Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation

PubMed Central

Pota, Vincenzo; Sansone, Pasquale; Aurilio, Caterina; Pace, Maria Caterina

2017-01-01

Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation. PMID:29359045

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

PubMed Central

Breser, María L.; Salazar, Florencia C.; Rivero, Viginia E.; Motrich, Rubén D.

2017-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain. PMID:28824626

The effect of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on semen parameters in human males: a systematic review and meta-analysis.

PubMed

Fu, Weihua; Zhou, Zhansong; Liu, Shijian; Li, Qianwei; Yao, Jiwei; Li, Weibing; Yan, Junan

2014-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the risk factors of impaired male fertility potential. Studies have investigated the effect of CP/CPPS on several semen parameters but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the association between CP/CPPS and basic semen parameters in adult men. Systematic literature searches were conducted with PubMed, EMBASE and the Cochrane Library up to August 2013 for case-control studies that involved the impact of CP/CPSS on semen parameters. Meta-analysis was performed with Review Manager and Stata software. Standard mean differences (SMD) of semen parameters were identified with 95% confidence intervals (95% CI) in a random effects model. Twelve studies were identified, including 999 cases of CP/CPPS and 455 controls. Our results illustrated that the sperm concentration and the percentage of progressively motile sperm and morphologically normal sperm from patients with CP/CPPS were significantly lower than controls (SMD (95% CI) -14.12 (-21.69, -6.63), -5.94 (-8.63, -3.25) and -8.26 (-11.83, -4.66), respectively). However, semen volume in the CP/CPPS group was higher than in the control group (SMD (95% CI) 0.50 (0.11, 0.89)). There was no significant effect of CP/CPPS on the total sperm count, sperm total motility, and sperm vitality. The present study illustrates that there was a significant negative effect of CP/CPPS on sperm concentration, sperm progressive motility, and normal sperm morphology. Further studies with larger sample sizes are needed to better illuminate the negative impact of CP/CPPS on semen parameters.

Chronic prostatitis/chronic pelvic pain syndrome in adolescents compared with that in young adults.

PubMed

Lee, Keon-Cheol; Cho, In-Rae

2017-07-01

Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) has been studied mainly in adults; reports in adolescents are rare. We compared the clinical characteristics of adolescent CP/CPPS patients with those of young adults. We retrospectively analyzed 20 adolescents with CP/CPPS aged <20 years who visited our outpatient department from August 2005 to April 2012. The control group comprised 120 young adult CP/CPPS patients. A complete medical history, physical examination, the national institute of health-chronic prostatitis symptoms index (NIH-CPSI) questionnaire, urinalysis, expressed prostatic secretion (EPS) or semen analysis, transrectal prostate ultrasonography, and prostate-specific antigen (PSA) were performed. Based on the EPS or semen analysis, patients were divided into category III-A or III-B. The mean age was 16.5±2.0 and 32.8±5.0 years in the adolescent and control groups, respectively. A sexual activity history was seen in 2 patients; 9 and 11 patients were in category III-A and III-B, respectively. The PSA was 0.65±0.39 and 1.22±0.48 ng/mL in the adolescent and control groups, respectively. The prostate size was 12.4±4.4 and 21.0±4.9 g in the adolescent and control groups, respectively. The NIH-CPSI scores in the adolescent group were 9.2±5.2, 5.5±3.5, 7.5±3.2, and 22.2±8.1 for pain, voiding, quality of life (QoL) domains, and total scores, respectively. The adolescent group showed a tendency to exhibit high voiding symptom scores. CPPS has an equally severe impact on QoL in adults and adolescents. Apart from high voiding symptom scores in adolescents, no difference was found in terms of urologic clinical parameters.

[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

PubMed

Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

2017-12-01

This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

New paradigms in understanding chronic pelvic pain syndrome.

PubMed

Konkle, Katy S; Clemens, J Quentin

2011-08-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male pain condition that is associated with significant discomfort and disability. Despite significant efforts, there remains no definitive etiology or treatment of the spectrum of pelvic symptoms reported by these patients. The purpose of this review is to summarize important clinical and scientific findings related to CP/CPPS from the previous 2 years, and to evaluate their impact on our understanding of, and approach to, the disease.

Negative Illness Perceptions are Associated with a Pro-nociceptive Modulation Profile and Augmented Pelvic Pain.

PubMed

Grinberg, Keren; Granot, Michal; Lowenstein, Lior; Abramov, Liora; Weissman-Fogel, Irit

2018-05-25

A patient's personal interpretations of a health threat or "illness perceptions" (IPs) are associated with their clinical outcomes. This study explored whether IPs are associated with pain severity and ability to modulate pain in women with chronic pelvic pain syndrome (CPPS), as well as the predictive value of IPs on Myofascial Physical Therapy (MPT) success. Illness Perceptions Questionnaire - Revised (IPQ-R), mechanical and heat pain thresholds, mechanical temporal summation (mTS), and conditioned pain modulation (CPM) were evaluated in CPPS patients (n=39) before, and 3 months after MPT. CPPS severity was obtained by the Brief Pain Inventory (BPI). Stronger perceptions of illness chronicity were correlated with less efficient CPM (r=0.488, P=0.002) and increased mechanical pain intensity (r=0.405, P=0.02). Lower perceptions of control over illness were associated with enhanced mTS (r=0.399, P=0.01). Higher BPI scores were correlated with emotional representations ("negative emotional representations") and severe consequences due to CPPS. Regression analyses revealed that negative IPs predict less efficient MPT. Cognitive representations play a unique role in CPPS expression and MPT outcomes. The interplay between negative IPs and a pro-nociceptive modulation profile, mediated by enhanced facilitatory and reduced inhibitory processes, may be involved in the manifestation of CPPS.

Anti-nanobacterial therapy for men with chronic prostatitis/chronic pelvic pain syndrome and prostatic stones: preliminary experience.

PubMed

Shoskes, Daniel A; Thomas, Kim D; Gomez, Eyda

2005-02-01

Category III chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a common debilitating condition of unclear etiology. Patients often have prostatic calcifications but a link to symptoms is controversial. Nanobacteria are implicated in stone formation in the urinary tract and, therefore, therapy to eliminate nanobacteria and the stones that they produce might have an impact on CPPS symptoms. A total of 16 men with recalcitrant CPPS refractory to multiple prior therapies were treated with comET (Nanobac Life Sciences, Tampa, Florida), which consists of 500 mg tetracycline, a proprietary nutraceutical and an ethylenediaminetetraacetic acid suppository daily. The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), transrectal ultrasound, and blood and urine tests for nanobacterial antigen were performed at the start and conclusion of 3 months of therapy. One patient was lost to followup. Mean NIH-CPSI total score +/- SD decreased from 25.7 +/- 1.6 to 13.7 +/- 2.0 (p <0.0001). Significant improvement was seen in each subscore domain. A total of 12 patients (80%) had at least 25% improvement on NIH-CPSI and 8 (53%) had at least 50% improvement. Nanobacterial antigen or antibody was found in 60% of serum and 40% of urine samples. In 10 patients who underwent transrectal ultrasound after therapy prostatic stones were decreased in size or resolved in 50%. Therapy designed to eliminate nanobacteria resulted in significant improvement in the symptoms of recalcitrant CPPS in the majority of men, whether due to the treatment of stone producing nanobacteria or through some other mechanism. Prospective placebo controlled trials are warranted.

Chronic pelvic pain syndrome: role of a thorough clinical assessment.

PubMed

Quaghebeur, Jörgen; Wyndaele, Jean-Jacques

2015-04-01

Chronic pelvic pain syndrome (CPPS) presents with a variety of symptoms affecting multiple systems. There is no universal treatment that can be given to all patients with CPPS. The results of treatment depend greatly on an accurate diagnosis. A thorough clinical assessment, including a "four-step plan", should include paying special attention to the musculoskeletal system. This assessment is not difficult to perform and provides valuable information on possible muscular problems and neuropathy.

A prospective study on association of prostatic calcifications with sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

PubMed

Zhao, Zhigang; Xuan, Xujun; Zhang, Jingwei; He, Jun; Zeng, Guohua

2014-10-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common debilitating condition of unclear etiology. Sexual dysfunction is an important component of the clinical phenotype of CP/CPPS. Patients often have prostatic calcifications, but a link to sexual dysfunction is unknown. The aim of this study was to evaluate the association of prostatic calcifications with sexual dysfunction in this condition. A total of 358 males with CP/CPPS were consecutively enrolled, and a prospectively maintained database of these patients was analyzed. Calcifications were diagnosed using ultrasound imaging of the prostate. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Sexual dysfunction was evaluated using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire and 5-item Premature Ejaculation Diagnostic Tool scales. The variables were compared between patients with prostatic calcifications and those without using the Student's t-test, Wilcoxon unpaired test, or chi-square test. Logistic regression models were developed to explore a possible association between prostatic calcifications and sexual dysfunction. Measurable calcifications in the prostate were found in 175 (48.9%) of the 358 patients. Patients with calcifications were more likely to have higher white blood cell counts or positive bacteria cultures in their prostatic fluid, longer symptoms duration, and lower scores for the total IIEF-15, IIEF-erectile function, and IIEF-intercourse satisfaction domains (P < 0.001 for each). However, the scores for CPSI, premature ejaculation, and IIEF-orgasmic function, IIEF-sexual desire, and IIEF-overall satisfaction domains were identical between men with and without calcifications (P > 0.05 for each). Furthermore, logistic regression analyses revealed that intraprostatic calcification is significantly associated with self-assessed erectile dysfunction (ED) (odds ratio:3.632, 95% confidence interval: 2.405-5.822, P < 0.001). Our results showed that prostatic calcifications are significantly associated with the presence of ED in CP/CPPS males. © 2014 International Society for Sexual Medicine.

Common Questions About Chronic Prostatitis.

PubMed

Holt, James D; Garrett, W Allan; McCurry, Tyler K; Teichman, Joel M H

2016-02-15

Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%. Risk factors include conditions that facilitate introduction of bacteria into the urethra and prostate (which also predispose the patient to urinary tract infections) and conditions that can lead to chronic neuropathic pain. Chronic prostatitis must be differentiated from other causes of chronic pelvic pain, such as interstitial cystitis/bladder pain syndrome and pelvic floor dysfunction; prostate and bladder cancers; benign prostatic hyperplasia; urolithiasis; and other causes of dysuria, urinary frequency, and nocturia. The National Institutes of Health divides prostatitis into four syndromes: acute bacterial prostatitis, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNP)/chronic pelvic pain syndrome (CPPS), and asymptomatic inflammatory prostatitis. CBP and CNP/CPPS both lead to pelvic pain and lower urinary tract symptoms. CBP presents as recurrent urinary tract infections with the same organism identified on repeated cultures; it responds to a prolonged course of an antibiotic that adequately penetrates the prostate, if the urine culture suggests sensitivity. If four to six weeks of antibiotic therapy is effective but symptoms recur, another course may be prescribed, perhaps in combination with alpha blockers or nonopioid analgesics. CNP/CPPS, accounting for more than 90% of chronic prostatitis cases, presents as prostatic pain lasting at least three months without consistent culture results. Weak evidence supports the use of alpha blockers, pain medications, and a four- to six-week course of antibiotics for the treatment of CNP/CPPS. Patients may also be referred to a psychologist experienced in managing chronic pain. Experts on this condition recommend a combination of treatments tailored to the patient's phenotypic presentation. Urology referral should be considered when appropriate treatment is ineffective. Additional treatments include pelvic floor physical therapy, phytotherapy, and pain management techniques. The UPOINT (urinary, psychosocial, organ-specific, infection, neurologic/systemic, tenderness) approach summarizes the various factors that may contribute to presentation and can guide treatment.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

2016-04-01

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats. © 2015 Blackwell Verlag GmbH.

Long-term effect of extracorporeal shock wave therapy on the treatment of chronic pelvic pain syndrome due to non bacterial prostatitis.

PubMed

Moayednia, Amir; Haghdani, Saeid; Khosrawi, Saeid; Yousefi, Elham; Vahdatpour, Babak

2014-04-01

There is limited evidence about the chronic pelvic pain syndrome (CPPS) treatment by shockwave therapy, and the aim of this study was to evaluate the effect of extracorporeal shockwave therapy on CPPS due to non bacterial prostatitis in a long-term period. In a follow-up survey, 40 patients with CPPS (that were randomly distributed into the treatment or sham groups were evaluated at 16, 20, and 24 weeks. In the treatment group, patients were treated by extracorporeal shock wave therapy (ESWT) once a week for 4 weeks by a protocol of 3000 impulses, 0.25 mJ/m(2) and 3 Hz of frequency. 0.05 mJ/m(2) were added in each week. In the sham group, the same protocol was applied, but with the probe being turned off. The follow-up assessments were done by visual analog scale for pain and National Institutes of Health-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Data were compared using independent t-test or analysis of variences. Three patients did not complete the study protocol, 37 patients were evlauated (19 patients in treatment and 18 patients in the sham group). At week 24, the mean of pain score, urinary score, quality-of-life and NIH-CPSI score between two groups were not statistically different. Although, ESWT therapy as a safe and effective therapy in CPPS in short-term follow-up has been established, its long-term efficacy was not supported by this study.

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

PubMed

Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

PubMed Central

Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

2014-01-01

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS

PubMed Central

Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang

2018-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n = 50; median age 39.8, range 23–65) and age-matched controls (n = 61; median age 36.8, range 20–69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 –treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 –treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy. PMID:29731970

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.

PubMed

Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang; Wagenlehner, Florian; Schagdarsurengin, Undraga

2018-04-13

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( n = 50; median age 39.8, range 23-65) and age-matched controls ( n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes ( ESR1 and ESR2 ) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E 2 ) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E 2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E 2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E 2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E 2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.

Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy on Men With Chronic Pelvic Pain Syndrome Refractory to 3-As Therapy.

PubMed

Guu, Shiao-Jin; Geng, Jiun-Hung; Chao, I-Ting; Lin, Hui-Tzu; Lee, Yung-Chin; Juan, Yung-Shun; Liu, Chia-Chu; Wang, Chii-Jye; Tsai, Chia-Chun

2018-03-01

Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm prospective study. Patients with CPPS without more than a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH-CPSI, visual analog scale (VAS) score, International Prostate Symptom Score (IPSS), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT. Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist circumference was the only significant predictor of a successful response to LI-ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to traditional 3-As therapy. Further studies are needed to determine an adequate therapeutic protocol and important predictors in patients with different CPPS etiologies.

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome

PubMed Central

Lin, Guiting; Reed-Maldonado, Amanda B.; Lin, Maofan; Xin, Zhongcheng; Lue, Tom F.

2016-01-01

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS. PMID:27376284

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

PubMed

Lin, Guiting; Reed-Maldonado, Amanda B; Lin, Maofan; Xin, Zhongcheng; Lue, Tom F

2016-07-01

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.

Therapy-related longitudinal brain perfusion changes in patients with chronic pelvic pain syndrome.

PubMed

Weisstanner, Christian; Mordasini, Livio; Thalmann, George N; Verma, Rajeev K; Rummel, Christian; Federspiel, Andrea; Kessler, Thomas M; Wiest, Roland

2017-08-03

The imaging method most frequently employed to identify brain areas involved in neuronal processing of nociception and brain pain perception is blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Arterial spin labelling (ASL), in contrast, offers advantages when slow varying changes in brain function are investigated. Chronic pelvic pain syndrome (CPPS) is a disorder of, mostly, young males that leads to altered pain perceptions in structures related to the pelvis. We aimed to investigate the potential of ASL to monitor longitudinal cranial blood flow (CBF) changes in patients with CPPS. In a randomised, placebo-controlled, double-blind single centre trial, we investigated treatment effects in CPPS after 12 weeks in patients that underwent sono-electro-magnetic therapy vs placebo. We investigated changes of CBF related to treatment outcome using pseudo-continuous arterial spin labelling (pCASL)-MRI. We observed CBF downregulation in the prefrontal cortex and anterior cingulate cortex and upregulation in the dorsolateral prefrontal cortex in responders. Nonresponders presented with CBF upregulation in the hippocampus. In patients with a history of CPPS of less than 12 months, there were significant correlations between longitudinal CBF changes and the Chronic Prostatitis Symptom Index pain subscore within the joint clusters anterior cingulate cortex and left anterior prefrontal cortex in responders, and the right hippocampus in nonresponders. We demonstrated therapy-related and stimulus-free longitudinal CBF changes in core areas of the pain matrix using ASL. ASL may act as a complementary noninvasive method to functional MRI and single-photon emission computed tomography / positron emission tomography, especially in the longitudinal assessment of pain response in clinical trials.

Toe spreading ability in men with chronic pelvic pain syndrome

PubMed Central

Yilmaz, Ugur; Rothman, Ivan; Ciol, Marcia A; Yang, Claire C; Berger, Richard E

2005-01-01

Background We examined toe-spreading ability in subjects with chronic pelvic pain syndrome (CPPS) to test the hypothesis that subjects with CPPS could have deficiencies in lower extremity functions innervated by sacral spinal roots. Methods Seventy two subjects with CPPS and 98 volunteer controls were examined as part of a larger study on CPPS. All the subjects underwent a detailed urologic and neurological examination including a toe-spreading examination with a quantitative scoring system. We compared the groups in terms of ability of toe-spreading as either "complete" (all toes spreading) or "incomplete" (at least one interdigital space not spreading) and also by comparing the number of interdigital spaces. For CPPS subjects only, we also analyzed the variation of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scales by toe-spreading categories. Results CPPS subjects were less often able to spread all toes than subjects without CPPS (p = 0.005). None of the NIH-CPSI sub-scales (pain, urinary symptoms, and quality of life), nor the total score showed an association with toe spreading ability. Conclusion We found toe spreading to be diminished in subjects with CPPS. We hypothesize that incomplete toe spreading in subjects with CPPS may be related to subtle deficits involving the most caudal part of the spinal segments. PMID:15949041

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP)

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90–95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17’s role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS. PMID:25933188

Complementary and Alternative Medicine for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

2005-01-01

To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross-searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPPS. Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder. PMID:16322807

[Modern view on etiology, pathogenesis and treatment of chronic pelvic pain syndrome].

PubMed

Vinarov, A Z

2017-04-01

The manuscript presents the analysis of scientific manuscripts written by Russian and foreign researchers devoted to chronic pelvic pain syndrome (CPPS) studies. In spite of widespread disease, there is no clear understanding on etiopathogenetic mechanisms of CPPS development and it is shown that besides infectious process cardiovascular, neuronal, locomotor, endocrine and immune systems are involved into pathological process of CPPS. Mentioned factors complicate the doctors task on effective therapy choice and stress the reasonability of complex approach to CPPS treatment. Combination drug containing affinity purified antibodies to endothelial NO-synthase and prostate-specific antigen in released-active form influences different pathogenetic mechanisms of CPPS and thereby reveals pronounced clinical efficacy.

The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes.

PubMed

Shoskes, Daniel A; Altemus, Jessica; Polackwich, Alan S; Tucky, Barbara; Wang, Hannah; Eng, Charis

2016-06-01

To study the urinary microbiome of patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) compared with controls. We identified 25 patients with CP/CPPS and 25 men who were either asymptomatic or only had urinary symptoms. Midstream urine was collected. Symptom severity was measured with the National Institutes of Health Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the urine pellet and bacterial-specific 16Sr-DNA-capture identified by MiSeq sequencing. Taxonomic and functional bioinformatic analyses used principal coordinate analysis (PCoA)/MacQIIME, LEfSe, and PiCRUSt algorithms. Patients and controls were similar ages (52.3 vs 57.0 years, P = .27). For patients, median duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0, and mean UPOINT domains was 3.6. Weighted 3D UniFrac PCoA revealed tighter clustering of controls distinct from the wider clustering of cases (P = .001; α-diversity P = .005). Seventeen clades were overrepresented in patients, for example, Clostridia, and 5 were underrepresented, eg, Bacilli, resulting in predicted perturbations in functional pathways. PiCRUSt inferred differentially regulated pathways between cases and controls that may be of relevance including sporulation, chemotaxis, and pyruvate metabolism. PCoA-derived microbiomic differences were noted for neurologic/systemic domains (P = .06), whereas LEfSe identified differences associated with each of the 6 clinical features. Urinary microbiomes from patients with CP/CPPS have significantly higher alpha(phylogenetic) diversity which cluster differently from controls, and higher counts of Clostridia compared with controls, resulting in predicted perturbations of functional pathways which could suggest metabolite-specific targeted treatment. Several measures of severity and clinical phenotype have significant microbiome differences. Copyright © 2016 Elsevier Inc. All rights reserved.

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

PubMed

Morgia, Giuseppe; Russo, Giorgio Ivan; Urzì, Daniele; Privitera, Salvatore; Castelli, Tommaso; Favilla, Vincenzo; Cimino, Sebastiano

2017-06-30

The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies with greater sample size.

Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.

PubMed

Wagenlehner, Florian M E; van Till, J W Olivier; Houbiers, Jos G A; Martina, Reynaldo V; Cerneus, Dirk P; Melis, Joost H J M; Majek, Antoni; Vjaters, Egils; Urban, Michael; Ramonas, Henrikas; Shoskes, Daniel A; Nickel, J Curtis

2017-05-01

To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors. In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions, and analysis of the efficacy variables. The study was stopped for futility at preplanned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25 mg group showed the largest reduction of the primary end point National Institutes of Health Chronic Prostatitis Symptom Index total score (7.0 points), but the placebo group showed a mean reduction of 7.3 points (difference: 0.3 [95% confidence interval: -1.9, 2.6]). Micturition outcomes improved compared with placebo in all ASP3652 groups; for example, in the 300 mg twice daily group, voiding frequency decreased by -1.10 (95% CI: -2.0, -0.2) voids/24 hours vs placebo. Safety outcomes were comparable across the treatment groups. ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, the results indicate that FAAH inhibition may attenuate lower urinary tract symptoms. Dedicated studies in patients with lower urinary tract dysfunction are needed to confirm this. Copyright © 2017 Elsevier Inc. All rights reserved.

Social Determinants of Chronic Prostatitis/Chronic Pelvic Pain Syndrome Related Lifestyle and Behaviors among Urban Men in China: A Case-Control Study

PubMed Central

Chen, Chen; Chen, Liang; Han, Qingrong; Ye, Huarong

2016-01-01

Purpose. In order to find key risk factors of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among urban men in China, an age-matched case-control study was performed from September 2012 to May 2013 in Yichang, Hubei Province, China. Methodology. A total of 279 patients and 558 controls were recruited in this study. Data were collected by a self-administered questionnaire, including demographics, diet and lifestyle, psychological status, and a physical exam. Conditional logistic regression model was used to analyze collected data. Results. Chemical factors exposure, night shift, severity of mood, and poor self-health cognition were entered into the regression model, and result displayed that these four factors had odds ratios of 1.929 (95% CI, 1.321–2.819), 1.456 (95% CI, 1.087–1.949), 1.619 (95% CI, 1.280–2.046), and 1.304 (95% CI, 1.094–1.555), respectively, which suggested that these four factors could significantly affect CP/CPPS. Conclusion. These results suggest that many factors affect CP/CPPS, including biological, social, and psychological factors. PMID:27579305

Efficacy of Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome: A Randomized, Controlled Trial

PubMed Central

Vahdatpour, Babak; Moayednia, Amir; Emadi, Masoud; Khorami, Mohammad Hatef; Haghdani, Saeid

2013-01-01

Objectives. To investigate the effectiveness of extracorporeal shock wave therapy (ESWT) for symptoms alleviation in chronic pelvic pain syndrome (CPPS). Materials and Methods. 40 patients with CPPS were randomly allocated into either the treatment or sham group. In the first group, patients were treated by ESWT once a week for 4 weeks by a defined protocol. In the sham group, the same protocol was applied but with the probe being turned off. The follow-up assessments were done at 1, 2, 3, and 12 weeks by Visual Analogue Scale (VAS) for pain and NIH-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Results. Pain domain scores at follow-up points in both treatment and sham groups were reduced, more so in the treatment group, which were significant at weeks 2, 3, and 12. Urinary scores became significantly different at weeks 3 and 12. Also, quality of life (QOL) and total NIH-CPSI scores at all four follow-up time points reduced more significantly in the treatment group as compared to the sham group. Noticeably, at week 12 a slight deterioration in all variables was observed compared to the first 3 weeks of the treatment period. Conclusions. our findings confirmed ESWT therapy as a safe and effective method in CPPS in short term. PMID:24000311

Efficacy of extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome: a randomized, controlled trial.

PubMed

Vahdatpour, Babak; Alizadeh, Farshid; Moayednia, Amir; Emadi, Masoud; Khorami, Mohammad Hatef; Haghdani, Saeid

2013-01-01

Objectives. To investigate the effectiveness of extracorporeal shock wave therapy (ESWT) for symptoms alleviation in chronic pelvic pain syndrome (CPPS). Materials and Methods. 40 patients with CPPS were randomly allocated into either the treatment or sham group. In the first group, patients were treated by ESWT once a week for 4 weeks by a defined protocol. In the sham group, the same protocol was applied but with the probe being turned off. The follow-up assessments were done at 1, 2, 3, and 12 weeks by Visual Analogue Scale (VAS) for pain and NIH-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Results. Pain domain scores at follow-up points in both treatment and sham groups were reduced, more so in the treatment group, which were significant at weeks 2, 3, and 12. Urinary scores became significantly different at weeks 3 and 12. Also, quality of life (QOL) and total NIH-CPSI scores at all four follow-up time points reduced more significantly in the treatment group as compared to the sham group. Noticeably, at week 12 a slight deterioration in all variables was observed compared to the first 3 weeks of the treatment period. Conclusions. our findings confirmed ESWT therapy as a safe and effective method in CPPS in short term.

A prospective, 1-year trial using saw palmetto versus finasteride in the treatment of category III prostatitis/chronic pelvic pain syndrome.

PubMed

Kaplan, Steven A; Volpe, Michael A; Te, Alexis E

2004-01-01

This study was designed to assess the safety and efficacy of saw palmetto or finasteride in men with category III prostatitis/chronic pelvic pain syndrome (CP/CPPS). A prospective, randomized, open label, 1-year study was designed to assess the safety and efficacy of saw palmetto and finasteride in the treatment of men diagnosed with CP/CPPS. Patients were randomized to finasteride (5 mg once daily) or saw palmetto (325 mg daily) for 1 year. Patients were evaluated using the National Institutes of Health Chronic Prostatitis Symptom Index, individual domains (pain, urinary symptoms, quality of life and mean pain score) and the American Urological Association Symptom Score at baseline, 3, 6 and 12 months. A total of 64 consecutive men 24 to 58 years old (mean age 43.2) with a diagnosis of CP/CPPS were equally randomized to the 2 treatment arms. All 64 men had previously received antibiotics (duration of 3 to 93 weeks), 52 (82%) had been on alpha-blockade. There were 61, 57 and 56 patients evaluable at 3, 6 and 12 months, respectively. At 1 year mean total National Institutes of Health Chronic Prostatitis Symptom Index score decreased from 23.9 to 18.1 in the finasteride group (p <0.003), and from 24.7 to 24.6 in the saw palmetto arm (p = 0.41). In the finasteride arm the quality of life and pain domains were significantly improved at 1 year; however, urination was not. Adverse events included headache (3 cases) in the saw palmetto group and decreased libido (2 cases) in the finasteride group. At the end of the trial 13 of 32 (41%) and 21 of 32 (66%) opted to continue saw palmetto and finasteride, respectively. CP/CPPS treated with saw palmetto had no appreciable long-term improvement. In contrast, patients treated with finasteride had significant and durable improvement in all various parameters except voiding. Further studies are warranted to ascertain the mechanism and reproducibility of these effects in a placebo controlled trial.

A common pronociceptive pain modulation profile typifying subgroups of chronic pelvic pain syndromes is interrelated with enhanced clinical pain.

PubMed

Grinberg, Keren; Granot, Michal; Lowenstein, Lior; Abramov, Liora; Weissman-Fogel, Irit

2017-06-01

Provoked vestibulodynia (PVD) and painful bladder syndrome (PBS), subgroups of chronic pelvic pain syndromes (CPPS), are considered to share common biophysiological peripheral mechanisms. In addition, indications of a pronociceptive pain profile coexisting with psychological vulnerability suggest common dysfunctional pain processing and pain modulation in these 2 subgroups of CPPS. We therefore aimed at comparing the pain profile and psychological traits of patients with PVD and PBS to see whether the pain profile contributes to intersubject variability of clinical pain symptoms. Patients with PVD (n = 18) and PBS (n = 21) were compared with healthy controls (n = 20) in their responses to (1) pain psychophysical tests applied to both referred (suprapubis) and remote (hand) body areas and (2) pain-related psychological factors (pain catastrophizing, depression, anxiety, and somatization). We found a similar pronociceptive pain profile in the 2 subgroups of CPPS-enhanced facilitation (ie, hyperalgesia in the referred body area [P < 0.001]) and inefficient inhibition (ie, reduced conditioned pain modulation [P < 0.001] that were associated with both enhanced pain ratings evoked during trigger point examination [P < 0.037]) and higher Brief Pain Inventory ratings (P = 0.002). The latter was also correlated with pain catastrophizing (r = 0.504, P = 0.001) and depression symptoms (r = 0.361, P = 0.024). The findings suggest common mechanisms underlying a dysfunctional nociceptive system in both PVD and PBS. The intersubject variability in the level of dysfunction and its association with disease severity recommends a personalized pain treatment that may alleviate daily pain and dysfunction in patients with CPPS.

IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

2016-03-01

Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

[Prostatic inflammation-induced chronic pelvic pain: Roles of substance P and c-fos in the spinal cord].

PubMed

Liu, Ying-jia; Song, Guo-hong; Zhang, Chen

2015-08-01

To explore the possible pain mechanism of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The models of CP/CPPS were established in male Wistar rats by the autoimmune method. The paw withdrawal threshold (PWT) was detected using Von Frey filament. The expressions of the substance P and c-fos in the prostate and spinal L5-S2 segments were determined by immunohistochemistry followed by analysis of their correlation with CP/CPPS. Compared with the control rats, the CP/CPPS models showed significantly decreased PWT (P < 0.05), remarkable prostatic inflammation, enlarged scope of lesions, and obvious interstitial lymphocytic infiltration (P < 0.05). Both the expressions of substance P and c-fos were markedly elevated in the prostate and spinal dorsal horn (L5-S2) of the rat models (P < 0.05), but the expression of substance P in the prostate exhibited no correlation with that in the spinal cord (r = 0.099, P = 0.338), nor did that of c-fos (r = 0.027, P = 0.454). The upregulated expressions of substance P and c-fos in the spinal cord L5-S2 sections may be associated with the pain mechanism of CP/CPPS.

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

2012-10-01

Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P < 0.001), -9.7 (95% CI -14.2 to -5.3; P < 0.001) and -1.7 (95% CI -3.2 to -0.2; P= 0.032) respectively, while α-blockers plus antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P < 0.001). • With respect to responder analysis compared with placebo, anti-inflammatories showed the greatest response rates (risk ratio 1.7, 95% CI 1.4-2.1; P < 0.001) followed by α-blockers (risk ratio 1.4, 95% CI 1.1-1.8; P= 0.013) and antibiotics (risk ratio 1.2, 95% CI 0.7-1.9; P= 0.527). α-blockers, antibiotics and/or anti-inflammatory/immune modulation therapy appear to be beneficial for some patients with CP/CPPS. • The magnitude of effect and the disconnect between mean CPSI decrease and response rates compared with placebo suggest that directed multimodal therapy, rather than mono-therapy, with these agents should be considered for optimal management of CP/CPPS. © 2012 BJU INTERNATIONAL.

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP

PubMed Central

Kutch, Jason J.; Yani, Moheb S.; Asavasopon, Skulpan; Kirages, Daniel J.; Rana, Manku; Cosand, Louise; Labus, Jennifer S.; Kilpatrick, Lisa A.; Ashe-McNalley, Cody; Farmer, Melissa A.; Johnson, Kevin A.; Ness, Timothy J.; Deutsch, Georg; Harris, Richard E.; Apkarian, A. Vania; Clauw, Daniel J.; Mackey, Sean C.; Mullins, Chris; Mayer, Emeran A.

2015-01-01

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing. PMID:26106574

Therapeutic effects of Qian-Yu decoction and its three extracts on carrageenan-induced chronic prostatitis/chronic pelvic pain syndrome in rats.

PubMed

Zhang, Keda; Zeng, Xiaobin; Chen, Yonggang; Zhao, Rong; Wang, Hui; Wu, Jinhu

2017-01-25

Qian-Yu decoction (QYD) is a traditional Chinese medicinal recipe composed of Radix astragali (Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao, Fabaceae ), Herba epimedii (Epimedium brevicornum Maxim., Berberidaceae), Herba leonuri (Leonurus japonicus Houtt., Lamiaceae), Cortex phellodendri (Phellodendron chinense Schneid., Rutaceae) and Radix achyranthis bidentatae (Achyranthes bidentata Bl., Amaranthaceae). This study aimed to evaluate the therapeutic activity of QYD against carrageenan-induced chronic prostatic/chronic pelvic pain syndrome (CP/CPPS) in rats and further elucidate its effective components. Three types of components, total polysaccharides, total flavonoids and total saponins were separately extracted from QYD. Carrageenan-induced CP/CPPS rats were intragastrically administered with lyophilized product of QYD, individual extracts and all the combined forms of extracts for three weeks. Prostatic index (PI) was determined and histopathological analysis was performed. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PEG2) in rat prostate tissues were measured using ELISA. The production of inducible nitric oxide synthase (iNOS) was evaluated by an enzymatic activity assay, and the release of nitric oxide (NO) was determined by a nitrate/nitrite assay. Treatment with QYD significantly ameliorated the histological changes of CP/CPPS rats and reduced the PI by 44.3%, with a marked downregulation of TNF-α (42.8% reduction), IL-1β (45.3%), COX-2 (36.6%), PGE2 (44.2%), iNOS (54.1%) and NO (46.0%). Each of three extracts attenuated the symptom of CP/CPPS, but much more weakly than QYD. The combined administration of three extracts showed efficacy comparable to that of QYD while better than that of any combination of two extracts. A principal component analysis of the six inflammatory mediators as variables indicated that the effects of TS on CP/CPPS were rather different from those of TF and TP, which were similar. QYD can be beneficial in prevention and treatment of CP/CPPS. Polysaccharides, flavonoids and saponins, as the major effective components of QYD, exert a cooperative effect on CP/CPPS.

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

PubMed

Hu, Y; Niu, X; Wang, G; Huang, J; Liu, M; Peng, B

2016-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function. © 2016 American Society of Andrology and European Academy of Andrology.

Sono-electro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial.

PubMed

Kessler, Thomas M; Mordasini, Livio; Weisstanner, Christian; Jüni, Peter; da Costa, Bruno R; Wiest, Roland; Thalmann, George N

2014-01-01

To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6) than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023). Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. ClinicalTrials.gov NCT00688506.

[International focuses in the studies of chronic pelvic pain syndrome: A social network analysis].

PubMed

Wen, Li-Jie; Pan, Xian-Wei; Yang, Bo

2016-10-01

To analyze the internationally published literature relevant to chronic pelvic pain syndrome (CPPS) using bibliometrics and social network analysis, and investigate the current status and focuses of CPPS studies. We identified 692 publications on CPPS by searching PubMed up to December 2015, extracted their subject headings, calculated the frequencies of the headings, and constructed a co-occurrence network of the high-frequency (≥10) subject headings. Then we studied the features and structure of the co-occurrence network by analyzing its attributes and topological structure. The density of the constructed co-occurrence network was 0.111, with an average distance of 2.886 and a clustering coefficient of 0.685. Its low density, long average distance and high clustering coefficient indicated that it was a sparse network, with a slow speed of information spreading among nodes but a strong potential coherence, which suggested that the current topics in the study of CPPS were scattered and weakly correlated, with a high possibility of being integrated. Based on the topological structure of the co-occurrence network, the topics in the study of CPPS were divided into six aspects: diagnosis and classification, drug therapy, treatment, etiology, microbiology, psychology, and epidemiology, the more important of which were diagnosis and classification, drug therapy, treatment and etiology. A system has been formed in the studies of CPPS, focusing on the diagnosis, drug therapy, and etiology of the disease. However, the research topics are relatively scattered and frequently repeated. Therefore, more attention should be paid to the macrocosmic guidance and rational coordination of the researches on CPPS.

A standard for terminology in chronic pelvic pain syndromes: A report from the chronic pelvic pain working group of the international continence society.

PubMed

Doggweiler, Regula; Whitmore, Kristene E; Meijlink, Jane M; Drake, Marcus J; Frawley, Helena; Nordling, Jørgen; Hanno, Philip; Fraser, Matthew O; Homma, Yukio; Garrido, Gustavo; Gomes, Mario J; Elneil, Sohier; van de Merwe, Joop P; Lin, Alex T L; Tomoe, Hikaru

2017-04-01

Terms used in the field of chronic pelvic pain (CPP) are poorly defined and often confusing. An International Continence Society (ICS) Standard for Terminology in chronic pelvic pain syndromes (CPPS) has been developed with the aim of improving diagnosis and treatment of patients affected by chronic pelvic pain syndromes. The standard aims to facilitate research, enhance therapy development and support healthcare delivery, for healthcare providers, and patients. This document looks at the whole person and all the domains (organ systems) in a systematic way. A dedicated working group (WG) was instituted by the ICS Standardisation Steering Committee according to published procedures. The WG extracted information from existing relevant guidelines, consensus documents, and scientific publications. Medline and other databases were searched in relation to each chronic pelvic pain domain from 1980 to 2014. Existing ICS Standards for terminology were utilized where appropriate to ensure transparency, accessibility, flexibility, and evolution. Consensus was based on majority agreement. The multidisciplinary CPPS Standard reports updated consensus terminology in nine domains; lower urinary tract, female genital, male genital, gastrointestinal, musculoskeletal, neurological aspects, psychological aspects, sexual aspects, and comorbidities. Each is described in terms of symptoms, signs and further evaluation. The document presents preferred terms and definitions for symptoms, signs, and evaluation (diagnostic work-up) of female and male patients with chronic pelvic pain syndromes, serving as a platform for ongoing development in this field. Neurourol. Urodynam. 36:984-1008, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparison of National Institutes of Health-Chronic Prostatitis Symptom Index with International Index of Erectile Function 5 in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Large Cross-Sectional Study in China.

PubMed

Gao, Jingjing; Gao, Pan; Hao, Zongyao; Zhou, Zengrong; Liu, Jihong; Li, Hongjun; Xing, Junping; Zhou, Zhansong; Deng, Chunhua; Deng, Liwen; Wei, Qiang; Zhang, Xiansheng; Zhou, Jun; Fan, Song; Tai, Sheng; Yang, Chen; Shi, Kai; Huang, Yuanyuan; Ye, Zhangqun; Liang, Chaozhao

2015-01-01

The purpose of the study is to evaluate the relationship between NIH-CPSI and IIEF-5 in Chinese men with CP/CPPS. A large cross-sectional and multicenter survey was conducted from July 2012 to January 2014. Men were recruited from urology clinics which were located at the five cities in China. All men participated in the survey by completing a verbal questionnaire (consisted of sociodemographics, past medical history, sexual history, and self-estimated scales). The results showed that 1,280 men completed the survey. Based on the CP/CPPS definition, a total of 801 men were diagnosed as having CP/CPPS. Men with CP/CPPS reported higher scores of NIH-CPSI and lower scores of IIEF-5 than men without CP/CPPS. NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. The total scores of NIH-CPSI were significantly more strongly correlated with question 5 than other questions of IIEF-5. The total scores of IIEF-5 were significantly more strongly correlated with pain symptoms scores of NIH-CPSI. Strongest correlation was found between QoL impact and question 5 of IIEF-5. The findings suggested that NIH-CPSI scores were significantly negatively correlated with IIEF-5 scores. Strongest correlation was found between QoL impact and question 5 of IIEF-5.

