%) with complete healing in the control group (P = .46). Although a 13% difference in healing rate between the two arms of the study was found, this difference was not statistically significant. At almost all points along the healing curve, the proportion not healed was higher in the control arm.

The Use of Bovine Collagen-glycosaminoglycan Matrix for Atypical Lower Extremity Ulcers.

PubMed

Garwood, Caitlin S; Kim, Paul J; Matai, Vinay; Steinberg, John S; Evans, Karen K; Mitnick, Carol Deane B; Attinger, Christopher E

2016-09-01

The primary purpose of this study was to evaluate the use of bovine collagen-glycosaminoglycan matrix on atypical lower extremity ulcers. A retrospective chart review was performed on patients who underwent application of bovine collagen matrix to a lower extremity ulcer with an atypical etiology including autoimmune disease, sickle cell anemia, radiation therapy, connective tissue disease, vasculitis, or coagulopathy from January 2009 to October 2014. The following outcomes were evaluated: rate of ulcer healing and closure, number of ulcers that received a split-thickness skin graft, improvement in pain, and complications related to the ulcer. Thirty-eight patients with 71 lower extremity ulcers were analyzed. The most common ulcer etiolo- gies included rheumatoid arthritis, sickle cell anemia, and coagulopa- thy. After application of the bovine collagen matrix, 30 (42.3%) ulcers healed at a mean of 220.9 days. Of the 71 ulcers, 26 (36.6%) re- ceived a split-thickness skin graft after application of the matrix and 17 (65.4%) of those went on to complete healing. Ten patients had a local infection noted during follow-up, and 5 patients had dehiscence or dissociation of the matrix. Atypical lower extremity ulcers, such as those caused by autoimmune diseases and sickle cell anemia, proved difficult to heal. This case series shows that bovine collagen matrix can be a successful adjunctive therapy for the treatment of these challenging ulcers.

Roles of pro-angiogenic and anti-angiogenic factors as well as matrix metalloproteinases in healing of NSAID-induced small intestinal ulcers in rats.

PubMed

Gyenge, Melinda; Amagase, Kikuko; Kunimi, Shino; Matsuoka, Rie; Takeuchi, Koji

2013-10-06

We examined changes in the expression of a pro-angiogenic factor, vascular endothelial growth factor (VEGF), and an anti-angiogenic factor, endostatin, as well as matrix metalloproteinase (MMP)-2 and MMP-9 in the rat small intestine after administration of indomethacin and investigated the roles of these factors in the healing of indomethacin-induced small intestinal ulcers. Male SD rats were given indomethacin (10mg/kg) p.o. and euthanized at various time points (3-24h and 2-7days) after the administration. To impair the healing of these lesions, low-dose of indomethacin (2mg/kg) was given p.o. once daily for 6days starting 1day after ulceration. Levels of VEGF, endostatin, MMP-2 and MMP-9 were determined by Western blotting. The expression of both VEGF and endostatin was upregulated after the ulceration. Repeated administration of low-dose indomethacin impaired the ulcer healing with a decrease of VEGF expression and a further increase of endostatin expression, resulting in a marked decrease in the ratio of VEGF/endostatin expression. The levels of MMP-2 and MMP-9 were both significantly increased after the ulceration, but these responses were suppressed by the repeated indomethacin treatment. The healing of these ulcers was significantly delayed by the repeated administration of MMP inhibitors such as ARP-101 and SB-3CT. The results confirm the importance of the balance between pro-angiogenic and anti-angiogenic activities in the healing of indomethacin-induced small intestinal damage and further suggest that the increased expression of MMP-2 and MMP-9 is another important factor for ulcer healing in the small intestine. © 2013.

Gastric ulcer and the anti-arthritic drugs

PubMed Central

Emmanuel, J. H.; Montgomery, R. D.

1971-01-01

Sixteen cases are described of gastric ulcer in patients receiving anti-arthritic drugs. Half of the ulcers were in the antrum or on the greater curve. Ten patients were under treatment with indomethacin and/or prednisone, seven of them receiving both drugs. The ulcers healed readily when the drugs were withdrawn, and in the case of prednisone a continued daily dose of 10 mg or less did not prevent healing. All the patients with haemorrhage were taking aspirin, with or without other drugs. The literature is reviewed, and it is suggested that the increased incidence of peptic ulcer in patients receiving anti-arthritic drugs is confined to gastric ulcer. There is suggestive evidence of an increased susceptibility to antral ulcer in severe rheumatoid disease, which may largely account for the ‘steroid ulcer’. Indomethacin is potentially ulcerogenic, and its combined use with steroids may be inadvisable. Apart from its tendency to produce haemorrhagic erosions, the role of aspirin in the aetiology of chronic ulcer remains doubtful. No serious ill-effects have been reported in the use of ibuprofen or Distalgesic in ulcer subjects. PMID:5576491

Ozone Gas Bath Combined with Endovenous Laser Therapy for Lower Limb Venous Ulcers: A Randomized Clinical Trial.

PubMed

Zhou, Yi-Ting; Zhao, Xu-Dong; Jiang, Jian-Wei; Li, Xin-Sheng; Wu, Zhen-Hai

2016-10-01

Endovenous laser therapy (EVLT) is safe and effective for lower limb venous ulcers. However, severe necrosis and infection in the ulcer area are contraindications of puncture and EVLT. Local bath with ozone gas has been shown to improve the condition of ulcer areas. The aim of this study was to evaluate the clinical efficacy of ozone gas bath combined with EVLT in comparison with EVLT alone for the treatment for lower limb venous ulcers. Ninety-two patients with venous ulcers were randomized to receive ozone gas bath combined with EVLT (OEVLT group) or EVLT alone (EVLT group). In the OEVLT group, the venous ulcers were preconditioned with ozone gas bath prior to EVLT. The minimum follow-up time was 12 months. The two groups were compared in terms of complete occlusion of the treated veins, ulcer healing ratio, ratio of ulcer recurrence, patient satisfaction, complications, and side effects. There was no significant difference in venous occlusion between the two groups. The ratio of ulcer healing in the OEVLT group was significantly higher than the EVLT group at 12 months follow-up. Patients in the OEVLT group showed better satisfaction and a lower recurrence ratio than the OEVLT group. No severe complications or side effects occurred in either groups. Ozone gas bath combined with EVLT showed improved efficacy for the treatment of lower limb venous ulcers and lower recurrence ratio comparison with EVLT alone. This procedure is a safe and technically feasible.

Optimization and Evaluation of Gastroretentive Ranitidine HCl Microspheres by Using Factorial Design with Improved Bioavailability and Mucosal Integrity in Ulcer Model.

PubMed

Khattab, Abeer; Zaki, Nashwah

2017-05-01

The purpose of our investigation was to develop and optimize the drug entrapment efficiency and bioadhesion properties of mucoadhesive chitosan microspheres containing ranitidine HCl prepared by an ionotropic gelation method as a gastroretentive delivery system; thus, we improved their protective and therapeutic gastric effects in an ulcer model. A 3 × 2 2 full factorial design was adopted to study the effect of three different factors, i.e., the type of polymer at three levels (chitosan, chitosan/hydroxypropylmethylcellulose, and chitosan/methylcellulose), the type of solvent at two levels (acetic acid and lactic acid), and the type of chitosan at two levels (low molecular weight (LMW) and high molecular weight (HMW)). The studied responses were particle size, swelling index, drug entrapment efficiency, bioadhesion (as determined by wash-off and rinsing tests), and T 80% of drug release. Studies of the in vivo mucoadhesion and in vivo protective and healing effects of the optimized formula against gastric ulcers were carried out using albino rats (with induced gastric ulceration) and were compared to the effects of free ranitidine powder. A pharmacokinetic study in rabbits showed a significant, 2.1-fold increase in theAUC 0-24 of the ranitidine microspheres compared to free ranitidine after oral administration. The optimized formula showed higher drug entrapment efficiency and mucoadhesion properties and had more protective and healing effects on induced gastric ulcers in rats than ranitidine powder. In conclusion, the prolonged gastrointestinal residence time and the stability of the mucoadhesive microspheres of ranitidine as well as the synergistic healing effect of chitosan could contribute to increasing the potential of its anti-gastric ulcer activity.

Combined application of alginate dressing and human granulocyte-macrophage colony stimulating factor promotes healing in refractory chronic skin ulcers.

PubMed

Huang, Guobao; Sun, Tangqing; Zhang, Lei; Wu, Qiuhe; Zhang, Keyan; Tian, Qingfen; Huo, Ran

2014-06-01

The aim of the present study was to evaluate the clinical therapeutic effect of the combined application of alginate and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the healing of refractory chronic skin ulcers. A single center, three arm, randomized study was performed at Jinan Central Hospital (Jinan, Shandong, China). A total of 60 patients with refractory chronic skin ulcers, which persisted for >1 month, were enrolled and randomly assigned into one of the following three groups: alginate dressing/rhGM-CSF group (group A), rhGM-CSF only group (group B) and conventional (vaseline dressing) group (group C). The wound area rate was measured, granulation and color were observed and pain was evaluated. The data were summarized and statistical analysis was performed. The results demonstrated that group A exhibited a significantly faster wound healing rate and lower pain score compared with the other groups (P<0.01). In conclusion, the combined application of alginate dressing and rhGM-CSF for the treatment of refractory chronic skin ulcers demonstrated significant advantages. It promoted the growth of granulation tissue, accelerated re-epithelialization and also effectively reduced wound pain, and thus improved the quality of life for the patient. This suggests that the combined application of alginate and rhGM-CSF may be an effective therapeutic strategy for the clinical treatment of refractory chronic skin ulcers.

Moist exposed burn ointment for treating pressure ulcers

PubMed Central

Li, Wei; Ma, Yubo; Yang, Qi; Pan, Yu; Meng, Qinggang

2017-01-01

Abstract Background: Pressure ulcers often seriously affect the quality of life of patients. Moist Exposed Burn Ointment (MEBO) has been developed to treat patients with pressure ulcers. The present study aimed to evaluate the efficacy and safety of MEBO in the treatment of pressure ulcers in Chinese patients. Methods: Seventy-two patients with pressure ulcers were randomly assigned to 2 groups who received a placebo or MEBO for 2 months. The primary outcomes included the wound surface area (WSA) and pressure ulcer scale for healing (PUSH) tool. The secondary outcomes included a visual analog scale (VAS), questionnaire of ulcer status, and adverse effects. Results: Sixty-seven patients completed the study. After 2 months of treatment, the difference of mean change from the baseline was greater for MEBO (vs placebo) for WSA mean (SD) −6.0 (−8.8, −3.3), PUSH Tool −2.6 (−4.7, −1.5), and VAS score −2.9 (−4.4, −1.7). On the basis of the questionnaire, the pressure ulcers were “completely healed” (50.0% vs 16.7%) (P < .05) in patients after 2 months of treatment with MEBO versus placebo. No major adverse effects were found in the 2 groups. Conclusion: We showed that MEBO is effective and well tolerated for improving wound healing in Chinese patients with pressure ulcers. PMID:28723796

Clinical outcome of diabetic foot ulcers treated with negative pressure wound therapy and the transition from acute care to home care.

PubMed

Wu, Stephanie C; Armstrong, David G

2008-06-01

Diabetic foot ulcers affect millions of people in the United States of America and impose tremendous medical, psychosocial and financial loss or burden. Negative pressure wound therapy (NPWT) is generally well tolerated and appears to stimulate a robust granulation tissue response compared with other wound healing modalities. This device may be a cost-effective adjunctive wound healing therapy. This literature review will focus on the clinical outcome of diabetic foot ulcers treated with NPWT, its implication in the transition from acute care to home care, factors that might influence clinical outcomes in home care as well as quality-of-life aspects in these patients. Patient care for diabetic foot ulceration is complex and necessitates multiprofessional collaboration to provide comprehensive wound care. It is clear that when we strive for limb preservation in this most high-risk population, it is important to have an available versatile, efficacious wound healing modality. There is a need for an easy transition from acute care to home care. Resources need to be combined in a collaborative and synergistic fashion to allow patient to perform many daily living activities while receiving the potential benefits of an advanced wound healing modality.

Evaluation of wound healing in diabetic foot ulcer using platelet-rich plasma gel: A single-arm clinical trial.

PubMed

Mohammadi, Mohammad Hossein; Molavi, Behnam; Mohammadi, Saeed; Nikbakht, Mohsen; Mohammadi, Ashraf Malek; Mostafaei, Shayan; Norooznezhad, Amir Hossein; Ghorbani Abdegah, Ali; Ghavamzadeh, Ardeshir

2017-04-01

The aim of the present study was to evaluate the effectiveness of using autologous platelet-rich plasma (PRP) gel for treatment of diabetic foot ulcer (DFU) during the first 4 weeks of the treatment. In this longitudinal and single-arm trial, 100 patients were randomly selected after meeting certain inclusion and exclusion criteria; of these 100 patients, 70 (70%) were enrolled in the trial. After the primary care actions such as wound debridement, the area of each wound was calculated and recorded. The PRP therapy (2mL/cm 2 of ulcers) was performed weekly until the healing time for each patient. We used one sample T-test for healing wounds and Bootstrap resampling approach for reporting confidence interval with 1000 Bootstrap samples. The p-value<0.05 were considered statistically significant. The mean (SD) of DFU duration was 19.71 weeks (4.94) for units sampling. The ratio of subjects who withdrew from the study was calculated to be 2 (2.8%). Average area of 71 ulcers in the mentioned number of cases was calculated to be 6.11cm 2 (SD: 4.37). Also, the mean, median (SD) of healing time was 8.7, 8 weeks (SD: 3.93) except for 2 mentioned cases. According to one sample T-test, wound area (cm 2 ), on average, significantly decreased to 51.9% (CI: 46.7-57.1) through the first four weeks of therapy. Furthermore, significant correlation (0.22) was not found between area of ulcers and healing duration (p-value>0.5). According to the results, PRP could be considered as a candidate treatment for non-healing DFUs as it may prevent future complications such as amputation or death in this pathological phenomenon. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Bioengineered Living Cell Construct Activates an Acute Wound Healing Response in Venous Leg Ulcers

PubMed Central

Stone, Rivka C.; Stojadinovic, Olivera; Rosa, Ashley M.; Ramirez, Horacio A.; Badiavas, Evangelos; Blumenberg, Miroslav; Tomic-Canic, Marjana

2017-01-01

Chronic non-healing venous leg ulcers (VLUs) are widespread and debilitating, with high morbidity and associated costs; approximately $15 billion is spent annually on the care of VLUs in the US. Despite this, there is a paucity of treatments for VLUs, due to the lack of pathophysiologic insight into ulcer development as well as the lack of knowledge regarding biologic actions of existing VLU-targeted therapies. The bioengineered bilayered living cellular construct (BLCC) skin substitute is an FDA-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with non-healing VLUs were treated with either standard care (compression therapy) or the BLCC together with standard care. Tissue was collected from the VLU edge before and 1 week after treatment, and samples underwent comprehensive microarray, mRNA, and protein analyses. Ulcers treated with the BLCC skin substitute displayed three distinct transcriptomic patterns, suggesting that BLCC induced a shift from a non-healing to a healing tissue response involving modulation of inflammatory and growth factor signaling, keratinocyte activation, and attenuation of Wnt/β-catenin signaling. In these ways, BLCC application orchestrated a shift from the chronic non-healing ulcer microenvironment to a distinctive healing milieu resembling that of an acute, healing wound. Our findings provide in vivo evidence in patient VLU biopsies of pathways that can be targeted in the design of new therapies to promote healing of chronic VLUs. PMID:28053158

Topical lavender oil for the treatment of recurrent aphthous ulceration.

PubMed

Altaei, D Tagreed

2012-02-01

To determine the laboratory and clinical efficacy of lavender oil in the treatment of recurrent aphthous ulceration (RAU). This was a randomized double-blind, placebo-controlled study performed firstly to treat the induced ulcers by different methods in experimental animals (rabbits) treated with lavender oil or placebo. Clinical and histological healing was established by measuring the area of the ulcer and inflammation levels in each test group. Secondly, safety/toxicity; the median lethal dose (LD50) was studied in albino mice, and dermal irritation test was performed by primary irritation to the skin and measured by a patch-test technique on the intact skin of the albino rabbit. Thirdly, antibacterial effect; lavender oil was screened against bacteria obtained from swab specimen of human subjects' RAU using disc diffusion method. Fourthly, clinical study; 115 subjects (mean age 38 years, mean weight 75 kg) were divided into two groups of subjects topically treated with lavender oil or placebo. The clinical efficacy was assessed by inflammation level, erythema, edema, ulcer duration, ulcer size, mean area under the curve of ulcer area, healing time, and associated pain intensity and reduction. Animals treated with lavender oil showed a significant ulcer size reduction, increased rate of mucosal repair, and healing within 3 days of treatment compared to baseline and placebo groups [2-3 days (90%), 4 days (10%)] (P=0.001). The intraperitoneal LD50 value in mice was 6.5 gm/kg; clinical dermal irritation test showed no sign of irritation in the tested products. Lavender oil showed a broad antibacterial activity against all tested strains; it exhibited significant inhibition on tested bacteria where the value of zone of inhibition ranged from 14.5-24 mm vs Streptomycin (25 microg/disc) 12-22 +/- 0.5 mm; MIC was > 6.4-36 mg/ml. RAU patients treated with lavender oil showed a significant reduction in inflammation level, ulcer size, healing time, from 2-4 days [2 days (40%), 3 days (50%), 4 days (10%)], and pain relief mostly from the first dose, compared to baseline and placebo. No side effects were reported.

Effect of low-level laser therapy on the healing process of donor site in patients with grade 3 burn ulcer after skin graft surgery (a randomized clinical trial).

PubMed

Vaghardoost, Reza; Momeni, Mahnoush; Kazemikhoo, Nooshafarin; Mokmeli, Soheila; Dahmardehei, Mostafa; Ansari, Fereshteh; Nilforoushzadeh, Mohammad Ali; Sabr Joo, Parisa; Mey Abadi, Sara; Naderi Gharagheshlagh, Soheila; Sassani, Saeed

2018-04-01

Skin graft is a standard therapeutic technique in patients with deep ulcers, but managing donor site after grafting is very important. Although several modern dressings are available to enhance the comfort of donor site, using techniques that accelerate wound healing may enhance patient satisfaction. Low-level laser therapy (LLLT) has been used in several medical fields, including healing of diabetic, surgical, and pressure ulcers, but there is not any report of using this method for healing of donor site in burn patients. The protocols and informed consent were reviewed according to Medical Ethics Board of Shahid Beheshti University of Medical Sciences (IR.SBMU.REC.1394.363) and Iranian Registry of Clinical Trials (IRCT2016020226069N2). Eighteen donor sites in 11 patients with grade 3 burn ulcer were selected. Donor areas were divided into 2 parts, for laser irradiation and control randomly. Laser area was irradiated by a red, 655-nm laser light, 150 mW, 2 J/cm 2 , on days 0 (immediately after surgery), 3, 5, and 7. Dressing and other therapeutic care for both sites were the same. The patients and the person who analyzed the results were blinded. The size of donor site reduced in both groups during the 7-day study period (P < 0.01) and this reduction was significantly greater in the laser group (P = 0.01). In the present study, for the first time, we evaluate the effects of LLLT on the healing process of donor site in burn patients. The results showed that local irradiation of red laser accelerates wound healing process significantly.

Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice.

PubMed

Kawahara, Y; Nakase, Y; Isomoto, Y; Matsuda, N; Amagase, K; Kato, S; Takeuchi, K

2011-08-01

We examined the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice. Male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration. The numbers of macrophages and microvessels in the gastric mucosa were determined immunohistochemically with anti-CD68 and anti-CD31 antibodies, respectively. Expression of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) mRNA was determined via real-time reverse transcription-polymerase chain reaction (RT-PCR), and the mucosal content of prostaglandin (PG) E(2) was determined via enzyme immunoassay on day 10 after ulceration. The healing of gastric ulcers was significantly delayed in op/op mice compared with +/? mice. Further, significantly fewer macrophages were observed in the normal gastric mucosa of op/op mice than in +/? mice. Ulcer induction caused a marked accumulation of macrophages around the ulcer base in +/? mice, but this response was attenuated in op/op mice. The mucosal PGE(2) content as well as the expression of COX-2, VEGF, and TNF-α mRNA were all upregulated in the ulcerated area of +/? mice but significantly suppressed in op/op mice. The degree of vascularization in the ulcerated area was significantly lower in op/op mice than in +/? mice. Taken together, these results suggest that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production.

Maggots as a wound debridement agent for chronic venous leg ulcers under graduated compression bandages: A randomised controlled trial.

PubMed

Davies, C E; Woolfrey, G; Hogg, N; Dyer, J; Cooper, A; Waldron, J; Bulbulia, R; Whyman, M R; Poskitt, K R

2015-12-01

Slough in chronic venous leg ulcers may be associated with delayed healing. The purpose of this study was to assess larval debridement in chronic venous leg ulcers and to assess subsequent effect on healing. All patients with chronic leg ulcers presenting to the leg ulcer service were evaluated for the study. Exclusion criteria were: ankle brachial pressure indices <0.85 or >1.25, no venous reflux on duplex and <20% of ulcer surface covered with slough. Participants were randomly allocated to either 4-layer compression bandaging alone or 4-layer compression bandaging + larvae. Surface areas of ulcer and slough were assessed on day 4; 4-layer compression bandaging was then continued and ulcer size was measured every 2 weeks for up to 12 weeks. A total of 601 patients with chronic leg ulcers were screened between November 2008 and July 2012. Of these, 20 were randomised to 4-layer compression bandaging and 20 to 4-layer compression bandaging + larvae. Median (range) ulcer size was 10.8 (3-21.3) cm(2) and 8.1 (4.3-13.5) cm(2) in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Mann-Whitney U test, P = 0.184). On day 4, median reduction in slough area was 3.7 cm(2) in the 4-layer compression bandaging group (P < 0.05) and 4.2 cm(2) (P < 0.001) in the 4-layer compression bandaging + larvae group. Median percentage area reduction of slough was 50% in the 4-layer compression bandaging group and 84% in the 4-layer compression bandaging + larvae group (Mann-Whitney U test, P < 0.05). The 12-week healing rate was 73% and 68% in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Kaplan-Meier analysis, P = 0.664). Larval debridement therapy improves wound debridement in chronic venous leg ulcers treated with multilayer compression bandages. However, no subsequent improvement in ulcer healing was demonstrated. © The Author(s) 2014.

[Efficacy of compression knee-high socks ULCER X in treatment of venous-genesis trophic ulcers].

PubMed

Bogdanets, L I; Bogachev, V Iu; Lobanov, V N; Smirnova, E S

2013-01-01

The study was aimed at comparatively assessing the efficacy of treatment for venous trophic ulcers at stages II-III of the wound process using special compression knee-length socks of the ULCER X kit (Sigvaris AG, St. Gallen, Switzerland) and long-stretch bandages Lauma. Compression therapy was included into the programme of outpatient treatment of forty 31-to-74-year-old patients presenting with trophic ulcers (stage II-III of the wound process) with an average area of 5,36±1,1 cm2. The Study Group consisting of 20 patients used compression knitted fabrics in the form of knee-length socks ULCER X and the comparison group (n=20) used long-stretch bandages Lauma. The obtained findings (6 months) demonstrated that using compression therapy exerted a positive effect on the process of healing of venous trophic ulcers, also proving advantages of compression therapy with the knee-length socks ULCER X that create an adequate level of pressure on the crus and maintain it in long-term daily use, reliably accelerating the healing of venous trophic ulcers as compared with elastic long-stretch bandages. The use of long-stretch elastic bandages in treatment of venous trophic ulcers turned out to be not only ineffective but fraught with a possibility of the development of various complications. During 6 months of follow up the patients using the special knee-length socks ULCER X were found to have 80 % of ulcers healed (16 patients), mainly within the first 2 months, whereas using elastic bandages resulted in only 30 % of healing (6 patients) by the end of the study. Along with it, we documented a considerable decrease in the malleolar circumference in the study group patients (from 30,05±0,78 to 28,35±0,86 cm) and in the control group from 31,2±30,35 to 30,25±0,75 cm), accompanied and followed by more than a two-fold increase in quality of life of the patients along all the parameters in the study group and a 1.4-fold increase in the control group patients.

Healing, Antioxidant and Cytoprotective Properties of Indigofera truxillensis in Different Models of Gastric Ulcer in Rats

PubMed Central

Luiz-Ferreira, Anderson; Cola, Maira; Barbastefano, Victor; de-Faria, Felipe Meira; de Almeida, Ana Beatriz A.; Farias-Silva, Elisângela; Calvo, Tamara Regina; Hiruma-Lima, Clélia A.; Vilegas, Wagner; Souza-Brito, Alba Regina M.

2012-01-01

The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE2 production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes. PMID:23203107

Effect of negative pressure wound therapy on molecular markers in diabetic foot ulcers.

PubMed

Karam, Rehab A; Rezk, Noha A; Abdel Rahman, Tamer M; Al Saeed, Mohamed

2018-08-15

Diabetic foot ulcers are one of the most common complications of diabetes with high morbidity and mortality. Negative pressure wound therapy (NPWT) is one of the treatment modalities that facilitates the wound healing process; however, its molecular mechanism remains unclear. The aim of this study was to investigate the mechanism of action of NPWT in the treatment of diabetic foot ulcers via measuring the tissue expression of genes related to the wound healing process. The study included 40 patients with diabetic foot ulceration, 20 of them received NPWT and the other 20 were a control group treated with advanced moist therapy. Granulation tissue biopsies were obtained before and 10 days after treatment in both groups and subjected to real-time polymerase chain reaction to measure the mRNA expression of TGF-β1, VEGF, TNF-α, IL-1β, MMP-1, MMP-9 and TIMP-1 which are involved in the wound healing pathway. After 10 days of treatment with NPWT, the mRNA levels of IL-1β, TNF-α, MMP-1, and MMP-9 were significantly downregulated, while the levels of VEGF, TGF-β1 and TIMP-1 were significantly increased. Our study demonstrated that NPWT promotes wound healing in diabetic foot ulcers possibly by affecting growth factors, inflammatory cytokines, and matrix metalloproteinases. Copyright © 2018 Elsevier B.V. All rights reserved.

Quality of ulcer healing in gastrointestinal tract: Its pathophysiology and clinical relevance

PubMed Central

Arakawa, Tetsuo; Watanabe, Toshio; Tanigawa, Tetsuya; Tominaga, Kazunari; Fujiwara, Yasuhiro; Morimoto, Ken’ichi

2012-01-01

In this paper, we review the concept of quality of ulcer healing (QOUH) in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease (PUD) has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori (H. pylori), which is also the cause of ulcer recurrence. However, H. pylori-negative ulcers are present in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macrophages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer recurrence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a deficiency and/or an imbalance of endogenous growth factors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn’s disease and ulcerative colitis. PMID:23002355

The influence of polymorbidity, revascularization, and wound therapy on the healing of arterial ulceration.

PubMed

Tautenhahn, Joerg; Lobmann, Ralf; Koenig, Brigitte; Halloul, Zuhir; Lippert, Hans; Buerger, Thomas

2008-01-01

An ulcer categorized as Fontaine's stage IV represents a chronic wound, risk factor of arteriosclerosis, and co-morbidities which disturb wound healing. Our objective was to analyze wound healing and to assess potential factors affecting the healing process. 199 patients were included in this 5-year study. The significance levels were determined by chi-squared and log-rank tests. The calculation of patency rate followed the Kaplan-Meier method. Mean age and co-morbidities did not differ from those in current epidemiological studies. Of the patients with ulcer latency of more than 13 weeks (up to one year), 40% required vascular surgery. Vascular surgery was not possible for 53 patients and they were treated conservatively. The amputation rate in the conservatively treated group was 37%, whereas in the revascularizated group it was only 16%. Ulcers in patients with revascularization healed in 92% of cases after 24 weeks. In contrast, we found a healing rate of only 40% in the conservatively treated group (p<0.001). Revascularization appeared more often in diabetic patients (n=110; p<0.01) and the wound size and number of infections were elevated (p=0.03). Among those treated conservatively, wound healing was decelerated (p=0.01/0.02; chi(2) test). The success of revascularization, presence of diabetes mellitus, and wound treatment proved to be prognostic factors for wound healing in arterial ulcers.

Gastroprotective Mechanism and Ulcer Resolution Effect of Cyrtocarpa procera Methanolic Extract on Ethanol-Induced Gastric Injury

PubMed Central

Escobedo-Hinojosa, Wendy Itzel; García-Martínez, Karina; Guerrero Alquicira, Raquel; Cardoso-Taketa, Alexandre

2018-01-01

Gastric ulcers are a worldwide health problem and their poor healing is one of the most important causes for their recurrence. We have previously reported the remarkable gastroprotective and anti-Helicobacter pylori activities of the methanolic extract (CpMet) of Cyrtocarpa procera bark. This work investigates, in a murine model, the CpMet gastroprotective mechanism and establishes its preclinical efficacy in the resolution of ethanol-induced gastric ulcers. The results showed that the gastroprotective activity of CpMet is mainly associated with endogenous NO and prostaglandins, followed by sulfhydryl groups and KATP channels. Furthermore, CpMet (300 mg/kg, twice a day) orally administered during 20 consecutive days promoted an ulcer area reduction of 62.65% at the 20th day of the treatment. The effect was confirmed macroscopically by the alleviation of gastric mucosal erosions and microscopically by an increase in mucin content and a reduction in the inflammatory infiltration at the site of the ulcer. No clinical symptoms or signs of toxicity were observed in the treated animals. The results indicate the safety and efficacy of CpMet in promoting high quality of ulcer healing by different mechanisms, but mostly through cytoprotective and anti-inflammatory effects, making it a promising phytodrug for ulcer treatment. PMID:29507589

Factors affecting the healing of pressure ulcers in a Korean acute care hospital.

PubMed

Sung, Young Hee; Park, Kyung Hee

2011-01-01

We sought to determine the factors affecting pressure ulcer (PU) healing in an acute care facility in Korea. Data were collected between October 1, 2006, and September 30, 2007, regarding PU status and factors hypothesized to influence wound healing. We developed a form that queried factors thought to affect PU healing based on literature review. We also administered the Pressure Ulcer Scale for Healing (PUSH) tool to assess healing of PUs and calculated change in PUSH scale as the outcome variable reflecting the magnitude of the healing of PU. One hundred fifty eight patients with a total of 326 PUs in an acute care hospital located in Seoul, Korea, comprised the sample. The variables found to significantly affect PU healing included mean arterial pressure (MAP), serum albumin level, urinary incontinence, consultation with nutritionist, Braden Scale scale, wound size, and exudate amount. Pressure ulcer healing was improved when the MAP was higher (B = 0.034) and the serum albumin level was more than 2.8 g/dL (20.8 grams/liter) (B = 1.107). When managing patients in an acute care setting, PU healing may be improved by maintaining MAP and providing protein supplements to keep serum albumin level greater than 2.8 g/dL (20.8 grams/liter).

Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study

PubMed Central

Yang, Rui-Qi; Mao, Hua; Huang, Li-Yun; Su, Pei-Zhu; Lu, Min

2017-01-01

AIM To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group (P < 0.05). There were significant differences (P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group (P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group (P < 0.05). CONCLUSION Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa. PMID:28275307

Evaluation of the wound healing property of Boesenbergia longiflora rhizomes.

PubMed

Sudsai, Teeratad; Wattanapiromsakul, Chatchai; Nakpheng, Titpawan; Tewtrakul, Supinya

2013-10-28

The rhizomes of Boesenbergia longiflora (Wall.) Kuntze (Zingiberaceae) have been traditionally used for treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess by decoction with alcohol. The rhizomes of Boesenbergia longiflora were carried out to investigate for anti-inflammatory and wound healing activities in order to support the traditional use. The ethanolic extract of Boesenbergia longiflora and its fractions were tested using relevant in vitro anti-inflammatory and wound healing assays. For the in vitro studies, murine macrophage RAW264.7 cells and mouse fibroblast L929 cells were assessed for anti-inflammatory and fibroblast stimulatory activities, respectively. In vivo anti-inflammatory activity was determined by carrageenan-induced rat paw edema model as well as acute toxicity estimated by the up-and-down method in mice. The present study has demonstrated that the ethanolic extract of Boesenbergia longiflora rhizomes possesses a potent anti-inflammatory and wound healing activities. Among the isolated fractions, the CHCl3 fraction showed potent anti-inflammatory effect through nitric oxide inhibitory activity (IC50=5.5 μg/ml) and reduction of carrageenan-induced rat paw edema (ED50=222.7 mg/kg), whereas this fraction exhibited wound healing property via fibroblast migration on both day 1 (77.3%) and day 2 (100%) as well as enhanced collagen production (187.5 μg/ml) at concentration of 3 μg/ml, compared to that of the controls, 39.4% for fibroblast and 60.8 μg/ml for collagen, respectively. The anti-inflammatory mechanism of the CHCl3 fraction is found to suppress the iNOS and COX-2 mRNA expression. The scientific investigation of wound healing activity of Boesenbergia longiflora rhizomes support the Thai traditional uses for treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess. The EtOH extract and CHCl3 fraction exert potential wound healing property through NO inhibition, anti-oxidant effect and stimulation of fibroblast migration and collagen production. The phytochemical screening revealed that the CHCl3 fraction of Boesenbergia longiflora rhizomes contains diarylheptanoids, flavonoids and terpenes. The isolation of the compounds responsible for the wound healing effect is now in progress. © 2013 Elsevier Ireland Ltd. All rights reserved.

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.

PubMed

Cholapranee, A; Hazlewood, G S; Kaplan, G G; Peyrin-Biroulet, L; Ananthakrishnan, A N

2017-05-01

Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD. © 2017 John Wiley & Sons Ltd.

A Comparative Clinical Study on Five Types of Compression Therapy in Patients with Venous Leg Ulcers

PubMed Central

Dolibog, Pawel; Franek, Andrzej; Taradaj, Jakub; Dolibog, Patrycja; Blaszczak, Edward; Polak, Anna; Brzezinska-Wcislo, Ligia; Hrycek, Antoni; Urbanek, Tomasz; Ziaja, Jacek; Kolanko, Magdalena

2014-01-01

The aim of this study was to compare five types of compression therapy in venous leg ulcers (intermittent pneumatic vs. stockings vs. multi layer vs. two layer short stretch bandages vs. Unna boots). Primary study endpoints were analysis of changes of the total ulcer surface area, volume and linear dimensions inside observed groups. The secondary end points were comparisons between all groups the number of completely healed wounds (ulcer healing rates), Gilman index and percentage change of ulcer surface area. In total, 147 patients with unilateral venous leg ulcers were included to this study. Participants were randomly allocated to the groups: A, B, C, D and E. After two months the healing rate was the highest in group A (intermittent pneumatic compression) - 57.14%, 16/28 patients, B (ulcer stocking system) - 56.66%, 17/30 patients and C (multi layer short stretch bandage) - 58.62%, 17/29 patients. Significantly much worse rate found in group D (two layer short stretch bandages) - only 16.66%, 5/30 patients and E (Unna boots) - 20%, 6/30 patients. The analysis of changes of the percentage of Gilman index and wound total surface area confirmed that intermittent pneumatic compression, stockings and multi layer bandages are the most efficient. The two layer short - stretch bandages and Unna boots appeared again much less effective. PMID:24396284

Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: In vitro and in vivo studies.

PubMed

da Silva, Luisa Mota; Boeing, Thaise; Somensi, Lincon Bordignon; Cury, Benhur Judah; Steimbach, Viviane Miranda Bispo; Silveria, Alessandro Conrado de Oliveira; Niero, Rivaldo; Cechinel Filho, Valdir; Santin, José Roberto; de Andrade, Sérgio Faloni

2015-12-04

Maytenus robusta Reissek (Celastraceae) is traditionally used in Brazilian folk medicine to treat gastric ulcer, as a substitute for M. ilicifolia, which is almost extinct. The gastroprotective properties of M. robusta were demonstrated previously using only preventive approaches, such as acute gastric ulcer models. However, the healing effect of M. robusta in gastric ulcers remains unclear. The current study was carried out to investigate the healing effectiveness of M. robusta hydroalcoholic extract (HEMR) from aerial parts in the acetic acid-induced chronic ulcer model and to determine its effect on cell proliferation, scavenging free radicals, and inflammatory and oxidative damage. To evaluate the healing properties of HEMR in vivo, chronic gastric ulcer was induced in rats by 80% acid acetic. Next, different groups of animals (n=6) were treated orally with vehicle (water plus 1% tween, 1 ml/kg), omeprazole (20mg/kg), or HEMR (1-10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm(2)) was measured and a sample of gastric tissue was taken for histological and histochemical analysis. Evaluation of GSH and LOOH levels, GST, SOD, CAT and MPO activity was also performed at the site of the lesion. In parallel, radical scavenging activity, cytoprotective effect, and cell proliferation activity in fibroblasts (L929 cells) were determined by in vitro trials. The antisecretory properties were evaluated using the pylorus ligature model in rats, and the anti-Helicobacter pylori activity was determined in vitro. Acute toxicity was evaluated by relative organ weight and biochemical parameters in serum. The prokinetic properties were also evaluated in mice. Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0 ± 8.3mm(2)), the regeneration of gastric mucosa was evidenced in histological analysis. Moreover, HEMR treatment increased gastric mucin content and reduced oxidative stress and inflammatory parameters at the site of the ulcer. In vitro, HEMR (1-1000 µg/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1-100 µg/ml. Moreover, HEMR healing properties also were confirmed by enhancement of proliferation and coverage of scratched wounds in fibroblast monolayer. However, HEMR (10mg/kg) by the intraduodenal route did not promote changes in volume, pH, total acidity or pepsin activity in the pylorus ligature model, and HEMR up to 2000 µg/ml also did not present considerable activity against H. pylori. In relation to gastrointestinal motility, HEMR (10mg/kg, p.o) did not provoke alterations. It is also important to mention that oral administration of HEMR did not produce any sign of acute toxicity in animals. The data here obtained show that M. robusta has evident ulcer healing potential, mainly through the strengthening of protective factors of gastric mucosa, such as mucus layer, antioxidant defenses and cell proliferation. Taking into account the advantages of cultivation and harvesting of M. robusta compared to M. ilicifolia, and the evidence presented here, it is plausible to conclude that hydroalcoholic extract obtained from aerial parts of M. robusta is an interesting source for the development of a phytotherapeutic formulation to treat gastric ulcer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The molecular biology in wound healing & non-healing wound.

PubMed

Qing, Chun

2017-08-01

The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Débridement and Autologous Lipotransfer for Chronic Ulceration of the Diabetic Foot and Lower Limb Improves Wound Healing.

PubMed

Stasch, Tilman; Hoehne, Julius; Huynh, Tuan; De Baerdemaeker, Randy; Grandel, Siegfried; Herold, Christian

2015-12-01

The application of autologous lipotransfer (fat grafting, lipofilling) in reconstructive surgery is steadily becoming more popular as evidence of the regenerative and reparative effects of fat becomes better known. The authors investigated the use of autologous lipotransfer for treatment of chronic diabetic and other foot and lower limb ulcers. Twenty-six patients with nonhealing wounds were treated with surgical débridement and autologous lipotransfer (using the débridement and autologous lipotransfer method). The mean age of the wounds before intervention was 16.7 months. Wound size after débridement averaged 5.1 ± 2.6 cm2. On average, 7.1 ± 3.3 cc of lipoaspirate was transferred into the wound area. Twenty-two of 25 wounds (88 percent) healed completely within a mean of 68.0 ± 33.0 days. A reduction of wound size by 50 percent was achieved after an average of 4 weeks. In one patient with an ulcer within particularly scarred tissues on the lower limb, a repeated session of lipotransfer led to complete wound healing after another 4 weeks. The authors describe a simple and useful technique to improve wound healing in diabetic feet and chronic lower limb ulcers with a background of peripheral vascular disease, where other interventional options to achieve wound healing have failed.

A comparison of two doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial.

PubMed

Sykes, B W; Sykes, K M; Hallowell, G D

2014-07-01

Studies on omeprazole have reported that doses as low as 0.7 mg/kg bwt per os are potent suppressors of acid production. Yet, to date, no studies have compared treatment efficacy of different doses in clinical cases of equine gastric ulceration. Furthermore, no studies have been performed to compare the healing response of the squamous and glandular mucosa to acid suppression therapy. To compare: 1) the efficacy of 2 doses of omeprazole in the treatment of primary squamous and glandular gastric ulceration; and 2) the healing response of primary squamous and glandular gastric ulceration to acid suppression therapy. A blinded, randomised, dose-response clinical trial. Twenty Thoroughbred racehorses with grade ≥2/4 glandular ulceration were identified on gastroscopy. Seventeen horses also had grade ≥2/4 squamous ulceration. Horses were randomly assigned to one of 2 groups. Horses received either 2.0 g (high dose: 4.0 mg/kg bwt) or 0.8 g (low dose: 1.6 mg/kg bwt) of oral omeprazole per os once daily. Gastroscopy was repeated at 28-35 days. Time and dose significantly affected grades of squamous (P<0.0001, P = 0.02) and glandular (P = 0.006 and 0.005) ulceration. Data analysis did not support our hypothesis that the lower dose would have similar effects (i.e. be noninferior) to the higher dose when considering ulcer healing and ulcer improvement. Improvement was more likely with the high dose for the squamous (P = 0.05) but not glandular (P = 0.4) mucosa. The percentage of glandular ulcers that improved was less than squamous ulcers (P = 0.02). The results suggest that a dose-response exists for the treatment of both squamous and glandular ulcers. Improvement of glandular ulcers was not as complete as observed with squamous ulcers and current equine gastric ulcer syndrome treatment recommendations may not be appropriate for glandular disease. © 2013 EVJ Ltd.

[Pathophysiological aspects of wound healing in normal and diabetic foot].

PubMed

Maksimova, N V; Lyundup, A V; Lubimov, R O; Melnichenko, G A; Nikolenko, V N

2014-01-01

The main cause of long-term healing of ulcers in patients with diabetic foot is considered to be direct mechanical damage when walking due to reduced sensitivity to due to neuropathy, hyperglycemia, infection and peripheral artery disease. These factors determine the standard approaches to the treatment of diabeticfoot, which include: offloading, glycemic control, debridement of ulcers, antibiotic therapy and revascularization. Recently, however, disturbances in the healing process of the skin in diabetes recognized an additional factor affecting the timing of healing patients with diabetic foot. Improved understanding and correction of cellular, molecular and biochemical abnormalities in chronic wound in combination with standard of care for affords new ground for solving the problem of ulcer healing in diabetes.

Adaptive compression therapy for venous leg ulcers: a clinically effective, patient-centred approach.

PubMed

Harding, Keith G; Vanscheidt, Wolfgang; Partsch, Hugo; Caprini, Joseph A; Comerota, Anthony J

2016-06-01

A prospective, randomised, 12-week study was performed to evaluate the efficacy and tolerability of two compression methods for venous leg ulcers (VLUs); a new adaptive compression therapy (ACT) system, combining intermittent and sustained pneumatic compression (n = 38) and a conventional four-layer bandage system (n = 52). Primary outcomes were ulcer healing and safety. Secondary outcomes were comfort, compliance, ulcer pain, patient-perceived product performance and quality of life. Ulcer healing rate was similar (31·6% versus 42·3%, respectively, P = 0·30) between the treatments. Adverse events and patient-rated comfort were also similar. Average daily usage for the dual system was 10·5 and 1·8 hours in the sustained and intermittent modes, respectively, representing its use during 71% of waking hours. Predicted final ulcer pain was also similar (P = 0·68). Performance was subjectively better for adaptive compression and significantly higher for exudate management (P = 0·04), skin protection (P < 0·001), removal ease (P = 0·0007), bathing (P < 0·0001) and sleep comfort (P = 0·0405). The adjusted final quality-of-life score was 0·1025 higher for adaptive compression (P = 0·0375). Subjects with healed ulcers attained higher final scores than unhealed subjects (P = 0·0004). This study provides evidence that ACT is comparably efficacious to successfully heal VLUs compared with four-layer bandage management but is better accepted and achieves higher patient-reported quality-of-life scores in these challenging patients. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

PubMed Central

Bonnevie, O; Svendsen, L B; Holst-Christensen, J; Johansen, T S; Søltoft, J; Christiansen, P M

1979-01-01

In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer. PMID:385457

Arginine glutamate improves healing of radiation-induced skin ulcers in guinea pigs.

PubMed

Khalin, Igor; Kocherga, Ganna

2013-12-01

The increase in the incidence of the radiation-induced skin injury cases and the absence of standard treatments escalate the interest in finding new and effective drugs for these lesions. We studied the effect of a 40% solution of arginine glutamate on the healing of radiation-induced skin ulcers in guinea pigs. Radiation skin injury was produced on the thigh of guinea pigs by 60 Gy local X-ray irradiation. Treatment was started 6 weeks after the irradiation when ulcers had been formed. Arginine glutamate was administered by subcutaneous injections around the wound edge. Methyluracil was chosen as the comparison drug. The animals were sacrificed on day 21 after the start of treatment and the irradiated skin tissues were subjected to histological evaluation, cytokines analysis, lipid peroxidation and antioxidant enzymes analysis. We have shown that arginine glutamate significantly (p < 0.05) decreased levels of pro-inflammatory cytokines in the wound, restored the balance between lipid peroxidation formation and antioxidant enzymes activity and promoted cell proliferation as well as collagen synthesis. These results demonstrate that arginine glutamate successfully improves the healing of radiation-induced skin ulcers. In all probability, the curative effect is associated with the interaction of arginine with nitric oxide synthase II and arginase I, but further investigations are needed to validate this.

Combined therapy of Ulmo honey (Eucryphia cordifolia) and ascorbic acid to treat venous ulcers1

PubMed Central

Calderon, Mariano del Sol; Figueroa, Carolina Schencke; Arias, Jessica Salvo; Sandoval, Alejandra Hidalgo; Torre, Felipe Ocharan

2015-01-01

OBJECTIVE: to assess the clinical effect of topical treatment using Ulmo honey associated with oral ascorbic acid in patients with venous ulcers. METHOD: longitudinal and descriptive quantitative study. During one year, 18 patients were assessed who were clinically diagnosed with venous ulcer in different stages, male and female, adult, with a mean injury time of 13 months. Ulmo honey was topically applied daily. The dressing was applied in accordance with the technical standard for advanced dressings, combined with the daily oral consumptions of 500 mg of ascorbic acid. The monitoring instrument is the assessment table of venous ulcers. RESULTS: full healing was achieved in 100% of the venous ulcers. No signs of complications were observed, such as allergies or infection. CONCLUSION: the proposed treatment showed excellent clinical results for the healing of venous ulcers. The honey demonstrated debriding and non-adherent properties, was easy to apply and remove and was well accepted by the users. The described results generated a research line on chronic wound treatment. PMID:26039296

The use of immunosuppressive agents in the management of recalcitrant lower limb ulcers.

PubMed

Millen, A; Coulston, J; Brennan, J; Kennedy, T

2014-08-01

Lower limb ulcers that are resistant to standard forms of treatment place a significant burden on both patients and health services. There is no widely agreed definition of a recalcitrant ulcer but failure to heal following 6-12 months of focused treatment would identify a small group of patients with highly resistant ulceration. We describe a series of patients with recalcitrant ulceration for which immunosuppressive agents have been used. This is a case series of 13 patients who underwent immunomodulation therapy for lower limb ulcers at a tertiary referral university hospital. Regimens of immunomodulation used mainly ciclosporin and/or cyclophosphamide, with concurrent antibiotic therapy. Case notes and computer systems were analysed by two reviewers. A patient was deemed to have a success if their ulcer fully healed while on immunomodulation therapy. Over a period of eight years, from 2004-2012, 13 patients underwent immunomodulation therapy. Among these patients there were 18 ulcerated limbs. Ulcer healing occurred in 10 limbs out of 18 (55.6%) and full healing occurred in six patients (46.2%). Ulcers were present for a median of five years (range 2-40 years), with a median diameter of 7.5 cm (range 4-18 cm) before treatment. Treatment of truly recalcitrant ulceration can be very frustrating for both the patient and physician, with poor success from more standard forms of treatment. We report experience with immunomodulation therapy that suggests there may be benefit from using this treatment in a subset of patients with this debilitating disease.