Positioning, telling, and performing a male illness: Chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wood, Nicholas; Qureshi, Annum; Mughal, Fahim

2017-11-01

There is a paucity of illness accounts of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), despite a significant level of prevalence and burden of disease. This qualitative study thus elicited twelve accounts from men suffering with CP/CPPS. Narrative analysis was employed, focusing primarily on narrative content. Three major narrative themes were identified: (1) Medical stories: Blame and shame; (2) The Erratic nature of CP/CPPS; and (3) Ongoing struggles for coping and cures and the Search for meaning. Recommendations were made for health care providers and increasing the internal agency, support and activism of men with this debilitating condition. Statement of contribution What is already known on this subject? One qualitative account of this male illness (CP/CPPS) exists: an IPA study. Five cross-sectional themes: (1) Need for repeated confirmation - disease not life-threatening nor leading inexorably towards cancer; (2) Disturbed sleep and fatigue; (3) Concealing pain and problems - 'normalizing'; (4) Enduring pain by performing activities; and (5) Abrupt mood swings and limited sociality. What does this study add? Narrative analysis adds information as to how this illness is managed and survived over time. It challenges the findings (above) by providing an insider perspective. Novel narrative themes include meaning-making amongst others. Masculine performance and experiences are also crucial to this stigmatized illness. © 2017 The British Psychological Society.

Acupuncture versus Sham Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain

PubMed Central

Lee, Shaun Wen Huey; Liong, Men Long; Yuen, Kah Hay; Leong, Wing Seng; Chee, Christopher; Cheah, Phaik Yeong; Choong, Weng Pho; Wu, Yue; Khan, Nurzalina; Choong, Wooi Long; Yap, Hin Wai; Krieger, John N.

2015-01-01

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) afflicts 2–10% of adult men. Available therapies offer little or no proven benefit. Because acupuncture represents an attractive “natural” therapy, we compared the efficacy of acupuncture to sham acupuncture for CP/CPPS Methods Participants met US National Institutes of Health (NIH) consensus criteria for CP/CPPS, aged ≥ 20 years old, with total score ≥ 15 on the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) and symptoms for at least 3 of the preceding 6 months were randomized 1:1 to acupuncture or sham acupuncture. Treatment consisted of twice weekly 30-minute sessions for 10 weeks (20 sessions total), without needle stimulation, herbs or adjuvants. The primary response criterion was a six-point decrease from baseline to week 10 in NIH-CPSI total score (range 0–43). Results Thirty-two (73%) of 44 participants responded in the acupuncture group compared to 21 (47%) of 45 sham group participants (relative risk [RR] 1.81, 95% confidence interval [CI], 1.3–3.1, p=0.02,). Long-term responses 24 weeks after completing therapy without additional treatment occurred in 14 (32%) of 44 acupuncture group participants and in 6 (13%) of 45 sham group participants (RR 2.39, 95% CI, 1.0–5.6, p=0.04). Conclusion After 10 weeks of treatment, acupuncture proved almost twice as likely as sham to improve CP/CPPS symptoms. Participants receiving acupuncture were 2.4 fold more likely to experience long-term benefit than participants receiving sham acupuncture. PMID:18187077

Effect of acupuncture on clinical symptoms and laboratory indicators for chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis.

PubMed

Liu, Bu-Ping; Wang, Yun-Ting; Chen, Si-da

2016-12-01

To systematically review the efficacy and safety of acupuncture for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PubMed, Cochrane library Central, Web of Science, Wang-fang Database, and CNKI were searched from their inception to June 30, 2016. Data of acupuncture for CP/CPPS following randomized controlled trials (RCTs) was included. The data were analyzed using the Cochrane Collaboration Review Manager. The primary data were the National Institute of Health-Chronic Prostatitis Index (NIH-CPSI) score at the end of follow-up. Ten RCTs were enrolled. Acupuncture was superior to the control in NIH-CPSI (MD -3.98, [95 % CI -5.78 to -2.19]; P < 0.0001) and response rate (RR 4.12, [95 % CI 1.67-10.18]; P = 0.002). Acupuncture was superior to sham acupuncture on NIH-CPSI, response rate, pain, urinary, and quality of life (QOL). Standard medication was inferior to acupuncture in terms of NIH-CPSI (MD -3.08, [95 % CI -5.57 to -0.60]; P = 0.02) and response rate (RR 2.03, [95 % CI 1.04-3.97]; P = 0.04), but standard medication was superior to acupuncture on improving urinary symptoms. There was no significant difference in the adverse events. Acupuncture/acupuncture plus standard medication significantly down-regulated IL-1β compared with standard medication in prostatic fluid. Acupuncture treating CP/CPPS is effective and safe. The effects of acupuncture on NIH-CPSI, response rate, pain symptoms, and QOF were superior to the control, but standard medication significantly improved urinary symptoms compared with acupuncture. Acupuncture can decrease the IL-1β in prostatic fluid for CP/CPPS.

Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats.

PubMed

Liu, Y-J; Song, G-H; Liu, G T

2016-08-01

According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect. © 2016 Blackwell Verlag GmbH.

Contemporary treatment options for chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Ismail, M; Mackenzie, K; Hashim, H

2013-07-01

The prostate gland, about the size a walnut, forms part of the male reproductive system and sits directly underneath the bladder surrounding the urethra. It is a fibromuscular exocrine gland that secretes a complex proteolytic fluid which constitutes one-third of the volume of the seminal fluid. Prostatitis refers to a group of disorders that affect the prostate and cause genitourinary pain, dysuria, urinary frequency and sexual dysfunction. The prevalence of prostatitis in the United States has been estimated to be around 9%, while the worldwide prevalence ranges from 2 to 10%, and 15% of men experience prostatitis-like symptoms at some point in their lives. There are a number of treatments which have been used for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), with only a small amount of high-level evidence. The current recommended treatment for CP/CPPS is predominantly a multimodal approach using a combination of antibiotics, α-blockers, antimuscarinic and anti-inflammatory drugs. The response to treatment and improvement in symptoms is very variable; therefore, as the evidence evolves, it is likely that treatment will become symptom specific rather than a generic, 'one strategy fits all' treatment for CP/CPPS. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, Xianjin; Zhong, Shan; Xu, Tianyuan; Xia, Leilei; Zhang, Xiaohua; Zhu, Zhaowei; Zhang, Minguang; Shen, Zhoujun

2015-02-01

A variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models. We firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis-diphtheria-tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology. Histologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin. The histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.

Chronic prostatitis and comorbid non-urological overlapping pain conditions: A co-twin control study.

PubMed

Gasperi, Marianna; Krieger, John N; Forsberg, Christopher; Goldberg, Jack; Buchwald, Dedra; Afari, Niloofar

2017-11-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs. Data from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations. There were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome. CP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities. Published by Elsevier Inc.

Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

PubMed

Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

2018-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

Immune mediators of chronic pelvic pain syndrome

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Thumbikat, Praveen

2016-01-01

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease. PMID:24686526

Systematic Review of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Zhou, Jing; Liu, Zhishun

2016-01-01

Abstract Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects >15% of adult men worldwide. The aim of the study was to assess the effects and safety of the use of acupuncture for CP/CPPS. MEDLINE, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wang-Fang Database, JCRM, and CiNii were searched from their inception through 30 November 2015. Grey literature databases and websites were also searched. No language limits were applied. Only randomized controlled trials (RCTs) with CP/CPPS treated by acupuncture were included. Two reviewers extracted data and assessed the risk of bias of RCTs using the Cochrane Risk of Bias Tools, respectively. Seven trials were included, involving 471 participants. The result of meta-analysis indicated that compared with sham acupuncture (MD: −6.09 [95%CI: −8.12 to −5.68]) and medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) (MD: −4.57 [95%CI: −7.58 to −1.56]), acupuncture was more effective at decreasing the total NIH-CPSI score. Real acupuncture was superior to sham acupuncture in improving symptoms (pain, voiding) and quality of life (Qof) domain subscores. Compared to sham acupuncture and medicine, acupuncture appears to be more effective at improving the global assessment. Two trials found that there is no significant difference between acupuncture and sham acupuncture in decreasing the IPSS score. Acupuncture failed to show more favorable effects in improving both symptoms and the Qof domain compared with medicine. Overall, current evidence supports acupuncture as an effective treatment for CP/CPPS-induced symptoms, particularly in relieving pain. Based on the meta-analysis, acupuncture is superior to sham acupuncture in improving symptoms and Qof. Acupuncture might be similar to medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) in its long-term effects, but evidence was limited due to high ROB among included trials as well as potential heterogeneity. Acupuncture is associated with rare and slightly adverse events. Protocol registration PROSPERO CRD42015027522. PMID:26986148

Predictors of symptom severity in patients with chronic prostatitis and interstitial cystitis.

PubMed

Clemens, J Quentin; Brown, Sheila O; Kozloff, Lara; Calhoun, Elizabeth A

2006-03-01

Numerous studies have been performed to identify potential risk factors for CP/CPPS and IC. However, few studies have been done to identify predictors of disease severity. A total of 174 men with CP/CPPS and 111 women with IC completed questionnaires to quantify symptom severity and identify demographic, medical and psychosocial characteristics. Symptom severity was assessed with the National Institutes of Health CPSI in men, and the O'Leary-Sant ICSI and problem index in women. Univariate and multivariate analyses were performed to identify characteristics predictive of worse symptoms. The mean National Institutes of Health CPSI score in men was 15.32, and the mean O'Leary-Sant ICSI and problem index in women was 19.17. The most commonly reported comorbidities were allergies, sinusitis, erectile dysfunction and irritable bowel syndrome in men, and allergies, urinary incontinence, sinusitis and irritable bowel syndrome in women. In the 2 sexes self-reported urinary frequency and urgency, worse depression scores and lower education level were independent predictors of worse symptom severity. In men additional independent predictors were self-reported pelvic pain, fibromyalgia and previous heart attack, and in women an additional independent predictor was postmenopausal status. There are several common medical conditions associated with urological pelvic pain syndromes in men and women. Few of them were predictive of symptoms severity in this analysis. Self-reported pelvic pain symptoms, education and depression severity were the factors most strongly predictive of symptom severity in patients with CP/CPPS and IC.

Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) induced by immunization with a novel peptide T2.

PubMed

Ihsan, Awais Ullah; Khan, Farhan Ullah; Nawaz, Waqas; Khan, Muhammad Zahid; Yang, Mengqi; Zhou, Xiaohui

2017-07-01

The exact etiological mechanism of Chronic Prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be beneficial in elucidating mechanisms involved in the pathogenesis of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). 40 male Sprague-Dawley rats with an average weight of 180-220g were equally distributed into five groups. The normal control group was injected with normal saline (.9% NACL), the CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA. Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin staining and Immunohistochemistry were used to investigate inflammatory cell infiltration and IL-1β in the prostate tissue respectively. ELISA technique was used to measure the serum level of CRP and TNF-α. T-test was used to analyze the results. Maximum infiltration of inflammatory cells and the highest level of IL-1β in the prostate tissue was observed in T2+AL(OH)3+CFA group as revealed by histopathology and Immunohistochemistry, respectively. Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-α and CRP as determined by ELISA technique. Our results demonstrated that T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We believe that our present model will be highly beneficial for investigation of the pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Relationship between premature ejaculation and chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Lee, Jun Ho; Lee, Sung Won

2015-03-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common etiology of premature ejaculation (PE). However, the current data are insufficient to explain this relationship and to support routine screening of men with PE. This study aims to evaluate the relationship between PE and CP/CPPS. A cross-sectional study was conducted that included 8,261 men who had participated in a health examination. The Premature Ejaculation Diagnostic Tool (PEDT), the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and the International Index of Erectile Function-5 (IIEF) were used for assessment of symptoms. A full metabolic work-up and serum testosterone level checks were also performed. We then investigated the relationship using the Spearman correlation test, multiple linear regression, and logistic regression analyses. Associations of PEDT with NIH-CPSI. The mean age was 50.4 ± 5.5 years. In total, 2,205 (24.9%) men had prostatitis-like symptoms (NIH-CPSI pain score of ≥4 and perineal or ejaculatory pain), and 618 (7.0%) men had moderate to severe symptoms (NIH-CPSI pain score of ≥8). Additionally, 2,144 men (24.2%) were classified as demonstrating PE (PEDT > 10). The PEDT score was found to have a significant positive correlation with the NIH-CPSI pain domain score (correlation coefficient = 0.206; P < 0.001). After adjusting for age, metabolic syndrome status, testosterone level, and IIEF score, there was no change in the positive correlation between the NIH-CPSI pain domain score and PEDT score (Beta = 0.175; P < 0.001). After adjusting for age, testosterone level, metabolic syndrome, and IIEF score, the odds ratio (OR) for PE significantly increased with the severity of pelvic pain (mild prostatitis-like symptoms, OR for PE: 1.269, 95% confidence interval: 1.113-1.447; moderate to severe symptoms, OR for PE: 2.134: 95% confidence interval: 1.782-2.557). Our data showed a significant correlation between the PEDT score and the NIH-CPSI score. We suggest routine screening for CP/CPPS in men with PE and PE in men with CP/CPPS. © 2014 International Society for Sexual Medicine.

Pregabalin for the Treatment of Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Pontari, Michel A.; Krieger, John N.; Litwin, Mark S.; White, Paige C.; Anderson, Rodney U.; McNaughton-Collins, Mary; Nickel, J. Curtis; Shoskes, Daniel A.; Alexander, Richard B.; O'Leary, Michael; Zeitlin, Scott; Chuai, Shannon; Landis, J. Richard; Cen, Liyi; Propert, Kathleen J.; Kusek, John W.; Nyberg, Leroy M.; Schaeffer, Anthony J.

2013-01-01

Background Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic. Methods This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006–2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed. Results Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIHCPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and sub-scores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups. Conclusion Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS. Trial Registration clinicaltrials.gov Identifier: NCT00371033 PMID:20876412

Chinese urologists' practice patterns of diagnosing and treating chronic pelvic pain syndrome: a questionnaire survey.

PubMed

Zhang, Kai; Xu, Ben; Xiao, Yun-xiang; Shang, Xue-jun; Bai, Wen-jun; Wang, Xiao-feng; Liu, Ji-hong; Deng, Chun-hua

2014-08-18

To investigate the application of the Chinese Urological Association (CUA) guidelines on prostatitis and the effects on the clinical practice patterns of diagnosing and treating chronic pelvic pain syndrome (CPPS) among Chinese urologists. We conducted a questionnaire investigation of the CUA guidelines on prostatitis among the urologists from 399 hospitals in 63 cities of China, and performed statistical analyses on all the eligible questionnaires collected. Of the 2 251 questionnaires distributed, 2 046 (90.9%) were eligible, of which 92.5% were from the urologists in tertiary or secondary hospitals, of whom 72.3% had senior or intermediate professional titles, and 90.2% had studied the CUA guidelines. Most respondents agreed that Type III prostatitis was a clinical syndrome, of which the diagnosis should be made after other conditions with similar symptoms had been ruled out and the aim was to relieve pain, alleviate urination symptoms and improve quality of life. Those who had and those who had not studied the CUA guidelines differed in their viewpoints on CPPS as illustrated in the guidelines. In clinical practice, the most common treatment options for CPPS were pharmaceutical therapy (95.0%), life style adjustment (88.9%), and psychotherapy (79.9%), and the most frequently prescribed drugs were phytotherapy (84.5%), α-blockers (79.0%) and antibiotics (64.0%). CUA guidelines on prostatitis has gained a nationwide application and promoted the standardization of the management of CPPS in China.

Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Tian, Jinhui; Zhou, Jing; Liu, Yali; Liu, Zhishun

2016-01-01

Alpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96–6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27–7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07–2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57–3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95–4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08–4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07–2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS. PMID:27759111

COMPARISON OF BASELINE UROLOGIC SYMPTOMS IN MEN AND WOMEN IN THE MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN (MAPP) RESEARCH COHORT

PubMed Central

Clemens, J. Quentin; Clauw, Daniel J.; Kreder, Karl; Krieger, John N.; Kusek, John W.; Lai, H. Henry; Rodriguez, Larissa; Williams, David A.; Hou, Xiaoling; Stephens, Alisa; Landis, J Richard

2015-01-01

INTRODUCTION The clinical features of interstitial cystitis/ bladder pain syndrome (IC/BPS) are similar to those of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have directly compared the characteristics of these syndromes in men and women. METHODS The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network recruited 191 men and 233 women with IC/BPS or CP/CPPS. Baseline data included demographics, the Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), the Genitourinary Pain Index (GUPI), the American Urological Association Symptom Index (AUASI), Likert scales to assess urinary urgency, frequency, pain and overall symptom severity, and a single question about the most bothersome pelvic symptom. RESULTS After adjustment for age, income and symptom duration, measures of pain severity were similar across genders. Mean scores for the ICSI, ICPI and AUASI were significantly higher in women than men, reflecting more bladder-focused symptoms in women. The most bothersome single symptom in both men and women was pain in the pubic/bladder area (34% of men, 58% of women). The characteristics of the men and women in the MAPP cohort were similar to those reported in other research cohorts of IC/BPS and CP/CPPS. CONCLUSIONS Our findings indicate that pain severity is similar in both sexes, and that bladder-focused symptoms (urgency, suprapubic pain, frequency) are more common in women. However, a substantial proportion of men also report these types of bladder symptoms. PMID:25463989

A novel murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by immunization with a spermine binding protein (p25) peptide

PubMed Central

Altuntas, Cengiz Z.; Veizi, Elias; Izgi, Kenan; Bicer, Fuat; Ozer, Ahmet; Grimberg, Kerry O.; Bakhautdin, Bakytzhan; Sakalar, Cagri; Tasdemir, Cemal; Tuohy, Vincent K.

2013-01-01

The pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is poorly understood. Inflammatory and autoimmune mechanisms may play a role. We developed a murine model of experimental autoimmune prostatitis (EAP) that mimics the human phenotype of CP/CPPS. Eight-week-old mice were immunized subcutaneously with prostate-specific peptides in an emulsion of complete Freund's adjuvant. Mice were euthanized 10 days after immunization, and lymph node cells were isolated and assessed for recall proliferation to each peptide. P25 99–118 was the most immunogenic peptide. T-cell and B-cell immunity and serum levels of C-reactive protein and nitrate/nitrite levels were evaluated over a 9-wk period. Morphometric studies of prostate, 24-h micturition frequencies, and urine volume per void were evaluated. Tactile referred hyperalgesia was measured using von Frey filaments to the pelvic region. The unpaired Student's t-test was used to analyze differences between EAP and control groups. Prostates from p25 99–118-immunized mice demonstrated elevated gene expression levels of TNF-α, IL-17A, IFN-γ, and IL-1β, not observed in control mice. Compared with controls, p25 99–118-immunized mice had significantly higher micturition frequency and decreased urine output per void, and they demonstrated elevated pelvic pain response. p25 99–118 immunization of male SWXJ mice induced prostate-specific autoimmunity characterized by prostate-confined inflammation, increased micturition frequency, and pelvic pain. This autoimmune prostatitis model provides a useful tool for exploring the pathophysiology and new treatments. PMID:23344231

Clinical study of duloxetine hydrochloride combined with doxazosin for the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome: An observational study.

PubMed

Zhang, Mingxin; Li, Hanzhong; Ji, Zhigang; Dong, Dexin; Yan, Su

2017-03-01

To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker (alpha-blocker) doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).In all, 150 patients were enrolled and 126 patients completed the study (41 patients in the doxazosin group, 41 patients in the sertraline group, and 44 patients in the duloxetine group). This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ± 1.29, 2.66 ± 1.57, and 3.24 ± 1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ± 2.17, 4 ± 2.11, and 4.90 ± 2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63.41% after 1, 3, and 6 months, respectively. The SF-MPQ score in the sertraline group decreased to 1.76 ± 1.28, 3.07 ± 2, and 3.93 ± 2.53 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the sertraline group decreased to 3.56 ± 4.11, 5.73 ± 5.26, and 7.27 ± 6.50 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the duloxetine group was 36.36%, 88.64%, and 88.64% after 1, 3, and 6 months, respectively. The SF-MPQ score in the duloxetine group decreased to 3.61 ± 2.54, 6.05 ± 3.66, and 7.41 ± 4.26 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the duloxetine group decreased to 3.14 ± 3.28, 6.93 ± 3.90, and 9.43 ± 4.67 after 1, 3, and 6 months, respectively (P < 0.05). There were significant differences in the reduction of the NIH-CPSI score and the SF-MPQ score between the duloxetine group and the sertraline group and between the duloxetine group and the doxazosin group (P < 0.01). There were significant differences in the reduction of the HAD score at 3 months between the duloxetine group and the doxazosin group, and there were significant differences in the reduction of the HAD score at 6 months among the groups (P < 0.05). The incidence rates of adverse reactions in the duloxetine group, the sertraline group, and the duloxetine group were 29.5%, 17%, and 7.3%, respectively, with adverse events ranging from mild to moderate.There was a clear relationship between the extent of pain and mental factors in CP/CPPS with the main symptom of pain. Doxazosin combined with duloxetine exhibited good safety and efficacy in the treatment of pain disorder in CP/CPPS.

Chronic Obstructive Pulmonary Disease: official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care.

PubMed

Koblizek, Vladimir; Chlumsky, Jan; Zindr, Vladimir; Neumannova, Katerina; Zatloukal, Jakub; Zak, Jaroslav; Sedlak, Vratislav; Kocianova, Jana; Zatloukal, Jaromir; Hejduk, Karel; Pracharova, Sarka

2013-06-01

COPD is a global concern. Currently, several sets of guidelines, statements and strategies to managing COPD exist around the world. The Czech Pneumological and Phthisiological Society (CPPS) has commissioned an Expert group to draft recommended guidelines for the management of stable COPD. Subsequent revisions were further discussed at the National Consensus Conference (NCC). Reviewers' comments contributed to the establishment of the document's final version. The hallmark of the novel approach to COPD is the integrated evaluation of the patient's lung functions, symptoms, exacerbations and identifications of clinical phenotype(s). The CPPS defines 6 clinically relevant phenotypes: frequent exacerbator, COPD-asthma overlap, COPD-bronchiectasis overlap, emphysematic phenotype, bronchitic phenotype and pulmonary cachexia phenotype. Treatment recommendations can be divided into four steps. 1(st) step = Risk exposure elimination: reduction of smoking and environmental tobacco smoke (ETS), decrease of home and occupational exposure risks. 2(nd) step = Standard treatment: inhaled bronchodilators, regular physical activity, pulmonary rehabilitation, education, inhalation training, comorbidity treatment, vaccination. 3(rd) step = Phenotype-specific therapy: PDE4i, ICS+LABA, LVRS, BVR, AAT augmentation, physiotherapy, mucolytic, ABT. 4(th) step = Care for respiratory insufficiency and terminal COPD: LTOT, lung transplantation, high intensity-NIV and palliative care. Optimal treatment of COPD patients requires an individualised, multidisciplinary approach to the patient's symptoms, clinical phenotypes, needs and wishes. The new Czech COPD guideline reflects and covers these requirements.

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Franco, Juan Va; Turk, Tarek; Jung, Jae Hung; Xiao, Yu-Tian; Iakhno, Stanislav; Garrote, Virginia; Vietto, Valeria

2018-01-26

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture reduces prostatitis symptoms in an appreciable number of participants compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference in adverse events (moderate QoE). It probably also decreases prostatitis symptoms compared with standard medical therapy in an appreciable number of participants (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2. Circumcision: (one study, 713 participants) based on short-term follow-up, early circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD -3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a greater incidence of adverse events compared with control (a waiting list to be circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants) based on short-term follow-up, we are uncertain of the effects of the use of an electromagnetic chair on prostatitis symptoms. It may be associated with a greater incidence of adverse events compared with sham procedure (low to very low QoE).4. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a greater improvement in prostatitis symptoms in an appreciable number of participants compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events.5. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events.7. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE).8. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events.9. Other interventions: there is uncertainty about the effects of other interventions included in this review. We found no information regarding psychological support or prostatic surgery. Some of the interventions can decrease prostatitis symptoms in an appreciable number without a greater incidence of adverse events. The QoE was mostly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

Phosphorylated Codonopsis pilosula polysaccharide could inhibit the virulence of duck hepatitis A virus compared with Codonopsis pilosula polysaccharide.

PubMed

Ming, Ke; Chen, Yun; Yao, Fangke; Shi, Jintong; Yang, Jingjing; Du, Hongxu; Wang, Xunyi; Wang, Yixuan; Liu, Jiaguo

2017-01-01

To screen effective anti-duck hepatitis A virus (DHAV) drugs, we applied STMP-STPP method to prepare phosphorylated Codonopsis pilosula polysaccharide (pCPPS), the phosphorylation-modified product of Codonopsis pilosula polysaccharide (CPPS). The IR spectrum and field emission scanning electron microscope (FE-SEM) were subsequently used to analyze the structure of pCPPS. Several tests were conducted to compare the anti-DHAV activities of CPPS and pCPPS. The MTT method was used to compare the effect of the drugs on DHAV-infected duck embryonic hepatocytes (DEHs), and the Reed-Muench assay was employed to observe changes in the virulence of DHAV. We also applied real-time PCR to examine the relationship between virus replication and the expression of IFN-β. The results indicated that CPPS could not inhibit the replication of DHAV. In contrast, pCPPS increased the virus TCID 50 , inhibited viral replication and, accordingly, increased the survival rate of DEHs infected with DHAV. Because DHAV induced the expression of IFN-β, and the IFN-β expression level was positively associated with the number of DHAV, the reduction of IFN-β expression levels after pCPPS treatment demonstrated a decrease in the number of virus particles. These results indicated that pCPPS, which reduces the number of DHAV, was more effective than CPPS in anti-DHAV activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic bacterial prostatitis and chronic pelvic pain syndrome.

PubMed

Bowen, Diana K; Dielubanza, Elodi; Schaeffer, Anthony J

2015-08-27

Chronic prostatitis can cause pain and urinary symptoms, and can occur either with an active infection (chronic bacterial prostatitis [CBP]) or with only pain and no evidence of bacterial causation (chronic pelvic pain syndrome [CPPS]). Bacterial prostatitis is characterised by recurrent urinary tract infections or infection in the prostate with the same bacterial strain, which often results from urinary tract instrumentation. However, the cause and natural history of CPPS are unknown and not associated with active infection. We conducted a systematic overview and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 131 studies. After deduplication and removal of conference abstracts, 67 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 51 studies and the further review of 16 full publications. Of the 16 full articles evaluated, three systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for 14 PICO combinations. In this systematic overview, we categorised the efficacy for 12 interventions based on information relating to the effectiveness and safety of 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, quercetin, sitz baths, transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP).

Characterization of casein phosphopeptides from fermented milk products.

PubMed

Kawahara, Takeshi; Aruga, Kaori; Otani, Hajime

2005-10-01

This study dealt with the potential of fermented milk products as a source of functional casein phosphopeptides (CPPs) using plain yogurts and Camembert cheeses. The CPPs were prepared by tryptic digestion from four commercially available plain yogurts (P1-P4), five Camembert cheeses (C1-C5), and raw milk. From portions with a 1-g protein content of the plain yogurts, the Camembert cheeses, and the raw milk, 171 mg, 139 mg, and 146 mg of CPPs were obtained, respectively. The Camembert cheeses retained high amounts of organic phosphorus (32 microg) per 1 mg CPPs compared to the raw milk (15 microg) and plain yogurts (16 microg). Reverse-phase high-performance liquid chromatographic analysis showed that the elution patterns and retention times of the three major peaks of CPPs from P1 and C1 were similar to those from raw milk. Moreover, CPPs from P1 and C1 showed a mitogenic effect, while CPPs from C1 showed an IgA-enhancing effect in mouse spleen cell cultures. These results suggest that fermented milk products such as plain yogurts and Camembert cheeses generate functional CPPs in the body and exert beneficial effects on the immune system.

Separation of water-soluble polysaccharides from Cyclocarya paliurus by ultrafiltration process.

PubMed

Xie, Jian-Hua; Shen, Ming-Yue; Nie, Shao-Ping; Zhao, Qiang; Li, Chang; Xie, Ming-Yong

2014-01-30

In this study, ultrafiltration membrane process was employed to separate polysaccharides from Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) to simulate industrial production. Meanwhile, the molecular weight distribution of C. paliurus polysaccharides was investigated by gel permeation chromatography. Four fractions were obtained and named as CPPS-A, CPPS-B, CPPS-C and CPPS-D, respectively. CPPS-A and CPPS-B contained approximately 69.5% and 12.7% of polysaccharides, whose molecular weight were in the range of 100-300 kDa and 120 kDa, respectively. CPPS-C was comprised of two polysaccharides with average molecular weight of 40 kDa and 15 kDa. Results showed that ultrafiltration resulted in the removal of parts of small molecule weight polysaccharides, the increase of proportion of high molecule weight ones and the obvious improvement of quality of products. Compared with ethanol precipitation and gel permeation chromatography techniques, ultrafiltration showed many advantages, and also provided theoretical support for industrial manufacturing of C. paliurus polysaccharides in separation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predicting Voice Disorder Status From Smoothed Measures of Cepstral Peak Prominence Using Praat and Analysis of Dysphonia in Speech and Voice (ADSV).

PubMed

Sauder, Cara; Bretl, Michelle; Eadie, Tanya

2017-09-01

The purposes of this study were to (1) determine and compare the diagnostic accuracy of a single acoustic measure, smoothed cepstral peak prominence (CPPS), to predict voice disorder status from connected speech samples using two software systems: Analysis of Dysphonia in Speech and Voice (ADSV) and Praat; and (2) to determine the relationship between measures of CPPS generated from these programs. This is a retrospective cross-sectional study. Measures of CPPS were obtained from connected speech recordings of 100 subjects with voice disorders and 70 nondysphonic subjects without vocal complaints using commercially available ADSV and freely downloadable Praat software programs. Logistic regression and receiver operating characteristic (ROC) analyses were used to evaluate and compare the diagnostic accuracy of CPPS measures. Relationships between CPPS measures from the programs were determined. Results showed acceptable overall accuracy rates (75% accuracy, ADSV; 82% accuracy, Praat) and area under the ROC curves (area under the curve [AUC] = 0.81, ADSV; AUC = 0.91, Praat) for predicting voice disorder status, with slight differences in sensitivity and specificity. CPPS measures derived from Praat were uniquely predictive of disorder status above and beyond CPPS measures from ADSV (χ 2 (1) = 40.71, P < 0.001). CPPS measures from both programs were significantly and highly correlated (r = 0.88, P < 0.001). A single acoustic measure of CPPS was highly predictive of voice disorder status using either program. Clinicians may consider using CPPS to complement clinical voice evaluation and screening protocols. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Resource use efficiency of closed plant production system with artificial light: Concept, estimation and application to plant factory

PubMed Central

KOZAI, Toyoki

2013-01-01

Extensive research has recently been conducted on plant factory with artificial light, which is one type of closed plant production system (CPPS) consisting of a thermally insulated and airtight structure, a multi-tier system with lighting devices, air conditioners and fans, a CO2 supply unit, a nutrient solution supply unit, and an environment control unit. One of the research outcomes is the concept of resource use efficiency (RUE) of CPPS. This paper reviews the characteristics of the CPPS compared with those of the greenhouse, mainly from the viewpoint of RUE, which is defined as the ratio of the amount of the resource fixed or held in plants to the amount of the resource supplied to the CPPS. It is shown that the use efficiencies of water, CO2 and light energy are considerably higher in the CPPS than those in the greenhouse. On the other hand, there is much more room for improving the light and electric energy use efficiencies of CPPS. Challenging issues for CPPS and RUE are also discussed. PMID:24334509

Resource use efficiency of closed plant production system with artificial light: concept, estimation and application to plant factory.

PubMed

Kozai, Toyoki

2013-01-01

Extensive research has recently been conducted on plant factory with artificial light, which is one type of closed plant production system (CPPS) consisting of a thermally insulated and airtight structure, a multi-tier system with lighting devices, air conditioners and fans, a CO2 supply unit, a nutrient solution supply unit, and an environment control unit. One of the research outcomes is the concept of resource use efficiency (RUE) of CPPS.This paper reviews the characteristics of the CPPS compared with those of the greenhouse, mainly from the viewpoint of RUE, which is defined as the ratio of the amount of the resource fixed or held in plants to the amount of the resource supplied to the CPPS.It is shown that the use efficiencies of water, CO2 and light energy are considerably higher in the CPPS than those in the greenhouse. On the other hand, there is much more room for improving the light and electric energy use efficiencies of CPPS. Challenging issues for CPPS and RUE are also discussed.

Coffee polyphenols extracted from green coffee beans improve skin properties and microcirculatory function.

PubMed

Fukagawa, Satoko; Haramizu, Satoshi; Sasaoka, Shun; Yasuda, Yuka; Tsujimura, Hisashi; Murase, Takatoshi

2017-09-01

Coffee polyphenols (CPPs), including chlorogenic acid, exert various physiological activities. The purpose of this study was to investigate the effects of CPPs on skin properties and microcirculatory function in humans. In this double-blind, placebo-controlled study, 49 female subjects with mildly xerotic skin received either a test beverage containing CPPs (270 mg/100 mL/day) or a placebo beverage for 8 weeks. The ingestion of CPPs significantly lowered the clinical scores for skin dryness, decreased transepidermal water loss, skin surface pH, and increased stratum corneum hydration and the responsiveness of skin blood flow during local warming. Moreover, the amounts of free fatty acids and lactic acid in the stratum corneum significantly increased after the ingestion of CPPs. These results suggest that an 8-week intake of CPPs improve skin permeability barrier function and hydration, with a concomitant improvement in microcirculatory function, leading to efficacy in the alleviation of mildly xerotic skin.

Implementation of Cyber-Physical Production Systems for Quality Prediction and Operation Control in Metal Casting.

PubMed

Lee, JuneHyuck; Noh, Sang Do; Kim, Hyun-Jung; Kang, Yong-Shin

2018-05-04

The prediction of internal defects of metal casting immediately after the casting process saves unnecessary time and money by reducing the amount of inputs into the next stage, such as the machining process, and enables flexible scheduling. Cyber-physical production systems (CPPS) perfectly fulfill the aforementioned requirements. This study deals with the implementation of CPPS in a real factory to predict the quality of metal casting and operation control. First, a CPPS architecture framework for quality prediction and operation control in metal-casting production was designed. The framework describes collaboration among internet of things (IoT), artificial intelligence, simulations, manufacturing execution systems, and advanced planning and scheduling systems. Subsequently, the implementation of the CPPS in actual plants is described. Temperature is a major factor that affects casting quality, and thus, temperature sensors and IoT communication devices were attached to casting machines. The well-known NoSQL database, HBase and the high-speed processing/analysis tool, Spark, are used for IoT repository and data pre-processing, respectively. Many machine learning algorithms such as decision tree, random forest, artificial neural network, and support vector machine were used for quality prediction and compared with R software. Finally, the operation of the entire system is demonstrated through a CPPS dashboard. In an era in which most CPPS-related studies are conducted on high-level abstract models, this study describes more specific architectural frameworks, use cases, usable software, and analytical methodologies. In addition, this study verifies the usefulness of CPPS by estimating quantitative effects. This is expected to contribute to the proliferation of CPPS in the industry.

Reinventing Cell Penetrating Peptides Using Glycosylated Methionine Sulfonium Ion Sequences.

PubMed

Kramer, Jessica R; Schmidt, Nathan W; Mayle, Kristine M; Kamei, Daniel T; Wong, Gerard C L; Deming, Timothy J

2015-05-27

Cell penetrating peptides (CPPs) are intriguing molecules that have received much attention, both in terms of mechanistic analysis and as transporters for intracellular therapeutic delivery. Most CPPs contain an abundance of cationic charged residues, typically arginine, where the amino acid compositions, rather than specific sequences, tend to determine their ability to enter cells. Hydrophobic residues are often added to cationic sequences to create efficient CPPs, but typically at the penalty of increased cytotoxicity. Here, we examined polypeptides containing glycosylated, cationic derivatives of methionine, where we found these hydrophilic polypeptides to be surprisingly effective as CPPs and to also possess low cytotoxicity. X-ray analysis of how these new polypeptides interact with lipid membranes revealed that the incorporation of sterically demanding hydrophilic cationic groups in polypeptides is an unprecedented new concept for design of potent CPPs.

Reinventing cell penetrating peptides using glycosylated methionine sulfonium ion sequences

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

Kramer, Jessica R.; Schmidt, Nathan W.; Mayle, Kristine M.

2015-04-15

Cell penetrating peptides (CPPs) are intriguing molecules that have received much attention, both in terms of mechanistic analysis and as transporters for intracellular therapeutic delivery. Most CPPs contain an abundance of cationic charged residues, typically arginine, where the amino acid compositions, rather than specific sequences, tend to determine their ability to enter cells. Hydrophobic residues are often added to cationic sequences to create efficient CPPs, but typically at the penalty of increased cytotoxicity. Here, we examined polypeptides containing glycosylated, cationic derivatives of methionine, where we found these hydrophilic polypeptides to be surprisingly effective as CPPs and to also possess lowmore » cytotoxicity. X-ray analysis of how these new polypeptides interact with lipid membranes revealed that the incorporation of sterically demanding hydrophilic cationic groups in polypeptides is an unprecedented new concept for design of potent CPPs.« less

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

PubMed

Lin, Li; Zhu, Bao-Ping; Cai, Liang

2017-06-01

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Trace Detection of Metalloporphyrin-Based Coordination Polymer Particles via Modified Surface-Enhanced Raman Scattering Assisted by Surface Metallization.

PubMed

Sun, Yu; Caravella, Alessio

2016-01-01

This study proposed a facile method to detect metalloporphyrin-based coordination polymer particles (Z-CPPs) in aqueous solution by modified surface-enhanced Raman scattering (SERS). The SERS-active particles are photodeposited on the surface of Z-CPPs, offering an enhanced Raman signal for the trace detection of Z-CPPs.

Implementation of Cyber-Physical Production Systems for Quality Prediction and Operation Control in Metal Casting

PubMed Central

Lee, JuneHyuck; Noh, Sang Do; Kim, Hyun-Jung; Kang, Yong-Shin

2018-01-01

The prediction of internal defects of metal casting immediately after the casting process saves unnecessary time and money by reducing the amount of inputs into the next stage, such as the machining process, and enables flexible scheduling. Cyber-physical production systems (CPPS) perfectly fulfill the aforementioned requirements. This study deals with the implementation of CPPS in a real factory to predict the quality of metal casting and operation control. First, a CPPS architecture framework for quality prediction and operation control in metal-casting production was designed. The framework describes collaboration among internet of things (IoT), artificial intelligence, simulations, manufacturing execution systems, and advanced planning and scheduling systems. Subsequently, the implementation of the CPPS in actual plants is described. Temperature is a major factor that affects casting quality, and thus, temperature sensors and IoT communication devices were attached to casting machines. The well-known NoSQL database, HBase and the high-speed processing/analysis tool, Spark, are used for IoT repository and data pre-processing, respectively. Many machine learning algorithms such as decision tree, random forest, artificial neural network, and support vector machine were used for quality prediction and compared with R software. Finally, the operation of the entire system is demonstrated through a CPPS dashboard. In an era in which most CPPS-related studies are conducted on high-level abstract models, this study describes more specific architectural frameworks, use cases, usable software, and analytical methodologies. In addition, this study verifies the usefulness of CPPS by estimating quantitative effects. This is expected to contribute to the proliferation of CPPS in the industry. PMID:29734699

Multidisciplinary pain facility treatment outcome for pain-associated fatigue.

PubMed

Fishbain, David A; Lewis, John; Cole, Brandly; Cutler, Brian; Smets, Eve; Rosomoff, Hubert; Rosomoff, Rennee Steele

2005-01-01

Fatigue is frequently found in chronic pain patients (CPPs) and may be etiologically related to the presence of pain. Fishbain et al. have recently demonstrated that chronic low back pain (LBP) and chronic neck pain patients are more fatigued than controls. The purpose of this study was to determine whether chronic LBP- and chronic neck pain-associated fatigue responded to multidisciplinary multimodal treatment not specifically targeted to the treatment of fatigue. A total of 85 chronic LBP and 33 chronic neck pain patients completed the Multidimensional Fatigue Inventory (MFI), Neuropathic Pain Scale (NPS), and Beck Depression Inventory on admission. In addition, an information tool was completed on each CPP by the senior author. This tool listed demographic information, primary and secondary pain diagnoses, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) psychiatric diagnoses assigned, pain location, pain precipitating event, type of injury, years in pain, number of surgeries, type of surgery, type of pain pattern, opioids consumed per day in morphine equivalents, worker compensation status, and whether, according to the clinical examination, the CPP had a neuropathic pain component. At completion of the multidisciplinary multimodal treatment, each CPP again completed the MFI. Student's t-test was utilized to test for statistical changes on the MFI five scales from pre- to post-treatment. Pearson and point-biserial correlations were utilized to determine which variables significantly correlated with MFI change scores. Variables found significant at less than or equal to 0.01 were utilized in a stepwise aggression analysis to find variables predictive of change in MFI scores. Multidisciplinary pain facility. Chronic LBP and chronic neck pain patients. Multidisciplinary multimodal treatment significantly improved CPP fatigue as measured by the MFI. The available variables utilized to predict fatigue best explained only a small percentage (28.9%) of the variance. Improvement in fatigue was related to NPS-10 scale scores (neuropathic pain) and a previous diagnosis of fibromyalgia. Multidisciplinary multimodal pain facility treatment improves chronic LBP- and neck pain-associated fatigue. At the present time we cannot predict this improvement with significant accuracy.

Prediction of cell penetrating peptides by support vector machines.

PubMed

Sanders, William S; Johnston, C Ian; Bridges, Susan M; Burgess, Shane C; Willeford, Kenneth O

2011-07-01

Cell penetrating peptides (CPPs) are those peptides that can transverse cell membranes to enter cells. Once inside the cell, different CPPs can localize to different cellular components and perform different roles. Some generate pore-forming complexes resulting in the destruction of cells while others localize to various organelles. Use of machine learning methods to predict potential new CPPs will enable more rapid screening for applications such as drug delivery. We have investigated the influence of the composition of training datasets on the ability to classify peptides as cell penetrating using support vector machines (SVMs). We identified 111 known CPPs and 34 known non-penetrating peptides from the literature and commercial vendors and used several approaches to build training data sets for the classifiers. Features were calculated from the datasets using a set of basic biochemical properties combined with features from the literature determined to be relevant in the prediction of CPPs. Our results using different training datasets confirm the importance of a balanced training set with approximately equal number of positive and negative examples. The SVM based classifiers have greater classification accuracy than previously reported methods for the prediction of CPPs, and because they use primary biochemical properties of the peptides as features, these classifiers provide insight into the properties needed for cell-penetration. To confirm our SVM classifications, a subset of peptides classified as either penetrating or non-penetrating was selected for synthesis and experimental validation. Of the synthesized peptides predicted to be CPPs, 100% of these peptides were shown to be penetrating.

The MAPP research network: a novel study of urologic chronic pelvic pain syndromes

PubMed Central

2014-01-01

Urologic chronic pelvic pain syndrome (UCPPS) may be defined to include interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The hallmark symptom of UCPPS is chronic pain in the pelvis, urogenital floor, or external genitalia often accompanied by lower urinary tract symptoms. Despite numerous past basic and clinical research studies there is no broadly identifiable organ-specific pathology or understanding of etiology or risk factors for UCPPS, and diagnosis relies primarily on patient reported symptoms. In addition, there are no generally effective therapies. Recent findings have, however, revealed associations between UCPPS and “centralized” chronic pain disorders, suggesting UCPPS may represent a local manifestation of more widespread pathology in some patients. Here, we describe a new and novel effort initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the U.S. National Institutes of Health (NIH) to address the many long standing questions regarding UCPPS, the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. The MAPP Network approaches UCPPS in a systemic manner, in which the interplay between the genitourinary system and other physiological systems is emphasized. The network’s study design expands beyond previous research, which has primarily focused on urologic organs and tissues, to utilize integrated approaches to define patient phenotypes, identify clinically-relevant subgroups, and better understand treated natural history and pathophysiology. Thus, the MAPP Network provides an unprecedented, multi-layered characterization of UCPPS. Knowledge gained is expected to provide important insights into underlying pathophysiology, a foundation for better segmenting patients for future clinical trials, and ultimately translation into improved clinical management. In addition, the MAPP Network’s integrated multi-disciplinary research approach may serve as a model for studies of urologic and non-urologic disorders that have proven refractory to past basic and clinical study. Trial registration ClinicalTrials.gov identifier: NCT01098279 “Chronic Pelvic Pain Study of Individuals with Diagnoses or Symptoms of Interstitial Cystitis and/or Chronic Prostatitis (MAPP-EP)”. PMID:25085007

Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides.

PubMed

Dissanayake, Shama; Denny, William A; Gamage, Swarna; Sarojini, Vijayalekshmi

2017-03-28

Efficient intracellular trafficking and targeted delivery to the site of action are essential to overcome the current drawbacks of cancer therapeutics. Cell Penetrating Peptides (CPPs) offer the possibility of efficient intracellular trafficking, and, therefore the development of drug delivery systems using CPPs as cargo carriers is an attractive strategy to address the current drawbacks of cancer therapeutics. Additionally, the possibility of incorporating Tumor Targeting Peptides (TTPs) into the delivery system provides the necessary drug targeting effect. Therefore the conjugation of CPPs and/or TTPs with therapeutics provides a potentially efficient method of improving intracellular drug delivery mechanisms. Peptides used as cargo carriers in DDS have been shown to enhance the cellular uptake of drugs and thereby provide an efficient therapeutic benefit over the drug on its own. After providing a brief overview of various drug targeting approaches, this review focusses on peptides as carriers and targeting moieties in drug-peptide covalent conjugates and summarizes the most recent literature examples where CPPs on their own or CPPs together with TTPs have been conjugated to anticancer drugs such as Doxorubicin, Methotrexate, Paclitaxel, Chlorambucil etc. A short section on CPPs used in multicomponent drug delivery systems is also included. Copyright © 2017 Elsevier B.V. All rights reserved.

Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice

PubMed Central

Khan, Yasmin; Pandy, Vijayapandi

2016-01-01

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence. PMID:27729866

Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice.

PubMed

Khan, Yasmin; Pandy, Vijayapandi

2016-01-01

Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC), on compulsive ethanol-seeking behavior using the mouse conditioned place preference (CPP) test. CPP was established by injections of ethanol (2 g/kg, i.p.) in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM), on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3, and 5 g/kg) and ACAM (300 mg/kg) 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction), during which the treatment groups received MMC (1, 3, and 5 g/kg, p.o.) or ACAM (300 mg/kg, p.o.). Finally, a priming injection of a low dose of ethanol (0.4 g/kg, i.p.) in the home cage (Reinstatement) was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5 g/kg, p.o.) and ACAM (300 mg/kg, p.o.) significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

A gene delivery system for insect cells mediated by arginine-rich cell-penetrating peptides.

PubMed

Chen, Yung-Jen; Liu, Betty Revon; Dai, Yun-Hao; Lee, Cheng-Yi; Chan, Ming-Huan; Chen, Hwei-Hsien; Chiang, Huey-Jenn; Lee, Han-Jung

2012-02-10

Most bioactive macromolecules, such as protein, DNA and RNA, basically cannot permeate into cells freely from outside the plasma membrane. Cell-penetrating peptides (CPPs) are a group of short peptides that possess the ability to traverse the cell membrane and have been considered as candidates for mediating gene and drug delivery into living cells. In this study, we demonstrate that three arginine-rich CPPs (SR9, HR9 and PR9) are able to form stable complexes with plasmid DNA and deliver DNA into insect Sf9 cells in a noncovalent manner. The transferred plasmid DNA containing enhanced green fluorescent protein (EGFP) and red fluorescent protein (RFP) coding regions could be expressed in cells functionally assayed at both the protein and RNA levels. Furthermore, treatment of cells with CPPs and CPP/DNA complexes resulted in a viability of 84-93% indicating these CPPs are not cytotoxic. These results suggest that arginine-rich CPPs appear to be a promising tool for insect transgenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

CCL2 and CCL3 are essential mediators of pelvic pain in experimental autoimmune prostatitis

PubMed Central

Quick, Marsha L.; Mukherjee, Soumi; Rudick, Charles N.; Done, Joseph D.; Schaeffer, Anthony J.

2012-01-01

Experimental autoimmune prostatitis (EAP) is a murine model of chronic prostatitis/chronic pelvic pain syndrome (CPPS) in men, a syndrome characterized by chronic pelvic pain. We have demonstrated that chemokine ligands CCL2 and CCL3 are biomarkers that correlate with pelvic pain symptoms. We postulated that CCL2 and CCL3 play a functional role in CPPS and therefore examined their expression in EAP. Upon examination of the prostate 5 days after induction of EAP, CCL2 mRNA was elevated 2- to 3-fold, CCL8 by 15-fold, CCL12 by 12- to 13-fold, and CXCL9 by 2- to 4-fold compared with control mice. At 10 days the major chemokines were CXCL13 and CXCL2; at 20 days CCL2 (1- to 2-fold), CCL3 (2- to 3-fold) and CCL11 (2- to 3-fold); and at 30 days, CCL12 (20- to 35-fold) and smaller increases in CCL2, CCL3, and XCL1. Chemokine elevations were accompanied by increases in mast cells and B cells at 5 days, monocytes and neutrophils at day 10, CD4+ T cells at day 20, and CD4+ and CD8+ T cells at day 30. Anti-CCL2 and anti-CCL3 neutralizing antibodies administered at EAP onset attenuated pelvic pain development, but only anti-CCL2 antibodies were effective therapeutically. CCL2- and its cognate receptor CCR2-deficient mice were completely protected from development of pain symptoms but assumed susceptibility after reconstitution with wild-type bone marrow. CCL3-deficient mice showed resistance to the maintenance of pelvic pain while CCR5-deficient mice did not show any lessening of pelvic pain severity. These results suggest that the CCL2-CCR2 axis and CCL3 are important mediators of chronic pelvic pain in EAP. PMID:22814670

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

Cell Penetrating Peptides in the Delivery of Biopharmaceuticals

PubMed Central

Munyendo, Were LL; Lv, Huixia; Benza-Ingoula, Habiba; Baraza, Lilechi D.; Zhou, Jianping

2012-01-01

The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development. PMID:24970133

Molecular cloning and analysis of the ergopeptine assembly system in the ergot fungus Claviceps purpurea.

PubMed

Correia, Telmo; Grammel, Nicolas; Ortel, Ingo; Keller, Ullrich; Tudzynski, Paul

2003-12-01

Claviceps purpurea produces the pharmacological important ergopeptines, a class of cyclol-structured alkaloid peptides containing D-lysergic acid. These compounds are assembled from D-lysergic acid and three different amino acids by the nonribosomal peptide synthetase enzymes LPS1 and LPS2. Cloning of alkaloid biosynthesis genes from C. purpurea has revealed a gene cluster including two NRPS genes, cpps 1 and cpps 2. Protein sequence data had assigned earlier cpps1 to encode the trimodular LPS1 assembling the tripeptide portion of ergopeptines. Here, we show by transcriptional analysis, targeted inactivation, analysis of disruption mutants, and heterologous expression that cpps 2 encodes the monomodular LPS2 responsible for D-lysergic acid activation and incorporation into the ergopeptine backbone. The presence of two distinct NRPS subunits catalyzing formation of ergot peptides is the first example of a fungal NRPS system consisting of different NRPS subunits.

[Application of quality by design in granulation process for Ginkgo leaf tablet (Ⅲ)： process control strategy based on design space].

PubMed

Cui, Xiang-Long; Xu, Bing; Sun, Fei; Dai, Sheng-Yun; Shi, Xin-Yuan; Qiao, Yan-Jiang

2017-03-01

In this paper, under the guidance of quality by design (QbD) concept, the control strategy of the high shear wet granulation process of the ginkgo leaf tablet based on the design space was established to improve the process controllability and product quality consistency. The median granule size (D50) and bulk density (Da) of granules were identified as critical quality attributes (CQAs) and potential critical process parameters (pCPPs) were determined by the failure modes and effect analysis (FMEA). The Plackeet-Burmann experimental design was used to screen pCPPs and the results demonstrated that the binder amount, the wet massing time and the wet mixing impeller speed were critical process parameters (CPPs). The design space of the high shear wet granulation process was developed within pCPPs range based on the Box-Behnken design and quadratic polynomial regression models. ANOVA analysis showed that the P-values of model were less than 0.05 and the values of lack of fit test were more than 0.1, indicating that the relationship between CQAs and CPPs could be well described by the mathematical models. D₅₀ could be controlled within 170 to 500 μm, and the bulk density could be controlled within 0.30 to 0.44 g•cm⁻³ by using any CPPs combination within the scope of design space. Besides, granules produced by process parameters within the design space region could also meet the requirement of tensile strength of the ginkgo leaf tablet.. Copyright© by the Chinese Pharmaceutical Association.

Molecular imaging analysis of intestinal insulin absorption boosted by cell-penetrating peptides by using positron emission tomography.

PubMed

Kamei, Noriyasu; Morishita, Mariko; Kanayama, Yousuke; Hasegawa, Koki; Nishimura, Mie; Hayashinaka, Emi; Wada, Yasuhiro; Watanabe, Yasuyoshi; Takayama, Kozo

2010-08-17

Molecular imaging technique by use of positron emission tomography (PET) is a noninvasive tool that allows one to quantitatively analyze the function of endogenous molecules and the pharmacokinetics of therapeutic agents in vivo. This technique is expected to be useful for evaluating the effectiveness of diverse drug delivery systems. We demonstrated previously that intestinal insulin absorption is increased significantly by coadministration of cell-penetrating peptides (CPPs), which are taken up effectively by several cells. However, the distribution behavior of insulin whose absorption is increased by CPPs is not clear. We used PET imaging and quantitatively analyzed the intestinal absorption and subsequent distribution of insulin and the effect of CPPs on its absorption and distribution. An unlabeled insulin solution containing tracer insulin, (68)Ga-DOTA-insulin, was administered with or without CPPs into a rat ileal closed loop. PET imaging showed that the CPPs, particularly D-R8 and L-penetratin, significantly increased the (68)Ga-DOTA-insulin level in the liver, kidney, and circulation. After absorption from the intestine, the (68)Ga-DOTA-insulin passed rapidly through the liver and accumulated in the kidney. The increase in the hepatic and renal distribution of (68)Ga-DOTA-insulin by each CPP coadministration was similar manner as that in intestinal absorption, suggesting that the increased accumulation of insulin in the liver and kidney induced by coadministration of CPPs was associated with the increased intestinal absorption of insulin. This is the first study to show that PET imaging enables one to quantitatively analyze the distribution behavior of intestinally absorbed insulin in several organs. This imaging methodology is likely to be useful for developing effective drug delivery systems targeted to specific organs. Copyright 2010 Elsevier B.V. All rights reserved.

Direct effects of casein phosphopeptides on growth and differentiation of in vitro cultured osteoblastic cells (MC3T3-E1).

PubMed

Tulipano, Giovanni; Bulgari, Omar; Chessa, Stefania; Nardone, Alessandro; Cocchi, Daniela; Caroli, Anna

2010-02-25

Casein phosphopeptides (CPPs) obtained by enzymatic hydrolysis in vitro of caseins, have been shown to enhance calcium solubility and to increase the calcification of embryonic rat bones in their diaphyseal area. Little is known about the direct effects of CPPs on cultured osteoblastic cells. Calcium in the microenvironment surrounding bone cells is not only important for the mineralization of the extracellular matrix, but it is believed to provide preosteblasts with a signal that modulates their proliferation and differentiation. The aim of the present study was to investigate the direct effects of four selected casein phosphopeptides on osteoblastic cell (MC3T3-E1 cells) viability and differentiation. The selected peptides have been obtained by chemical synthesis and differed in the number of phosphorylated sites and in the amino acid spacing out two phosphorylated sites, in order to further characterize the relationship between structure and function. The results obtained in this work demonstrated that CPPs may directly affect osteoblast-like cell growth, calcium uptake and ultimately calcium deposition in the extracellular matrix. The effects exerted by distinct CPPs on osteogenesis in vitro can be either stimulatory or inhibitory. Differential short amino acid sequences in their molecules, like the -SpEE- and the -SpTSpEE-motifs, are likely the molecular determinants for their biological activities on osteoblastic cells. Moreover, two genetic variants of CPPs showing one amino acid change in their sequence may profoundly differ in their biological activities. Finally, our data may also suggest important clues about the role of intrinsic phosphorylated peptides derived from endogenous phosphorylated proteins in bone metabolism, apart from extrinsic CPPs. Copyright 2009 Elsevier B.V. All rights reserved.

Synthesis of CuO by Cu-CPPs with the determination of Cu(II) coordination modes from a novel complex of [Cu(terpyOH){sub 2}]·(HBTC)·2H{sub 2}O

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

Wang, Yu, E-mail: wangyu1012@hit.edu.cn; Chen, Gang, E-mail: gchen@hit.edu.cn; Han, Li

2013-10-15

In this study, we investigated the synthesis of CuO microrods by simple calcination of copper-based coordination polymer particles (Cu-CPPs) at high temperature in air. The photocatalytic activity of the CuO microrods was tested by the decomposition of aqueous solution of RhB, which was completely decomposed by irradiation with light. To analyze the relationship of metal ions and ligands in the Cu-CPPs, the single crystal of [Cu(terpyOH){sub 2}]∙(HBTC)∙2H{sub 2}O (1) (terpyOH=4′-hydroxy-2,2′:6′,2″-terpyridine, BTC=1,3,5-benzene tricarboxylate) was first prepared and characterized by X-ray single crystal structural analysis. A variety of hydrogen bonds constructing the 3D complex structure in [Cu(terpyOH){sub 2}]∙(HBTC)∙2H{sub 2}O (1) were observed.more » - Graphical abstract: Demonstrating a general method to synthesize CuO microrods via simple calcination of Cu-CPPs and Cu(II) coordination modes from a novel complex of [Cu(terpyOH){sub 2}]∙(HBTC)·2H{sub 2}O constructed by hydrogen bonding. Display Omitted - Highlights: • The formation of microrods CuO from thermal treatment of Cu-CPPs through an “escape-by-crafty-scheme” strategy has been studied. • Determination of Cu(II) coordination modes in Cu-CPPs from a novel complex of [Cu(terpyOH){sub 2}]∙(HBTC) 2H{sub 2}O. • Invested the behave of hydrogen bonding to construct the 3D complex structure. • Commendable photodegradation performance was observed.« less

CiPerGenesis, A Mutagenesis Approach that Produces Small Libraries of Circularly Permuted Proteins Randomly Opened at a Focused Region: Testing on the Green Fluorescent Protein.

PubMed

Gaytán, Paul; Roldán-Salgado, Abigail; Yáñez, Jorge A; Morales-Arrieta, Sandra; Juárez-González, Víctor R

2018-06-12

Circularly permuted proteins (cpPs) represent a novel type of mutant proteins with original termini that are covalently linked through a peptide connector and opened at any other place of the polypeptide backbone to create new ends. cpPs are finding wide applications in biotechnology because their properties may be quite different from those of the parental protein. However, the actual challenge for the creation of successful cpPs is to identify those peptide bonds that can be broken to create new termini and ensure functional and well-folded cpPs. Herein, we describe CiPerGenesis, a combinatorial mutagenesis approach that uses two oligonucleotide libraries to amplify a circularized gene by PCR, starting and ending from a focused target region. This approach creates small libraries of circularly permuted genes that are easily cloned in the correct direction and frame using two different restriction sites encoded in the oligonucleotides. Once expressed, the protein libraries exhibit a unique sequence diversity, comprising cpPs that exhibit ordinary breakpoints between adjacent amino acids localized at the target region as well as cpPs with new termini containing user-defined truncations and repeats of some amino acids. CiPerGenesis was tested at the lid region G134-H148 of green fluorescent protein (GFP), revealing that the most fluorescent variants were those starting at Leu141 and ending at amino acids Tyr145, Tyr143, Glu142, Leu141, Lys140, and H139. Purification and biochemical characterization of some variants suggested a differential expression, solubility and maturation extent of the mutant proteins as the likely cause for the variability in fluorescence intensity observed in colonies.

Cell-penetrating peptides and antimicrobial peptides: how different are they?

PubMed Central

Henriques, Sónia Troeira; Melo, Manuel Nuno; Castanho, Miguel A. R. B.

2006-01-01

Some cationic peptides, referred to as CPPs (cell-penetrating peptides), have the ability to translocate across biological membranes in a non-disruptive way and to overcome the impermeable nature of the cell membrane. They have been successfully used for drug delivery into mammalian cells; however, there is no consensus about the mechanism of cellular uptake. Both endocytic and non-endocytic pathways are supported by experimental evidence. The observation that some AMPs (antimicrobial peptides) can enter host cells without damaging their cytoplasmic membrane, as well as kill pathogenic agents, has also attracted attention. The capacity to translocate across the cell membrane has been reported for some of these AMPs. Like CPPs, AMPs are short and cationic sequences with a high affinity for membranes. Similarities between CPPs and AMPs prompted us to question if these two classes of peptides really belong to unrelated families. In this Review, a critical comparison of the mechanisms that underlie cellular uptake is undertaken. A reflection and a new perspective about CPPs and AMPs are presented. PMID:16956326

(R-X-R)4 -Motif Peptides Containing Conformationally Constrained Cyclohexane-Derived Spacers: Effect on Cellular Uptake.

PubMed

Bhosle, Govind S; Fernandes, Moneesha

2017-11-08

Arginine-rich peptides having the (R-X-R) n motif are among the most effective cell-penetrating peptides (CPPs). Herein we report a several-fold increase in the efficacy of such CPPs if the linear flexible spacer (-X-) in the (R-X-R) motif is replaced by constrained cyclic 1,4-substituted-cyclohexane-derived spacers. Internalization of these oligomers in mammalian cell lines was found to be an energy-dependent process. Incorporation of these constrained, non-proteinogenic amino acid spacers in the CPPs is shown to enhance their proteolytic stability. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Portfolio for Optimal Collaboration of Human and Cyber Physical Production Systems in Problem-Solving

ERIC Educational Resources Information Center

Ansari, Fazel; Seidenberg, Ulrich

2016-01-01

This paper discusses the complementarity of human and cyber physical production systems (CPPS). The discourse of complementarity is elaborated by defining five criteria for comparing the characteristics of human and CPPS. Finally, a management portfolio matrix is proposed for examining the feasibility of optimal collaboration between them. The…

Discrimination between biologically relevant calcium phosphate phases by surface-analytical techniques

NASA Astrophysics Data System (ADS)

Kleine-Boymann, Matthias; Rohnke, Marcus; Henss, Anja; Peppler, Klaus; Sann, Joachim; Janek, Juergen

2014-08-01

The spatially resolved phase identification of biologically relevant calcium phosphate phases (CPPs) in bone tissue is essential for the elucidation of bone remodeling mechanisms and for the diagnosis of bone diseases. Analytical methods with high spatial resolution for the discrimination between chemically quite close phases are rare. Therefore the applicability of state-of-the-art ToF-SIMS, XPS and EDX as chemically specific techniques was investigated. The eight CPPs hydroxyapatite (HAP), β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), octacalcium phosphate (OCP), dicalcium phosphate dihydrate (DCPD), dicalcium phosphate (DCP), monocalcium phosphate (MCP) and amorphous calcium phosphate (ACP) were either commercial materials in high purity or synthesized by ourselves. The phase purity was proven by XRD analysis. All of the eight CPPs show different mass spectra and the phases can be discriminated by applying the principal component analysis method to the mass spectrometric data. The Ca/P ratios of all phosphates were determined by XPS and EDX. With both methods some CPPs can be distinguished, but the obtained Ca/P ratios deviate systematically from their theoretical values. It is necessary in any case to determine a calibration curve, respectively the ZAF values, from appropriate standards. In XPS also the O(1s)-satellite signals are correlated to the CPPs composition. Angle resolved and long-term XPS measurements of HAP clearly prove that there is no phosphate excess at the surface. Decomposition due to X-ray irradiation has not been observed.

[Efficacy and safety of Longjintonglin Capsule for the treatment of type III prostatitis].

PubMed

Shang, Xue-Jun; Geng, Qiang; Duan, Jian-Min; Zheng, De-Quan; Xie, Lei; Guo, Jun

2014-12-01

To study the therapeutic effect and safety of Longjintonglin Capsule in the treatment of type III prostatitis (chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS). We selected 240 patients with type III prostatitis according to the diagnostic standards of the American National Institute of Health (NIH) and treated them with Longjintonglin Capsule orally 3 capsules once tid for 12 weeks. Based on the NIH chronic prostatitis symptom index (NIH-CPSI), traditional Chinese medicine (TCM) syndrome score, and leukocyte count in the expressed prostatic secretion (EPS), we evaluated the results of treatment. Totally 238 patients completed the treatment, including 108 IIIA and 120 III B prostatitis cases. Before and after 4, 8, and 12 weeks of treatment, the total NIH-CPSI scores were 23.12 ± 6.99, 18.22 ± 6.39, 14.12 ± 5.88, and 12.36 ± 6.04 (P < 0.01) in the IIIA prostatitis patients and 22.01 ± 6.28, 17.56 ± 5.89, 13.67 ± 5.18, and 11.45 ± 5.22 in the III prostatitis patients (P < 0.01), the TCM syndrome scores were 52.12 ± 13.08, 48.13 ± 12.11, 43.05 ± 11.19, and 40.78 ± 10. 59 in the former (P < 0.01) and 53.02 ± 12.12, 49.32 ± 12.78, 44.01 ± 11.79, and 39.67 ± 10.26 in the latter (P < 0.01), and the leukocyte counts were 26.09 ± 21.55, 23.02 ± 18.61, 18.25 ± 17.79, and 15.36 ± 16.38 in the IIIA cases (P < 0.01). Neither abnormalities in liver and renal function nor obvious adverse events were observed during the experiment. Longjintonglin Capsule, with its advantages of safety, effectiveness, and no obvious adverse reactions in the treatment of type III prostatitis, deserves to be recommended for clinical application.

Test Review: Children's Psychological Processing Scale (CPPS)

ERIC Educational Resources Information Center

McGill, Ryan J.

2013-01-01

The Children's Psychological Processing Scale (CPPS), authored by Milton J. Dehn and published by Schoolhouse Educational Services in 2012, is a third-party rating scale that can be administered to teachers who are familiar with children ages 5 to 12. The measure is designed to identify psychological processing deficits in children who are…

Characterization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate Bayesian approach.

PubMed

Fu, Zhibiao; Baker, Daniel; Cheng, Aili; Leighton, Julie; Appelbaum, Edward; Aon, Juan

2016-05-01

The principle of quality by design (QbD) has been widely applied to biopharmaceutical manufacturing processes. Process characterization is an essential step to implement the QbD concept to establish the design space and to define the proven acceptable ranges (PAR) for critical process parameters (CPPs). In this study, we present characterization of a Saccharomyces cerevisiae fermentation process using risk assessment analysis, statistical design of experiments (DoE), and the multivariate Bayesian predictive approach. The critical quality attributes (CQAs) and CPPs were identified with a risk assessment. The statistical model for each attribute was established using the results from the DoE study with consideration given to interactions between CPPs. Both the conventional overlapping contour plot and the multivariate Bayesian predictive approaches were used to establish the region of process operating conditions where all attributes met their specifications simultaneously. The quantitative Bayesian predictive approach was chosen to define the PARs for the CPPs, which apply to the manufacturing control strategy. Experience from the 10,000 L manufacturing scale process validation, including 64 continued process verification batches, indicates that the CPPs remain under a state of control and within the established PARs. The end product quality attributes were within their drug substance specifications. The probability generated with the Bayesian approach was also used as a tool to assess CPP deviations. This approach can be extended to develop other production process characterization and quantify a reliable operating region. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:799-812, 2016. © 2016 American Institute of Chemical Engineers.

In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides.

PubMed

Bolhassani, Azam; Jafarzade, Behnaz Sadat; Mardani, Golnaz

2017-01-01

The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full-length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose-dependent approach. A major disadvantage of PTD-fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non-covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP-based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

A Peptide-based Vector for Efficient Gene Transfer In Vitro and In Vivo

PubMed Central

Lehto, Taavi; Simonson, Oscar E; Mäger, Imre; Ezzat, Kariem; Sork, Helena; Copolovici, Dana-Maria; Viola, Joana R; Zaghloul, Eman M; Lundin, Per; Moreno, Pedro MD; Mäe, Maarja; Oskolkov, Nikita; Suhorutšenko, Julia; Smith, CI Edvard; Andaloussi, Samir EL

2011-01-01

Finding suitable nonviral delivery vehicles for nucleic acid–based therapeutics is a landmark goal in gene therapy. Cell-penetrating peptides (CPPs) are one class of delivery vectors that has been exploited for this purpose. However, since CPPs use endocytosis to enter cells, a large fraction of peptides remain trapped in endosomes. We have previously reported that stearylation of amphipathic CPPs, such as transportan 10 (TP10), dramatically increases transfection of oligonucleotides in vitro partially by promoting endosomal escape. Therefore, we aimed to evaluate whether stearyl-TP10 could be used for the delivery of plasmids as well. Our results demonstrate that stearyl-TP10 forms stable nanoparticles with plasmids that efficiently enter different cell-types in a ubiquitous manner, including primary cells, resulting in significantly higher gene expression levels than when using stearyl-Arg9 or unmodified CPPs. In fact, the transfection efficacy of stearyl-TP10 almost reached the levels of Lipofectamine 2000 (LF2000), however, without any of the observed lipofection-associated toxicities. Most importantly, stearyl-TP10/plasmid nanoparticles are nonimmunogenic, mediate efficient gene delivery in vivo, when administrated intramuscularly (i.m.) or intradermally (i.d.) without any associated toxicity in mice. PMID:21343913

Cell penetration: scope and limitations by the application of cell-penetrating peptides.

PubMed

Reissmann, Siegmund

2014-10-01

The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell-penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored in in vivo studies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging. This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood-brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Clinical pharmacology of antiepileptic drug use: "clinical pearls about the perils of patty".

PubMed

Schraeder, P L; Lathers, C M

1995-12-01

This Clinical Pharmacology Problem Solving (CPPS) Unit is for use with fourth- or fifth-year pharmacy students and third- or fourth-year medical students during conferences held when they are taking either a rotation in Neurology or Clinical Pharmacology. It may also be used for house staff teaching of residents in Neurology, Pediatrics, Internal Medicine, and Family Practice and fellows in Clinical Pharmacology. This material was prepared for a Teaching Clinic in Clinical Pharmacology taught by Claire M. Lathers, PhD, FCP, Hugh J. Burford, PhD, FCP, and Cedric M. Smith, MD, FCP, and sponsored by the American College of Clinical Pharmacology, September 19-20, 1992, Washington, DC. This workbook includes: (1) an introduction to the Clinical Pharmacology Problem Solving (CPPS) Unit; (2) the learning objectives of the clinical simulation; (3) a pretest; (4) four clinical episodes occurring over many years in the life of a patient; (5) answers to the pretest; (6) a posttest; (7) answers to the posttest.

Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

PubMed

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

PubMed Central

Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

2018-01-01

Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents. PMID:29563797

Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

PubMed

Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

2017-01-01

We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

On the importance of electrostatic interactions between cell penetrating peptides and membranes: a pathway toward tumor cell selectivity?

PubMed

Jobin, Marie-Lise; Alves, Isabel D

2014-12-01

Cell-penetrating peptides (CPPs) are small molecules of major interest due to their ability to efficiently transport cargos across cell membranes in a receptor- and energy-independent way and without being cytotoxic to cells. Since their discovery 20 years ago their potential interest in drug delivery and diagnosis became undeniable. CPPs are being used to deliver inside cells a large variety of cargos such as proteins, DNA, antibodies, imaging agents and nanoparticle drug carriers. Their cellular uptake mechanisms are still debated and may vary depending on their structure, nature and size of cargo they transport and type of cell line targeted. CPPs are generally rich in positively charged residues, thus they are prone to establish electrostatic interactions with anionic membrane components (sugars and lipids). Understanding the molecular basis of CPP membrane interaction and cellular uptake is crucial to improve their in vivo efficiency target-specificity. A great number of studies demonstrated the high potential of CPPs to translocate efficiently therapeutic cargos into cells and some peptides are even in clinical phase studies. Although these molecules seem perfect for a therapeutic or diagnosis purpose, they still possess a small but non negligible drawback: a complete lack of cell type specificity. Tumor cells have recently been shown to over-express certain glycosaminoglycans at the cell membrane surface and to possess a higher amount of anionic lipids in their outer leaflet than healthy cells. Such molecules confer the cell membrane an enhanced anionic character, property that could be used by CPPs to selectively target these cells. Moreover previous studies demonstrate the importance of electrostatic interactions between basic residues in the peptide, especially Arg, and the lipid headgroups and glycosaminoglycans in the cell membrane. Electrostatic interactions put at stake in this process might be one of the keys to resolve the puzzle of CPP cell type specificity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines.

PubMed

Wierzbicki, Piotr M; Kogut-Wierzbicka, Marzena; Ruczynski, Jaroslaw; Siedlecka-Kroplewska, Kamila; Kaszubowska, Lucyna; Rybarczyk, Agnieszka; Alenowicz, Magdalena; Rekowski, Piotr; Kmiec, Zbigniew

2014-01-01

Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5-5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

Calcium-containing phosphopeptides pave the secretory pathway for efficient protein traffic and secretion in fungi.

PubMed

Martín, Juan F

2014-09-10

Casein phosphopeptides (CPPs) containing chelated calcium drastically increase the secretion of extracellular homologous and heterologous proteins in filamentous fungi. Casein phosphopeptides released by digestion of alpha - and beta-casein are rich in phosphoserine residues (SerP). They stimulate enzyme secretion in the gastrointestinal tract and enhance the immune response in mammals, and are used as food supplements. It is well known that casein phosphopeptides transport Ca2+ across the membranes and play an important role in Ca2+ homeostasis in the cells. Addition of CPPs drastically increases the production of heterologous proteins in Aspergillus as host for industrial enzyme production. Recent proteomics studies showed that CPPs alter drastically the vesicle-mediated secretory pathway in filamentous fungi, apparently because they change the calcium concentration in organelles that act as calcium reservoirs. In the organelles calcium homeostasis a major role is played by the pmr1 gene, that encodes a Ca2+/Mn2+ transport ATPase, localized in the Golgi complex; this transporter controls the balance between intra-Golgi and cytoplasmic Ca2+ concentrations. A Golgi-located casein kinase (CkiA) governs the ER to Golgi directionality of the movement of secretory proteins by interacting with the COPII coat of secretory vesicles when they reach the Golgi. Mutants defective in the casein-2 kinase CkiA show abnormal targeting of some secretory proteins, including cytoplasmic membrane amino acid transporters that in ckiA mutants are miss-targeted to vacuolar membranes. Interestingly, addition of CPPs increases a glyceraldehyde-3-phpshate dehydrogenase protein that is known to associate with microtubules and act as a vesicle/membrane fusogenic agent. In summary, CPPs alter the protein secretory pathway in fungi adapting it to a deregulated protein traffic through the organelles and vesicles what results in a drastic increase in secretion of heterologous and also of some homologous proteins.

Single-crystal phosphors for high-brightness white LEDs/LDs

NASA Astrophysics Data System (ADS)

Víllora, Encarnación G.; Arjoca, Stelian; Inomata, Daisuke; Shimamura, Kiyoshi

2016-03-01

White light-emitting diodes (wLEDs) are the new environmental friendly sources for general lighting purposes. For applications requiring a high-brightness, current wLEDs present overheating problems, which drastically decrease their emission efficiency, color quality and lifetime. This work gives an overview of the recent investigations on single-crystal phosphors (SCPs), which are proposed as novel alternative to conventional ceramic powder phosphors (CPPs). This totally new approach takes advantage of the superior properties of single-crystals in comparison with ceramic materials. SCPs exhibit an outstanding conversion efficiency and thermal stability up to 300°C. Furthermore, compared with encapsulated CPPs, SCPs possess a superior thermal conductivity, so that generated heat can be released efficiently. The conjunction of all these characteristics results in a low temperature rise of SCPs even under high blue irradiances, where conventional CPPs are overheated or even burned. Therefore, SCPs represent the ideal, long-demanded all-inorganic phosphors for high-brightness white light sources, especially those involving the use of high-density laser-diode beams.

Role of the visual experience-dependent nascent proteome in neuronal plasticity

PubMed Central

Liu, Han-Hsuan; McClatchy, Daniel B; Schiapparelli, Lucio; Shen, Wanhua; Yates, John R

2018-01-01

Experience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experience-dependent plasticity, we conducted a quantitative proteomic screen of the nascent proteome in response to visual experience in Xenopus optic tectum using bio-orthogonal metabolic labeling (BONCAT). We identified 83 differentially synthesized candidate plasticity proteins (CPPs). The CPPs form strongly interconnected networks and are annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs revealed the requirement for eukaryotic initiation factor three subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity in tectal neurons and behavioral plasticity in tadpoles. These results demonstrate that the nascent proteome is dynamic in response to visual experience and that de novo synthesis of machinery that regulates RNA splicing and protein translation is required for experience-dependent plasticity. PMID:29412139

Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway.

PubMed

Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Flórez, Martha G; Jami, Mohammad S; Paniagua, Miguel A; Martín, Juan F

2012-01-10

The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins.