Effect of Hydro-alcoholic Extract of Persian Oak (Quercus brantii) in Experimentally Gastric Ulcer

PubMed Central

Azizi, Shahrzad; Ghasemi Pirbalouti, Abdollah; Amirmohammadi, Mahdi

2014-01-01

Persian oak (Quercus brantii Lindl.) belongs the family Fagaceae, is a medicinal plant which seed flour is used to treat inflammatory and gastric ulcers by the tribes in south western Iran. The current study was done to evaluate the effect of hydro-alcoholic extract of Q. brantii seed flour for treatment of gastric ulcers induced by ethanol in Wistar rats. The hydro-alcoholic extract of Q. brantii was tested orally at doses of 250, 500, and 1000 mg/Kg, control group and standard drug (omperazole) on experimentally gastric ulceration. At the 3, 6, 9, and 14th days, ulcer index in mm2 and histopathological findings were evaluated. Results indicated the size of ulcers significantly reduced at 9, and 14 days after of Q. brantii extract treatment. Curative effect in the hydro-alcoholic induced gastric damage was 100% at 1000 mg/Kg and omeprazole, 99.8 % at 500 mg/Kg, and 95.4% at 250 mg/Kg after 14 days. Results of histopathological investigation showed the thickness of ulcerated mucosa was similar to the normal mucosa with 1000 mg/Kg of Q. brantii hydro-alcoholic extract after 14 days but in the groups treated by 250, and 500 mg/Kg, superficial erosions were visible in the central portion of the healed ulcers. In conclusion, the hydro-alcoholic extract of Q. brantii had active components (tannin = 8.2%) that accelerates ulcer healing and thus supported its traditional use. PMID:25276198

Effect of Hydro-alcoholic Extract of Persian Oak (Quercus brantii) in Experimentally Gastric Ulcer.

PubMed

Azizi, Shahrzad; Ghasemi Pirbalouti, Abdollah; Amirmohammadi, Mahdi

2014-01-01

Persian oak (Quercus brantii Lindl.) belongs the family Fagaceae, is a medicinal plant which seed flour is used to treat inflammatory and gastric ulcers by the tribes in south western Iran. The current study was done to evaluate the effect of hydro-alcoholic extract of Q. brantii seed flour for treatment of gastric ulcers induced by ethanol in Wistar rats. The hydro-alcoholic extract of Q. brantii was tested orally at doses of 250, 500, and 1000 mg/Kg, control group and standard drug (omperazole) on experimentally gastric ulceration. At the 3, 6, 9, and 14(th) days, ulcer index in mm(2) and histopathological findings were evaluated. Results indicated the size of ulcers significantly reduced at 9, and 14 days after of Q. brantii extract treatment. Curative effect in the hydro-alcoholic induced gastric damage was 100% at 1000 mg/Kg and omeprazole, 99.8 % at 500 mg/Kg, and 95.4% at 250 mg/Kg after 14 days. Results of histopathological investigation showed the thickness of ulcerated mucosa was similar to the normal mucosa with 1000 mg/Kg of Q. brantii hydro-alcoholic extract after 14 days but in the groups treated by 250, and 500 mg/Kg, superficial erosions were visible in the central portion of the healed ulcers. In conclusion, the hydro-alcoholic extract of Q. brantii had active components (tannin = 8.2%) that accelerates ulcer healing and thus supported its traditional use.

Effects of a pulsatile electrostatic field on ischemic injury to the diabetic foot: evaluation of refractory ulcers.

PubMed

Liani, Mario; Trabassi, Ernesto; Cusaro, Claudio; Zoppis, Elisabetta; Maduli, Elisabetta; Pezzato, Roberto; Piccoli, Paola; Maraschin, Maddalena; Bau, Piero; Cortese, Pietro; Cogo, Albero; Salvati, Filippo; Liani, Rossella

2014-10-01

The macro- and microcirculation disease, in patients with type 2 diabetes mellitus (T2DM), induces ischemic wounds of the lower limbs. We have tried to reduce the aggregation of red blood cells and to improve the O2 supply to the tissues and speed the healing of ulcers in T2DM patients. We enrolled 25 obese subjects without glucose intolerance (group A; BMI greater than 30 kg/m2), 20 obese adults intolerant to glucose (group B) and two subgroups, groups C and D, with T2DM and with leg ulcers. The groups A, B and C were treated with PESF. Body weight, O2 extraction, the capillary pulse, blood pressure and the surface of the ulcers were monitored. The technique PESF shows to have positive effects on the metabolism, on the reduction of body weight in the groups A and B, increasing extraction of O2 in group C and increase the speed of healing of wounds in group C compared to group D. In group A, there was a significant reduction in systolic and diastolic blood pressure. The technique PESF has affected the metabolic processes and the speed of wound healing ulcer in patients with T2DM. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

NeutroPhase® in chronic non-healing wounds

PubMed Central

Crew, John; Varilla, Randell; Rocas, Thomas Allandale; Debabov, Dmitri; Wang, Lu; Najafi, Azar; Rani, Suriani Abdul; Najafi, Ramin (Ron); Anderson, Mark

2012-01-01

Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient’s morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase® as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase® is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase® with and without NPWT. NeutroPhase® was non-toxic to living tissues. PMID:23272294

Cost-effectiveness of becaplermin gel on wound healing of diabetic foot ulcers.

PubMed

Gilligan, Adrienne M; Waycaster, Curtis R; Motley, Travis A

2015-01-01

We sought to determine the long-term cost effectiveness (payer's perspective) of becaplermin gel plus good wound care (BGWC) vs. good wound care (GWC) alone in terms of wound healing and risk of amputation in patients with diabetic foot ulcers (DFUs). Outcomes data were derived from a propensity score-matched cohort from the Curative Health Services database between 1998 and 2004, which was followed for 20 weeks. A four-state Markov model was used to predict costs and outcomes of wound healing and risk of amputation for BGWC vs. GWC alone over 1 year in patients with DFU. The primary outcome was closed-wound weeks. Transition probabilities for healing and amputation were derived from the aforementioned propensity score-matched cohorts. Ulcer recurrence was estimated from the medical literature. Utilization for becaplermin was calculated using the dosing algorithm in the product labeling. Of 24,898 eligible patients, 9.6% received BGWC. Based on the model, patients treated with BGWC had substantially more closed-wound weeks compared with GWC (16.1 vs. 12.5 weeks, respectively). More patients receiving BGWC had healed wounds at 1 year compared with those receiving GWC (48.1% vs. 38.3%). Risk of amputation was lower in the BGWC cohort (6.8% vs. 9.8%). Expected annual direct costs for DFU were $21,920 for BGWC and $24,640 for GWC. BGWC was economically dominant over GWC, providing better outcomes at a lower cost in patients with DFU. Compared with GWC alone, BGWC is more effective in healing wounds and lowering amputation risk, thereby decreasing long-term costs for DFU. © 2015 by the Wound Healing Society.

Sustained compression and healing of chronic venous ulcers.

PubMed Central

Blair, S. D.; Wright, D. D.; Backhouse, C. M.; Riddle, E.; McCollum, C. N.

1988-01-01

STUDY OBJECTIVE--Comparison of four layer bandage system with traditional adhesive plaster bandaging in terms of (a) compression achieved and (b) healing of venous ulcers. DESIGN--Part of larger randomised trial of five different dressings. SETTING--Outpatient venous ulcer clinic in university hospital. PATIENTS--(a) Pressure exerted by both bandage systems was measured in the same 20 patients. (b) Healing with the four layer bandage was assessed in 148 legs in 126 consecutive patients (mean age 71 (SE 2); range 30-96) with chronic venous ulcers that had resisted treatment with traditional bandaging for a mean of 27.2 (SE 8) months. INTERVENTIONS--(a) Four layer bandage system or traditional adhesive plaster bandaging for pressure studies; (b) four layer bandaging applied weekly for studies of healing. END POINTS--(a) Comparison of pressures achieved at the ankle for up to one week; (b) complete healing within 12 weeks. MEASUREMENTS AND MAIN RESULTS--(a) Four layer bandage produced higher initial pressures at the ankle of 42.5 (SE 1) mm Hg compared with 29.8 (1.8) for the adhesive plaster (p less than 0.001; 95% confidence interval 18.5 to 6.9). Pressure was maintained for one week with the four layer bandage but fell to 10.4 (3.5) mm Hg at 24 hours with adhesive plaster bandaging. (b) After weekly bandaging with the four layer bandage 110 of 48 venous ulcers had healed completely within 12 (mean 6.3 (0.4)) weeks. CONCLUSION--Sustained compression of over 40 mm Hg achieved with a multilayer bandage results in rapid healing of chronic venous ulcers that have failed to heal in many months of compression at lower pressures with more conventional bandages. PMID:3144330

Nurse clinic versus home delivery of evidence-based community leg ulcer care: A randomized health services trial

PubMed Central

Harrison, Margaret B; Graham, Ian D; Lorimer, Karen; VandenKerkhof, Elizabeth; Buchanan, Maureen; Wells, Phil S; Brandys, Tim; Pierscianowski, Tadeusz

2008-01-01

Background International studies report that nurse clinics improve healing rates for the leg ulcer population. However, these studies did not necessarily deliver similar standards of care based on evidence in the treatment venues (home and clinic). A rigorous evaluation of home versus clinic care is required to determine healing rates with equivalent care and establish the acceptability of clinic-delivered care. Methods Health Services RCT was conducted where mobile individuals were allocated to either home or nurse clinic for leg ulcer management. In both arms, care was delivered by specially trained nurses, following an evidence protocol. Primary outcome: 3-month healing rates. Secondary outcomes: durability of healing (recurrence), time free of ulcers, HRQL, satisfaction, resource use. Data were collected at base-line, every 3 months until healing occurred, with 1 year follow-up. Analysis was by intention to treat. Results 126 participants, 65 randomized to receive care in their homes, 61 to nurse-run clinics. No differences found between groups at baseline on socio-demographic, HRQL or clinical characteristics. mean age 69 years, 68% females, 84% English-speaking, half with previous episode of ulceration, 60% ulcers at inclusion < 5 cm2 for < 6 months. No differences in 3-month healing rates: clinic 58.3% compared to home care at 56.7% (p = 0.5) or in secondary outcomes. Conclusion Our findings indicate that organization of care not the setting where care is delivered influences healing rates. Key factors are a system that supports delivery of evidence-based recommendations with care being provided by a trained nursing team resulting in equivalent healing rates, HRQL whether care is delivered in the home or in a community nurse-led clinic. Trial registration ClinicalTrials.gov Protocol Registration System: NCT00656383 PMID:19036149

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

PubMed

Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial.

PubMed

Armstrong, D G; Hanft, J R; Driver, V R; Smith, A P S; Lazaro-Martinez, J L; Reyzelman, A M; Furst, G J; Vayser, D J; Cervantes, H L; Snyder, R J; Moore, M F; May, P E; Nelson, J L; Baggs, G E; Voss, A C

2014-09-01

Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and β-hydroxy-β-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and β-hydroxy-β-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and β-hydroxy-β-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and β-hydroxy-β-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and β-hydroxy-β-methylbutyrate in these high-risk subgroups might prove clinically valuable. © 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcers: A Health Technology Assessment

PubMed Central

Lambrinos, Anna; Chan, Brian; Wells, David; Holubowich, Corinne

2017-01-01

Background About 15% to 25% of people with diabetes will develop a foot ulcer. These wounds are often resistant to healing; therefore, people with diabetes experience lower limb amputation at about 20 times the rate of people without diabetes. If an ulcer does not heal with standard wound care, other therapeutic interventions are offered, one of which is hyperbaric oxygen therapy (HBOT). However, the effectiveness of this therapy is not clearly known. The objectives of this health technology assessment were to assess the safety, clinical effectiveness, and cost-effectiveness of standard wound care plus HBOT versus standard wound care alone for the treatment of diabetic foot ulcers. We also investigated the preferences and perspectives of people with diabetic foot ulcers through lived experience. Methods We performed a review of the clinical and economic literature for the effectiveness and cost-effectiveness of hyperbaric oxygen therapy, as well as the budget impact of HBOT from the perspective of the Ministry of Health and Long-Term Care. We assessed the quality of the body of clinical evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. To better understand the preferences, perspectives, and values of patients with diabetic foot ulcers and their experience with HBOT, we conducted interviews and administered an online survey. Results Seven randomized controlled trials and one nonrandomized controlled trial met the inclusion criteria. Comparing standard wound care plus HBOT with standard wound care alone, we found mixed results for major amputation rates (GRADE quality of evidence: low), a significant difference in favour of standard wound care plus HBOT on ulcers healed (GRADE quality of evidence: low), and no difference in terms of adverse events (GRADE quality of evidence: moderate). There is a large degree of uncertainty associated with the evaluation of the cost-effectiveness of standard wound care plus HBOT. However, results appear to suggest that this treatment results in lower costs and better outcomes than standard wound care alone. Funding HBOT will result in a budget impact of $4 million per year in immediate treatment costs for the Ontario Ministry of Health and Long-Term Care. This cost decreases to $0.5 million per year when downstream costs are considered. There is a substantial daily burden of care and emotional weight associated with living with diabetic foot ulcers, both of which are compounded by concern regarding possible amputation. Patients feel that HBOT is an effective treatment and reported that they were satisfied with how their ulcers healed and that this improved their quality of life. Conclusions The evidence makes it difficult to draw any definitive conclusions on the clinical and cost effectiveness of standard wound care plus HBOT versus standard wound care alone for the treatment of diabetic foot ulcers. PMID:28572866

Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: potential role for CTGF in human diabetic foot ulcer healing.

PubMed

Henshaw, F R; Boughton, P; Lo, L; McLennan, S V; Twigg, S M

2015-01-01

Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P < 0.001). These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

Case series of topical and orally administered β-glucan for the treatment of diabetic wounds: clinical study.

PubMed

Karaaslan, Onder; Kankaya, Yuksel; Sungur, Nezih; Kocer, Ugur; Sedat Cuzdan, Suat; Sahin, Belma; Uysal, Afsin

2012-01-01

Chronic, nonhealing wounds, foot ulcers, and lower extremity amputations are among the most problematic complications associated with diabetes mellitus. Standard care for diabetes-related chronic ulcers has included treatment of infection, weight off-loading, aggressive surgical débridement, and maintenance of a moist wound environment with frequent dressing changes. Yeast glucan is a particular high-molecular-weight polymer of β-(1,3)-glycosidic linkages of glycopyranose. We report our observations about the effectiveness of topically and orally administrated β-(1,3)-glucan for the treatment of chronic diabetic wounds and compare them to the literature results previously reported for similar wounds. Twenty-two patients with nonhealing ulcers associated with diabetes were included in this study. β-Glucan was given both orally and topically for the treatment of nonhealing ulcers. Macroscopic changes and surface areas of diabetic ulcers were recorded, and complete healing times were noted for each patient. A rapid decrease in size and healthy granulation were significantly observed in most patients. The duration of complete healing averaged 10.8 weeks (range 6-20 weeks). No adverse events were observed in the treatment period. The complete healing time was shorter than the results previously reported in the literature. Our observations support the view that application of glucan hastens epithelialization and wound closure, so topically and orally administered β-(1,3)-glucan therapy can help reverse some of the deficits in impaired healing diseases such as diabetes mellitus.

[Non-Helicobacter pylori, Non-nonsteroidal Anti-inflammatory Drug Peptic Ulcer Disease].

PubMed

Chang, Young Woon

2016-06-25

Non-Helicobacter pylori, non-NSAID peptic ulcer disease (PUD), termed idiopathic PUD, is increasing in Korea. Diagnosis is based on exclusion of common causes such as H. pylori infection, infection with other pathogens, surreptitious ulcerogenic drugs, malignancy, and uncommon systemic diseases with upper gastrointestinal manifestations. The clinical course of idiopathic PUD is delayed ulcer healing, higher recurrence, higher re-bleeding after initial ulcer healing, and higher mortality than the other types of PUD. Genetic predisposition, older age, chronic mesenteric ischemia, cigarette smoking, concomitant systemic diseases, and psychological stress are considered risk factors for idiopathic PUD. Diagnosis of idiopathic PUD should systematically explore all possible causes. Management of this disease is to treat underlying disease followed by regular endoscopic surveillance to confirm ulcer healing. Continuous proton pump inhibitor therapy is an option for patients who respond poorly to the standard ulcer regimen.

Olive oil-induced reduction of oxidative damage and inflammation promotes wound healing of pressure ulcers in mice.

PubMed

Donato-Trancoso, Aline; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

2016-07-01

The overproduction of reactive oxygen species (ROS) and exacerbated inflammatory response are the main events that impair healing of pressure ulcers. Therefore, olive oil may be a good alternative to improve the healing of these chronic lesions due to its anti-inflammatory and antioxidant properties. This study investigated the effect of olive oil administration on wound healing of pressure ulcers in mice. Male Swiss mice were daily treated with olive oil or water until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induced pressure ulcer formation. The olive oil administration accelerated ROS and nitric oxide (NO) synthesis and reduced oxidative damage in proteins and lipids when compared to water group. The inflammatory cell infiltration, gene tumor necrosis factor-α (TNF-α) expression and protein neutrophil elastase expression were reduced by olive oil administration when compared to water group. The re-epithelialization and blood vessel number were higher in the olive oil group than in the water group. The olive oil administration accelerated protein expression of TNF-α, active transforming growth factor-β1 and vascular endothelial growth factor-A when compared to water group. The collagen deposition, myofibroblastic differentiation and wound contraction were accelerated by olive oil administration when compared to water group. Olive oil administration improves cutaneous wound healing of pressure ulcers in mice through the acceleration of the ROS and NO synthesis, which reduces oxidative damage and inflammation and promotes dermal reconstruction and wound closure. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

[Impact of topical application of autologous platelet-rich gel on medical expenditure and length of stay in hospitals in diabetic patients with refractory cutaneous ulcers].

PubMed

Li, Lan; Wang, Chun; Wang, Yan; He, Li-Ping; Yang, Yan-Zhi; Chen, Li-Hong; Chen, Da-Wei; Li, Xiu-Jun; Ran, Xing-Wu

2012-09-01

To evaluate the potential financial benefit of topical application of autologous platelet-rich gel (APG) in treating diabetic refractory cutaneous ulcers. A single-center prospective randomized controlled trial was undertaken, with 117 patients with proven diabetic refractory cutaneous ulcers participating in the study. The patients who gave informed consents were randomly assigned into standard care group (n = 58) or standard care plus topical application of APG treatment group (n = 59). The outcome of healing and the medical expenditur and length of stay in the patients were compared between the two groups. The APG-treated group had better healing outcomes than the standard-treated group. The APG-treated group had 84.750 (50/59) complete healing and 98.31% improvement, higher than the 68.97% (40/58) and 75.86%, respectively, in the standard-treated group (P = 0.026). The median length for healing in the APG-treated patients was 36 days, shorter than the 45 days in the standard-treated patients (P = 0.012). The total medical expenditure and length of stay in hospitals were not significantly different between APG-treated patients [yen 38223 (23070-57398); 57 (41-94) days] and standard-treated patients [yen 35070 (24436-53649); 58 (31.75-58.50) days) (P = 0.455 and 0.301 respectively). Spendings on items such as medicine, artificial treatment, materials, interventional operation, surgical procedures, laboratory tests and other auxiliary examination, accommodations, meals, nursing care and debridement and dressing change were similar between the two groups (P > 0.05). There is an advantage for the topical application of APG on diabetic refractory cutaneous ulcers in terms of the healing outcomes. APG is a cost-effective choice for patients with diabetic refractory cutaneous ulcers.

Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers.

PubMed

Brem, Harold; Young, Jan; Tomic-Canic, Marjana; Isaacs, Cary; Ehrlich, H Paul

2003-01-01

Bilayered living human skin equivalent (HSE) consists of cultured keratinocytes residing on the surface of a fibroblast-populated collagen lattice. Although HSE is FDA-approved for treatment of diabetic foot and venous stasis ulcers, its clinical efficacy remains limited, because the molecular mechanisms underlying its therapeutic effect are not fully understood. It is, therefore, often applied mistakenly as a skin graft. In this report, we delineate a mechanism of HSE biological effect and consequent optimal clinical use in accelerating closure of diabetic foot ulcers. HSE was grafted onto nude mice and the release of various growth factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Clinical: HSE was grafted onto 11 consecutive patients with diabetes who had 13 non-ischemic foot ulcers and healing was measured as time to 100% closure (e.g., no drainage and 100% epithelialized). HSE cellular components were determined to express 15 different growth factors/cytokine genes known to promote wound healing. Histological evidence from the nude mice showed that the collagen component of HSE underwent remodeling within the first seven days of grafting. Clinical: All diabetic foot ulcers healed in 31.8 12.4 days. Local release of a unique combination of 15 growth factors expressed by HSE keratinocyte and fibroblast components generates closure of diabetic foot ulcers. HSE should be applied with the same surgical conditions for a skin graft (i.e., no cellulitis, no drainage, and negligible bacteria). We hypothesize that bilayered HSE generates its effect by way of the local synthesis and release of multiple growth factors in specific combination and concentration, which improves the impaired reparative process of chronic wounds.

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy.

PubMed

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-11-15

The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

PubMed Central

Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

2016-01-01

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID:27282261

The Canadian Bandaging Trial: Evidence-informed leg ulcer care and the effectiveness of two compression technologies

PubMed Central

2011-01-01

Background Objective: To determine the relative effectiveness of evidence-informed practice using two high compression systems: four-layer (4LB) and short-stretch bandaging (SSB) in community care of venous leg ulcers. Design and Setting: Pragmatic, multi-centre, parallel-group, open-label, randomized controlled trial conducted in 10 centres. Cognitively intact adults (≥18 years) referred for community care (home or clinic) with a venous ulceration measuring ≥0.7cm and present for ≥1 week, with an ankle brachial pressure index (ABPI) ≥0.8, without medication-controlled Diabetes Mellitus or a previous failure to improve with either system, were eligible to participate. Methods Consenting individuals were randomly allocated (computer-generated blocked randomization schedule) to receive either 4LB or SSB following an evidence-informed protocol. Primary endpoint: time-to- healing of the reference ulcer. Secondary outcomes: recurrence rates, health-related quality of life (HRQL), pain, and expenditures. Results 424 individuals were randomized (4LB n = 215; SSB n = 209) and followed until their reference ulcer was healed (or maximum 30 months). An intent-to-treat analysis was conducted on all participants. Median time to ulcer healing in the 4LB group was 62 days [95% confidence interval (CI) 51 to 73], compared with 77 days (95% CI 63 to 91) in the SSB group. The unadjusted Kaplan-Meier curves revealed the difference in the distribution of cumulative healing times was not significantly different between group (log rank χ2 = 0.001, P = 0.98) nor ulcers recurrence (4LB, 10.1%; SSB, 13.3%; p = 0.345). Multivariable Cox Proportional Hazard Modeling also showed no significant between-bandage differences in healing time after controlling for significant covariates (p = 0.77). At 3-months post-baseline there were no differences in pain (no pain: 4LB, 22.7%; SSB, 26.7%; p = 0.335), or HRQL (SF-12 Mental Component Score: 4LB, 55.1; SSB, 55.8; p = 0.615; SF-12 Physical Component Score: 4LB, 39.0; SSB, 39.6; p = 0.675). The most common adverse events experienced by both groups included infection, skin breakdown and ulcer deterioration. Conclusions The Canadian Bandaging Trial revealed that in the practice context of trained RNs using an evidence-informed protocol, the choice of bandage system (4LB and SSB) does not materially affect healing times, recurrence rates, HRQL, or pain. From a community practice perspective, this is positive news for patient-centred care allowing individual/family and practitioner choice in selecting compression technologies based on circumstances and context. Trial registration clinicaltrials.gov Identifier: NCT00202267 PMID:21995267

Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate (De-Nol).

PubMed Central

Baron, J H; Barr, J; Batten, J; Sidebotham, R; Spencer, J

1986-01-01

Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks' treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion. PMID:3084345

Antibiotics and antiseptics for venous leg ulcers.

PubMed

O'Meara, Susan; Al-Kurdi, Deyaa; Ologun, Yemisi; Ovington, Liza G; Martyn-St James, Marrissa; Richardson, Rachel

2014-01-10

Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. Two main strategies are used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics. The objective of this review was to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers. In May 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 24 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 4); Ovid MEDLINE (1948 to Week 3 May 2013); Ovid MEDLINE (In-Process & Other Non-indexed Citations, 22 May 2013); Ovid EMBASE (1980 to Week 20 2013); and EBSCO CINAHL (1982 to 17 May 2013). No language or publication date restrictions were applied. Randomised controlled trials (RCTs) recruiting people with venous leg ulceration, evaluating at least one systemic antibiotic, topical antibiotic or topical antiseptic that reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by two review authors while working independently. Information on the characteristics of participants, interventions and outcomes was recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including randomisation, allocation concealment, blinding of participants and outcome assessors, incomplete outcome data and study group comparability at baseline. Data extraction and validity assessment were conducted by one review author and were checked by a second. Data were pooled when appropriate. Forty-five RCTs reporting 53 comparisons and recruiting a total of 4486 participants were included, Many RCTs were small, and most were at high or unclear risk of bias. Ulcer infection status at baseline and duration of follow-up varied across RCTs. Five RCTs reported eight comparisons of systemic antibiotics, and the remainder evaluated topical preparations: cadexomer iodine (11 RCTs reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antiseptics Cadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care. At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.

Low level laser therapy (GaAlInP 660 nm) in healing of a chronic venous ulcer: a case study

NASA Astrophysics Data System (ADS)

Botaro, C. A.; Faria, L. A.; Oliveira, R. G.; Bruno, R. X.; Rocha, C. A. Q. C.; Paiva-Oliveira, E. L.

2015-07-01

The venous ulcer represents approximately 70% to 90% of inferior member ulcers, and the most common etiological factor is venous insufficiency, triggered by venous hypertension. Currently in Brazil there are several types of lasers used in physiotherapy, which benefit biological potential, emitting low power radiation, with anti-inflammatory, analgesic, healing and circulatory effects. This study aimed at the analysis of low level laser therapy effects (LLLT) on the process of tissue repair in chronic venous ulcers. We conducted a case study of a patient with a venous ulcer in the lateral region of the right inferior member. The patient underwent LLLT, which used a GaAlInP diode laser, with a wavelength of 660 nm and energy density of 4 J cm-2 applied punctually at the edges of the wound, with an average distance of 1 cm between the points with a pen-laser perpendicular wrapped in paper and a plastic wrap, keeping contact with the tissue. After four months of therapy and a total of 21 sessions, an improvement was noticeable in the gross appearance of the wound, but after a month and a half without therapy, the dimensions of the wound increased in length and width. Analyzing the results of this case study allows us to conclude that the LLLT GaAlInP (660 nm) with an energy density of 4 J cm-2, was not successful in the healing of venous ulcers.

Clopidogrel inhibits angiogenesis of gastric ulcer healing via downregulation of vascular endothelial growth factor receptor 2.

PubMed

Luo, Jiing-Chyuan; Peng, Yen-Ling; Chen, Tseng-Shing; Huo, Teh-Ia; Hou, Ming-Chih; Huang, Hui-Chun; Lin, Han-Chieh; Lee, Fa-Yauh

2016-09-01

Although clopidogrel does not cause gastric mucosal injury, it does not prevent peptic ulcer recurrence in high-risk patients. We explored whether clopidogrel delays gastric ulcer healing via inhibiting angiogenesis and to elucidate the possible mechanisms. Gastric ulcers were induced in Sprague Dawley rats, and ulcer healing and angiogenesis of ulcer margin were compared between clopidogrel-treated rats and controls. The expressions of the proangiogenic growth factors and their receptors including basic fibroblast growth factor (bFGF), bFGF receptor (FGFR), vascular endothelial growth factor (VEGF), VEGFR1, VEGFR2, platelet-derived growth factor (PDGF)A, PDGFB, PDGFR A, PDGFR B, and phosphorylated form of mitogenic activated protein kinase pathways over the ulcer margin were compared via western blot and reverse transcription polymerase chain reaction. In vitro, human umbilical vein endothelial cells (HUVECs) were used to elucidate how clopidogrel inhibited growth factors-stimulated HUVEC proliferation. The ulcer sizes were significantly larger and the angiogenesis of ulcer margin was significantly diminished in the clopidogrel (2 and 10 mg/kg/d) treated groups. Ulcer induction markedly increased the expression of phosphorylated form of extracellular signal-regulated kinase (pERK), FGFR2, VEGF, VEGFR2, and PDGFRA when compared with those of normal mucosa. Clopidogrel treatment significantly decreased pERK, FGFR2, VEGF, VEGFR2, and PDGFRA expression at the ulcer margin when compared with those of the respective control group. In vitro, clopidogrel (10(-6)M) inhibited VEGF-stimulated (20 ng/mL) HUVEC proliferation, at least, via downregulation of VEGFR2 and pERK. Clopidogrel inhibits the angiogenesis of gastric ulcer healing at least partially by the inhibition of the VEGF-VEGFR2-ERK signal transduction pathway. Copyright © 2015. Published by Elsevier B.V.

Candida albicans infection delays duodenal ulcer healing in cysteamine-induced duodenal ulcers in rats.

PubMed

Jin, Longxue; Yoshida, Masashi; Nakamura, Tetsuya; Ishikawa, Hideki; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Shinoda, Masahiro; Saikawa, Yoshiro; Wada, Norihito; Kameyama, Kaori; Kumai, Koichiro; Kubota, Tetsuro; Sano, Katsuko; Nagao, Keisuke; Amagai, Masayuki; Kitagawa, Yuko; Kitajima, Masaki

2008-11-01

A low curability of ulcers infected with Candida has been reported in the literature. The aim of the study reported here was to investigate experimentally whether Candida infection affects the healing of ulcers. Candida albicans (the Candida group) or saline (the control group) was administered intragastrically into rats with a cysteamine-induced duodenal ulcer. The duodenal lesions, vascular endothelial growth factor A (VEGF-A) and proliferating cell nuclear antigen (PCNA) were assessed. On Day 7 post-administration, 70.4% rats of the Candida group had a duodenal ulcer compared with 33.3% in the control group (P < 0.05). The duodenal ulcer in the Candida group was significantly larger and deeper than that in the control group. The number of VEGF-A- and PCNA-positive cells was smaller and the area of VEGF-A expression was lower in the Candida group. Using a rat model, we have demonstrated that Candida infection can delay the wound healing process of duodenal ulcers by means of a low expression of VEGF-A and PCNA.

Roles of calcitonin gene-related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis.

PubMed

Ohno, Takashi; Hattori, Youichiro; Komine, Rie; Ae, Takako; Mizuguchi, Sumito; Arai, Katsuharu; Saeki, Takeo; Suzuki, Tatsunori; Hosono, Kanako; Hayashi, Izumi; Oh-Hashi, Yoshio; Kurihara, Yukiko; Kurihara, Hiroki; Amagase, Kikuko; Okabe, Susumu; Saigenji, Katsunori; Majima, Masataka

2008-01-01

The gastrointestinal tract is known to be rich in neural systems, among which afferent neurons are reported to exhibit protective actions. We tested whether an endogenous neuropeptide, calcitonin gene-related peptide (CGRP), can prevent gastric mucosal injury elicited by ethanol and enhance healing of acetic acid-induced ulcer using CGRP knockout mice (CGRP(-/-)). The stomach was perfused with 1.6 mmol/L capsaicin or 1 mol/L NaCl, and gastric mucosal injury elicited by 50% ethanol was estimated. Levels of CGRP in the perfusate were determined by enzyme immunoassay. Gastric ulcers were induced by serosal application of absolute acetic acid. Capsaicin inhibited injured area dose-dependently. Fifty percent ethanol containing capsaicin immediately increased intragastric levels of CGRP in wild-type (WT) mice, although 50% ethanol alone did not. The protective action of capsaicin against ethanol was completely abolished in CGRP(-/-). Preperfusion with 1 mol/L NaCl increased CGRP release and reduced mucosal damage during ethanol perfusion. However, 1 mol/L NaCl was not effective in CGRP(-/-). Healing of ulcer elicited by acetic acid in CGRP(-/-) mice was markedly delayed, compared with that in WT. In WT, granulation tissues were formed at the base of ulcers, and substantial neovascularization was induced, whereas those were poor in CGRP(-/-). Expression of vascular endothelial growth factor was more markedly reduced in CGRP(-/-) than in WT. CGRP has a preventive action on gastric mucosal injury and a proangiogenic activity to enhance ulcer healing. These results indicate that the CGRP-dependent pathway is a good target for regulating gastric mucosal protection and maintaining gastric mucosal integrity.

Heberprot-P: a novel product for treating advanced diabetic foot ulcer.

PubMed

Berlanga, Jorge; Fernández, José I; López, Ernesto; López, Pedro A; del Río, Amaurys; Valenzuela, Carmen; Baldomero, Julio; Muzio, Verena; Raíces, Manuel; Silva, Ricardo; Acevedo, Boris E; Herrera, Luis

2013-01-01

Diabetic foot ulcer is a principal diabetic complication. It has been shown that diabetic patients have decreased growth factor concentrations in their tissues, particularly epidermal growth factor. Growth factor shortage impairs wound healing, which leads to chronic nonhealing wounds and sometimes eventual amputation. Ischemic diabetic foot ulcer is the most difficult to treat and confers the highest amputation risk. Injecting epidermal growth factor deep into the wound bottom and contours encourages a more effective pharmacodynamic response in terms of granulation tissue growth and wound closure. Epidermal growth factor injected into the ulcer matrix may also result in association with extracellular matrix proteins, thus enhancing cell proliferation and migration. Heberprot-P is an innovative Cuban product containing recombinant human epidermal growth factor for peri- and intra-lesional infiltration; evidence reveals it accelerates healing of deep and complex ulcers, both ischemic and neuropathic, and reduces diabetes-related amputations. Clinical trials of Heberprot-P in patients with diabetic foot ulcers have shown that repeated local infiltration of this product can enhance healing of chronic wounds safely and efficaciously. As a result, Heberprot-P was registered in Cuba in 2006, and in 2007 was included in the National Basic Medications List and approved for marketing. It has been registered in 15 other countries, enabling treatment of more than 100,000 patients. Heberprot-P is a unique therapy for the most complicated and recalcitrant chronic wounds usually associated with high amputation risk. Local injection in complex diabetic wounds has demonstrated a favorable risk-benefit ratio by speeding healing, reducing recurrences and attenuating amputation risk. Further testing and deployment worldwide of Heberprot-P would provide an opportunity to assess the product's potential to address an important unmet medical need.

Supervised exercise training as an adjunct therapy for venous leg ulcers: a randomized controlled feasibility trial.

PubMed

Klonizakis, M; Tew, G A; Gumber, A; Crank, H; King, B; Middleton, G; Michaels, J A

2018-05-01

Venous leg ulcers (VLUs) are typically painful and heal slowly. Compression therapy offers high healing rates; however, improvements are not usually sustained. Exercise is a low-cost, low-risk and effective strategy for improving physical and mental health. Little is known about the feasibility and efficacy of supervised exercise training used in combination with compression therapy patients with VLUs. To assess the feasibility of a 12-week supervised exercise programme as an adjunct therapy to compression in patients with VLUs. This was a two-centre, two-arm, parallel-group, randomized feasibility trial. Thirty-nine patients with venous ulcers were recruited and randomized 1 : 1 either to exercise (three sessions weekly) plus compression therapy or compression only. Progress/success criteria included exercise attendance rate, loss to follow-up and patient preference. Baseline assessments were repeated at 12 weeks, 6 months and 1 year, with healing rate and time, ulcer recurrence and infection incidents documented. Intervention and healthcare utilization costs were calculated. Qualitative data were collected to assess participants' experiences. Seventy-two per cent of the exercise group participants attended all scheduled exercise sessions. No serious adverse events and only two exercise-related adverse events (both increased ulcer discharge) were reported. Loss to follow-up was 5%. At 12 months, median ulcer healing time was lower in the exercise group (13 vs. 34·7 weeks). Mean National Health Service costs were £813·27 for the exercise and £2298·57 for the control group. The feasibility and acceptability of both the supervised exercise programme in conjunction with compression therapy and the study procedures is supported. © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

[Leg ulcers of venous origin and their development around the year 1955].

PubMed

Marmasse, J

1984-01-01

"Eventual sclerosis of varicose veins, elastic support, methodical ambulation": the teachings of R. Tournay remains the golden rule for healing leg ulcers of venous origin. Their frequent relapse has been perceptibly reduced by the therapeutic developments of the "Sixties", and notably the phlebosurgical routine collaboration in many cases of varicose ulcers Conference on Stripping, Paris, 1960); and the use of stockings calculated scientifically to benefit healed phlebitic ulcers (Van der Molen, Passien).

Prediction of venous wound healing with laser speckle imaging.

PubMed

van Vuuren, Timme Maj; Van Zandvoort, Carina; Doganci, Suat; Zwiers, Ineke; tenCate-Hoek, Arina J; Kurstjens, Ralph Lm; Wittens, Cees Ha

2017-12-01

Introduction Laser speckle imaging is used for noninvasive assessment of blood flow of cutaneous wounds. The aim of this study was to assess if laser speckle imaging can be used as a predictor of venous ulcer healing. Methods After generating the flux speckle images, three regions of interest (ROI) were identified to measure the flow. Sensitivity, specificity, negative predictive value, and positive predictive value for ulcer healing were calculated. Results In total, 17 limbs were included. A sensitivity of 92.3%, specificity of 75.0%, PPV of 80.0%, and NPV 75.0% were found in predicting wound healing based on laser speckle images. Mean flux values were lowest in the center (ROI I) and showed an increase at the wound edge (ROI II, p = 0.03). Conclusion Laser speckle imaging shows acceptable sensitivity and specificity rates in predicting venous ulcer healing. The wound edge proved to be the best probability for the prediction of wound healing.

Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre-existing gastric ulcers.

PubMed

Magierowski, Marcin; Magierowska, Katarzyna; Hubalewska-Mazgaj, Magdalena; Sliwowski, Zbigniew; Ginter, Grzegorz; Pajdo, Robert; Chmura, Anna; Kwiecien, Slawomir; Brzozowski, Tomasz

2017-10-01

Carbon monoxide (CO), a gaseous mediator produced by haem oxygenases (HOs), has been shown to prevent stress-, ethanol-, aspirin- and alendronate-induced gastric damage; however, its role in gastric ulcer healing has not been fully elucidated. We investigated whether CO released from tricarbonyldichlororuthenium (II) dimer (CORM-2) can affect gastric ulcer healing and determined the mechanisms involved in this healing action. Gastric ulcers were induced in Wistar rats by serosal application of acetic acid. Animals received 9 days of treatment with RuCl 3 [2.5 mg·kg -1 intragastrically (i.g.)], haemin (5 mg·kg -1 i.g.), CORM-2 (0.1-10 mg·kg -1 i.g.) administered alone or with zinc protoporphyrin IX (ZnPP, 10 mg·kg -1 i.g.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 mg·kg -1 i.g.), N G -nitro-l-arginine (l-NNA, 15 mg·kg -1 i.g.), indomethacin (5 mg·kg -1 i.g.) or glibenclamide (10 mg·kg -1 i.g.). Gastric ulcer area and gastric blood flow (GBF) were assessed planimetrically, microscopically and by laser flowmeter respectively. Gastric mRNA/protein expressions of EGF, EGF receptors, VEGFA, HOs, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), COX-2, hypoxia-inducible factor (HIF)-1α and pro-inflammatory iNOS, IL-1β and TNF-α were determined by real-time PCR or Western blots. CORM-2 and haemin but not RuCl 3 or ZnPP decreased ulcer size while increasing GBF. These effects were reduced by ODQ, indomethacin, l-NNA and glibenclamide. CORM-2 significantly decreased the expression of pro-inflammatory markers, Nrf2/HO1 and HIF-1α, and up-regulated EGF. CO released from CORM-2 or endogenously produced by the HO1/Nrf2 pathway accelerates gastric ulcer healing via an increase in GBF, an up-regulation in EGF expression and down-regulation of the inflammatory response. © 2017 The British Pharmacological Society.

Foam dressings for treating pressure ulcers.

PubMed

Walker, Rachel M; Gillespie, Brigid M; Thalib, Lukman; Higgins, Niall S; Whitty, Jennifer A

2017-10-12

Pressure ulcers, also known as pressure injuries and bed sores, are localised areas of injury to the skin or underlying tissues, or both. Dressings made from a variety of materials, including foam, are used to treat pressure ulcers. An evidence-based overview of dressings for pressure ulcers is needed to enable informed decision-making on dressing use. This review is part of a suite of Cochrane Reviews investigating the use of dressings in the treatment of pressure ulcers. Each review will focus on a particular dressing type. To assess the clinical and cost effectiveness of foam wound dressings for healing pressure ulcers in people with an existing pressure ulcer in any care setting. In February 2017 we searched: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase; EBSCO CINAHL Plus and the NHS Economic Evaluation Database (NHS EED). We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Published or unpublished randomised controlled trials (RCTs) and cluster-RCTs, that compared the clinical and cost effectiveness of foam wound dressings for healing pressure ulcers (Category/Stage II or above). Two review authors independently performed study selection, risk of bias and data extraction. A third reviewer resolved discrepancies between the review authors. We included nine trials with a total of 483 participants, all of whom were adults (59 years or older) with an existing pressure ulcer Category/Stage II or above. All trials had two arms, which compared foam dressings with other dressings for treating pressure ulcers.The certainty of evidence ranged from low to very low due to various combinations of selection, performance, attrition, detection and reporting bias, and imprecision due to small sample sizes and wide confidence intervals. We had very little confidence in the estimate of effect of included studies. Where a foam dressing was compared with another foam dressing, we established that the true effect was likely to be substantially less than the study's estimated effect.We present data for four comparisons.One trial compared a silicone foam dressing with another (hydropolymer) foam dressing (38 participants), with an eight-week (short-term) follow-up. It was uncertain whether alternate types of foam dressing affected the incidence of healed pressure ulcers (RR 0.89, 95% CI 0.45 to 1.75) or adverse events (RR 0.37, 95% CI 0.04 to 3.25), as the certainty of evidence was very low, downgraded for serious limitations in study design and very serious imprecision.Four trials with a median sample size of 20 participants (230 participants), compared foam dressings with hydrocolloid dressings for eight weeks or less (short-term). It was uncertain whether foam dressings affected the probability of healing in comparison to hydrocolloid dressings over a short follow-up period in three trials (RR 0.85, 95% CI 0.54 to 1.34), very low-certainty evidence, downgraded for very serious study limitations and serious imprecision. It was uncertain if there was a difference in risk of adverse events between groups (RR 0.88, 95% CI 0.37 to 2.11), very low-certainty evidence, downgraded for serious study limitations and very serious imprecision. Reduction in ulcer size, patient satisfaction/acceptability, pain and cost effectiveness data were also reported but we assessed the evidence as being of very low certainty.One trial (34 participants), compared foam and hydrogel dressings over an eight-week (short-term) follow-up. It was uncertain if the foam dressing affected the probability of healing (RR 1.00, 95% CI 0.78 to 1.28), time to complete healing (MD 5.67 days 95% CI -4.03 to 15.37), adverse events (RR 0.33, 95% CI 0.01 to 7.65) or reduction in ulcer size (MD 0.30 cm 2 per day, 95% CI -0.15 to 0.75), as the certainty of the evidence was very low, downgraded for serious study limitations and very serious imprecision.The remaining three trials (181 participants) compared foam with basic wound contact dressings. Follow-up times ranged from short-term (8 weeks or less) to medium-term (8 to 24 weeks). It was uncertain whether foam dressings affected the probability of healing compared with basic wound contact dressings, in the short term (RR 1.33, 95% CI 0.62 to 2.88) or medium term (RR 1.17, 95% CI 0.79 to 1.72), or affected time to complete healing in the medium term (MD -35.80 days, 95% CI -56.77 to -14.83), or adverse events in the medium term (RR 0.58, 95% CI 0.33 to 1.05). This was due to the very low-certainty evidence, downgraded for serious to very serious study limitations and imprecision. Reduction in ulcer size, patient satisfaction/acceptability, pain and cost effectiveness data were also reported but again, we assessed the evidence as being of very low certainty.None of the included trials reported quality of life or pressure ulcer recurrence. It is uncertain whether foam dressings are more clinically effective, more acceptable to users, or more cost effective compared to alternative dressings in treating pressure ulcers. It was difficult to make accurate comparisons between foam dressings and other dressings due to the lack of data on reduction of wound size, complete wound healing, treatment costs, or insufficient time-frames. Quality of life and patient (or carer) acceptability/satisfaction associated with foam dressings were not systematically measured in any of the included studies. We assessed the certainty of the evidence in the included trials as low to very low. Clinicians need to carefully consider the lack of robust evidence in relation to the clinical and cost-effectiveness of foam dressings for treating pressure ulcers when making treatment decisions, particularly when considering the wound management properties that may be offered by each dressing type and the care context.

The Effect of Combined Ultrasound and Electric Field Stimulation on Wound Healing in Chronic Ulcerations.

PubMed

Avrahami, Ram; Rosenblum, Jonathan; Gazes, Michael; Rosenblum, Sean; Litman, Leib

2015-07-01

Ultrasound and electric stimulation are known therapies for the treatment of chronic ulcerations. Combined modulated ultrasound and electric field stimulation (CUSEFS) have never been studied as a single modality. The authors evaluate the results of CUSEFS (BRH Medical Ltd, Jerusalem, Israel) on a variety of wound types in a number of clinics. This retrospective analysis looked at ulcers treated with CUSEFS in 4 clinics. Wounds were evaluated by an independent assessor and data was evaluated by an independent statistician. Of the 300 wounds treated with the CUSEFS device, only those classified as diabetic foot ulcers (DFUs) or venous leg ulcers (VLUs) were evaluated. A treatment was deemed successful if the wound was 50% closed within 4 weeks. Subjects were then followed to see if their wounds completely closed within 16 weeks. Of the 27 DFUs treated, 59.3% (16) achieved 50% closure within 4 weeks. Of the 38 VLUs treated, 71.1% (27) achieved 50% closure within 4 weeks. It was found that variables such as gender, size of the wound at presentation, and longevity of the wound had no bearing on the outcome. The age of the patient had an effect on the outcome of the VLUs. The wound healing trajectory was supported in that there was a significant difference in the achievement of total closure between those subjects who had a successful trial and those who did not. Combined modulated ultrasound and electric field stimulation has a place as adjunct therapy that aids wound healing and provides an effective noninvasive treatment option.

Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy.

PubMed Central

Morgan, A G; McAdam, W A; Pacsoo, C; Darnborough, A

1982-01-01

One hundred patients with benign gastric ulceration were treated in a single-blind, endoscopically controlled trial to assess the relative efficacy of cimetidine (1 g daily) and Caved-S (six tablets daily). Ulcer healing was assessed after six weeks' treatment, and, if incomplete, after a further six weeks. There was no significant difference between the two drug regimens (approximately 63% at six weeks and 91% at 12 weeks). If an ulcer remains unhealed after 10 weeks' treatment the patient should undergo surgery. There was no difference in the relief of day pain between the two drug regimens but cimetidine was more effective over the first two weeks of treatment relieving night pain, than was Caved-S (p less than 0 . 02). After ulcer healing, drug dosage was reduced (cimetidine to 400 mg at night and Caved-S to two tablets twice daily). So far, 56 patients, 28 in each group, have completed the first year's maintenance treatment, and there have been four ulcer recurrences in each group (14%). PMID:7042486

Comparative gastroprotective effects of natural honey, Nigella sativa and cimetidine against acetylsalicylic acid induced gastric ulcer in albino rats.

PubMed

Bukhari, Mulazim Hussain; Khalil, Javed; Qamar, Samina; Qamar, Zahid; Zahid, Muhammad; Ansari, Navid; Bakhshi, Irfan Manzoor

2011-03-01

Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). Experimental, case control study. Pharmacology and Pathology Department of King Edward Medical University, Lahore, from June to August 2007. The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines.