Evidence of structural invariance across three groups of Meehlian schizotypes

PubMed Central

Chan, Raymond CK; Gooding, Diane C; Shi, Hai-song; Geng, Fu-lei; Xie, Dong-jie; Yang, Zhuo-Ya; Liu, Wen-hua; Wang, Yi; Yan, Chao; Shi, Chuan; Lui, Simon SY; Cheung, Eric FC

2016-01-01

According to Meehl’s model of schizotypy, there is a latent personality organization associated with the diathesis for schizophrenia that can be identified in several ways. We sought to examine the structural invariance of four Chapman psychosis–proneness scales (CPPS) across three groups of putative schizotypes, namely, clinically-, biologically-, and psychometrically-identified schizotypes. We examined the factor structure of the Perceptual Aberration (PER), Magical Ideation (MIS), Revised Social Anhedonia (RSAS), and Revised Physical Anhedonia (RPAS) scales in 196 schizophrenia patients, 197 non-psychotic first-degree relatives, and 1,724 non-clinical young adults. The confirmatory factor analyses indicated that the best-fitting model was one in which there is a two-factor model with negative schizotypy (RSAS and RPAS) and positive schizotypy (PER and MIS). All three samples fit the model well, with Comparative Fit Indices>0.95 and Tucker Lewis Indices>0.90. The root mean square error of approximations were all small (P values⩽0.01). We also observed that for both anhedonia scales, the groups’ mean scale scores varied in the hypothesized direction, as predicted by Meehl’s model of schizotypy. All three Chinese samples, namely, the patients (clinical schizotypes), relatives (biologically-identified schizotypes), and non-clinical young adults (containing psychometrically-identified schizotypes) showed the same factorial structure. This finding supports the suitability of the CPPS for cross-cultural and/or genetic investigations of schizotypy. PMID:27336057

Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway

PubMed Central

2012-01-01

Background The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Results Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. Conclusions In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins. PMID:22234238

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

PubMed

de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

2017-05-01

To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

PubMed

Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

2017-10-01

The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

Imprinting continuously varying topographical structure onto large-aperture optical surfaces using magnetorheological finishing

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

Menapace, J A; Davis, P J; Dixit, S

2007-03-07

Over the past four years we have advanced Magnetorheological Finishing (MRF) techniques and tools to imprint complex continuously varying topographical structures onto large-aperture (430 x 430 mm) optical surfaces. These optics, known as continuous phase plates (CPPs), are important for high-power laser applications requiring precise manipulation and control of beam-shape, energy distribution, and wavefront profile. MRF's unique deterministic-sub-aperture polishing characteristics make it possible to imprint complex topographical information onto optical surfaces at spatial scale-lengths approaching 1 mm and surface peak-to-valleys as high as 22 {micro}m. During this discussion, we will present the evolution of the MRF imprinting technology and themore » MRF tools designed to manufacture large-aperture 430 x 430 mm CPPs. Our results will show how the MRF removal function impacts and limits imprint fidelity and what must be done to arrive at a high-quality surface. We also present several examples of this imprinting technology for fabrication of phase correction plates and CPPs for use in high-power laser applications.« less

A Preliminary Analysis of Calcifying Particles in the Serum and Prostates of Patients with Prostatic Inflammation

NASA Technical Reports Server (NTRS)

Jones, Jeffrey A.; Carlson, Grant; Kajander, E. Olavi; Warmflash, David; Taylor, Karen; Ayala, Gustavo; Shoskes, Daniel; Everett, Meg; Feedback, Dan; Ciftcioglu, Neva

2006-01-01

Chronic diseases of the prostate such as benign prostatic hyperplasia (BPH) & chronic pelvic pain syndrome (CPPS) have associated findings of chronic inflammation, despite a lack of causal relationship. Numerous attempts to define an infectious agent responsible for the clinical findings have been inconsistent. The possibility of an infectious agent, that has not been uncovered with routine culturing methods, forms the basis for this study. Serum from 940 healthy Finnish men were compared with serum from 40 Crohn's, 40 path dx prostatitis, & 40 with path dx carcinoma, using an enzyme-linked immunosorbant assay (ELISA), to detect antigens specific to Nanobacteria(NB) utilizing monoclonal antibodies (Ab) 5/3 and 8D10. This ELISA has not been validated for detecting NB-associated with clinical prostatic disease, yet cross-reactivity with other bacterial species is low. Immunohistochemistry was performed on de-paraffinized prostatic tissue slides, de-calcified with EDTA and stained with the DAKO Catalyzed Signal Amplification kit, employing 8D10 as the primary (target/antigen-detecting) Ab. The mean (plus or minus SD) & median concentrations of NB antigen (U/50 L) were 379.59 (plus or minus 219.28) & 640.00 for patients with prostatitis (BPH) vs 3.31 (plus or minus 3.55) & 2.94 for prostate adenocarcinoma, 1.88 (plus or minus 2.94) & 0.80 for Crohn's disease, & 7.43 (plus or minus 25.57) & 0.00 for patients with no clinical prostatic disease. Unpaired t-tests revealed statistically significant differences between the prostatitis (BPH) sera & each of the other groups with p less than 0.005, but no differences between the other groups themselves. Preliminary studies with immunohistochemistry & 3-D confocal microscopy reveal 16/24 tissue sections + for NB Ag in BPH vs. only 2/22 tissue sections with prostate cancer. The preliminary findings of this serum screening study suggest that NB antigen may be commonly found in the serum of patients with the pathological diagnosis of prostatitis. Preliminary immunohistologic studies, suggest that NB may be found within the gland itself at a higher rate in patients with BPH relative to patients with adenocarcinoma, however confirmatory studies with a more specific ELISA technique, primary cultures, & with larger numbers of patients in a prospective design are required to determine if 1) NB are a causative organism for clinical hyperplastic and inflammatory disease, & if 2) serological testing can be used to discriminate patients with nanobacterial-associated prostatic disease.

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Constant proportion harvest policies: dynamic implications in the Pacific halibut and Atlantic cod fisheries.

PubMed

Yakubu, Abdul-Aziz; Li, Nianpeng; Conrad, Jon M; Zeeman, Mary-Lou

2011-07-01

Overfishing, pollution and other environmental factors have greatly reduced commercially valuable stocks of fish. In a 2006 Science article, a group of ecologists and economists warned that the world may run out of seafood from natural stocks if overfishing continues at current rates. In this paper, we explore the interaction between a constant proportion harvest policy and recruitment dynamics. We examine the discrete-time constant proportion harvest policy discussed in Ang et al. (2009) and then expand the framework to include stock-recruitment functions that are compensatory and overcompensatory, both with and without the Allee effect. We focus on constant proportion policies (CPPs). CPPs have the potential to stabilize complex overcompensatory stock dynamics, with or without the Allee effect, provided the rates of harvest stay below a threshold. If that threshold is exceeded, CPPs are known to result in the sudden collapse of a fish stock when stock recruitment exhibits the Allee effect. In case studies, we analyze CPPs as they might be applied to Gulf of Alaska Pacific halibut fishery and the Georges Bank Atlantic cod fishery based on harvest rates from 1975 to 2007. The best fit models suggest that, under high fishing mortalities, the halibut fishery is vulnerable to sudden population collapse while the cod fishery is vulnerable to steady decline to zero. The models also suggest that CPP with mean harvesting levels from the last 30 years can be effective at preventing collapse in the halibut fishery, but these same policies would lead to steady decline to zero in the Atlantic cod fishery. We observe that the likelihood of collapse in both fisheries increases with increased stochasticity (for example, weather variability) as predicted by models of global climate change. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of cell-penetrating peptides (CPPs) as vehicles for intracellular delivery of antisense peptide nucleic acid (PNA).

PubMed

Bendifallah, Nadia; Rasmussen, Frank Winther; Zachar, Vladimir; Ebbesen, Peter; Nielsen, Peter E; Koppelhus, Uffe

2006-01-01

Cell-penetrating peptides (CPPs) are characterized by their ability to be internalized in mammalian cells. To investigate the relative potency of CPPs as carriers of medicinally relevant cargo, a positive read-out assay based on the ability of a peptide nucleic acid (PNA) oligomer to promote correct expression of a recombinant luciferase gene was employed. Seven different CPPs were included in the study: Transportan, oligo-arginine (R7-9), pTat, Penetratin, KFF, SynB3, and NLS. The CPP-PNA conjugates were synthesized by different conjugation chemistries: continuous synthesis, maleimide coupling, and ester or disulfide linkage. Under serum-free conditions PNA-SS-Transportan-amide (ortho)-PNA was found to be the most potent conjugate, resulting in maximum luciferase signal at a concentration of 1-2 microM. (D-Arg)9-PNA showed optimal efficacy at 5 microM but gave rise to only one-third of the luciferase signal obtained with the Transportan conjugate. The pTat- and KFF-PNA conjugates showed significantly lower efficacy. The penetratin-, SynB3-. and NLS-PNA conjugates showed only minimal or no activity. Serum was found to have a drastic negative impact on CPP-driven cellular uptake. PNA-SS-Transportan-acid (ortho) and (D-Arg)9-PNA were least sensitive to the presence of serum. Both the chemical nature and, in the case of Transportan, the position of the peptide PNA coupling were found to have a major impact on the transport capacity of the peptides. However, no simple relationship between linker type and antisense activity of the conjugates could be deduced from the data.

Cepstral analysis of normal and pathological voice in Spanish adults. Smoothed cepstral peak prominence in sustained vowels versus connected speech.

PubMed

Delgado-Hernández, Jonathan; León-Gómez, Nieves M; Izquierdo-Arteaga, Laura M; Llanos-Fumero, Yanira

In recent years, the use of cepstral measures for acoustic evaluation of voice has increased. One of the most investigated parameters is smoothed cepstral peak prominence (CPPs). The objectives of this paper are to establish the usefulness of this acoustic measure in the objective evaluation of alterations of the voice in Spanish and to determine what type of voice sample (sustained vowels or connected speech) is the most sensitive in evaluating the severity of dysphonia. Forty subjects participated in this study 40, 20 controls and 20 with dysphonia. Two voice samples were recorded for each subject (one sustained vowel/a/and four phonetically balanced sentences) and the CPPs was calculated using the Praat programme. Three raters perceptually evaluated the voice sample with the Grade parameter of GRABS scale. Significantly lower values were found in the dysphonic voices, both for/a/(t [38] = 4.85, P<.000) and for phrases (t [38] = 5,75, P<.000). In relation to the type of voice sample most suitable for evaluating the severity of voice alterations, a strong correlation was found with the acoustic-perceptual scale of CPPs calculated from connected speech (r s = -0.73) and moderate correlation with that calculated from the sustained vowel (r s = -0,56). The results of this preliminary study suggest that CPPs is a good measure to detect dysphonia and to objectively assess the severity of alterations in the voice. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Electronic transport properties in [n]cycloparaphenylenes molecular devices

NASA Astrophysics Data System (ADS)

Hu, Lizhi; Guo, Yandong; Yan, Xiaohong; Zeng, Hongli; Zhou, Jie

2017-07-01

The electronic transport of [n]cycloparaphenylenes ([n]CPPs) is investigated based on nonequilibrium Green's function formalism in combination with the density-functional theory. Negative differential resistance (NDR) phenomenon is observed. Further analysis shows that the reduction of the transmission peak induced by the bias changing near Fermi energy results in the NDR effect. Replacing the electrode (from carbon chain to Au electrode), doping with N atom and changing the size of the nanohoop (n = 5, 6, 8, 10) have also been studied and the NDR still exists, suggesting the NDR behavior is the intrinsic feature of such [n]CPPs systems, which would be quite useful in future nanoelectronic devices.

Singlet and triplet excitons and charge polarons in cycloparaphenylenes. A density functional theory study

DOE PAGES

Liu, Jin; Adamska, Lyudmyla; Doorn, Stephen K.; ...

2015-05-14

Conformational structure and the electronic properties of various electronic excitations in cycloparaphenylenes (CPPs) are calculated using hybrid Density Functional Theory (DFT). The results demonstrate that wavefunctions of singlet and triplet excitons as well as the positive and negative polarons remain fully delocalized in CPPs. In contrast, these excitations in larger CPP molecules become localized on several phenyl rings, which are locally planarized, while the undeformed ground state geometry is preserved on the rest of the hoop. As evidenced by the measurements of bond-length alternation and dihedral angles, localized regions show stronger hybridization between neighboring bonds and thus enhanced electronic communication.more » This effect is even more significant in the smaller hoops, where phenyl rings have strong quinoid character in the ground state. Thus, upon excitation, electron–phonon coupling leads to the self-trapping of the electronic wavefunction and release of energy from fractions of an eV up to two eVs, depending on the type of excitation and the size of the hoop. The impact of such localization on electronic and optical properties of CPPs is systematically investigated and compared with the available experimental measurements.« less

Bioactive Peptides Isolated from Casein Phosphopeptides Enhance Calcium and Magnesium Uptake in Caco-2 Cell Monolayers.

PubMed

Cao, Yong; Miao, Jianyin; Liu, Guo; Luo, Zhen; Xia, Zumeng; Liu, Fei; Yao, Mingfei; Cao, Xiaoqiong; Sun, Shengwei; Lin, Yanyin; Lan, Yaqi; Xiao, Hang

2017-03-22

The ability of casein phosphopeptides (CPPs) to bind and transport minerals has been previously studied. However, the single bioactive peptides responsible for the effects of CPPs have not been identified. This study was to purify calcium-binding peptides from CPPs and to determine their effects on calcium and magnesium uptake by Caco-2 cell monolayers. Five monomer peptides designated P1 to P5 were isolated and the amino acid sequences were determined using LC-MS/MS. Compared with the CPP-free control, all five monomeric peptides exhibited significant enhancing effects on the uptake of calcium and magnesium (P < 0.05). Interestingly, when calcium and magnesium were presented simultaneously with P5, magnesium was taken up with priority over calcium in the Caco-2 cell monolayers. For example, at 180 min, the amount of transferred magnesium and calcium was 78.4 ± 0.95 μg/well and 2.56 ± 0.64 μg/well, respectively, showing a more than 30-fold difference in the amount of transport caused by P5. These results provide novel insight into the mineral transport activity of phosphopeptides obtained from casein.

Purification, Characterization, and Antioxidant Activity of Polysaccharides Isolated from Cortex Periplocae.

PubMed

Wang, Xiaoli; Zhang, Yifei; Liu, Zhikai; Zhao, Mingqin; Liu, Pengfei

2017-10-31

In this study, crude Cortex Periplocae polysaccharides (CCPPs) were extracted with water. CCPPs were decolored with AB-8 resin and deproteinated using papain-Sevage methods. Then, they were further purified and separated through DEAE-52 anion exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Three main fractions-CPP1, CPP2, and CPP3, (CPPs)-were obtained. The average molecular weights, monosaccharide analysis, surface morphology, and chemical compositions of the CPPs were investigated by high-performance gel permeation chromatography (HPGPC), gas chromatography-mass spectrometry (GC/MS), UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectrum, and nuclear magnetic resonance (NMR). In addition, the antioxidant activities of these three polysaccharides were investigated. The results indicated that all of the CPPs were composed of rhamnose, arabinose, mannose, glucose, and galactose. These three polysaccharides exhibited antioxidant activities in four assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical, reducing power, and total antioxidant activity in vitro. The data indicated that these three polysaccharides could be utilized as potential natural sources of alternative additives in the functional food, cosmetics, and pharmaceutical industries.

The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

PubMed

Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

2014-03-01

Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to deliver neuroprotective drugs to the CNS following injury and/or potential neuroprotectants in their own right.

A quality by design study applied to an industrial pharmaceutical fluid bed granulation.

PubMed

Lourenço, Vera; Lochmann, Dirk; Reich, Gabriele; Menezes, José C; Herdling, Thorsten; Schewitz, Jens

2012-06-01

The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale. The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides.

PubMed

Liu, Betty R; Winiarz, Jeffrey G; Moon, Jong-Sik; Lo, Shih-Yen; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2013-11-01

Semiconductor nanoparticles, also known as quantum dots (QDs), are widely used in biomedical imaging studies and pharmaceutical research. Cell-penetrating peptides (CPPs) are a group of small peptides that are able to traverse cell membrane and deliver a variety of cargoes into living cells. CPPs deliver QDs into cells with minimal nonspecific absorption and toxic effect. In this study, water-soluble, monodisperse, carboxyl-functionalized indium phosphide (InP)/zinc sulfide (ZnS) QDs coated with polyethylene glycol lipids (designated QInP) were synthesized for the first time. The physicochemical properties (optical absorption, fluorescence and charging state) and cellular internalization of QInP and CPP/QInP complexes were characterized. CPPs noncovalently interact with QInP in vitro to form stable CPP/QInP complexes, which can then efficiently deliver QInP into human A549 cells. The introduction of 500nM of CPP/QInP complexes and QInP at concentrations of less than 1μM did not reduce cell viability. These results indicate that carboxylated and polyethylene-glycolylated (PEGylated) bifunctionalized QInP are biocompatible nanoparticles with potential for use in biomedical imaging studies and drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Traps of carnivorous pitcher plants as a habitat: composition of the fluid, biodiversity and mutualistic activities

PubMed Central

Adlassnig, Wolfram; Peroutka, Marianne; Lendl, Thomas

2011-01-01

Background Carnivorous pitcher plants (CPPs) use cone-shaped leaves to trap animals for nutrient supply but are not able to kill all intruders of their traps. Numerous species, ranging from bacteria to vertrebrates, survive and propagate in the otherwise deadly traps. This paper reviews the literature on phytotelmata of CPPs. Pitcher Fluid as a Habitat The volumes of pitchers range from 0·2 mL to 1·5 L. In Nepenthes and Cephalotus, the fluid is secreted by the trap; the other genera collect rain water. The fluid is usually acidic, rich in O2 and contains digestive enzymes. In some taxa, toxins or detergents are found, or the fluid is extremely viscous. In Heliamphora or Sarracenia, the fluid differs little from pure water. Inquiline Diversity Pitcher inquilines comprise bacteria, protozoa, algae, fungi, rotifers, crustaceans, arachnids, insects and amphibia. The dominant groups are protists and Dipteran larvae. The various species of CPPs host different sets of inquilines. Sarracenia purpurea hosts up to 165 species of inquilines, followed by Nepenthes ampullaria with 59 species, compared with only three species from Brocchinia reducta. Reasons for these differences include size, the life span of the pitcher as well as its fluid. Mutualistic Activities Inquilines closely interact with their host. Some live as parasites, but the vast majority are mutualists. Beneficial activities include secretion of enzymes, feeding on the plant's prey and successive excretion of inorganic nutrients, mechanical break up of the prey, removal of excessive prey and assimilation of atmospheric N2. Conclusions There is strong evidence that CPPs influence their phytotelm. Two strategies can be distinguished: (1) Nepenthes and Cephalotus produce acidic, toxic or digestive fluids and host a limited diversity of inquilines. (2) Genera without efficient enzymes such as Sarracenia or Heliamphora host diverse organisms and depend to a large extent on their symbionts for prey utilization. PMID:21159782

Traps of carnivorous pitcher plants as a habitat: composition of the fluid, biodiversity and mutualistic activities.

PubMed

Adlassnig, Wolfram; Peroutka, Marianne; Lendl, Thomas

2011-02-01

Carnivorous pitcher plants (CPPs) use cone-shaped leaves to trap animals for nutrient supply but are not able to kill all intruders of their traps. Numerous species, ranging from bacteria to vertrebrates, survive and propagate in the otherwise deadly traps. This paper reviews the literature on phytotelmata of CPPs. Fluid as a Habitat The volumes of pitchers range from 0·2 mL to 1·5 L. In Nepenthes and Cephalotus, the fluid is secreted by the trap; the other genera collect rain water. The fluid is usually acidic, rich in O(2) and contains digestive enzymes. In some taxa, toxins or detergents are found, or the fluid is extremely viscous. In Heliamphora or Sarracenia, the fluid differs little from pure water. Diversity Pitcher inquilines comprise bacteria, protozoa, algae, fungi, rotifers, crustaceans, arachnids, insects and amphibia. The dominant groups are protists and Dipteran larvae. The various species of CPPs host different sets of inquilines. Sarracenia purpurea hosts up to 165 species of inquilines, followed by Nepenthes ampullaria with 59 species, compared with only three species from Brocchinia reducta. Reasons for these differences include size, the life span of the pitcher as well as its fluid. MUTUALISTIC: Activities Inquilines closely interact with their host. Some live as parasites, but the vast majority are mutualists. Beneficial activities include secretion of enzymes, feeding on the plant's prey and successive excretion of inorganic nutrients, mechanical break up of the prey, removal of excessive prey and assimilation of atmospheric N(2). There is strong evidence that CPPs influence their phytotelm. Two strategies can be distinguished: (1) Nepenthes and Cephalotus produce acidic, toxic or digestive fluids and host a limited diversity of inquilines. (2) Genera without efficient enzymes such as Sarracenia or Heliamphora host diverse organisms and depend to a large extent on their symbionts for prey utilization.

Q-marker based strategy for CMC research of Chinese medicine: A case study of Panax Notoginseng saponins.

PubMed

Zhong, Yi; Zhu, Jieqiang; Yang, Zhenzhong; Shao, Qing; Fan, Xiaohui; Cheng, Yiyu

2018-01-31

To ensure pharmaceutical quality, chemistry, manufacturing and control (CMC) research is essential. However, due to the inherent complexity of Chinese medicine (CM), CMC study of CM remains a great challenge for academia, industry, and regulatory agencies. Recently, quality-marker (Q-marker) was proposed to establish quality standards or quality analysis approaches of Chinese medicine, which sheds a light on Chinese medicine's CMC study. Here manufacture processes of Panax Notoginseng Saponins (PNS) is taken as a case study and the present work is to establish a Q-marker based research strategy for CMC of Chinese medicine. The Q-markers of Panax Notoginseng Saponins (PNS) is selected and established by integrating chemical profile with pharmacological activities. Then, the key processes of PNS manufacturing are identified by material flow analysis. Furthermore, modeling algorithms are employed to explore the relationship between Q-markers and critical process parameters (CPPs) of the key processes. At last, CPPs of the key processes are optimized in order to improving the process efficiency. Among the 97 identified compounds, Notoginsenoside R 1 , ginsenoside Rg 1 , Re, Rb 1 and Rd are selected as the Q-markers of PNS. Our analysis on PNS manufacturing show the extraction process and column chromatography process are the key processes. With the CPPs of each process as the inputs and Q-markers' contents as the outputs, two process prediction models are built separately for the extraction process and column chromatography process of Panax notoginseng, which both possess good prediction ability. Based on the efficiency models of extraction process and column chromatography process we constructed, the optimal CPPs of both processes are calculated. Our results show that the Q-markers derived from CMC research strategy can be applied to analyze the manufacturing processes of Chinese medicine to assure product's quality and promote key processes' efficiency simultaneously. Copyright © 2018 Elsevier GmbH. All rights reserved.

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model

PubMed Central

Pérez-Alvarado, Carlos; Gómez, Consuelo; Reyes, Miguel; García, Mario; Pérez, Elizabeth; Pérez de la Mora, Carlos; Sanchez, Virginia

2017-01-01

Objective. To evaluate the anti-inflammatory properties of Dialyzable Leukocyte Extract (DLE) in a murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods. Histopathological characterization, prostatein Enzyme-Linked Immunosorbent Assay, and immunohistochemical analysis for CD45, TNF-α, IFN-γ, IL-6, IL-17, and IL-4 molecules were done in prostatic Wistar rats treated with DLE, placebo, or Dexamethasone. Results. Histopathological analysis of animals induced to prostatitis showed inflammatory infiltrate, mainly constituted by leucocytes and mast cells as well as Benign Prostatic Hyperplasia. Serum prostatein concentrations were 14 times higher than those displayed by healthy animals. After DLE and Dexamethasone treatments, the inflammatory infiltrate decreased; the tissue morphology was similar to that of a normal prostate, and the prostatein decreased to the basal levels of healthy animals. DLE treatment produced a decreased expression of the cell surface marker CD45 and the proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17. On the other hand, the expression of anti-inflammatory cytokine IL-4 increased in both the Dexamethasone and DLE groups. Conclusion. DLE is able to modulate the inflammatory response in Experimental Autoimmune Prostatitis (EAP). PMID:28386549

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model.

PubMed

Pérez-Alvarado, Carlos; Gómez, Consuelo; Reyes, Miguel; García, Mario; Pérez, Elizabeth; Pérez de la Mora, Carlos; Sanchez, Virginia; Pérez Ishiwara, D Guillermo

2017-01-01

Objective. To evaluate the anti-inflammatory properties of Dialyzable Leukocyte Extract (DLE) in a murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods. Histopathological characterization, prostatein Enzyme-Linked Immunosorbent Assay, and immunohistochemical analysis for CD45, TNF- α , IFN- γ , IL-6, IL-17, and IL-4 molecules were done in prostatic Wistar rats treated with DLE, placebo, or Dexamethasone. Results. Histopathological analysis of animals induced to prostatitis showed inflammatory infiltrate, mainly constituted by leucocytes and mast cells as well as Benign Prostatic Hyperplasia. Serum prostatein concentrations were 14 times higher than those displayed by healthy animals. After DLE and Dexamethasone treatments, the inflammatory infiltrate decreased; the tissue morphology was similar to that of a normal prostate, and the prostatein decreased to the basal levels of healthy animals. DLE treatment produced a decreased expression of the cell surface marker CD45 and the proinflammatory cytokines TNF- α , IFN- γ , IL-6, and IL-17. On the other hand, the expression of anti-inflammatory cytokine IL-4 increased in both the Dexamethasone and DLE groups. Conclusion. DLE is able to modulate the inflammatory response in Experimental Autoimmune Prostatitis (EAP).

Comprehensive overview of prostatitis.

PubMed

Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

2017-10-01

Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

PubMed

Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

2016-01-01

Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

Application of ICH Q9 Quality Risk Management Tools for Advanced Development of Hot Melt Coated Multiparticulate Systems.

PubMed

Stocker, Elena; Becker, Karin; Hate, Siddhi; Hohl, Roland; Schiemenz, Wolfgang; Sacher, Stephan; Zimmer, Andreas; Salar-Behzadi, Sharareh

2017-01-01

This study aimed to apply quality risk management based on the The International Conference on Harmonisation guideline Q9 for the early development stage of hot melt coated multiparticulate systems for oral administration. N-acetylcysteine crystals were coated with a formulation composing tripalmitin and polysorbate 65. The critical quality attributes (CQAs) were initially prioritized using failure mode and effects analysis. The CQAs of the coated material were defined as particle size, taste-masking efficiency, and immediate release profile. The hot melt coated process was characterized via a flowchart, based on the identified potential critical process parameters (CPPs) and their impact on the CQAs. These CPPs were prioritized using a process failure mode, effects, and criticality analysis and their critical impact on the CQAs was experimentally confirmed using a statistical design of experiments. Spray rate, atomization air pressure, and air flow rate were identified as CPPs. Coating amount and content of polysorbate 65 in the coating formulation were identified as critical material attributes. A hazard and critical control points analysis was applied to define control strategies at the critical process points. A fault tree analysis evaluated causes for potential process failures. We successfully demonstrated that a standardized quality risk management approach optimizes the product development sustainability and supports the regulatory aspects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

η6-Cycloparaphenylene transition metal complexes: synthesis, structure, photophysical properties, and application to the selective monofunctionalization of cycloparaphenylenes.

PubMed

Kubota, Natsumi; Segawa, Yasutomo; Itami, Kenichiro

2015-01-28

The synthesis, structure, photophysical properties, and reactivity of cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are described. The η(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo, W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W). In the (1)H NMR spectra of these complexes, characteristic upfield-shifted singlet signals corresponding to the four hydrogen atoms attached to the coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the solid state and in solution. TD-DFT calculations suggested that the emerging high-wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP-Cr(CO)3, a rapid and highly monoselective CPP functionalization has been achieved. The established one-pot method, consisting of complexation, deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl-, boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to reacted starting material.

Experimental autoimmune prostatitis induces microglial activation in the spinal cord.

PubMed

Wong, Larry; Done, Joseph D; Schaeffer, Anthony J; Thumbikat, Praveen

2015-01-01

The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. © 2014 Wiley Periodicals, Inc.

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

PubMed Central

Wong, Larry; Done, Joseph D.; Schaeffer, Anthony J.; Thumbikat, Praveen

2014-01-01

Background The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host’s immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Methods Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S4–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Results Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Conclusion Our data shows that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. PMID:25263093

Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes

NASA Astrophysics Data System (ADS)

Weinberger, Andreas; Walter, Vivien; MacEwan, Sarah R.; Schmatko, Tatiana; Muller, Pierre; Schroder, André P.; Chilkoti, Ashutosh; Marques, Carlos M.

2017-03-01

Although cationic cell-penetrating peptides (CPPs) are able to bind to cell membranes, thus promoting cell internalization by active pathways, attachment of cargo molecules to CPPs invariably reduces their cellular uptake. We show here that CPP binding to lipid bilayers, a simple model of the cell membrane, can be recovered by designing cargo molecules that self-assemble into spherical micelles and increase the local interfacial density of CPP on the surface of the cargo. Experiments performed on model giant unilamellar vesicles under a confocal laser scanning microscope show that a family of thermally responsive elastin-like polypeptides that exhibit temperature-triggered micellization can promote temperature triggered attachment of the micelles to membranes, thus rescuing by self-assembly the cargo-induced loss of the CPP affinity to bio-membranes.

Studies of proteoglycan involvement in CPP-mediated delivery.

PubMed

Wittrup, Anders; Zhang, Si-He; Belting, Mattias

2011-01-01

Cell-penetrating peptides (CPPs) are widely used to deliver macromolecular cargoes to intracellular sites of action. Many CPPs have been demonstrated to rely on cell surface heparan sulfate proteoglycans (HSPGs) for efficient cellular entry and delivery. In this chapter, we describe methods for the study of PG involvement in CPP uptake. We provide descriptions of how to determine whether uptake of a CPP of interest is dependent on PGs. We also provide detailed protocols for the purification of PGs by anion-exchange chromatography as well as the characterization of the HSPG core protein composition of a cell line of interest. Finally, we present methods for modulating the expression level of specific HSPG core proteins as a means to determine the core protein specificity in the uptake of a particular CPP.

Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease.

PubMed

Dinca, Ana; Chien, Wei-Ming; Chin, Michael T

2016-02-22

Protein therapy exhibits several advantages over small molecule drugs and is increasingly being developed for the treatment of disorders ranging from single enzyme deficiencies to cancer. Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa). Recombinant proteins that include a CPP tag to promote intracellular delivery show promise as therapeutic agents with encouraging success rates in both animal and human trials. This review highlights recent advances in protein-CPP therapy and discusses optimization strategies and potential detrimental effects.

Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells.

PubMed

Kaitsuka, Taku; Tomizawa, Kazuhito

2015-11-06

Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

Using an innovative combination of quality-by-design and green analytical chemistry approaches for the development of a stability indicating UHPLC method in pharmaceutical products.

PubMed

Boussès, Christine; Ferey, Ludivine; Vedrines, Elodie; Gaudin, Karen

2015-11-10

An innovative combination of green chemistry and quality by design (QbD) approach is presented through the development of an UHPLC method for the analysis of the main degradation products of dextromethorphan hydrobromide. QbD strategy was integrated to the field of green analytical chemistry to improve method understanding while assuring quality and minimizing environmental impacts, and analyst exposure. This analytical method was thoroughly evaluated by applying risk assessment and multivariate analysis tools. After a scouting phase aimed at selecting a suitable stationary phase and an organic solvent in accordance with green chemistry principles, quality risk assessment tools were applied to determine the critical process parameters (CPPs). The effects of the CPPs on critical quality attributes (CQAs), i.e., resolutions, efficiencies, and solvent consumption were further evaluated by means of a screening design. A response surface methodology was then carried out to model CQAs as function of the selected CPPs and the optimal separation conditions were determined through a desirability analysis. Resulting contour plots enabled to establish the design space (DS) (method operable design region) where all CQAs fulfilled the requirements. An experimental validation of the DS proved that quality within the DS was guaranteed; therefore no more robustness study was required before the validation. Finally, this UHPLC method was validated using the concept of total error and was used to analyze a pharmaceutical drug product. Copyright © 2015 Elsevier B.V. All rights reserved.

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists.

PubMed

Grabus, Sheri D; Martin, Billy R; Brown, Sharon E; Damaj, M Imad

2006-03-01

Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.

Development of a design space and predictive statistical model for capsule filling of low-fill-weight inhalation products.

PubMed

Faulhammer, E; Llusa, M; Wahl, P R; Paudel, A; Lawrence, S; Biserni, S; Calzolari, V; Khinast, J G

2016-01-01

The objectives of this study were to develop a predictive statistical model for low-fill-weight capsule filling of inhalation products with dosator nozzles via the quality by design (QbD) approach and based on that to create refined models that include quadratic terms for significant parameters. Various controllable process parameters and uncontrolled material attributes of 12 powders were initially screened using a linear model with partial least square (PLS) regression to determine their effect on the critical quality attributes (CQA; fill weight and weight variability). After identifying critical material attributes (CMAs) and critical process parameters (CPPs) that influenced the CQA, model refinement was performed to study if interactions or quadratic terms influence the model. Based on the assessment of the effects of the CPPs and CMAs on fill weight and weight variability for low-fill-weight inhalation products, we developed an excellent linear predictive model for fill weight (R(2 )= 0.96, Q(2 )= 0.96 for powders with good flow properties and R(2 )= 0.94, Q(2 )= 0.93 for cohesive powders) and a model that provides a good approximation of the fill weight variability for each powder group. We validated the model, established a design space for the performance of different types of inhalation grade lactose on low-fill weight capsule filling and successfully used the CMAs and CPPs to predict fill weight of powders that were not included in the development set.

Metabolic engineering of the Stevia rebaudiana ent-kaurene biosynthetic pathway in recombinant Escherichia coli.

PubMed

Kong, Min Kyung; Kang, Hyun-Jun; Kim, Jin Ho; Oh, Soon Hwan; Lee, Pyung Cheon

2015-11-20

The ent-kaurene is a dedicated precursor pool and is responsible for synthesizing natural sweeteners such as steviol glycosides. In this study, to produce ent-kaurene in Escherichia coli, we modularly constructed and expressed two ent-kaurene genes encoding ent-copalyl diphosphate synthase (CPPS) and ent-kaurene synthase (KS) from Stevia rebaudiana known as a typical plant producing steviol glycoside. The CPPS and KS from S. rebaudiana were functionally expressed in a heterologous host E. coli. Furthermore, in order to enhance ent-kaurene production in E. coli, six geranylgeranyl diphosphate synthases (GGPPS) from various microorganisms and eight strains of E. coli as host were compared by measuring ent-kaurene production. The highest ent-kaurene production of approximately 41.1mg/L was demonstrated in E. coli strain MG1655 co-expressing synthetic CPPS-KS module and GGPPS from Rhodobacter sphaeroides. The ent-kaurene production was further increased up to 179.6 mg/L by overexpression of the three key enzymes for isoprenoid precursor, 1-deoxyxylulose-5-phosphate synthase (DXS), farnesyl diphosphate synthase (IspA) and isopentenyl diphosphate isomerase (IDI) from E. coli. Finally, the highest titer of ent-kaurene (578 mg/L) with a specific yield of ent-kaurene of 143.5mg/g dry cell weight was obtained by culturing E. coli strain MG1655 co-expressing the ent-kaurene module, DXS, IDI and IspA in 1L bioreactor containing 20 g/L glycerol. Copyright © 2015 Elsevier B.V. All rights reserved.

Translocation of cell-penetrating peptides into Candida fungal pathogens.

PubMed

Gong, Zifan; Karlsson, Amy J

2017-09-01

Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

Clinical applications of low-intensity pulsed ultrasound and its potential role in urology

PubMed Central

Lin, Guiting; Lei, Hongen; Lue, Tom F.; Guo, Yinglu

2016-01-01

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that delivered at a much lower intensity (<3 W/cm2) than traditional ultrasound energy and output in the mode of pulse wave, and it is typically used for therapeutic purpose in rehabilitation medicine. LIPUS has minimal thermal effects due to its low intensity and pulsed output mode, and its non-thermal effects which is normally claimed to induce therapeutic changes in tissues attract most researchers’ attentions. LIPUS have been demonstrated to have a rage of biological effects on tissues, including promoting bone-fracture healing, accelerating soft-tissue regeneration, inhibiting inflammatory responses and so on. Recent studies showed that biological effects of LIPUS in healing morbid body tissues may be mainly associated with the upregulation of cell proliferation through activation of integrin receptors and Rho/ROCK/Src/ERK signaling pathway, and with promoting multilineage differentiation of mesenchyme stem/progenitor cell lines through ROCK-Cot/Tpl2-MEK-ERK signaling pathway. Hopefully, LIPUS may become an effective clinical procedure for the treatment of urological diseases, such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), erectile dysfunction (ED), and stress urinary incontinence (SUI) in the field of urology. It still needs an intense effort for basic-science and clinical investigators to explore the biomedical applications of ultrasound. PMID:27141455

Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

PubMed

Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

2016-11-01

This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

Testosterone and Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Propensity Score-Matched Analysis.

PubMed

Lee, Jun Ho; Lee, Sung Won

2016-07-01

A recent study investigated the role of testosterone (T) in chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS). However, only a small amount of data is available to date, and the results are inconsistent. To evaluate the relation between total T (TT) and CP/CPPS. We conducted a propensity-matched study by identifying men with a TT level lower than 3.5 ng/mL among 8,336 men in their 40s and 50s. A control group of men with a TT level of at least 3.5 ng/mL matched for age, metabolic syndrome, and body mass index at a 5:1 ratio was selected for comparison. Using the same cohort and methods, another case group (TT < 3.0 ng/mL) and control group (TT ≥ 3.0 ng/mL) were selected. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) was administered. A χ(2) test, a t-test and logistic regression analyses were used to evaluate the relation between TT and prostatitis-like symptoms. Association of TT with NIH-CPSI score. After propensity score matching, 948 cases (TT < 3.5 ng/mL) and 4,740 controls (TT ≥ 3.5 ng/mL) were included. The ratio of mild and moderate to severe prostatitis-like symptoms was higher in the case group than in the control group (24.0% vs 27.4%, P = .001). The ratio of moderate to severe prostatitis-like symptoms also was higher in the case group than in the control group (6.2% vs 9.2%, P = .028). The pain domain of the NIH-CPSI, quality of life, and total NIH-CPSI scores also were higher in the case group. Ratios of severe lower urinary tract symptoms (12.6% vs 15.1%, P = .044) to maximal flow rate no higher than 10 mL/sec (3.8% vs 5.3%, P = .044) and postvoid residual urine volume of at least 100 mL (4.0% vs 5.6%, P = .035), which suggest high pressure in the prostate urethra, were higher in the case group. After adjusting for voided volume during uroflowmetry and total prostate volume, the relations of a TT level lower than 3.5 ng/mL to a maximal flow rate no higher than 10 mL/sec (odds ratio = 1.402, 95% CI = 1.017-1.934, P = .039) and to a postvoid residual urine volume of at least 100 mL (odds ratio = 1.410, 95% CI = 1.031-1.927, P = .031) were maintained. Using the cutoff TT value of 3.0 ng/mL, 437 cases (TT < 3.0 ng/mL) and 2,185 controls (TT ≥ 3.0 ng/mL) were included. The result of the 3.0-ng/mL cutoff value for TT showed a higher incidence of prostatitis-like symptoms in the group with a TT level lower than 3.0 ng/mL, but this was not statistically significant. Low TT level (<3.5 ng/mL) was significantly correlated with prostatitis-like symptoms in this study. Copyright © 2016. Published by Elsevier Inc.

Range-expanding pests and pathogens in a warming world.

PubMed

Bebber, Daniel Patrick

2015-01-01

Crop pests and pathogens (CPPs) present a growing threat to food security and ecosystem management. The interactions between plants and their natural enemies are influenced by environmental conditions and thus global warming and climate change could affect CPP ranges and impact. Observations of changing CPP distributions over the twentieth century suggest that growing agricultural production and trade have been most important in disseminating CPPs, but there is some evidence for a latitudinal bias in range shifts that indicates a global warming signal. Species distribution models using climatic variables as drivers suggest that ranges will shift latitudinally in the future. The rapid spread of the Colorado potato beetle across Eurasia illustrates the importance of evolutionary adaptation, host distribution, and migration patterns in affecting the predictions of climate-based species distribution models. Understanding species range shifts in the framework of ecological niche theory may help to direct future research needs.

Synthesis of cell-penetrating peptides and their application in neurobiology.

PubMed

Dietz, Gunnar P H; Bähr, Mathias

2007-01-01

Short basic amino acid sequences, often called cell-penetrating peptides (CPPs), allow the delivery of proteins and other molecules into cells and across the blood-brain barrier (BBB). Although the ability of basic proteins to facilitate such trafficking is known for a long time, only the application of genetic methods and overexpression of fusion proteins in Escherichia coli has lead to a wide application of CPP in many research areas, including signal transduction, cancer, angiogenesis, apoptosis, bone development, cardioprotection, cell cycle, neurobiology, and many others. For the neuroscientist, CPPs are particularly attractive, as a number of articles in the last 5 years have reported their use for neuronal rescue in a number of models for neurodegenerative diseases in vitro and in vivo in rats, mice, or gerbils. Here, we give a detailed description of the protein purification methodology and applications in neuroscience.

Optimization of a Coupling Process for Insulin Degludec According to a Quality by Design (QbD) Paradigm.

PubMed

Nie, Lei; Hu, Mingming; Yan, Xu; Guo, Tingting; Wang, Haibin; Zhang, Sheng; Qu, Haibin

2018-05-03

This case study described a successful application of the quality by design (QbD) principles to a coupling process development of insulin degludec. Failure mode effects analysis (FMEA) risk analysis was first used to recognize critical process parameters (CPPs). Five CPPs, including coupling temperature (Temp), pH of desB30 solution (pH), reaction time (Time), desB30 concentration (Conc), and molar equivalent of ester per mole of desB30 insulin (MolE), were then investigated using a fractional factorial design. The curvature effect was found significant, indicating the requirement of second-order models. Afterwards, a central composite design was built with an augmented star and center points study. Regression models were developed for the CPPs to predict the purity and yield of predegludec using above experimental data. The R 2 and adjusted R 2 were higher than 96 and 93% for the two models respectively. The Q 2 values were more than 80% indicating a good predictive ability of models. MolE was found to be the most significant factor affecting both yield and purity of predegludec. Temp, pH, and Conc were also significant for predegludec purity, while Time appeared to remarkably influence the yield model. The multi-dimensional design space and normal operating region (NOR) with a robust setpoint were determined using a probability-based Monte-Carlo simulation method. The verified experimental results showed that the design space was reliable and effective. This study enriches the understanding of acetylation process and is instructional to other complicated operations in biopharmaceutical engineering.

Unit operation optimization for the manufacturing of botanical injections using a design space approach: a case study of water precipitation.

PubMed

Gong, Xingchu; Chen, Huali; Chen, Teng; Qu, Haibin

2014-01-01

Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

Calcium absorption is not increased by caseinophosphopeptides.

PubMed

Teucher, Birgit; Majsak-Newman, Gosia; Dainty, Jack R; McDonagh, David; FitzGerald, Richard J; Fairweather-Tait, Susan J

2006-07-01

One of the suggested health benefits of caseinophosphopeptides (CPPs) is their ability to enhance calcium absorption. This possibility is based on the assumption that they resist proteolysis in the upper gastrointestinal tract and maintain calcium in a soluble form at alkaline pH in the distal ileum. The effects of CPP-enriched preparations (containing candidate functional food ingredients) on calcium absorption from a calcium lactate drink were tested. A randomized crossover trial was undertaken in 15 adults in whom we measured the absorption of calcium from a calcium lactate drink (drink A: 400 mg Ca as lactate) and 2 preparations enriched with forms of CPP (1.7 g each; drinks B and C). Both drinks B and C contained 400 mg Ca as calcium lactate plus approximately 100 mg CPP-derived calcium). Each volunteer received the 3 drinks in random order. Absorption was measured by the dual-label calcium stable-isotope technique. The quantity of calcium absorbed was significantly lower from drink A (103 mg) than from drink B (117 mg; P = 0.012) or drink C (121 mg; P = 0.002), which indicated a positive effect of the CPPs. However, because the CPP preparations contributed additional calcium besides that found in the calcium lactate (drink A), fractional absorption of calcium from drink B (23%) was slightly but significantly (P = 0.015) lower than that from drink A (26%). The differences in calcium absorption are unlikely to have any biological significance. CPPs are unsuitable as candidate ingredients for functional foods that are designed to deliver improved calcium nutrition.

Membrane Crossing and Membranotropic Activity of Cell-Penetrating Peptides: Dangerous Liaisons?

PubMed

Walrant, Astrid; Cardon, Sébastien; Burlina, Fabienne; Sagan, Sandrine

2017-12-19

Living organisms have to maintain a stable balance in molecules and ions in the changing environment in which they are living, a process known as homeostasis. At the level of cells, the plasma membrane has a major role in homeostasis, since this hydrophobic film prevents passive diffusion of large and hydrophilic molecules between the extracellular and intracellular milieu. Living organisms have evolved with highly sophisticated transport systems to control exchanges across this barrier: import of nutrients and fuel essential for their survival; recognition of chemical or physical messengers allowing information interchanges with surrounding cells. Besides specialized proteins, endocytosis mechanisms at the level of the lipid bilayer can transport molecules from the outside across the cell membrane, in an energy-dependent manner. The cell membrane is highly heterogeneous in its molecular composition (tens of different lipids, proteins, polysaccharides, and combinations of these) and dynamic with bending, deformation, and elastic properties that depend on the local composition of membrane domains. Many viruses, microorganisms, and toxins exploit the plasma membrane to enter into cells. Chemists develop strategies to target the plasma membrane with molecules capable of circumventing this hydrophobic barrier, in particular to transport and deliver nonpermeable drugs in cells for biotechnological or pharmaceutical purposes. Drug delivery systems are numerous and include lipid-, sugar-, protein-, and peptide-based delivery systems, since these biomolecules generally have good biocompatibility, biodegradability, environmental sustainability, cost effectiveness, and availability. Among those, cell-penetrating peptides (CPPs), reported for the first time in the early 1990s, are attracting major interest not only as potential drug delivery systems but also at the level of fundamental research. It was indeed demonstrated very early that these peptides, which generally correspond to highly cationic sequences, can still cross the cell membrane at 4 °C, a temperature at which all active transport and endocytosis pathways are totally inhibited. Therefore, how these charged hydrophilic peptides cross the hydrophobic membrane barrier is of utmost interest as a pure basic and physicochemical question. In this Account, we focus on cationic cell-penetrating peptides (CPPs) and the way they cross cell membranes. We summarize the history of this field that emerged around 20 years ago. CPPs were indeed first identified as protein-transduction domains from the human immunodeficiency virus (HIV) TAT protein and the Antennapedia homeoprotein, a transcription factor from Drosophila. We highlight our contribution to the elucidation of CPP internalization pathways, in particular translocation, which implies perturbation and reorganization of the lipid bilayer, and endocytosis depending on sulfated glycosaminoglycans. We show a particular role of Trp (indole side chain) and Arg (guanidinium side chain), which are essential amino acids for CPP internalization. Interactions with the cell-surface are not only Coulombic; H-bonds and hydrophobic interactions contribute also significantly to CPP entry. The capacity of CPPs to cross cell membrane is not related to their strength of membrane binding. Finally, we present optimized methods based on mass spectrometry and fluorescence spectroscopy that allow unequivocal quantification of CPPs inside cells or bound to the outer leaflet of the membrane, and discuss some limitations of the technique of flow cytometry that we have recently highlighted.

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS Nano GO Consortium

PubMed Central

Xia, Tian; Hamilton, Raymond F.; Bonner, James C.; Crandall, Edward D.; Elder, Alison; Fazlollahi, Farnoosh; Girtsman, Teri A.; Kim, Kwang; Mitra, Somenath; Ntim, Susana A.; Orr, Galya; Tagmount, Mani; Taylor, Alexia J.; Telesca, Donatello; Tolic, Ana; Vulpe, Christopher D.; Walker, Andrea J.; Wang, Xiang; Witzmann, Frank A.; Wu, Nianqiang; Xie, Yumei; Zink, Jeffery I.; Nel, Andre

2013-01-01

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells. Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μg/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β. Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity. PMID:23649538

The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned positive but not the negative effects of cocaine in rats

PubMed Central

Wenzel, Jennifer M.; Su, Zu-In; Shelton, Kerisa; Dominguez, Hiram M.; von Furstenberg, Victoria A.; Ettenberg, Aaron

2013-01-01

Human cocaine users report that the initial “high” produced by cocaine administration is followed by an anxiogenic “crash”. Given that cocaine has such robust and opposing properties, it is likely that both the positive and negative effects of cocaine contribute to an individual’s motivation to administer the drug. Despite this likelihood, the neurobiology underlying cocaine’s dual processes remains unclear. While much literature supports a role for dopamine (DA) in cocaine reward, it is uncertain if DA also contributes to the drug’s negative effects. Our laboratory has extensively utilized a modified conditioned place test to explore cocaine’s opponent processes. In this paradigm rats develop conditioned place preferences (CPPs) for an environment paired with the immediate/positive effects of cocaine, and conditioned place aversions (CPAs) for an environment paired with the delayed/negative effects present 15-min after i.v. injection. In the current study rats were conditioned to associate an environment with either the immediate or delayed effects of i.v. cocaine (1 mg/kg/0.1 ml) three hours after i.p. pre-treatment with either the DA D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg/ml) or saline vehicle. As expected, vehicle-treated control animals developed the normal pattern of CPPs for cocaine’s immediate effects or CPAs for the delayed effects of cocaine. However, while DA receptor antagonism prevented the expression of cocaine CPPs it did not alter the expression of cocaine-induced CPAs. These data confirm a role for DA transmission in cocaine reward but suggest that different neural pathways mediate the drug’s negative/anxiogenic properties. PMID:24012795

The heparin-binding domain of HB-EGF as an efficient cell-penetrating peptide for drug delivery.

PubMed

Luo, Zhao; Cao, Xue-Wei; Li, Chen; Wu, Miao-Dan; Yang, Xu-Zhong; Zhao, Jian; Wang, Fu-Jun

2016-11-01

Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30-HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C-terminus of MAP30 promoted the cellular uptake of recombinant MAP30-HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30-induced apoptosis through the activation of the mitochondrial- and death receptor-mediated signaling pathways. In addition, the MAP30-HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30-HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB-EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Quality by Design in the development of hydrophilic interaction liquid chromatography method with gradient elution for the analysis of olanzapine.

PubMed

Tumpa, Anja; Stajić, Ana; Jančić-Stojanović, Biljana; Medenica, Mirjana

2017-02-05

This paper deals with the development of hydrophilic interaction liquid chromatography (HILIC) method with gradient elution, in accordance with Analytical Quality by Design (AQbD) methodology, for the first time. The method is developed for olanzapine and its seven related substances. Following step by step AQbD methodology, firstly as critical process parameters (CPPs) temperature, starting content of aqueous phase and duration of linear gradient are recognized, and as critical quality attributes (CQAs) separation criterion S of critical pairs of substances are investigated. Rechtschaffen design is used for the creation of models that describe the dependence between CPPs and CQAs. The design space that is obtained at the end is used for choosing the optimal conditions (set point). The method is fully validated at the end to verify the adequacy of the chosen optimal conditions and applied to real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Carbon fiber content measurement in composite

NASA Astrophysics Data System (ADS)

Wang, Qiushi

Carbon fiber reinforced polymers (CFRPs) have been widely used in various structural applications in industries such as aerospace and automotive because of their high specific stiffness and specific strength. Their mechanical properties are strongly influenced by the carbon fiber content in the composites. Measurement of the carbon fiber content in CFRPs is essential for product quality control and process optimization. In this work, a novel carbonization-in-nitrogen method (CIN) is developed to characterize the fiber content in carbon fiber reinforced thermoset and thermoplastic composites. In this method, a carbon fiber composite sample is carbonized in a nitrogen environment at elevated temperatures, alongside a neat resin sample. The carbon fibers are protected from oxidization while the resin (the neat resin and the resin matrix in the composite sample) is carbonized under the nitrogen environment. The residue of the carbonized neat resin sample is used to calibrate the resin carbonization rate and calculate the amount of the resin matrix in the composite sample. The new method has been validated on several thermoset and thermoplastic resin systems and found to yield an accurate measurement of fiber content in carbon fiber polymer composites. In order to further understand the thermal degradation behavior of the high temperature thermoplastic polymer during the carbonization process, the mechanism and the kinetic model of thermal degradation behavior of carbon fiber reinforced poly (phenylene sulfide) (CPPS) are studied using thermogravimetry analysis (TGA). The CPPS is subjected to TGA in an air and nitrogen atmosphere at heating rates from 5 to 40°C min--1. The TGA curves obtained in air are different from those in nitrogen. This demonstrates that weight loss occurs in a single stage in nitrogen but in two stages in air. To elucidate this difference, thermal decomposition kinetics is analyzed by applying the Kissinger, Flynn-Wall-Ozawa, Coat-Redfern and Malek methods. The activation energy (Ea) of the solid-state process is determined to be 202 kJ mol--1 in an oxidative atmosphere using Kissinger's method, which is 10-15 kJ mol--1 more than the results calculated in a nitrogen atmosphere. The value of the activation energy obtained using Ozawa-Flynn methods is in agreement with that using the Kissinger method. Different degradation mechanisms are used to compare with this value. Based on the analytical result, the actual thermal degradation mechanism of the CPPS is a Dn deceleration type. The carbonization temperature range of the CPPS is the same as pure PPS resin.

Cell penetrating peptides: a comparative transport analysis for 474 sequence motifs.

PubMed

Ramaker, Katrin; Henkel, Maik; Krause, Thorsten; Röckendorf, Niels; Frey, Andreas

2018-11-01

Delivering reagents into cells is a key demand in molecular medicine. The vehicle of choice is often cell penetrating peptides (CPPs), which can ferry conjugated cargo across membranes. Although numerous peptides have been shown to promote such uptake events, there has been no comprehensive comparison of individual performance under standardized conditions. We have devised a method to rapidly analyze the ability of a multitude of CPP conjugates to carry a model cargo into HeLa cells. Sequence information for 474 CPPs was collected from literature sources, and the respective peptides were synthesized and modified with carboxyfluorescein (FAM) as model cargo. All candidates were evaluated in an identical uptake test, and transport was quantified using cellular fluorescence intensities. Substantial differences in the ability to carry the fluorophore into the cells were observed, with transport performance differing by a factor of 70 between the best CPP investigated and cargo alone. Strong correlations were observed between uptake efficiency and both sequence length and the presence of positive net charge. A compilation of the 20 top performers with regard to cargo delivery performance and cell compatibility is provided.

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS Nano GO Consortium

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

Xia, Tian; Hamilton, Raymond F.; Bonner, James C.

2013-06-01

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different speciesmore » (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells. Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μ g/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β. Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity.« less

Developing a bright 17 keV x-ray source for probing high-energy-density states of matter at high spatial resolution

NASA Astrophysics Data System (ADS)

Huntington, C. M.; Park, H.-S.; Maddox, B. R.; Barrios, M. A.; Benedetti, R.; Braun, D. G.; Hohenberger, M.; Landen, O. L.; Regan, S. P.; Wehrenberg, C. E.; Remington, B. A.

2015-04-01

A set of experiments were performed on the National Ignition Facility (NIF) to develop and optimize a bright, 17 keV x-ray backlighter probe using laser-irradiated Nb foils. High-resolution one-dimensional imaging was achieved using a 15 μm wide slit in a Ta substrate to aperture the Nb Heα x-rays onto an open-aperture, time integrated camera. To optimize the x-ray source for imaging applications, the effect of laser pulse shape and spatial profile on the target was investigated. Two laser pulse shapes were used—a "prepulse" shape that included a 3 ns, low-intensity laser foot preceding the high-energy 2 ns square main laser drive, and a pulse without the laser foot. The laser spatial profile was varied by the use of continuous phase plates (CPPs) on a pair of shots compared to beams at best focus, without CPPs. A comprehensive set of common diagnostics allowed for a direct comparison of imaging resolution, total x-ray conversion efficiency, and x-ray spectrum between shots. The use of CPPs was seen to reduce the high-energy tail of the x-ray spectrum, whereas the laser pulse shape had little effect on the high-energy tail. The measured imaging resolution was comparably high for all combinations of laser parameters, but a higher x-ray flux was achieved without phase plates. This increased flux was the result of smaller laser spot sizes, which allowed us to arrange the laser focal spots from multiple beams and produce an x-ray source which was more localized behind the slit aperture. Our experiments are a first demonstration of point-projection geometry imaging at NIF at the energies (>10 keV) necessary for imaging denser, higher-Z targets than have previously been investigated.

Synthesis and evaluation of amphiphilic peptides as nanostructures and drug delivery tools

NASA Astrophysics Data System (ADS)

Sayeh, Naser Ali

Intracellular delivery of cell-impermeable compounds in a variety cells using delivery systems have been extensively studied in recent years. Obtaining desirable cellular uptake levels often requires the administration of high quantities of drugs to achieve the expected intracellular biological effect. Thus, improving the translocation process across the plasma membrane will significantly reduce the quantity of required administered drug and consequently minimize the side effects in most of the cases. Efficient delivery of these molecules to the cells and tissues is a difficult challenge. Compounds with low cellular permeability are commonly considered to be of limited therapeutic value. Over the past few decades, several biomedical carriers, such as polymers, nanospheres, nanocapsules, liposomes, micelles, peptides and dendrimers have been widely used to deliver therapeutic and diagnostic agents to the cells. Biomaterials generated from nano-scale compounds have shown some promising data for delivery of many compounds in a number of diseases, such as viral infections, cancer, and genetic disorders. Although much progress has been achieved in this field, many challenges still remain, such as toxicity and limited stability. Liposomes suffer from poor stability in the bloodstream and leakage during storage. They tend to aggregate and fuse with or leak entrapped drugs, especially highly hydrophilic small molecules. For solid lipid nanoparticles (SLNs), drug expulsion after polymorphic transition during storage, inadequate loading capacity, and relatively high water content of the dispersions have been observed. Poly(lactic-coglycolic acid (PLGA) degrades in the body producing its original monomers of lactic acid and glycolic acid, which are the by-products of various metabolic pathways. However, this acidic microenvironment that occurs during degradation could negatively affect the stability of the loaded compound. Dendrimers can carry drugs as complexes or as conjugates although one limitation lies in the effort of controlling the rate of drug release. The encapsulated or complexed drugs tend to be released rapidly (before reaching the target site) and in the dendrimer--drug conjugates, it is the chemical linkage that controls the drug release. Thus, future studies in this field are urgently required to create more efficient and stable biomaterials. Peptides are considered as efficient vectors for achieving optimal cellular uptake. The potential use of peptides as drug delivery vectors received much attention by the discovery of several cell-penetrating peptides (CPPs). The first CPPs discovered in 1988, that were sequences from HIV-1 encoded TAT protein, TAT (48--60), and penetrated very efficiently through cell membranes of cultured mammalian cells. CPPs are a class of diverse peptides, typically with 8--25 amino acids, and unlike most peptides, they can cross the cellular membrane with more efficiency. CPPs have also shown to undergo self-assembly and generate nanostructures. The generation of self-assembled peptides and nanostructures occur through various types of interactions between functional groups of amino acid residues, such as electrostatic, hydrophobic, and hydrogen bonding. Appropriate design and functionalization of peptides are critical for generating nanostructures. Chemically CPPs are classified into two major groups: linear and cyclic peptides. It has been previously reported that linear peptides containing hydrophilic and hydrophobic amino acids could act as membrane protein stabilizers. These compounds are short hydrophilic or amphiphilic peptides that have positively charged amino acids, such as arginine, lysine or histidine, which can interact with the negative charge phospholipids layer on the cell membrane and translocate the cargo into the cells. Conjugation to cationic linear CPPs, such as TAT, penetratin, or oligoarginine efficiently improves the cellular uptake of large hydrophilic molecules, but the cellular uptake is predominantly via an unproductive endosomal pathway. Therefore, the biological effect is very limited, as the compounds are trapped in these compartments and cannot reach their biological targets in the cytoplasm or the nucleus. Mechanisms that promote endosomal escape or avoid endosomal route are required for improving bioavailability. Highly cationic CPPs preferentially interact with particular cell types, have limited plasma half-life, show toxicity, do not cross multicellular barriers such as vasculature epithelia or the blood-brain barrier, and efficient cargo delivery requires 9-15 arginine residues. Highly cationic CPPs are, therefore not ideal small molecule drug delivery vehicles. Linear CPPs are susceptible to hydrolysis by endogenous peptidases. Conjugation to cationic CPPs, such as TAT, penetratin, or oligoarginine efficiently improves the cellular uptake of large hydrophilic molecules, but the cellular uptake occurs predominantly via an unproductive endosomal pathway. Therefore, the biological effect is very limited, as the compounds are trapped in these compartments and cannot reach their biological targets in the cytoplasm or the nucleus. Mechanisms that promote endosomal escape or avoid endosomal route are required for improving bioavailability. Highly cationic CPPs preferentially interact with particular cell types, have limited plasma half-life, show toxicity, do not cross multicellular barriers such as vasculature epithelia or the blood-brain barrier, and efficient cargo delivery requires 9-15 arginine residues. Highly cationic linear CPPs are, therefore, have not become optimized as small molecule drug delivery vehicles. On the other hand, cyclic peptides containing hydrophilic and hydrophobic amino acids have shown greater potential as drug delivery tools due to their enhanced chemical and enzymatic stability. Parang's laboratory has reported that Amphiphilic Cyclic Peptides (ACPs) containing positively charged arginine and hydrophobic tryptophan residues as potential candidates for drug delivery. Cyclic peptides have several benefits compared to linear peptides, such as rigidness of structure and stability against proteolytic enzymes. The rigidity of the structure can enhance the binding affinity of ligands toward receptors by reducing the freedom of possible structural conformations. Cyclic peptides are also present in nature and have been developed as therapeutics. Cyclosporine, gramicidin S, polymoxin B, and daptomycin are well-known examples of cyclic peptide drugs. Parang's laboratory designed amphiphilic cyclic CPPs containing alternative tryptophan and arginine residues as the positively charged and hydrophobic residues, respectively. The peptides were efficient in improving the cellular delivery of anticancer and antiviral drugs. The cellular uptake mechanism of CPPs into cells is still a matter of some debate. The cellular entry of CPP can be influenced by the type of CPP, the cell line, the nature of the cargo, and the conditions of incubation. As described above, linear CPPs pass through the plasma membrane mostly via an energy-independent or endocytosis pathway. Moreover, the cellular delivery of CPP-conjugated molecules also occurs through endosomal pathway and a strong enzymatic degradation and an inadequate cytoplasmic release of intact molecules from the conjugates are expected, thus leading to an inefficient transfer into the cytoplasm. The best strategy to overcome this issue is to designing CPP that by pass the endosomal uptake or by increasing the escape rate from the endosome to improve the intracellular delivery of CPP-attached molecules. Parang laboratory has reported the cellular uptake of a number of cyclic peptides independent of endocytotic pathway. The extraordinary ability of cyclic peptides containing tryptophan and arginine, [WR]4 and [WR] 5 to spontaneously translocate across bilayers independent of an energy source is distinctly different from the behavior of the well-known, highly cationic CPPs, such as TAT and Arg9, which do not translocate across phospholipid bilayers, and enter cells mostly by active endocytosis. Alternatively, researchers have found that an effective cellular delivery vector can be improved developed by conjugating a CPP with a fatty acid chain. Amphiphilic peptides have also become a subject of major interest as potent antibacterial agents. Antimicrobial peptides (AMPs) are produced naturally by bacteria and are considered as the first line of host defense protecting living organisms from microorganisms. Various types of AMPs has been discovered, such as defensins, cecropins, magainins and cathelicidins, with significant different structures and bioactivity profiles. The mechanism of actions for these peptides were reported as effectors and regulators of the innate immune system by increasing production and release of chemokine, and enhancing wound healing and angiogenesis. They were able to suppress biofilm formation and induce the dissolution of existing biofilms. Thus, design of new AMPs and more cost effective sequences with highly activity are urgently needed. Although a number of cyclic peptides were discovered and reported as efficient cellular delivery agents or antimicrobial agent, a more systematic investigation is required to identify design rules for optimal entrapment, drug loading, and stability. The balance of many small forces determines the overall morphology, size, and functionality of the structures. A deeper understanding of these factors is required for guiding future research, and for customizing cyclic peptides for drug loading and cellular delivery applications. Thus, additional amphiphilic cyclic and linear peptides were designed with variable electrostatic and hydrophobic residues to optimize drug encapsulation. The diversity in ring size, amino acid number, position and sequences, number of rings, net charge, and hydrophobicity of side chains in cyclic peptides will allow us to explore requirements for generating peptides with optimized drug encapsulation and to establish correlations between the structure of peptides with their drug entrapment properties. Thus, the general objective of this dissertation was to design and evaluate additional cyclic or amphiphilic peptides as nanostructures, compare their efficiency in delivery of small molecules with the previously reported cyclic peptides containing tryptophan and arginine residues. This dissertation consists of three chapters. Chapter 1. MANUSCRIPT (published in Current Organic Chemistry 2014). The objective of this work was to design amphiphilic linear and cyclic peptides containing hydrophobic tryptophan W residues that were linked through a triazole ring to positively charged arginine R and lysine (K) residues. The peptides were synthesized through click chemistry between hydrophobic peptides containing alkyne and positively charged peptides containing azide groups. Characterization of their structures like solubility, CD, TEM, cytotoxicity were investigated. The conjugates were showed minimal cytotoxicity at two cell lines. The secondary structures of both peptides were similar to a distorted α-helix as shown by CD spectroscopy. TEM imaging also showed that linear-linear (WG(triazole-KR-NH2))3 and cyclic-linear [WG(triazole-KR-NH2)]3 peptides formed nano-sized structures. Chapter 2. MANUSCRIPT I (Submitted to Journal of Molecular Modeling). In this work, we investigated the structural and dynamical aspects of cyclic-linear peptide ([WG(triazole-KR-NH2)] 3 and linear-linear peptide (WG(triazole-KR-NH2))3) formed nanostructures compared to a drug delivery system with [WR]4. While [WR]4 was found to be an efficient molecular transporter for small molecule drugs, such as lamivudine and dasatinib, cyclic-linear peptide ([WG(triazole-KR-NH2)]3 was inefficient. Molecular modeling was used to explain the differential behavior of these peptides. We showed how the morphology of these systems can affect the drug delivery efficiency. The result of this work provided insights about optimizing the amphiphilic cyclic-linear trizaolyl peptides can be used to design compounds with more efficient drug delivery capabilities. Chapter 3. MANUSCRIPT II. The objective of this Chapter was to synthesize a different series of amphiphilic peptides for different objectives. First, the amphiphilic trizaolyl peptides in Chapter I were systematically modified by increasing the number of arginine and tryptophan sequence in cyclic and linear peptides. The rationale for the modification was to enhance the possibility of interaction with the cell membrane and therefore improving the cellular uptake process. Moreover, a new class of amphiphilic peptides consist of tryptophan and glutamic acid were conjugated with a peptide containing arginine and lysine residues using Fmoc chemistry. These peptides have an amide bond that generates more flexibility compared to a triazole ring. The chemical and biological properties will be evaluated in future and compared with amphiphilic triazolyl peptides. Finally, additional fatty acids with different length chains were conjugated with positively charged peptides to be evaluated as antibacterial agents. Stearic acid (C16) and myristic acid (C14) were conjugated with a peptides consisting of arginine azide and lysine amino acids to enhance the antibacterial activity. In summary, the work in this dissertation provided insights about the synthesis and characterization of a new class of amphiphilic triazolyl peptides as drug delivery carriers and amphiphilic peptides as antibacterial agents. Molecular modeling was used to explain why triazolyl peptides were unable to enhance the delivery of small molecule drugs compared to the previously synthesized cyclic peptides [WR]4 (Chapter 2) Modification of synthesized peptides in Chapter 1, by addition of more positively charged amino acids or reducing the rigidity by incorporating amide bonds instead of triazoly groups can be used to improve the cell penetrating properties. Finally, we conjugated amphiphilic peptides with different fatty acids (Chapter 3) to investigate their application as antibacterial agents.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

PubMed

Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration and secretion of inflammatory mediators. Our results corroborate and support the notion that mice with different genetic background have different susceptibility to EAP induction. Prostate 77:94-104, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Optimization of lime milk precipitation process of Lonicera Japonica aqueous extract based on quality by design concept].

PubMed

Shen, Jin-Jing; Gong, Xing-Chu; Pan, Jian-Yang; Qu, Hai-Bin

2017-03-01

Design space approach was applied in this study to optimize the lime milk precipitation process of Lonicera Japonica (Jinyinhua) aqueous extract. The evaluation indices for this process were total organic acid purity and amounts of 6 organic acids obtained from per unit mass of medicinal materials. Four critical process parameters (CPPs) including drop speed of lime milk, pH value after adding lime milk, settling time and settling temperature were identified by using the weighted standardized partial regression coefficient method. Quantitative models between process evaluation indices and CPPs were established by a stepwise regression analysis. A design space was calculated by a Monte-Carlo simulation method, and then verified. The verification test results showed that the operation within the design space can guarantee the stability of the lime milk precipitation process. The recommended normal operation space is as follows： drop speed of lime milk of 1.00-1.25 mL•min⁻¹, pH value of 11.5-11.7, settling time of 1.0-1.2 h, and settling temperature of 10-20 ℃.. Copyright© by the Chinese Pharmaceutical Association.

Process signatures in glatiramer acetate synthesis: structural and functional relationships.

PubMed

Campos-García, Víctor R; Herrera-Fernández, Daniel; Espinosa-de la Garza, Carlos E; González, German; Vallejo-Castillo, Luis; Avila, Sandra; Muñoz-García, Leslie; Medina-Rivero, Emilio; Pérez, Néstor O; Gracia-Mora, Isabel; Pérez-Tapia, Sonia Mayra; Salazar-Ceballos, Rodolfo; Pavón, Lenin; Flores-Ortiz, Luis F

2017-09-21

Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

Evaluating the process parameters of the dry coating process using a 2(5-1) factorial design.

PubMed

Kablitz, Caroline Désirée; Urbanetz, Nora Anne

2013-02-01

A recent development of coating technology is dry coating, where polymer powder and liquid plasticizer are layered on the cores without using organic solvents or water. Several studies evaluating the process were introduced in literature, however, little information about the critical process parameters (CPPs) is given. Aim of the study was the investigation and optimization of CPPs with respect to one of the critical quality attributes (CQAs), the coating efficiency of the dry coating process in a rotary fluid bed. Theophylline pellets were coated with hydroxypropyl methylcellulose acetate succinate as enteric film former and triethyl citrate and acetylated monoglyceride as plasticizer. A 2(5-1) design of experiments (DOEs) was created investigating five independent process parameters namely coating temperature, curing temperature, feeding/spraying rate, air flow and rotor speed. The results were evaluated by multilinear regression using the software Modde(®) 7. It is shown, that generally, low feeding/spraying rates and low rotor speeds increase coating efficiency. High coating temperatures enhance coating efficiency, whereas medium curing temperatures have been found to be optimum in terms of coating efficiency. This study provides a scientific base for the design of efficient dry coating processes with respect to coating efficiency.

The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide.

PubMed

Michiue, Hiroyuki; Sakurai, Yoshinori; Kondo, Natsuko; Kitamatsu, Mizuki; Bin, Feng; Nakajima, Kiichiro; Hirota, Yuki; Kawabata, Shinji; Nishiki, Tei-ichi; Ohmori, Iori; Tomizawa, Kazuhito; Miyatake, Shin-ichi; Ono, Koji; Matsui, Hideki

2014-03-01

New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. The median survival of BNCT patients with glioblastoma was almost twice as long as those receiving standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. We simulated the energy transfer against the nucleus at different locations of boron from outside the cell to the nuclear region with neutron irradiation and concluded that there was a marked difference between inside and outside the cell in boron localization. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH fused to 11R with a dendritic lysine structure was synthesized and administrated to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at the cell nucleus and showed a very high boron value in ICP results. With neutron irradiation, the 8BSH-11R administrated group showed a significant cancer killing effect compared to the 100 times higher concentration of BSH-administrated group. We concluded that BSH-fused CPPs were one of the most improved and potential boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the clinical setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

How Membrane-Active Peptides Get into Lipid Membranes.

PubMed

Sani, Marc-Antoine; Separovic, Frances

2016-06-21

The structure-function relationship for a family of antimicrobial peptides (AMPs) from the skin of Australian tree frogs is discussed and compared with that of peptide toxins from bee and Australian scorpion venoms. Although these membrane-active peptides induce a similar cellular fate by disrupting the lipid bilayer integrity, their lytic activity is achieved via different modes of action, which are investigated in relation to amino acid sequence, secondary structure, and membrane lipid composition. In order to better understand what structural features govern the interaction between peptides and lipid membranes, cell-penetrating peptides (CPPs), which translocate through the membrane without compromising its integrity, are also discussed. AMPs possess membrane lytic activities that are naturally designed to target the cellular membrane of pathogens or competitors. They are extremely diverse in amino acid composition and often show specificity against a particular strain of microbe. Since our antibiotic arsenal is declining precariously in the face of the rise in multiantibiotic resistance, AMPs increasingly are seen as a promising alternative. In an effort to understand their molecular mechanism, biophysical studies of a myriad of AMPs have been reported, yet no unifying mechanism has emerged, rendering difficult the rational design of drug leads. Similarly, a wide variety of cytotoxic peptides are found in venoms, the best known being melittin, yet again, predicting their activity based on a particular amino acid composition or secondary structure remains elusive. A common feature of these membrane-active peptides is their preference for the lipid environment. Indeed, they are mainly unstructured in solution and, in the presence of lipid membranes, quickly adsorb onto the surface, change their secondary structure, eventually insert into the hydrophobic core of the membrane bilayer, and finally disrupt the bilayer integrity. These steps define the molecular mechanism by which these membrane-active peptides lyse membranes. The last class of membrane-active peptides discussed are the CPPs, which translocate across the lipid bilayer without inducing severe disruption and have potential as drug vehicles. CPPs are typically highly charged and can show antimicrobial activity by targeting an intracellular target rather than via a direct membrane lytic mechanism. A critical aspect in the structure-function relationship of membrane-active peptides is their specific activity relative to the lipid membrane composition of the cell target. Cell membranes have a wide diversity of lipids, and those of eukaryotic and prokaryotic species differ greatly in composition and structure. The activity of AMPs from Australian tree frogs, toxins, and CPPs has been investigated within various lipid systems to assess whether a relationship between peptide and membrane composition could be identified. NMR spectroscopy techniques are being used to gain atomistic details of how these membrane-active peptides interact with model membranes and cells, and in particular, competitive assays demonstrate the difference between affinity and activity for a specific lipid environment. Overall, the interactions between these relatively small sized peptides and various lipid bilayers give insight into how these peptides function at the membrane interface.

JPRS Report, Environmental Issues

DTIC Science & Technology

1991-06-26

been coordinated by the National Environ- mental Policy Commission [Comision Nacional de Politica Ambiental ]. The first step was the creation of a...May 91 [Text] Santiago, 30 May (EFE)—The Permanent South Pacific Commission (CPPS), which comprises Colombia, Chile, Ecuador , and Peru, has lodged a...decisions. We are adopting measures that will create the State Secretariat for the Environment [Secretaria de Estado del Medio Ambiente ], which will be

Quality by design in the chiral separation strategy for the determination of enantiomeric impurities: development of a capillary electrophoresis method based on dual cyclodextrin systems for the analysis of levosulpiride.

PubMed

Orlandini, S; Pasquini, B; Del Bubba, M; Pinzauti, S; Furlanetto, S

2015-02-06

Quality by design (QbD) concepts, in accordance with International Conference on Harmonisation Pharmaceutical Development guideline Q8(R2), represent an innovative strategy for the development of analytical methods. In this paper QbD principles have been comprehensively applied in the set-up of a capillary electrophoresis method aimed to quantify enantiomeric impurities. The test compound was the chiral drug substance levosulpiride (S-SUL) and the developed method was intended to be used for routine analysis of the pharmaceutical product. The target of analytical QbD approach is to establish a design space (DS) of critical process parameters (CPPs) where the critical quality attributes (CQAs) of the method have been assured to fulfil the desired requirements with a selected probability. QbD can improve the understanding of the enantioseparation process, including both the electrophoretic behavior of enantiomers and their separation, therefore enabling its control. The CQAs were represented by enantioresolution and analysis time. The scouting phase made it possible to select a separation system made by sulfated-β-cyclodextrin and a neutral cyclodextrin, operating in reverse polarity mode. The type of neutral cyclodextrin was included among other CPPs, both instrumental and related to background electrolyte composition, which were evaluated in a screening phase by an asymmetric screening matrix. Response surface methodology was carried out by a Doehlert design and allowed the contour plots to be drawn, highlighting significant interactions between some of the CPPs. DS was defined by applying Monte-Carlo simulations, and corresponded to the following intervals: sulfated-β-cyclodextrin concentration, 9-12 mM; methyl-β-cyclodextrin concentration, 29-38 mM; Britton-Robinson buffer pH, 3.24-3.50; voltage, 12-14 kV. Robustness of the method was examined by a Plackett-Burman matrix and the obtained results, together with system repeatability data, led to define a method control strategy. The method was validated and was finally applied to determine the enantiomeric purity of S-SUL in pharmaceutical dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Endoscopic monoportal removal of a choroid plexus papilloma in the posterior third ventricle in a child.

PubMed

Sufianov, Albert A; Gaibov, Saidi S K; Sufianov, Rinat A

2015-07-01

Currently, only a few reports describe the minimally invasive removal of choroid plexus papillomas (CPPs) and, to the best of the authors' knowledge, no reports detail the resection of such a papilloma through an endoscopic approach in infants. The authors here describe the endoscopic removal of a third ventricle CPP in a child. A 5-month-old male infant presented with progressive macrocephaly, vomiting, and convulsions. A lesion in the posterior third ventricle was detected on brain MRI. Because of the patient's very young age, neuroendoscopy was used as the least invasive technique. The tumor was completely resected through a monoportal neuroendoscopic approach. Histologically, the tumor was classified as a WHO Grade I CPP. After surgery, the patient's condition improved, with no complications during his recovery. Ten-month follow-up neuroimaging revealed no evidence of tumor recurrence or progressive hydrocephaly. In view of the successful neuroendoscopic excision of this posterior third ventricle CPP, the authors believe that this method seems promising in the treatment of young children with intraventricular lesions.

Quantitative fluorescence spectroscopy and flow cytometry analyses of cell-penetrating peptides internalization pathways: optimization, pitfalls, comparison with mass spectrometry quantification

NASA Astrophysics Data System (ADS)

Illien, Françoise; Rodriguez, Nicolas; Amoura, Mehdi; Joliot, Alain; Pallerla, Manjula; Cribier, Sophie; Burlina, Fabienne; Sagan, Sandrine

2016-11-01

The mechanism of cell-penetrating peptides entry into cells is unclear, preventing the development of more efficient vectors for biotechnological or therapeutic purposes. Here, we developed a protocol relying on fluorometry to distinguish endocytosis from direct membrane translocation, using Penetratin, TAT and R9. The quantities of internalized CPPs measured by fluorometry in cell lysates converge with those obtained by our previously reported mass spectrometry quantification method. By contrast, flow cytometry quantification faces several limitations due to fluorescence quenching processes that depend on the cell line and occur at peptide/cell ratio >6.108 for CF-Penetratin. The analysis of cellular internalization of a doubly labeled fluorescent and biotinylated Penetratin analogue by the two independent techniques, fluorometry and mass spectrometry, gave consistent results at the quantitative and qualitative levels. Both techniques revealed the use of two alternative translocation and endocytosis pathways, whose relative efficacy depends on cell-surface sugars and peptide concentration. We confirmed that Penetratin translocates at low concentration and uses endocytosis at high μM concentrations. We further demonstrate that the hydrophobic/hydrophilic nature of the N-terminal extremity impacts on the internalization efficiency of CPPs. We expect these results and the associated protocols to help unraveling the translocation pathway to the cytosol of cells.

Nanoparticle transport across in vitro olfactory cell monolayers.

PubMed

Gartziandia, Oihane; Egusquiaguirre, Susana Patricia; Bianco, John; Pedraz, José Luis; Igartua, Manoli; Hernandez, Rosa Maria; Préat, Véronique; Beloqui, Ana

2016-02-29

Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

PubMed

Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

2015-01-01

Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells

PubMed Central

Liu, Betty R.; Huang, Yue-Wern; Aronstam, Robert S.; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy. PMID:26942714

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

PubMed

Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

Intelligent "Peptide-Gathering Mechanical Arm" Tames Wild "Trojan-Horse" Peptides for the Controlled Delivery of Cancer Nanotherapeutics.