Complete healing of chronic wounds of a lower leg with haemoglobin spray and regeneration of an accompanying severe dermatoliposclerosis with intermittent normobaric oxygen inhalation (INBOI): a case report

PubMed Central

Barnikol, Wolfgang K. R.; Pötzschke, Harald

2011-01-01

A new healing procedure has been developed on the basis of the successful treatment of therapy-resistant hypoxic (and practically anoxic) leg ulcerations located within a heavy dermatoliposclerosis. The procedure involves an initial intra-ulceral application of haemoglobin followed by the intermittent administration of normobaric oxygen via inhalation. Haemoglobin is capable of externally supplying the granulating wound bed with oxygen at low partial pressure in a physiological manner, like a micro lung, so that oxidative stress can be avoided. A long-term daily administration of oxygen from within – including the peri-ulceral skin – is achieved by intermittent normobaric oxygen inhalation (INBOI) regularly throughout the day in the form of 1-hour sessions. Using this combined healing treatment during haemoglobin applications the ulcerations healed within about 1 month, and subsequently with INBOI therapy within further approx. 4 months the peri-ulceral skin regenerated as far as the oxygenation status was concerned: The peri-ulceral transcutaneous oxygen partial pressure (tcPO2) of zero (measured during breathing of normal air) rose to a satisfactory value of approx. 35 mmHg. After 28 months of treatment, the completely hypoxic and degenerated skin on the leg had practically returned to normal with a PO2 of 45 mmHg. Furthermore, the skin dermatoliposclerosis regressed. The skin regeneration was long-lasting, which was probably related to cellular tissue regeneration with an increase in the capillary density, whereby it had to be maintained by regular oxygen inhalation (INBOI maintaining treatment). By unintended intra-individual therapy variations it is evidenced that local hypoxia was the reason for skin degeneration: 3 x 1 h oxygen inhalation were sufficient for the healing treatment; 2 x 1 h sufficed for maintenance, whereas 2 x 0.5 h did not. The new procedure carries practically no risks, is simple, cheap and effective. Whereas the application of haemoglobin requires professional supervision, the oxygen inhalation can be carried out at home following initial guidance and monitoring by a physician. Using this novel method, the therapy-resistant ulceration could be closed within 5 months, during which daily outpatient care was only necessary for 1 month. The successful outcome of the treatment in terms of improvement of oxygen supply can monitored at any time using peri-ulceral tcPO2 measurements, whereby, due to the inhomogeneity of the values, measurements at a minimum of two locations at the wound edge are strongly recommended and more measurements at more skin locations would be preferable. Besides its use in the healing of ulcers, the new procedure is also suitable for the prevention of ulceration development (prophylactic INBOI treatment) in skin rendered susceptible due to the presence of hypoxia. Here, peri-ulceral transcutaneous oxygen partial pressures of below 10 mmHg should be considered as being critical and are an indication for a prophylactic oxygen inhalation treatment. The new procedure may also be suitable even before the peri-ulceral oxygen partial pressure falls below 10 mmHg. Four measures for rehabilitation, conservation, and prevention with regard to a healed chronic wound are proposed. PMID:21468328

[Ambulant compression therapy for crural ulcers; an effective treatment when applied skilfully].

PubMed

de Boer, Edith M; Geerkens, Maud; Mooij, Michael C

2015-01-01

The incidence of crural ulcers is high. They reduce quality of life considerably and create a burden on the healthcare budget. The key treatment is ambulant compression therapy (ACT). We describe two patients with crural ulcers whose ambulant compression treatment was suboptimal and did not result in healing. When the bandages were applied correctly healing was achieved. If correctly applied ACT should provide sufficient pressure to eliminate oedema, whilst taking local circumstances such as bony structures and arterial qualities into consideration. To provide pressure-to-measure regular practical training, skills and regular quality checks are needed. Knowledge of the properties of bandages and the proper use of materials for padding under the bandage enables good personalised ACT. In trained hands adequate compression and making use of simple bandages and dressings provides good care for patients suffering from crural ulcers in contrast to inadequate ACT using the same materials.

[Comparison of the effectiveness and cost of treatment with humid environment as compared to traditional cure. Clinical trial on primary care patients with venous leg ulcers and pressure ulcers].

PubMed

Capillas Pérez, R; Cabré Aguilar, V; Gil Colomé, A M; Gaitano García, A; Torra i Bou, J E

2000-01-01

The discovery of moist environment dressings as alternatives to the traditional treatments based on exposing wounds to air, opened new expectations for the care and treatment of chronic wounds. Over the years, these expectations have led to the availability of new moist environment dressings which have made it possible to improve the care provided to patients suffering this kind of wounds, as well as providing important reasons to weigh in terms of cost-benefit-effectiveness at the time of selecting which type of treatment should be employed. The lack of comparative analysis among traditional treatments and moist environment treatments for chronic wounds among patients receiving primary health care led the authors to perform an analysis comparing these aforementioned options of treatment on patients suffering venous leg ulcers or pressure ulcers. The authors designed a Randomized Clinical Trial involving patients receiving ambulatory care in order to compare the effectiveness and cost-benefit of traditional versus moist environment dressing during the treatment of patients suffering stage II or III pressure ulcers or venous leg ulcers. In this trial, variables related to effectiveness of both treatments, as well as their costs were analyzed. 70 wounds were included in this Randomized Clinical Trial, 41 were venous leg ulcers of which 21 received a moist environment treatment while 20 received traditional cure, the other 29 wounds were pressure ulcers of which 15 received moist environment dressings treatment and 14 received traditional dressings. No statistically significant differences were found among the defining variables for these lesions in either group under treatment. In the venous leg ulcer study group, the authors conclusions were an average of 18.13 days, 16.33 treatment sessions and a cost of 10,616 pesetas to heal one square centimeter of the initial surface area of a wound on patients treated with traditional treatment compared to an average of 18.22 days, 4.54 treatment sessions and a cost of 2409 pesetas to heal one square centimeter of the initial surface area of a wound on patients treated with moist environment dressings. In the pressure ulcers study group, the authors conclusions were an average of 12.18 days, 12.1 treatment sessions and a cost of 15,490 pesetas to heal one square centimeter of the initial surface area of a wound on patients treated with traditional treatment compared to an average of 7.12 days, 1.86 treatment sessions and a cost of 2610 pesetas to heal one square centimeter of the initial surface area of a wound on patients treated with moist environment dressings. The results of this randomized clinical trial demosntrated that the moist environment treatment group was more effective and had a better cost-benefit ratio than the traditional treatment group in the treatment of pressure ulcers and venous leg ulcers on patients cared for by nursing personnel in primary health care centers all of which agrees with publications consulted by authors.

An Automatic Assessment System of Diabetic Foot Ulcers Based on Wound Area Determination, Color Segmentation, and Healing Score Evaluation.

PubMed

Wang, Lei; Pedersen, Peder C; Strong, Diane M; Tulu, Bengisu; Agu, Emmanuel; Ignotz, Ron; He, Qian

2015-08-07

For individuals with type 2 diabetes, foot ulcers represent a significant health issue. The aim of this study is to design and evaluate a wound assessment system to help wound clinics assess patients with foot ulcers in a way that complements their current visual examination and manual measurements of their foot ulcers. The physical components of the system consist of an image capture box, a smartphone for wound image capture and a laptop for analyzing the wound image. The wound image assessment algorithms calculate the overall wound area, color segmented wound areas, and a healing score, to provide a quantitative assessment of the wound healing status both for a single wound image and comparisons of subsequent images to an initial wound image. The system was evaluated by assessing foot ulcers for 12 patients in the Wound Clinic at University of Massachusetts Medical School. As performance measures, the Matthews correlation coefficient (MCC) value for the wound area determination algorithm tested on 32 foot ulcer images was .68. The clinical validity of our healing score algorithm relative to the experienced clinicians was measured by Krippendorff's alpha coefficient (KAC) and ranged from .42 to .81. Our system provides a promising real-time method for wound assessment based on image analysis. Clinical comparisons indicate that the optimized mean-shift-based algorithm is well suited for wound area determination. Clinical evaluation of our healing score algorithm shows its potential to provide clinicians with a quantitative method for evaluating wound healing status. © 2015 Diabetes Technology Society.

Specific nutritional support accelerates pressure ulcer healing and reduces wound care intensity in non-malnourished patients.

PubMed

van Anholt, R D; Sobotka, L; Meijer, E P; Heyman, H; Groen, H W; Topinková, E; van Leen, M; Schols, J M G A

2010-09-01

We investigated the potential of a high-protein, arginine- and micronutrient-enriched oral nutritional supplement (ONS) to improve healing of pressure ulcers in non-malnourished patients who would usually not be considered for extra nutritional support. Forty-three non-malnourished subjects with stage III or IV pressure ulcers were included in a multicountry, randomized, controlled, double-blind, parallel group trial. They were offered 200 mL of the specific ONS or a non-caloric control product three times per day, in addition to their regular diet and standard wound care, for a maximum of 8 wk. Results were compared with repeated-measures mixed models (RMMM), analysis of variance, or Fisher's exact tests for categorical parameters. Supplementation with the specific ONS accelerated pressure ulcer healing, indicated by a significantly different decrease in ulcer size compared with the control, over the period of 8 wk (P

Acellular Flowable Matrix in the Treatment of Tunneled or Cavity Ulcers in Diabetic Feet: A Preliminary Report.

PubMed

Campitiello, Ferdinando; Mancone, Manfredi; Della Corte, Angela; Guerniero, Raffaella; Canonico, Silvestro

2018-06-01

The authors aimed to explore the feasibility and safety of an advanced, acellular, flowable wound matrix (FWM) in patients with diabetes-related cavity or tunnel lesions involving deep structures. Patients with diabetic foot ulcers were hospitalized at the General and Geriatric Surgery Unit of the University of Campania in Naples, Italy, between March 2015 and December 2015. Twenty-three patients with tunneled or cavity ulcers were treated. The lesions were filled with the FWM. Surgical wound edges were either approximated with stitches or left to heal by secondary intention. After 6 weeks, 78.26% of patients completely healed after a single application of the FWM. The healing time for all healed wounds was 30.85 ± 12.62 days, or 26.11 ± 5.43 days in patients for whom wound edges were approximated by stitches, and 57.66 ± 3.05 days in the patients who healed by secondary intention (P = .01). Permanent tissue regeneration was observed in a high percentage of patients, and shorter healing time was achieved. Study authors observed a low rate of complications such as major amputation and increased hospitalization. The FWM seems ideal for tunneled and cavity ulcers with irregular geometry. This new porous matrix allows closure of the lesion while reducing healing time and demolition surgery.

Dressings and topical agents for treating pressure ulcers.

PubMed

Westby, Maggie J; Dumville, Jo C; Soares, Marta O; Stubbs, Nikki; Norman, Gill

2017-06-22

Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers. Such a review would ideally help people with pressure ulcers and health professionals assess the best treatment options. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents. To assess the effects of dressings and topical agents for healing pressure ulcers in any care setting. We aimed to examine this evidence base as a whole, determining probabilities that each treatment is the best, with full assessment of uncertainty and evidence quality. In July 2016 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Published or unpublished randomised controlled trials (RCTs) comparing the effects of at least one of the following interventions with any other intervention in the treatment of pressure ulcers (Stage 2 or above): any dressing, or any topical agent applied directly to an open pressure ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factor treatments, platelet gels and larval therapy. Two review authors independently performed study selection, risk of bias assessment and data extraction. We conducted network meta-analysis using frequentist mega-regression methods for the efficacy outcome, probability of complete healing. We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (saline gauze). We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals for individual treatments compared with every other, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole. We included 51 studies (2947 participants) in this review and carried out NMA in a network of linked interventions for the sole outcome of probability of complete healing. The network included 21 different interventions (13 dressings, 6 topical agents and 2 supplementary linking interventions) and was informed by 39 studies in 2127 participants, of whom 783 had completely healed wounds.We judged the network to be sparse: overall, there were relatively few participants, with few events, both for the number of interventions and the number of mixed treatment contrasts; most studies were small or very small. The consequence of this sparseness is high imprecision in the evidence, and this, coupled with the (mainly) high risk of bias in the studies informing the network, means that we judged the vast majority of the evidence to be of low or very low certainty. We have no confidence in the findings regarding the rank order of interventions in this review (very low-certainty evidence), but we report here a summary of results for some comparisons of interventions compared with saline gauze. We present here only the findings from evidence which we did not consider to be very low certainty, but these reported results should still be interpreted in the context of the very low certainty of the network as a whole.It is not clear whether regimens involving protease-modulating dressings increase the probability of pressure ulcer healing compared with saline gauze (risk ratio (RR) 1.65, 95% confidence interval (CI) 0.92 to 2.94) (moderate-certainty evidence: low risk of bias, downgraded for imprecision). This risk ratio of 1.65 corresponds to an absolute difference of 102 more people healed with protease modulating dressings per 1000 people treated than with saline gauze alone (95% CI 13 fewer to 302 more). It is unclear whether the following interventions increase the probability of healing compared with saline gauze (low-certainty evidence): collagenase ointment (RR 2.12, 95% CI 1.06 to 4.22); foam dressings (RR 1.52, 95% CI 1.03 to 2.26); basic wound contact dressings (RR 1.30, 95% CI 0.65 to 2.58) and polyvinylpyrrolidone plus zinc oxide (RR 1.31, 95% CI 0.37 to 4.62); the latter two interventions both had confidence intervals consistent with both a clinically important benefit and a clinically important harm, and the former two interventions each had high risk of bias as well as imprecision. A network meta-analysis (NMA) of data from 39 studies (evaluating 21 dressings and topical agents for pressure ulcers) is sparse and the evidence is of low or very low certainty (due mainly to risk of bias and imprecision). Consequently we are unable to determine which dressings or topical agents are the most likely to heal pressure ulcers, and it is generally unclear whether the treatments examined are more effective than saline gauze.More research is needed to determine whether particular dressings or topical agents improve the probability of healing of pressure ulcers. The NMA is uninformative regarding which interventions might best be included in a large trial, and it may be that research is directed towards prevention, leaving clinicians to decide which treatment to use on the basis of wound symptoms, clinical experience, patient preference and cost.

Gastric emptying abnormal in duodenal ulcer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holt, S.; Heading, R.C.; Taylor, T.V.

1986-07-01

To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison ofmore » emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.« less

Nizatidine versus placebo in active benign gastric ulcer disease: an eight-week, multicenter, randomized, double-blind comparison. The Nizatidine Benign Gastric Ulcer Disease Study Group.

PubMed

Cloud, M L; Enas, N; Offen, W W

1992-09-01

To determine if 150 mg nizatidine twice daily or 300 mg nizatidine at bedtime are similarly effective and to compare each dose with placebo in healing benign gastric ulcers and relieving peptic ulcer symptoms. This study was a randomized, double-blind, placebo-controlled parallel comparison. The study was conducted at 74 gastroenterology and internal medicine clinics in the United States and Canada. Four hundred fifty-six patients with active benign gastric ulcer documented by endoscopy participated in the study. On the basis of a computer-generated randomization list, patients were assigned sequentially to receive either 150 mg nizatidine twice daily (n = 151), 300 mg nizatidine once daily at bedtime and identically appearing placebo capsules in the morning (n = 153), or placebo capsules twice daily (n = 152). Treatment lasted for 8 weeks unless healing was documented by endoscopy after 4 weeks. Antacid tablets (aluminum hydroxide, magnesium hydroxide, simethicone combination) were supplied for relief of symptoms. Both doses of nizatidine significantly improved healing rates at 8 weeks compared with placebo. Daytime and nighttime symptom severity was improved by both nizatidine regimens at end point (p less than 0.015 versus placebo, two-tailed test). Antacid use was similar for all groups in the end point analysis. Patient well-being was significantly better in patients treated with nizatidine than in patients in the placebo group ((p less than 0.04, two-tailed test). No clinically significant differences in the incidence of adverse clinical or laboratory events were noted. Nizatidine, 300 mg at bedtime and 150 mg twice daily, resulted in greater healing of benign gastric ulcers than placebo treatment after 8 weeks. Relief of the symptoms of gastric ulcer was significantly better in the patients receiving nizatidine treatment versus placebo treatment.

[Evaluation of pressure ulcers area using the softwares Motic and AutoCAD®].

PubMed

Reis, Camila Letícia Dias dos; Cavalcante, Janaína Mortosa; Rocha Júnior, Edvar Ferreira da; Neves, Rinaldo Souza; Santana, Levy Aniceto; Guadagnin, Renato da Veiga; Brasil, Lourdes Mattos

2012-01-01

Pressure ulcer is a lesion that affects skin layers in some regions of the body and its healing can be followed up using image processing. The analysis of pressure ulcer area is relevant to evaluate its evolution and response to therapeutic procedures. Such areas can be evaluated through contour marking with the softwares Motic and AutoCAD®. In this study 35 volunteers computed areas from two grade III pressure ulcers using these instruments. It was possible to conclude that results are clinically equivalent and so can be considered to follow up healing evolution from pressure ulcers.

Providing cost-effective treatment of hard-to-heal wounds in the community through use of NPWT.

PubMed

Hampton, Jane

2015-06-01

The treatment of non-healing wounds accounts for a high proportion of wound care costs. Advanced technology treatments, such as negative pressure wound therapy (NPWT), could be cost-effective if they result in faster healing. The objective of this study is to assess the effect on healing and the cost-effectiveness of a single-use NPWT (i.e PICO by Smith & Nephew) when used on hard-to-heal wounds in a community setting. This was a cohort case study in which wounds were treated with NWPT for 2 weeks. Wounds were assessed every 2-4 weeks to a healed state. The weekly cost of treatment prior to intervention, that is, the products used and nurse time, were compared with treatment costs associated with NWPT and after a return to standard treatment. The study included 9 patients with leg ulcers or pressure ulcers that had been slow healing or non-healing for at least 6 weeks. While treated with NPWT, the average weekly reduction in wound size was 21%. The wound size achieved with NPWT was reached on average 10 weeks earlier than predicted. The increased healing rate continued after PICO stopped and 5 wounds healed on average 8 weeks later. Frequency of dressing changes fell from 4 times weekly at baseline to 2 times a week with NPWT and to 1.8 after NPWT stopped. Weekly cost of treatment with NPWT was, on average, 1.6 times higher than the baseline, but fell to 3 times less when NPWT stopped owing to the reduction in dressing changes. The amount of change in healing rate was considerably higher than the increase in costs associated with NPWT. NWPT is a cost-effective treatment for hard-to-heal wounds. Wounds decreased in size and healed more quickly under NWPT treatment than under standard treatment. Additional NPWT costs can be quickly offset by faster healing and a shortened treatment period.

Foot ulcers in the diabetic patient, prevention and treatment.

PubMed

Wu, Stephanie C; Driver, Vickie R; Wrobel, James S; Armstrong, David G

2007-01-01

Lower extremity complications in persons with diabetes have become an increasingly significant public health concern in both the developed and developing world. These complications, beginning with neuropathy and subsequent diabetic foot wounds frequently lead to infection and lower extremity amputation even in the absence of critical limb ischemia. In order to diminish the detrimental consequences associated with diabetic foot ulcers, a common-sense-based treatment approach must be implemented. Many of the etiological factors contributing to the formation of diabetic foot ulceration may be identified using simple, inexpensive equipment in a clinical setting. Prevention of diabetic foot ulcers can be accomplished in a primary care setting with a brief history and screening for loss of protective sensation via the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy, plantar foot pressure, and assess vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, may enable clinicians to stratify patients based on risk and help determine the type of intervention. Other effective clinical interventions may include patient education, optimizing glycemic control, smoking cessation, and diligent foot care. Recent technological advanced combined with better understanding of the wound healing process have resulted in a myriad of advanced wound healing modalities in the treatment of diabetic foot ulcers. However, it is imperative to remember the fundamental basics in the healing of diabetic foot ulcers: adequate perfusion, debridement, infection control, and pressure mitigation. Early recognition of the etiological factors along with prompt management of diabetic foot ulcers is essential for successful outcome.

Foot ulcers in the diabetic patient, prevention and treatment

PubMed Central

Wu, Stephanie C; Driver, Vickie R; Wrobel, James S; Armstrong, David G

2007-01-01

Lower extremity complications in persons with diabetes have become an increasingly significant public health concern in both the developed and developing world. These complications, beginning with neuropathy and subsequent diabetic foot wounds frequently lead to infection and lower extremity amputation even in the absence of critical limb ischemia. In order to diminish the detrimental consequences associated with diabetic foot ulcers, a com-mon-sense-based treatment approach must be implemented. Many of the etiological factors contributing to the formation of diabetic foot ulceration may be identified using simple, inexpensive equipment in a clinical setting. Prevention of diabetic foot ulcers can be accomplished in a primary care setting with a brief history and screening for loss of protective sensation via the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy, plantar foot pressure, and assess vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, may enable clinicians to stratify patients based on risk and help determine the type of intervention. Other effective clinical interventions may include patient education, optimizing glycemic control, smoking cessation, and diligent foot care. Recent technological advanced combined with better understanding of the wound healing process have resulted in a myriad of advanced wound healing modalities in the treatment of diabetic foot ulcers. However, it is imperative to remember the fundamental basics in the healing of diabetic foot ulcers: adequate perfusion, debridement, infection control, and pressure mitigation. Early recognition of the etiological factors along with prompt management of diabetic foot ulcers is essential for successful outcome. PMID:17583176

Healing mechanisms of the hydroalcoholic extract and ethyl acetate fraction of green tea (Camellia sinensis (L.) Kuntze) on chronic gastric ulcers.

PubMed

Borato, Débora Gasparin; Scoparo, Camila Toledo; Maria-Ferreira, Daniele; da Silva, Luísa Mota; de Souza, Lauro Mera; Iacomini, Marcello; Werner, Maria Fernanda de Paula; Baggio, Cristiane Hatsuko

2016-03-01

Green tea is an infusion of unfermented leaves of Camellia sinensis (L.) Kuntze (Theaceae), traditionally used for the treatment of obesity, hypercholesterolemia, and gastric complaints. This study evaluated the mechanisms involved in the gastric ulcer healing of the hydroalcoholic extract from green tea (GEt), its ethyl acetate fraction, (GEAc) and epigallocatechin gallate (EGCG) using the model of acetic acid-induced gastric ulcer in rats. The chronic gastric ulcer was induced by application of 80 % acetic acid on serosal mucosa of rats. After 7 days of oral treatment with GEt and GEAc, the ulcer area, mucin content, inflammatory parameters (MPO and NAG), and antioxidant system (GSH and LOOH levels, SOD and GST activities) were evaluated. In vitro, the scavenging activity of GEt and GEAc were also measured. The antisecretory action was studied on the pylorus ligature method in rats. Oral treatment with GEt and GEAc reduced significantly the gastric ulcer area induced by acetic acid. The gastric ulcer healing was accompanied by increasing of mucin content, restoration of GSH levels and SOD activity, and reduction of MPO and LOOH levels. In addition, GEt and GEAc reduced the DPPH free radicals in vitro. Furthermore, the oral treatment of animals with GEt and GEAc did not alter the gastric acid secretion or cause signs of toxicity. Collectively, these results showed that GEt had a pronounced antiulcer effect, possibly through maintenance of mucin content and reduction of inflammation and oxidative stress. In addition, the compounds present in its ethyl acetate fraction could be responsible for the extract activity.

A serosa-searing apparatus for producing gastric ulcer in rats.

PubMed

Kagoshima, M; Suzuki, T; Katagiri, S; Shimada, H

1994-12-01

Chronic ulcer models produced by serosa-searing method are very similar histologically to the ulcer healing process occurring in humans. In an effort to produce a serosa-searing chronic ulcer model in rats, we devised a new balance-type apparatus. This searing apparatus is capable of changing adequately both temperature and duration of time. Furthermore, the pressure which serves to bring the searing iron tip into contact with the stomach serosa surface can also be precisely changed. Optimal conditions for reproducing the serosa-searing ulcer model were at 65 degrees C and in 5 sec. Moreover, in order to evaluate the effects of pressure, various pressure levels (A: 5 g, 17.68 g/cm2; B: 10 g, 35.37 g/cm2; C: 15 g, 53.05 g/cm2; D: 20 g, 70.74 g/cm2; E: 25 g, 88.42 g/cm2; F: 30 g, 106.10 g/cm2; G: 35 g, 123.79 g/cm2 (+/- 1 g, 0.149 g/cm2)) of 5-sec duration at 65 +/- 0.1 degrees C were used. Macroscopically, gastric mucosal lesions were most clearly observed in a pressure-related manner 7 days after the procedure. Histologically, definite deep ulcerations (UI-III or UI-IV) were observed at pressure level C (15 g, 53.05 g/cm2) or more. The highest incidence (87%) of histological gastric ulcers (UI-IV) was observed in pressure level E (25 g, 88.42 g/cm2). The healing process was observed at 40 to 60 days postoperatively. At 100 days after the procedure, recurrences were observed both macroscopically and histologically. In conclusion, this new apparatus is very useful for reproducing a chronic ulcer model for observing the healing and recurrence process.

Treatment of infectious skin defects or ulcers with electrolyzed strong acid aqueous solution.

PubMed

Sekiya, S; Ohmori, K; Harii, K

1997-01-01

A chronic ulcer with an infection such as methicillin-resistant Staphylococcus aureus is hard to heal. Plastic and reconstructive surgeons often encounter such chronic ulcers that are resistant to surgical or various conservative treatments. We applied conservative treatment using an electrolyzed strong acid aqueous solution and obtained satisfactory results. The lesion was washed with the solution or soaked in a bowl of the solution for approximately 20 min twice a day. Fresh electrolyzed strong acid aqueous solution is unstable and should be stored in a cool, dark site in a sealed bottle. It should be used within a week after it has been produced. Here we report on 15 cases of infectious ulcers that were treated by electrolyzed strong acid aqueous solution. Of these cases, 7 patients were healed, 3 were granulated, and in 5, infection subsided. In most cases the lesion became less reddish and less edematous. Discharge or foul odor from the lesion was decreased. Electrolyzed strong acid aqueous solution was especially effective for treating a chronic refractory ulcer combined with diabetes melitus or peripheral circulatory insufficiency. This clinically applied therapy of electrolyzed strong acid aqueous solution was found to be effective so that this new therapeutic technique for ulcer treatment can now be conveniently utilized.

Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers.

PubMed

Emanuelli, T; Burgeiro, A; Carvalho, E

2016-12-01

Diabetic foot ulcers affect 15-20 % of all diabetic patients and remain an important challenge since the available therapies have limited efficacy and some of the novel therapeutic approaches, which include growth factors and stem cells, are highly expensive and their safety remains to be evaluated. Despite its low cost and safety, the interest for topical insulin as a healing agent has increased only in the last 20 years. The molecular mechanisms of insulin signaling and its metabolic effects have been well studied in its classical target tissues. However, little is known about the specific effects of insulin in healthy or even diabetic skin. In addition, the mechanisms involved in the effects of insulin on wound healing have been virtually unknown until about 10 years ago. This paper will review the most recent advances in the cellular and molecular mechanisms that underlie the beneficial effects of insulin on skin wound healing in diabetes. Emerging evidence that links dysfunction of key cellular organelles, namely the endoplasmic reticulum and the mitochondria, to changes in the autophagy response, as well as the impaired wound healing in diabetic patients will also be discussed along with the putative mechanisms whereby insulin could regulate/modulate these alterations.

Long-term outcome study of growth factor-treated pressure ulcers.

PubMed

Payne, W G; Ochs, D E; Meltzer, D D; Hill, D P; Mannari, R J; Robson, L E; Robson, M C

2001-01-01

Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds. Most of the trials were of brief duration with short to no follow-up periods. Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30% for both operative and nonoperative treatments. Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded, placebo-controlled cytokine clinical trial of pressure ulcers. Fifty-four of 61 patients completed the follow-up period with 68.5% of the patients (37 of 54) being healed after 1 year. Of patients healing > or =85% during the active treatment phase, 84.6% were healed after 1 year compared with 61% of those that healed <85% during treatment (P <0.05). Long-term outcome was better in this growth factor trial than with surgical or standard nonoperative treatment of pressure ulcers. Since only patients receiving exogenously applied cytokines achieved >85% closure during the treatment phase of the trial, the excellent long-term outcome appears attributable to the cytokine therapy.

Application of photodynamic therapy, laser therapy, and a cellulose membrane for calcaneal pressure ulcer treatment in a diabetic patient: A case report.

PubMed

Rosa, Luciano Pereira; da Silva, Francine Cristina; Vieira, Regiane Lima; Tanajura, Beatriz Rocha; da Silva Gusmão, Alana Gonçalves; de Oliveira, Janeide Muritiba; Dos Santos, Nathalia Aparecida Campanário; Bagnato, Vanderlei Salvador

2017-09-01

Diabetes mellitus is a metabolic disorder in which a person has high blood glucose levels due to inadequate insulin production by the pancreas. Wounds in these individuals cannot heal properly over time due to circulatory changes that hinder and stagnate the healing process. We report the case of an 82-year-old female type 2 diabetes mellitus carrier, presenting to clinical-dermatological examination pressure ulcer (PU) in the right calcaneus region. The patient was treated with photodynamic therapy using curcumin and blue light-emitting diodes (LEDs), laser therapy, and the application of a cellulose membrane in order to promote ulcer decontamination by local action, accelerate wound healing, and maintain favorable conditions of asepsis and moisture, respectively. The ulcer healing occurred after 30days of treatment and total epithelialization was observed. From the results obtained in this case report, we conclude that the combination of photodynamic therapy, laser therapy, and coating with a cellulose membrane is a promising treatment for the healing of PU in diabetic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

[Laser's biostimulation in healing or crural ulcerations].

PubMed

Król, P; Franek, A; Huńka-Zurawińska, W; Bil, J; Swist, D; Polak, A; Bendkowski, W

2001-11-01

The objective of this paper was to evaluate effect of laser's biostimulation on the process of healing of crural ulcerations. Three comparative groups of patients, A, B and C, were made at random from the patients with venous crural ulcerations. The group A consisted of 17, the group B 15, the group C 17 patients. The patients in all comparative groups were treated pharmacologically and got compress therapy. Ulcerations at patients in group A were additionally irradiated by light of biostimulation's laser (810 nm) in this way that every time ulcerations got dose of energy 4 J/cm2. The patient's in-group B additionally got blind trial (with placebo in the form of quasi-laserotherapy). The evaluated factors were to estimate how laser's biostimulation causes any changes of the size of the ulcers and of the volume of tissue defect. The speed of changes of size and volume of tissue defect per week was calculated. After the treatment there was statistically significant decrease of size of ulcers in all comparative groups while there was no statistically significant difference between the groups observed. After the treatment there was statistically significant decrease of volume of ulcers only in groups A and C but there was no statistically significant difference between the groups observed.

Thyroid hormones increase stomach goblet cell numbers and mucin expression during indomethacin induced ulcer healing in Wistar rats.

PubMed

Namulema, Jackline; Nansunga, Miriam; Kato, Charles Drago; Kalange, Muhammudu; Olaleye, Samuel Babafemi

2018-01-01

Gastric ulcers are mucosal discontinuities that may extend into the mucosa, submucosa or even deeper. They result from an imbalance between mucosal aggressors and protective mechanisms that include the mucus bicarbonate layer. Thyroid hormones have been shown to accelerate gastric ulcer healing in part by increasing the adherent mucus levels. However, the effects of thyroid hormones on goblet cell numbers and expression of neutral and acidic mucins during ulcer healing have not been investigated. Thirty six adult male Wistar rats were randomly divided into six groups each with six animals. Group 1 (normal control) and group 2 (negative control) were given normal saline for eight weeks. Groups 3 and 4 were given 100 μg/kg per day per os of thyroxine so as to induce hyperthyroidism. Groups 5 and 6 received 0.01% ( w / v ) Propylthiouracil (PTU) for 8 weeks so as to induce hypothyroidism. After thyroid hormonal levels were confirmed using radioimmunoassay and immunoradiometric assays, ulcer induction was done using 40 mg/kg intragastric single dose of Indomethacin in groups 2, 3 and 5. Stomachs were extracted after day 3 and 7 of ulcer induction for histological examination. Histochemistry was carried out using Periodic Acid Shiff and Alcian Blue. The number of acidic and neutral goblet cells were determined by counting numbers per field. Mucin expression (%) was determined using Quick Photo Industrial software version 3.1. The numbers of neutral goblet cells (cells/field) increased significantly ( P  < 0.05) in the ulcer+thyroxine (14.67 ± 0.33), thyroxine (17.04 ± 1.71) and ulcer+PTU (12.89 ± 1.06) groups compared to the normal control (10.78 ± 1.07) at day 3. For the acidic goblet cells, differences between treatment groups were more pronounced at day 7 between the ulcer+thyroxine (22.56 ± 1.26) and thyroxine (22.89 ± 0.80). We further showed that percentage expression of both neutral and acidic mucins was significantly higher in the ulcer+thyroxine (9.23 ± 0.17 and 6.57 ± 0.35 respectively) and thyroxine groups (9.66 ± 0.21 and 6.33 ± 0.38 respectively) as compared to the normal control group (4.08 ± 0.20 and 4.38 ± 0.11 respectively) at day 3 after ulcer induction. This study confirms the role played by thyroid hormones in healing of indomethacin induced gastric ulcers. The study further demonstrates increased numbers of both neutral and acidic goblet cells and the increase in expression of both neutral and acidic mucins during healing of indomethacin induced ulcers.

The Effect of a Common Antibiotics Doxycycline on Non-Healing Chronic Wound.

PubMed

Xu, Dixon H; Zhu, Ziwen; Fang, Yujiang

2017-01-01

Up to 25% of diabetic patients will develop a diabetic foot ulcer. Chronic wounds such as diabetic foot ulcers often fail to heal with conventional therapies. In recent years, it has been identified that chronic wounds are usually associated with elevated level of matrix metalloproteinases (MMPs). Doxycycline, a cheap tetracycline antibiotic, has been shown to inhibit MMPs both in vitro and in vivo independent of its antimicrobial property. We undertook a search through PUBMED for peer-reviewed research literature with doxycycline, chronic wound, diabetes, MMPs as key words. Seventy papers were included in the review. This review identified doxycycline is a very promising drug to be used in patients with diabetic foot ulcers because higher efficacy even in a very low dosage, little side effects in a lower dosage, inhibition of MMP as well as prevention/treatment of infection in the ulcers, beneficial to cardiovascular complications and cheap to manufacture. In this review, we provide an overview of the roles of MMPs in the pathogenesis of chronic wounds and explore the potential application of doxycycline as a treatment option in managing chronic wounds such as diabetic foot ulcers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification.

PubMed

Kumar, Mohan; Gautam, Manish Kumar; Singh, Amit; Goel, Raj Kumar

2013-11-05

The present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat. MSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures. An increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds. MSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer.

Increasing gastric juice pH level prior to anti-Helicobacter pylori therapy may be beneficial to the healing of duodenal ulcers.

PubMed

Fan, Hong-Yun; Wang, Juan; Yan, Guo-Chao; Huo, Xiao-Hui; Mu, Li-Juan; Chu, Jian-Kun; Niu, Wei-Wei; Duan, Zhi-Ying; Ma, Jin-Cheng; Wang, Jing; Wang, Zhi-Yu

2013-03-01

The aim of this study was to observe the efficacy of clarithromycin-based triple therapy for Helicobacter pylori (Hp)-infected duodenal ulcer when combined with different pH levels of gastric juices. A total of 160 patients with Hp-infected duodenal ulcers were randomly allocated into two groups. Patients in the treatment group (n=80) were administered a 20-mg dose of omeprazole twice daily for 1 week and then the treatment and control groups (n=80) received therapy for Hp infection and duodenal ulcers. We observed the ulcer healing stage, the content of anti-Hp IgA in gastric juice and the Hp eradication rate before and after proton pump inhibitor therapy in the two groups. Results revealed that the Hp eradication rate in the treatment group was 93% compared with 81% in the control group, and the difference was statistically significant (P<0.05). The ulcer healing rate in the treatment group was 93%, compared with 70% in the control group (P<0.05). A positive linear correlation was observed between gastric pH and the content of anti-Hp IgA in gastric juice (P<0.05). Increasing gastric pH prior to anti-Hp therapy may be beneficial to the eradication of Hp and for promoting the healing of duodenal ulcers.

[EFFECT OF BONE MARROW MESENCHYMAL STEM CELLS ON GASTRIC ULCER REPAIRING].

PubMed

Wang, Guozhong; Li, Chengjun; Fan, Xichao; Li, Bo; Xiao, Wei; Jin, Li

2015-07-01

To explore the ettect and mechanisms of bone marrow mesenchymal stem cells (BMSCs) on healing quality of acetic acid-induced gastric ulcer. Forty-eight clean grade male Wistar rats were used to establish the model of gastric ulcer with acetic acid and were randomly divided into 3 groups after 3 days of modeling, 16 rats each group. After the abdominal cavity was open and stomach was pulled out, no treatment was given in group A, 150 µL phosphate buffered saline (PBS) and 150 µL BMSCs at passage 4+PBS (1 x 10(8) cells/100 µL) were injected into the gastric wall surrounding the ulcer at 5 different points in groups B and C respectively. After 10 days, the ulcer area was measured, the mucosal thickness and the number of dilated glands were tested in the regenerative mucosa by histological method. And the expression of vascular endothelial growth factor (VEGF) was detected at ulcerative margin by immunohistochemical method. The ulcer area in group C was significantly smaller than that of groups A and B (P < 0.01), but no significant difference was found between groups A and B (P > 0.05). HE staining showed that group C had thicker regenerative gastric mucosa, less dilated glands, and more regular mucosal structure than groups A and B, showing significant differences in regenerative gastric mucosa thickness and dilated glands number (P < 0.01), but no significant difference between groups A and B (P > 0.05). Immunohistochemical staining showed that the positive expression of VEGF in the ulcer margin mucosa of group C was significantly higher than that of groups A and B. The integral absorbance (IA) value of VEGF expression in group C was significantly higher than that in groups A and B (P < 0.01), but no significant difference between groups A and B (P > 0.05). BMSCs can accelerate ulcer healing by the secretion of VEGF, and improve the quality of ulcer healing.

Clinical Application of Growth Factors and Cytokines in Wound Healing

PubMed Central

Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

2016-01-01

Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies and future research possibilities. In this review we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy. PMID:24942811

Three-Dimensional Human Tissue Models That Incorporate Diabetic Foot Ulcer-Derived Fibroblasts Mimic In Vivo Features of Chronic Wounds

PubMed Central

Maione, Anna G.; Brudno, Yevgeny; Stojadinovic, Olivera; Park, Lara K.; Smith, Avi; Tellechea, Ana; Leal, Ermelindo C.; Kearney, Cathal J.; Veves, Aristidis; Tomic-Canic, Marjana; Mooney, David J.

2015-01-01

Diabetic foot ulcers (DFU) are a major, debilitating complication of diabetes mellitus. Unfortunately, many DFUs are refractory to existing treatments and frequently lead to amputation. The development of more effective therapies has been hampered by the lack of predictive in vitro methods to investigate the mechanisms underlying impaired healing. To address this need for realistic wound-healing models, we established patient-derived fibroblasts from DFUs and site-matched controls and used them to construct three-dimensional (3D) models of chronic wound healing. Incorporation of DFU-derived fibroblasts into these models accurately recapitulated the following key aspects of chronic ulcers: reduced stimulation of angiogenesis, increased keratinocyte proliferation, decreased re-epithelialization, and impaired extracellular matrix deposition. In addition to reflecting clinical attributes of DFUs, the wound-healing potential of DFU fibroblasts demonstrated in this suite of models correlated with in vivo wound closure in mice. Thus, the reported panel of 3D DFU models provides a more biologically relevant platform for elucidating the cell–cell and cell–matrix-related mechanisms responsible for chronic wound pathogenesis and may improve translation of in vitro findings into efficacious clinical applications. PMID:25343343

The n-Hexane, ethylacetate, and butanol fractions from Hydnocarpi Semen enhanced wound healing in a mice ulcer model.

PubMed

Lee, Geum Seon; Yim, Dongsool; Cheong, Jae Hoon; Kang, Tae Jin

2012-12-01

Our previous report showed that Hydnocarpi Semen (HS) extract has wound repair activity at ulcer lesion in diabetic mice. In this study, fractions of n-Hexane, ethylacetate (EtOAc), and butanol (BuOH) from HS crude extract were evaluated for their wound healing activity by using in vivo diabetic ulcer models and in vitro acute inflammation model. Although n-Hexane and EtOAc fractions promote wound healing in mice with ulcer, the BuOH fraction exhibited the most potent wound healing activity and the wound area score significantly decreased after treatment of BuOH fraction even at dose of 2 mg/kg. BuOH fraction stimulated macrophages to increase the production of nitric oxide (NO) and TNF-α. The BuOH fraction also enhanced the production of TGF-β and VEGF, which were involved in fibroblast activation and angiogenesis. The mRNA expression and activation of MMP-9 were increased by three fractions and the activity was higher in BuOH fraction-treated group compared to the other groups. The mechanism that the HS helps to promote healing of diabetic ulcer is possibly associated with the production of TNF-α, a proinflammatory cytokine, as well as the secretion of VEGF, TGF-β, and MMP-9, which were involved in proliferation of capillaries and fibroblasts. These results suggest that HS can be a new candidate material for the treatment of wound in skin ulcer.

Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese herbal formula to promote diabetic wound healing.

PubMed

Lau, Kit-Man; Lai, Kwok-Kin; Liu, Cheuk-Lun; Tam, Jacqueline Chor-Wing; To, Ming-Ho; Kwok, Hin-Fai; Lau, Ching-Po; Ko, Chun-Hay; Leung, Ping-Chung; Fung, Kwok-Pui; Poon, Simon Kar-Sing; Lau, Clara Bik-San

2012-05-07

Astragali Radix (AR) and Rehmanniae Radix (RR) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic foot ulcer. In our previous study, a herbal formula NF3 comprising AR and RR in the ratio of 2:1 was found effective in enhancing diabetic wound healing in rats through the actions of tissue regeneration, angiogenesis promotion and inflammation inhibition. The aims of the present study were to investigate the herb-herb interaction (or the possible synergistic effect) between AR and RR in NF3 to promote diabetic wound healing and to identify the principal herb in the formula by evaluating the potencies of individual AR and RR in different mechanistic studies. A chemically induced diabetic foot ulcer rat model was used to examine the wound healing effect of NF3 and its individual herbs AR and RR. For mechanistic studies, murine macrophage cell (RAW 264.7) inflammation, human fibroblast (Hs27) proliferation and human endothelial cell (HMEC-1) migration assays were adopted to investigate the anti-inflammatory, granulation formation and angiogenesis-promoting activities of the herbal extracts, respectively. In the foot ulcer animal model, neither AR nor RR at clinical relevant dose (0.98g/kg) promoted diabetic wound healing. However, when they were used in combination as NF3, synergistic interaction was demonstrated, of which NF3 could significantly reduce the wound area of rats when compared to water group (p<0.01). For anti-inflammation and granulation formation, AR was more effective than RR in inhibiting lipopolysaccharide (LPS)-induced nitric oxide production from RAW 264.7 cells and promoting Hs27 fibroblast proliferation. In the aspect of angiogenesis promotion, only NF3 promoted cell migration of HMEC-1 cells. AR plays a preeminent role in the anti-inflammatory and fibroblast-proliferating activities of NF3. The inclusion of RR, however, is crucial for NF3 to exert its overall wound-healing as well as the underlying angiogenesis-promoting effects. The results of present study justified the combined usage of AR and RR in the ratio of 2:1 as NF3 to treat diabetic foot ulcer and illustrated that AR is the principal herb in this herbal formula. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Treatment for Peptic Ulcer Disease

MedlinePlus

... NSAID-induced peptic ulcer when you have an H. pylori infection? If you have an H. pylori ... ulcers are healing. How do doctors treat an H.pylori -induced peptic ulcer? Doctors may prescribe triple ...

Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

PubMed Central

Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M.; Longatto-Filho, Adhemar; Castro, António G.; Pedrosa, Jorge; Fraga, Alexandra G.

2015-01-01

Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial.

PubMed

Tilbrook, Helen; Forsythe, Rachael O; Rolfe, Debbie; Clark, Laura; Bland, Martin; Buckley, Hannah; Chetter, Ian; Cook, Liz; Dumville, Jo; Gabe, Rhian; Harding, Keith; Layton, Alison; Lindsay, Ellie; McDaid, Catriona; Moffatt, Christine; Phillips, Ceri; Stansby, Gerard; Vowden, Peter; Williams, Laurie; Torgerson, David; Hinchliffe, Robert J

2015-11-10

Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014).

Four-year to Eight-year Results of Vagotomy and Simple Drainage for Benign Lesser Curve Gastric Ulcer

PubMed Central

Burge, H.; Gill, A. Morton; Maclean, C.; Stedeford, R.

1970-01-01

The results of vagotomy and simple drainage for recurrent benign lesser curve gastric ulcer are recorded. Seventy-two consecutive cases were treated from 1962 to 1965. The follow-up is therefore from five to eight years. In only two cases did the ulcer fail to heal and remain healed. Four years after operation both these had persistent ulceration and persistent gastric retention. Both have apparently been cured by gastrojejunostomy done to improve gastric drainage. ImagesFIG. 1FIG. 2FIG. 3 PMID:5451588

Chronic leg ulceration in homozygous sickle cell disease: the role of venous incompetence.

PubMed

Clare, Andrea; FitzHenley, Michael; Harris, June; Hambleton, Ian; Serjeant, Graham R

2002-11-01

Chronic leg ulceration is a common cause of morbidity in Jamaican patients with homozygous sickle cell (SS) disease. Ulcers heal more rapidly on bed rest and deteriorate on prolonged standing, suggesting a role of venous hypertension in their persistence. This hypothesis has been tested by Doppler detection of venous competence in SS patients and in matched controls with a normal haemoglobin (AA) genotype in the Jamaican Cohort Study. Venous incompetence was significantly more frequent in SS disease [137/183 (75%)] than in non-pregnant AA controls [53/137 (39%)]. Past or present ulceration occurred in 78 (43%) SS patients, with a highly significant association between leg ulceration and venous incompetence in the same leg (P < 0.001). Prominence and/or varicosities of the veins and spontaneous leg ulcers were more common among patients with multiple sites of incompetence. The association of venous incompetence with chronic leg ulceration identifies a further pathological mechanism contributing to the morbidity of SS disease. The cause of venous incompetence is unknown but the sluggish circulation associated with dependency, turbidity and impaired linear flow at venous valves, hypoxia-induced sickling, the rheological effects of high white cell counts, and activation of components of the coagulation system may all contribute. Venous hypertension in SS patients with leg ulceration suggests that firm elastic supportive dressings might promote healing of chronic leg ulcers.

Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

PubMed Central

Silva, Sandra Y; Rueda, Ligia C; Márquez, Gustavo A; López, Marcos; Smith, Daniel J; Calderón, Carlos A; Castillo, Juan C; Matute, Jaime; Rueda-Clausen, Christian F; Orduz, Arturo; Silva, Federico A; Kampeerapappun, Piyaporn; Bhide, Mahesh; López-Jaramillo, Patricio

2007-01-01

Background Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers. Methods and design A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patient's health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients. Trial registration NCT00428727. PMID:17897470

Topical antimicrobial agents for treating foot ulcers in people with diabetes.