PubMed

Shi, Nian-Qiu; Li, Yan; Zhang, Yong; Shen, Nan; Qi, Ling; Wang, Shu-Ran; Qi, Xian-Rong

2017-12-06

Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R 9 -liposome-based cargo delivery for tumor targeting. The peptide NGR, serving as a cell-targeting peptide for anchoring, and peptide PLGLAG, serving as a substrate peptide for deanchoring, were embedded in the Int PMA motif. The Int PMA construct was designed to be sensitive to tumor microenvironmental stimuli, including aminopeptidase N (CD13) and matrix metalloproteinases (MMP-2/9). Moreover, Int PMA could be specifically recognized by tumor tissues via CD13-mediated anchoring and released for cell entry by MMP-2/9-mediated deanchoring. To test the Int PMA design, a series of experiments were conducted in vitro and in vivo. Functional conjugates Int PMA-R 9 -poly(ethylene glycol) (PEG) 2000 -distearoylphosphatidyl-ethanolamine (DSPE) and R 9 -PEG 2000 -DSPE were synthesized by Michael addition reaction and were characterized by thin-layer chromatography and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The Int PMA-R 9 -modified doxorubicin-loaded liposomes (Int PMA-R 9 -Lip-DOX) exhibited a proper particle diameter (approximately 155 nm) with in vitro sustained release characteristics. Cleavage assay showed that Int PMA-R 9 peptide molecules could be cleaved by MMP-2/9 for completion of deanchoring. Flow cytometry and confocal microscopy studies indicated that Int PMA-R 9 -Lip-DOX can respond to both endogenous and exogenous stimuli in the presence/absence of excess MMP-2/9 and MMP-2/9 inhibitor (GM6001) and effectively function under competitive receptor-binding conditions. Moreover, Int PMA-R 9 -Lip-DOX generated more significant subcellular dispersions that were especially evident within endoplasmic reticulum (ER) and Golgi apparatus. Notably, Int PMA-R 9 -Lip-DOX could induce enhanced apoptosis, during which caspase 3/7 might be activated. In addition, Int PMA-R 9 -Lip-DOX displayed enhanced in vitro and in vivo antitumor efficacy versus "wild" R 9 -Lip-DOX. On the basis of investigations at the molecular level, cellular level, and animals' level, the control of Int PMA was effective and promoted selective delivery of R 9 -liposome cargo to the target site and reduced nonspecific uptake. This Int PMA-controlled strategy based on aminopeptidase-guided anchoring and protease-triggered deanchoring effectively curbed the wildness of CPPs and bolstered their effectiveness for in vivo delivery of nanotherapeutics. The specific nanocarrier delivery system used here could be adapted using a variety of intelligent designs based on combinations of multifunctional peptides that would specifically and preferentially bind to tumors versus nontumor tissues for tumor-localized accumulation in vivo. Thus, CPPs have a strong advantage for the development of intelligent nanomedicines for targeted tumor therapy.

Poly-arginine and arginine-rich peptides are neuroprotective in stroke models

PubMed Central

Meloni, Bruno P; Brookes, Laura M; Clark, Vince W; Cross, Jane L; Edwards, Adam B; Anderton, Ryan S; Hopkins, Richard M; Hoffmann, Katrin; Knuckey, Neville W

2015-01-01

Using cortical neuronal cultures and glutamic acid excitotoxicity and oxygen-glucose deprivation (OGD) stroke models, we demonstrated that poly-arginine and arginine-rich cell-penetrating peptides (CPPs), are highly neuroprotective, with efficacy increasing with increasing arginine content, have the capacity to reduce glutamic acid-induced neuronal calcium influx and require heparan sulfate preotoglycan-mediated endocytosis to induce a neuroprotective effect. Furthermore, neuroprotection could be induced with immediate peptide treatment or treatment up to 2 to 4 hours before glutamic acid excitotoxicity or OGD, and with poly-arginine-9 (R9) when administered intravenously after stroke onset in a rat model. In contrast, the JNKI-1 peptide when fused to the (non-arginine) kFGF CPP, which does not rely on endocytosis for uptake, was not neuroprotective in the glutamic acid model; the kFGF peptide was also ineffective. Similarly, positively charged poly-lysine-10 (K10) and R9 fused to the negatively charged poly-glutamic acid-9 (E9) peptide (R9/E9) displayed minimal neuroprotection after excitotoxicity. These results indicate that peptide positive charge and arginine residues are critical for neuroprotection, and have led us to hypothesize that peptide-induced endocytic internalization of ion channels is a potential mechanism of action. The findings also question the mode of action of different neuroprotective peptides fused to arginine-rich CPPs. PMID:25669902

A quality by design approach using artificial intelligence techniques to control the critical quality attributes of ramipril tablets manufactured by wet granulation.

PubMed

Aksu, Buket; Paradkar, Anant; de Matas, Marcel; Özer, Özgen; Güneri, Tamer; York, Peter

2013-02-01

Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

31P Solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

PubMed Central

Desai, Pinaki R.; Cormier, Ashley R.; Shah, Punit P.; Patlolla, Ram R.; Paravastu, Anant K.; Singh, Mandip

2013-01-01

The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11 and YKA) through skin intercellular lipids using 31P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, sections (0–60, 61–120 and 121–180 µm) were collected and analyzed for 31P NMR signal. The concentration dependent shift of 0, 25, 50, 100 and 200 mg/ml of TAT on skin layers, diffusion of TAT, R8, R11 and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using 31P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in 31P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180 µm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, 31P solid-state NMR can be used to track CPP penetration into different skin layers. PMID:23702274

Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo

PubMed Central

EL Andaloussi, Samir; Lehto, Taavi; Mäger, Imre; Rosenthal-Aizman, Katri; Oprea, Iulian I.; Simonson, Oscar E.; Sork, Helena; Ezzat, Kariem; Copolovici, Dana M.; Kurrikoff, Kaido; Viola, Joana R.; Zaghloul, Eman M.; Sillard, Rannar; Johansson, Henrik J.; Said Hassane, Fatouma; Guterstam, Peter; Suhorutšenko, Julia; Moreno, Pedro M. D.; Oskolkov, Nikita; Hälldin, Jonas; Tedebark, Ulf; Metspalu, Andres; Lebleu, Bernard; Lehtiö, Janne; Smith, C. I. Edvard; Langel, Ülo

2011-01-01

While small interfering RNAs (siRNAs) have been rapidly appreciated to silence genes, efficient and non-toxic vectors for primary cells and for systemic in vivo delivery are lacking. Several siRNA-delivery vehicles, including cell-penetrating peptides (CPPs), have been developed but their utility is often restricted by entrapment following endocytosis. Hence, developing CPPs that promote endosomal escape is a prerequisite for successful siRNA implementation. We here present a novel CPP, PepFect 6 (PF6), comprising the previously reported stearyl-TP10 peptide, having pH titratable trifluoromethylquinoline moieties covalently incorporated to facilitate endosomal release. Stable PF6/siRNA nanoparticles enter entire cell populations and rapidly promote endosomal escape, resulting in robust RNAi responses in various cell types (including primary cells), with minimal associated transcriptomic or proteomic changes. Furthermore, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by serum proteins. Finally, these nanoparticles promote strong RNAi responses in different organs following systemic delivery in mice without any associated toxicity. Strikingly, similar knockdown in liver is achieved by PF6/siRNA nanoparticles and siRNA injected by hydrodynamic infusion, a golden standard technique for liver transfection. These results imply that the peptide, in addition to having utility for RNAi screens in vitro, displays therapeutic potential. PMID:21245043

Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

PubMed

Moulton, H M; Fletcher, S; Neuman, B W; McClorey, G; Stein, D A; Abes, S; Wilton, S D; Buchmeier, M J; Lebleu, B; Iversen, P L

2007-08-01

The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.

A quality by design (QbD) study on enoxaparin sodium loaded polymeric microspheres for colon-specific delivery.

PubMed

Hales, Dana; Vlase, Laurian; Porav, Sebastian Alin; Bodoki, Andreea; Barbu-Tudoran, Lucian; Achim, Marcela; Tomuță, Ioan

2017-03-30

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of enoxaparin sodium microspheres for colon-specific delivery. The Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified. A central composite experimental design was used in order to develop the design space of microspheres for colon-specific delivery that have the desired Quality Target Product Profile (QTPP). The CPPs studied were Eudragit® FS-30D/Eudragit® RS-PO ratio, poly(vinyl alcohol) (PVA) concentration and sodium chloride (NaCl) concentration. The encapsulation efficiency increased with NaCl concentration increase, the percentages of enoxaparin sodium reaching 94% for some formulations. Increasing the ratio Eudragit® FS-30D/Eudragit® RS-PO ensured a relatively complete release of enoxaparin sodium in the environment simulating the colonic pH. Based on these results, the optimum conditions were decided and the optimum formulation was prepared. The results obtained for the latter in terms of in vitro enoxaparin sodium release were good, the microparticles releasing only 9.42% enoxaparin sodium in acidic environment and 15.16% in the medium which simulated duodenal pH, but allowing the release of up to 89.24% in the medium which simulated colonic pH. The in vitro release profile of enoxaparin sodium was close to the ideal one, therefore the system was successfully designed using QbD approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Interactions between Membranes and "Metaphilic" Polypeptide Architectures with Diverse Side-Chain Populations.

PubMed

Lee, Michelle W; Han, Ming; Bossa, Guilherme Volpe; Snell, Carly; Song, Ziyuan; Tang, Haoyu; Yin, Lichen; Cheng, Jianjun; May, Sylvio; Luijten, Erik; Wong, Gerard C L

2017-03-28

At physiological conditions, most proteins or peptides can fold into relatively stable structures that present on their molecular surfaces specific chemical patterns partially smeared out by thermal fluctuations. These nanoscopically defined patterns of charge, hydrogen bonding, and/or hydrophobicity, along with their elasticity and shape stability (folded proteins have Young's moduli of ∼1 × 10 8 Pa), largely determine and limit the interactions of these molecules, such as molecular recognition and allosteric regulation. In this work, we show that the membrane-permeating activity of antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) can be significantly enhanced using prototypical peptides with "molten" surfaces: metaphilic peptides with quasi-liquid surfaces and adaptable shapes. These metaphilic peptides have a bottlebrush-like architecture consisting of a rigid helical core decorated with mobile side chains that are terminated by cationic or hydrophobic groups. Computer simulations show that these flexible side chains can undergo significant rearrangement in response to different environments, giving rise to adaptable surface chemistry of the peptide. This quality makes it possible to control their hydrophobicity over a broad range while maintaining water solubility, unlike many AMPs and CPPs. Thus, we are able to show how the activity of these peptides is amplified by hydrophobicity and cationic charge, and rationalize these results using a quantitative mean-field theory. Computer simulations show that the shape-changing properties of the peptides and the resultant adaptive presentation of chemistry play a key enabling role in their interactions with membranes.

Nonviral Vectors for Gene Delivery

NASA Astrophysics Data System (ADS)

Baoum, Abdulgader Ahmed

2011-12-01

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was also explored. Positively charged CPPs were complexed with pDNA or siRNA, which resulted in 'loose' (˜1 micron) particles. These were then condensed into small nanoparticles by using calcium, which formed "soft" crosslinks by interacting with both phosphates on nucleic acids and amines on CPPs. An optimal amount of CaCl2 produced stable, ˜100 nm complexes that exhibited higher transfection efficiency and gene silencing than PEI polyplexes. CPPs also displayed negligible cytotoxicity up to 5 mg/mL. Biophysical studies of the pDNA structure within complexes suggested that pDNA within CPP complexes (condensed with calcium) had similar structure, but enhanced thermal stability compared to PEI complexes. Thus, CPP complexes emerged as simple, attractive candidates for future studies on nonviral gene delivery in vivo.

Optimization of the Ethanol Recycling Reflux Extraction Process for Saponins Using a Design Space Approach

PubMed Central

Gong, Xingchu; Zhang, Ying; Pan, Jianyang; Qu, Haibin

2014-01-01

A solvent recycling reflux extraction process for Panax notoginseng was optimized using a design space approach to improve the batch-to-batch consistency of the extract. Saponin yields, total saponin purity, and pigment yield were defined as the process critical quality attributes (CQAs). Ethanol content, extraction time, and the ratio of the recycling ethanol flow rate and initial solvent volume in the extraction tank (RES) were identified as the critical process parameters (CPPs) via quantitative risk assessment. Box-Behnken design experiments were performed. Quadratic models between CPPs and process CQAs were developed, with determination coefficients higher than 0.88. As the ethanol concentration decreases, saponin yields first increase and then decrease. A longer extraction time leads to higher yields of the ginsenosides Rb1 and Rd. The total saponin purity increases as the ethanol concentration increases. The pigment yield increases as the ethanol concentration decreases or extraction time increases. The design space was calculated using a Monte-Carlo simulation method with an acceptable probability of 0.90. Normal operation ranges to attain process CQA criteria with a probability of more than 0.914 are recommended as follows: ethanol content of 79–82%, extraction time of 6.1–7.1 h, and RES of 0.039–0.040 min−1. Most of the results of the verification experiments agreed well with the predictions. The verification experiment results showed that the selection of proper operating ethanol content, extraction time, and RES within the design space can ensure that the CQA criteria are met. PMID:25470598

Application of quality by design concept to develop a dual gradient elution stability-indicating method for cloxacillin forced degradation studies using combined mixture-process variable models.

PubMed

Zhang, Xia; Hu, Changqin

2017-09-08

Penicillins are typical of complex ionic samples which likely contain large number of degradation-related impurities (DRIs) with different polarities and charge properties. It is often a challenge to develop selective and robust high performance liquid chromatography (HPLC) methods for the efficient separation of all DRIs. In this study, an analytical quality by design (AQbD) approach was proposed for stability-indicating method development of cloxacillin. The structures, retention and UV characteristics rules of penicillins and their impurities were summarized and served as useful prior knowledge. Through quality risk assessment and screen design, 3 critical process parameters (CPPs) were defined, including 2 mixture variables (MVs) and 1 process variable (PV). A combined mixture-process variable (MPV) design was conducted to evaluate the 3 CPPs simultaneously and a response surface methodology (RSM) was used to achieve the optimal experiment parameters. A dual gradient elution was performed to change buffer pH, mobile-phase type and strength simultaneously. The design spaces (DSs) was evaluated using Monte Carlo simulation to give their possibility of meeting the specifications of CQAs. A Plackett-Burman design was performed to test the robustness around the working points and to decide the normal operating ranges (NORs). Finally, validation was performed following International Conference on Harmonisation (ICH) guidelines. To our knowledge, this is the first study of using MPV design and dual gradient elution to develop HPLC methods and improve separations for complex ionic samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Birth-death models and coalescent point processes: the shape and probability of reconstructed phylogenies.

PubMed

Lambert, Amaury; Stadler, Tanja

2013-12-01

Forward-in-time models of diversification (i.e., speciation and extinction) produce phylogenetic trees that grow "vertically" as time goes by. Pruning the extinct lineages out of such trees leads to natural models for reconstructed trees (i.e., phylogenies of extant species). Alternatively, reconstructed trees can be modelled by coalescent point processes (CPPs), where trees grow "horizontally" by the sequential addition of vertical edges. Each new edge starts at some random speciation time and ends at the present time; speciation times are drawn from the same distribution independently. CPPs lead to extremely fast computation of tree likelihoods and simulation of reconstructed trees. Their topology always follows the uniform distribution on ranked tree shapes (URT). We characterize which forward-in-time models lead to URT reconstructed trees and among these, which lead to CPP reconstructed trees. We show that for any "asymmetric" diversification model in which speciation rates only depend on time and extinction rates only depend on time and on a non-heritable trait (e.g., age), the reconstructed tree is CPP, even if extant species are incompletely sampled. If rates additionally depend on the number of species, the reconstructed tree is (only) URT (but not CPP). We characterize the common distribution of speciation times in the CPP description, and discuss incomplete species sampling as well as three special model cases in detail: (1) the extinction rate does not depend on a trait; (2) rates do not depend on time; (3) mass extinctions may happen additionally at certain points in the past. Copyright © 2013 Elsevier Inc. All rights reserved.

Engineering of an inhalable DDA/TDB liposomal adjuvant: a quality-by-design approach towards optimization of the spray drying process.

PubMed

Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle; Nielsen, Hanne Mørck; Rantanen, Jukka; Foged, Camilla

2013-11-01

The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB). A quality by design (QbD) approach was applied to identify and link critical process parameters (CPPs) of the spray drying process to critical quality attributes (CQAs) using risk assessment and design of experiments (DoE), followed by identification of an optimal operating space (OOS). A central composite face-centered design was carried out followed by multiple linear regression analysis. Four CQAs were identified; the mass median aerodynamic diameter (MMAD), the liposome stability (size) during processing, the moisture content and the yield. Five CPPs (drying airflow, feed flow rate, feedstock concentration, atomizing airflow and outlet temperature) were identified and tested in a systematic way. The MMAD and the yield were successfully modeled. For the liposome size stability, the ratio between the size after and before spray drying was modeled successfully. The model for the residual moisture content was poor, although, the moisture content was below 3% in the entire design space. Finally, the OOS was drafted from the constructed models for the spray drying of trehalose stabilized DDA/TDB liposomes. The QbD approach for the spray drying process should include a careful consideration of the quality target product profile. This approach implementing risk assessment and DoE was successfully applied to optimize the spray drying of an inhalable DDA/TDB liposomal adjuvant designed for pulmonary vaccination.

Nose-to-Brain Delivery of Peptide Drugs Enhanced by Coadministration of Cell-penetrating Peptides: Therapeutic Potential for Dementia.

PubMed

Kamei, Noriyasu

2017-01-01

Recent reports suggest that peptide drugs such as insulin have the potential to serve as therapeutics in neurodegenerative diseases such as Alzheimer's disease. However, the transport of these drugs to the therapeutic target, the brain, is significantly hindered by the blood-brain barrier (BBB). Intranasal administration appears to be an ideal solution for drug delivery to the brain, bypassing the BBB, however the entry of peptide drugs into neuronal and epithelial cells in the olfactory mucosa remains low. In this study, we therefore examined whether intranasal coadministration of cell-penetrating peptides (CPPs) could improve nose-to-brain drug transport. In both mice and rats, we found that direct transport of insulin into the brain was significantly facilitated when coadministered with amphipathic CPP penetratin, and eventually insulin reached the deeper regions of the brain such as the hippocampus. In the mouse line senescence-accelerated mouse prone-8 (SAMP8), spatial learning tests demonstrated that long-term intranasal coadministration of insulin with penetratin improved mild memory loss in the early stages of dementia. In contrast, the severe cognitive dysfunction in the aged SAMP8 mice was preserved despite intranasal coadministration of insulin with penetratin. The immunohistological examination of the hippocampus suggested that enhanced nose-to-brain delivery of insulin had a partial neuroprotective effect but unexpectedly increased amyloid β plaque deposition. In conclusion, intranasal coadministration of insulin with CPPs has the potential to serve as a therapeutic for mild cognitive dysfunction. To identify suitable pharmacotherapy for dementia with severe pathology, further studies of nose-to-brain delivery of molecularly appropriate biopharmaceuticals are necessary.

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

PubMed

Abes, Saïd; Moulton, Hong M; Clair, Philippe; Prevot, Paul; Youngblood, Derek S; Wu, Rebecca P; Iversen, Patrick L; Lebleu, Bernard

2006-12-01

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.

Generation of GFP Native Protein for Detection of Its Intracellular Uptake by Cell-Penetrating Peptides.

PubMed

Kadkhodayan, S; Sadat, S M; Irani, S; Fotouhi, F; Bolhassani, A

2016-01-01

Different types of lipid- and polymer-based vectors have been developed to deliver proteins into cells, but these methods showed relatively poor efficiency. Recently, a group of short, highly basic peptides known as cell-penetrating peptides (CPPs) were used to carry polypeptides and proteins into cells. In this study, expression and purification of GFP protein was performed using the prokaryotic pET expression system. We used two amphipathic CPPs (Pep-1 and CADY-2) as a novel delivery system to transfer the GFP protein into cells. The morphological features of the CPP/GFP complexes were studied by scanning electron microscopy (SEM), Zetasizer, and SDS-PAGE. The efficiency of GFP transfection using Pep-1 and CADY-2 peptides and TurboFect reagent was compared with FITC-antibody protein control delivered by these transfection vehicles in the HEK-293T cell line. SEM data confirmed formation of discrete nanoparticles with a diameter of below 300 nm. Moreover, formation of the complexes was detected using SDS-PAGE as two individual bands, indicating non-covalent interaction. The size and homogeneity of Pep-1/GFP and CADY-2/GFP complexes were dependent on the ratio of peptide/cargo formulations, and responsible for their biological efficiency. The cells transfected by Pep-1/GFP and CADY-2/GFP complexes at a molar ratio of 20 : 1 demonstrated spreading green regions using fluorescent microscopy. Flow cytometry results showed that the transfection efficiency of Pep-based nanoparticles was similar to CADY-based nanoparticles and comparable with TurboFect-protein complexes. These data open an efficient way for future therapeutic purposes.

Process analytical technology (PAT) in insect and mammalian cell culture processes: dielectric spectroscopy and focused beam reflectance measurement (FBRM).

PubMed

Druzinec, Damir; Weiss, Katja; Elseberg, Christiane; Salzig, Denise; Kraume, Matthias; Pörtner, Ralf; Czermak, Peter

2014-01-01

Modern bioprocesses demand for a careful definition of the critical process parameters (CPPs) already during the early stages of process development in order to ensure high-quality products and satisfactory yields. In this context, online monitoring tools can be applied to recognize unfavorable changes of CPPs during the production processes and to allow for early interventions in order to prevent losses of production batches due to quality issues. Process analytical technologies such as the dielectric spectroscopy or focused beam reflectance measurement (FBRM) are possible online monitoring tools, which can be applied to monitor cell growth as well as morphological changes. Since the dielectric spectroscopy only captures cells with intact cell membranes, even information about dead cells with ruptured or leaking cell membranes can be derived. The following chapter describes the application of dielectric spectroscopy on various virus-infected and non-infected cell lines with respect to adherent as well as suspension cultures in common stirred tank reactors. The adherent mammalian cell lines Vero (African green monkey kidney cells) and hMSC-TERT (telomerase-immortalized human mesenchymal stem cells) are thereby cultured on microcarrier, which provide the required growth surface and allow the cultivation of these cells even in dynamic culture systems. In turn, the insect-derived cell lines S2 and Sf21 are used as examples for cells typically cultured in suspension. Moreover, the FBRM technology as a further monitoring tool for cell culture applications has been included in this chapter using the example of Drosophila S2 insect cells.

Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials.gov: a systematic review of registration details.

PubMed

Buffel du Vaure, Céline; Dechartres, Agnès; Battin, Constance; Ravaud, Philippe; Boutron, Isabelle

2016-09-27

To systematically assess registration details of ongoing randomised controlled trials (RCTs) targeting 10 common chronic conditions and registered at ClinicalTrials.gov and to determine the prevalence of (1) trial records excluding patients with concomitant chronic condition(s) and (2) those specifically targeting patients with concomitant chronic conditions. Systematic review of trial registration records. ClinicalTrials.gov register. All ongoing RCTs registered from 1 January 2014 to 31 January 2015 that assessed an intervention targeting adults with coronary heart disease (CHD), hypertension, heart failure, stroke/transient ischaemic attack, atrial fibrillation, type 2 diabetes, chronic obstructive pulmonary disease, painful condition, depression and dementia with a target sample size ≥100. From the trial registration records, 2 researchers independently recorded the trial characteristics and the number of exclusion criteria and determined whether patients with concomitant chronic conditions were excluded or specifically targeted. Among 319 ongoing RCTs, despite the high prevalence of the concomitant chronic conditions, patients with these conditions were excluded in 251 trials (79%). For example, although 91% of patients with CHD had a concomitant chronic condition, 69% of trials targeting such patients excluded patients with concomitant chronic condition(s). When considering the co-occurrence of 2 chronic conditions, 31% of patients with chronic pain also had depression, but 58% of the trials targeting patients with chronic pain excluded patients with depression. Only 37 trials (12%) assessed interventions specifically targeting patients with concomitant chronic conditions; 31 (84%) excluded patients with concomitant chronic condition(s). Despite widespread multimorbidity, more than three-quarters of ongoing trials assessing interventions for patients with chronic conditions excluded patients with concomitant chronic conditions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chronic widespread musculoskeletal pain in patients with obstructive sleep apnea syndrome and the relationship between sleep disorder and pain level, quality of life, and disability.

PubMed

Aytekin, Ebru; Demir, Saliha Eroglu; Komut, Ece Akyol; Okur, Sibel Caglar; Burnaz, Ozer; Caglar, Nil Sayiner; Demiryontar, Dilay Yilmaz

2015-09-01

[Purpose] The aim of this study was to ascertain the prevalence of chronic widespread musculoskeletal pain in patients with obstructive sleep apnea syndrome and to assess the relationship between sleep disorder and pain, quality of life, and disability. [Subjects and Methods] Seventy-four patients were included in the study and classified as having mild, moderate, or severe obstructive sleep apnea. Chronic widespread pain, quality of life, and disability were evaluated. [Results] Forty-one patients (55.4%) had chronic widespread pain. Female patients had a higher incidence of chronic pain, and female patients with chronic pain had higher body mass indexes, pain levels, and disability scores than did male patients. Physical component scores of female patients with chronic pain were lower than those of male patients. No correlation was observed between the degree of sleep disorder and severity of pain, pain duration, disability, or quality of life in obstructive sleep apnea patients with pain. [Conclusion] This study showed a 55.4% prevalence of chronic widespread pain in patients with obstructive sleep apnea and a greater risk of chronic pain in female than in male patients. Female patients with obstructive sleep apnea and chronic pain have higher pain and disability levels and a lower quality of life.

Intrahospital Transfer of Patients with Traumatic Brain Injury: Increase in Intracranial Pressure.

PubMed

Trofimov, Alex; Kalentiev, George; Yuriev, Michail; Pavlov, Vladislav; Grigoryeva, Vera

2016-01-01

To assess the dynamic of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and dynamic pressure reactivity index (PRx) during intrahospital transport. There were 33 comatose patients with severe traumatic brain injury (TBI). The mean age was 36.3 ± 4.8 years (range 19-45 years), and there were 17 men and 16 women. The median Glasgow Coma Scale score at admission was 6.2 ± 0.7. Computed tomography (CT) included native CT, perfusion CT, and CT angiography. The mean CPPs before and after the CT scans were 95.9 ± 10.7 and 81.5 ± 12.5 mmHg respectively. The mean ICP before transport was 19.98 ± 5.3 mmHg (minimum 11.7; maximum 51.7). It was statistically significantly lower (p < 0.001) than during the transfer (26.1 ± 13.5 mmHg). During the period described all patients had increased ICP, especially during vertical movement in an elevator. During horizontal movement on the floor ICP remained higher (p < 0.05). The mean dynamic PRx before and after intrahospital transport was 0.23 ± 0.14 and 0.52 ± 0.04, respectively (p < 0.001). Average duration of the transfer and CT study was 15.3 ± 3.4 min. Intrahospital transport of patients with TBI may lead to a significant increase in ICP, dynamic PRx, and decreased CPP. The results suppose that the decision to perform brain CT in comatose patients with TBI should be carefully considered by clinicians.

[Disorder of mineral density of the bone tissue in patients with chronic pancreatitis].

PubMed

Chernyshova, I V; Drozdov, V N; Vinokurova, L V; Embutnieks, Iu V; Viazhevich, Iu V

2008-01-01

OMD was examined in 50 patients with chronic pancreatitis. The disturbances of OMD was revealed in 46% of the patients with chronic pancreatitis. Influence of chronic pancreatitis to the reduce of OMD was proved, especially in the patients with prolonged desease, analysis of the osteoporosis and osteopenia localization was performed in the patients with chronic pancreatitis.

The Association of Patient Chronic Disease Burden and Self-Management Requirements With Shared Decision Making in Primary Care Visits

PubMed Central

Drum, Melinda; Cooper, Lisa A.

2014-01-01

Background: Shared decision making (SDM) is associated with positive health outcomes and may be particularly relevant for patients with chronic disease. Objectives: To investigate whether (1) patients with chronic diseases, particularly those requiring self-management, are more likely to engage in SDM behaviors than patients without chronic diseases and (2) patients with chronic diseases are more likely to have their physicians engage them in SDM. Design: A cross-sectional study of patients who were enrolled in a randomized controlled trial to improve patient–physician communication. Participants: Adult patients with hypertension at community health clinics in Baltimore, Maryland. Approach: We used multivariable regression models to examine the associations of the following predictor variables: (1) chronic disease burden and (2) diseases requiring self-management with the following outcome variables measuring SDM components: (1) patient information sharing, (2) patient decision making, and (3) physician SDM facilitation. Key Results: Patients with greater chronic disease burden and more diseases requiring self-management reported more information sharing (β = .07, P = .03 and β = .12, P = .046, respectively) and decision making (β = .06, P = .02 and β = .21, P < .001) as did patients who reported poor general health. Physician facilitation of SDM was not associated with chronic disease burden or with diseases requiring self-management but was associated with higher patient income. Conclusions: Patients with chronic diseases, particularly those requiring self-management, may be more likely to engage in SDM behaviors, but physicians may not be more likely to engage such patients in SDM. Targeting patients with chronic disease for SDM may improve health outcomes among the chronically ill, particularly among vulnerable patients (eg, minorities, low-income patients) who suffer disproportionately from such conditions. PMID:26640812

Comparative Efficacy of Bilateral Thoracoscopic Splanchnicectomy for Intractable Pain Secondary to Pancreatic Cancer vs Chronic Pancreatitis.

PubMed

Bhutiani, Neal; Cheadle, Gerald A; Bahr, Michael H; Vitale, Gary C

2017-04-01

Splanchnicectomy has been evaluated for treatment of chronic pain in both pancreatic cancer and chronic pancreatitis patients, although its efficacy has not been compared in these 2 patient populations. This study aimed to compare bilateral thoracoscopic splanchnicectomy in treatment of abdominal pain secondary with pancreatic cancer and chronic pancreatitis. A University of Louisville database was evaluated from July 1998 to March 2016 for patients undergoing bilateral thoracoscopic splanchnicectomy for intractable pain secondary to pancreatic cancer (n = 48) or chronic pancreatitis (n = 75). Patients were evaluated pre- and postoperatively with regard to abdominal pain and related symptoms, narcotic analgesic requirements, and hospital admissions. Narcotic use was quantified using the Kentucky All Schedule Prescription Electronic Reporting system. After bilateral thoracoscopic splanchnicectomy, 28% of pancreatic cancer patients continued to experience abdominal pain compared with 57% of chronic pancreatitis patients. Daily narcotic dose decreased for 74% of pancreatic cancer compared with 32% of chronic pancreatitis patients (p < 0.001). Sixty-seven percent of pancreatic cancer patients discontinued pain medications completely compared with 14% of chronic pancreatitis patients (p < 0.001). Hospitalizations decreased significantly in both groups (p < 0.001; p = 0.001), although mean number of postoperative hospitalizations was lower for pancreatic cancer (0.5) compared with chronic pancreatitis patients (2.80) (p < 0.001). Mean follow-up was significantly shorter for pancreatic cancer patients than for chronic pancreatitis patients (8 months vs 32 months; p < 0.001). Bilateral thoracoscopic splanchnicectomy safely, effectively, and durably relieves abdominal pain in patients with both pancreatic cancer and chronic pancreatitis. However, it is more effective in providing pain relief and preventing pain-related hospitalizations in patients with pancreatic cancer compared with those with chronic pancreatitis. Copyright © 2017. Published by Elsevier Inc.

High-quality chronic care delivery improves experiences of chronically ill patients receiving care

PubMed Central

Cramm, Jane Murray; Nieboer, Anna Petra

2013-01-01

Objective Investigate whether high-quality chronic care delivery improved the experiences of patients. Design This study had a longitudinal design. Setting and Participants We surveyed professionals and patients in 17 disease management programs targeting patients with cardiovascular diseases, chronic obstructive pulmonary disease, heart failure, stroke, comorbidity and eating disorders. Main Outcome Measures Patients completed questionnaires including the Patient Assessment of Chronic Illness Care (PACIC) [T1 (2010), 2637/4576 (58%); T2 (2011), 2314/4330 (53%)]. Professionals' Assessment of Chronic Illness Care (ACIC) scores [T1, 150/274 (55%); T2, 225/325 (68%)] were used as a context variable for care delivery. We used two-tailed, paired t-tests to investigate improvements in chronic illness care quality and patients' experiences with chronic care delivery. We employed multilevel analyses to investigate the predictive role of chronic care delivery quality in improving patients' experiences with care delivery. Results Overall, care quality and patients' experiences with chronic illness care delivery significantly improved. PACIC scores improved significantly from 2.89 at T1 to 2.96 at T2 and ACIC-S scores improved significantly from 6.83 at T1 to 7.18 at T2. After adjusting for patients' experiences with care delivery at T1, age, educational level, marital status, gender and mental and physical quality of life, analyses showed that the quality of chronic care delivery at T1 (P < 0.001) and changes in care delivery quality (P < 0.001) predicted patients' experiences with chronic care delivery at T2. Conclusion This research showed that care quality and changes therein predict more positive experiences of patients with various chronic conditions over time. PMID:24123243

Prevalence of chronic itch and associated factors in haemodialysis patients: a representative cross-sectional study.

PubMed

Weiss, Melanie; Mettang, Thomas; Tschulena, Ulrich; Passlick-Deetjen, Jutta; Weisshaar, Elke

2015-09-01

Chronic itch is a common symptom in haemodialysis (HD) patients, which is often underestimated. The aim of this cross-sectional study was to investigate the prevalence and factors associated with chronic itch in HD patients. A total of 860 HD patients from a randomly selected cluster-sample of patients attending dialysis units in Germany were included. The patients' mean?±?SD age was 67.2?±?13.5 years, 57.2% were male. The point prevalence of chronic itch was 25.2% (95% CI 22.4-28.1), 12-month prevalence was 27.2% (95% CI 24.1-30.3) and lifetime prevalence was 35.2% (95% CI 31.9-38.3). Chronic itch was significantly less prevalent in patients with secondary glomerulonephritis as primary renal disease. A history of dry skin, eczema, and age

Psychological comorbidity in patients with chronic tinnitus: analysis and comparison with chronic pain, asthma or atopic dermatitis patients.

PubMed

Zirke, N; Seydel, C; Szczepek, A J; Olze, H; Haupt, H; Mazurek, B

2013-03-01

To determine the prevalence and severity of psychological comorbidity in patients with chronic tinnitus in comparison with other chronic illnesses, namely chronic pain, chronic asthma and atopic dermatitis. Psychological diagnoses were done according to ICD-10 Chapter V(F). Subjective impairment was evaluated using 5 psychometric questionnaires: tinnitus questionnaire, Berlin mood questionnaire, sense of coherence (SOC-L9) and perceived stress questionnaire. Sleep disturbance was measured by the subdomain 'exhaustion' of the Giessen physical complaints inventory. Somatoform or affective disorders were most frequent in all disease groups. Patients with chronic tinnitus had a stronger SOC and better subjective mood, stronger commitment, and less anger and anxious depression than the patients with chronic pain, chronic asthma or atopic dermatitis. However, in patients with higher tinnitus annoyance, psychological comorbidity was similar to that found in patients with other chronic diseases. Besides collecting medical and social history, special psychometric instruments should be used for the diagnosis of tinnitus patients. Based on relative high frequency of psychological comorbidity, we recommend interdisciplinary cooperation between otorhinolaryngologists and other specialists (psychosomatic medicine, psychology or psychiatry) during the treatment of tinnitus patients, especially when high degree of tinnitus annoyance is involved.

Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

PubMed

Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

2011-01-01

Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy.

PubMed

Vasconcelos, Luís; Lehto, Tõnis; Madani, Fatemeh; Radoi, Vlad; Hällbrink, Mattias; Vukojević, Vladana; Langel, Ülo

2018-02-01

Peptides able to translocate cell membranes while carrying macromolecular cargo, as cell-penetrating peptides (CPPs), can contribute to the field of drug delivery by enabling the transport of otherwise membrane impermeable molecules. Formation of non-covalent complexes between amphipathic peptides and oligonucleotides is driven by electrostatic and hydrophobic interactions. Here we investigate and quantify the coexistence of distinct molecular species in multiple equilibria, namely peptide monomer, peptide self-aggregates and peptide/oligonucleotide complexes. As a model for the complexes, we used a stearylated peptide from the PepFect family, PF14 and siRNA. PF14 has a cationic part and a lipid part, resembling some characteristics of cationic lipids. Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) were used to detect distinct molecular entities in solution and at the plasma membrane of live cells. For that, we labeled the peptide with carboxyrhodamine 6G and the siRNA with Cyanine 5. We were able to detect fluorescent entities with diffusional properties characteristic of the peptide monomer as well as of peptide aggregates and peptide/oligonucleotide complexes. Strategies to avoid peptide adsorption to solid surfaces and self-aggregation were developed and allowed successful FCS measurements in solution and at the plasma membrane. The ratio between the detected molecular species was found to vary with pH, peptide concentration and the proximity to the plasma membrane. The present results suggest that the diverse cellular uptake mechanisms, often reported for amphipathic CPPs, might result from the synergistic effect of peptide monomers, self-aggregates and cargo complexes, distributed unevenly at the plasma membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.

PubMed

Tudzynski, P; Hölter, K; Correia, T; Arntz, C; Grammel, N; Keller, U

1999-02-01

A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that catalyzes the first specific step in the biosynthesis of ergot alkaloids, was cloned from a strain of Claviceps purpurea that produces alkaloids in axenic culture. The derived gene product (CPD1) shows only 70% similarity to the corresponding gene previously isolated from Claviceps strain ATCC 26245, which is likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most probably represents the first C. purpurea gene coding for an enzymatic step of the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene named cpps1, which codes for a 356-kDa polypeptide showing significant similarity to fungal modular peptide synthetases. The protein contains three amino acid-activating modules, and in the second module a sequence is found which matches that of an internal peptide (17 amino acids in length) obtained from a tryptic digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome walking revealed the presence of additional genes upstream of cpd1 which are probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase), and a second putative oxidoreductase gene, cpox2, is closely linked to it in inverse orientation. RT-PCR experiments confirm that all four genes are expressed under conditions of peptide alkaloid biosynthesis. These results strongly suggest that at least some genes of ergot alkaloid biosynthesis in C. purpurea are clustered, opening the way for a detailed molecular genetic analysis of the pathway.

Direct cytosolic delivery of cargoes in vivo by a chimera consisting of D- and L-arginine residues.

PubMed

Ma, Yan; Gong, Cheng; Ma, Yilong; Fan, Fengkai; Luo, Meijie; Yang, Fei; Zhang, Yu-Hui

2012-09-10

The ability of cell-penetrating peptides (CPPs) to deliver a range of membrane-impermeable molecules into living cells makes them attractive potential vehicles for therapeutics. However, in vivo, the efficiency of CPP delivery to the cytosol remains unsatisfactory owing to endosomal entrapment and/or systemic toxicity, which severely restrict their bioavailability and efficacy in in vivo applications. In this study, we developed a series of novel chimeras consisting of various numbers of d- and l-arginine residues and investigated their cellular uptake behaviors and systemic toxicities. We demonstrated that the intracellular distribution, uptake efficiency, and systemic toxicity of these oligoarginines were all significantly affected by the number of d-arginine residues in the peptide sequence. We also found that a hybrid peptide, (rR)(3)R(2), possessed low systemic toxicity, high uptake efficiency, and, remarkably, achieved efficient cytosolic delivery not only in cultured cells but also in living tissue cells in mice after intravenous injection, implying that this heterogeneous motif might have promising applications in the delivery of cargoes of small sizes directed to cytosolic targets in vivo. Our studies into the uptake mechanism of (rR)(3)R(2) indicate that its cellular uptake was not affected by pharmacological or physical inhibitors of endocytosis but by the elimination of the membrane potential, suggesting that (rR)(3)R(2) does not enter the cells via endocytosis but rather through direct membrane translocation driven by the membrane potential. The results here might provide useful guidelines for the design and application of CPPs in drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Perceptual structure of adductor spasmodic dysphonia and its acoustic correlates.

PubMed

Cannito, Michael P; Doiuchi, Maki; Murry, Thomas; Woodson, Gayle E

2012-11-01

To examine the perceptual structure of voice attributes in adductor spasmodic dysphonia (ADSD) before and after botulinum toxin treatment and identify acoustic correlates of underlying perceptual factors. Reliability of perceptual judgments is considered in detail. Pre- and posttreatment trial with comparison to healthy controls, using single-blind randomized listener judgments of voice qualities, as well as retrospective comparison with acoustic measurements. Oral readings were recorded from 42 ADSD speakers before and after treatment as well as from their age- and sex-matched controls. Experienced judges listened to speech samples and rated attributes of overall voice quality, breathiness, roughness, and brokenness, using computer-implemented visual analog scaling. Data were adjusted for regression to the mean and submitted to principal components factor analysis. Acoustic waveforms, extracted from the reading samples, were analyzed and measurements correlated with perceptual factor scores. Four reliable perceptual variables of ADSD voice were effectively reduced to two underlying factors that corresponded to hyperadduction, most strongly associated with roughness, and hypoadduction, most strongly associated with breathiness. After treatment, the hyperadduction factor improved, whereas the hypoadduction factor worsened. Statistically significant (P<0.01) correlations were observed between perceived roughness and four acoustic measures, whereas breathiness correlated with aperiodicity and cepstral peak prominence (CPPs). This study supported a two-factor model of ADSD, suggesting perceptual characterization by both hyperadduction and hypoadduction before and after treatment. Responses of the factors to treatment were consistent with previous research. Correlations among perceptual and acoustic variables suggested that multiple acoustic features contributed to the overall impression of roughness. Although CPPs appears to be a partial correlate of perceived breathiness, a physical basis of this percept remained less clear. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Impact of chronic kidney disease stage on lower-extremity arthroplasty.

PubMed

Deegan, Brian F; Richard, Raveesh D; Bowen, Thomas R; Perkins, Robert M; Graham, Jove H; Foltzer, Michael A

2014-07-01

End-stage renal disease and dialysis is commonly associated with poor outcomes after joint replacement surgery. The goal of this study was to evaluate postoperative complications in patients with less advanced chronic kidney disease undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients who underwent THA or TKA between 2004 and 2011 with stage 1, 2, or 3 chronic kidney disease were retrospectively reviewed via an electronic medical record. The authors compared 377 patients who had stage 1 to 2 chronic kidney disease with 402 patients who had stage 3 chronic kidney disease. No significant differences in 90-day readmission or revision rates were found between the stage 1 to 2 and stage 3 patient groups. For patients with stage 3 chronic kidney disease, the overall mortality rate was greater than that in patients with stage 1 to 2 chronic kidney disease. However, when adjusted for comorbid disease, no significant increases were seen in joint infection, readmission, or early revision between patients with stage 1 to 2 chronic kidney disease vs patients with stage 3 chronic kidney disease. The overall incidence of infection was high (3.5%) but far less than reported for patients with end-stage renal disease, dialysis, and kidney transplant. In conclusion, patients with stage 1, 2, or 3 chronic kidney disease may have a higher than expected rate of prosthetic joint infection (3.5%) after total joint arthroplasty. Patients with stage 3 chronic kidney disease are at higher risk for postoperative mortality compared with those with lesser stages of kidney disease. Copyright 2014, SLACK Incorporated.

Prevalence of chronic kidney disease among patients undergoing transradial percutaneous coronary interventions.

PubMed

Hossain, Mohammad A; Quinlan, Amy; Heck-Kanellidis, Jennifer; Calderon, Dawn; Patel, Tejas; Gandhi, Bhavika; Patel, Shrinil; Hetavi, Mahida; Costanzo, Eric J; Cosentino, James; Patel, Chirag; Dewan, Asa; Kuo, Yen-Hong; Salman, Loay; Vachharajani, Tushar J

2018-07-01

While transradial approach to conduct percutaneous coronary interventions offers multiple advantages, the procedure can cause radial artery damage and occlusion. Because radial artery is the preferred site for the creation of an arteriovenous fistula to provide dialysis, patients with chronic kidney disease are particularly dependent on radial artery for their long-term survival. In this retrospective study, we investigated the prevalence of chronic kidney disease in patients undergoing coronary interventions via radial artery. Stage of chronic kidney disease was based on estimated glomerular filtration rate and National Kidney Foundation - Kidney Disease Outcomes Quality Initiative guidelines. A total of 497 patients undergoing transradial percutaneous coronary interventions were included. Over 70.4% (350/497) of the patients had chronic kidney disease. Stage II chronic kidney disease was observed in 243 (69%) patients (estimated glomerular filtration rate = 76.0 ± 8.4 mL/min). Stage III was observed in 93 (27%) patients (estimated glomerular filtration rate = 49 ± 7.5 mL/min). Stage IV chronic kidney disease was observed in 5 (1%) patients (estimated glomerular filtration rate = 25.6 ± 4.3 mL/min) and Stage V chronic kidney disease was observed in 9 (3%) patients (estimated glomerular filtration rate = 9.3 ± 3.5 mL/min). Overall, 107 of 350 patients (30%) had advanced chronic kidney disease, that is, stage III-V chronic kidney disease. Importantly, 14 of the 107 (13%) patients had either stage IV or V chronic kidney disease. This study finds that nearly one-third of the patients undergoing transradial percutaneous coronary interventions have advanced chronic kidney disease. Because many of these patients may require dialysis, the use of radial artery to conduct percutaneous coronary interventions must be carefully considered in chronic kidney disease population.

Association between chronic urticaria and self-reported penicillin allergy.

PubMed

Silverman, Susanna; Localio, Russell; Apter, Andrea J

2016-04-01

Penicillin allergy is the most commonly reported drug allergy and often presents with cutaneous symptoms. Other common diagnoses, such as chronic urticaria, may be falsely attributed to penicillin allergy. Because chronic urticaria is fairly common in the general population, evaluation of its prevalence in patients with self-reported penicillin allergy was of interest. Similarly, the prevalence of self-reported penicillin allergy in patients with chronic urticaria is not well known and also becomes interesting in light of the high prevalence of self-reported penicillin allergy in the general population. To determine the prevalence of self-reported penicillin allergy in patients with chronic urticaria and the prevalence of chronic urticaria in patients with self-reported penicillin allergy. This was a retrospective medical record review of 11,143 patients completed using the electronic health record of the University of Pennsylvania Allergy and Immunology clinic. The prevalence of self-reported penicillin allergy in patients with chronic urticaria was found to be approximately 3 times greater than in the general population. The prevalence of chronic urticaria in patients with self-reported penicillin allergy was also found to be approximately 3 times greater than in the population. This link between chronic urticaria and self-reported penicillin allergy highlights the need for clinicians to inquire about self-reported penicillin allergy in patients with chronic urticaria and to consider penicillin skin testing. Furthermore, patients who report penicillin allergy might actually have chronic urticaria, indicating the importance of inquiring about chronic urticaria symptoms in patients with self-reported penicillin allergy. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum.

PubMed

Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

2016-12-01

Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients.

Diagnosis, treatment, and nursing care of patients with chronic leukemia.

PubMed

Breed, Cheryl D

2003-05-01

To provide an update on the impact of new information about the molecular biology of chronic leukemia and new treatment modalities available to patients. Published articles, books, and research studies. There has been significant progress in the diagnosis and management of chronic myeloid and chronic lymphocytic leukemia. New therapies provide more options for patients and longer treatment periods. With increasing treatment options and longer survival, patients with chronic myelogenous or chronic lymphocytic leukemia need increased education, support, and assistance with symptom management. Nurses caring for these patients must remain knowledgeable about new treatments and their management.

Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

PubMed Central

Bear, R.; Goldstein, M.; Phillipson, E.; Ho, M.; Hammeke, M.; Feldman, R.; Handelsman, S.; Halperin, M.

1977-01-01

Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis. PMID:21028

Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis.

PubMed

Czaja, A J; Ludwig, J; Baggenstoss, A H; Wolf, A

1981-01-01

To assess the prognosis of patients with severe chronic hepatitis after histologic examination had shown an improvement to chronic persistent hepatitis, we followed 52 such patients regularly for 54 +/- 4 months after the cessation of corticosteroid therapy. In 24 patients, the condition deteriorated 7 +/- 1 months after therapy and required further treatment with prednisone. Histologic features of chronic active hepatitis, including bridging and multilobular necrosis, were documented in all 14 patients in whom biopsies were performed. In 20 of 24 patients, the disease responded to retreatment, but 13 again had relapses, and cirrhosis developed in two. Of 28 patients who remained asymptomatic for 48 +/- 6 months, 17 retained features of chronic persistent hepatitis, and nine had improvement to normal histologic features. Cirrhosis developed in two patients without clinical manifestations of active inflammation. Findings before and after treatment did not predict outcome. We conclude that severe chronic active hepatitis that has been treated with prednisone and converted to chronic persistent hepatitis will often and unpredictably deteriorate after treatment has been stopped. Cirrhosis develops rarely but may occur with or without clinically overt chronic active hepatitis.

[Chronicity problems of the ambulatory patient].

PubMed

Schneider, P B; Carron, R

1980-01-01

This report is comprised of three parts: the first two parts give a very brief summary of two research projects carried out on groups of chronic, psychiatric out-patients within the framework of the University Psychiatric Policlinic of Lausanne. The third part is an attempt at discerning the fundamental, psychological aspects common to almost all chronic patients as well as the features typical of the relationship between the doctor and his chronic patient. The first piece of research consists of an epidemiological, clinical and catamnestic study of a group of 309 patients. Ten years after the original sample group was selected, 82 patients are still being treated. Various signs help to bring into focus the picture of the so-called chronic patient. They also reveal that the doctor-patient relationship deviated rather rapidly starting right from the first consultation towards a relationship described under the title maintenance service relationship. Furthermore it can be seen that in those groups studied, it was not possible to discern which patients would become seriously chronic at the time when they were first taken in charge. The object of the second study was the medical prescriptions given to a group of 65 chronic patients in treatment from 1965 through 1977. As can be expected in a public service with its frequent change of physicians, the patients were followed by several, not to say numerous, physicians. Regarding the different reasons causing a change of prescription, it is interesting to note that the psychic state of the patient played a much more important role here than the change of the treating physician. Thus the observation of chronic, somatic patients is very useful for the psychological understanding of chronicity. There is, in fact, no concordance between the condition of a person suffering from a chronic, physical illness and a person who is psychologically chronic. A description is given of those factors related to personality structure whose interrelation--defined as a basic psychodynamic triad--is necessary for psychological chronicity to set in. Furthermore, the reflections underline the fact that a better understanding psychological chronicity is also very closely subordinated to increasing our knowledge of the doctor-patient relationship.

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases.

PubMed

Dostalikova-Cimburova, Marketa; Kratka, Karolina; Stransky, Jaroslav; Putova, Ivana; Cieslarova, Blanka; Horak, Jiri

2012-01-01

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

PubMed Central

Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard

2017-01-01

Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain. PMID:28046033

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

PubMed

Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard; Holzer, Barbara M

2017-01-01

Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain.

Localizing chronic Q fever: a challenging query

PubMed Central

2013-01-01

Background Chronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed. Methods Fifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded. Results According to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively. Conclusions If chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions. PMID:24004470

Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

PubMed Central

Kremers, Marjolein N. T.; Hodemaekers, Hennie M.; Hagenaars, Julia C. J. P.; Koning, Olivier H. J.; Renders, Nicole H. M.; Hermans, Mirjam H. A.; de Klerk, Arja; Notermans, Daan W.; Wever, Peter C.; Janssen, Riny

2015-01-01

A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites. PMID:25924761

Access to Care and Satisfaction Among Health Center Patients With Chronic Conditions.

PubMed

Shi, Leiyu; Lee, De-Chih; Haile, Geraldine Pierre; Liang, Hailun; Chung, Michelle; Sripipatana, Alek

This study examined access to care and satisfaction among health center patients with chronic conditions. Data for this study were obtained from the 2009 Health Center Patient Survey. Dependent variables of interest included 5 measures of access to and satisfaction with care, whereas the main independent variable was number of chronic conditions. Results of bivariate analysis and multiple logistic regressions showed that patients with chronic conditions had significantly higher odds of reporting access barriers than those without chronic conditions. Our results suggested that additional efforts and resources are necessary to address the needs of health center patients with chronic conditions.

Adjustment to chronic pain in back pain patients classified according to the motivational stages of chronic pain management.

PubMed

Zenker, Stefanie; Petraschka, Michael; Schenk, Michael; Reisshauer, Anett; Newie, Tanja; Hermanns, Kai; Wernecke, Klaus-Dieter; Spies, Claudia

2006-06-01

According to Prochaska's transtheoretical model, the Freiburg Questionnaire stages of chronic pain management (FQ-STAPM) were used to classify chronic back patients into 4 distinct motivational stages. The FQ-STAMP was completed by 163 chronic back pain patients. Pain chronicity was measured by the Mainz Pain Staging System; pain intensity was measured by the numeric rating scale. Healthcare system expenses were considered as number of consulted physicians, number of stays in hospital, and number of rehabilitation programs. As psychometric tests, the lower pain disability index (PDI), the Hospital Anxiety and Depression Scale (HADS), and a quality of life score (SF36) were used. Patients were in the following motivational stages: precontemplation in 30%, preparation in 19%, action in 30%, maintenance in 21%. The intensity of pain in the precontemplation stage patients was significantly higher compared to patients in the maintenance stage. A lower pain chronicity was related to a significantly higher motivation. Moreover, there was a significant increase in healthcare system expenses by the lesser motivated patients. Patients in the maintenance stage used significantly less opioids than patients in the precontemplation stage. The higher motivated patients had a significantly lower PDI, a significantly lower HADS, and a significantly higher quality of life compared to less motivated patients. The study indicates that the FQ-STAPM might be a useful tool to classify chronic back pain patients and to work out a strategy together with the patient relevant to the outcome of pain management among chronic back pain patients.

The Results of Autologous Skin Test in Patients with Chronic Urticaria in Hamadan, Iran

PubMed Central

Safari, Mojgan; Sayemiri, Hooshyar

2016-01-01

Introduction The etiology of chronic urticaria is unknown in many cases. In this study, we demonstrated the presence of autoimmune antibodies in patients with chronic urticaria by using of the Autologous Serum Skin Test (ASST). Methods We performed a cross-sectional study to detect the presence of autologous antibodies in the serum of 38 patients (25 females and 13 males) with idiopathic chronic urticaria who were referred to the Hamedan Allergy Clinic in 2014. All of the necessary tests for demonstrating chronic urticaria were performed, including complete blood count (CBC), thyroid and liver functionality tests, and the prick test but they did not confirm the cause of chronic urticaria. We conducted the Autologous Serum Skin Test on the patients and analyzed the results. Results In 15 patients (39%), the ASST was positive. Of the 15 patients with positive autoimmune chronic urticaria, five patients (33%) were males, and 10 patients (67%) were females. Conclusion We concluded that many patients with chronic urticaria have autoimmune urticaria. It is the reason for the lack of the response to treatment with common medications for urticaria. New ways of treatment must be considered for them. PMID:27504169

Doctors and patients in pain: Conflict and collaboration in opioid prescription in primary care.

PubMed

Esquibel, Angela Y; Borkan, Jeffrey

2014-12-01

Use of chronic opioid therapy (COT) for chronic noncancer pain has dramatically increased in the United States. Patients seek compassionate care and relief while physicians struggle to manage patients' pain effectively without doing harm. This study explores the narratives of chronic noncancer pain patients receiving chronic opioid therapy and those of their physicians to better understand the effects of COT on the doctor-patient relationship. A mixed method study was conducted that included in-depth interviews and qualitative analysis of 21 paired patients with chronic pain and their physicians in the following groups: patients, physicians, and patient-physician pairs. Findings revealed that patients' narratives focus on suffering from chronic pain, with emphasis on the role of opioid therapy for pain relief, and physicians' narratives describe the challenges of treating patients with chronic pain on COT. Results elucidate the perceptions of ideal vs difficult patients and show that divergent patterns surrounding the consequences, utility, and goals of COT can negatively affect the doctor-patient relationship. The use of paired interviews through a narrative lens in this exploratory study offers a novel and informative approach for clinical practice and research. The findings have significant implications for improving doctor-patient communication and health outcomes by encouraging shared decision making and goal-directed health care encounters for physicians and patients with chronic pain on COT. This study found patterns of understanding pain, opioid pain medications, and the doctor-patient relationship for patients with chronic pain and their physicians using a narrative lens. Thematic findings in this exploratory study, which include a portrayal of collaborative vs conflictual relationships, suggest areas of future intervention and investigation. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Primary and secondary arterial fistulas during chronic Q fever.

PubMed

Karhof, Steffi; van Roeden, Sonja E; Oosterheert, Jan J; Bleeker-Rovers, Chantal P; Renders, Nicole H M; de Borst, Gert J; Kampschreur, Linda M; Hoepelman, Andy I M; Koning, Olivier H J; Wever, Peter C

2018-04-20

After primary infection with Coxiella burnetii, patients may develop acute Q fever, which is a relatively mild disease. A small proportion of patients (1%-5%) develop chronic Q fever, which is accompanied by high mortality and can be manifested as infected arterial or aortic aneurysms or infected vascular prostheses. The disease can be complicated by arterial fistulas, which are often fatal if they are left untreated. We aimed to assess the cumulative incidence of arterial fistulas and mortality in patients with proven chronic Q fever. In a retrospective, observational study, the cumulative incidence of arterial fistulas (aortoenteric, aortobronchial, aortovenous, or arteriocutaneous) in patients with proven chronic Q fever (according to the Dutch Chronic Q Fever Consensus Group criteria) was assessed. Proven chronic Q fever with a vascular focus of infection was defined as a confirmed mycotic aneurysm or infected prosthesis on imaging studies or positive result of serum polymerase chain reaction for C. burnetii in the presence of an arterial aneurysm or vascular prosthesis. Of 253 patients with proven chronic Q fever, 169 patients (67%) were diagnosed with a vascular focus of infection (42 of whom had a combined vascular focus and endocarditis). In total, 26 arterial fistulas were diagnosed in 25 patients (15% of patients with a vascular focus): aortoenteric (15), aortobronchial (2), aortocaval (4), and arteriocutaneous (5) fistulas (1 patient presented with both an aortocaval and an arteriocutaneous fistula). Chronic Q fever-related mortality was 60% for patients with and 21% for patients without arterial fistula (P < .0001). Primary fistulas accounted for 42% and secondary fistulas for 58%. Of patients who underwent surgical intervention for chronic Q fever-related fistula (n = 17), nine died of chronic Q fever-related causes (53%). Of patients who did not undergo any surgical intervention (n = 8), six died of chronic Q fever-related causes (75%). The proportion of patients with proven chronic Q fever developing primary or secondary arterial fistulas is high; 15% of patients with a vascular focus of infection develop an arterial fistula. This observation suggests that C. burnetii, the causative agent of Q fever, plays a role in the development of fistulas in these patients. Chronic Q fever-related mortality in patients with arterial fistula is very high, in both patients who undergo surgical intervention and patients who do not. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

[Metabolic disturbances and ways of their pharmacological correction in acute poisoning with ethanol in patients with chronic alcoholism].

PubMed

Livanov, G A; Lodyagin, A N; Lubsanova, S V; Kovalenko, A L; Batotsyrenov, B V; Sergeev, O A; Loladze, A T; Andrianov, A Yu

2015-01-01

To study an influence of chronic alcoholism on the clinical course and severity of metabolic disturbances in patients with acute poisoning with ethanol and to improve the treatment. Authors examined 93 patients stratified into three groups (acute poisoning with ethanol in patients with chronic alcoholism, without chronic alcoholism and those treated with reamberin). The presence of chronic alcoholism significantly augmented metabolic disturbances and influenced the disturbance of oxygen-transport function and free-radical processes in patients with acute intoxication with ethanol. Using of reamberin in the complex intensive therapy led to the decrease in metabolic disorders, which improved the clinical course of acute poisoning with ethanol in patients with chronic alcoholism.

Individual care plans for chronically ill patients within primary care in the Netherlands: Dissemination and associations with patient characteristics and patient-perceived quality of care.

PubMed

Jansen, Daphne L; Heijmans, Monique; Rijken, Mieke

2015-06-01

To examine the use of individual care plans (ICPs) within primary chronic illness care in the Netherlands, and to explore the relationships between ICP use, patient characteristics, and patient-perceived quality of care. Cross-sectional study using survey data from a panel of chronically ill patients and medical registration data provided by their general practices. A sample of 1377 patients with somatic chronic disease(s) randomly selected in general practices throughout the Netherlands, supplemented with a sample of 225 COPD patients, also recruited from general practices. (i) Percentage of ICP use based on self-report by chronically ill patients, and (ii) patient-perceived quality of care as assessed using the Patient Assessment of Chronic Illness Care (PACIC). ICP use among the total generic sample was low (9%), but slightly higher (13%) among patients diagnosed with diabetes or COPD, diseases for which disease management programmes have been set up in the Netherlands. Patients with a low educational level and patients with poor(er) self-rated health were more likely to have an ICP. Compared with patients without an ICP, patients with an ICP more often reported that the care they received was patient-centred, proactive, planned, and included collaborative goal setting, problem-solving, and follow-up support. Findings reveal a discrepancy between practice and policy aspirations regarding ICP use in primary chronic illness care. More research is needed to gain insight into the effectiveness of ICPs to improve the quality of chronic illness care in various patient populations.

Defects in α-Cell Function in Patients With Diabetes Due to Chronic Pancreatitis Compared With Patients With Type 2 Diabetes and Healthy Individuals.

PubMed

Mumme, Lena; Breuer, Thomas G K; Rohrer, Stephan; Schenker, Nina; Menge, Björn A; Holst, Jens J; Nauck, Michael A; Meier, Juris J

2017-10-01

Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis. Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed. Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects ( P < 0.0001). Insulin and C-peptide levels were reduced, and the glucose-induced suppression of glucagon was impaired in both groups with diabetes (all P < 0.0001 vs. control subjects). During hypoglycemia, glucagon concentrations were reduced in patients with chronic pancreatitis and with type 2 diabetes ( P < 0.05). The increase in glucagon during the clamp was inversely related to the glucose-induced glucagon suppression and positively related to β-cell function. Growth hormone responses to hypoglycemia were lower in patients with type 2 diabetes ( P = 0.0002) but not in patients with chronic pancreatitis. α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology. © 2017 by the American Diabetes Association.

Chronic Q Fever in the Netherlands 5 Years after the Start of the Q Fever Epidemic: Results from the Dutch Chronic Q Fever Database

PubMed Central

Delsing, Corine E.; Groenwold, Rolf H. H.; Wegdam-Blans, Marjolijn C. A.; Bleeker-Rovers, Chantal P.; de Jager-Leclercq, Monique G. L.; Hoepelman, Andy I. M.; van Kasteren, Marjo E.; Buijs, Jacqueline; Renders, Nicole H. M.; Nabuurs-Franssen, Marrigje H.; Oosterheert, Jan Jelrik; Wever, Peter C.

2014-01-01

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P = 0.004 and 0.010), proven chronic Q fever (P = 0.020 and 0.002), vascular chronic Q fever (P = 0.024 and 0.005), acute presentation with chronic Q fever (P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever (P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively. PMID:24599987

Two rare diagnoses during chronic lymphocytic leukaemia follow-up: Kaposi's sarcoma and Merkel cell carcinoma.

PubMed

Dogu, Mehmet H; Sari, Ismail; Hacioglu, Sibel; Degirmencioglu, Serkan; Şen, Nilay; Keskin, Ali

2016-02-01

Chronic lymphocytic leukaemia often has a clinical presentation characterised by increased neoplastic lymphocytes which are mostly mature looking due to B lymphocytes. Increased secondary cancer prevalence has been detected among patients with chronic lymphocytic leukaemia diagnosis. In this report, we present three chronic lymphocytic leukaemia patients who developed secondary rare cancers during their follow-up at our clinic. Case 1: A 54-year-old female patient was diagnosed with stage I chronic lymphocytic leukaemia in 2003 and was diagnosed with Merkel cell carcinoma in February 2013. Case 2: A 66-year-old male patient was diagnosed with stage II chronic lymphocytic leukaemia in 2009 and was diagnosed with Kaposi's sarcoma in March 2013. Case 3: A 77-year-old male patient was diagnosed with stage I chronic lymphocytic leukaemia in 2006 and was diagnosed with Kaposi's sarcoma in 2011. In conclusion, secondary cancers are observed in patients diagnosed with chronic lymphocytic leukaemia. Therefore, follow-up of chronic lymphocytic leukaemia requires additional attention in this context. © The Author(s) 2016.

Perceived quality of chronic illness care is associated with self-management: Results of a nationwide study in the Netherlands.

PubMed

van Houtum, L; Heijmans, M; Rijken, M; Groenewegen, P

2016-04-01

Healthcare providers are increasingly expected to help chronically ill patients understand their own central role in managing their illness. The aim of this study was to determine whether experiencing high-quality chronic illness care and having a nurse involved in their care relate to chronically ill people's self-management. Survey data from 699 people diagnosed with chronic diseases who participated in a nationwide Dutch panel-study were analysed using linear regression analysis, to estimate the association between chronic illness care and various aspects of patients' self-management, while controlling for their socio-demographic and illness characteristics. Chronically ill patients reported that the care they received was of high quality to some extent. Patients who had contact with a practise nurse or specialised nurse perceived the quality of the care they received as better than patients who only had contact with a GP or medical specialist. Patients' perceptions of the quality of care were positively related to all aspects of their self-management, whereas contact with a practise nurse or specialised nurse in itself was not. Chronically ill patients who have the experience to receive high-quality chronic illness care that focusses on patient activation, decision support, goal setting, problem solving, and coordination of care are better self-managers. Having a nurse involved in their care seems to be positively valued by chronically ill patients, but does not automatically imply better self-management. Copyright © 2016. Published by Elsevier Ireland Ltd.

Experience and management of chronic pain among patients with other complex chronic conditions.

PubMed

Butchart, Amy; Kerr, Eve A; Heisler, Michele; Piette, John D; Krein, Sarah L

2009-05-01

Managing multiple chronic health conditions is a significant challenge. The purpose of this study was to examine the experience and management of chronic pain among adult patients with other complex chronic conditions, specifically diabetes and heart failure (HF). We surveyed 624 US Department of Veterans Affairs primary care patients in 3 study groups: 184 with HF, 221 with diabetes, and 219 general primary care users. We compared health status and function between those with and without chronic pain within the 3 study groups. Among those with chronic pain, we compared pain location, severity, and treatment across groups. More than 60% in each group reported chronic pain, with the majority reporting pain in the back, hip, or knee. In all groups, patients with chronic pain were more likely to report fair or poor health than those without pain (P<0.05). In the HF and diabetes groups, a higher percentage of patients with pain were not working because of health reasons. Of those with pain, more than 70% in each group took medications for pain; more than one-half managed pain with rest or sedentary activities; and less than 50% used exercise for managing their pain. Chronic pain is a prevalent problem that is associated with poor functioning among multimorbid patients. Better management of chronic pain among complex patients could lead to significant improvements in health status, functioning, and quality of life and possibly also improve the management of their other major chronic health conditions.

[Exocrine function of the pancreas at chronic pancreatitis: diagnosis an drug correction].

PubMed

Vinokurova, L V; Drozdov, V N; Nevmerzhitskiĭ, V N; Chernyshova, I V; gubina, A V; Trubitsyna, I E; Barvanina, G G

2009-01-01

Estimation of respiratory test with 13C- mixed triglytcherides and gastrointestinal hormones effeciancy for the diagnosis of extrasecretory pancreatic with chronic pancreatitis was the aim of this examination. Test 13C- mixed triglytcherides was examined vercus test with pancreatic elastase of feces (E-1). 45 patients with chronic pancreatitis and 20 patients in 2 control groups were examined. The resuets testify to the lowering of pancreatic exocrine function in the patients with complicated chronic pancreatitis. The levels of E-1 and CPRDF (360) were trustworthy low the patients with complicated chronic pancreatitis versus the patients with chronic pancreatitis without complications and in control groups (p < 0.05). Correlative analysis the levels of E-1 and CPRDF (360) had demonstrated high degrel of results similarity. Persons correlation index was r = 0.64 (p < 0.001). The secretines level after standart breakfast in the patients with chronic pancreatitis was lowering, but was increasing in the healthy persons. Secretine lowering may lead to the bicarbonates secretion lowering. These results testify to the necessity of fermental treatment in the patients with chronic pancreatitis accordingly the pancreatitis stage.

Healing of chronic wounds with adjunctive ablative fractional laser resurfacing in two pediatric patients.

PubMed

Krakowski, Andrew C; Diaz, Lucia; Admani, Shehla; Uebelhoer, Nathan S; Shumaker, Peter R

2016-02-01

The development of chronic non-healing wounds is multifactorial and can lead to increased patient morbidity. When traditional wound care methods fail, alternative treatments are needed to prevent chronic ulcer complications. Ablative fractional laser resurfacing (AFR) is an emerging therapy for chronic wounds. We report the successful use of AFR to facilitate the healing of chronic wounds in two pediatric patients. This is a case series including two patients with chronic wounds within scars that were treated with a micro-fractionated carbon dioxide (CO2 ) laser in a single pass at a pulse energy of 50 mJ and a treatment density of 5%. One patient had one treatment and the other had two treatments 1 month apart. AFR led to rapid healing of chronic wounds in both pediatric patients. The wounds remained epithelialized after 9 months in one patient and 4 months in the other. There were no complications. The combination of tolerability and efficacy observed in these cases introduces AFR as a potential promising adjunct to existing treatments for chronic, non-healing wounds in the pediatric population. © 2015 Wiley Periodicals, Inc.

Is Fibroblast growth factor 23 the leading cause of increased mortality among chronic kidney disease patients? A narrative review.

PubMed

Sharaf El Din, Usama A; Salem, Mona M; Abdulazim, Dina O

2017-05-01

The death rate among chronic kidney disease patients is the highest compared to other chronic diseases. 60% of these fatalities are cardiovascular. Cardiovascular calcifications and chronic inflammation affect almost all chronic kidney disease patients and are associated with cardiovascular mortality. Fibroblast growth factor 23 is associated with vascular calcification. Systemic inflammation in chronic kidney disease patients is multifactorial. The role of systemic inflammation in the pathogenesis of vascular calcification was recently reappraised. Fibroblast growth factor 23 was accused as a direct stimulus of left ventricular hypertrophy, uremic inflammation, and impaired neutrophil function. This review will discuss the underlying mechanisms that underlie the link between Fibroblast growth factor 23 and increased mortality encountered among chronic kidney disease patients.

Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach.

PubMed

Breccia, Massimo; Alimena, Giuliana

2015-02-01

New selective and more potent drugs for the cure of chronic phase chronic myeloid leukemia patients are now available: physicians in some countries must decide the best option, selecting one of the drugs available. What the main prognostic factors are in order to make this selection remains a matter of discussion. Introducing a 'holistic approach' for the first time in chronic myeloid leukemia, as practiced in other diseases, and looking at the patient in a complete picture, considering several variables, such as comorbidities, age, concomitant drugs, lifestyle and patient expectations, may be of help to understand, patient by patient, the best therapeutic strategy.

"They don't want anything to do with you": patient views of primary care management of chronic pain.

PubMed

Upshur, Carole C; Bacigalupe, Gonzalo; Luckmann, Roger

2010-12-01

Chronic pain is one of the most frequent complaints of patients in primary care, yet both patients and providers report low satisfaction with chronic pain care. This study was designed to explore the views held by a diverse sample of patients with chronic pain complaints about their care experiences to identify ways to improve care. Qualitative analysis of 17 patient focus groups (size 3-7 participants). Groups used structured questions and were tape recorded, transcribed, and coded using qualitative software. Eleven groups were conducted in English, six groups in Spanish. Convenience sample of 72 adult patients (68% female, 44% Latino, mean age=48.1 years) recruited from four diverse primary care practices in Central Massachusetts. Across all 17 groups, and all gender, ethnicity, and age groups, most patients reported suboptimal interactions with their providers when seeking care for chronic pain. Subjects acknowledged feeling disrespected and distrusted, suspected of drug-seeking, and having their symptoms dismissed as trivial and/or not warranting medical care. Patients reported more satisfaction when they felt a provider listened to them, trusted them, was accessible to address pain concerns between visits, and used patient-centered approaches to establish goals and treatment plans. Patients also recommended some management techniques related to the chronic disease management model to improve pain care. Implementing patient-centered approaches in caring for individuals with chronic pain and using principles drawn from the chronic disease management model to improve care systems may improve both patient and provider satisfaction with chronic pain care. Wiley Periodicals, Inc.

Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

PubMed

Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

2013-03-01

Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

Nursing Activities for Patients With Chronic Disease in Primary Care Settings: A Practice Analysis.

PubMed

Poitras, Marie-Eve; Chouinard, Maud-Christine; Gallagher, Frances; Fortin, Martin

Nurses in primary care organizations play a central role for patients with chronic disease. Lack of clarity in role description may be associated with underutilization of nurse competencies that could benefit the growing population of patients with chronic disease. The purpose of the research was to describe nursing activities in primary care settings with patients with chronic disease. A Web-based survey was sent to nurses practicing in Family Medicine Groups in the Canadian Province of Québec. Participants rated the frequency with which they carried out nursing activities in five domains: (a) global assessment, (b) care and case management, (c) health promotion, (d) nurse-physician collaboration, and (e) planning services for patients with chronic disease. Findings were summarized with descriptive statistics (means, standard deviations, and ranges). The survey was completed by 266 of the 322 nurses who received the survey (82.6%). Activities in the health promotion and global assessment of the patient domains were carried out most frequently. Planning services for patients with chronic disease were least frequently performed. This study provides a broad description of nursing activities with patients with chronic disease in primary care. The findings provide a baseline for clinicians and researchers to document and improve nursing activities for optimal practice for patients with chronic disease.

Brain-derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria.

PubMed

Rössing, K; Novak, N; Mommert, S; Pfab, F; Gehring, M; Wedi, B; Kapp, A; Raap, U

2011-10-01

Chronic spontaneous urticaria is triggered by many direct and indirect aggravating factors including autoreactive/autoimmune mechanisms, infections, non-allergic and pseudoallergic intolerance reactions. However, the role of neuroimmune mechanisms in chronic spontaneous urticaria so far is unclear. Thus, we wanted to address the regulation of the neurotrophin brain-derived neurotrophic factor (BDNF) in serum and inflammatory skin of patients with chronic spontaneous urticaria in comparison to subjects with healthy skin. Fifty adult patients with chronic spontaneous urticaria and 23 skin-healthy subjects were studied. Chronic spontaneous urticaria was defined as recurrent weals for more than 6 weeks. Autologous serum skin test was performed in all patients with chronic spontaneous urticaria and BDNF serum levels were analysed by enzyme immunoassay in all subjects. Furthermore, skin biopsies were taken from weals of eight patients with chronic spontaneous urticaria as well as from healthy skin of eight controls to evaluate the expression of BDNF and its receptors including tyrosine kinase (trk) B and pan-neurotrophin receptor p75(NTR) by immunohistochemistry. BDNF serum levels were detectable in all subjects studied. However, BDNF levels were significantly higher in patients with chronic spontaneous urticaria compared to non-atopic skin-healthy controls (P<0.001). Furthermore, epidermal and dermal expression of BDNF and epidermal expression of p75(NTR) was significantly higher in patients with chronic spontaneous urticaria compared with controls (P<0.05-0.001). There was no difference with regard to the expression of trkB between chronic spontaneous urticaria and controls and no difference in BDNF serum levels between autologous serum skin test-positive (n=23) and -negative (n=27) patients with chronic spontaneous urticaria. This study shows that BDNF is increased in serum and diseased skin of patients with chronic spontaneous urticaria, suggesting a role for neurotrophins in the pathophysiology of this chronic inflammatory skin disease. Further studies are needed to address the functional role of BDNF on key target effector cells in chronic spontaneous urticaria to establish new therapeutic implications. © 2011 Blackwell Publishing Ltd.

Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in Turkey.

PubMed

Tulek, Necla; Ozsoy, Metin; Moroglu, Cigdem; Cagla Sonmezer, Meliha; Temocin, Fatih; Tuncer Ertem, Gunay; Sebnem Erdinc, Fatma

2015-01-01

Hepatitis A virus (HAV) can cause significant pathology in patients with chronic hepatitis B virus (HBV), however, HAV can be prevented by vaccination. The aim of this study was to determine the implication of vaccination against HAV vaccine in patients with chronic hepatitis B. The seroprevalence of anti-HAV IgG antibodies was investigated in the patients with chronic hepatitis B. Anti-HAV IgG antibodies were detected by commercially available ELISA kit. A total of 673 patients (354 males, 319 females with age range of 17-78 years) with chronic hepatitis B were included the study. Hepatitis A virus seropositivity rate was 34% in the patients younger than 20 years, 79% in the age group of 20 to 29 years, and 100% after 35 years of age. Hepatitis A virus vaccination may be recommended for young adult patients with chronic hepatitis B in Turkey. Tulek N, Ozsoy M, Moroglu C, Sonmezer MC, Temocin F, Ertem GT, Erdinc FS. Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in Turkey. Euroasian J Hepato-Gastroenterol 2015;5(2):95-97.

Prevalence, Incidence, and Classification of Chronic Fatigue Syndrome in Olmsted County, Minnesota, as Estimated Using the Rochester Epidemiology Project

PubMed Central

Vincent, Ann; Brimmer, Dana J.; Whipple, Mary O.; Jones, James F.; Boneva, Roumiana; Lahr, Brian D.; Maloney, Elizabeth; St. Sauver, Jennifer L.; Reeves, William C.

2012-01-01

Objective To estimate the prevalence and incidence of chronic fatigue syndrome in Olmsted County, Minnesota, using the 1994 case definition and describe exclusionary and comorbid conditions observed in patients who presented for evaluation of long-standing fatigue. Patients and Methods We conducted a retrospective medical record review of potential cases of chronic fatigue syndrome identified from January 1, 1998, through December 31, 2002, using the Rochester Epidemiology Project, a population-based database. Patients were classified as having chronic fatigue syndrome if the medical record review documented fatigue of 6 months' duration, at least 4 of 8 chronic fatigue syndrome–defining symptoms, and symptoms that interfered with daily work or activities. Patients not meeting all of the criteria were classified as having insufficient/idiopathic fatigue. Results We identified 686 potential patients with chronic fatigue, 2 of whom declined consent for medical record review. Of the remaining 684 patients, 151 (22%) met criteria for chronic fatigue syndrome or insufficient/idiopathic fatigue. The overall prevalence and incidence of chronic fatigue syndrome and insufficient/idiopathic fatigue were 71.34 per 100,000 persons and 13.16 per 100,000 person-years vs 73.70 per 100,000 persons and 13.58 per 100,000 person-years, respectively. The potential cases included 482 patients (70%) who had an exclusionary condition, and almost half the patients who met either criterion had at least one nonexclusionary comorbid condition. Conclusion The incidence and prevalence of chronic fatigue syndrome and insufficient/idiopathic fatigue are relatively low in Olmsted County. Careful clinical evaluation to identify whether fatigue could be attributed to exclusionary or comorbid conditions rather than chronic fatigue syndrome itself will ensure appropriate assessment for patients without chronic fatigue syndrome. PMID:23140977

Chronic disease detection and access: does access improve detection, or does detection make access more difficult?

PubMed

Anwar, Mohammed Saqib; Baker, Richard; Walker, Nicola; Mainous, Arch G; Bankart, M John

2012-05-01

The recorded detection of chronic disease by practices is generally lower than the prevalence predicted by population surveys. To determine whether patient-reported access to general practice predicts the recorded detection rates of chronic diseases in that setting. A cross-sectional study involving 146 general practices in Leicestershire and Rutland, England. The numbers of patients recorded as having chronic disease (coronary heart disease, chronic obstructive pulmonary disease, hypertension, diabetes) were obtained from Quality and Outcomes Framework (QOF) practice disease registers for 2008-2009. Characteristics of practice populations (deprivation, age, sex, ethnicity, proportion reporting poor health, practice turnover, list size) and practice performance (achievement of QOF disease indicators, patient experience of being able to consult a doctor within 2 working days and book an appointment >2 days in advance) were included in regression models. Patient characteristics (deprivation, age, poor health) and practice characteristics (list size, turnover, QOF achievement) were associated with recorded detection of more than one of the chronic diseases. Practices in which patients were more likely to report being able to book appointments had reduced recording rates of chronic disease. Being able to consult a doctor within 2 days was not associated with levels of recorded chronic disease. Practices with high levels of deprivation and older patients have increased rates of recorded chronic disease. As the number of patients recorded with chronic disease increased, the capacity of practices to meet patients' requests for appointments in advance declined. The capacity of some practices to detect and manage chronic disease may need improving.