PubMed

Dumville, Jo C; Lipsky, Benjamin A; Hoey, Christopher; Cruciani, Mario; Fiscon, Marta; Xia, Jun

2017-06-14

People with diabetes are at high risk for developing foot ulcers, which often become infected. These wounds, especially when infected, cause substantial morbidity. Wound treatments should aim to alleviate symptoms, promote healing, and avoid adverse outcomes, especially lower extremity amputation. Topical antimicrobial therapy has been used on diabetic foot ulcers, either as a treatment for clinically infected wounds, or to prevent infection in clinically uninfected wounds. To evaluate the effects of treatment with topical antimicrobial agents on: the resolution of signs and symptoms of infection; the healing of infected diabetic foot ulcers; and preventing infection and improving healing in clinically uninfected diabetic foot ulcers. We searched the Cochrane Wounds Specialised Register, CENTRAL, Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus in August 2016. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We used no restrictions with respect to language, date of publication, or study setting. We included randomised controlled trials conducted in any setting (inpatient or outpatient) that evaluated topical treatment with any type of solid or liquid (e.g., cream, gel, ointment) antimicrobial agent, including antiseptics, antibiotics, and antimicrobial dressings, in people with diabetes mellitus who were diagnosed with an ulcer or open wound of the foot, whether clinically infected or uninfected. Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction. Initial disagreements were resolved by discussion, or by including a third review author when necessary. We found 22 trials that met our inclusion criteria with a total of over 2310 participants (one study did not report number of participants). The included studies mostly had small numbers of participants (from 4 to 317) and relatively short follow-up periods (4 to 24 weeks). At baseline, six trials included only people with ulcers that were clinically infected; one trial included people with both infected and uninfected ulcers; two trials included people with non-infected ulcers; and the remaining 13 studies did not report infection status.Included studies employed various topical antimicrobial treatments, including antimicrobial dressings (e.g. silver, iodides), super-oxidised aqueous solutions, zinc hyaluronate, silver sulphadiazine, tretinoin, pexiganan cream, and chloramine. We performed the following five comparisons based on the included studies: Antimicrobial dressings compared with non-antimicrobial dressings: Pooled data from five trials with a total of 945 participants suggest (based on the average treatment effect from a random-effects model) that more wounds may heal when treated with an antimicrobial dressing than with a non-antimicrobial dressing: risk ratio (RR) 1.28, 95% confidence interval (CI) 1.12 to 1.45. These results correspond to an additional 119 healing events in the antimicrobial-dressing arm per 1000 participants (95% CI 51 to 191 more). We consider this low-certainty evidence (downgraded twice due to risk of bias). The evidence on adverse events or other outcomes was uncertain (very low-certainty evidence, frequently downgraded due to risk of bias and imprecision). Antimicrobial topical treatments (non dressings) compared with non-antimicrobial topical treatments (non dressings): There were four trials with a total of 132 participants in this comparison that contributed variously to the estimates of outcome data. Evidence was generally of low or very low certainty, and the 95% CIs spanned benefit and harm: proportion of wounds healed RR 2.82 (95% CI 0.56 to 14.23; 112 participants; 3 trials; very low-certainty evidence); achieving resolution of infection RR 1.16 (95% CI 0.54 to 2.51; 40 participants; 1 trial; low-certainty evidence); undergoing surgical resection RR 1.67 (95% CI 0.47 to 5.90; 40 participants; 1 trial; low-certainty evidence); and sustaining an adverse event (no events in either arm; 81 participants; 2 trials; very low-certainty evidence). Comparison of different topical antimicrobial treatments: We included eight studies with a total of 250 participants, but all of the comparisons were different and no data could be appropriately pooled. Reported outcome data were limited and we are uncertain about the relative effects of antimicrobial topical agents for each of our review outcomes for this comparison, that is wound healing, resolution of infection, surgical resection, and adverse events (all very low-certainty evidence). Topical antimicrobials compared with systemic antibiotics : We included four studies with a total of 937 participants. These studies reported no wound-healing data, and the evidence was uncertain for the relative effects on resolution of infection in infected ulcers and surgical resection (very low certainty). On average, there is probably little difference in the risk of adverse events between the compared topical antimicrobial and systemic antibiotics treatments: RR 0.91 (95% CI 0.78 to 1.06; moderate-certainty evidence - downgraded once for inconsistency). Topical antimicrobial agents compared with growth factor: We included one study with 40 participants. The only review-relevant outcome reported was number of ulcers healed, and these data were uncertain (very low-certainty evidence). The randomised controlled trial data on the effectiveness and safety of topical antimicrobial treatments for diabetic foot ulcers is limited by the availability of relatively few, mostly small, and often poorly designed trials. Based on our systematic review and analysis of the literature, we suggest that: 1) use of an antimicrobial dressing instead of a non-antimicrobial dressing may increase the number of diabetic foot ulcers healed over a medium-term follow-up period (low-certainty evidence); and 2) there is probably little difference in the risk of adverse events related to treatment between systemic antibiotics and topical antimicrobial treatments based on the available studies (moderate-certainty evidence). For each of the other outcomes we examined there were either no reported data or the available data left us uncertain as to whether or not there were any differences between the compared treatments. Given the high, and increasing, frequency of diabetic foot wounds, we encourage investigators to undertake properly designed randomised controlled trials in this area to evaluate the effects of topical antimicrobial treatments for both the prevention and the treatment of infection in these wounds and ultimately the effects on wound healing.

Gastroprotective and ulcer healing effects of Piptadeniastrum Africanum on experimentally induced gastric ulcers in rats.

PubMed

Ateufack, Gilbert; Domgnim Mokam, Elisabeth Carol; Mbiantcha, Marius; Dongmo Feudjio, Rostand Breuil; David, Nana; Kamanyi, Albert

2015-07-08

Gastric peptic ulcer is one of the common disorders of gastrointestinal tract, which occur due to an imbalance between the offensive and defensive factors. It is an illness that affects a considerable number of people worldwide. This study was conducted to evaluate the antiulcerogenic and antiulcer effects and recognize the basic mechanism of action of Piptadeniastrum africanum stem bark extracts. The aqueous and methanol extracts of Piptadeniastrum africanum were administered at the doses 125, 250 and 500 mg/kg to evaluate their effects on gastric ulcer induced by the HCl/ethanol mixture, indomethacin and acetic acid in Wistar strain male adult rats, aged between 12 and 16 weeks and weighing between 180 and 220 g. Ranitidine, Maalox and Misoprostol were used as standard drugs. Histopathological examination and nitric oxide level were performed to evaluate the basic mechanism of action of Piptadeniastrum africanum. Phytochemical screening was carried out to identify known phytochemicals present in these extracts. The aqueous and methanol extracts of stem bark of Piptadeniastrum africanum significantly inhibited (p < 0.01) gastric ulceration induced by HCl/ethanol to the percentages of inhibition of 81.38; 98.75 and 100 % for the aqueous extract and then 75.83, 89.76 and 96.52 % for the methanol extract, and with the Indomethacin-induced ulcers, aqueous and methanol extracts of bark of Piptadeniastrum africanum reduce significantly (p < 0.01) induced gastric lesions in rats, with percentage of cure 35.75; 52.33 and 98.58 % for the aqueous extract, and 33.7; 51.97; and 65.93 to the methanol extract. The results revealed a significant reduction of ulcerated surface in both extracts and increase of nitric oxide (NO) level with methanol extract. When compared to methanol extract, aqueous extract showed more pronounced effects, corresponding to percentages of healing of 59. 92; 84.12 and 59.65 % for the aqueous extract; and 70.43; 55.49 and 57.59 % for the methanol extract in the ulcer induced by acetic acid, all at the respective doses of 125, 250 and 500 mg/kg. Histopathological observations also demonstrated curative effect. As such, both extracts were found to exhibit preventive and curative effects through the release of NO and growth factors. This could also be due to the presence of phytochemicals such as alkaloids, flavonoids, phenols and saponins which act as antisecretory agents. Piptadeniastrum africanum stem bark extracts thus have gastroprotective and ulcer healing effects, which could result from their activities by stimulating important cellular mechanisms such as migration and proliferation of epithelial cells that may have a cytoprotective effect by stimulating the release of prostaglandins. These results are required to confirm the ethnopharmacological use of Piptadeniastrum africanum stem bark in the treatment of ulcer.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

NASA Astrophysics Data System (ADS)

Cadena, M. S. Reyes; Chapul, L. Sánchez; Pérez, Javiér; García, M. N. Jiménez; López, M. A. Jiménez; Espíndola, M. E. Sánchez; Perez, R. Paniagua; Hernández, N. A.; Paniagua, G.; Uribe, F.; Nava, J. J. Godina; Segura, M. A. Rodríguez

2008-08-01

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-β) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animals subjected to ELF together with the transfer factor.

The Effect of Electrical Stimulation Combined with Foam Dressing on Ulcer Healing in Rats with Spinal Cord Injury.

PubMed

Yu, Ki-Pi; Yoo, Seol Bong; Yang, Seok Jeong; Yoon, Yong-Soon

2015-11-01

To evaluate the effect of electrical stimulation (ES) combined with foam dressing on wound healing in rats with spinal cord injury. Complete spinal cord injury was induced in 49 male Sprague-Dawley rats at the T11-L1 level, after which a pressure ulcer was induced on the left thigh. The newly invented surface electrode, which was fitted with foam inside, was applied to the ulcers. Rats were divided into 2 groups as follows: the ES group, which received foam dressings and ES (2 Hz and 200-microsecond duration, 15 mA) for 4 times a day, 30 minutes each, for 3 weeks; and the control group, which received the foam dressings without ES. The ulcer area was measured by taking a photograph daily from day 0 to day 21. Histopathologic and immune-histochemical evaluations were performed on day 1 and days 7, 14, and 21. The area of the ulcers of the ES group was smaller than that of the control group after day 14 (P < .05). In the ES group, the vascularity was significantly greater on day 14 and more decreased on day 21 compared with day 7 than that in the control group (P < .05). In the ES group, the area of positive reaction to anti-α-SMA antibody was increased compared with the control group on days 7 and 14 and decreased on day 21 (P > .05). Electrical stimulation combined with foam dressing by means of newly invented surface electrodes facilitates and accelerates the wound-healing process.

Treatment of Diabetic Foot Ulcer Using Matriderm In Comparison with a Skin Graft

PubMed Central

Jeon, Hyojin; Yeo, Hyeonjung; Jeong, Hoijoon; Son, Daegu; Han, Kihwan

2013-01-01

Background For patients with neuropathy, vasculopathy, and impairment of wound healing, treatment of a diabetic foot ulcer poses many challenges. A large number of dermal analogues have been invented in an effort to overcome these challenges. Matriderm, a dermal analogue, is made from bovine collagen and elastin. This study was conducted in order to evaluate the effectiveness of Matriderm for treatment of diabetic foot ulcers, in comparison with skin grafting. Methods Sixty patients with diabetic foot ulcer were included in this prospective study. The average age of the patients, who had type II diabetes mellitus, was 58 years old. The patients were allocated to an experimental or control group with their consents. The patients were selected with their consent for inclusion in an experimental group and a control group. Patients in the experimental group received a Matriderm appliance and a split-thickness skin graft, while those in the control group received only a split-thickness skin graft. Results A shorter hospitalization period (7.52 weeks) was observed in the experimental group than in the control group (9.22 weeks), and a shorter period of time (8.61 weeks) was required for complete healing, compared with the control group (12.94 weeks), with statistical significance (P<0.05). A higher elasticity ratio of the affected side to the non-affected side was observed in the experimental group, compared with the control group (P<0.01). Conclusions Matriderm enables effective healing and improves elasticity in treatment of patients with diabetic foot ulcer. PMID:23898439

Acellular fetal bovine dermal matrix in the treatment of nonhealing wounds in patients with complex comorbidities.

PubMed

Lullove, Eric

2012-01-01

In contrast to the narrow indications for living skin equivalents, extracellular matrix biomaterials are clinically used in a wide range of wound-healing applications. Given the breadth of possible uses, the goal of this study was to retrospectively compile and analyze the clinical application and effectiveness of an extracellular matrix biomaterial derived from fetal bovine dermis (PriMatrix; TEI Biosciences, Boston, Massachusetts) in patients treated by a single physician and monitored postsurgically in an outpatient wound care center. A retrospective medical record review was conducted of consecutive patients treated from January 2007 through January 2009 with meshed PriMatrix after sharp/surgical debridement and coverage with standard moist wound therapy dressings. Twenty-nine patients and 34 wounds were compiled. All of the wounds were unresponsive to conservative treatment owing to complications, including infection, exposed bone or tendon, and other comorbidities known to delay healing. Wounds included 11 diabetic ulcers, 8 venous stasis ulcers, 10 nonhealing traumatic wounds, and 5 other chronic wounds. Thirty of 34 wounds healed, with four patients lost to follow-up. Mean time to healing for diabetic foot ulcers was 105 days with an average of 2.6 PriMatrix applications. Mean time to healing for venous, traumatic, and other chronic wounds was 74 to 82 days with an average of 1.2 to 1.4 PriMatrix applications. In patients with comorbidities known to delay healing, the implantation of PriMatrix promoted the healing and, ultimately, full reepithelialization of otherwise unresponsive wounds of varied etiology, including those with complications of infection or exposed bone or tendon.

Skin flaps and grafts - self-care

MedlinePlus

... Free flap - self-care; Skin autografting - self-care; Pressure ulcer skin flap self-care; Burns skin flap self- ... skin infection Surgery for skin cancer Venous ulcers , pressure ulcers , or diabetic ulcers that DO NOT heal After ...

The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study.

PubMed

Kavros, Steven J; Dutra, Timothy; Gonzalez-Cruz, Renier; Liden, Brock; Marcus, Belinda; McGuire, James; Nazario-Guirau, Luis

2014-08-01

The objective of this multicenter study was to prospectively evaluate the healing outcomes of chronic diabetic foot ulcers (DFUs) treated with PriMatrix (TEI Biosciences, Boston, Massachusetts), a fetal bovine acellular dermal matrix. Inclusion criteria required the subjects to have a chronic DFU that ranged in area from 1 to 20 cm² and failed to heal more than 30% during a 2-week screening period when treated with moist wound therapy. For qualifying subjects, PriMatrix was secured into a clean, sharply debrided wound; dressings were applied to maintain a moist wound environment, and the DFU was pressure off-loaded. Wound area measurements were taken weekly for up to 12 weeks, and PriMatrix was reapplied at the discretion of the treating physician. A total of 55 subjects were enrolled at 9 US centers with 46 subjects progressing to study completion. Ulcers had been in existence for an average of 286 days, and initial mean ulcer area was 4.34 cm². Of the subjects completing the study, 76% healed by 12 weeks with a mean time to healing of 53.1 ± 21.9 days. The mean number of applications for these healed wounds was 2.0 ± 1.4, with 59.1% healing with a single application of PriMatrix and 22.9% healing with 2 applications. For subjects not healed by 12 weeks, the average wound area reduction was 71.4%. The results of this multicenter prospective study demonstrate that the use of PriMatrix integrated with standard-of-care therapy is a successful treatment regimen to heal DFUs.

Pseudomonas aeruginosa uses T3SS to inhibit diabetic wound healing.

PubMed

Goldufsky, Josef; Wood, Stephen J; Jayaraman, Vijayakumar; Majdobeh, Omar; Chen, Lin; Qin, Shanshan; Zhang, Chunxiang; DiPietro, Luisa A; Shafikhani, Sasha H

2015-01-01

Diabetic foot ulcers are responsible for more hospitalizations than any other complication of diabetes. Bacterial infection is recognized as an important factor associated with impaired healing in diabetic ulcers. Pseudomonas aeruginosa is the most frequently detected Gram-negative pathogen in diabetic ulcers. P. aeruginosa infection has been shown to impair healing in diabetic wounds in a manner that correlates with its ability to form biofilm. While the majority of infections in diabetic ulcers are biofilm associated, 33% of infections are nonbiofilm in nature. P. aeruginosa is the most prevalent Gram-negative pathogen in all diabetic wound types, which suggests that the deleterious impact of P. aeruginosa on healing in diabetic wounds goes beyond its ability to form biofilm and likely involves other factors. The Type III Secretion System (T3SS) virulence structure is required for the pathogenesis of all P. aeruginosa clinical isolates, suggesting that it may also play a role in the inhibition of wound repair in diabetic skin ulcers. We evaluated the role of T3SS in mediating P. aeruginosa-induced tissue damage in the wounds of diabetic mice. Our data demonstrate that P. aeruginosa establishes a robust and persistent infection in diabetic wounds independent of its ability to form biofilm and causes severe wound damage in a manner that primarily depends on its T3SS. © 2015 by the Wound Healing Society.

Ulcer dressings and management.

PubMed

Sussman, Geoff

2014-09-01

Chronic leg ulcers caused by venous disease, arterial disease or a combination of both need to be clearly identified before treatment can be commenced. Their management will depend on the diagnosis, combining direct management of the ulcer as well as management of patient factors. Other chronic wounds commonly observed in practice include pressure wounds, skin tears, atypical leg ulcers. This paper will outline a simple way to manage people with chronic ulcers. Conclusion The prevalence of chronic wounds is expected to rise given that people are living longer and that the incidence of diabetes is increasing. There is a need is to clearly identify the underlying cause of any wound, including factors that may delay healing, and to treat appropriately. Treatment should address the wound environment, tissue base, presence of bacteria and the level of slough. If there is no improvement in wound healing after 4 weeks then seek help from a wound specialist. The prevalence of chronic ulcers in Australia has been estimated at 2-5%. Comprehensive assessment of the ulcer, the region and the whole person is an important first step in treatment. The aim of management is to promote healing and minimise the impact on the patient.

A multi-center, randomized, clinical trial comparing adhesive polyurethane foam dressing and adhesive hydrocolloid dressing in patients with grade II pressure ulcers in primary care and nursing homes.

PubMed

Guillén-Solà, Mireia; Soler Mieras, Aina; Tomàs-Vidal, Antònia M

2013-12-21

Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14.

Twice-daily Budesonide 2-mg Foam Induces Complete Mucosal Healing in Patients with Distal Ulcerative Colitis.

PubMed

Naganuma, Makoto; Aoyama, Nobuo; Suzuki, Yasuo; Nishino, Haruo; Kobayashi, Kiyonori; Hirai, Fumihito; Watanabe, Kenji; Hibi, Toshifumi

2016-07-01

Mucosal healing is an important therapeutic goal for ulcerative colitis. Once-daily administration of budesonide 2-mg foam is widely used for inducing clinical remission. No study has assessed the usefulness of twice-daily budesonide 2mg foam on mucosal healing in ulcerative colitis patients. We explored the efficacy for mucosal healing of once- or twice-daily budesonide foam in distal ulcerative colitis patients. This study was a multicentre, randomised, double-blind, placebo-controlled trial. In all, 165 patients with active, mild to moderate distal ulcerative colitis were randomised to three groups: once- or twice-daily budesonide 2mg/25ml foam, or placebo foam, for 6 weeks. Complete mucosal healing [endoscopic subscore = 0] and the safety profile were assessed at Week 6. Prespecified and post hoc analyses were used. The percentages of complete mucosal healing in the twice-daily budesonide foam group were 46.4% compared with 23.6% in the once-daily group [p = 0.0097], or 5.6% in the placebo group [p < 0.0001]. The percentages of clinical remission and the percentages of endoscopic subscore ≤ 1 in the twice-daily budesonide foam group were 48.2% and 76.8%, compared with 50.9% and 69.1% in the once-daily group [no difference], or 20.4% and 46.3% in the placebo group [p = 0.0029 and p = 0.0007], respectively. In the subgroup of patients with previous use of a 5-aminosalicylic acid suppository or enema, there was a greater percentage of complete mucosal healing in the twice-daily budesonide foam group [32.0%] compared with that in the once-daily [8.7%, p = 0.0774] or placebo groups [4.8%, p = 0.0763], though there was no significant difference. No serious adverse event occurred. A significantly greater percentage of patients receiving twice-daily administration of budesonide foam compared with once-daily administration/placebo achieved complete mucosal healing. This is the first study to evaluate the endoscopic efficacy of twice-daily administration of 6-week budesonide foam treatment for ulcerative colitis. © European Crohn’s and Colitis Organisation 2015.

Twice-daily Budesonide 2-mg Foam Induces Complete Mucosal Healing in Patients with Distal Ulcerative Colitis

PubMed Central

Aoyama, Nobuo; Suzuki, Yasuo; Nishino, Haruo; Kobayashi, Kiyonori; Hirai, Fumihito; Watanabe, Kenji; Hibi, Toshifumi

2016-01-01

Background and Aims: Mucosal healing is an important therapeutic goal for ulcerative colitis. Once-daily administration of budesonide 2-mg foam is widely used for inducing clinical remission. No study has assessed the usefulness of twice-daily budesonide 2mg foam on mucosal healing in ulcerative colitis patients. We explored the efficacy for mucosal healing of once- or twice-daily budesonide foam in distal ulcerative colitis patients. Methods: This study was a multicentre, randomised, double-blind, placebo-controlled trial. In all, 165 patients with active, mild to moderate distal ulcerative colitis were randomised to three groups: once- or twice-daily budesonide 2mg/25ml foam, or placebo foam, for 6 weeks. Complete mucosal healing [endoscopic subscore = 0] and the safety profile were assessed at Week 6. Prespecified and post hoc analyses were used. Results: The percentages of complete mucosal healing in the twice-daily budesonide foam group were 46.4% compared with 23.6% in the once-daily group [p = 0.0097], or 5.6% in the placebo group [p < 0.0001]. The percentages of clinical remission and the percentages of endoscopic subscore ≤ 1 in the twice-daily budesonide foam group were 48.2% and 76.8%, compared with 50.9% and 69.1% in the once-daily group [no difference], or 20.4% and 46.3% in the placebo group [p = 0.0029 and p = 0.0007], respectively. In the subgroup of patients with previous use of a 5-aminosalicylic acid suppository or enema, there was a greater percentage of complete mucosal healing in the twice-daily budesonide foam group [32.0%] compared with that in the once-daily [8.7%, p = 0.0774] or placebo groups [4.8%, p = 0.0763], though there was no significant difference. No serious adverse event occurred. Conclusions: A significantly greater percentage of patients receiving twice-daily administration of budesonide foam compared with once-daily administration/placebo achieved complete mucosal healing. This is the first study to evaluate the endoscopic efficacy of twice-daily administration of 6-week budesonide foam treatment for ulcerative colitis. PMID:26577683

Evaluation of wound healing activity of extracts of plantain banana (Musa sapientum var. paradisiaca) in rats.

PubMed

Agarwal, P K; Singh, A; Gaurav, K; Goel, Shalini; Khanna, H D; Goel, R K

2009-01-01

Plantain banana (M. sapientum var. paradisiaca, MS) has been shown to possess ulcer healing activity. The present work with plantain banana was undertaken with the premise that the drug promoting ulcer healing could have effect on wound healing also. Wound healing activity of MS was studied in terms of (i) percent wound contraction, epithelization period and scar area; (ii) wound breaking strength and (iii) on granulation tissue antioxidant status [estimation of superoxide dismutase (SOD) and reduced glutathione (GSH), free radical (lipid peroxidation, an indicator of tissue damage) and connective tissue formation and maturation (hexuronic acid, hydroxyproline and hexosamine levels)] in excision, incision and dead space wound models respectively. The rats were given graded doses (50-200 mg/kg/day) of aqueous (MSW) and methanolic (MSE) extracts of MS orally for a period of 10-21 days depending upon the type of study. Both extracts (100 mg/kg) when studied for incision and dead space wounds parameters, increased wound breaking strength and levels of hydroxyproline, hexuronic acid, hexosamine, superoxide dismutase, reduced glutathione in the granulation tissue and decreased percentage of wound area, scar area and lipid peroxidation when compared with the control group. Both the extracts showed good safety profile. Plantain banana thus, favoured wound healing which could be due to its antioxidant effect and on various wound healing biochemical parameters.

Efficacy of mummy on healing of pressure ulcers: A randomized controlled clinical trial on hospitalized patients in intensive care unit

PubMed Central

Moghadari, Masoud; Rezvanipour, Mozafar; Mehrabani, Mitra; Ahmadinejad, Mehdi; Hashempur, Mohammad Hashem

2018-01-01

Background Mummy is a mineral substance which according to Persian medicine texts, may be useful in treatment of chronic ulcers. Objective The present study was performed with the aim of determining the effect of mummy on healing of pressure in male patients who had been hospitalized due to cerebrospinal injury in the Intensive Care Unit. Methods This randomized, placebo-controlled clinical trial was performed on 75 patients who had pressure ulcer at Shahid Bahonar Hospital in Kerman, Iran, from September 2016 to March 2017. The control group received normal saline and routine wound dressing, while the intervention group received mummy water solution 20% in addition to normal saline and routine wound dressing on a daily basis. Data was recorded based on the PUSH method. In both groups, ulcers were evaluated on days 0, 7, 14, 21 and 28 for the variables of ulcer surface area, the amount of exudate and type of tissue. Data analysis was done through SPSS 21 and using t-test, Repeated Measure Analysis, Cox Regression and Chi-square. Results Both groups showed reduction in the average ulcer surface area (3.26 to 0.53 in the intervention group and 5.1 to 3.46 in the control group), the average exudate amount (1.26 to 0.26 in the intervention group and 1.83 to 1.06 in the control group) and the average tissue score (1.36 to 0.23 in the intervention group and 2.13 to 1.26 in the control group). Over the entire study period, the intervention group showed more acceptable signs of healing compared to the control group (p<0.05). Conclusion The healing process was more prominent in the intervention group than the control group. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials with registered NO. (IRCT2014042917494N1) (29/04/2014). Funding No financial support for the research. PMID:29588812

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

PubMed

Hinojosa, C A; Olivares-Cruz, S; Laparra-Escareno, H; Sanchez-Castro, S; Tamayo-Garcia, B; Anaya-Ayala, J E

2016-12-02

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only four healed the ulcers with an mean of 72 months (range: 2-204) (p=0.94). There seems to be an association between an optimal anticoagulation therapy with Warfarin monitored by INR and wound healing rates in thrombophilic patients with chronic venous ulcers. Further research is warranted. The authors have no conflict of interest.

Protective Effect of Cod (Gadus macrocephalus) Skin Collagen Peptides on Acetic Acid-Induced Gastric Ulcer in Rats.

PubMed

Niu, Huina; Wang, Zhicong; Hou, Hu; Zhang, Zhaohui; Li, Bafang

2016-07-01

This research was performed to explore the protective effect of cod skin collagen peptides (CCP) on gastric ulcer induced by acetic acid. The CCP were fractionated into low molecular CCP (LMCCP, Mw < 3 kDa) and high molecular CCP (HMCCP, Mw > 3 kDa). In HMCCP and LMCCP, glycine of accounted for about one-third of the total amino acids without cysteine and tryptophan, and hydrophobic amino acids accounted for about 50%. After 21 d CCP treatment (60 or 300 mg/kg, p.o./daily), the healing effects on acetic acid-induced gastric ulcers were evaluated by macroscopic measure, microscopic measure, and immune histochemistry. Moreover, the expression levels of the growth factors, such as vascular endothelial growth factor, epidermal growth factor, transforming growth factor β1 (TGFβ1), and the heat shock protein 70 (HSP70) was detected. The results showed that both LMCCP and HMCCP could significantly decrease the ulcer areas and promote the healing of the lesions. They also could improve the levels of hexosamine, glutathione, superoxide dismutase, and glutathione peroxidase, and reduce the content of malondialdehyde and inducible nitric oxide synthase. In addition, the expression level of TGFβ1 gene and HSP70 mRNA was significantly improved by the treatment. It suggested that CCP could be able to improve symptoms of gastric ulcer and probably be used in the treatment of gastric ulcer. © 2016 Institute of Food Technologists®

Verification of echo amplitude envelope analysis method in skin tissues for quantitative follow-up of healing ulcers

NASA Astrophysics Data System (ADS)

Omura, Masaaki; Yoshida, Kenji; Akita, Shinsuke; Yamaguchi, Tadashi

2018-07-01

We aim to develop an ultrasonic tissue characterization method for the follow-up of healing ulcers by diagnosing collagen fibers properties. In this paper, we demonstrated a computer simulation with simulation phantoms reflecting irregularly distributed collagen fibers to evaluate the relationship between physical properties, such as number density and periodicity, and the estimated characteristics of the echo amplitude envelope using the homodyned-K distribution. Moreover, the consistency between echo signal characteristics and the structures of ex vivo human tissues was verified from the measured data of normal skin and nonhealed ulcers. In the simulation study, speckle or coherent signal characteristics are identified as periodically or uniformly distributed collagen fibers with high number density and high periodicity. This result shows the effectiveness of the analysis using the homodyned-K distribution for tissues with complicated structures. Normal skin analysis results are characterized as including speckle or low-coherence signal components, and a nonhealed ulcer is different from normal skin with respect to the physical properties of collagen fibers.

Role of argon laser as an adjunctive therapy for treatment of resistant infected corneal ulcers

PubMed Central

Khater, Mohammad M; Selima, Adel A; El-Shorbagy, Mohammad S

2014-01-01

Purpose To evaluate the role of argon laser as an adjunctive therapy in ten patients with resistant infected corneal ulcers with or without hypopyon. Methods The study included 20 patients, split into two groups of ten, with resistant infected corneal ulcers with or without hypopyon. One group was considered as the control group and treated with local and systemic specific antimicrobial drugs guided with culture and sensitivity tests. The other group started with the same specific therapy as the control group for 1 week with no obvious improvement and then was further treated with argon laser. The ten patients in the control group included five cases of fungal ulcers, three mixed (fungal and bacterial) ulcers, and two viral ulcers. The ten patients in the other group included three cases of fungal ulcers, three mixed (fungal and viral) ulcers, three viral ulcers, and one bacterial ulcer as proven with microbial culture and sensitivity tests. Eight cases of the control group and seven cases of the other group were associated with hypopyon. Before laser treatment, a drop of benoxinate hydrochloride 0.4% and a single drop of fluorescein sodium 0.25% were instilled. Argon laser irradiation of the affected cornea was performed using an argon 532 nm wavelength (Carl Zeiss LSL 532s AG; Carl Zeiss Meditec AG, Jena, Germany). A spot size of 500 μm, pulse duration of 0.2 seconds, and power of 900 mW were used. All cases were followed up for 3 months after healing was achieved. Results During the first 4 weeks after laser treatment, all patients showed complete healing of the epithelial defect and resolution of stromal infiltration with no adverse effects. In the control group, four cases needed an amniotic membrane graft due to thinning and the other six cases were healed in a duration that ranged from 3 to 7 weeks. Conclusion Argon laser phototherapy is useful as an adjunctive treatment for resistant infected corneal ulcers. More cases are needed to get more reliable results and to confirm our findings. PMID:24920878

Role of argon laser as an adjunctive therapy for treatment of resistant infected corneal ulcers.

PubMed

Khater, Mohammad M; Selima, Adel A; El-Shorbagy, Mohammad S

2014-01-01

To evaluate the role of argon laser as an adjunctive therapy in ten patients with resistant infected corneal ulcers with or without hypopyon. The study included 20 patients, split into two groups of ten, with resistant infected corneal ulcers with or without hypopyon. One group was considered as the control group and treated with local and systemic specific antimicrobial drugs guided with culture and sensitivity tests. The other group started with the same specific therapy as the control group for 1 week with no obvious improvement and then was further treated with argon laser. The ten patients in the control group included five cases of fungal ulcers, three mixed (fungal and bacterial) ulcers, and two viral ulcers. The ten patients in the other group included three cases of fungal ulcers, three mixed (fungal and viral) ulcers, three viral ulcers, and one bacterial ulcer as proven with microbial culture and sensitivity tests. Eight cases of the control group and seven cases of the other group were associated with hypopyon. Before laser treatment, a drop of benoxinate hydrochloride 0.4% and a single drop of fluorescein sodium 0.25% were instilled. Argon laser irradiation of the affected cornea was performed using an argon 532 nm wavelength (Carl Zeiss LSL 532s AG; Carl Zeiss Meditec AG, Jena, Germany). A spot size of 500 μm, pulse duration of 0.2 seconds, and power of 900 mW were used. All cases were followed up for 3 months after healing was achieved. During the first 4 weeks after laser treatment, all patients showed complete healing of the epithelial defect and resolution of stromal infiltration with no adverse effects. In the control group, four cases needed an amniotic membrane graft due to thinning and the other six cases were healed in a duration that ranged from 3 to 7 weeks. Argon laser phototherapy is useful as an adjunctive treatment for resistant infected corneal ulcers. More cases are needed to get more reliable results and to confirm our findings.

Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate the Oral Wound Healing in Rats.

PubMed

Coelho, Fernanda Hack; Salvadori, Gabriela; Rados, Pantelis Varvaki; Magnusson, Alessandra; Danilevicz, Chris Krebs; Meurer, Luise; Martins, Manoela Domingues

2015-07-01

The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re-epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi-quantitative analyses, was performed using the Kruskal-Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats. Copyright © 2015 John Wiley & Sons, Ltd.

Hymenaea stigonocarpa Mart. ex Hayne: a Brazilian medicinal plant with gastric and duodenal anti-ulcer and antidiarrheal effects in experimental rodent models.

PubMed

Rodrigues Orsi, Patricia; Bonamin, Flávia; Aparecida Severi, Juliana; Cássia Santos, Raquel; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko; Stasi, Luiz Claudio Di

2012-08-30

Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae) is a medicinal species commonly found in the Brazilian savannah. The stem bark of this medicinal plant, popularly known as "jatobá-do-cerrado", is widely used in tea form to treat gastric pain, ulcers, diarrhoea and inflammation, whereas its fruits pulp is edible. The aim of this study was to investigate the antidiarrheal and anti-ulcer effects of a methanolic extract derived from the stem bark (MHs) and diet with fruit pulp of H. stigonocarpa. The antidiarrheal action of MHs was measured against the intestinal motility and diarrhoea induced by castor oil in mice. The preventive action of MHs (50, 100, 150 and 200mg/Kg, by oral route (p.o.)) against peptic ulcers was evaluated in experimental rodent models challenged with absolute ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (I/R) (200mg/Kg, p.o.) and cysteamine (200mg/Kg, p.o.). The main anti-ulcer mechanisms of action of MHs were analysed as follows: evaluation of the gastric juice parameters, assessment of mucus adherence to the gastric wall, determination of the role of nitric oxide (NO) and sulfhydryl compounds (SH), glutathione (GSH) levels and myeloperoxidase (MPO) activity. The healing effects from MHs (200mg/Kg) and diet with fruit pulp (10%) against gastric and duodenal ulcers induced by acetic acid were also evaluated by treating rats over 7 or 14 consecutive days of treatment. The phytochemical profile of MHs and fruit pulp indicated the presence of phenolic compounds (mainly flavonoids and condensed tannins). MHs (200mg/Kg, p.o.) displayed an antidiarrheal effect and were able to protect gastric mucosa against absolute ethanol (68% protection) and also against the injurious effect of NSAIDs (86% protection) when compared to the group treated with vehicle. These results were accompanied by the prevention of GSH depletion and an inhibition of MPO activity when compared to animals treated with vehicle (P<0.05). MHs markedly protected duodenal mucosa against injuries caused by cysteamine (98%) and also against I/R induced gastric ulceration (80%) when compared to the group treated with vehicle. Furthermore, MHs also prevented the GSH depletion of gastric mucosa relative to the control group treated with vehicle. NO appeared to be involved in this gastroprotective effect. MHs and diet with fruit pulp clearly demonstrated gastric healing actions after treatment for 7 (MHs - 53% inhibition) or 14 days (MHs - 60% inhibition and fruit pulp - 61% inhibition). Treatment with diet with fruit pulp for 7 days demonstrates a significant duodenal healing effect (71% inhibition) without any signs of toxicity. MHs clearly demonstrate antidiarrheal, gastroprotective and cicatrising effects in experimental gastric and duodenal ulcers, and the diet with fruit pulp displays duodenal healing effects. The observed effects may be associated with the antioxidant effect, which may be due the presence of condensed tannins and flavonoids in the bark and fruit of H. stigonocarpa. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Evaluation of a foam dressing for acute and chronic wound exudate management.

PubMed

Bullough, Lindsay; Johnson, Sue; Forder, Rebecca

2015-09-01

This article discusses the use of a foam dressing for exudate management in both chronic and acute wounds, such as surgical wounds, pressure ulcers, diabetic ulcers, trauma wounds, and leg ulcers. The primary objective of the study was to observe patients' wound progression in terms of wound size and the condition of the wound bed, when using this foam dressing as either a primary or secondary dressing. The outcome of the evaluation demonstrated that ActivHeal Foam Contact dressing effectively managed exudate. It was also observed that the dressing can assist in autolysis and support improvements in peri-wound status. Choosing an appropriate dressing to manage a wound is essential. Clinicians working in the NHS are under pressure to deliver good-quality clinical outcomes, and the ActivHeal Foam Contact dressing supports this outcome.

Honey as a topical treatment for wounds.

PubMed

Jull, Andrew B; Walker, Natalie; Deshpande, Sohan

2013-02-28

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (e.g. burns, lacerations) and chronic wounds (e.g. skin ulcers, infected surgical wounds). For this first update of the review we searched the Cochrane Wounds Group Specialised Register (searched 13 June 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2008 to May Week 5 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 12 June 2012); Ovid EMBASE (2008 to 2012 Week 23); and EBSCO CINAHL (2008 to 8 June 2012). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. We identified 25 trials (with a total of 2987 participants) that met the inclusion criteria, including six new trials that were added to this update. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and 12 trials evaluated the effect of honey in burns. In chronic wounds, two trials evaluated the effect of honey in venous leg ulcers, and single trials investigated its effect in infected post-operative wounds, pressure injuries, cutaneous Lieshmaniasis, diabetic foot ulcers and Fournier's gangrene. Three trials recruited people into mixed groups of chronic or acute wounds. Most trials were at high or unclear risk of bias. In acute wounds, specifically partial-thickness burns, honey might reduce time to healing compared with some conventional dressings (WMD -4.68 days, 95%CI -4.28 to -5.09 days), but, when compared with early excision and grafting, honey delays healing in partial- and full-thickness burns (WMD 13.6 days, 95% CI 10.02 to 17.18 days). In chronic wounds, honey does not significantly increase healing in venous leg ulcers when used as an adjuvant to compression (RR 1.15, 95% CI 0.96 to 1.38), and may delay healing in cutaneous Leishmaniasis when used as an adjuvant to meglumine antimoniate compared to meglumine antimoniate alone (RR 0.72, 95% CI 0.51 to 1.01). Honey dressings do not increase rates of healing significantly in venous leg ulcers when used as an adjuvant to compression. Honey may delay healing in partial- and full-thickness burns in comparison to early excision and grafting, and in cutaneous Leishmaniasis when used as an adjuvant with meglumine antimoniate. Honey might be superior to some conventional dressing materials, but there is considerable uncertainty about the replicability and applicability of this evidence. There is insufficient evidence to guide clinical practice in other types of wounds, and purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available.

Low Grade Elastic Compression Regimen for Venous Leg Ulcers-An Effective Compromise for Patients Requiring Daily Dressing Changes

PubMed Central

Dabiri, Ganary; Hammerman, Scott; Falanga, Vincent

2014-01-01

Venous leg ulcers affect millions of patients worldwide and are a tremendous financial burden on our healthcare system. The hallmark of venous disease of the lower extremities is venous hypertension, and compression is the current mainstay of treatment. However, many patients are noncompliant, in part because of the complexity of the dressings and the difficulties with application and removal. The aim of our study was to determine an effective compression dressing regimen for patients with venous leg ulcers who require changing the ulcer primary dressing twice daily. We used two layers of a latex free tubular elastic bandage for compression. The primary endpoint of our study was increased wound healing rate and our secondary endpoint was complete wound closure. All active study subjects had positive healing rates at week 4 and week 8. Two subjects achieved complete wound closure by week 8. We conclude that compression with a latex-free tubular elastic bandage can be safely used in patients with venous leg ulcers requiring frequent dressing changes. This type of compression allows for daily inspection of wounds, dressing changes at home, flexibility in the context of clinical trials, and is a compromise for patients that are intolerant to compression dressings. PMID:24267477

Pressure ulcer multidisciplinary teams via telemedicine: a pragmatic cluster randomized stepped wedge trial in long term care.

PubMed

Stern, Anita; Mitsakakis, Nicholas; Paulden, Mike; Alibhai, Shabbir; Wong, Josephine; Tomlinson, George; Brooker, Ann-Sylvia; Krahn, Murray; Zwarenstein, Merrick

2014-02-24

The study was conducted to determine the clinical and cost effectiveness of enhanced multi-disciplinary teams (EMDTs) vs. 'usual care' for the treatment of pressure ulcers in long term care (LTC) facilities in Ontario, Canada We conducted a multi-method study: a pragmatic cluster randomized stepped-wedge trial, ethnographic observation and in-depth interviews, and an economic evaluation. Long term care facilities (clusters) were randomly allocated to start dates of the intervention. An advance practice nurse (APN) with expertise in skin and wound care visited intervention facilities to educate staff on pressure ulcer prevention and treatment, supported by an off-site hospital based expert multi-disciplinary wound care team via email, telephone, or video link as needed. The primary outcome was rate of reduction in pressure ulcer surface area (cm2/day) measured on before and after standard photographs by an assessor blinded to facility allocation. Secondary outcomes were time to healing, probability of healing, pressure ulcer incidence, pressure ulcer prevalence, wound pain, hospitalization, emergency department visits, utility, and cost. 12 of 15 eligible LTC facilities were randomly selected to participate and randomized to start date of the intervention following the stepped wedge design. 137 residents with a total of 259 pressure ulcers (stage 2 or greater) were recruited over the 17 month study period. No statistically significant differences were found between control and intervention periods on any of the primary or secondary outcomes. The economic evaluation demonstrated a mean reduction in direct care costs of $650 per resident compared to 'usual care'. The qualitative study suggested that onsite support by APN wound specialists was welcomed, and is responsible for reduced costs through discontinuation of expensive non evidence based treatments. Insufficient allocation of nursing home staff time to wound care may explain the lack of impact on healing. Enhanced multi-disciplinary wound care teams were cost effective, with most benefit through cost reduction initiated by APNs, but did not improve the treatment of pressure ulcers in nursing homes. Policy makers should consider the potential yield of strengthening evidence based primary care within LTC facilities, through outreach by APNs. ClinicalTrials.gov identifier NCT01232764.

In vivo study of non-invasive effects of non-thermal plasma in pressure ulcer treatment.

PubMed

Chatraie, Maedeh; Torkaman, Giti; Khani, Mohammadreza; Salehi, Hossein; Shokri, Babak

2018-04-04

According to high incidence and prevalence of pressure ulcers worldwide, the purpose of this study is using of non-thermal atmospheric plasma as a novel therapy for pressure ulcers. Cold plasma was produced by applying a high-voltage (5 kV) and high-frequency (25 kHz), to helium gas. Under general anesthesia and sterile conditions, two circular magnets were used to create pressure ulcers on the dorsal skin of adult rats. The wounds were divided randomly into control and plasma-treated groups. Animals in the plasma-treated group received plasma radiation for 5 days, each day 3 times and every time 60 s. Mechanical assays were performed to determine plasma effects on the mechanical strength of the repaired tissue. The results showed that mechanical strength of repaired wound in the plasma-treated group was significantly higher than that in the control group (p < 0.05). In addition, evidence from histological studies indicates a significantly accelerated wound re-epithelialization in comparison with the control group; angiogenesis and fibrosis (collagen synthesis) were also significantly increased and the inflammation phase of wound healing was shorter in the plasma-treated group. The plasma treatment also resulted in significant wound contraction and acceleration of wound healing. The findings of present study indicate the effects of cold plasma on pressure ulcer treatment.

Enhancement of Gastric Ulcer Healing and Angiogenesis by Hepatocyte Growth Factor Gene Mediated by Attenuated Salmonella in Rats.

PubMed

Ha, Xiaoqin; Peng, Junhua; Zhao, Hongbin; Deng, Zhiyun; Dong, Juzi; Fan, Hongyan; Zhao, Yong; Li, Bing; Feng, Qiangsheng; Yang, Zhihua

2017-02-01

The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 10⁹ cfu), vehicle (TP, 1 × 10⁹ cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm², which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm², respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm², which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site.

Enhancement of Gastric Ulcer Healing and Angiogenesis by Hepatocyte Growth Factor Gene Mediated by Attenuated Salmonella in Rats

PubMed Central

2017-01-01

The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 109 cfu), vehicle (TP, 1 × 109 cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm2, which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm2, respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm2, which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site. PMID:28049228

[Repair of cervical postradiation ulcer following radical mastectomy with lower trapezius myocutaneous flap].

PubMed

Ning, Fanggang; Qin, Fengjun; Chen, Xin; Zhang, Guoan

2015-12-01

To explore the clinical effects of ipsilateral lower trapezius myocutaneous flap for repairing cervical ulcer as a result of radiotherapy after radical mastectomy. Six patients with cervical ulcers as a result of radiotherapy after radical mastectomy were hospitalized from March 2010 to February 2015, suffering from persistent pain in different degrees. The wound area ranged from 6 cm × 4 cm to 10 cm × 6 cm before debridement, 8 cm × 5 cm to 16 cm × 10 cm after debridement. Ipsilateral lower trapezius myocutaneous flap was used to repair the wound after thorough debridement, with the area ranging from 10 cm × 7 cm to 20 cm × 13 cm. The donor sites were sutured directly or covered with medium-thickness skin graft obtained from the back. Pain was obviously relieved in all the patients 2 days after surgery. The wounds in five patients were healed, while necrosis of superficial skin approximately 1 cm in diameter appeared at the distal end of one myocutaneous flap, and it healed after dressing change. During the follow-up period of 3 to 18 months, no recurrence of ulcer was found, the texture of the myocutaneous flaps was soft with good appearance, and the donor sites healed well. On the basis of thorough debridement, it is feasible to repair the cervical ulcer as a result of radiotherapy after radical mastectomy with the ipsilateral lower trapezius myocutaneous flap.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cadena, M. S. Reyes; Chapul, L. Sanchez; Perez, Javier

2008-08-11

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-{beta}) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animalsmore » subjected to ELF together with the transfer factor.« less

Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer.

PubMed

Hotkar, Mukesh S; Avachat, Amelia M; Bhosale, Sagar S; Oswal, Yogesh M

2015-04-01

Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes-induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin-induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes-induced foot ulcer. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Leptin promotes wound healing in the oral mucosa.

PubMed

Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

2014-01-01

Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.

Challenges in the Treatment of Chronic Wounds

PubMed Central

Frykberg, Robert G.; Banks, Jaminelli

2015-01-01

Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use. PMID:26339534

Comparison of healing rate in diabetes-related foot ulcers with low frequency ultrasonic debridement versus non-surgical sharps debridement: a randomised trial protocol

PubMed Central

2014-01-01

Background Foot ulceration has been reported as the leading cause of hospital admission and amputation in individuals with diabetes. Diabetes-related foot ulcers require multidisciplinary management and best practice care, including debridement, offloading, dressings, management of infection, modified footwear and management of extrinsic factors. Ulcer debridement is a commonly applied management approach involving removal of non-viable tissue from the ulcer bed. Different methods of debridement have been reported in the literature including autolytic debridement via moist wound healing, mechanical debridement utilising wet to dry dressings, theatre based sharps debridement, biological debridement, non-surgical sharps debridement and newer technology such as low frequency ultrasonic debridement. Methods People with diabetes and a foot ulcer, referred to and treated by the Podiatry Department at Monash Health and who meet the inclusion criteria will be invited to participate in this randomised controlled trial. Participants will be randomly and equally allocated to either the non-surgical sharps debridement (control) or low frequency ultrasonic debridement (intervention) group (n = 322 ulcers/n = 108 participants). Where participants have more than one ulcer, only the participant will be randomised, not the ulcer. An investigator not involved in participant recruitment or assessment will be responsible for preparing the random allocation sequence and envelopes. Each participant will receive weekly treatment for six months including best practice podiatric management. Each ulcer will be measured on a weekly basis by calculating total area in centimetres squared. Measurement will be undertaken by a trained research assistant to ensure outcomes are blinded from the treating podiatrist. Another member of the research team will assess the final primary outcome. Discussion The primary aim of this study is to compare healing rates for diabetes-related foot ulcers using non-surgical sharps debridement versus low frequency ultrasonic debridement over a six month period. The primary outcome measure for this study is the proportion of ulcers healed by the six month follow-up period. Secondary outcomes will include a quality of life measure, assessment of pain and health care resource use between the two treatment modalities. Trial registration Australian New Zealand Clinical Trial Registry: ACTRN12612000490875. PMID:24423411

Topical propolis improves wound healing in patients with diabetic foot ulcer: a randomized controlled trial.

PubMed

Afkhamizadeh, Mozhgan; Aboutorabi, Robab; Ravari, Hassan; Fathi Najafi, Mohsen; Ataei Azimi, Sajad; Javadian Langaroodi, Adineh; Yaghoubi, Mohammad Ali; Sahebkar, Amirhossein

2017-08-22

In this randomized controlled trial, diabetic patients with foot ulcers (Wagner grades 1 and 2) were randomly assigned to conventional therapies for diabetic foot ulcer plus topical propolis ointment (5%; twice daily) or conventional therapies alone. The process of ulcer healing was observed during 4 weeks and compared between the two groups regarding the size, erythema, exudates, white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). The process of ulcer size reduction during the four-week period of study was significantly different between the groups. However, this difference was not significant between the third and fourth weeks. There was no significant difference between two groups regarding erythema and exudate reduction as well as WBC count and ESR. Administration of topical propolis ointment in addition to the conventional treatments of diabetic foot ulcer could reduce the size of ulcers with Wagner grades 1 and 2.

Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification

PubMed Central

2013-01-01

Background The present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat. Methods MSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures. Results An increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds. Conclusion MSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer. PMID:24192345

Self-Care-Based Treatment Using Ordinary Elastic Bandages for Venous Leg Ulcers

PubMed Central

Suehiro, Kotaro; Morikage, Noriyasu; Harada, Takasuke; Samura, Makoto; Takeuchi, Yuriko; Mizoguchi, Takahiro; Hamano, Kimikazu

2017-01-01

Objective: We aimed to study venous leg ulcer (VLU) healing and recurrence rates of VLU using a self-care-based treatment strategy. Methods: The study included 36 patients (43 legs) who visited our clinic between April 2009 and June 2015 because of non-healing VLUs and who had been treated by us for more than a year (until June 2016). Patients or their caregivers were first provided instructions for performing the “no-intentional-stretch” bandaging technique using ordinary elastic bandages. Wounds were cleansed with tepid water daily, and bandages were re-applied by patients or their caregivers; this was continued until VLUs were healed. Compression was discontinued after healing, but was restarted if persistent swelling and/or dermatitis was noticed on their legs. Results: The median ulcer size was 6.5 cm2 (range, 1–105 cm2). The median number of clinic visits until healing was six (range, 3–35). The 6- and 12-month healing rates were 67% and 86%, respectively. Twenty (44%) legs required compression therapy after VLU healing. The cumulative recurrence-free rate at 60 months was 86%. Conclusion: Reasonable healing and recurrence rates were achieved by applying a self-care-based VLU treatment strategy. PMID:29147163

Wound size measurement of lower extremity ulcers using segmentation algorithms

NASA Astrophysics Data System (ADS)

Dadkhah, Arash; Pang, Xing; Solis, Elizabeth; Fang, Ruogu; Godavarty, Anuradha

2016-03-01

Lower extremity ulcers are one of the most common complications that not only affect many people around the world but also have huge impact on economy since a large amount of resources are spent for treatment and prevention of the diseases. Clinical studies have shown that reduction in the wound size of 40% within 4 weeks is an acceptable progress in the healing process. Quantification of the wound size plays a crucial role in assessing the extent of healing and determining the treatment process. To date, wound healing is visually inspected and the wound size is measured from surface images. The extent of wound healing internally may vary from the surface. A near-infrared (NIR) optical imaging approach has been developed for non-contact imaging of wounds internally and differentiating healing from non-healing wounds. Herein, quantitative wound size measurements from NIR and white light images are estimated using a graph cuts and region growing image segmentation algorithms. The extent of the wound healing from NIR imaging of lower extremity ulcers in diabetic subjects are quantified and compared across NIR and white light images. NIR imaging and wound size measurements can play a significant role in potentially predicting the extent of internal healing, thus allowing better treatment plans when implemented for periodic imaging in future.

Impact of a nutritional formula enriched in fish oil and micronutrients on pressure ulcers in critical care patients.

PubMed

Theilla, Miriam; Schwartz, Betty; Cohen, Jonathan; Shapiro, Haim; Anbar, Ronit; Singer, Pierre

2012-07-01

Pressure ulcers are an important source of morbidity and suffering for patients and a formidable burden on caregivers. To assess the impact of a feeding formula enriched with fish oil on healing of preexisting pressure ulcers and serum levels of C-reactive protein in critical care patients. Adult patients with pressure ulcers grade II or higher were randomly allocated to receive either a formula enriched with fish oil or an isocaloric control formula. Wound healing was assessed by using the Pressure Ulcer Scale for Healing tool on days 7, 14, and 28. Blood levels of C-reactive protein were measured on days 0, 7, and 14. Baseline demographics did not differ between the study (n = 20) and the control (n = 20) groups. The mean score on the ulcer healing tool increased significantly (P = .02) from day 0 to day 28 in the control group (from 9.25 [SD, 2.12] to 10.75 [SD, 3.41]) compared with the study group (from 9.10 [SD, 2.84] to 9.40 [SD, 3.72]). Mean levels of C-reactive protein decreased significantly (P= .02) from day 0 to day 14 in the study group (from 191 [SD, 104.4] mg/L to 111.7 [SD, 97.8] mg/L) compared with the control group (from 145 [SD, 90] mg/L to 139 [SD, 62] mg/L). Administration of a feeding formula enriched with fish oil was associated with decreased progression of pressure ulcers and a decrease in blood concentrations of C-reactive protein.

Effect of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy)benzamido)ethyl) benzoic acid (CJ-42794), a selective antagonist of prostaglandin E receptor subtype 4, on ulcerogenic and healing responses in rat gastrointestinal mucosa.

PubMed

Takeuchi, Koji; Tanaka, Akiko; Kato, Shinichi; Aihara, Eitaro; Amagase, Kikuko

2007-09-01

Recent research showed the involvement of prostaglandin E receptor subtype 4 (EP4) in hypersensitivity to inflammatory pain and suggested that the EP4 receptor is a potential target for the pharmacological treatment of inflammatory pain. We examined the effects of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy) benzamido)ethyl) benzoic acid (CJ-42794), a selective EP4 antagonist, on gastrointestinal ulcerogenic and healing responses in rats, in comparison with those of various cyclooxygenase (COX) inhibitors. CJ-42794 alone, given p.o., did not produce any damage in the gastrointestinal mucosa, similar to 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) (COX-1 inhibitor) or rofecoxib (COX-2 inhibitor), whereas indomethacin (nonselective COX inhibitor) caused gross lesions. Rofecoxib but not CJ-42794, however, damaged these tissues when coadministered with SC-560 and aggravated gastric lesions produced by aspirin. Indomethacin and SC-560 worsened the gastric ulcerogenic response to cold-restraint stress, yet neither CJ-42794 nor rofecoxib had any effect. Furthermore, indomethacin and SC-560 at lower doses damaged the stomach and small intestine of adjuvant arthritic rats. In arthritic rats, rofecoxib but not CJ-42794 provoked gastric ulceration, whereas CJ-42794 produced little damage in the small intestine. The repeated administration of CJ-42794 and rofecoxib as well as indomethacin impaired the healing of chronic gastric ulcers with a down-regulation of vascular endothelial growth factor expression in the ulcerated mucosa. These results suggest that CJ-42794 does not cause any damage in the normal rat gastrointestinal mucosa and in the arthritic rat stomach and does not worsen the gastric ulcerogenic response to stress or aspirin in normal rats, although this agent slightly damages the small intestine of arthritic rats and impairs the healing of gastric ulcers.

Healing Rates in a Multicenter Assessment of a Sterile, Room Temperature, Acellular Dermal Matrix Versus Conventional Care Wound Management and an Active Comparator in the Treatment of Full-Thickness Diabetic Foot Ulcers.

PubMed

Walters, Jodi; Cazzell, Shawn; Pham, Hau; Vayser, Dean; Reyzelman, Alexander

2016-01-01

The purpose of this 16-week, multicenter, randomized, controlled trial was to assess the healed ulcer rate of a human acellular dermal matrix, DermACELL, compared with conventional care and a second acellular dermal matrix, Graftjacket, in the treatment of full-thickness diabetic foot ulcers. One hundred sixty-eight patients were randomized into DermACELL, conventional care, and Graftjacket treatment arms in a 2:2:1 ratio. Patients in the acellular dermal matrix groups received either 1 or 2 applications of the graft at the discretion of the investigator. Weekly follow-up visits were conducted until the ulcer healed or the endpoint was reached. At 16 weeks, the DermACELL arm had a significantly higher proportion of completely healed ulcers than the conventional care arm (67.9% vs 48.1%; P = .0385) and a nonsignificantly higher proportion than the Graftjacket arm (67.9% vs 47.8%; P = .1149). The DermACELL arm also exhibited a greater average percent reduction in wound area than the conventional care arm (91.4% vs 80.3%; P = .0791) and the Graftjacket arm (91.4% vs 73.5%; P = .0762). The proportion of severe adverse events and the proportion of overall early withdrawals were similar among the 3 groups based on relative population size (P ≥ .05). The results presented here indicate that DermACELL is an appropriate clinical option in the treatment of diabetic foot ulcers, with significant increases in healing rates and rate of percentage wound closure as compared with conventional care options.

Tumor necrosis factor alpha blocking agents as treatment for ulcerative colitis intolerant or refractory to conventional medical therapy: a meta-analysis.

PubMed

Lv, Ruxi; Qiao, Weiguang; Wu, Zhiyong; Wang, Yinjun; Dai, Shixue; Liu, Qiang; Zheng, Xuebao

2014-01-01

Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results. To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy. Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects. Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23). TNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.

Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients.

PubMed

Ochoa-Gonzalez, Fatima; Cervantes-Villagrana, Alberto R; Fernandez-Ruiz, Julio C; Nava-Ramirez, Hilda S; Hernandez-Correa, Adriana C; Enciso-Moreno, Jose A; Castañeda-Delgado, Julio E

2016-01-01

Several epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation. HaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5. Metformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin. Metformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.

Ischemic duodenal ulcer, an unusual presentation of sickle cell disease.

PubMed

Julka, Rahul N; Aduli, Farshad; Lamps, Laura W; Olden, Kevin W

2008-03-01

Sickle cell disease is caused by molecular abnormalities in the formation of hemoglobin, leading to pain crisis from recurrent vascular occlusion by sickled hemoglobin. Impaired flow in the microvasculature can lead to ischemia, tissue infarction and ulceration. Abdominal pain, a common complaint in sickle cell disease, can be due to an uncommon etiology, ischemic duodenal ulceration. This is due to primary mucosal infarction caused by sickling, leading to poor healing of infarcted areas. Prompt endoscopic and/or urgent surgical intervention should be considered, particularly if anticoagulation is an issue, as proton pump inhibitor use is ineffective in healing this type of ulcer.

[Treatment of infected diabetic foot ulcers clinical effectiveness of a dressing of alginate and hydrocolloid, with silver fiber. Analysis of results of a series of cases].

PubMed

Lázaro-Martínez, J L; Cecilia-Matilla, A; Aragón-Sánchez, J; García-Morales, E; Garcia-Alvarez, Y; Alvaro-Afonso, F

2013-11-01

High levels of bacterial load have shown a deleterious influence on wound healing. Using antimicrobial dressings can control ulcers' bioburden. The aim of our study was to evaluate the improving of infected diabetic foot ulcers due an alginate's fiber and hydrocolloid silver dressing. We analysed a case series of 6 patients with diabetic foot ulcers without peripheral vascular disease and diagnosed from critical colonization and/or local infection according the presence of inflammation clinical signs. Patients were treated for a minimum period of two weeks. We analysed the percentage reduction in ulcer area from the day of enrolment to antimicrobial dressing removal. The duration of treatment had a median of 5 weeks with a minimum of 2 weeks and up to 6. The median percentage of area reduction of the wounds was 47.7% (range: 0.5%-90%). The mean percentage reduction on the lesion was 58% from 2 weeks and 67.14% at 3 weeks. All patients had reduced significantly their size at 3 weeks from beginning of treatment (p < 0.05). The use of an alginate's fiber and hydrocolloid silver dressing promotes healing on diabetic foot ulcers with local infection, reducing the inflammatory clinical signs significantly over a period of three weeks.

What is the existing evidence supporting the efficacy of compression bandage systems containing both elastic and inelastic components (mixed-component systems)? A systematic review.

PubMed

Welsh, Lynn

2017-05-01

To analyse current evidence on the efficacy of bandage systems containing both elastic and inelastic components (mixed-component systems). International consensus on the efficacy of types of compression systems is difficult to achieve; however, mixed-component systems are being promoted as combining the best properties of both elastic and inelastic bandage systems and increasingly being used to treat venous leg ulcers in practice. A systematic literature review. Search terms such as venous leg ulcer, varicose ulcer, leg ulcer, compression, bandage, elastic, inelastic, short stretch, healing rate, interface pressure, mixed component, two-layer, four-layer and multi-layer were used in database and hand searches in several combinations. Limits were set for years 2005-March 2015 and English-language publications. A total of 475 studies were identified at initial search, and following elimination from abstract and title, this was reduced to 7. A further study was identified on Google Scholar, bringing the final number of studies fitting inclusion criteria to 8. The following subgroups relating to outcomes of efficacy were identified: ulcer healing, maintenance of interface pressure, slippage, ease of application and patient quality of life. Mixed-component systems were found to have comparable ulcer healing rates to alternative compression systems and be easy to apply; have similar abilities to maintain pressure as four-layer bandages and better abilities than short-stretch bandages; have less slippage than alternative systems; and to be significantly associated with several favourable quality of life outcomes. Clinician skill in bandage application was an uncontrolled variable in all eight papers included in the review, which may limit reliability of findings. This review synthesises existing evidence on the efficacy of mixed-component systems and encourages clinicians to regard them as an effective alternative to purely elastic or inelastic compression systems. Additionally, it highlights the importance of clinician skill in bandage application as a crucial determinant of effective compression. © 2016 John Wiley & Sons Ltd.

CO2 laser for the treatment of diabetic foot ulcers with exposed bone. A consecutive series of type 2 diabetic patients.

PubMed

Monami, M; Mirabella, C; Scatena, A; Nreu, B; Zannoni, S; Aleffi, S; Giannoni, L; Mannucci, E

2017-08-01

The treatment of foot ulcers with exposed bone is challenging, because of the risk of infection and of difficulties in the development of granulation tissue. A CO 2 laser beam could be used to produce discontinuities in periosteum, allowing the exposure of blood containing multipotent stem cells, capable of initiating the healing process. The local application of platelet-rich plasma (PRP) has been proposed as a therapeutic tool for accelerating healing in foot ulcers, including those in patients with diabetes. Aim of the present pilot, proof-of-concept study is the assessment of the therapeutic potential of CO 2 laser treatment, either alone or combined with PRP, in the treatment of diabetic foot ulcers with exposed bone. We performed a pilot, uncontrolled 3-month observation study on a consecutive series of 9 type two diabetic patients and foot ulcers with exposed bone. A CO 2 -laser was used for producing nine discontinuities on periosteum for each cm 2 , by directing the focused laser beam on the bone until bleeding. The procedure was repeated up to 6 times, at a distance of 1 week and ulcers assessed weekly until the end of the study (3 months). In the last 5 of the 14 patients, the treatment described above was associated with PRP. Of the nine patients treated, four healed, and one more patient developed granulation tissue covering entirely bone surface. Out of the four patients who did not heal, one underwent minor amputation. Among the five patients treated with a combination of CO 2 laser and PRP, two healed within 3 months, and two more patients developed granulation tissue covering entirely bone surface; the fifth patient did not show any improvement and underwent amputation. The present pilot experience represents a novelty in this field showing a possible use of CO 2 -laser in the treatment of diabetic foot ulcers.

Short-term effect and adverse events of adalimumab versus placebo in inducing remission for moderate-to-severe ulcerative colitis: a meta-analysis.

PubMed

Yang, Zheng; Ye, Xiao-Qing; Zhu, Yu-Zhen; Liu, Zhou; Zou, Ying; Deng, Ying; Guo, Can-Can; Garg, Sushil Kumar; Feng, Jin-Shan

2015-01-01

Adalimumab is used in an attempt to maintain remission for Ulcerative colitis. This study was to evaluate the efficacy and adverse events of adalimumab compared with placebo in inducing remission of Ulcerative colitis. MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID, BIOSIS, CNKI, and Google were searched. All randomized trials comparing adalimumab with placebo in inducing remission of moderate-to-severe ulcerative colitis were included. Two randomized controlled trials with a total of 754 participants met the inclusion criteria. The pooled risk ratio (RR) of clinical remission was 1.85 (95% confidence interval (CI) 1.26 to 2.72) following adalimumab treatment. RR of clinical response was 1.40 (95% CI 1.19 to 1.65) while that of mucosal healing was 1.23 (95% CI 1.03 to 1.47). RR of any adverse events was 1.00 (95% CI 0.93 to 1.09). Compared with placebo, administration of adalimumab may increase the proportion of patients with moderate-to-severe ulcerative colitis attaining clinical remission, clinical response and mucosal healing. Adalimumab is also tolerated well in these patients.

Endoscopic Carbon Dioxide Laser Photocoagulation Of Bleeding Canine Gastric Ulcers

NASA Astrophysics Data System (ADS)

Gal, Dov; Ron, Nimrod; Orgad, Uri; Katzir, Abraham

1987-04-01

This is the first report which describes carbon dioxide laser photocoagulation of upper gastrointestinal bleeding via a flexible endoscope, using an infrared transmitting siver nalide fiber. Various laser parameters were checked to determine the optimal conditions for hemostasis. Both the acute effects of laser irradiation on tissue and the chronic effects on healing process were examined. Preliminary results indicate that carbon dioxide laser beam can successfully photocoagulate moderately bleeding ulcers.

Efficacy and cost-effectiveness of octenidine wound gel in the treatment of chronic venous leg ulcers in comparison to modern wound dressings.

PubMed

Hämmerle, Gilbert; Strohal, Robert

2016-04-01

The aim of this study was to determine the efficacy, safety and cost-effectiveness of an octenidine-based wound gel in the treatment of chronic venous leg ulcers. For this purpose, 49 wounds were treated with either modern wound-phase-adapted dressings alone (treatment arm 1; n = 17), octenidine wound gel plus modern wound-phase-adapted dressings (treatment arm 2; n = 17) or octenidine wound gel alone (treatment arm 3; n = 15). During the study period of 42 days with dressing changes every 3-5 days, wound healing characteristics and treatment costs of different dressings were analysed. Wound size reduction was significantly better (P = 0·028) in both octenidine wound gel treatment arms compared to modern dressings alone with total reductions of 14·6%, 64·1% and 96·2% in treatment arms 1-3. Early wound healing was merely observed under octenidine wound gel treatment (n = 9), whereby lowest treatment costs were generated by octenidine wound gel alone (€20·34/dressing change). As a result, the octenidine wound gel is cost-effective and well suitable for the treatment of chronic venous leg ulcers, considering both safety and promotion of wound healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Pentoxifylline for treating venous leg ulcers.

PubMed

Jull, Andrew B; Arroll, Bruce; Parag, Varsha; Waters, Jill

2012-12-12

Healing of venous leg ulcers is improved by the use of compression bandaging but some venous ulcers remain unhealed, and some people are unsuitable for compression therapy. Pentoxifylline, a drug which helps blood flow, has been used to treat venous leg ulcers. To assess the effects of pentoxifylline (oxpentifylline or Trental 400) for treating venous leg ulcers, compared with a placebo or other therapies, in the presence or absence of compression therapy. For this fifth update we searched the Cochrane Wounds Group Specialised Register (searched 20 July 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); Ovid MEDLINE (2010 to July Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, July 19, 2012); Ovid EMBASE (2010 to 2012 Week 28); and EBSCO CINAHL (2010 to July 13 2012). Randomised trials comparing pentoxifylline with placebo or other therapy in the presence or absence of compression, in people with venous leg ulcers. One review author extracted and summarised details from eligible trials using a coding sheet. One other review author independently verified data extraction. No new trials were identified for this update. We included twelve trials involving 864 participants. The quality of trials was variable. Eleven trials compared pentoxifylline with placebo or no treatment. Pentoxifylline is more effective than placebo in terms of complete ulcer healing or significant improvement (RR 1.70, 95% CI 1.30 to 2.24). Pentoxifylline plus compression is more effective than placebo plus compression (RR 1.56, 95% CI 1.14 to 2.13). Pentoxifylline in the absence of compression appears to be more effective than placebo or no treatment (RR 2.25, 95% CI 1.49 to 3.39).More adverse effects were reported in people receiving pentoxifylline (RR 1.56, 95% CI 1.10 to 2.22). Nearly three-quarters (72%) of the reported adverse effects were gastrointestinal. Pentoxifylline is an effective adjunct to compression bandaging for treating venous ulcers and may be effective in the absence of compression. The majority of adverse effects were gastrointestinal disturbances.

Effects of esomeprazole on healing of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers in the presence of a continued NSAID treatment: Characterization of molecular mechanisms.

PubMed

Fornai, Matteo; Colucci, Rocchina; Antonioli, Luca; Awwad, Oriana; Ugolini, Clara; Tuccori, Marco; Fulceri, Federica; Natale, Gianfranco; Basolo, Fulvio; Blandizzi, Corrado

2011-01-01

Proton pump inhibitors promote ulcer repair in nonsteroidal anti-inflammatory drug (NSAID)-treated patients with ongoing NSAID-induced gastric toxicity, although the underlying mechanisms remain unclear. We examined the healing mechanisms of esomeprazole on NSAID-induced gastric ulcerations in the presence of a continued NSAID treatment. Ulcerations were induced in rats by oral indomethacin (6μmol/kg/day) for 14 days. Indomethacin administration was continued, alone or combined with equivalent acid inhibitory doses of esomeprazole (5μmol/kg/day), lansoprazole (15μmol/kg/day) or famotidine (20μmol/kg/day), for additional 7 days. Stomachs were then processed for: histomorphometric analysis of mucosal injury; mucosal levels of prostaglandin E(2) (PGE(2)) and malondialdehyde (MDA); expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), caspase-3, and cyclooxygenase-2 (COX-2) (Western blot); expression of Ki-67 (immunohistochemistry). Indomethacin for 14 days elicited mucosal damage, reduced PGE(2) levels and increased MDA. After additional 7 days, indomethacin induced the following effects: further enhancement of mucosal damage and MDA content; decrease in PGE(2) levels; increase in COX-2 and activated caspase-3 expression; decrease in VEGF, PCNA and Ki-67 expression. In the presence of indomethacin, esomeprazole and lansoprazole were more effective than famotidine in promoting resolution of mucosal damage. Concomitantly, esomeprazole and lansoprazole, but not famotidine, restored PCNA and Ki-67 expression, and normalized MDA levels. Moreover, esomeprazole, lansoprazole and famotidine partly counteracted caspase-3 activation, without affecting VEGF expression. The healing activity of esomeprazole on indomethacin-induced gastric ulcerations can be ascribed to two mechanisms: (1) acid-dependent reduction of pro-apoptotic signalling; (2) acid-independent restoration of proliferating/repairing pathways. Copyright © 2010 Elsevier Ltd. All rights reserved.

Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries.

PubMed

Gomes, Ana; Teixeira, Cátia; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, Paula

2017-10-18

As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based) to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections.

Accidental sulfur mustard exposure: A case report.

PubMed

Schmidt, Annette; Steinritz, Dirk; Rudolf, Klaus-Dieter; Thiermann, Horst; Striepling, Enno

2018-09-01

The clinical progression following a sulfur mustard-induced skin exposure is well documented in the literature. Upon skin contact and a characteristic latency period, sulfur mustard (SM) causes erythema, blister formation and ulceration, which is associated with wound healing disorders that may require surgical treatment. Here, we present a case report of accidental exposure to SM in a laboratory setting which required surgical treatment of the skin. The case was illustrated at close intervals over a period of two years and underlines that exposure to SM has to be taken into account when typical clinical symptoms occur. Moreover skin grafts appear to be effective in SM-induced non healing skin ulcerations. Copyright © 2017 Elsevier B.V. All rights reserved.

Healed corneal ulcer with keloid formation.

PubMed

Alkatan, Hind M; Al-Arfaj, Khalid M; Hantera, Mohammed; Al-Kharashi, Soliman

2012-04-01

We are reporting a 34-year-old Arabic white female patient who presented with a white mass covering her left cornea following multiple ocular surgeries and healed corneal ulcer. The lesion obscured further view of the iris, pupil and lens. The patient underwent penetrating keratoplasty and the histopathologic study of the left corneal button showed epithelial hyperplasia, absent Bowman's layer and subepithelial fibrovascular proliferation. The histopathologic appearance was suggestive of a corneal keloid which was supported by further ultrastructural study. The corneal graft remained clear 6 months after surgery and the patient was satisfied with the visual outcome. Penetrating keratoplasty may be an effective surgical option for corneal keloids in young adult patients.

Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers.

PubMed

Delgado-Enciso, Iván; Madrigal-Perez, Violeta M; Lara-Esqueda, Agustin; Diaz-Sanchez, Martha G; Guzman-Esquivel, Jose; Rosas-Vizcaino, Luis E; Virgen-Jimenez, Oscar O; Kleiman-Trujillo, Juleny; Lagarda-Canales, Maria R; Ceja-Espiritu, Gabriel; Rangel-Salgado, Viridiana; Lopez-Lemus, Uriel A; Delgado-Enciso, Josuel; Lara-Basulto, Agustin D; Soriano Hernández, Alejandro D

2018-02-01

Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients tolerated the interventions well. At the end of the treatment period, ulcers in the control group had decreased by 38% whereas those in the intervention group decreased by 73% (P<0.009). The degree of decrease was also investigated; the ulcer size was ≥50% decreased in 40% of patients in the control group and in 86% of patients in the intervention group (P=0.02). In conclusion, the results of the present study indicate that topical potassium permanganate is well tolerated and significantly accelerates the healing process of diabetic foot ulcers.

Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers

PubMed Central

Delgado-Enciso, Iván; Madrigal-Perez, Violeta M.; Lara-Esqueda, Agustin; Diaz-Sanchez, Martha G.; Guzman-Esquivel, Jose; Rosas-Vizcaino, Luis E.; Virgen-Jimenez, Oscar O.; Kleiman-Trujillo, Juleny; Lagarda-Canales, Maria R.; Ceja-Espiritu, Gabriel; Rangel-Salgado, Viridiana; Lopez-Lemus, Uriel A.; Delgado-Enciso, Josuel; Lara-Basulto, Agustin D.; Soriano Hernández, Alejandro D.

2018-01-01

Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients tolerated the interventions well. At the end of the treatment period, ulcers in the control group had decreased by 38% whereas those in the intervention group decreased by 73% (P<0.009). The degree of decrease was also investigated; the ulcer size was ≥50% decreased in 40% of patients in the control group and in 86% of patients in the intervention group (P=0.02). In conclusion, the results of the present study indicate that topical potassium permanganate is well tolerated and significantly accelerates the healing process of diabetic foot ulcers. PMID:29435274

Hyperbaric oxygen therapy stimulates colonic stem cells and induces mucosal healing in patients with refractory ulcerative colitis: a prospective case series

PubMed Central

Bekheit, Mohamed; Baddour, Nahed; Katri, Khaled; Taher, Yousry; El Tobgy, Khaled; Mousa, Essam

2016-01-01

Background Hyperbaric oxygen (HBO) is used as part of treatment in a variety of clinical conditions. Its use in the treatment of ulcerative colitis has been reported in few clinical reports. Objective We report the effect of HBO on refractory ulcerative colitis exploring one potential mechanism of action. Design A review of records of patients with refractory ulcerative colitis who received HBO was conducted. Clinical and histopathological scoring was utilised to evaluate the response to HBO therapy (HBOT). Results All patients manifested clinical improvement by the 40th cycle of HBOT. The median number of stool frequency dropped from seven motions/day (range=3–20) to 1/day (range=0.5–3), which was significant (z=−4.6, p<0.001). None of the patients manifested persistent blood passage after HBOT (z=−3.2, p=0.002). The severity index significantly improved after HBOT (z=−4.97, p<0.001). Histologically, a significant reduction of the scores of activity was recorded accompanied by a significant increase in the proliferating cell nuclear antigen labelling index of the CD44 cells of the colonic mucosa (p=0.001). Conclusions HBOT is effective in the setting of refractory ulcerative colitis. The described protocol is necessary for successful treatment. HBOT stimulates colonic stem cells to promote healing. PMID:27195128

A skin substitute based on human amniotic membrane.

PubMed

Tauzin, Hélène; Rolin, Gwenaël; Viennet, Céline; Saas, Philippe; Humbert, Philippe; Muret, Patrice

2014-06-01

Human amniotic membrane (HAM) has biological properties which are useful for wound healing. HAM is notably one of the therapeutic alternatives for venous leg ulcer care. Indeed, a prospective clinical study has demonstrated that cryopreserved HAM transplantation for leg ulcer is feasible, safe and has beneficial effects: 80 % of the patients had a significant clinical response. Nevertheless, at the end of the 3-month follow-up period, only 20 % of the ulcers were totally closed. The aim of this work was to create and characterize a model of epidermized HAM. The method of HAM desepithelialization was validated by histology, immunohistochemistry and scanning electron microscopy. Then, de-epithelialized HAM was seeded with primary keratinocytes. After 21 days of culture, 15 at the air-liquid interface, the model obtained was analyzed histologically and by immunohistochemistry. The amniotic basement membrane was preserved during enzymatic desepithelialization of HAM. Primary keratinocytes proliferated on HAM: the model obtained showed involucrin expression and had a good basement membrane. As re-epithelialization is an important step for ulcer closure, a model of epidermized HAM could be used to speed up the healing of such wounds.

Current and Future Targets for Mucosal Healing in Inflammatory Bowel Disease

PubMed Central

Atreya, Raja; Neurath, Markus F.

2017-01-01

The induction and subsequent maintenance of mucosal healing has emerged as one of the central therapeutic goals in the management of patients with inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). Current and novel treatment options are assessed regarding their therapeutic efficacy on the basis of their ability to induce mucosal healing. However, there is still substantial debate about the precise definition of mucosal healing. Here, we will give an overview regarding the definitions of mucosal healing as well as its probable effects on long-term disease behavior and finally focus on current and potential therapeutic targets to achieve this therapeutic goal in IBD patients. PMID:28612022

A non-randomised, controlled clinical trial of an innovative device for negative pressure wound therapy of pressure ulcers in traumatic paraplegia patients.

PubMed

Srivastava, Rajeshwar N; Dwivedi, Mukesh K; Bhagat, Amit K; Raj, Saloni; Agarwal, Rajiv; Chandra, Abhijit

2016-06-01

The conventional methods of treatment of pressure ulcers (PUs) by serial debridement and daily dressings require prolonged hospitalisation, associated with considerable morbidity. There is, however, recent evidence to suggest that negative pressure wound therapy (NPWT) accelerates healing. The commercial devices for NPWT are costly, cumbersome, and electricity dependent. We compared PU wound healing in traumatic paraplegia patients by conventional dressing and by an innovative negative pressure device (NPD). In this prospective, non-randomised trial, 48 traumatic paraplegia patients with PUs of stages 3 and 4 were recruited. Patients were divided into two groups: group A (n = 24) received NPWT with our NPD, and group B (n = 24) received conventional methods of dressing. All patients were followed up for 9 weeks. At week 9, all patients on NPD showed a statistically significant improvement in PU healing in terms of slough clearance, granulation tissue formation, wound discharge and culture. A significant reduction in wound size and ulcer depth was observed in NPD as compared with conventional methods at all follow-up time points (P = 0·0001). NPWT by the innovative device heals PUs at a significantly higher rate than conventional treatment. The device is safe, easy to apply and cost-effective. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Noninvasive assessment of diabetic foot ulcers with diffuse photon density wave methodology: pilot human study

NASA Astrophysics Data System (ADS)

Papazoglou, Elisabeth S.; Neidrauer, Michael; Zubkov, Leonid; Weingarten, Michael S.; Pourrezaei, Kambiz

2009-11-01

A pilot human study is conducted to evaluate the potential of using diffuse photon density wave (DPDW) methodology at near-infrared (NIR) wavelengths (685 to 830 nm) to monitor changes in tissue hemoglobin concentration in diabetic foot ulcers. Hemoglobin concentration is measured by DPDW in 12 human wounds for a period ranging from 10 to 61 weeks. In all wounds that healed completely, gradual decreases in optical absorption coefficient, oxygenated hemoglobin concentration, and total hemoglobin concentration are observed between the first and last measurements. In nonhealing wounds, the rates of change of these properties are nearly zero or slightly positive, and a statistically significant difference (p<0.05) is observed in the rates of change between healing and nonhealing wounds. Differences in the variability of DPDW measurements over time are observed between healing and nonhealing wounds, and this variance may also be a useful indicator of nonhealing wounds. Our results demonstrate that DPDW methodology with a frequency domain NIR device can differentiate healing from nonhealing diabetic foot ulcers, and indicate that it may have clinical utility in the evaluation of wound healing potential.

Clinical outcomes and changes in venous hemodynamics after subfascial endoscopic perforating vein surgery.

PubMed

Ting, A C W; Cheng, S W K; Ho, P; Wu, L L H; Cheung, G C Y

2003-08-01

We evaluated the clinical results of subfascial endoscopic perforating vein surgery (SEPS) in patients with severe chronic venous insufficiency (CVI) (clinical class 4-6) and assessed the hemodynamic changes associated with SEPS using air plethysmography (APG). Forty-five patients with severe CVI who had undergone SEPS were evaluated. Clinical score and venous hemodynamics, as measured by APG before operation and at 1 month and 1 year after operation, were compared using the Wilcoxon signed rank test. Patient satisfaction (on a visual analogue scale of 0 to 100%) was also assessed. There were 29 men and 16 women; their mean age was 60 years (range, 37-83). Thirty-five patients (78%) had active venous ulcers; the ulcers' mean size was 7.8 +/- 11.9 cm2 and the mean duration of ulceration was 9 +/- 10 months. There were no hospital deaths. Postoperative complications were uncommon (one groin wound infection and one case of thrombophlebitis). At a mean follow-up of 15 +/- 9 months, 34 ulcers (97%) had healed. The cumulative ulcer healing was 82% at 3 months. There were five recurrent ulcers (15%). Significant improvement was seen in the clinical scores (10 +/- 3 before operation, 6 +/- 4 at 1 month, and 4 +/- 3 at 1 year after operation). The venous filling index was also significantly improved after operation; this improvement was maintained at 1-year follow-up (7.36 +/- 6.23 ml/sec before operation, 3.63 +/- 3.90 ml/sec at 1 month, and 3.14 +/- 2.06 ml/sec at 1 year). The degree of patient satisfaction was also remarkable, with 74 +/- 17% and 90 +/- 12% satisfaction at 1-month and 1-year follow-up, respectively. SEPS is a safe and effective treatment for patients with severe CVI. It leads to hemodynamic improvement, with rapid ulcer healing, and it is associated with a high degree of patient satisfaction.

Predictive validity of granulation tissue color measured by digital image analysis for deep pressure ulcer healing: a multicenter prospective cohort study.

PubMed

Iizaka, Shinji; Kaitani, Toshiko; Sugama, Junko; Nakagami, Gojiro; Naito, Ayumi; Koyanagi, Hiroe; Konya, Chizuko; Sanada, Hiromi

2013-01-01

This multicenter prospective cohort study examined the predictive validity of granulation tissue color evaluated by digital image analysis for deep pressure ulcer healing. Ninety-one patients with deep pressure ulcers were followed for 3 weeks. From a wound photograph taken at baseline, an image representing the granulation red index (GRI) was processed in which a redder color represented higher values. We calculated the average GRI over granulation tissue and the proportion of pixels exceeding the threshold intensity of 80 for the granulation tissue surface (%GRI80) and wound surface (%wound red index 80). In the receiver operating characteristics curve analysis, most GRI parameters had adequate discriminative values for both improvement of the DESIGN-R total score and wound closure. Ulcers were categorized by the obtained cutoff points of the average GRI (≤80, >80), %GRI80 (≤55, >55-80, >80%), and %wound red index 80 (≤25, >25-50, >50%). In the linear mixed model, higher classes for all GRI parameters showed significantly greater relative improvement in overall wound severity during the 3 weeks after adjustment for patient characteristics and wound locations. Assessment of granulation tissue color by digital image analysis will be useful as an objective monitoring tool for granulation tissue quality or surrogate outcomes of pressure ulcer healing. © 2012 by the Wound Healing Society.

Pseudomonas aeruginosa uses T3SS to inhibit diabetic wound healing

PubMed Central

Goldufsky, Josef; Wood, Stephen J.; Jayaraman, Vijayakumar; Majdobeh, Omar; Chen, Lin; Qin, Shanshan; Zhang, Chunxiang; DiPietro, Luisa A.; Shafikhani, Sasha H.

2015-01-01

Diabetic foot ulcers are responsible for more hospitalizations than any other complication of diabetes. Bacterial infection is recognized as an important factor associated with impaired healing in diabetic ulcers. Pseudomonas aeruginosa is the most frequently detected Gram-negative pathogen in diabetic ulcers. P. aeruginosa infection has been shown to impair healing in diabetic wounds in a manner that correlates with its ability to form biofilm. While the majority of infections in diabetic ulcers are biofilm associated, 33% of infections are nonbiofilm in nature. P. aeruginosa is the most prevalent Gram-negative pathogen in all diabetic wound types, which suggests that the deleterious impact of P. aeruginosa on healing in diabetic wounds goes beyond its ability to form biofilm and likely involves other factors. The Type III Secretion System (T3SS) virulence structure is required for the pathogenesis of all P. aeruginosa clinical isolates, suggesting that it may also play a role in the inhibition of wound repair in diabetic skin ulcers. We evaluated the role of T3SS in mediating P. aeruginosa–induced tissue damage in the wounds of diabetic mice. Our data demonstrate that P. aeruginosa establishes a robust and persistent infection in diabetic wounds independent of its ability to form biofilm and causes severe wound damage in a manner that primarily depends on its T3SS. PMID:25912785

Intervention with Formulated Collagen Gel for Chronic Heel Pressure Ulcers in Older Adults with Diabetes.

PubMed

Agosti, Jennifer K; Chandler, Lois A

2015-11-01

Chronic pressure ulcers (PrUs), ulcers that fail to progress through the expected phases of wound healing in a timely fashion, are not only a concern for the patients afflicted with them, but are also a significant burden for the long-term-care facilities in which patients reside. The heel is the second most common location for PrUs. Morbidity and mortality rates for heel PrUs, particularly in the diabetic population, are alarming. Therefore, a consistently effective, cost-conscious, and user-friendly topical treatment for heel ulcers would be welcomed by patients and clinicians. This article describes a marked and rapid improvement in wound granulation in 3 older adult patients following weekly treatment for 8 weeks of chronic (≥1-year duration) heel ulcers with an easy-to-use, cost-effective, topical, formulated collagen gel.

A multi-center, randomized, clinical trial comparing adhesive polyurethane foam dressing and adhesive hydrocolloid dressing in patients with grade II pressure ulcers in primary care and nursing homes

PubMed Central

2013-01-01

Background Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. Methods/design This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. Discussion This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. Trial registration This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14. PMID:24359122

The impact of glycaemic variability on wound healing in the diabetic foot - A retrospective study of new ulcers presenting to a specialist multidisciplinary foot clinic.

PubMed

Dhatariya, Ketan K; Li Ping Wah-Pun Sin, Edwin; Cheng, Joyce Oi Suet; Li, Francesca Yan Nok; Yue, Anson Wei Yue; Gooday, Catherine; Nunney, Ian

2018-01-01

Glycaemic variability - the visit-to-visit variation in HbA1c - plays a possible role in the development of micro and macrovascular disease in patients with diabetes. Whether HbA1c variability is a factor determining wound healing in diabetic foot ulcers remains unknown. We aimed to determine whether HbA1c variability is associated with foot ulcer healing time. A retrospective analysis of patients presenting to our specialist multidisciplinary foot clinic between July 2013 and March 2015, with at least three HbA1c measurements within five years of presentation and more than two follow-up reviews. HbA1c variation was measured by magnitude of standard deviation. 629 new referrals were seen between July 2013 and March 2015. Of these, 172 patients had their number of days to healing recorded and sufficient numbers of HbA1c values to determine variability. The overall geometric mean days to heal was 91.1 days (SD 80.8-102.7). In the low HbA1c variability group the geometric mean days to heal was 78.0 days (60.2-101.2) vs 126.9 days (102.0-158.0) in the high Hb1Ac variability group (p = .032). Those with low HbA1c (<58 mmol/mol) and low variability healed faster than those with high HbA1c and high variability (73.5 days [59.5-90.8] vs 111.0 days [92.0-134.0], p = .007). Additionally, our results show that time to healing is more dependent on the mean HbA1c than the variability in HbA1c (p = .007). Our data suggest that there was a significant association between HbA1c variability and healing time in diabetic foot ulcers. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of Collagen Extracellular Matrix Dressing for the Treatment of a Recurrent Venous Ulcer in a 52-Year-Old Patient.

PubMed

González, Arturo

2016-01-01

This case study describes treatment for a 52-year-old man with a recurrent venous leg ulcer using a collagen dressing with extracellular matrix. The patient was admitted to the wound care service for a 3-week-old recurrent venous ulcer. Treatment included application of a collagen dressing with extracellular matrix twice weekly or as needed by the patient; application of a secondary dressing (4 × 4 gauze); and coverage with an expandable netting or gauze using a conforming stretch gauze bandage and latex-free dressing retention tape. The initial venous leg ulcer in this patient required 10 weeks to achieve closure. Ninety-eight percent resolution of the recurrent ulcer had occurred within 4 weeks of treatment, with complete closure at 7 weeks. The average healing time for recurrent venous ulcers is reported in the literature to be longer than initial venous ulcers. In the case provided, collagen ECM dressings promoted complete wound healing in 49 days.

Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in Tertiary Hospital in Indonesia.

PubMed

Soewondo, Pradana; Suyono, Slamet; Sastrosuwignyo, Mpu Kanoko; Harahap, Alida R; Sutrisna, Bambang; Makmun, Lukman H

2017-01-01

to evaluate the role of clinical characteristics, functional markers of vasodilation, inflammatory response, and atherosclerosis in predicting wound healing in diabetic foot ulcer. a cohort study (February - October 2010) was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia. Each subject underwent at least two variable measurements, i.e. during inflammatory phase and proliferation phase. The studied variables were clinical characteristics, complete peripheral blood count (CBC) and differential count, levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG), marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin-1/ET-1, and flow-mediated dilation/FMD of brachial artery), and marker of vascular calcification (osteoprotegerin/OPG). median of time achieving 50% granulation tissue in our study was 21 days. There were nine factors that contribute in the development of 50% granulation tissue, i.e. family history of diabetes mellitus (DM), previous history of wound, wound area, duration of existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and OPG. There were three out of the nine factors that significantly correlated with wound healing, i.e. wound area, OPG levels, and simvastatin medications. in acute diabetic foot ulcers, wound area and OPG levels had positive correlation with wound healing, whereas simvastatin medications had negative correlation with wound healing.

Lesion Size Correlates with Leishmania Antigen-Stimulated TNF-Levels in Human Cutaneous Leishmaniasis

PubMed Central

Oliveira, Fabiano; Bafica, Andre; Rosato, Andrea B.; Favali, Cecilia B. F.; Costa, Jackson M.; Cafe, Virginia; Barral-Netto, Manoel; Barral, Aldina

2011-01-01

Cutaneous leishmaniasis (CL) is a worldwide disease endemic in several regions of the globe. The hallmark of CL is skin ulcers likely driven by efforts of the immune system to control Leishmania growth. Cytokines, such as tumor necrosis factor (TNF) and interferon-gamma can control disease progression in animal models. Nevertheless, the impact of these cytokines in CL ulcer outcome is not well established in humans. In this study, 96 CL patients from an endemic area of Leishmania braziliensis were enrolled for a follow-up study that consisted of clinical and immunological evaluations in a 2-year period. Statistical analysis revealed that healing time (P = 0.029), age (P = 0.002), and TNF levels (P = 0.0002) positively correlate with ulcer size at the time of the first clinical evaluation. Our findings suggest that ulcer size correlates with healing time and TNF levels support the use of TNF inhibitors combined with standard therapy to improve healing in CL patients with severe lesions. PMID:21734128

Macrophages - sensors and effectors coordinating skin damage and repair.

PubMed

Willenborg, Sebastian; Eming, Sabine A

2014-03-01

Restoration of skin integrity and homeostasis following injury is a vital process. Wound healing disorders, including chronic skin ulcers and pathological scarring, are of major clinical impact. The current therapeutic approaches are often not sufficient. The development of novel efficient therapies requires a thorough understanding of the underlying molecular mechanisms. A cardinal feature of non-healing skin ulcers and excessive scarring is a prolonged inflammatory response at the wound site, which aborts the healing response. Modulation of the local immune response may be an effective therapeutic strategy to correct impaired healing conditions. Yet, the specific mechanisms of inflammation, particularly the role of the diverse leukocyte lineages attracted to the site of tissue damage, have not been resolved. Recent findings in diverse experimental model systems and clinical studies have refined the understanding of monocyte/macrophage biology and the role of cells of the monocytic lineage in tissue regeneration. Thus, monocytes/macrophages are emerging as novel and interesting therapeutic targets to interfere in wound healing pathologies. In this article we will review the role of monocytes/macrophages in skin repair in the light of the recent literature and findings from our own group. This article will provide a rationale for monocyte/macrophage-based therapies to facilitate the healing response. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

A prospective, randomized clinical trial to assess the cost-effectiveness of a modern foam dressing versus a traditional saline gauze dressing in the treatment of stage II pressure ulcers.

PubMed

Payne, Wyatt G; Posnett, John; Alvarez, Oscar; Brown-Etris, Marie; Jameson, Gayle; Wolcott, Randall; Dharma, Hussein; Hartwell, Samantha; Ochs, Diane

2009-02-01

Modern dressings such as hydrocolloids, gels, and foams are typically more expensive than traditional dressings such as gauze. However, if modern dressings require fewer changes, the overall cost of treatment may be lower despite the higher initial purchase price. If healing rates are comparable or better, modern dressings also may be cost-effective. A 4-week, prospective, randomized clinical trial to assess differences in treatment costs and cost-effectiveness between a modern foam dressing and saline-soaked gauze was conducted among 36 patients (22 men, 14 women, mean age 72.8 years) with a Stage II pressure ulcer (mean duration 35 weeks) at five centers in the United States. Participants were randomized to treatment with a self-adhesive polyurethane foam (n = 20) or saline-soaked gauze dressing (n = 16). No difference in time to wound closure was observed (P = 0.817). Patients in the foam group had less frequent dressing changes (P <0.001). Total cost over the study period was lower by $466 per patient (P = 0.055) and spending on dressings was lower by $92 per patient in the foam group (P = 0.025). Cost per ulcer healed was lower by $1,517 and cost per ulcer-free day was lower by $80 for patients in the foam group. On the evidence of this study, the foam dressing is a more cost-effective treatment than saline-soaked gauze for the treatment of Stage II pressure ulcers.

Estimating the Clinical Outcomes and Cost Differences Between Standard Care With and Without Cadexomer Iodine in the Management of Chronic Venous Leg Ulcers Using a Markov Model.

PubMed

Nherera, Leo M; Woodmansey, Emma; Trueman, Paul; Gibbons, Garry W

2016-06-01

Chronic venous leg ulcers (VLUs) affect up to 1% of the adult population in the developed world and present a significant financial and resource burden to health care systems. Cadexomer iodine (CI) is an antimicrobial dressing indicated for use in chronic exuding wounds. The aim of this study was to estimate the cost utility of using CI + standard care (SC) - ie, high compression multicomponent bandaging including debridement - compared with SC alone in the management of chronic (>6 months' duration) VLUs from a payer's perspective. A Markov model was constructed to evaluate the cost and clinical benefits (healing and decreased infection rates) of the 2 treatment modalities over a 1-year period using data from 4 randomized, controlled clinical studies (RCTs) included in a recent Cochrane review and cost data from a recently published economic evaluation of VLUs. Costs were calculated using 2014 United States dollars; wound outcomes in- cluded complete healing in 212 patients reported in the Cochrane meta-analysis and quality-adjusted life years (QALYs), with utility values obtained from 200 patients with VLUs calculated using standard gamble. Treatment with CI over 1 year was $7,259 compared to $7,901 for SC. This resulted in a cost savings of $643/patient in favor of CI compared with SC. More patients treated with CI (61%) had their wounds healed compared to 54% treated with SC. Furthermore, patients treated with CI+SC experienced 6 additional ulcer-free weeks compared to persons treated with SC alone (ie, 25 ulcer- free weeks compared to 19 ulcer-free weeks, respectively). Overall, CI resulted in 0.03 more QALYs (ie, 0.86 QALYs compared to 0.83 for SC). The use of CI in addition to SC compared to SC alone over 52 weeks resulted in more wounds healed and more QALYs along with a decrease of overall costs The results of this study suggest CI is cost effective com- pared to SC alone in the management of patients with chronic VLUs. Prospective, controlled clinical studies are needed to elucidate the effect and cost effectiveness of CI on VLUs with and without signs of infection as compared to SC, other antiseptics, and more advanced topical treatment modalities.

Can non-adhesive short stretch bandages change a life?

PubMed

Laginja, Stanislava; Seremet, Jasmina; Stiglić, Damir; Jancić, Ervin

2014-12-01

Venous stasis ulcers are common in patients who have a history of leg swelling, varicose veins, or a history of blood clots in either the superficial or the deep veins of their legs. The treatment is long and hard but the main aim of it is to create such an environment that allows skin to grow over an ulcer. Chronic wounds are a growing social, economical and health issue throughout the world. The purpose of this retrospective study was to establish detailed characterization of how effective a compression is in reducing the time of wound healing. A total of 176 patients with leg ulcers were included in our three years study. The measurements were taken based on the anamnesis, presenting clinical symptoms, digital photography at each dressing foam change, and, finally, wounds. During a 3 years period (2011-2013) a total of 176 patients (61 male and 115 female, 34.66% and 65.34% respectively) with different types of leg ulcers were treated at our Hospital. The average age is 68.94 years (male 68 years, female 70 years). We measured how long the patient had the wound before starting the treatment, and also how long the treatment lasted. This led us to the conclusion that compression therapy shortened the time of treatment by two thirds, compared to the usual therapy. Compression systems improve the healing of venous leg ulcers and should be used routinely regarding venous ulcers.

The Mechanism of Hyperbaric Oxygen Therapy in the Treatment of Chronic Wounds and Diabetic Foot Ulcers.

PubMed

Johnston, Benjamin R; Ha, Austin Y; Brea, Bielinsky; Liu, Paul Y

2016-02-01

Non-healing wounds are a growing public health concern, and more than $25 billion per year in the US are spent caring for patients with chronic wounds. Many of these patients are referred to specialized wound centers, where hyperbaric oxygen therapy (HBO2T) has become a mainstay in healing wounds, especially diabetic foot ulcers (DFU). However, it is costly, with a typical course of therapy running into the tens of thousands of dollars. Presently, as many as 30-40% of DFU patients with Wagner's Grade 3 and 4 ulcers treated with HBO2T fail to heal by 24 weeks. Unfortunately, the patient will have already received lengthy therapy (30-60 daily treatments over 6-10 week time period) before having the wound deemed non-responsive. Currently, practitioners employ a combination of clinical markers, diagnostic testing and a four-week preliminary healing response, but this approach is inaccurate and delays definitive identification of HBO2T responder and non-responder phenotypes.

Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by ulcers: Open label study

PubMed Central

Matsumoto, Satohiro; Tsuji, Kenichiro; Shirahama, Satoshi

2008-01-01

AIM: To attempt rectal administration of rebamipide in the treatment of ischemic colitis patients with ulcers, and evaluate its effects. METHODS: We compared 9 ischemic colitis patients (2 men, 7 women) with ulcers treated by bowel rest only from 2000 to 2005 (conventional therapy group), with 6 patients (2 men, 4 women) treated by rebamipide enema therapy in 2006 (rebamipide enema therapy group) and analyzed the mean duration of fasting and hospitalization, degree of ulcer healing, and decrease in WBC count for the two groups. RESULTS: The mean duration of fasting and hospitalization were 2.7 ± 1.8 d and 9.2 ± 1.5 d in the rebamipide group and 7.9 ± 4.1 d and 17.9 ± 6.8 d in the control group, respectively, and significantly reduced in the rebamipide group (t = -2.915; P = 0.0121 and t = -3.054; P = 0.0092). As for the degree of ulcer healing at 7 d after admission, the ulcer score was reduced by 3.5 ± 0.5 (points) in the rebamipide group and 2.8 ± 0.5 (points) in the control group (t = 1.975; P = 0.0797), while the decrease in WBC count was 120.0 ± 55.8 (× 102/μL) in the rebamipide group and 85.9 ± 56.8 (× 102/μL) in the control group (t = 1.006; P = 0.3360). CONCLUSION: In left-sided ischemic colitis patients with ulcers, rebamipide enema therapy significantly reduced the duration of fasting and hospitalization, recommending its use as a new and effective therapeutic alternative. PMID:18609691

Topical wound oxygen therapy in the treatment of severe diabetic foot ulcers: a prospective controlled study.

PubMed

Blackman, Eric; Moore, Candice; Hyatt, John; Railton, Richard; Frye, Christian

2010-06-01

Diabetic foot ulcers (DFU) are common, difficult-to-treat, and prone to complications. A prospective, controlled study was conducted to: 1) examine the clinical efficacy of a pressurized topical oxygen therapy (TWO(2)) device in outpatients (N = 28) with severe DFU referred for care to a community wound care clinic and 2) assess ulcer reoccurrence rates after 24 months. Seventeen (17) patients received TWO(2) five times per week (60-minute treatment, pressure cycles between 5 and 50 mb) and 11 selected a silver-containing dressing changed at least twice per week (control). Patient demographics did not differ between treatment groups but wounds in the treatment group were more severe, perhaps as a result of selection bias. Ulcer duration was longer in the treatment (mean 6.1 months, SD 5.8) than in the control group (mean 3.2 months, SD 0.4) and mean baseline wound area was 4.1 cm2 (SD 4.3) in the treatment and 1.4 cm2 (SD 0.6) in the control group (P = 0.02). Fourteen (14) of 17 ulcers (82.4%) in the treatment group and five of 11 ulcers (45.5%) in the control group healed after a median of 56 and 93 days, respectively (P = 0.04). No adverse events were observed and there was no reoccurrence at the ulcer site after 24 months' follow-up in either group. Although the absence of randomization and blinding may have under- or overestimated the treatment effect of either group, the significant differences in treatment outcomes confirm the potential benefits of TWO(2) in the management of difficult-to-heal DFUs. Clinical efficacy and cost-effectiveness studies as well as studies to elucidate the mechanisms of action of TWO(2) are warranted.

Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers.

PubMed

García-Honduvilla, Natalio; Cifuentes, Alberto; Ortega, Miguel A; Pastor, Marta; Gainza, Garazi; Gainza, Eusebio; Buján, Julia; Álvarez-Mon, Melchor

2018-04-01

Wound healing is a complex process that can be severely impaired due to pathological situations such as diabetes mellitus. Diabetic foot ulcers are a common complication of this pathology and are characterized by an excessive inflammatory response. In this work, the effects of local treatment with recombinant human epidermal growth factor (rhEGF) were studied using a full-thickness wound healing model in streptozotocin-induced diabetic rats. Wound healing process was assessed with different concentrations of rhEGF (0.1, 0.5, 2.0 and 8.0 µg/mL), placebo and both diabetic and non-diabetic controls ( n  = 53). The macroscopic healing observed in treated diabetic rats was affected by rhEGF concentration. Histologically, we also observed an improvement in the epithelialization, granulation tissue formation and maturation in treated groups, finding again the best response at doses of 0.5 and 2.0 µg/mL. Afterwards, the tissue immune response over time was assessed in diabetic rats using the most effective concentrations of rhEGF (0.5 and 2.0 µg/mL), compared to controls. The presence of macrophages, CD4 + T lymphocytes and CD8 + T lymphocytes, in the reparative tissue was quantified, and cytokine expression was measured by quantitative real-time PCR. rhEGF treatment caused a reduction in the number of infiltrating macrophages in the healing tissue of diabetic, as well as diminished activation of these leukocytes. These findings show that local administration of rhEGF improves the healing process of excisional wounds and the quality of the neoformed tissue in a dose-dependent manner. Besides, this treatment reduces the local inflammation associated with diabetic healing, indicating immuno-modulatory properties. © 2018 The authors.

[Innovation in pressure ulcer care: application of electrotherapy].

PubMed

Navarro Susana Postigo; Puerta Francisco Rivera

2013-02-01

Nowadays, pressure ulcers are a mayor health problem with serious consequences for the patient, directly influence by the increase of morbid-mortality and the detriment of the quality of life. Today we know that the best care for pressure ulcers is the prevention and every effort must be oriented in this direction, specially when it is estimated that almost the 95% of the pressure ulcers are preventable and a 60% of the occasions are initiated and developed in hospital. The study's objective is to promote healing of ulcers with a joint technical nursing care and the application of electric current by physiotherapist. This is a descriptive research design and intervention. The sample is composed grade IV ulcer patients who are admitted to the high level of nursing care unit in Complejo Asistencial Benito Menni (Ciempozuelos-Madrid). These patients have different associated pathologies and the study shows the process from the beginning of the ulcer until the end of treatment. The most relevant results show that the application of electric currents favors nursing techniques, promoting a better and faster cleaning, vascularization and subsequent the healing of ulcers.

Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: A prospective cohort study.

PubMed

Thomas, Kim S; Ormerod, Anthony D; Craig, Fiona E; Greenlaw, Nicola; Norrie, John; Mitchell, Eleanor; Mason, James M; Johnston, Graham A; Wahie, Shyamal; Williams, Hywel C

2016-11-01

Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG. This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence. Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence. Our study did not include a randomized comparator. Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Neighborhood socioeconomic disadvantage is not associated with wound healing in diabetic foot ulcer patients treated in a multidisciplinary setting.

PubMed

Hicks, Caitlin W; Canner, Joseph K; Mathioudakis, Nestoras; Sherman, Ronald L; Hines, Kathryn; Lippincott, Christopher; Black, James H; Abularrage, Christopher J

2018-04-01

Socioeconomic deprivation is associated with poor glycemic control and higher hospital admission rates in patients with diabetes. We sought to quantify the effects of neighborhood socioeconomic deprivation on wound healing among a cohort of patients with diabetic foot ulceration (DFU) treated in a multidisciplinary setting. Socioeconomic disadvantage was calculated for all patients using the area deprivation index (ADI) stratified by quartile (from ADI-0: least through ADI-3: most). Predictors of wound healing were assessed using Cox proportional hazards models accounting for patient demographics, wound characteristics, and ADI category. Six hundred twenty-one wounds were evaluated, including 59% ADI-0, 7% ADI-1, 12% ADI-2, and 22% ADI-3. After accounting for patient demographics and wound characteristics, the likelihood of wound healing was similar between groups (ADI-3 versus ADI-0: hazards ratio [HR] 1.03 [95% confidence interval 0.76-1.41]). Independent predictors of poor wound healing included peripheral arterial disease (HR 0.75), worse wound stage (stage 4: HR 0.48), larger wound area (HR 0.99), and partially dependent functional status (HR 0.45) (all, P < 0.05). In a multidisciplinary setting, wound healing was largely dependent on wound characteristics and vascular status rather than patient demographics or neighborhood socioeconomic disadvantage. Use of a multidisciplinary approach to the management of DFU may overcome the negative effects of socioeconomic disadvantage frequently described in the diabetic population. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary Phytosterols Protective Against Peptic Ulceration

PubMed Central

Tovey, Frank I; Capanoglu, Doga; Langley, G. John; Herniman, Julie M; Bor, Serhat; Ozutemiz, Omer; Hobsley, Michael; Bardhan, Karna Dev; Linclau, Bruno

2011-01-01

Background In developing countries the prevalence of duodenal ulceration is related to the staple diet and not to the prevalence of Helicobacter pylori. Experiments using animal peptic ulcer models show that the lipid fraction in foods from the staple diets of low prevalence areas gives protection against ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promotes healing of ulceration. The lipid from the pulse Dolichos biflorus (Horse gram) was highly active and used for further investigations. Further experiments showed the phospholipids, sterol esters and sterols present in Horse gram lipid were gastroprotective. Dietary phospholipids are known to be protective, but the nature of protective sterols in staple diets is not known. The present research investigates the nature of the protective phytosterols. Methods Sterol fractions were extracted from the lipid in Dolichos biflorus and tested for gastroprotection using the rat ethanol model. The fractions showing protective activity were isolated and identification of the components was investigated by Gas Chromatography-Mass Spectrometry (GC-MS). Results The protective phytosterol fraction was shown to consist of stigmasterol, β-sitosterol and a third as yet unidentified sterol, isomeric with β-sitosterol. Conclusions Dietary changes, affecting the intake of protective phospholipids and phytosterols, may reduce the prevalence of duodenal ulceration in areas of high prevalence and may reduce the incidence of recurrent duodenal ulceration after healing and elimination of Helicobacter pylori infection. A combination of phospholipids and phytosterols, such as found in the lipid fraction of ulceroprotecive foods, may be of value in giving protection against the ulcerogenic effect of NSAIDs. PMID:27942332

Rehabilitation nutrition in pressure ulcer management with type 2 diabetes: a case report.

PubMed

Saino, Yoko; Wakabayashi, Hidetaka; Maeda, Keisuke; Nishioka, Shinta; Hao, Takako; Mimatsu, Kenji

2018-01-01

Severe infection, inadequate food intake, and pressure ulcers in patients with type 2 diabetes can result in malnutrition. We describe a case in which rehabilitation nutrition was effective for treat-ing a pressure ulcer in a malnourished patient with type 2 diabetes. A 58-year-old man with type 2 diabetes was diagnosed with hidradenitis suppurativa on the left buttock and thigh and a severe pres-sure ulcer on his left kneecap. Malnutrition was related to hypermetabolism caused by chronic hidradenitis suppu-rativa and inadequate protein-energy intake before admission. We initiated a rehabilitation nutrition intervention to improve physical function and to treat a pressure ulcer by prescribing 2,000 kcal/day of food, including 80 g of protein, and physical rehabilitation for 40 minutes/day. The patient showed good progress in terms of his physical function and healing of the pressure ulcer. After prescribing 2,250 kcal/day of food, including 85 g of protein, and physical rehabilitation for 60 minutes/day, HbA1c levels increased to 7.4%. The energy prescription was de-creased to 2,000 kcal/day to improve glycemic levels. Then, the patient's weight decreased and his hand grip strength became weaker. On day 134 and discharge the patient could walk independently with a t-cane and ankle supporter. By day 14 after discharge, the pressure ulcer had epithelialized. Rehabilitation nutrition management improved physical function and facilitated pressure ulcer healing in a malnourished patient with type 2 diabetes. Close conjoint management of hyperglycemia was also necessary.

Economic evaluation of Vacuum Assisted Closure® Therapy for the treatment of diabetic foot ulcers in France.

PubMed

Whitehead, Sarah J; Forest-Bendien, Véronique L; Richard, Jean-Louis; Halimi, Serge; Van, Georges Ha; Trueman, Paul

2011-02-01

The objective of the study was to assess the cost-effectiveness of Vacuum Assisted Closure® (V.A.C.®) Therapy compared with advanced wound care (AWC) for the treatment of diabetic foot ulcers (DFUs) in France. A cost-effectiveness model intended to reflect the management of DFUs was updated for the French setting. The Markov model follows the progression of 1000 hypothetical patients over a 1-year period. The model was populated with French-specific data, obtained from published sources and clinical experts. The analysis evaluated costs and health outcomes, in terms of quality-adjusted life-years (QALYs), wounds healed and amputations, from the perspective of the payer. The patients treated with V.A.C.® Therapy experienced more QALYs (0.787 versus 0.784) and improved healing rates (50.2% versus 48.5%) at a lower total cost of care (€24,881 versus €28,855 per patient per year) when compared with AWC. Sensitivity analyses conducted around key model parameters indicated that the results were affected by hospital resource use and costs. DFU treatment using V.A.C.® Therapy in France was associated with lower costs, additional QALYs, more healed ulcers and fewer amputations than treatment with AWC. V.A.C.® Therapy was therefore found to be the dominant treatment option. © 2010 The Authors. © 2010 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Success Rate of Split-Thickness Skin Grafting of Chronic Venous Leg Ulcers Depends on the Presence of Pseudomonas aeruginosa: A Retrospective Study

PubMed Central

Høgsberg, Trine; Bjarnsholt, Thomas; Thomsen, Jens Schiersing; Kirketerp-Møller, Klaus

2011-01-01

The last years of research have proposed that bacteria might be involved in and contribute to the lack of healing of chronic wounds. Especially it seems that Pseudomonas aeruginosa play a crucial role in the healing. At Copenhagen Wound Healing Centre it was for many years clinical suspected that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous leg ulcers on 91 extremities, from the 1st of March 2005 until the 31st of August 2006. This was achieved by analysing the microbiology, demographic data, smoking and drinking habits, diabetes, renal impairment, co-morbidities, approximated size and age of the wounds, immunosuppressive treatment and complicating factors on the clinical outcome of each patient. The results were evaluated using a Student T-test for continuous parameters, chi-square test for categorical parameters and a logistic regression analysis to predict healing after 12 weeks. The analysis revealed that only 33,3% of ulcers with P. aeruginosa, isolated at least once from 12 weeks prior, to or during surgery, were healed (98% or more) by week 12 follow-up, while 73,1% of ulcers without P. aeruginosa were so by the same time (p = 0,001). Smoking also significantly suppressed the outcome at the 12-week follow-up. Subsequently, a logistic regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p = 0,001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts. PMID:21655269

Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: a retrospective study.

PubMed

Høgsberg, Trine; Bjarnsholt, Thomas; Thomsen, Jens Schiersing; Kirketerp-Møller, Klaus

2011-01-01

The last years of research have proposed that bacteria might be involved in and contribute to the lack of healing of chronic wounds. Especially it seems that Pseudomonas aeruginosa play a crucial role in the healing. At Copenhagen Wound Healing Centre it was for many years clinical suspected that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous leg ulcers on 91 extremities, from the 1(st) of March 2005 until the 31(st) of August 2006. This was achieved by analysing the microbiology, demographic data, smoking and drinking habits, diabetes, renal impairment, co-morbidities, approximated size and age of the wounds, immunosuppressive treatment and complicating factors on the clinical outcome of each patient. The results were evaluated using a Student T-test for continuous parameters, chi-square test for categorical parameters and a logistic regression analysis to predict healing after 12 weeks. The analysis revealed that only 33,3% of ulcers with P. aeruginosa, isolated at least once from 12 weeks prior, to or during surgery, were healed (98% or more) by week 12 follow-up, while 73,1% of ulcers without P. aeruginosa were so by the same time (p = 0.001). Smoking also significantly suppressed the outcome at the 12-week follow-up. Subsequently, a logistic regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p = 0.001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts.

Infection in Venous Leg Ulcers: Considerations for Optimal Management in the Elderly.

PubMed

Pugliese, Douglas J

2016-02-01

Venous leg ulcers are the most common cause of chronic leg wounds, accounting for up to 70 % of all chronic leg ulcers and carrying with them a significant morbidity, especially for elderly patients. Among people aged 65 years and older, the annual prevalence is 1.7 %. Billions of dollars per year are spent caring for patients with these often difficult-to-heal and sometimes recurrent chronic wounds. Chronic non-healing wounds of the lower extremities are susceptible to microbial invasion and can lead to serious complications, such as delayed healing, cellulitis, enlargement of wound size, debilitating pain, and deeper wound infections causing systemic illness. Recognition and treatment of the infected venous leg ulcer is an essential skill set for any physician caring for geriatric patients. Most physicians rely on subjective clinical signs and patient-reported symptoms in the evaluation of infected chronic wounds. The conventional bacterial culture is a widely available tool for the diagnosis of bacterial infection but can have limitations. Systemic antibiotics, as well as topical antiseptics and antibiotics, can be employed to treat and control infection and critical colonization. Better understanding of microbial biofilms in the wound environment have caused them to emerge as an important reason for non-healing and infection due to their increased resistance to antimicrobial, immunological, and chemical attack. A sound understanding of the microbial-host environment and its complexities, as well as the pathophysiology of venous hypertension, must be appreciated to understand the need for a multimodality approach to treating an infected venous leg ulcer. Other treatment measures are often required, in addition to systemic and topical antibiotics, such as the application of wound bandages, compression therapy, and wound debridement, which can hasten clearance of the infection and help to promote healing.

[Endoscopic nasobiliary and nasopancreatic drainage contributing to healing of duodenal ulcer perforation: a case report].

PubMed

Enokida, Kohei; Kikuyama, Masataka; Kurokami, Takafumi; Shirane, Naofumi; Aoyama, Haruna; Aoyama, Hiroyuki; Sato, Tatsunori; Taki, Yusuke

2015-10-01

A 75-year-old man with vomiting and right abdominal pain was admitted to the Department of Surgery in our hospital. With a diagnosis of perforated duodenal ulcer, he was treated conservatively. On the day 8 of hospitalization, his general condition worsened and he underwent surgery. During operation, the perforated duodenal ulcer and paraduodenal fluid collection was observed, and percutaneous drainage was accordingly established. After this procedure, renal dysfunction was exacerbated and he was transferred to our department for endoscopic treatment. On day 28 of hospitalization, nasobiliary and nasopancreatic drainage was administered. Renal dysfunction gradually improved, and healing of the perforated duodenal ulcer was recognized on day 93. On day 112, the patient was discharged.

Disrupted lives: investigating coping strategies for non-healing leg ulcers.

PubMed

Hopkins, Alison

The aim of this study was to explore the lived experience of people who have non-healing venous ulcers using hermeneutic phenomenology. Unstructured interviews were carried out with five people who also completed a diary. Interpretative phenomenological analysis was utilized to identify themes and patterns. The core themes identified through analysis were biographical disruption, ways of coping, social implications and therapeutic relationships. The emergent themes reveal the impact of chronicity in participants' experience of chronic leg ulcers, their various emotional and problem-focused coping strategies and the positive role the district nurse plays in their lives. This study places leg ulceration within the body of literature on chronicity, linking nursing theory with the insights offered from health psychology.

Systematic review with meta-analysis: Comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials

PubMed Central

Cholapranee, Aurada; Hazlewood, Glen S; Kaplan, Gilaad G.; Peyrin-Biroulet, Laurent; Ananthakrishnan, Ashwin N

2017-01-01

Background Mucosal healing is an important therapeutic endpoint in the management of Crohn’s disease (CD) and ulcerative colitis (UC). Limited data exists regarding the comparative efficacy of various therapies in achieving this outcome. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumor necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pair-wise treatment comparisons evaluated using a Bayesian network meta-analysis. Results A total of 12 RCTs were included in the meta-analysis (CD – 2 induction, 4 maintenance; UC – 8 induction, 5 maintenance). Duration of follow-up was 6–12 weeks for induction and 32–54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing (28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51 – 110.84). In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab (OR 0.45, 95% credible interval (CrI) 0.25 – 0.82) and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12 – 0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Conclusion Anti-TNF and anti-integrin biologic agents are effective in inducing mucosal healing in UC with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD. PMID:28326566

An evaluation of the efficacy of a topical gel with Triester Glycerol Oxide (TGO) in the treatment of minor recurrent aphthous stomatitis in a Turkish cohort: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Ofluoglu, D; Ergun, S; Warnakulasuriya, S; Namdar-Pekiner, F; Tanyeri, H

2017-03-01

Triester glycerol oxide gel (Protefix® Queisser Pharma, Germany) is a new topical agent that has the property of adherence to the oral mucosa by forming a lipid film which protects against mechanical trauma and may help to reduce oral tissue moisture loss and inflammation. The aim of this clinical trial was to determine the efficacy of a topical TGO gel and to also compare it with triamcinolone acetonide pomade in the treatment of minor recurrent aphthous stomatitis. This study was a randomized, double-blind, placebo-controlled clinical trial and 180 patients with the complaint of minor aphthous ulcers were enrolled in this study. The sociodemographic data and clinical characteristics of the ulcer were collected by questionnaire. Ulcer size and pain level measurements were performed and the efficacy indices for ulcer pain and size were calculated at day 0,2,4,6 by the same investigator. Significant differences were not detected among the demographics and ulcer histories including age, gender, onset of ulcer, mean healing time, family RAS history and ulcer localization between three groups. The pain score in TGO group was found statistically lower at day 2,4, and 6. Efficacy index and improvement rate of TGO group, regarding pain score, was higher than the other two groups at day 2 and 4. The reduction in ulcer size was statistically higher in TGO group than the other two groups at day 4 and 6. Topical application of TGO gel could decrease pain intensity, accelerate ulcer healing without any side effects, utilizing an easy appliable and accessible procedure. Therefore TGO gel could be a well-tolerated, safe, topical therapeutic agent in the clinical practice of RAS treatment.

Nutritional Aspects of Gastrointestinal Wound Healing

PubMed Central

Mukherjee, Kaushik; Kavalukas, Sandra L.; Barbul, Adrian

2016-01-01

Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with pro- and antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures. PMID:27867755

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

PubMed

Brownrigg, J R W; Hinchliffe, R J; Apelqvist, J; Boyko, E J; Fitridge, R; Mills, J L; Reekers, J; Shearman, C P; Zierler, R E; Schaper, N C

2016-01-01

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation. Copyright © 2015 John Wiley & Sons, Ltd.

Increased ratio of serum matrix metalloproteinase-9 against TIMP-1 predicts poor wound healing in diabetic foot ulcers.

PubMed

Li, Zhihong; Guo, Shuqin; Yao, Fang; Zhang, Yunliang; Li, Tingting

2013-01-01

Little is known about serum concentrations of Matrix Metalloproteinase-9 (MMP-9), MMP-2, TIMP-1 and TIMP-2 in diabetic patients with foot ulcers. This study demonstrates their relationship with wound healing. Ninety-four patients with diabetic foot ulcers were recruited in the study. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured at the first clinic visit and the end of 4-week treatment and followed up till 12 weeks. According to the decreasing rate of ulcer healing area at the fourth week, we divided those cases into good and poor healers. Through analyses, we explore the possible relationship among those factors and degree of wound healing. The median level of serum MMP-9 in good healers was lower than poor healers at first visit (124.2 μg/L vs 374.6 μg/L, p<0.05), and after 4-week therapy it decreased 5-fold approximately. In contrast, the change in MMP-9 concentration did not reach statistical significance in poor healers. MMP-2, TIMP-1 and TIMP-2 varied slightly in both good healers and poor healers. The MMP-9/TIMP-1 ratio better reflected the healing than MMP-9 alone before therapy and after 4 week treatment (r = -0.6475 vs -0.3251, r = -0.7096 vs -0.1231, respectively). Receiver Operator Curve (ROC) showed that the cutoff for MMP-9/TIMP-1 ratio at <0.395 best predicted a reduction in wound area of 82% at the end of 4-week treatment with a sensitivity of 63.6% and a specificity of 58.6% (area under the curve 0.658, p < 0.001). Detecting serum MMP-9/TIMP-1 ratio on admission might be a predictor of healing and might provide a novel target for the future therapy in diabetic foot ulcers. Copyright © 2013 Elsevier Inc. All rights reserved.

SCI Survey to Determine Pressure Ulcer Vulnerability in the Outpatient Population

DTIC Science & Technology

2011-10-01

ULCER HX # DAYS TO 1ST PU SINCE INJURY # PUs SINCE INJURY AVG. LENGTH TO HEAL PU SURGERY NEEDED FOR PUs SURGERY TYPE TROCHANTER SACRUMISCHIUM HEELS OTHER PRESSURE ULCER LOCATIO OTHER MENTAL STATUS EDUC LEVEL: HGB HBA1C 8

Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study.

PubMed

Ulrich, C; Kluschke, F; Patzelt, A; Vandersee, S; Czaika, V A; Richter, H; Bob, A; Hutten, J von; Painsi, C; Hüge, R; Kramer, A; Assadian, O; Lademann, J; Lange-Asschenfeldt, B

2015-05-01

In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.

Retrospective analysis of pulsed radiofrequency energy therapy use in the treatment of chronic pressure ulcers.

PubMed

Conner-Kerr, Teresa; Isenberg, Richard A

2012-06-01

: The purpose of the study was to evaluate the benefit of using pulsed radiofrequency energy (PRFE) therapy in the treatment of chronic pressure ulcers. : A retrospective analysis was performed using case series data from the Provant Wound Registry, which consists of demographic characteristics and wound healing outcomes for patients treated with the Provant Therapy System. : The analysis subset consisted of data from 39 distinct centers, including both residential and ambulatory care facilities. : The analysis included data from 89 patients. The majority of patients (89%) were cared for in residential facilities, whereas 11% of patients were cared for in ambulatory care facilities. : Specific outcomes that assessed wound healing between the initial time point and at the 4-week follow-up were as follows: percent wound surface area reduction (PWAR), proportion of wounds achieving 50% reduction or greater in wound surface area (50% PWAR), and the rate of wound healing (wound healing trajectory in centimeters squared per day). : Overall, there was a 51% median reduction in wound surface area (PWAR) after 4 weeks of PRFE therapy for wounds in the study, with 51% of wounds (56/110) achieving 50% reduction or greater in wound surface area (50% PWAR). Rate of healing measurements for the overall study group showed a median wound healing trajectory of 0.13 cm/d at 4 weeks. : Compared with historical controls and other studies using similar surrogate wound healing markers, these results suggest PRFE therapy is a beneficial adjuvant treatment option for healing chronic pressure ulcers.

Smoking, chronic wound healing, and implications for evidence-based practice.

PubMed

McDaniel, Jodi C; Browning, Kristine K

2014-01-01

Chronic wounds are rising in prevalence and creating significant socioeconomic burdens for patients and healthcare systems worldwide. Therefore, it is now more important than ever that clinicians follow evidence-based guidelines for wound care when developing personalized treatment plans for their patients with chronic wounds. Evidence-based guidelines for treating venous leg ulcers, diabetic foot ulcers, and pressure ulcers, the 3 main categories of chronic wounds, focus primarily on biologic therapies. However, there are also evidence-based guidelines for treating behavioral risks to poor healing, such as smoking, which should be incorporated into treatment plans when appropriate. The purpose of this article was to review the mechanisms through which smoking adversely impacts the wound healing process, and propose strategies for incorporating evidence-based guidelines for treating tobacco dependence into treatment plans for patients with chronic wounds who smoke.

Guilty as charged: bugs and drugs in gastric ulcer.

PubMed

Sontag, S J

1997-08-01

Gastric ulcer disease remains a cause of hemorrhage, perforation, outlet obstruction, and death. Recent advances in the understanding of peptic ulcer disease indicate that infection with Helicobacter pylori and ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) are the cause of almost all gastric and duodenal ulcers. Our therapy, therefore, is in a state of transition: the old acid-suppressive temporary therapy that allows frequent ulcer recurrences and complications is being replaced by curative therapies. The old therapy, by reducing gastric acid secretion or enhancing gastric mucosal defenses, inhibited the cofactors needed for ulcer development. Acid suppression relieved symptoms and healed ulcers, while defense enhancers, such as prostaglandin analogs healed and prevented acute NSAID-induced gastric ulcers. These benefits were maintained, however, only as long as acid-reducing agents or mucosal defense enhancers were continued. On the other hand, curative therapies (such as eradicating H. pylori infection and/or stopping the use of NSAIDs) eliminate the causes of ulcer. Curative combination regimens consisting of antibiotics, ranitidine bismuth citrate, bismuth, and proton pump inhibitors have been approved by the Food and Drug Administration. These new regimens can cure benign gastric ulcer. Unfortunately, we cannot always determine which gastric ulcers are benign, and concern about gastric cancer remains. All gastric ulcers therefore still require biopsy and histological examination. With new treatment regimens, the time may be rapidly approaching when ulcer disease will be "history."

Evaluation of negative-pressure wound therapy for patients with diabetic foot ulcers: systematic review and meta-analysis

PubMed Central

Liu, Si; He, Chao-zhu; Cai, Yan-ting; Xing, Qiu-ping; Guo, Ying-zhen; Chen, Zhi-long; Su, Ji-liang; Yang, Li-ping

2017-01-01

Objectives The aim of this study was to perform an updated systematic review and meta-analysis to assess the clinical efficacy, safety, and cost-effectiveness of negative-pressure wound therapy (NPWT) in the treatment of diabetic foot ulcers (DFUs). Methods We searched the Cochrane Library, MEDLINE, EMBASE, Ovid, and Chinese Biological Medicine databases up to June 30, 2016. We also manually searched the articles from reference lists of the retrieved articles, which used the NPWT system in studies of vacuum-assisted closure therapy. Studies were identified and selected, and two independent reviewers extracted data from the studies. Results A total of eleven randomized controlled trials, which included a total of 1,044 patients, were selected from 691 identified studies. Compared with standard dressing changes, NPWT had a higher rate of complete healing of ulcers (relative risk, 1.48; 95% confidence interval [CI]: 1.24–1.76; P<0.001), shorter healing time (mean difference, −8.07; 95% CI: −13.70– −2.45; P=0.005), greater reduction in ulcer area (mean difference, 12.18; 95% CI: 8.50–15.86; P<0.00001), greater reduction in ulcer depth (mean difference, 40.82; 95% CI: 35.97–45.67; P<0.00001), fewer amputations (relative risk, 0.31; 95% CI: 0.15–0.62; P=0.001), and no effect on the incidence of treatment-related adverse effects (relative risk, 1.12; 95% CI: 0.66–1.89; P=0.68). Meanwhile, many analyses showed that the NPWT was more cost-effective than standard dressing changes. Conclusion These results indicate that NPWT is efficacious, safe, and cost-effective in treating DFUs. PMID:28458556

Efficacy of Cellular Therapy for Diabetic Foot Ulcer: A Meta-Analysis of Randomized Controlled Clinical Trials.

PubMed

Zhang, Ye; Deng, Hong; Tang, Zhouping

2017-12-01

Diabetes mellitus is a widely spread chronic disease with growing incidence worldwide, and diabetic foot ulcer is one of the most serious complications of diabetes. Cellular therapy has shown promise in the management of diabetic foot ulcer in many preclinical experiments and clinical researches. Here, we performed a meta-analysis to evaluate the efficacy and safety of cellular therapy in the management of diabetic foot ulcer. We systematically searched PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to May 2017 for randomized controlled trials assessing the efficacy of cellular therapy in diabetic foot ulcer, and a meta-analysis was conducted. A total of 6 randomized controlled clinical trials involving 241 individuals were included in this meta-analysis. The results suggested that cellular therapy could help accelerating the healing of diabetic foot ulcer, presented as higher ankle-brachial index (mean difference = 0.17, 95% confidence interval [CI] = 0.11 to 0.23), higher transcutaneous oxygen pressure (standardized mean difference [SMD] = 1.43; 95% CI, 1.09- to 1.78), higher ulcer healing rate (relative risk [RR] = 1.78; 95% CI, 1.41 to 2.25), higher amputation-free survival (RR = 1.25; 95% CI, 1.11 to 1.40), and lower scale of pain (SMD = -1.69; 95% CI, -2.05 to -1.33). Furthermore, cellular therapy seemed to be safe, with no serious complications and low risk of short-term slight complications. Cellular therapy could accelerate the rate of diabetic foot ulcer healing and may be more efficient than standard therapy for diabetic foot treatment.

A pilot randomised controlled trial of negative pressure wound therapy to treat grade III/IV pressure ulcers [ISRCTN69032034

PubMed Central

2012-01-01

Background Negative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community), pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC) (spun hydrocolloid, alginate or foam dressings). Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8%) were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group) during follow-up (time to healing 79 days). The mean number of treatment visits per week was 3.1 (NPWT) and 5.7 (SC); 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT) and 5.0 (SC) months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034. PMID:22839453

A novel fully synthetic and self-assembled peptide solution for endoscopic submucosal dissection-induced ulcer in the stomach.

PubMed

Uraoka, Toshio; Ochiai, Yasutoshi; Fujimoto, Ai; Goto, Osamu; Kawahara, Yoshiro; Kobayashi, Naoya; Kanai, Takanori; Matsuda, Sachiko; Kitagawa, Yuko; Yahagi, Naohisa

2016-06-01

Endoscopic submucosal dissection (ESD) can remove early stage GI tumors of various sizes en bloc; however, success requires reducing the relatively high postprocedure bleeding rate. The aim of this study was to assess the safety and efficacy of a novel, fully synthetic, and self-assembled peptide solution that functions as an extracellular matrix scaffold material to facilitate reconstruction of normal tissues in ESD-induced ulcers. Consecutive patients who underwent gastric ESD were prospectively enrolled. Immediately after the resection, the solution was applied to the site with a catheter. Gastric ulcers were evaluated by endoscopy and classified as active, healing, or scarring stages at weeks 1, 4, and 8 after ESD. Forty-seven patients with 53 lesions, including 14 (29.8%) previously on antithrombotic therapy and 2 (4.3%) requiring heparin bridge therapy, were analyzed; 2 patients were excluded, 1 with perforations and 1 with persistent coagulopathy. The mean size of the en bloc resected specimens was 36.5 ± 11.3 mm. The rate of post-ESD bleeding was 2.0% (1/51; 95% CI, 0.03-10.3). Transitional rate to the healing stage of ESD-induced ulcers at week 1 was 96% (49/51). Subsequent endoscopies demonstrated the scarring stage in 19% (9/48) and 98% (41/42) at weeks 4 and 8, respectively. No adverse effects related to this solution occurred. The use of this novel peptide solution may potentially aid in reducing the delayed bleeding rate by promoting mucosal regeneration and speed of ulcer healing after large endoscopic resections in the stomach. Further studies, particularly randomized controlled studies, are needed to fully evaluate its efficacy. ( 000011548.). Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Effectiveness of platelet-rich plasma and hyaluronic acid for the treatment and care of pressure ulcers.

PubMed

Ramos-Torrecillas, Javier; García-Martínez, Olga; De Luna-Bertos, Elvira; Ocaña-Peinado, Francisco Manuel; Ruiz, Concepción

2015-03-01

Platelet-rich growth factor (PRGF) is a natural source of growth factors (GF), while hyaluronic acid (HA) is a biopolymer present in the extracellular matrix of skin, cartilage, bone, and brain, among other tissues. Both are involved in the pathophysiological mechanisms underlying wound healing. The objective of this study was to evaluate the clinical efficacy (as measured by ulcer area) and safety (as measured by signs of infection) of PRGF and PRGF plus HA in the treatment of pressure ulcers (PUs). Patients (N = 100) with 124 Stage II-III PUs were randomized to a control group (n = 25 PUs) for standard care or to case groups for treatment with one (n = 34 PUs) or two (n = 25 PUs) doses of PRGF from their own peripheral blood, or two doses of PRGF plus HA (n = 40 PUs). All ulcers were followed up every 3 days for a 36-day period. At 36 days, a significant reduction in ulcer area (p ≤ .001) was observed in all treatment groups, with a mean reduction of more than 48.0% versus baseline. The greatest mean reduction (80.4% vs. baseline) was obtained with the PRGF plus HA regimen. Complete wound healing was observed in 32.0% of PUs treated with two doses of PRGF (p ≤ .002) and in 37.5% of those treated with two doses of PRGF plus HA (p ≤ .004). There were no signs of infection in any PUs during the 36-day follow-up period. The degree of wound healing was inversely correlated with the consumption of drugs such as statins and with the peripheral blood platelet levels of patients at baseline. © The Author(s) 2014.

Successful Endoscopic Management of Non-Healing Perforated Duodenal Ulcer with Polyglycolic Acid Sheet and Fibrin Glue.

PubMed

Mishiro, Tsuyoshi; Shibagaki, Kotaro; Matsuda, Kayo; Fukuyama, Chika; Okada, Mayumi; Mikami, Hironobu; Izumi, Daisuke; Yamashita, Noritsugu; Okimoto, Eiko; Fukuda, Naoki; Aimi, Masahito; Fukuba, Nobuhiko; Oshima, Naoki; Takanashi, Toshihiro; Matsubara, Takeshi; Ishimura, Norihisa; Ishihara, Shunji; Kinoshita, Yoshikazu

2016-08-01

In recent years, treatment techniques in which polyglycolic acid sheets are applied to various situations with fibrin glue have exhibited great clinical potential, and previous studies have reported safety and efficacy. We describe closure of a non-healing perforated duodenal ulcer with the use of a polyglycolic acid sheet and fibrin glue in an elderly patient who was not a candidate for surgery.

[The gold standard in diabetic foot treatment: total contact cast].

PubMed

Lozano-Platonoff, Adriana; Florida Mejía-Mendoza, Melissa Desireé; Ibáñez-Doria, Mónica; Contreras-Ruiz, José

2014-01-01

In patients with diabetes, foot complications remain one of the main health issues, with ulcers representing one of the most common. These ulcerations originate from repetitive trauma on a foot with neuropathy. Inadequate care of the diabetic foot may lead to one of the gravest complications of the diabetic foot: amputation. The key to the treatment of the diabetic foot is the control of comorbidities (glucose levels and vascular disease), debridement, exudate control with the available modern dressings, treatment of infection, and offloading the affected foot. A common error in this basic treatment is the method used for offloading, leading to delayed healing as a result, and maybe even amputation. For this purpose we propose the total contact cast considered the "gold standard" in diabetic foot offloading. The objective of the present review is to present the existing evidence in the medical literature on the effectiveness of its use for healing diabetic foot ulcers and hence preventing amputations.

Hydrogen gas inhalation protects against cutaneous ischaemia/reperfusion injury in a mouse model of pressure ulcer.

PubMed

Fang, Wei; Wang, Guizhen; Tang, Luyan; Su, Huilin; Chen, Huyan; Liao, Wanqing; Xu, Jinhua

2018-06-19

Pressure ulcer formation depends on various factors among which repetitive ischaemia/reperfusion(I/R) injury plays a vital role. Molecular hydrogen (H 2 ) was reported to have protective effects on I/R injuries of various internal organs. In this study, we investigated the effects of H 2 inhalation on pressure ulcer and the underlying mechanisms. H 2 inhalation significantly reduced wound area, 8-oxo-dG level (oxidative DNA damage) and cell apoptosis rates in skin lesions. H 2 remarkably decreased ROS accumulation and enhanced antioxidant enzymes activities by up-regulating expression of Nrf2 and its downstream components in wound tissue and/or H 2 O 2 -treated endothelia. Meanwhile, H 2 inhibited the overexpression of MCP-1, E-selectin, P-selectin and ICAM-1 in oxidant-induced endothelia and reduced inflammatory cells infiltration and proinflammatory cytokines (TNF-α, IL-1, IL-6 and IL-8) production in the wound. Furthermore, H 2 promoted the expression of pro-healing factors (IL-22, TGF-β, VEGF and IGF1) and inhibited the production of MMP9 in wound tissue in parallel with acceleration of cutaneous collagen synthesis. Taken together, these data indicated that H 2 inhalation suppressed the formation of pressure ulcer in a mouse model. Molecular hydrogen has potentials as a novel and alternative therapy for severe pressure ulcer. The therapeutic effects of molecular hydrogen might be related to its antioxidant, anti-inflammatory, pro-healing actions. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Treatment for diabetic ulcer wounds using a fern tannin optimized hydrogel formulation with antibacterial and antioxidative properties.

PubMed

Lai, Jordan Chia-Yung; Lai, How-Yee; Nalamolu, Koteswara Rao; Ng, Shiow-Fern

2016-08-02

Blechnum orientale Linn. (B. orientale) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin. To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds. The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05). One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis. The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A budesonide prodrug accelerates treatment of colitis in rats.

PubMed Central

Cui, N; Friend, D R; Fedorak, R N

1994-01-01

Although oral glucocorticoids are the treatment of choice for moderate to severe ulcerative pancolitis, their systemic side effects and adrenal suppression account for considerable morbidity. An oral glucocorticoid-conjugate (prodrug), budesonide-beta-D-glucuronide, which is not absorbed in the small intestine but is hydrolysed by colonic bacterial and mucosal beta-glucuronidase to release free budesonide into the colon was synthesised. The objective of this study was to compare treatment with budesonide-beta-D-glucuronide with treatment with free budesonide by examining: (1) the healing of experimental colitis and (2) the extent of adrenal suppression. Pancolitis was induced with 4% acetic acid. Animals were then randomised to receive oral therapy for 72 hours with (1) budesonide-beta-D-glucuronide, (2) free budesonide, or (3) vehicle. Drug efficacy and colitic healing was determined by measuring gross colonic ulceration, myeloperoxidase activity, and in vivo colonic fluid absorption. Adrenal suppression was determined by measuring plasma adrenocorticotrophic hormone and serum corticosterone. Vehicle-treated colitis animals had gross ulceration, increased myeloperoxidase activity, and net colonic fluid secretion. Treatment with oral budesonide-beta-D-glucuronide accelerated all measures of colitis healing at a fourfold lower dose than did free budesonide. Furthermore, treatment with budesonide-beta-D-glucuronide did not result in adrenal suppression whereas free budesonide treatment did. A newly synthesised orally administered glucocorticoid-conjugate accelerates colitis healing with limited adrenal suppression. Development of an orally administered colon-specific steroid delivery system represents a novel approach to inflammatory bowel disease treatment. PMID:7959202

Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis.

PubMed

Nilforoushzadeh, Mohammad Ali; Jaffary, Fariba; Moradi, Shahram; Derakhshan, Roya; Haftbaradaran, Elaheh

2007-04-27

Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar. In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan-Mayer tests. In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime. Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04). Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.

Antiulcerogenic and antiinflammatory studies with shilajit.

PubMed

Goel, R K; Banerjee, R S; Acharya, S B

1990-04-01

In folk medicine, shilajit has been used to treat diverse clinical conditions ranging from peptic ulcer to bone healing. The present study was conducted to evaluate the possible antiulcerogenic and antiinflammatory activities of shilajit obtained from the rocky mountains of Zarlek, Badekshan, Afghanistan. Shilajit increased the carbohydrate/protein ratio and decreased gastric ulcer index, indicating an increased mucus barrier. Shilajit was found to have significant antiinflammatory effect in carrageenan-induced acute pedal oedema, granuloma pouch and adjuvant-induced arthritis in rats. The results of the present study thus substantiate the use of shilajit in peptic ulcer and inflammation.

Use of ultraportable vacuum therapy systems in the treatment of venous leg ulcer.

PubMed

Cuomo, Roberto; Nisi, Giuseppe; Grimaldi, Luca; Brandi, Cesare; D'Aniello, Carlo

2017-10-23

The high incidence of venous leg ulcers and the difficult to give a complete healing involves in an increase of costs for National Health System. Main therapies to obtain a fast healing are compressive bandages, treatment of abnormal venous flow and in-situ-strategies of wound care. Negative pressure therapy does not conventionally used, because these systems not allow the use of compression bandages. Recently the development of ultraportable devices has improved the compliance and the results. Ten patients with venous chronic ulcer on the lower extremities were recruited for this study: all patients had venous leg ulcers from at least one year. We treated the patients with autologous partial thickness skin graft and subsequently we applied NANOVA device included in compressive bandage. We used NANOVA for fourteen days and after we made traditional medications. We submitted a questionnaire to evaluate the impact of dressing and NANOVA device in the quality of life of patients. The device contributed to the formation of granulation tissue and increased the success rate of autologous skin graft without limiting mobility of patient. In addition to this, we have been able to perform compression bandages thanks to small size of this device. Eight ulcers healed within 90 days of medication. We believe that ultraportable negative pressure systems are useful devices for treatment of venous leg ulcers because them allows to realize a compressive bandage without mobility limitations.

Transdermal deferoxamine prevents pressure-induced diabetic ulcers

PubMed Central

Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

2015-01-01

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice.

PubMed

Sikiric, P; Seiwerth, S; Mise, S; Staresinic, M; Bedekovic, V; Zarkovic, N; Borovic, S; Gjurasin, M; Boban-Blagaic, A; Batelja, L; Rucman, R; Anic, T

2003-06-01

The amelioration of corticosteroid-impairment of healing by a stable gastric pentadecapeptide BPC-157 (GEPPPGKPADDAGLV, M(w) 1419, currently in early clinical trials for inflammatory bowel disease) was studied in thermally injured mice. Its effects on corticosteroid impaired healing of deep partial skin thickness burns, and burn-gastric lesions were investigated. Male NMRI-Hannover mice (sacrificed at 1-3,7,14 and 21 days following burning 20% of total burn area at the back (open flame for 7s) received intraperitoneally (per kg bw) 6alpha-methylprednisolone (Depo-medrol, 1.0 or 10.0mg), or an equal volume of saline (5.0 ml), once daily, first application 30 min after injury, last 24h before sacrifice. The injury was subsequently treated by topical application of a thin layer of pentadecapeptide BPC-157 cream at three different levels a neutral cream of no treatment. Pentadecapeptide BPC-157 consistently improved given burn healing (both microscopical and tensionmetry assessment), and counteracted corticosteroid-impairment of burn healing. In burn-gastric lesions investigation of the effects of BPC showed an anti-ulcer effect of its own in burned non-corticosteroid-treated mice and potentiated the anti-ulcer effect observed in 6alpha-methylprednisolone-treated mice. Pentadecapeptide BPC-157 inhibited corticosteroid immunosuppression. In vitro, in spleenic cells assessment, animals (sacrificed at day 21) treated with 6alpha-methylprednisolone 1mg showed decreased reactivity to nitrogen in comparison with control, healthy animals, while the addition of BPC-157 (1 microg/g cream) returned cell reactivity to values noted in control healthy animals.

Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration.

PubMed

Collum, L M; Logan, P; McAuliffe-Curtin, D; Hung, S O; Patterson, A; Rees, P J

1985-11-01

Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant.

Scientific Evaluation of Edible Fruits and Spices Used for the Treatment of Peptic Ulcer in Traditional Iranian Medicine

PubMed Central

Farzaei, Mohammad Hosein; Shams-Ardekani, Mohammad Reza; Abbasabadi, Zahra; Rahimi, Roja

2013-01-01

In traditional Iranian medicine (TIM), several edible fruits and spices are thought to have protective and healing effects on peptic ulcer (PU). The present study was conducted to verify anti-PU activity of these remedies. For this purpose, edible fruits and spices proposed for the management of PU in TIM were collected from TIM sources, and they were searched in modern medical databases to find studies that confirmed their efficacy. Findings from modern investigations support the claims of TIM about the efficacy of many fruits and spices in PU. The fruit of Phyllanthus emblica as a beneficial remedy for PU in TIM has been demonstrated to have antioxidant, wound healing, angiogenic, anti-H. pylori, cytoprotective, antisecretory, and anti-inflammatory properties. The fruit of Vitis vinifera has been found to be anti-H. pylori, anti-inflammatory, wound healing, angiogenic, cytoprotective, and antioxidant. The fruit and aril of seed from Myristica fragrans exert their beneficial effects in PU by increasing prostaglandin, modulation of nitric oxide and inflammatory mediators, wound healing, antisecretory, antacid, antioxidant, and anti-H. pylori activities, and improving angiogenesis. Pharmacological and clinical studies for evaluation of efficacy of all TIM fruits and spices in PU and their possible mechanisms of action are recommended. PMID:24066235

A Prospective, Postmarket, Compassionate Clinical Evaluation of a Novel Acellular Fish-skin Graft Which Contains Omega-3 Fatty Acids for the Closure of Hard-to-heal Lower Extremity Chronic Ulcers.

PubMed

Yang, Chun K; Polanco, Thais O; Lantis, John C

2016-04-01

A novel piscine acellular fish-skin graft product has 510k clearance on the US market. This product (Omega3, Kerecis, Isafjordur, Iceland) is to be used similarly to extracellular matrices (ECMs) on the market (eg, bovine and porcine) except that it contains fats, including omega-3 polyunsaturated fatty acids that have been associated with anti-inflammatory properties in many studies. While many current ECMs are effective on open wounds, studies have largely excluded application to hard-to-heal ulcers. To test this product in a real-world environment, the authors chose to look specifically at hard-to-heal ulcers based on previously defined wound and patient factors. The primary objective was to assess the percentage of wound closure area from baseline after 5 weekly fish-skin graft applications in 18 patients with at least 1 "hard-to-heal" criteria. Patients underwent application of the fish skin for 5 sequential weeks, followed by 3 weeks of standard of care. Wound area, skin assessments, and pain were assessed weekly. A 40% decrease in wound surface area (P < 0.05) and a 48% decrease in wound depth was seen with 5 weekly applications of the fish-skin graft and secondary dressing (P < 0.05). Complete closure was seen in 3 of 18 patients by the end of the study phase. This fish-skin product appears to provide promise as an effective wound closing adjunctive ECM. This is true when used in this compassionate setting, where many other products fail. This study lacks a control arm and an aggressive application schedule, but the investigators believe it represents real-world practice.

Magnetic resonance index of activity (MaRIA) and Clermont score are highly and equally effective MRI indices in detecting mucosal healing in Crohn's disease.

PubMed

Buisson, Anthony; Pereira, Bruno; Goutte, Marion; Reymond, Maud; Allimant, Christophe; Obritin-Guilhen, Hélène; Bommelaer, Gilles; Hordonneau, Constance

2017-11-01

Magnetic resonance index of activity (MaRIA) and Clermont score are currently the two main MRI indices that have been validated compared to endoscopy in Crohn's disease (CD). To compare the accuracy of MaRIA and Clermont score in assessing CD mucosal healing. Fourty-four CD patients underwent prospectively and consecutively MRI and colonoscopy. Considering 207 segments, MaRIA>7 and Clermont score>8.4 demonstrated substantial accuracy to detect endoscopic ulcerations (73.9% and 74.0%, respectively) and presented with high specificity (82.1% and 81.3%) and high negative predictive value (NPV) (82.1% and 82.4%) for MaRIA and Clermont score, respectively. The sensitivity for detecting deep ulcerations was 90.9% for both MaRIA>11 and Clermont score>12.5, with a specificity of 82.0% and 80.0%, respectively. Among 44 patients, deep MRI remission predicted mucosal healing with specificity=85.3% and NPV=85.3% according to Barcelona criteria (no segmental MaRIA>7), and specificity=88.2% and NPV=85.7% according to Clermont criteria (no segmental Clermont score>8.4). In addition, MRI remission predicted mucosal healing with specificity=76.5% and NPV=86.7% according to Barcelona criteria (no segmental MaRIA>11), and specificity=79.4% and NPV=84.4% according to Clermont criteria (no segmental Clermont score>12.5). MaRIA and Clermont score are equally effective in detecting CD endoscopic ulcerations supporting their use as therapeutic endpoints. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Comparison of pressure ulcer treatments in long-term care facilities: clinical outcomes and impact on cost.

PubMed

Narayanan, Siva; Van Vleet, John; Strunk, Billy; Ross, Robert N; Gray, Mikel

2005-01-01

This study compared clinical outcomes and nursing labor costs associated with (a) balsam Peru, hydrogenated castor oil, and trypsin (BCT) ointment; (b) BCT + Other; and (c) Other treatments in 2014 wound episodes occurring in 861 patients (mean 2.34 wounds/patient). Treatment with BCT ointment or BCT + Other was associated with a higher healing rate (P < .05). No Stage 1 or 2 ulcer treated with BCT ointment progressed, compared with 13.8% treated with BCT + Other and 13.4% treated with Other. The reported mean duration of treatment and time to heal were shorter for ulcers treated with BCT ointment, but differences did not reach significance, possibly because of the variability in reported treatment times. Mean daily nursing labor costs were lower for treatment with BCT than Other ($50.8 vs $61.7, P < .05). These data suggest that treatment of Stage 1 or 2 ulcers with BCT may be associated with shorter treatment time and time to heal and a potential reduction in treatment-related nursing labor costs.

The combined use of NPWT and instillation using an octenidine based wound rinsing solution: a case study.

PubMed

Matiasek, J; Djedovic, G; Mattesich, M; Morandi, E; Pauzenberger, R; Pikula, R; Verstappen, R; Pierer, G; Koller, R; Rieger, U M

2014-11-01

Effective wound bed preparation is an essential element in the healing of chronic wounds, including pressure ulcers (PUs). Negative pressure wound therapy (NPWT) reduces oedema, stimulates the formation of granulation tissue and helps remove wound exudate. This helps prepare the wound bed for secondary healing, skin grafting or coverage with flaps. Combining NPWT with an instillation phase using an antiseptic (octenidine based) irrigation solution is a novel approach to PU management. Three patients with Category 4 gluteal PUs were treated with NPWT and instillation fluid, following surgical debridement of necrotic tissue. The aim was to achieve optimal wound bed preparation prior to wound closure by local fasciocutaneous flap. The antiseptic efficacy of octenilin wound irrigation solution in microorganism eradication was quantified by in vitro tests simulating real conditions using leg ulcer vacuum exudates. All wounds completely healed after four weeks, and no adverse incidents occurred due to instillation of octenidine. No recurrence of the PU occurred during a one year follow-up.

Valentino's syndrome a perforated peptic ulcer mimicking acute appendicitis.

PubMed

Wijegoonewardene, Sandeep Indika; Stein, Joel; Cooke, David; Tien, Alan

2012-06-28

The authors present a case of a 30-year-old female who presented with symptoms and signs suggestive of appendicitis accompanied by elevated inflammatory markers. The patient was consented and taken to theatre for laparoscopic apendicectomy. At operation, the appendix was found to be normal but with surrounding turbid fluid in the right paracolic gutter and subhepatic space. On further inspection, a perforated pre pyloric ulcer was discovered. This was managed laparoscopically with a peritoneal lavage and falciform ligament patch repair. The patient made a good recovery and was discharged 2 days later. At 6 week follow-up the patient had an upper gastrointestinal (GI) endoscopy which showed complete healing of the ulcer. At 6 week follow-up the patient had an upper GI endoscopy which showed complete healing of the ulcer.

Venous leg ulcer healing with electric stimulation therapy: a pilot randomised controlled trial.

PubMed

Miller, C; McGuiness, W; Wilson, S; Cooper, K; Swanson, T; Rooney, D; Piller, N; Woodward, M

2017-03-02

Compression therapy is a gold standard treatment to promote venous leg ulcer (VLU) healing. Concordance with compression therapy is, however, often sub-optimal. The aim of this study was to evaluate the effectiveness of electric stimulation therapy (EST) to facilitate healing of VLUs among people who do not use moderate-to-high levels of compression (>25 mmHg). A pilot multicentre, single-blinded randomised controlled trial was conducted. Participants were randomised (2:1) to the intervention group or a control group where EST or a sham device was used 4 times daily for 20 minutes per session. Participants were monitored fortnightly for eight weeks. The primary outcome measure was percentage of area (wound size) change. In the 23 patients recruited, an average redution in wound size of 23.15% (standard deviation [SD]: 61.23) was observed for the control group compared with 32.67 % (SD: 42.54) for the intervention. A moderate effect size favouring the intervention group was detected from univariate [F(1,18)=1.588, p=0.224, partial eta squared=0.081] and multivariate repeated measures [F(1,18)=2.053, p=0.169, partial eta squared=0.102] analyses. The pilot study was not powered to detect statistical significance, however, the difference in healing outcomes are encouraging. EST may be an effective adjunct treatment among patients who have experienced difficulty adhering to moderate-to-high levels of compression therapy.

Diabetic foot ulcers. Pathophysiology, assessment, and therapy.

PubMed

Bowering, C K

2001-05-01

To review underlying causes of diabetic foot ulceration, provide a practical assessment of patients at risk, and outline an evidence-based approach to therapy for diabetic patients with foot ulcers. A MEDLINE search was conducted for the period from 1979 to 1999 for articles relating to diabetic foot ulcers. Most studies found were case series or small controlled trials. Foot ulcers in diabetic patients are common and frequently lead to lower limb amputation unless a prompt, rational, multidisciplinary approach to therapy is taken. Factors that affect development and healing of diabetic patients' foot ulcers include the degree of metabolic control, the presence of ischemia or infection, and continuing trauma to feet from excessive plantar pressure or poorly fitting shoes. Appropriate wound care for diabetic patients addresses these issues and provides optimal local ulcer therapy with débridement of necrotic tissue and provision of a moist wound-healing environment. Therapies that have no known therapeutic value, such as foot soaking and topical antiseptics, can actually be harmful and should be avoided. Family physicians are often primary medical contacts for patients with diabetes. Patients should be screened regularly for diabetic foot complications, and preventive measures should be initiated for those at risk of ulceration.

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

PubMed

Zhang, Qin-hong; Yue, Jin-huan; Li, Chao-ran; Sun, Zhong-ren

2014-12-30

Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. ChiCTR-TRC-13003959. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

PubMed

El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

2014-05-01

The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

Honey as a topical treatment for wounds.

PubMed

Jull, Andrew B; Cullum, Nicky; Dumville, Jo C; Westby, Maggie J; Deshpande, Sohan; Walker, Natalie

2015-03-06

Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective of this review was to assess the effects of honey compared with alternative wound dressings and topical treatments on the of healing of acute (e.g. burns, lacerations) and/or chronic (e.g. venous ulcers) wounds. For this update of the review we searched the Cochrane Wounds Group Specialised Register (searched 15 October 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9); Ovid MEDLINE (1946 to October Week 1 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October 2014); Ovid EMBASE (1974 to 13 October 2014); and EBSCO CINAHL (1982 to 15 October 2014). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. All data have been subsequently checked by two more authors. We identified 26 eligible trials (total of 3011 participants). Three trials evaluated the effects of honey in minor acute wounds, 11 trials evaluated honey in burns, 10 trials recruited people with different chronic wounds including two in people with venous leg ulcers, two trials in people with diabetic foot ulcers and single trials in infected post-operative wounds, pressure injuries, cutaneous Leishmaniasis and Fournier's gangrene. Two trials recruited a mixed population of people with acute and chronic wounds. The quality of the evidence varied between different comparisons and outcomes. We mainly downgraded the quality of evidence for risk of bias, imprecision and, in a few cases, inconsistency.There is high quality evidence (2 trials, n=992) that honey dressings heal partial thickness burns more quickly than conventional dressings (WMD -4.68 days, 95%CI -5.09 to -4.28) but it is unclear if there is a difference in rates of adverse events (very low quality evidence) or infection (low quality evidence).There is very low quality evidence (4 trials, n=332) that burns treated with honey heal more quickly than those treated with silver sulfadiazine (SSD) (WMD -5.12 days, 95%CI -9.51 to -0.73) and high quality evidence from 6 trials (n=462) that there is no difference in overall risk of healing within 6 weeks for honey compared with SSD (RR 1.00, 95% CI 0.98 to 1.02) but a reduction in the overall risk of adverse events with honey relative to SSD. There is low quality evidence (1 trial, n=50) that early excision and grafting heals partial and full thickness burns more quickly than honey followed by grafting as necessary (WMD 13.6 days, 95%CI 9.82 to 17.38).There is low quality evidence (2 trials, different comparators, n=140) that honey heals a mixed population of acute and chronic wounds more quickly than SSD or sugar dressings.Honey healed infected post-operative wounds more quickly than antiseptic washes followed by gauze and was associated with fewer adverse events (1 trial, n=50, moderate quality evidence, RR of healing 1.69, 95%CI 1.10 to 2.61); healed pressure ulcers more quickly than saline soaks (1 trial, n= 40, very low quality evidence, RR 1.41, 95%CI 1.05 to 1.90), and healed Fournier's gangrene more quickly than Eusol soaks (1 trial, n=30, very low quality evidence, WMD -8.00 days, 95%CI -6.08 to -9.92 days).The effects of honey relative to comparators are unclear for: venous leg ulcers (2 trials, n= 476, low quality evidence); minor acute wounds (3 trials, n=213, very low quality evidence); diabetic foot ulcers (2 trials, n=93, low quality evidence); Leishmaniasis (1 trial, n=100, low quality evidence); mixed chronic wounds (2 trials, n=150, low quality evidence). It is difficult to draw overall conclusions regarding the effects of honey as a topical treatment for wounds due to the heterogeneous nature of the patient populations and comparators studied and the mostly low quality of the evidence. The quality of the evidence was mainly downgraded for risk of bias and imprecision. Honey appears to heal partial thickness burns more quickly than conventional treatment (which included polyurethane film, paraffin gauze, soframycin-impregnated gauze, sterile linen and leaving the burns exposed) and infected post-operative wounds more quickly than antiseptics and gauze. Beyond these comparisons any evidence for differences in the effects of honey and comparators is of low or very low quality and does not form a robust basis for decision making.

Micronutrients and Natural Compounds Status and Their Effects on Wound Healing in the Diabetic Foot Ulcer.

PubMed

Kulprachakarn, Kanokwan; Ounjaijean, Sakaewan; Wungrath, Jukkrit; Mani, Raj; Rerkasem, Kittipan

2017-12-01

The diabetic foot ulcer (DFU) is an invariably common complication of diabetes mellitus, it is also a significant cause of amputation as well as extended hospitalization. As most patients with DFU suffer from malnutrition, which has been related to improper metabolic micronutrients status, alterations can affect impaired wound healing process. Micronutrients and herbal remedies applications present a wide range of health advantages to patients with DFU. The purpose of this review is to provide current evidence on the potential effect of dietary supplementations such as vitamins A, C, D, E, magnesium, zinc, copper, iron, boron, and such naturally occurring compounds as Aloe vera, Naringin, and Radix Astragali (RA) and Radix Rehmanniae (RR) in the administration of lower extremity wounds, especially in DFU, and to present some insights for applications in the treatment of DFU patients in the future.

Indications for treatment of Helicobacter pylori infection: a systematic overview.

PubMed

Veldhuyzen van Zanten, S J; Sherman, P M

1994-01-15

To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.

Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice.

PubMed

Choi, Seong Mi; Lee, Kyoung-Mi; Kim, Hyun Jung; Park, Ik Kyu; Kang, Hwi Ju; Shin, Hang-Cheol; Baek, Dawoon; Choi, Yoorim; Park, Kwang Hwan; Lee, Jin Woo

2018-01-15

Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm 2 ST-EGF or 1 μg/cm 2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm 2 ST-EGF or 1 μg/cm 2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were able to accelerate wound healing including re-epithelialization, neovascularization, and collagen deposition. Consequentially, these ST-EGF and ST-bFGF-loaded HCD matrix may be used as future therapeutic agents in patients with diabetic foot ulcers. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Wound healing property of isolated compounds from Boesenbergia kingii rhizomes.

PubMed

Sudsai, Teeratad; Wattanapiromsakul, Chatchai; Tewtrakul, Supinya

2016-05-26

Boesenbergia kingii have been traditionally used in the treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer, stomach discomfort, dysentery and abscess. Previously, we reported the B. kingii extract exert potential wound healing properties. Therefore the search of responsible constituents for wound healing property from these rhizomes is still relevant. This study was aimed to investigate for wound healing property of compounds from this plant in order to support its traditional uses. Wound healing activities were tested using in vitro assays including cell proliferation and migration assays, collagen production and H2O2-induced oxidative stress in mouse fibroblast L929 cells. The DPPH assay was also used to determine antioxidant activity. Fourteen compounds from the chloroform fraction possessed potent anti-oxidant and wound healing activities. Compound 11 exhibited the most potent anti-DPPH effect (IC50=21.0µM) and also active against 0.5mMH2O2-induced oxidative stress by increasing cell survival ability up to 60.3% at 10µM. In addition, compounds 3, 8 and 14 at 10µM significantly enhanced L929 viability with 119.2%, 122.7% and 113.7%, respectively. Compounds 2, 7, 8 and 14 markedly enhanced L929 migration on day 2 up to 60-76% at 10µM, whereas 7 and 14 strongly stimulated collagen production at 75.0 and 96.7µg/ml compared to the control group (57.5µg/ml), respectively. B. kingii is responsible for wound healing property via antioxidative effect, stimulation of fibroblast proliferation and migration as well as enhancement of collagen production. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Perianal and rectal ulcers due to abuse of paracetamol-codeine suppositories].

PubMed

Wagner, G; Sand, C; Sachse, M M

2015-03-01

A 61-year-old woman presented with a progressive perianal ulcer which had developed 4 months ago. Upon further examination, another ulcer of the rectum was detected. Anorectal malignancies, viral infections or primary inflammatory bowel disease were not found. It could be demonstrated that the ulcers were induced by paracetamol and codeine suppositories. After discontinuation of these suppositories, the perianal ulcers healed almost completely within 3 weeks. The pathogenesis of paracetamol-induced ulcers is unknown. However, dose-dependent vasoconstriction is a possible explanation.

Rebamipide May Be Comparable to H2 Receptor Antagonist in Healing Iatrogenic Gastric Ulcers Created by Endoscopic Mucosal Resection: A Prospective Randomized Pilot Study

PubMed Central

Kim, Yu Jin; Lee, Sang Kil; Kim, Jie Hyun; Lee, Yong Chan

2010-01-01

Endoscopic mucosal resection (EMR) results in the formation of iatrogenic gastric ulcers and the optimal treatments for such ulcers are still unclear. We aimed to evaluate the efficacy of rebamipide in the management of EMR-induced ulcers by comparing it with an H2 receptor antagonist. After EMR, patients were randomly assigned into either rebamipide or famotidine groups. All patients received a one-week lansoprazole 30 mg q.d. therapy followed by three-week famotidine (20 mg b.i.d.) or rebamipide (100 mg t.i.d.) therapy. Four weeks after the treatments, ulcer sizes, stages, bleeding rates, and ulcer-related symptoms were compared using endoscopy and a questionnaire. A total of 63 patients were enrolled in this study. Finally, 51 patients were analyzed, 26 in rebamipide and 25 in famotidine group. Baseline characteristics were not significantly different between the two groups. Four weeks after EMR, the two groups were comparable in terms of ulcer reduction ratio (P=0.297), and ulcer stage (P=1.000). Moreover, no difference was observed with regard to ulcer-related symptoms, drug compliance, adverse drug event rates, and bleeding rates. Our data suggest that rebamipide is not inferior to famotidine in healing iatrogenic gastric ulcers, and could be a therapeutic option in the treatment of such ulcers. PMID:20358002

Comparative trial of Aloe vera/olive oil combination cream versus phenytoin cream in the treatment of chronic wounds.

PubMed

Panahi, Y; Izadi, M; Sayyadi, N; Rezaee, R; Jonaidi-Jafari, N; Beiraghdar, F; Zamani, A; Sahebkar, A

2015-10-01

Aloe vera is a medicinal plant that has been traditionally used to accelerate wound healing. Olive oil is also a natural product that may contribute to wound healing owing to its antimicrobial and anti-inflammatory effects. The present study aimed to evaluate the effect of an Aloe vera-olive oil (AVO) combination cream on the healing process of chronic wounds. In this randomised, double-blind, comparator-controlled, parallel-group trial, patients with chronic wounds were treated with either AVO cream or phenytoin cream as the standard treatment for a period of 30 days. Wound healing was evaluated using Bates-Jensen assessment tool and the severity of pain was assessed using a visual analogue scale (VAS). After initial assessment, 60 patients with chronic wounds (41 with pressure ulcer, 13 with diabetic wounds and 6 with venous ulcers), were recruited and randomised into 2 groups of 30. After 30 days of treatment, significant improvements in the wound size, depth, and edges; necrotic tissue type and amount; exudate type and amount; colour of wound surroundings; and peripheral tissue oedema score were observed in the AVO cream group (p<0.001). The total score of wound healing showed significant improvement with both AVO (p<0.001) and phenytoin (p<0.01) creams, although AVO was more efficacious (p<0.001). Likewise, although both treatments reduced the initial VAS score, the efficacy of AVO was significantly greater (p<0.001). AVO cream significantly accelerates biological healing of chronic wounds and helps to reduce pain severity with a higher efficacy compared with phenytoin cream.

Evaluation of moxifloxacin 0.5% in treatment of nonperforated bacterial corneal ulcers: a randomized controlled trial.

PubMed

Sharma, Namrata; Goel, Manik; Bansal, Shubha; Agarwal, Prakashchand; Titiyal, Jeewan S; Upadhyaya, Ashish D; Vajpayee, Rasik B

2013-06-01

To compare the equivalence of moxifloxacin 0.5% with a combination of fortified cefazolin sodium 5% and tobramycin sulfate 1.3% eye drops in the treatment of moderate bacterial corneal ulcers. Randomized, controlled, equivalence clinical trial. Microbiologically proven cases of bacterial corneal ulcers were enrolled in the study and were allocated randomly to 1 of the 2 treatment groups. Group A was given combination therapy (fortified cefazolin sodium 5% and tobramycin sulfate) and group B was given monotherapy (moxifloxacin 0.5%). The primary outcome variable for the study was percentage of the ulcers healed at 3 months. The secondary outcome variables were best-corrected visual acuity and resolution of infiltrates. Of a total of 224 patients with bacterial keratitis, 114 patients were randomized to group A, whereas 110 patients were randomized to group B. The mean ± standard deviation ulcer size in groups A and B were 4.2 ± 2 and 4.41 ± 1.5 mm, respectively. The prevalence of coagulase-negative Staphylococcus (40.9% in group A and 48.2% in group B) was similar in both the study groups. A complete resolution of keratitis and healing of ulcers occurred in 90 patients (81.8%) in group A and 88 patients (81.4%) in group B at 3 months. The observed percentage of healing at 3 months was less than the equivalence margin of 20%. Worsening of ulcer was seen in 18.2% cases in group A and in 18.5% cases in group B. Mean time to epithelialization was similar, and there was no significant difference in the 2 groups (P = 0.065). No serious events attributable to therapy were reported. Corneal healing using 0.5% moxifloxacin monotherapy is equivalent to that of combination therapy using fortified cefazolin and tobramycin in the treatment of moderate bacterial corneal ulcers. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Wound healing and all-cause mortality in 958 wound patients treated in home care.

PubMed

Zarchi, Kian; Martinussen, Torben; Jemec, Gregor B E

2015-09-01

Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis. © 2015 by the Wound Healing Society.

Diamond burr debridement of 34 canine corneas with presumed corneal calcareous degeneration.

PubMed

Nevile, Jessica C; Hurn, Simon D; Turner, Andrew G; Morton, John

2016-07-01

To describe the signalment, presence of systemic and/or ocular comorbidities, times to detected healing and probabilities of recurrence after diamond burr debridement (DBD) of eyes with presumed corneal calcareous degeneration and secondary ulceration and/or ocular pain. Twenty-six dogs with 42 eyes affected, 34 eyes treated with DBD. A case series was conducted using medical records from a private veterinary ophthalmology referral practice. Dogs were included if they had white or gray corneal opacity consistent with corneal calcareous degeneration with either erosive or superficial ulceration and/or ocular pain in at least one eye and had at least one such eye treated with DBD. DBD was performed with a battery-operated handheld motorized burr (The Alger Company, Inc. Lago Vista, TX, USA), and a bandage contact lens was placed in the majority of eyes (30/34). Eyes were considered healed when the cornea was fluorescein negative, and there were no signs of ocular pain. Patient data (signalment, recurrence) were extracted from medical records. Dogs were first re-examined 7-62 days after treatment (median: 13 days). All DBD-treated eyes healed within 62 days (% healed: 100%; one-sided 97.5% CI: 90-100%, median: 14 days), 82% of eyes (28/34) were healed at first re-examination (median: 13 days after treatment), and all were healed by their second examination (median: 24 days). Of the 34 treated eyes, 11 were lost to follow up; 11 of the remaining 23 eyes recurred. Estimated 1-year recurrence probability was 58% (95% CI: 35-83%). Seven dogs had systemic disease; 7 had a history of prior ocular disease or intraocular surgery. Diamond burr debridement is a safe and effective treatment for rapid resolution of superficial corneal ulceration and ocular pain secondary to presumed corneal calcareous degeneration in dogs. © 2015 American College of Veterinary Ophthalmologists.

Retinoic Acid Engineered Amniotic Membrane Used as Graft or Homogenate: Positive Effects on Corneal Alkali Burns.

PubMed

Joubert, Romain; Daniel, Estelle; Bonnin, Nicolas; Comptour, Aurélie; Gross, Christelle; Belville, Corinne; Chiambaretta, Frédéric; Blanchon, Loïc; Sapin, Vincent

2017-07-01

Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment. Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified. AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins. Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.

Diabetic Foot Ulcers: The Importance of Patient Comorbidity Recognition and Total Contact Casting in Successful Wound Care.

PubMed

Jagadish, Mayuri; McNally, Michael M; Heidel, R Eric; Teffeteller, Susan; Arnold, Joshua D; Freeman, Michael; Stevens, Scott L; Grandas, Oscar H; Goldman, Mitchell H

2016-08-01

Diabetic foot ulcers (DFUs) are a major burden on the health-care system. The purpose of this study is to investigate factors affecting the healing rate of DFU in a university wound care center. Records of DFU patients treated between July 2013 and February 2015 were reviewed. Demographics, comorbidities, wound characteristics, and treatment modalities including offloading, hyperbaric oxygen treatment, total contact casting, and bioengineered skin were investigated. All patients underwent weekly debridement regardless of treatment modality. A total of 114 patients ages 18 to 98 comprised the study population. Total contact casting was the only treatment associated with increased healing (P = 0.02). Smoking (P = 0.004) and deep vein thrombosis history (P = 0.001) significantly decreased the likelihood of wound healing. Patients with past vascular event trended toward longer healing times (P = 0.07). Total contact casting in combination with weekly wound debridement showed benefit in DFU wound healing, whereas patients with a history of deep vein thrombosis and smoking were less likely to heal.

Bacterial Contribution in Chronicity of Wounds.

PubMed

Rahim, Kashif; Saleha, Shamim; Zhu, Xudong; Huo, Liang; Basit, Abdul; Franco, Octavio Luiz

2017-04-01

A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.

Comparison of Removable and Irremovable Walking Boot to Total Contact Casting in Offloading the Neuropathic Diabetic Foot Ulceration.

PubMed

Piaggesi, Alberto; Goretti, Chiara; Iacopi, Elisabetta; Clerici, Giacomo; Romagnoli, Fabio; Toscanella, Fabrizia; Vermigli, Cristiana

2016-08-01

Despite its efficacy in healing neuropathic diabetic foot ulcers (DFUs), total contact cast (TCC) is often underused because of technical limitations and poor patient acceptance. We compared TCC to irremovable and removable commercially available walking boots for DFU offloading. We prospectively studied 60 patients with DFUs, randomly assigned to 3 different offloading modalities: TCC (group A), walking boot rendered irremovable (i-RWD; group B), and removable walking boot (RWD; group C). Patients were followed up weekly for 90 days or up to complete re-epithelization; ulcer survival, healing time, and ulcer size reduction (USR) were considered for efficacy, whereas number of adverse events was considered for safety. Patients' acceptance and costs were also evaluated. Mean healing time in the 3 groups did not differ (P = .5579), and survival analysis showed no difference between the groups (logrank test P = .8270). USR from baseline to the end of follow-up was significant (P < .01) in all groups without differences between the groups. Seven patients in group A (35%), 2 in group B (10%), and 1 in group C (5%) (Fisher exact test P = .0436 group A vs group C) reported nonsevere adverse events. Patients' acceptance and costs were significantly better in group C (P < .05). Our results suggest that a walking boot was as effective and safe as TCC in offloading the neuropathic DFUs, irrespective of removability. The better acceptability and lesser costs of a removable device may actually extend the possibilities of providing adequate offloading. Level II, prospective comparative study. © The Author(s) 2016.

Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis.

PubMed

Flores, Brisas M; O'Connor, Anthony; Moss, Alan C

2017-12-01

Long-standing ulcerative colitis is an established risk factor for colorectal neoplasia. A number of observational studies have suggested that evidence of mucosal inflammation (endoscopic or histologic) is associated with a greater risk for colorectal neoplasia than is mucosal healing. Our goal was to systematically analyze the risk of colorectal neoplasia in patients with ulcerative colitis who have ongoing mucosal inflammation to better inform surveillance strategies. We performed a systematic review and meta-analysis of the effect of endoscopic and/or histologic inflammation on the risk of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. Six studies met the inclusion criteria, incorporating outcomes in 1443 patients. No study used a single validated measure for mucosal inflammation. The pooled odds ratio for colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those with histologic inflammation, when compared with those with mucosal healing. The overall quality of the studies was good. The presence of objective evidence of mucosal inflammation during follow-up in patients with ulcerative colitis is associated with a greater risk of subsequent colorectal neoplasia than in those with mucosal healing. This risk factor should be considered in guidelines on surveillance intervals for these patients. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Effects of topical hyaluronic acid on corneal wound healing in dogs: a pilot study.

PubMed

Gronkiewicz, Kristina M; Giuliano, Elizabeth A; Sharma, Ajay; Mohan, Rajiv R

2017-03-01

To investigate the efficacy of topical 0.2% hyaluronic acid in canine corneal ulcers in vivo. Six purpose-bred beagles were randomly assigned into two groups (three dogs/group): group A received experimental product (Optimend ™ , containing 0.2% hyaluronic acid, KineticVet ™ ); group B received control product (Optimend ™ without 0.2% hyaluronic acid and supplemented with carboxymethylcellulose). The clinical scorer was masked to product content and subject assignment. Under sedation and topical anesthesia, 6-mm axial corneal epithelial debridements were performed in the left eye. Wounded corneas received standard ulcer treatment and topical product (group A) or control product (group B) three times a day (TID) until ulcers were healed. Slit-lamp biomicroscopy was performed 6 h after wounding and then every 12 h; findings were graded according to modified McDonald-Shadduck scoring system; extraocular photography was performed after fluorescein stain application at all examination time points. Images were analyzed using NIH image j software to quantify rate of corneal epithelialization. Gelatin zymography was used to analyze matrix metalloproteinase (MMP) 2 and 9 protein expression in tears collected at set time points during the study period. No statistical differences in clinical ophthalmic examination scores, rate of corneal epithelialization, or MMP2 or MMP9 protein expression were found between groups at any tested time point. The application of 0.2% hyaluronic acid to standard ulcer medical management is well tolerated. Topical addition of the viscoelastic did not accelerate corneal wound healing compared to a topical control with similar viscosity in this study. © 2016 American College of Veterinary Ophthalmologists.

Argon laser photocoagulation versus intrastromal voriconazole injection in treatment of mycotic keratitis

PubMed Central

Khater, Mohammad M.; El-Shorbagy, Mohammad S.; Selima, Adel A.

2016-01-01

AIM To compare argon laser photocoagulation and intrastromal injection of voriconazole as adjunctive treatment modalities in cases of resistant mycotic corneal ulcers. METHODS Two groups each of them included 20 cases of resistant mycotic corneal ulcers. Both groups treated with local and systemic specific antimicrobial drugs guided with culture and sensitivity results. In one group argon laser photocoagulation was used as an adjunctive therapy to the specific antifungal drugs and in the other group, intrastromal injection of voriconazole was done besides the specific antifungal drugs. The 40 cases included in the study were proven according to culture and sensitivity to be 28 cases with pure fungal results and 12 cases with mixed (fungal and bacterial). In argon laser group, argon laser irradiation of the corneal ulcer was performed using argon laser 532 nm wavelength (Carl Zeiss LSL 532s AG; Meditec, Inc.) after fluorescein staining. In the other group, voriconazole solution (500 µg/mL) was prepared and injected in the corneal stroma. All cases were followed up for 3mo after healing was achieved. RESULTS Complete healing of the epithelial defect and resolution of stromal infiltration with no adverse effects were achieved in argon laser group in duration ranged from 2-4wk in 90% of cases. In voriconazole group 4 cases needed amniotic membrane graft due to thinning and 16 cases healed in duration ranged from 2-6wk (80% of cases). CONCLUSION Argon laser photocoagulation is superior to intrastromal voriconazole injection in treatment of resistant fungal corneal ulcers. PMID:26949639

Is the foot elevation the optimal position for wound healing of a diabetic foot?

PubMed

Park, D J; Han, S K; Kim, W K

2010-03-01

In managing diabetic foot ulcers, foot elevation has generally been recommended to reduce oedema and prevent other sequential problems. However, foot elevation may decrease tissue oxygenation of the foot more than the dependent position since the dependent position is known to increase blood flow within the arterial system. In addition, diabetic foot ulcers, which have peripheral vascular insufficiency, generally have less oedema than other wounds. Therefore, we argue that foot elevation may not be helpful for healing of vascularly compromised diabetic foot ulcers since adequate tissue oxygenation is an essential factor in diabetic wound healing. The purpose of this study was to evaluate the influence of foot height on tissue oxygenation and to determine the optimal foot position to accelerate wound healing of diabetic foot ulcers. This study included 122 cases (73 males and 47 females; two males had bilateral disease) of diabetic foot ulcer patients aged 40-93 years. Trans-cutaneous partial oxygen tension (TcpO(2)) values of diabetic feet were measured before and after foot elevation (n=21). Elevation was achieved by placing a foot over four cushions. We also measured foot TcpO(2) values before and after lowering the feet (n=122). Feet were lowered to the patient's tibial height, approximately 30-35 cm, beside a bed handrail. Due to the large number of lowering measurements, we divided them into five sub-groups according to initial TcpO(2.) Tissue oxygenation values were compared. Foot-elevation-lowered TcpO(2) values before and after elevation were 32.5+/-22.2 and 23.8+/-23.1 mmHg (p<0.01), respectively. Foot-lowering-augmented TcpO(2) values before and after lowering were 44.6+/-23.8 and 58.0+/-25.9 mmHg (p<0.01), respectively. The lower the initial TcpO(2) level, the more the TcpO(2) level increased. The foot lowering, rather than elevation, significantly augments TcpO(2) and may stimulate healing of diabetic foot ulcers. (c) 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Evaluation of the wound-healing activity of selected traditional medicinal plants from Perú.

PubMed

Villegas, L F; Fernández, I D; Maldonado, H; Torres, R; Zavaleta, A; Vaisberg, A J; Hammond, G B

1997-02-01

Folk medicine practitioners in Perú employ plant preparations as wound-healing agents on superficial and internal wounds (gastric ulcers). The results of a scientific evaluation of the wound-healing activity of nine plants found in the Amazon jungle near Iquitos and in the Andes mountains is presented. The species studied were: Peperomia galioides, Mentzelia cordifolia, Mutisia acuminata, Himatanthus sucuuba, Spondias mombin, Eleutherine bulbosa, Muehlenbeckia tamnifolia, Anredera diffusa and Jatropha curcas. These plants have also been examined for their toxicological properties, their effect on blood pressure, smooth muscle and capillary permeability. Significant wound-healing activity was detected in Peperomia galioides, Anredera diffusa and Jatropha curcas. Extracts from Peperomia galioides and Anredera diffusa had no effect on cell proliferation and did not exhibit mutagenic activity.

Controlled trial of Iodosorb in chronic venous ulcers.

PubMed Central

Ormiston, M C; Seymour, M T; Venn, G E; Cohen, R I; Fox, J A

1985-01-01

Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly. PMID:3926169

The pathophysiology of peptic ulcer disease.

PubMed

Brooks, F P

1985-11-01

Heterogeneity is the most important consideration in the pathophysiology of peptic ulcer disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or perforation. If they heal there is no predictable recurrence. Factors concerned with mucosal defense are relatively more important than aggressive factors such as acid and pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the muscularis mucosae) usually present with abdominal pain. Many duodenal ulcer patients report that the pain occurs when the stomach is empty or is relieved by food, and follows a pattern of relatively long periods of freedom from symptoms between recurrences. Approximately 50% of patients experience a recurrence within a year if anti-ulcer medication is stopped. In most western countries recurrent duodenal ulcer is more common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent evidence indicates genetic and familial factors in duodenal ulcer and increased acid-pepsin secretion in response to a variety of stimuli. However, it is also becoming clear that of all the abnormal functions noted, few are present in all subjects and many are clustered in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such as duodenogastric reflux and atrophic gastritis, seem to be more important than aggressive factors. Nevertheless, antisecretory medications accelerate the healing of such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric mucosal blood flow are impaired in chronic ulcer disease.

Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial

PubMed Central

Ormerod, Anthony D; Craig, Fiona E; Mitchell, Eleanor; Greenlaw, Nicola; Norrie, John; Mason, James M; Walton, Shernaz; Johnston, Graham A; Williams, Hywel C

2015-01-01

Objective To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. Design Multicentre, parallel group, observer blind, randomised controlled trial. Setting 39 UK hospitals, recruiting from June 2009 to November 2012. Participants 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). Intervention Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. Main outcome measures The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). Results Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was −0.21 (1.00) cm2/day in the ciclosporin group compared with −0.14 (0.42) cm2/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm2/day, 95% confidence interval −0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group. Conclusion Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459. PMID:26071094

Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.

PubMed

Ormerod, Anthony D; Thomas, Kim S; Craig, Fiona E; Mitchell, Eleanor; Greenlaw, Nicola; Norrie, John; Mason, James M; Walton, Shernaz; Johnston, Graham A; Williams, Hywel C

2015-06-12

To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. Multicentre, parallel group, observer blind, randomised controlled trial. 39 UK hospitals, recruiting from June 2009 to November 2012. 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was -0.21 (1.00) cm(2)/day in the ciclosporin group compared with -0.14 (0.42) cm(2)/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm(2)/day, 95% confidence interval -0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group. Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459. © Ormerod et al 2015.

Diffuse reflectance spectroscopy for monitoring diabetic foot ulcer - A pilot study

NASA Astrophysics Data System (ADS)

Anand, Suresh; Sujatha, N.; Narayanamurthy, V. B.; Seshadri, V.; Poddar, Richa

2014-02-01

Foot ulceration due to diabetes mellitus is a major problem affecting 12-25% of diabetic subjects in their lifetime. An untreated ulcer further gets infected which causes necrosis leading to amputation of lower extremities. Early identification of risk factors and treatment for these chronic wounds would reduce health care costs and improve the quality of life for people with diabetes. Recent clinical investigations have shown that a series of factors including reduced oxygen delivery and disturbed metabolism have been observed on patients with foot ulceration due to diabetes. Also, these factors can impair the wound healing process. Optical techniques based on diffuse reflectance spectroscopy provide characteristic spectral finger prints shed light on tissue oxygenation levels and morphological composition of a tissue. This study deals with the application of diffuse reflectance intensity ratios based on oxyhemoglobin bands (R542/R580), ratios of oxy- and deoxy-hemoglobin bands (R580/R555), total hemoglobin concentration and hemoglobin oxygen saturation between normal and diabetic foot ulcer sites. Preliminary results obtained are found to be promising indicating the application of reflectance spectroscopy in the assessment of foot ulcer healing.

Evaluation of the cost-effectiveness of electrical stimulation therapy for pressure ulcers in spinal cord injury.

PubMed

Mittmann, Nicole; Chan, Brian C; Craven, B Cathy; Isogai, Pierre K; Houghton, Pamela

2011-06-01

To evaluate the incremental cost-effectiveness of electrical stimulation (ES) plus standard wound care (SWC) as compared with SWC only in a spinal cord injury (SCI) population with grade III/IV pressure ulcers (PUs) from the public payer perspective. A decision analytic model was constructed for a 1-year time horizon to determine the incremental cost-effectiveness of ES plus SWC to SWC in a cohort of participants with SCI and grade III/IV PUs. Model inputs for clinical probabilities were based on published literature. Model inputs, namely clinical probabilities and direct health system and medical resources were based on a randomized controlled trial of ES plus SWC versus SWC. Costs (Can $) included outpatient (clinic, home care, health professional) and inpatient management (surgery, complications). One way and probabilistic sensitivity (1000 Monte Carlo iterations) analyses were conducted. The perspective of this analysis is from a Canadian public health system payer. Model target population was an SCI cohort with grade III/IV PUs. Not applicable. Incremental cost per PU healed. ES plus SWC were associated with better outcomes and lower costs. There was a 16.4% increase in the PUs healed and a cost savings of $224 at 1 year. ES plus SWC were thus considered a dominant economic comparator. Probabilistic sensitivity analysis resulted in economic dominance for ES plus SWC in 62%, with another 35% having incremental cost-effectiveness ratios of $50,000 or less per PU healed. The largest driver of the economic model was the percentage of PU healed with ES plus SWC. The addition of ES to SWC improved healing in grade III/IV PU and reduced costs in an SCI population. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

PubMed Central

2010-01-01

Background The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression. Methods/Design The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm2 or >10 cm2. Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process. Discussion The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes. Trial Registration ACTRN12608000599370 PMID:20214822

Ocular syphilis masquerading as bilateral peripheral ulcerative keratitis.

PubMed

Vignesh, A P; Srinivasan, R; Vijitha, Sai

2016-01-01

Ocular syphilis has varied manifestations in the eye. Peripheral ulcerative keratitis (PUK) is a crescent-shaped ulcer involving the peripheral cornea and associated with thinning. PUK is caused by both autoimmune and infectious diseases, such as rheumatoid arthritis, tuberculosis, and herpes. Here, we report a rare case of bilateral PUK caused by syphilis. A 55-year-old man presented with recurrent pain and redness in both eyes for 2 months. The cornea of both eyes had bilateral peripheral crescent-shaped ulcers suggestive of PUK. The patient was started on topical steroids elsewhere, but the lesion was not showing any signs of healing. A series of investigations were performed, with positive venereal disease research laboratory and fluorescent treponemal antibody absorption tests. The patient was then started on systemic penicillin, as well as topical steroids. The response to the treatment was good and the ulcer began to heal. PUK as the presenting feature of acquired syphilis is a rare scenario. Such infective causes should be managed with systemic antimicrobials for optimal outcomes.

A Descriptive, Retrospective Study of Using an Oblique Downward-design Gluteus Maximus Myocutaneous Flap for Reconstruction of Ischial Pressure Ulcers.

PubMed

Chou, Chang-Yi; Sun, Yu-Shan; Shih, Yu-Jen; Tzeng, Yuan-Sheng; Chang, Shun-Cheng; Dai, Niann-Tzyy; Lin, Chin-Ta

2018-03-01

Despite advances in reconstruction techniques, ischial pressure ulcers continue to present a challenge for the plastic surgeon. The purpose of this retrospective study was to evaluate outcomes of using an oblique downward gluteus maximus myocutaneous (GMM) flap for coverage of grade IV ischial ulcers. Data regarding defect size, flap size, operation time, duration of wound healing, and surgical outcome were abstracted from the medical records of patients whose ischial pressure ulcers had been reconstructed using GMM island flaps between January 2010 and December 2015. The 22 patients comprised 15 men and 7 women with a mean age of 52 (range 16-81) years. Twenty (20) had paraplegia, 6 had a recurrent ischial ulcer, 2 were bedridden following a cerebrovascular accident, 1 had a myelomeningocele status post operation, and 19 were spinal cord injury patients. Follow-up time ranged from 6 to 40 months. Pressure ulcer size ranged from 3 cm x 2 cm to 10 cm x 5 cm (average 22.3 cm2). The average flap size was 158 cm2 (15.9 cm x 9.7 cm); the largest was 286 cm2 (22 cm x 13 cm). The operating time ranged from 52 minutes to 110 minutes (average, 80 minutes). In 2 cases, wound dehiscence occurred but completely healed after resuturing. One (1) ischial pressure ulcer recurred 6 months following surgery and was successfully covered with a pedicled anterolateral thigh flap. No recurrences or problems were observed in the remaining 20 patients. Time to complete wound healing ranged from 14 to 24 days (average 17.8 days). Treatment of ischial pressure ulcers with GMM flaps allowed for an easy, simple procedure that provided the adequate thickness of soft tissue needed to cover the bony prominence, fill dead space, and cover the lesion. This technique was a reliable and safe reconstructive modality for the management of ischial pressure ulcers, even in recurrent cases.

Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

PubMed Central

Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

2015-01-01

Background Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. Conclusion PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and pharmacological targeting of endothelial dysfunction may represent a promising tool for the treatment of delayed wound healing or chronic ulcers. PMID:26473356

Diabetic foot ulcers. Pathophysiology, assessment, and therapy.

PubMed Central

Bowering, C. K.

2001-01-01

OBJECTIVE: To review underlying causes of diabetic foot ulceration, provide a practical assessment of patients at risk, and outline an evidence-based approach to therapy for diabetic patients with foot ulcers. QUALITY OF EVIDENCE: A MEDLINE search was conducted for the period from 1979 to 1999 for articles relating to diabetic foot ulcers. Most studies found were case series or small controlled trials. MAIN MESSAGE: Foot ulcers in diabetic patients are common and frequently lead to lower limb amputation unless a prompt, rational, multidisciplinary approach to therapy is taken. Factors that affect development and healing of diabetic patients' foot ulcers include the degree of metabolic control, the presence of ischemia or infection, and continuing trauma to feet from excessive plantar pressure or poorly fitting shoes. Appropriate wound care for diabetic patients addresses these issues and provides optimal local ulcer therapy with débridement of necrotic tissue and provision of a moist wound-healing environment. Therapies that have no known therapeutic value, such as foot soaking and topical antiseptics, can actually be harmful and should be avoided. CONCLUSION: Family physicians are often primary medical contacts for patients with diabetes. Patients should be screened regularly for diabetic foot complications, and preventive measures should be initiated for those at risk of ulceration. PMID:11398715

Pseudomonas oryzihabitans cutaneous ulceration from Octopus vulgaris bite: a case report and review of the literature.

PubMed

Aigner, Birgit Angela; Ollert, Markus; Seifert, Florian; Ring, Johannes; Plötz, Sabine Gisela

2011-08-01

Octopus vulgaris is a common marine animal that can be found in nearly all tropical and semitropical waters around the world. It is a peaceful sea dweller with a parrotlike beak, and its primary defense is to hide through camouflaging adjustments. Bites from animals of the class Cephalopoda are very rare. We describe a boy who was bitten on his forearm by an Octopus vulgaris. A 9 -year-old boy was bitten by an Octopus vulgaris while snorkeling. There was no strong bleeding or systemic symptoms; however, 2 days later, a cherry-sized, black, ulcerous lesion developed, surrounded by a red circle that did not heal over months and therefore had to be excised. Histologic examination showed ulceration with extensive necrosis of the dermis and the epidermis. A microbial smear revealed Pseudomonas (formerly known as Flavimonas) oryzihabitans. After excision, the wound healed within 2 weeks, without any complications or signs of infection. To the best of our knowledge, this case represents the first report of an Octopus vulgaris bite resulting in an ulcerative lesion with slow wound healing owing to P oryzihabitans infection. We recommend greater vigilance regarding bacterial contamination when treating skin lesions caused by marine animals.

Leg-ulcer care in the community, before and after implementation of an evidence-based service

PubMed Central

Harrison, Margaret B.; Graham, Ian D.; Lorimer, Karen; Friedberg, Elaine; Pierscianowski, Tadeusz; Brandys, Tim

2005-01-01

Background Leg ulcers usually occur in older patients, a growing population for which increasing health care resources are required. Treatment is mainly provided in patients' homes; however, patients often receive poorly integrated services in multiple settings. We report the results of a prospective study of a community-based care strategy for leg ulcers. Methods International practice recommendations and guidelines were adapted to make a new clinical protocol. The new model, for a dedicated service staffed by specially trained registered nurses, established initial and ongoing assessment time frames and provided enhanced linkages to medical specialists. Data were collected for 1 year before and after implementation; outcome measures included 3-month healing rates, quality of life and resource usage. Results Three-month healing rates more than doubled between the year before implementation (23% [18/78]) and the year afterward (56% [100/180]). The number of nursing visits per case declined, from a median of 37 to 25 (p = 0.041); the median supply cost per case was reduced from $1923 to $406 (p = 0.005). Interpretation Reorganization of care for people with leg ulcers was associated with improved healing and a more efficient use of nursing visits. PMID:15911859

Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds.

PubMed

Wilcox, James R; Carter, Marissa J; Covington, Scott

2013-09-01

Chronic wounds usually get trapped in the inflammatory stage of wound healing; however, aggressive debridement transforms chronic wounds to acute wounds and therefore complete healing. To investigate healing outcomes and debridement frequency in a large wound data set. Retrospective cohort study. Data collected from 525 wound care centers from June 1, 2008, through June 31, 2012, using a web-based clinical management system. Referred sample of 154 644 patients with 312 744 wounds of all causes (of an initial data set of 364 534 wounds) participated. A total of 47.1% were male. Median age was 69 years (age range, 19-112 years), with 59.2% having one wound. Eligibility criteria included age older than 18 years, receiving at least 1 debridement, and having been discharged from the system. Advanced therapeutic treatment was ineligible. Because of incomplete, questionable, or ineligible data, 57 190 wounds were not included. Most wounds were diabetic foot ulcers (19.0%), venous leg ulcers (26.1%), and pressure ulcers (16.2%). Debridement (removal of necrotic tissue and foreign bodies from the wound) at different frequencies. Wound healing (completely epithelialized with dimensions at 0 × 0 × 0 cm). A total of 70.8% of wounds healed. The median number of debridements was 2 (range, 1-138). Frequent debridement healed more wounds in a shorter time (P <  .001). In regression analysis, significant variables included male sex, physician category, wound type, increased patient age, and increased wound age, area, and depth. The odds ratio varied considerably for each variable. The more frequent the debridements, the better the healing outcome. Although limited by retrospective data, this study's strength was the analysis of the largest wound data set to date.

Vedolizumab Induces Long-term Mucosal Healing in Patients With Crohn's Disease and Ulcerative Colitis.

PubMed

Noman, Maja; Ferrante, Marc; Bisschops, Raf; De Hertogh, Gert; Van den Broeck, Karolien; Rans, Karen; Rutgeerts, Paul; Vermeire, Séverine; Van Assche, Gert

2017-09-01

Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia. Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia. Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

20 kHz ultrasound assisted treatment of chronic wounds with concurrent optic monitoring

NASA Astrophysics Data System (ADS)

Bawiec, Christopher R.; Sunny, Youhan; Diaz, David; Nadkarni, Sumati; Weingarten, Michael S.; Neidrauer, Michael; Margolis, David J.; Zubkov, Leonid; Lewin, Peter A.

2015-05-01

This paper describes a novel, wearable, battery powered ultrasound applicator that was evaluated as a therapeutic tool for healing of chronic wounds, such as venous ulcers. The low frequency and low intensity (~100mW/cm2) applicator works by generating ultrasound waves with peak-to-peak pressure amplitudes of 55 kPa at 20 kHz. The device was used in a pilot human study (n=25) concurrently with remote optical (diffuse correlation spectroscopy - DCS) monitoring to assess the healing outcome. More specifically, the ulcers' healing status was determined by measuring tissue oxygenation and blood flow in the capillary network. This procedure facilitated an early prognosis of the treatment outcome and - once verified - may eventually enable customization of wound management. The outcome of the study shows that the healing patients of the ultrasound treated group had a statistically improved (p<0.05) average rate of wound healing (20.6%/week) compared to the control group (5.3%/week). In addition, the calculated blood flow index (BFI) decreased more rapidly in wounds that decreased in size, indicating a correlation between BFI and wound healing prediction. Overall, the results presented support the notion that active low frequency ultrasound treatment of chronic venous ulcers accelerates healing when combined with the current standard clinical care. The ultrasound applicator described here provides a user-friendly, fully wearable system that has the potential for becoming the first device suitable for treatment of chronic wounds in patient's homes, which - in turn - would increase patients' compliance and improve quality of life.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis.

PubMed

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-05-21

To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.

Literature review on the management of diabetic foot ulcer

PubMed Central

Yazdanpanah, Leila; Nasiri, Morteza; Adarvishi, Sara

2015-01-01

Diabetic foot ulcer (DFU) is the most costly and devastating complication of diabetes mellitus, which affect 15% of diabetic patients during their lifetime. Based on National Institute for Health and Clinical Excellence strategies, early effective management of DFU can reduce the severity of complications such as preventable amputations and possible mortality, and also can improve overall quality of life. The management of DFU should be optimized by using a multidisciplinary team, due to a holistic approach to wound management is required. Based on studies, blood sugar control, wound debridement, advanced dressings and offloading modalities should always be a part of DFU management. Furthermore, surgery to heal chronic ulcer and prevent recurrence should be considered as an essential component of management in some cases. Also, hyperbaric oxygen therapy, electrical stimulation, negative pressure wound therapy, bio-engineered skin and growth factors could be used as adjunct therapies for rapid healing of DFU. So, it’s suggested that with appropriate patient education encourages them to regular foot care in order to prevent DFU and its complications. PMID:25685277

An evaluation of the efficacy of a topical gel with Triester Glycerol Oxide (TGO) in the treatment of minor recurrent aphthous stomatitis in a Turkish cohort: A randomized, double-blind, placebo-controlled clinical trial

PubMed Central

Ergun, Sertan; Warnakulasuriya, Saman; Namdar-Pekiner, Filiz; Tanyeri, Hakkı

2017-01-01

Background Triester glycerol oxide gel (Protefix® Queisser Pharma, Germany) is a new topical agent that has the property of adherence to the oral mucosa by forming a lipid film which protects against mechanical trauma and may help to reduce oral tissue moisture loss and inflammation. The aim of this clinical trial was to determine the efficacy of a topical TGO gel and to also compare it with triamcinolone acetonide pomade in the treatment of minor recurrent aphthous stomatitis. Material and Methods This study was a randomized, double-blind, placebo-controlled clinical trial and 180 patients with the complaint of minor aphthous ulcers were enrolled in this study. The sociodemographic data and clinical characteristics of the ulcer were collected by questionnaire. Ulcer size and pain level measurements were performed and the efficacy indices for ulcer pain and size were calculated at day 0,2,4,6 by the same investigator. Results Significant differences were not detected among the demographics and ulcer histories including age, gender, onset of ulcer, mean healing time, family RAS history and ulcer localization between three groups. The pain score in TGO group was found statistically lower at day 2,4, and 6. Efficacy index and improvement rate of TGO group, regarding pain score, was higher than the other two groups at day 2 and 4. The reduction in ulcer size was statistically higher in TGO group than the other two groups at day 4 and 6. Conclusions Topical application of TGO gel could decrease pain intensity, accelerate ulcer healing without any side effects, utilizing an easy appliable and accessible procedure. Therefore TGO gel could be a well-tolerated, safe, topical therapeutic agent in the clinical practice of RAS treatment. Key words:Topical therapy, triester glycerol oxide, triamcinolone acetonide, minor recurrent aphthous stomatitis. PMID:28160585

The influence of different sub-bandage pressure values on venous leg ulcers healing when treated with compression therapy.

PubMed

Milic, Dragan J; Zivic, Sasa S; Bogdanovic, Dragan C; Jovanovic, Milan M; Jankovic, Radmilo J; Milosevic, Zoran D; Stamenkovic, Dragan M; Trenkic, Marija S

2010-03-01

Venous leg ulcers (VLU) have a huge social and economic impact. An estimated 1.5% of European adults will suffer a venous ulcer at some point in their lives. Despite the widespread use of bandaging with high pressure in the treatment of this condition, recurrence rates range between 25% to 70%. Numerous studies have suggested that the compression system should provide sub-bandage pressure values in the range from 35 mm Hg to 45 mm Hg in order to achieve the best possible healing results. An open, randomized, prospective, single-center study was performed in order to determine the healing rates of VLU when treated with different compression systems and different sub-bandage pressure values. One hundred thirty-one patients (72 women, 59 men; mean age, 59-years-old) with VLU (ulcer surface >3 cm(2); duration >3 months) were randomized into three groups: group A - 42 patients who were treated using an open-toed, elastic, class III compression device knitted in tubular form (Tubulcus, Laboratoires Innothera, Arcueil, France); group B - 46 patients treated with the multi-component bandaging system comprised of Tubulcus and one elastic bandage (15 cm wide and 5 cm long with 200% stretch, Niva, Novi Sad, Serbia); and group C - forty-three patients treated with the multi-component bandaging system comprised of Tubulcus and two elastic bandages. Pressure measurements were taken with the Kikuhime device (TT MediTrade, Soro, Denmark) at the B1 measuring point in the supine, sitting, and standing positions under the three different compression systems. The median resting values in the supine and standing positions in examined study groups were as follows: group A - 36.2 mm Hg and 43.9 mm Hg; group B - 53.9 mm Hg and 68.2 mm Hg; group C - 74.0 mm Hg and 87.4 mm Hg. The healing rate during the 26-week treatment period was 25% (13/42) in group A, 67.4% (31/46) in group B, and 74.4% (32/43) in group C. The success of compression treatment in group A was strongly associated with the small ulcer surface (<5 cm(2)) and smaller calf circumference (CC; <38 cm). On the other hand, compliance in group A was good. In groups B and C, compliance was poor in patients with small CC, but the healing rate was high, especially in patients with large ulcers and a large CC (>43 cm). The results obtained in this study indicate that better healing results are achieved with two or multi-component compression systems than with single-component compression systems and that a compression system should be individually determined for each patient according to individual characteristics of the leg and CC. Target sub-bandage pressure value (B1 measuring point in the sitting position) of the compression system needed for the ulcer healing could be determined according to a simple formula, CC + CC/2.

Biophysical effects of repetitive removal of adhesive dressings on peri-ulcer skin.

PubMed

Zillmer, R; Agren, M S; Gottrup, F; Karlsmark, T

2006-05-01

To study the effect of repeated removal of four different adhesive dressings on peri-ulcer skin using quantitative non-invasive techniques. Forty-five patients with open (n = 29) or healed (n = 16) venous leg ulcers were included. Peri-ulcer skin was treated for 14 days with patches of two different hydrocolloid-based adhesive dressings, one polyurethane adhesive and one soft silicone adhesive dressing. Normal skin of the patients' ventral forearm was also treated identically. Adhesive patches of the dressings were replaced every second day. The skin barrier function was assessed by measuring transepidermal water loss and stratum corneum hydration by measuring electrical conductance. Thirty-nine patients completed the study. The hydrocolloid adhesives increased transepidermal water loss and conductance while the polyurethane and soft silicone adhesives did not influence these parameters significantly compared with adjacent non-treated peri-ulcer skin. For normal forearm skin, similar relative effects among the four adhesives were found. Repetitive treatment with hydrocolloid-based adhesive dressings induced major functional alterations of the stratum corneum. In contrast, a polyurethane adhesive and a soft silicone adhesive dressing did not alter transepidermal water loss or conductance of peri-ulcer skin.

In search of optimal compression therapy for venous leg ulcers: a meta-analysis of studies comparing diverse [corrected] bandages with specifically designed stockings.

PubMed

Amsler, Felix; Willenberg, Torsten; Blättler, Werner

2009-09-01

In search of an optimal compression therapy for venous leg ulcers, a systematic review and meta-analysis was performed of randomized controlled trials (RCT) comparing compression systems based on stockings (MCS) with divers bandages. RCT were retrieved from six sources and reviewed independently. The primary endpoint, completion of healing within a defined time frame, and the secondary endpoints, time to healing, and pain were entered into a meta-analysis using the tools of the Cochrane Collaboration. Additional subjective endpoints were summarized. Eight RCT (published 1985-2008) fulfilled the predefined criteria. Data presentation was adequate and showed moderate heterogeneity. The studies included 692 patients (21-178/study, mean age 61 years, 56% women). Analyzed were 688 ulcerated legs, present for 1 week to 9 years, sizing 1 to 210 cm(2). The observation period ranged from 12 to 78 weeks. Patient and ulcer characteristics were evenly distributed in three studies, favored the stocking groups in four, and the bandage group in one. Data on the pressure exerted by stockings and bandages were reported in seven and two studies, amounting to 31-56 and 27-49 mm Hg, respectively. The proportion of ulcers healed was greater with stockings than with bandages (62.7% vs 46.6%; P < .00001). The average time to healing (seven studies, 535 patients) was 3 weeks shorter with stockings (P = .0002). In no study performed bandages better than MCS. Pain was assessed in three studies (219 patients) revealing an important advantage of stockings (P < .0001). Other subjective parameters and issues of nursing revealed an advantage of MCS as well. Leg compression with stockings is clearly better than compression with bandages, has a positive impact on pain, and is easier to use.

TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats

PubMed Central

OLIVEIRA, Bruna Vasconcelos; BARROS SILVA, Paulo Goberlânio; NOJOSA, Jacqueline de Santiago; BRIZENO, Luiz André Cavalcante; FERREIRA, Jamile Magalhães; SOUSA, Fabrício Bitú; MOTA, Mário Rogério Lima; ALVES, Ana Paula Negreiros Nunes

2016-01-01

ABSTRACT Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). Conclusions Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression. PMID:27383710

GM-CSF produced by non-hematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa1,2

PubMed Central

Egea, Laia; McAllister, Christopher S.; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F.

2012-01-01

GM-CSF is a growth factor that promotes the survival and activation of macrophages and granulocytes, and dendritic cell (DC) differentiation and survival in vitro. The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn’s disease in humans and colitis in murine models has been considered mainly to reflect its activity on myeloid cells. We used GM-CSF deficient (GM-CSF−/−) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS) at doses that resulted in little epithelial damage and mucosal ulceration in wild type (WT) mice resulted in marked colon ulceration and delayed ulcer healing in GM-CSF−/− mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF−/− mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF−/− mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Non-hematopoietic cells and not myeloid cells produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury as revealed by bone marrow chimera and DC depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell produced GM-CSF has a novel non-redundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium. PMID:23325885

Healing process of venous ulcers: the role of microcirculation.

PubMed

Ambrózy, Ewald; Waczulíková, Iveta; Willfort, Andrea; Böhler, Kornelia; Cauza, Karla; Ehringer, Herbert; Heinz, Gottfried; Koppensteiner, Renate; Marić, Snezana; Gschwandtner, Michael E

2013-02-01

In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low. © 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice.

PubMed

El-Batal, Ahmed Ibrahim; Ahmed, Salwa Farid

2018-02-05

Radiation combined injury, a life-threatening condition, has higher mortality than simple radiation injury. The aim of the present study was to analyze the efficiency of Aloe vera and silver nanoparticles in improving the healing of ulcerated oral mucosa after irradiation. Thirty male Albino mice were divided into five groups: control, radiation, Aloe vera (AV), silver nanoparticles (NS), and AV+NS. The mice were exposed to whole body 6Gy gamma-radiation. After one hour, 20% acetic acid was injected into the submucosal layer of the lower lip for ulcer induction. The animals received topical treatment with the assigned substances for 5 days. Lip specimens were subjected to hematoxylin and eosin and anti alpha-smooth muscle actin immunohistochemical staining. Results demonstrated occurance of ulcer three days post irradiation in all groups except in the AV+NS group where only epithelial detachment was developed. After seven days, data revealed persistent ulcer in radiation group, and almost normal epithelium in the AV+NS group. A significant reduction of epithelial thickness was detected in all groups at the third day as compared to control. At the seventh day, only the AV+NS group restored the epithelial thickness. Area percent of alpha-smooth muscle actin expression was significantly decreased in radiation group at the third day followed by significant increase at the seventh day. However, all treatment groups showed significant increase in alpha-smooth muscle actin at the third day, which decreased to normal level at the seventh day. Our study demonstrated the efficiency of Aloe vera and silver nanoparticles in enhancing ulcer healing after irradiation.

Randomized controlled trial comparing treatment outcome of two compression bandaging systems and standard care without compression in patients with venous leg ulcers.

PubMed

Wong, I K Y; Andriessen, A; Charles, H E; Thompson, D; Lee, D T F; So, W K W; Abel, M

2012-01-01

In Hong Kong, at the time of the study, compression treatment was not considered usual care for venous leg ulcer patients. This randomized controlled trial compared quality of life (QOL) aspects in venous leg ulcer patients of over 55-years of age, of short-stretch compression (SSB), four-layer compression bandaging (4LB) and usual care (UC) (moist wound healing dressing, no compression). Study period was 24-weeks, the primary outcome was the patient functional status, disease-specific and generic health-related QOL measures and ulcer healing rates, comparing week 1 vs. week 24 (end) results. Assessments included photogrammetry, Brief Pain Inventory, SF-12 Health Survey, Charing Cross Venous Ulcer Questionnaire and Frenchay Activity Index. Data analysis was performed using, where appropriate; Kaplan Meier and log rank chi-square and the repeated measures analysis of variance test. A total of 321 patients participated in the study, 45 (14%) withdrew for various reasons. Compression bandaging in both groups significantly reduced pain (P < 0.0001) and improved functional status and QOL. Healing rate at 24 weeks for both compression groups was significant (P < 0.001); for SSB this was 72.0% (77/107) vs. 67.3% in the 4LB group (72/107) and 29.0% (31/107) with usual care. The reduction in ulcer area from weeks 12 to 24 was significant only for SSB (P < 0.047). Compression was shown to be feasible for elderly community care patients in Hong Kong and is currently implemented as part of standard venous leg ulcer treatment. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Micro-lightguide spectrophotometry (O2C®) as a predictor of intermediate outcome in patients with critical limb ischemia after percutaneous transluminal angioplasty (PTA).

PubMed

Weber, K; Gebauer, K; Lüders, F; Meyborg, M; Malyar, N; Goerge, T; Reinecke, H

2014-12-01

Micro-lightguide spectrophotometry (O2C®) provides easily and rapidly measurable parameters of tissue microcirculation. The aim of this study was to assess whether micro-lightguide spectrophotometer (O2C®) based parameters of the tissue microcirculation can serve as predictors of ulcer healing. Furthermore, we tried to identify cut off values to forecast patient outcome and check other diagnostic meanings of individual O2C-parameters. Forty individuals, all suffering from critical limb ischemia and arterial or arteriovenous ulcers were retrospectively investigated concerning O2C®- and ankle/toe brachial index-measurements before and up to two times after percutaneous transluminal angioplasty (PTA). At a median follow-up of 7 (range 3 to 14) months after PTA the current peripheral arterial disease (PAD) status, ulcer healing, adverse cardiovascular events including death and endovascular or surgical treatments were noted. We found in patients with healing wounds a significant increase in oxygen saturation (SO2, median 26.35±26.94%) compared to non-healers (-4.27±25.24%, P=0.006) as well as regarding blood flow (median 41.12±51.23AU vs. -9.46±24.01 AU, P=0.005). Additionally, the parameter rHb separated reliably between arterial and arteriovenous ulcers (P=0.024). In Cox regression models, increases after revascularisation of more than 6 % in SO2 (HRR=6.08, 95%CI 1.56-23.65, P=0.009) and flow decreases of less than 12 AU (HRR 4.95, 95%CI 1.42-17.31, P=0.012) were significantly associated with amputation-free survival. The O2C®-parameters SO2 and flow provide prognostic information for ulcer healing as well as for amputation-free survival, and rHB adds information about a possible arterial or arteriovenous genesis of an ulcer.

Evaluation of treatment with carboxymethylcellulose on chronic venous ulcers*

PubMed Central

Januário, Virginia; de Ávila, Dione Augusto; Penetra, Maria Alice; Sampaio, Ana Luisa Bittencourt; Noronha Neta, Maria Isabel; Cassia, Flavia de Freire; Carneiro, Sueli

2016-01-01

BACKGROUND: Among the chronic leg ulcers, venous ulcers are the most common and constitute a major burden to public health. Despite all technology available, some patients do not respond to established treatments. In our study, carboxymethylcellulose was tested in the treatment of refractory chronic venous ulcers. OBJECTIVE: To evaluate the efficacy of carboxymethylcellulose 20% on the healing of chronic venous ulcers refractory to conventional treatments. METHODS: This is an analytical, pre-experimental study. Thirty patients were included with refractory venous ulcers, and applied dressings with carboxymethylcellulose 20% for 20 weeks. The analysis was based on measurement of the area of ulcers, performed at the first visit and after the end of the treatment. RESULTS: There was a reduction of 3.9 cm2 of lesion area (p=0.0001), corresponding to 38.8% (p=0.0001). There was no interruption of treatment and no increase in lesion area in any patient. CONCLUSIONS: Carboxymethylcellulose 20% represents a low cost and effective therapeutic alternative for the treatment of refractory chronic venous ulcers. However, controlled studies are necessary to prove its efficacy. PMID:26982773

Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study

PubMed Central

Hachulla, Eric; Hatron, Pierre-Yves; Carpentier, Patrick; Agard, Christian; Chatelus, Emmanuel; Jego, Patrick; Mouthon, Luc; Queyrel, Viviane; Fauchais, Anne-Laure; Michon-Pasturel, Ulrique; Jaussaud, Roland; Mathian, Alexis; Granel, Brigitte; Diot, Elisabeth; Farge-Bancel, Dominique; Mekinian, Arsène; Avouac, Jérôme; Desmurs-Clavel, Hélène; Clerson, Pierre

2016-01-01

Objective To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). Methods Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05). Results Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12). Conclusions The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit. Trial registration number NCT01295736. PMID:25995322

[Drug-induced oral ulcerations].

PubMed

Madinier, I; Berry, N; Chichmanian, R M

2000-06-01

Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers.

PubMed

Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

2013-10-01

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32.0% ± 47.3% versus 97.1% ± 7.0% (P < 0.001) after 4 weeks, whereas at 6 weeks wounds were reduced by -1.8% ± 70.3% versus 98.4% ± 5.8% (P < 0.001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0.001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Promote pressure ulcer healing in individuals with spinal cord injury using an individualized cyclic pressure-relief protocol.

PubMed

Makhsous, Mohsen; Lin, Fang; Knaus, Evan; Zeigler, Mary; Rowles, Diane M; Gittler, Michelle; Bankard, James; Chen, David

2009-11-01

To evaluate whether an individualized cyclic pressure-relief protocol accelerates wound healing in wheelchair users with established pressure ulcers (PrUs). Randomized controlled study. Spinal cord injury clinics. Forty-four subjects, aged 18-79 years, with a Stage II or Stage III PrU, were randomly assigned to the control (n = 22) or treatment (n = 22) groups. Subjects in the treatment group used wheelchairs equipped with an individually adjusted automated seat that provided cyclic pressure relief, and those in the control group used a standard wheelchair. All subjects sat in wheelchairs for a minimum of 4 hours per day for 30 days during their PrU treatment. Wound characteristics were assessed using the Pressure Ulcer Scale for Healing (PUSH) tool and wound dimensions recorded with digital photographs twice a week. Median healing time for a 30% healing relative to initial measurements, the percentage reduction in wound area, and the percentage improvement in PUSH score achieved at the end of the trial were compared between groups. At the end of 30 days, both groups demonstrated a general trend of healing. However, the treatment group was found to take significantly less time to achieve 30% healing for the wound measurement compared with the control group. The percentage improvement of the wound area and PUSH scores were greater in using cyclic seating (45.0 +/- 21.0, P < .003; 29.9 +/- 24. 6, P < .003) compared with standard seating (10.2 +/- 34.9, 5.8 +/- 9.2). The authors' findings show that cyclically relieving pressure in the area of a wound for seated individuals can greatly aid wound healing. The current study provides evidence that the individualized cyclic pressure-relief protocol helps promote pressure wound healing in a clinical setting. The authors concluded that the individualized cyclic pressure relief may have substantial benefits in accelerating the healing process in wheelchair users with existing PrUs, while maintaining the mobility of individuals with SCI during the PrU treatment.

Pathophysiology of wound healing and alterations in venous leg ulcers-review.

PubMed

Raffetto, Joseph D

2016-03-01

Venous leg ulcer (VLU) is one of the most common lower extremity ulcerated wound, and is a significant healthcare problem with implications that affect social, economic, and the well-being of a patient. VLU can have debilitating related problems which require weekly medical care and may take months to years to heal. The pathophysiology of VLU is complex, and healing is delayed in many patients due to a persistent inflammatory condition. Patient genetic and environmental factors predispose individuals to chronic venous diseases including VLU. Changes in shear stress affecting the glycocalyx are likely initiating events, leading to activation of adhesion molecules on endothelial cells, and leukocyte activation with attachment and migration into vein wall, microcirculation, and in the interstitial space. Multiple chemokines, cytokines, growth factors, proteases and matrix metalloproteinases are produced. The pathology of VLU involves an imbalance of inflammation, inflammatory modulators, oxidative stress, and proteinase activity. Understanding the cellular and biochemical events that lead to the progression of VLU is critical. With further understanding of inflammatory pathways and potential mechanisms, certain biomarkers could be revealed and studied as both involvement in the pathophysiology of VLU but also as therapeutic targets for VLU healing. © The Author(s) 2016.

High-Frequency Generator in Wound Healing of Marjolin's Ulcer After Carcinoma Resection.

PubMed

Tacani, Pascale Mutti; Tacani, Rogério Eduardo; Machado, Aline Fernanda Perez; Montezello, Débora; Góes, João Carlos Guedes Sampaio; Marx, Angela Gonçalves; Liebano, Richard Eloin

2018-05-01

Marjolin's ulcers (MU) are skin malignancies that form over burn injuries. These very aggressive ulcers can result in functional and wound healing impairment, and require a well thought out treatment plan. Physiotherapy offers resources to help promote recovery of these patients, as described in this case report, in which the patient with a history of burn in the lower limbs evolved to malignancy 32 years later. This patient underwent tumor resection of the left foot, with recurrence and lymphadenectomy . Physical therapy included the application of high-frequency generator (HFG) for wound healing and exercises for functional recovery. The treatment lasted for many months and resulted in the improvement of the surgical wound areas, pain, swelling, sensitivity, strength muscle, and gait. It was observed that the use of HFG can be a tool in the tissue repair of surgical wound after the resection of MU; however, further studies need to be carried out to suit parameters and ensure safety of cancer patients.

Gastroduodenal ulceration in foals.

PubMed

Becht, J L; Byars, T D

1986-07-01

Gastroduodenal ulceration is becoming recognised as an important disease in foals during the first few months of life. Aetiopathogenesis is presumed to be similar to peptic disease in humans associated with back diffusion of hydrogen ions into the mucosa. Many factors have been incriminated as predisposing foals to ulceration but few have been proven. To date, use of non-steroidal anti-inflammatory agents has been the only documented cause of gastroduodenal ulceration in foals. The clustering of affected foals on certain farms suggests an infectious aetiology but attempts to identify a causative organism have been unsuccessful. Four clinical syndromes defined for foals with gastroduodenal ulceration include: silent ulcers, which occur most often in the non-glandular stomach along the margo plicatus and are identified as incidental findings at necropsy; active ulcers which are often manifested by abdominal pain, excessive salivation and bruxism; perforating ulcers which usually result in a severe, diffuse peritonitis; and pyloric or duodenal obstruction from a healing ulcer. General approaches to therapy of a foal with active ulceration consist of reduction of gastric acidity and enhancement of mucosal protection. Antacids and type 2 histamine receptor antagonists are used most often to neutralise or decrease acid secretion, respectively. Sucralfate, a locally active sulphated sucrose preparation, is commonly used as a cytoprotective agent. The efficacy and safety of many products used have not been evaluated adequately in foals. Perforating ulcers are usually associated with death or humane destruction of the foal because of fulminating peritonitis. Surgical intervention and bypass procedures are indicated in foals that develop pyloric or duodenal obstructions from healing ulcers.

Rebamipide solution: a novel submucosal injection material to promote healing speed and healing quality of ulcers induced by endoscopic submucosal dissection.

PubMed

Fujimoto, Ai; Uraoka, Toshio; Nishizawa, Toshihiro; Shimoda, Masayuki; Goto, Osamu; Ochiai, Yasutoshi; Maehata, Tadateru; Akimoto, Teppei; Mitsunaga, Yutaka; Sasaki, Motoki; Yamamoto, Hiroyuki; Yahagi, Naohisa

2018-04-01

Rebamipide is administered perorally to protect the gastric mucosa. We assessed the efficacy and safety of a novel rebamipide solution as a submucosal injection material for endoscopic submucosal dissection (ESD) using an in vivo porcine model. An endoscopist blinded to the test agents performed ESDs of hypothetical 30 mm lesions using a 2% rebamipide solution at 2 sites (rebamipide group) and a saline solution at 2 other sites (control group) in the stomachs of 8 pigs. The technical outcomes were compared between the 2 groups. The gastric ulcer stages were evaluated by endoscopy once weekly for 4 weeks after the ESD to determine the healing score (1-6). The pigs were killed at 1 week (n = 2), 2 weeks (n = 2), and 4 weeks (n = 4) after the ESD for pathologic evaluation of ESD-induced ulcers and scarring. There were no significant differences in any of the technical outcomes between the 2 groups, and no adverse events related to the ESD in any of the animals. The healing score was significantly higher in the rebamipide group than in the control group at 2 weeks (P = .027), 3 weeks (P = .034), and 4 weeks (P = .012). In the histopathologic assessment, fibrosis was significantly less extensive in the rebamipide group than in the control group at 2 weeks (P = .02) and 4 weeks (P = .04). The rebamipide solution appeared to promote both the speed and quality of healing of ESD-induced ulcers by suppressing fibrosis. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Antiseptic with modern wound dressings in the treatment of venous leg ulcers: clinical and microbiological aspects.

PubMed

Sopata, M; Kucharzewski, M; Tomaszewska, E

2016-08-01

To assess the impact of a two-period treatment on the clinical condition, bacteriological changes and results of treatment of venous leg ulcers (VLU) using octenidine dihydrochloride. Patients with a VLU were recruited and treated with octenidine dihydrochloride for one month, after which they were randomised and treated with hydrocolloids or foam dressings. The wounds were clinically assessed for the amount of necrotic tissue, granulation tissue, epithelialisation, amount of exudate and pain level. During the first period, bacterial colonisation and antimicrobial efficacy of octenidine dihydrochloride were also evaluated. In the second period the efficacy of treatment, time of treatment and healing rate were investigated. In the group of 50 VLU patients, all wounds (100%) improved after the first treatment period. No clinical signs of infection were observed. Statistically significant changes were observed in all the clinical parameters studied in the treated groups of VLU patients, including reduction of necrotic tissue, the amount of exudate and of pain, as well as increased granulation and epithelialisation. In the second period including treatment with the two dressings, no differences were observed in treatment efficacy, time of treatment or healing rate. As used in this study, octenidine dihydrochloride proved to be effective and useful, changing the clinical condition of VLU, preparing the wound for future treatment with modern dressings. High microbicidal activity of octenidine was observed, both against Gram-negative and Gram-positive bacteria isolated from the ulcers. Octenidine dihydrochloride caused an eradication of multiresistant strains (88%) as well as of bacteria qualified as alert-pathogens (100%) in the treated wounds after four weeks. However, no differences in the effects, time or rate of healing of VLU with two dressings were found in the second period. No side effects or significant local intolerance reactions used for treatment were observed.

Topical oxygen therapy results in complete wound healing in diabetic foot ulcers.

PubMed

Yu, Janelle; Lu, Suzanne; McLaren, Ann-Marie; Perry, Julie A; Cross, Karen M

2016-11-01

Diabetic foot ulcers (DFUs) are a significant problem in an aging population. Fifteen percent of diabetics develop a DFU over their lifetime, which can lead to potential amputation. The 5-year survival rate after amputation is 31%, which is greater than the lifetime risk of mortality from cancer. Topical oxygen is a promising technique for the adjunctive therapy of chronic wounds including DFUs, but few controlled studies exist to support its clinical adoption. The aim of this study was to compare a portable topical oxygen delivery system in patients with nonhealing DFUs to standard best practice. Twenty patients were randomized into a topical oxygen group (n = 10), and a nonplacebo control group with regular dressings and standard care (n = 10), and attended the diabetic foot clinic once weekly for 8 weeks. Ulcer surface area over time was analyzed using standardized digital imaging software. DFUs were present without healing for a mean duration of 76 weeks prior to the study. They found a significant difference in healing rate between patients receiving topical oxygen and those receiving standard care. Topical oxygen, therefore, represents a potentially exciting new technology to shorten healing time in patients with nonhealing DFUs. More prospective randomized and powered studies are needed to determine the benefits of topical oxygen, but our current results are very promising. © 2016 by the Wound Healing Society.

Diabetic complications do not hamper improvement of health-related quality of life over the course of treatment of diabetic foot ulcers - the Eurodiale study.

PubMed

Siersma, Volkert; Thorsen, Hanne; Holstein, Per E; Kars, Marleen; Apelqvist, Jan; Jude, Edward B; Piaggesi, Alberto; Bakker, Karel; Edmonds, Michael; Jirkovská, Alexandra; Mauricio, Didac; Reike, Heinrich; Spraul, Maximilian; Uccioli, Luigi; Urbancic, Vilma; van Acker, Kristien; van Baal, Jeff; Schaper, Nicolaas C

2017-07-01

Diabetic complications, and in particular diabetic foot ulcers (DFUs), are associated with low health-related quality of life (HRQoL). We evaluated whether the presence of diabetic complications also influenced the improvement of HRQoL during DFU treatment. 1088 patients presenting for DFU treatment at the centers participating in the Eurodiale study were followed prospectively up to one year. HRQoL was measured both at presentation and after healing or at end of follow up, using EQ-5D: a standardized instrument consisting of five domains and a summary index. The influence of diabetic comorbidity on the course of HRQoL was evaluated for each of the EQ-5D outcomes in multi-level linear regression analyses, adjusting for baseline characteristics. HRQoL improved in all EQ-5D outcomes over the course of treatment for those DFUs that healed. The few significant differences in the development of HRQoL between patients with and without comorbidity showed a more beneficial development for patients with comorbidity in DFUs that did not heal or healed slowly. Comorbidity does not hamper improvement of HRQoL in DFU treatment. On the contrary, HRQoL improved sometimes more in patients with certain comorbidity with hard-to-heal ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights.

PubMed

Baltzis, Dimitrios; Eleftheriadou, Ioanna; Veves, Aristidis

2014-08-01

Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes mellitus, as wound healing is impaired in the diabetic foot. Wound healing is a dynamic and complex biological process that can be divided into four partly overlapping phases: hemostasis, inflammation, proliferative and remodeling. These phases involve a large number of cell types, extracellular components, growth factors and cytokines. Diabetes mellitus causes impaired wound healing by affecting one or more biological mechanisms of these processes. Most often, it is triggered by hyperglycemia, chronic inflammation, micro- and macro-circulatory dysfunction, hypoxia, autonomic and sensory neuropathy, and impaired neuropeptide signaling. Research focused on thoroughly understanding these mechanisms would allow for specifically targeted treatment of diabetic foot ulcers. The main principles for DFU treatment are wound debridement, pressure off-loading, revascularization and infection management. New treatment options such as bioengineered skin substitutes, extracellular matrix proteins, growth factors, and negative pressure wound therapy, have emerged as adjunctive therapies for ulcers. Future treatment strategies include stem cell-based therapies, delivery of gene encoding growth factors, application of angiotensin receptors analogs and neuropeptides like substance P, as well as inhibition of inflammatory cytokines. This review provides an outlook of the pathophysiology in diabetic wound healing and summarizes the established and adjunctive treatment strategies, as well as the future therapeutic options for the treatment of DFUs.

Application of photo-magnetic therapy for treatment of skin radiation damage in rats.

PubMed

Simonova-Pushkar, L I; Gertman, V Z; Bilogurova, L V

2014-09-01

To improve methods of prevention and treatment of local radiation injury to the skin using the photomagnetic therapy. Materials and methods. Study was conducted on 60 male Wistar rats with 180-200 g bodyweight. The femoral area right hind limb of rats was locally irradiated by X-ray unit at a dose of 80.0 Gy. Exposed animals were divided into 2 groups: control and experimental. The rats of the experimental group received 2 courses of photo-magnetic therapy on the irradiated skin. The observations were carried out for 60 days. Methods - clinical, histological and statistical. Results. Local irradiation of rat skin causes the development of radiation ulcers in 60-70 % of the animals with the destruction of the structure in all layers of the skin. Spontaneous healing of radiation ulcer lasts at least two months with no complete skin recovery. Photo-magnetic therapy applied immediately after irradiation resulted in two-folddecrease of frequency of radiation ulcer incidence, accelerated the complete healing for 3 weeks and to ameliorated their progress. Histological examination showed that the photo-magnetic therapy reduced the extent of damage to all layers of the skin with restoration of epidermis and dermis structure and reduced the degree of inflammatory and destructive processes in the dermis. Conclusions. Photo-magnetic therapy produces a significant positive treatment effect by significantly reducing the inflammatory and destructive processes in all layers of the skin, stimulates the blood flow recovery in damaged tissue both with fibroblast proliferation and synthesis activation of native collagen fibers and other components of connective tissue, so almost a month accelerates ulcer healing radiation. L. I. Simonova-Pushkar, V. Z. Gertman, L. V. Bilogurova.

Laser photobiomodulation in pressure ulcer healing of human diabetic patients: gene expression analysis of inflammatory biochemical markers.

PubMed

Ruh, Anelice Calixto; Frigo, Lúcio; Cavalcanti, Marcos Fernando Xisto Braga; Svidnicki, Paulo; Vicari, Viviane Nogaroto; Lopes-Martins, Rodrigo Alvaro Brandão; Leal Junior, Ernesto Cesar Pinto; De Isla, Natalia; Diomede, Francesca; Trubiani, Oriana; Favero, Giovani Marino

2018-01-01

Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue under pressure suffers ischemia leading to cellular lesion and necrosis , its causes and the healing process depend on several factors. The aim of this study was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF, VEGF, and TGF, which take part in the tissue healing process under effects of low-level laser therapy (LLLT). In order to perform lesion area analysis, PUs were photographed and computer analyzed. Biochemical analysis was performed sa.mpling ulcer border tissue obtained through biopsy before and after laser therapy and quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU, classified as degree III and IV according to the National Pressure Ulcer Advisory Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660 nm), energy density 2 J/cm 2 , once a day, with intervals of 24 h, totaling 12 applications. The lesion area analysis revealed averaged improvement of the granulation tissue size up to 50% from pre- to post-treatment. qRT-PCR analysis revealed that IL6 values were not significantly different before and after treatment, TNF gene expression was reduced, and VEFG and TGF-β gene expression increased after treatment. After LLLT, wounds presented improvement in gross appearance, with increase in factors VEFG and TGF-β, and reduction of TNF; despite our promising results, they have to be analyzed carefully as this study did not have a control group.

Effectiveness of bridge V.A.C. dressings in the treatment of diabetic foot ulcers

PubMed Central

Nather, Aziz; Hong, Ng Yau; Lin, Wong Keng; Sakharam, Joshi Abhijit

2011-01-01

Objectives This is a prospective study of the clinical efficacy of the V.A.C. Granufoam Bridge Dressing for the treatment of diabetic foot ulcers. Materials and methods Five consecutive patients with diabetic foot ulcers were treated with V.A.C. Granufoam Bridge Dressings and studied over a period of 22–48 days. The indications for treatment included diabetic patients with open ray amputation wounds and wounds post-drainage for abscess with exposed deep structures. Clinical outcome was measured in terms of reduction in wound dimensions, presence of wound granulation, microbial clearance, and development of wound complications. Results Our results showed that with V.A.C. therapy, wound healing occurred in all patients. The number of dressings required ranged from 8 to 10. The baseline average wound size was 23.1 cm2. Wound areas shrunk by 18.4–41.7%. All subjects achieved 100% wound bed granulation with an average length of treatment of 33 days. Microbial clearance was achieved in all cases. All wounds healed by secondary intention in one case and four cases required split-thickness skin grafting. Conclusion The V.A.C. Granufoam Bridge Dressing is effective in the treatment of diabetic foot ulcers. It promotes reduction of wound area, wound bed granulation, and microbial clearance. By allowing placement of the suction pad outside the foot, it allowed patients to wear protective shoes and to walk non-weight bearing with crutches during V.A.C. therapy. PMID:22396825

[Clinical application of continuous douche and vacuum sealing drainage in refractory tissue, bone and joint infections after debridement].

PubMed

Yang, Ping-lin; He, Xi-jing; Li, Hao-peng; Wang, Guo-yu; Zang, Quan-jin

2010-01-01

To explore effect and the application value of continuous douche and vacuum sealing drainage (VSD) in refractory tissue, and joint infections after complete debridement. As retrospective analysis of treatment time and restoration or recurrence, from Jan. 2006 to Dec. 2007, 61 cases of refractory tissue, bone and joint infections underwent continuous douche and VSD combined with the treatment of anti-inflammatory and rehabilitation training after debridement in our hospital. The 61 patients included 39 males and 22 females with age ranging from 10 to 58 years with an average of (35 +/- 12) years, among whom 61 identified to have ankle ulcers combined with infections,open fracture combined with infections, sacrococcygeal pressure ulcers combined with infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation were 11, 15, 9, 3, 5 and 18 cases respectively. The course was from 2 weeks to 11 months with an average of 4 months. In all 61 patients,the mean healing time was 17, 36, 42, 24, 32, 29 and 28 days in ankle ulcers and infections, tibia and fibula open fracture and infections, femoral shaft fracture and infections, sacrococcygeal pressure ulcers and infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation respectively. The replacement of VSD was 1, 2-4, 3-5, 1-3, 2-4, 2-3 and 1-3 times in each group respectively. There was no wound recurrence except for 2 cases with recurrent in 61 cases with external fixation nail hole semi-pathological fracture in 1 case of femoral shaft fracture and infection and 1 case of tibia and fibula fracture and infection after follow-up at least one year. Application of continuous douche and VSD can effectively decrease incidence of complications and promote the refractory tissue, bone and joint infections wound growth, healing and considerably shorten the healing time.

Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat.

PubMed

Cerovecki, Tomislav; Bojanic, Ivan; Brcic, Luka; Radic, Bozo; Vukoja, Ivan; Seiwerth, Sven; Sikiric, Predrag

2010-09-01

We improved medial collateral ligament (MCL) healing throughout 90 days after surgical transection. We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier. Previously, as an effective peptide therapy, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide effective in inflammatory bowel disease therapy (PL 14736)) particularly improved healing of transected tendon and muscle and wound healing effect including the expression of the early growth response 1 (egr-1) gene. After MCL transection BPC 157 was effective in rats when given once daily intraperitoneally (10 microg or 10 ng/kg) or locally as a thin layer (1.0 microg dissolved in distilled water/g commercial neutral cream) at the site of injury, first application 30 min after surgery and the final application 24 h before sacrifice. Likewise, BPC 157 was effective given per-orally (0.16 microg/ml in the drinking water (12 ml/day/rat)) until sacrifice. Commonly, BPC 157 microg-ng-rats exhibited consistent functional, biomechanical, macroscopic and histological healing improvements. Thus, we suggest BPC 157 improved healing of acute ligament injuries in further ligament therapy. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Unusual Presentation of Duodenal Ulcer Presenting with Duodenal Intussusception.

PubMed

Lingala, Shilpa; Moore, Andrew; Kadire, Siri; Shankar, Sridhar; Das, Kanak; Howden, Colin W

2018-01-01

We present a unique case of duodeno-duodenal intussusception from a duodenal bulb ulcer. A 38-year-old man presented with nausea, vomiting, and abdominal pain. Computed tomography showed duodenal intussusception. Esophagogastroduodenoscopy (EGD) showed a linear gastric ulcer and a duodenal bulb ulcer with an overlying blood clot. Helicobacter pylori status was positive. Intussusception resolved spontaneously without intervention. He completed treatment for H. pylori infection, and repeat EGD showed ulcer healing. Duodenal intussusception is rarely reported; intussusception from an edematous duodenal ulcer with an overlying blood clot mimicking a mass lesion acting as lead point has never been reported to our knowledge.

Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

PubMed Central

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

2014-01-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage. PMID:25033386

Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

PubMed

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L; Schumacher, Michael A; Engevik, Amy C; Zavros, Yana; Ottemann, Karen M; Montrose, Marshall H

2014-07-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.

Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

PubMed

Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

2017-07-01

Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease: a systematic review.

PubMed

Hinchliffe, R J; Brownrigg, J R W; Andros, G; Apelqvist, J; Boyko, E J; Fitridge, R; Mills, J L; Reekers, J; Shearman, C P; Zierler, R E; Schaper, N C

2016-01-01

Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 articles were eligible for full-text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients. Copyright © 2015 John Wiley & Sons, Ltd.

Honey and Cancer: Sustainable Inverse Relationship Particularly for Developing Nations—A Review

PubMed Central

Othman, Nor Hayati

2012-01-01

Honey and cancer has a sustainable inverse relationship. Carcinogenesis is a multistep process and has multifactorial causes. Among these are low immune status, chronic infection, chronic inflammation, chronic non healing ulcers, obesity, and so forth. There is now a sizeable evidence that honey is a natural immune booster, natural anti-inflammatory agent, natural antimicrobial agent, natural cancer “vaccine,” and natural promoter for healing chronic ulcers and wounds. Though honey has substances of which the most predominant is a mixture of sugars, which itself is thought to be carcinogenic, it is understandable that its beneficial effect as anticancer agent raises skeptics. The positive scientific evidence for anticancer properties of honey is growing. The mechanism on how honey has anticancer effect is an area of great interest. Among the mechanisms suggested are inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest. Honey and cancer has sustainable inverse relationship in the setting of developing nations where resources for cancer prevention and treatment are limited. PMID:22761637

Validation of binding of SE-75 labeled sucralfate to sites of gastrointestinal ulceration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maurer, A.H.; Knight, L.C.; Kollman, M.

1985-05-01

This study was performed to determine if and for how long sucralfate (SU) binds selectively to sites of gastro-intestinal (GI) ulceration. Se-Su was prepared by sulfating sucrose with tracer Se-75 and precipitating it as the basic Al salt. All patients (pts) had endoscopy to confirm the presence of either: esophagitis (n=5), gastritis (GA) (n=5), gastric ulcers (GU) (n=5), duodenal ulcers (DU) (n=5), or no ulceration (NU) (n=5). Following an overnight fast the pts swallowed 1 gm with 100 ..mu..Ci of Se-SU and were imaged continuously over 24 hours or until no activity remained in the upper GI tract. Pts withmore » GU visually demonstrated focal SU binding at the ulcers for an average of 3.9 +- 1.1 hrs. with a mean GET of 68 +- 25 min. Mean GET for pts with DU was prolonged, 171 +- 63 min, however focal binding at duodenal ulcers was not seen. All pts with GA had diffuse retention of SU in the stomach with a mean GET of 118 +- 34 min. Focal binding of SU at all sites of esophagitis was seen with a T-1/2 of 65 +- 32 min at the ulcerations. In conclusion these data support the theory that the mechanism of ulcer healing with SU is related to its ability to adhere to the ulcer site forming a protective barrier. In addition Se-SU is a potential ulcer imaging agent which can be used to noninvasively assess healing.« less

Non-healing gastro-duodenal ulcer: A rare presentation of primary abdominal tuberculosis

PubMed Central

Merali, Nabeel; Chandak, Pankaj; Doddi, Sudeendra; Sinha, Prakash

2014-01-01

INTRODUCTION We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. PRESENTATION OF CASE A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. DISCUSSION Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. CONCLUSION This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient. PMID:25506841

Non-healing gastro-duodenal ulcer: A rare presentation of primary abdominal tuberculosis.

PubMed

Merali, Nabeel; Chandak, Pankaj; Doddi, Sudeendra; Sinha, Prakash

2015-01-01

We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.