Online self-management interventions for chronically ill patients: cognitive impairment and technology issues.

PubMed

Archer, Norm; Keshavjee, Karim; Demers, Catherine; Lee, Ryan

2014-04-01

As the fraction of the population with chronic diseases continues to grow, methods and/or technologies must be found to help the chronically ill to take more responsibility to self-manage their illnesses. Internet based and/or mobile support for disease self-management interventions have often proved effective, but patients with chronic illnesses may have co-occurring cognitive impairment, making it more difficult for them to cope with technologies. Many older patients are also not familiar with technologies or they may have cognitive disabilities or dementia that reduce their ability to self-manage their healthcare. On-line solutions to the needs of chronically ill patients must be investigated and acted upon with care in an integrated manner, since resources invested in these solutions will be lost if patients do not adopt and continue to use them successfully. To review the capabilities of online and mobile support for self-management of chronic illnesses, and the impacts that age and disease-related issues have on these interventions, including cognitive impairment and lack of access or familiarity with Internet or mobile technologies. This study includes a review of the co-occurrence of cognitive impairment with chronic diseases, and discusses how cognitive impairment, dyadic caregiver patient support, patient efficacy with technology, and smart home technologies can impact the effectiveness and sustainability of online support for disease self-management. Disease self-management interventions (SMIs) using online patient centered support can often enable patients to manage their own chronic illnesses. However, our findings show that cognitive impairment often co-occurs in patients with chronic disease. This, along with age-related increases in multiple chronic illnesses and lack of technology efficacy, can be obstacles to Internet and mobile support for chronic disease self-management. Patients with chronic diseases may have greater than expected difficulties in using Internet and mobile technologies for disease self-management, often due to cognitive impairment or unfamiliarity with technology. Approaches to dealing with such barriers include suitable integration of solutions involving patient-caregiver dyads, better design of online applications, careful attention to technology adoption and sustainability, and smart home technologies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparative Evaluation of Periodontal Status of Chronic Renal Failure Patients and Systemically Healthy Individuals.

PubMed

Gupta, Radhika; Kumar, Uttam; Mallapragada, Siddharth; Agarwal, Pallavi

2018-03-01

Periodontitis, a chronic infectious disease, affects most of the population at one time or the other and its expression is a combination of hosts, microbial agents, and environmental factors. Extensive literature exists for the relationship between periodontal disease and diabetes mellitus, cardiovascular diseases, and adverse pregnancy outcomes. Only a few studies performed in a limited number of patients have reported peri-odontal health status in chronic renal failure patients. Hence, the aim of the present study is to assess and compare the periodontal status of patients with chronic renal failure undergoing dialysis, predialysis with systemically healthy individuals. A total of 90 patients were divided into three groups. Group I: 30 renal dialysis patients. Group II: 30 predialysis patients. Control group comprised 30 systemically healthy patients who formed group III. Periodontal examination was carried out using oral hygiene index-simplified (OHI-S), plaque index (PI), gingival index (GI), probing depth, and clinical attachment loss. The results of the study showed that the periodontal status of patients with chronic renal failure undergoing dialysis (dialysis group) and patients with chronic renal failure not undergoing renal dialysis (predialysis) when compared with systemically healthy subjects showed significantly higher mean scores of OHI-S, PI, and clinical attachment loss. Thus, patients with chronic renal failure showed poor oral hygiene and higher prevalence of periodontal disease. The dental community's awareness of implications of poor health within chronic renal failure patients should be elevated.

Chronic bacterial seminal vesiculitis as a potential disease entity in men with chronic prostatitis.

PubMed

Park, Soo-Hwan; Ryu, Ji-Kan; Choo, Gwoan-Youb; Chung, Yeun-Goo; Seong, Do-Hwan; Kim, Chang-Ho; Choe, Won-Sik; Ryu, Dong-Soo; Hyun, In Young; Suh, Jun-Kyu

2015-05-01

To investigate bacterial infection in the seminal vesicles by bacteriological examination and radionuclide imaging in men with chronic prostatitis. The study included 50 patients with chronic prostatitis who showed hot uptake in seminal vesicles on Tc-99m ciprofloxacin imaging and eight patients who did not show hot uptake. The evaluation included the National Institutes of Health Chronic Prostatitis Symptom Index and four-glass test. In all participants, transperineal aspiration of seminal vesicle fluid under the guidance of transrectal ultrasonography and bacteriological examination was carried out. Of the 50 patients who showed hot uptake in the seminal vesicles on the isotope study, microorganisms were isolated from the seminal vesicle fluid in 17 patients (positive predictive value, 34%). The most common causative organisms were Escherichia coli in 13 patients (26%), followed by coagulase-negative Staphylococcus species in two patients (4%), Enterococcus faecalis in one patient (2%) and Chlamydia trachomatis in one patient (2%). No microorganisms were isolated in the eight patients who did not show hot uptake in the seminal vesicles (negative predictive value, 100%). However, there were no significant differences in National Institutes of Health Chronic Prostatitis Symptom Index total scores and subscores between the study groups. Chronic bacterial seminal vesiculitis might simultaneously affect a considerable portion of patients with chronic prostatitis, although the clinical implication of the disease remains to be further investigated. © 2015 The Japanese Urological Association.

Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination.

PubMed

Keeffe, Emmet B

2005-10-01

Retrospective and prospective studies have demonstrated that the occurrence of acute hepatitis A in patients with chronic liver disease is associated with higher rates of morbidity and mortality than in previously healthy individuals with acute hepatitis A. The mortality associated with acute hepatitis A may be particularly high in patients with preexisting chronic hepatitis C. Although acute hepatitis B in patients with preexisting chronic liver disease is less well studied, worse outcomes than in previously healthy individuals are apparent. However, numerous studies convincingly demonstrate that chronic hepatitis B virus coinfection with hepatitis C virus (or hepatitis D virus) is associated with an accelerated natural history of liver disease and worse outcomes. These observations led to studies that demonstrated the safety and efficacy of hepatitis A and hepatitis B vaccination in patients with mild-to-moderate chronic liver disease. Hepatitis A and B vaccination is less effective in patients with advanced liver disease, especially after decompensation, such as in patients awaiting liver transplantation, and in liver transplant recipients. The emerging lower rates of inherent immunity in younger individuals, higher morbidity and mortality of acute hepatitis A or B superimposed on chronic liver disease, and greater vaccine efficacy in milder forms of chronic liver disease suggest that it is a reasonable policy to recommend hepatitis A and B vaccination in patients early in the natural history of chronic liver disease.

Chronic Opioid Usage in Surgical Patients in a Large Academic Center

PubMed Central

Jiang, Xueying; Orton, Margaret; Feng, Rui; Hossain, Erik; Malhotra, Neil R.; Zager, Eric L.; Liu, Renyu

2017-01-01

Objective The objective of this study is to investigate the prevalence and disparity of chronic opioid usage in surgical patients and the potential risk factors associated with chronic opioid usage. Background Chronic opioid usage is common in surgical patients; however, the characteristics of opioid usage in surgical patients is unclear. In this study, we hypothesize that the prevalence of chronic opioid usage in surgical patients is high, and that significant disparities may exist among different surgical populations. Methods Data of opioid usage in outpatients among different surgical services were extracted from the electronic medical record database. Patient demographics, clinical characteristics of sex, age, race, body mass index (BMI), specialty visited, duration of opioid use, and opioid type were collected. Chronic opioid users were defined as patients who had been recorded as taking opioids for at least 90 days determined by the first and last visit dates under opioid usage during the investigation. Results There were 79,123 patients included in this study. The average prevalence is 9.2%, ranging from 4.4% to 23.8% among various specialties. The prevalence in orthopedics (23.8%), neurosurgery (18.7%), and gastrointestinal surgery (14.4%) ranked in the top three subspecialties. Major factors influencing chronic opioid use include age, Ethnicitiy, Subspecialtiy, and multiple specialty visits. Approximately 75% of chronic users took opioids that belong to the category II Drug Enforcement Administration classification. Conclusions Overall prevalence of chronic opioid usage in surgical patients is high with widespread disparity among different sex, age, ethnicity, BMI, and subspecialty groups. Information obtained from this study provides clues to reduce chronic opioid usage in surgical patients. PMID:27163960

ChronicOnline: Implementing a mHealth solution for monitoring and early alerting in chronic obstructive pulmonary disease.

PubMed

Bitsaki, Marina; Koutras, Christos; Koutras, George; Leymann, Frank; Steimle, Frank; Wagner, Sebastian; Wieland, Matthias

2017-09-01

Lack of time or economic difficulties prevent chronic obstructive pulmonary disease patients from communicating regularly with their physicians, thus inducing exacerbation of their chronic condition and possible hospitalization. Enhancing Chronic patients' Health Online proposes a new, sustainable and innovative business model that provides at low cost and at significant savings to the national health system, a preventive health service for chronic obstructive pulmonary disease patients, by combining human medical expertise with state-of-the-art online service delivery based on cloud computing, service-oriented architecture, data analytics, and mobile applications. In this article, we implement the frontend applications of the Enhancing Chronic patients' Health Online system and describe their functionality and the interfaces available to the users.

Assessing United States Patient and Dermatologist Experiences with Severe Chronic Hand Eczema

PubMed Central

Baranowski, Eileen; Zelt, Susan; Reynolds, Maria; Sherrill, Beth

2015-01-01

Objective: Patients with severe chronic hand eczema often have persistent symptoms that interfere with daily activities, social functioning, and employment. Many patients are refractory to topical corticosteroids. This survey-based study was performed to characterize treatment experiences, impact on productivity, and quality of life of patients with severe chronic hand eczema; understand dermatologists’ severe chronic hand eczema treatment patterns. Design: A web-based survey in the United States queried pre-identified patients with severe chronic hand eczema regarding symptoms, treatment history, quality of life, work productivity, treatment satisfaction, and healthcare utilization. In a separate survey, dermatologists were asked about treatment patterns and satisfaction with currently available therapies. Results: The most commonly reported symptoms currently experienced by patients (n=163) were dryness/flaking (81%), itchiness (75%), and cracking/tearing of the skin (71%). Over the last three months, 84 percent of patients with severe chronic hand eczema self-reported using topical steroids, and 30 percent used systemic corticosteroids or retinoids. Approximately 30 percent reported impairment while working and productivity loss. Patient quality of life was negatively impacted. Dermatologists (n=125) reported most often treating severe chronic hand eczema with topical corticosteroids (99%), followed by topical immunomodulators (71%) and systemic treatments (70%). Only two percent were very satisfied with currently available products. Conclusion: Patients with severe chronic hand eczema experience symptoms that negatively impact work productivity and quality of life. Few dermatologists are very satisfied with currently available severe chronic hand eczema treatment options. PMID:26705436

Combined branched-DNA and conventional HBV PCR assays for detection of serum HBV-DNA in hepatitis B e antigen-positive chronic hepatitis B patients.

PubMed

Ozdarendeli, Aykut; Toroman, Zulal Asci; Bulut, Yasemin; Demirbag, Kutbeddin; Kalkan, Ahmet; Ozden, Mehmet; Kilic, Suleyman Sirri

2006-01-01

Monitoring of HBV replication level is very useful for the management of patients with chronic HBV. However, the use of the correct tools to quantify HBV-DNA levels in serum and monitor the replication of HBV is of paramount importance in terms of diagnosis, and antiviral treatment of patients with chronic HBV infection. The aim of this study was to combine the bDNA assay and HBV PCR to improve detection of viremia the patients with HBeAg-positive chronic hepatitis B infection. In this study, 67 HBeAg-positive chronic hepatitis B patients were analyzed to determine viremia level using bDNA and HBV PCR assays. Sixty-four patients with HBeAg-positive chronic hepatitis B showed positivity by conventional HBV PCR, whereas 56 subjects with HBeAg-positive chronic hepatitis B showed HBV-DNA levels by bDNA. The results indicated that it is reasonable to use the bDNA assay to determine HBV replicative activity first, and use conventional HBV-PCR for HBeAg-positive chronic hepatitis B patient samples that are negative in bDNA assay.

Long-term follow-up of chronic pancreatitis patients with K-ras mutation in the pancreatic juice.

PubMed

Kamisawa, Terumi; Takuma, Kensuke; Tabata, Taku; Egawa, Naoto; Yamaguchi, Toshikazu

2011-01-01

Pancreatic cancer is known to occur during the course of chronic pancreatitis in some patients. This study aimed to identify a high risk group for developing pancreatic cancer associated with chronic pancreatitis, particularly the presence of K-ras mutations in the pancreatic juice. K-ras mutation was analyzed by enriched polymerase chain reaction-enzyme linked mini-sequence assay in endoscopically-collected pancreatic juice of 21 patients with chronic pancreatitis between 1995 and 2000. All of them were followed-up for 6.0 +/- 3.8 (mean +/- SD) years (range, 2.1-14.2 years). K-ras point mutation was observed in the pancreatic juice of 11 patients with chronic pancreatitis (2+, n=2; 1+, n=6; +/-, n=3). Of these, 2 chronic pancreatitis patients with 2+K-ras point mutation developed pancreatic cancer 4.5 and 10.8 years, respectively, after the examination. Two chronic pancreatitis patients with K-ras mutation developed pancreatic cancer 4.5 and 10.8 years later. Semiquantitative analysis of K-ras mutation in endoscopically-collected pancreatic juice appears to be a useful tool for identifying chronic pancreatitis patients at high risk for developing pancreatic cancer.

What Is the Prevalence of Symptomatic Obstructive Sleep Apnea Syndrome in Chronic Spinal Pain Patients? An Assessment of the Correlation of OSAS with Chronic Opioid Therapy, Obesity, and Smoking.

PubMed

Pampati, Sanjana; Manchikanti, Laxmaiah

2016-05-01

In modern medicine, obstructive sleep apnea syndrome (OSAS) is a commonly described sleep disorder with airway obstruction, disrupted sleep, and excessive daytime sleepiness. Since its description in 1976 by Guilleminault et al, numerous epidemiologic studies and systematic reviews, with multiple comorbidities related to cardiovascular sequelae, altered cognitive function, and multiple other potential complications have been described. Multiple risk factors have been identified included obesity, smoking, alcohol consumption, and other factors. Chronic pain and chronic opioid therapy also have been described to contribute to a large proportion of patients with OSAS. Chronic pain, obesity, smoking, and chronic opioid therapy are often found together, yet there is a paucity of literature describing OSAS in chronic pain patients. To assess the prevalence of symptomatic OSAS in chronic spinal pain patients receiving chronic opioid therapy and determine the association of OSAS with multiple risk factors and comorbidities. A retrospective assessment of patients who attend a single interventional pain management practice from January 1, 2010to December 31, 2014. A private interventional pain management practice in the United States. The data were collected from 4,036 consecutive patients presenting for assessment to a pain management center from January 1, 2010 to December 31, 2014. All assessments were comprehensive and performed by 2 physicians. The comprehensive assessment included a complete history, a physical examination, and a review of records. The prevalence of OSAS in patients with chronic spinal pain was 13.8%. The results showed a higher prevalence in males compared to females (15.1% versus 12.8%), a higher prevalence in those aged 45 or older compared to those 25-45 years and those 18-25 years (16.3% versus 10.7% or 2.5%), higher prevalence in Hispanics and Asians compared to African Americans and whites (23.7% versus 16.2% versus 13.4%), higher prevalence in patients with combined back and neck pain compared to patients with thoracic pain only or back pain only (16.3% versus 8.2% to 11%). Prevalence also varied by body mass index (BMI): 32.4% in morbidly obese patients, 20.3% in severely obese patients, 15.7% in obese patients, 9.2% in those who were overweight, and only 5.7% in those with normal weight. A significant correlation with OSAS was also observed in patients smoking more than 40 pack years and multiple respiratory symptoms except for chronic bronchitis and multiple cardiovascular ailments. The retrospective nature of the assessment. This retrospective assessment of over 4,000 patients suffering from chronic pain and receiving chronic opioid therapy indicated a prevalence of sleep apnea syndrome as 13.8%. Multiple risk factors including obesity, chronic obstructive pulmonary disease (COPD), chronic sinus and nasal discharge, and multiple comorbidities including cardiovascular and related ailments have been identified. Obstructive sleep apnea syndrome, chronic pain, chronic spinal pain, chronic opioid therapy, obesity, smoking, cardiovascular risk factors, pulmonary risk factors.

Patient-Staff Interactions and Mental Health in Chronic Dialysis Patients

ERIC Educational Resources Information Center

Swartz, Richard D.; Perry, Erica; Brown, Stephanie; Swartz, June; Vinokur, Amiram

2008-01-01

Chronic dialysis imposes ongoing stress on patients and staff and engenders recurring contact and long-term relationships. Thus, chronic dialysis units are opportune settings in which to investigate the impact of patients' relationships with staff on patient well-being. The authors designed the present study to examine the degree to which…

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

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

Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.

2007-02-01

Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grademore » 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.« less

[Monoclonal antibodies ICO-02 to blast cell antigens in patients with chronic myeloleukemia in blast crisis].

PubMed

Baryshnikov, A Iu

1984-01-01

Mice were immunized with blood cells of a patient with chronic granulocytic leukemia, and their cells were subsequently used for the preparation of hybridoma ICO-02. This hybridoma is continuously producing monoclonal antibodies which reacted with cells in 4 out of 13 patients with blastic crisis of chronic granulocytic leukemia and in 6 out of 38 patients with acute lymphoblastic leukemia. Antibodies reacted with blast cells in 2 out of 3 patients with undifferentiated blastic crisis of chronic myelocytic leukemia and in 2 out of 5 patients with lymphoid variant of blastic crisis of chronic granulocytic leukemia. Cells of 6 patients with acute lymphoblastic leukemia which reacted with the monoclonal antibodies had immunological markers of T lymphocytes bone-marrow precursors. Monoclonal antibodies did not react with cells of blood and bone marrow from healthy people and from patients with chronic lymphocytic leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, acute monoblastic leukemia and lymphosarcoma.

Increased risk of chronic liver disease in patients with bipolar disorder: A population-based study.

PubMed

Hsu, Jer-Hwa; Chien, I-Chia; Lin, Ching-Heng

2016-01-01

This study aimed to investigate the prevalence and incidence of chronic liver disease in patients with bipolar disorder. We used a random sample of 766,427 subjects aged ≥18 years from the National Health Research Institute database in the year 2005. Subjects with at least one primary diagnosis of bipolar disorder in 2005 were identified. Patients with a primary or secondary diagnosis of chronic liver disease were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with bipolar disorder and the general population in 2005. We also compared the incidence of chronic liver disease in patients with bipolar disorder and the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with bipolar disorder (13.9%) was 2.68 times higher than that of the general population (5.8%) in 2005. The average annual incidence of chronic liver disease in patients with bipolar disorder from 2006 to 2010 was also higher than that of the general population (2.95% vs. 1.73%; risk ratio: 1.71; 95% confidence interval: 1.46-2.01). Patients with bipolar disorder had a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with bipolar disorder have a much higher prevalence and incidence than those in the general population. Male sex, second-generation antipsychotic or antidepressant use, and hyperlipidemia were associated factors for chronic liver disease in patients with bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation of digital health use and chronic pain coping strategies.

PubMed

Ranney, Megan L; Duarte, Cassandra; Baird, Janette; Patry, Emily J; Green, Traci C

2016-01-01

Digital health is an increasingly popular tool for patient engagement, having shown great success in arenas such as medication adherence, management of chronic conditions, and patient safety. Given the growth of chronic pain diagnoses, it is imperative to find new technologies to improve care for this particular population. Little research has catalogued the use of digital health in the chronic pain patient population. This manuscript's objective was to describe current patterns of digital health usage among chronic pain patients and how digital health use correlates with health care utilization and health outcomes. A cross-sectional survey was administered to patients with a self-identified chronic pain diagnosis participating in 'Patients Like Me' ® (PLM), an organization that directly collects data from patients experiencing chronic health conditions, with emphasis on patient-centered outcomes and experiences interacting with the health care system. Validated measures of healthcare utilization, chronic pain management, and digital health use were adapted for the survey. Digital health was defined as the use of online sites, social media, and mobile phone applications before, during, or after healthcare utilization. Descriptive statistics, chi square tests, logistic regression, and linear regression were used as appropriate for analysis. Among 565 respondents (mean age 51.3, 87.2% female, 45.7% publicly insured), most participants (89.5%) reported some digital health use. Females and users below the age of 50 were more likely to use multiple forms of digital health. Healthcare utilization, education level, and race/ethnicity did not correlate with digital health use. Patients using more types of digital health reported significantly higher levels of pain coping skills in the realms of social support, relaxation, and exercise. Digital health use is common among a wide range of patients with chronic pain diagnoses. The use of multiple forms of digital health is associated with improved chronic pain coping mechanisms. Future work should explore the directional relationship between digital health tools and chronic pain coping skills, as well as which components of digital health have the most effect on chronic pain management and other patient-centered outcomes.

Correlation of digital health use and chronic pain coping strategies

PubMed Central

Duarte, Cassandra; Baird, Janette; Patry, Emily J.; Green, Traci C.

2016-01-01

Background Digital health is an increasingly popular tool for patient engagement, having shown great success in arenas such as medication adherence, management of chronic conditions, and patient safety. Given the growth of chronic pain diagnoses, it is imperative to find new technologies to improve care for this particular population. Little research has catalogued the use of digital health in the chronic pain patient population. This manuscript’s objective was to describe current patterns of digital health usage among chronic pain patients and how digital health use correlates with health care utilization and health outcomes. Methods A cross-sectional survey was administered to patients with a self-identified chronic pain diagnosis participating in ‘Patients Like Me’® (PLM), an organization that directly collects data from patients experiencing chronic health conditions, with emphasis on patient-centered outcomes and experiences interacting with the health care system. Validated measures of healthcare utilization, chronic pain management, and digital health use were adapted for the survey. Digital health was defined as the use of online sites, social media, and mobile phone applications before, during, or after healthcare utilization. Descriptive statistics, chi square tests, logistic regression, and linear regression were used as appropriate for analysis. Results Among 565 respondents (mean age 51.3, 87.2% female, 45.7% publicly insured), most participants (89.5%) reported some digital health use. Females and users below the age of 50 were more likely to use multiple forms of digital health. Healthcare utilization, education level, and race/ethnicity did not correlate with digital health use. Patients using more types of digital health reported significantly higher levels of pain coping skills in the realms of social support, relaxation, and exercise. Conclusions Digital health use is common among a wide range of patients with chronic pain diagnoses. The use of multiple forms of digital health is associated with improved chronic pain coping mechanisms. Future work should explore the directional relationship between digital health tools and chronic pain coping skills, as well as which components of digital health have the most effect on chronic pain management and other patient-centered outcomes. PMID:28293608

A closer look: Alternative pain management practices by heart failure patients with chronic pain.

PubMed

McDonald, Deborah Dillon; Soutar, Christina; Chan, Maria Agudelo; Afriyie, Angela

2015-01-01

To describe alternative non-pharmaceutical non-nutraceutical pain self-management strategies used by people with heart failure (HF) in order to reduce chronic non-cardiac pain. Little is known about alternative pain self-treatments used by HF patients with chronic pain. A cross-sectional descriptive design was used with 25 hospitalized HF patients who had chronic pain and used at least one alternative pain treatment. Pain intensity, pain interference with function, and current pain treatments were measured with the Brief Pain Inventory. Alternative treatments included walking, stretching, use of heat and cold. Five patients used evidence-based pain treatments for their chronic pain conditions. Patients reported moderate pain intensity and pain interference with activity. Patients with HF and chronic pain use few alternative pain treatments. Screening for chronic pain and referral to Integrative Medicine and/or Palliative care for a pain management consult might reduce the added burden of pain in people with HF. Copyright © 2015 Elsevier Inc. All rights reserved.

Depression and anxiety in patients on chronic hemodialysis in University Clinical Hospital Mostar.

PubMed

Klarić, Miro; Letica, Ivona; Petrov, Bozo; Tomić, Monika; Klarić, Branka; Letica, Ludvig; Francisković, Tanja

2009-12-01

Depression and anxiety are prevailing mental problem in patients on chronic hemodialysis and they have great influence on outcome of illness. Additionally, these disorders are rarely identified in that population of patients and they are insufficiently treated. The aim of this study was to assess the prevalence of depression and anxiety in patients on chronic hemodialysis in University Clinical Hospital Mostar and to examine the correlation between the demographic variables and the time spent on dialysis with depression and anxiety levels. The experimental group consisted of 56 patients on chronic hemodialysis in Mostar Clinical Hospital. The control group 1 consisted of 53 patients diagnosed with a chronic illness and treated for at least a year, while the control group 2 consisted of 51 persons who were not diagnosed with any chronic somatic or mental illness. Demographic data were collected using the constructed questionnaire. The Beck Depression Inventory-BDI was used to determine depression, while the Spielberger State-Trait Anxiety Inventory-STAI was used to determine anxiety. We recorded significantly higher prevalence of depression in patients on chronic dialysis (51.8%) than in patients with a chronic illness (41.5%) and persons without chronic illnesses (9.8%; p < 0.001). Trait anxiety level was significantly higher in hemodialysed patients compared to the other two groups (p = 0.006) but there were no significant differences in state anxiety level. The study has not shown any significant difference in the prevalence of depression and anxiety level regarding the differences in sex, gender and education level, apart from a higher level of state anxiety in patients with a lower education level (p = 0.032). These results indicate that patients on hemodialysis have a significantly higher level of depression and a higher level of trait anxiety compared to patients with chronic illnesses and especially compared to general population.

The diagnosis and treatment of chronic migraine

PubMed Central

2015-01-01

Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine. PMID:25954496

The experiences of chronically ill patients and registered nurses when they negotiate patient care in hospital settings: a feminist poststructural approach: A qualitative study that explores negotiation of patient care between patients and chronically ill patients in hospital settings.

PubMed

Griscti, Odette; Aston, Megan; Martin-Misener, Ruth; Mcleod, Deborah; Warner, Grace

2016-07-01

The aim of this study was to understand the experiences of chronically ill patients and registered nurse in negotiating patient care in hospital. Specifically, we explored how social and institutional discourses shaped power relations and negotiation of patient care. Current literature indicates that although nurses embrace this notion, such partnerships are not easily implemented. Most existing studies focus on the role of the nurse as the leader of the partnership with little attention paid to how social and institutional values, beliefs and practices shape nurse/patient power relations; or how these relationships are negotiated between nurses and patients. The theoretical and methodological approaches used in this study are based on the precepts of Foucault and feminist poststructural theorists. In depth interviews were conducted with eight chronically ill patients and 10 registered nurses. Both nurses and patients commented about the relationships that develop between nurses and chronically ill patients and how these relationships facilitate negotiation of patient care. Both parties described challenging moments and how institutional discourses may hinder positive negotiations of care. In this paper we highlight three themes that emerged: getting to know each other, they are not the sickest patients and finding time to listen. This study offers an innovative way of unpacking negotiation of care between chronically ill patients and registered nurses. It exposes how social and institutional discourses play a pivotal role in shaping negotiations between nurses and chronically ill patients. Negotiating care with chronically ill patients is not as asymmetric as portrayed in some of the literature and tends to be based on mutual agreements between nurses and patients. Nurses make it a point to listen to patients' needs and resist institutional discourses that preclude them from spending time with patients. © 2016 John Wiley & Sons Ltd.

The perceptions and perspectives of patients and health care providers on chronic diseases management in rural South Africa: a qualitative study.

PubMed

Maimela, Eric; Van Geertruyden, Jean-Pierre; Alberts, Marianne; Modjadji, Sewela E P; Meulemans, Herman; Fraeyman, Jesicca; Bastiaens, Hilde

2015-04-08

Preventive health care represents the future for health care delivery in South Africa to improve management of chronic diseases as this has been implemented for some time in several countries to tackle the increasing burden of chronic diseases. Individual person's health is unique, as they move in and out of chronic and acute health care phases, there is need to integrate chronic and acute care constructs to improve continuity of care and maximize health and improve wellbeing. The aim of this study was to determine the perceptions and perspectives of chronic patients' and nurses regarding chronic disease management in terms of barriers, facilitators and their experiences. To meet our aim we used qualitative methods involving the collection of information by means of focus group discussions in Dikgale Health and Demographic Surveillance System (HDSS). All data was recorded, transcribed verbatim and analysed using data-driven thematic analysis. Our study showed that chronic disease patients have a first contact with health care professionals at the primary health care level in the study area. The main barriers mentioned by both the health care workers and chronic disease patients are lack of knowledge on chronic diseases, shortage of medication and shortage of nurses in the clinics which causes patients to wait for a long periods in a clinic. Health care workers are poorly trained on the management of chronic diseases. Lack of supervision by the district and provincial health managers together with poor dissemination of guidelines has been found to be a contributing factor to lack of knowledge in nurses among the clinics within the study area. Both patients and nurses mentioned the need to involve community health workers and traditional healers and integrate their services in order to early detect and manage chronic diseases in the community. Nurses and chronic disease patients mentioned similar barriers to chronic disease management. Concerted action is needed to strengthen the delivery of medications at the clinics, improve the chronic disease knowledge for both nurses and patients by conducting in-service trainings or workshops, increase the involvement of community health workers and establish a link (through formal referral system) with traditional healers.

Vitamin D deficiency in chronic idiopathic urticaria.

PubMed

Movahedi, Masoud; Tavakol, Marzieh; Hirbod-Mobarakeh, Armin; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Tavakol, Zahra; Momenzadeh, Kaveh; Nabavi, Mohammad; Dabbaghzade, Abbas; Mosallanejad, Asieh; Rezaei, Nima

2015-04-01

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

The Chronic Illness Problem Inventory as a measure of dysfunction in chronic pain patients.

PubMed

Romano, J M; Turner, J A; Jensen, M P

1992-04-01

Assessment of physical and psychosocial dysfunction is recognized as essential in chronic pain patient evaluation. One instrument, the Sickness Impact Profile (SIP), has demonstrated good reliability and validity as a measure of dysfunction among chronic pain patients. An alternate measure, the Chronic Illness Problem Inventory (CIPI), is shorter and more easily scored than the SIP, but as yet has not been applied widely to chronic pain problems. In the present study, 95 chronic low back pain patients completed the SIP, the CIPI, activity diaries, the McGill Pain Questionnaire (MPQ), and the Center for Epidemiologic Studies-Depression scale (CES-D), before participating in a chronic pain treatment study. Overt pain behaviors were also coded from videotapes of a standardized assessment protocol. Seventy-five subjects completed the measures post-treatment. The results indicate that although the SIP and the CIPI are significantly correlated and appear to be measuring similar constructs, there is also substantial unshared variance between them, suggesting that they may tap somewhat different aspects of dysfunction in chronic pain. The CIPI shows promise as a useful alternative measure of dysfunction in chronic low back pain patients, but requires further validation for this purpose.

Mitochondrial transit peptide exhibits cell penetration ability and efficiently delivers macromolecules to mitochondria.

PubMed

Jain, Aastha; Chugh, Archana

2016-09-01

Mitochondrial malfunction under various circumstances can lead to a variety of disorders. Effective targeting of macromolecules (drugs) is important for restoration of mitochondrial function and treatment of related disorders. We have designed a novel cell-penetrating mitochondrial transit peptide (CpMTP) for delivery of macromolecules to mitochondria. Comparison between properties of cell-penetrating peptides (CPPs) and mitochondrial signal sequences enabled prediction of peptides with dual ability for cellular translocation and mitochondrial localization. Among the predicted peptides, CpMTP translocates across HeLa cells and shows successful delivery of noncovalently conjugated cargo molecules to mitochondria. CpMTP may have applications in transduction and transfection of mitochondria for therapeutics. © 2016 Federation of European Biochemical Societies.

Visuospatial and verbal memory in chronic pain patients: an explorative study.

PubMed

Busch, Hillevi; Montgomery, William; Melin, Bo; Lundberg, Ulf

2006-09-01

Cognitive bias, such as selective memory for pain-related information, is frequently observed in chronic pain patients and is assessed mostly using verbal material. Beside word lists, the current study used photographs of people presenting pain behaviors to assess memory bias in chronic pain patients. Chronic pain patients were hypothesized to show better recall of pain-related words and pictures as compared to pain-free controls. Twenty-eight female chronic neck patients and 28 pain-free female controls completed two computerized pictorial memory games and two word recall tasks. Patients and controls performed equally well in the neutral pictorial memory game. In the pain-related game, patients performed significantly worse than controls. No significant differences were found in the word recall task. The result is discussed in terms of cognitive avoidance.

Acute on chronic gastrointestinal bleeding: a unique clinical entity.

PubMed

Rockey, Don C; Hafemeister, Adam C; Reisch, Joan S

2017-06-01

Gastrointestinal bleeding is defined in temporal-spatial terms-as acute or chronic, and/or by its location in the gastrointestinal tract. Here, we define a distinct type of bleeding, which we have coined 'acute on chronic' gastrointestinal bleeding. We prospectively identified all patients who underwent endoscopic evaluation for any form of gastrointestinal bleeding at a University Hospital. Acute on chronic bleeding was defined as the presence of new symptoms or signs of acute bleeding in the setting of chronic bleeding, documented as iron deficiency anemia. Bleeding lesions were categorized using previously established criteria. We identified a total of 776, 254, and 430 patients with acute, chronic, or acute on chronic bleeding, respectively. In patients with acute on chronic gastrointestinal bleeding, lesions were most commonly identified in esophagus (28%), colon and rectum (27%), and stomach (21%) (p<0.0001 vs locations for acute or chronic bleeding). In those specifically with acute on chronic upper gastrointestinal bleeding (n=260), bleeding was most commonly due to portal hypertensive lesions, identified in 47% of subjects compared with 29% of acute and 25% of chronic bleeders, (p<0.001). In all patients with acute on chronic bleeding, 30-day mortality was less than that after acute bleeding alone (2% (10/430) vs 7% (54/776), respectively, p<0.001). Acute on chronic gastrointestinal bleeding is common, and in patients with upper gastrointestinal bleeding was most often a result of portal hypertensive upper gastrointestinal tract pathology. Reduced mortality in patients with acute on chronic gastrointestinal bleeding compared with those with acute bleeding raises the possibility of an adaptive response. Copyright © 2017 American Federation for Medical Research.

Addition of vitamin D reverses the decline in GFR following treatment with ACE inhibitors/angiotensin receptor blockers in patients with chronic kidney disease.

PubMed

Soares, Abel Esteves; Maes, Michael; Godeny, Paula; Matsumoto, Andressa Keiko; Barbosa, Décio Sabbatini; da Silva, Taysa Antonia F; Souza, Flávio Henrique M O; Delfino, Vinicius Daher Alvares

2017-12-15

Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m 2 ) patients with and without vitamin D deficiency. The patients ingested six-month cholecalciferol 50,000IU oral supplementation to chronic kidney disease patients with vitamin D deficiency. We hypothesize changes in estimated glomerular filtration rate over study period. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials. Copyright © 2017. Published by Elsevier Inc.

Role of zinc in chronic gastritis.

PubMed

Marjanović, Ksenija; Dovhanj, Jasna; Kljaić, Ksenija; Sakić, Katarina; Kondza, Goran; Tadzić, Refmir; Vcev, Aleksandar

2010-06-01

Oxidative stress occurs in inflammation of gastric mucosa. The role of zinc in modulating oxidative stress has recently been recognized. Zn deficiency results in an increased sensitivity to oxidative stress and have a higher risk of musoca damage in inflammation. The aim of this study was to determine wheather chronic inflammation affects on the concentration of Zn2+ ions in gastric mucosa of patients with chronic gastritis. Forthy-three patients with chronic gastitis were enrolled. Patients were endoscoped. Histology and scoring of gastritis was performed following the guidelines of the updated Sydney system. Endoscopic finding of mucosa were scored according to a Lanza scoring system. The diagnosis of Helicobacter pylori (H. pylori) infection, histopathologic changes, intensity of inflammation and zinc concentration were determined from biopsies of gastric mucosa. The atomic absorption spectrophotometer was used to determine tissue concentrations of zinc. Twenty of 43 patients with chronic gastritis were uninfected by H. pylori. There was no statistically significant difference in tissue concentrations of zinc between H. pylori-positive and H. pylori-negative patients. From those infected patients 53.3% had chronic active gastritis. There was no statistically significant difference in tissue concentrations of zinc between patients with chronic active gastritis and patients with chronic inactive gastritis (p = 0.966). Zn in antrum showed positive correlation with density of H. pylori in antrum (Spearman' rho = 0.481, p = 0.020), negative correlation with density of H. pylori in corpus (Spearman' rho = -0.492, p = 0.017) and with zinc in corpus (Spearman' rho = 0.631, p =0.001). Tissue concentration of zinc was not affected by chronic inflammation of gastric mucosa in patients with chronic gastritis.

Overcoming the Influence of Chronic Pain on Older Patients' Difficulty with Recommended Self-Management Activities

ERIC Educational Resources Information Center

Krein, Sarah L.; Heisler, Michele; Piette, John D.; Butchart, Amy; Kerr, Eve A.

2007-01-01

Purpose: Many older patients with common chronic conditions also experience chronic pain. We examined how chronic pain affects patients' difficulty with recommended self-management activities and the potential intervening role of self-efficacy (the level of confidence in one's own ability to perform a specific task). Design and Methods: We…

Treatment of Chronic Cough.

PubMed

Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

2017-01-01

Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

Gallbladder emptying to endogenous and exogenous stimulation in chronic pancreatitis patients.

PubMed

Meguro, T; Shimosegawa, T; Kashimura, J; Kikuchi, Y; Koizumi, M; Toyota, T

1994-02-01

The present study was designed to analyze the underlying mechanism of gallbladder motor disturbance in chronic pancreatitis patients. Gallbladder emptying to endogenous (oral test meal, Daiyan 13 g) and exogenous stimulation (iv cerulein, 30 ng/kg for 5 min) was examined by real-time ultrasonography in 12 patients with chronic pancreatitis and 10 normal subjects (controls). Plasma cholecystokinin levels during the endogenous stimulation were measured by bioassay. In chronic pancreatitis patients compared with controls, the fasting gallbladder volume was significantly increased (29.5 +/- 2.2 vs. 21.5 +/- 2.8 ml), whereas the gallbladder emptying (percent change of the basal volume) to oral test meal was significantly decreased. Neither cholecystokinin secretion induced by the test meal, nor the gallbladder emptying response to intravenous cerulein, differed significantly between the two groups. However, when chronic pancreatitis patients were divided according to pathogenesis, it became clear that gallbladder emptying to intravenous cerulein was significantly greater in patients with alcoholic chronic pancreatitis than in patients with idiopathic pancreatitis. Gallbladder emptying during the intestinal phase is generally reduced in patients with chronic pancreatitis, but gallbladder responsiveness to exogenous stimulation might be heterogeneous according to the pathogenesis.

Use and abuse of opioid analgesics in chronic pain.

PubMed Central

Goldman, B.

1993-01-01

Primary care physicians are frequently required to treat patients with chronic debilitating pain. Opioid analgesics can successfully manage chronic pain. To prescribe opioid analgesics effectively, physicians must identify appropriate patients. Several methods can be used to identify and distinguish appropriate patients, addicted patients, and for-profit drug seekers. PMID:8097128

Chronic Liver Disease in Peru: Role of Viral Hepatitis

DTIC Science & Technology

1994-01-01

hepatocellular carcinoma . Only two (1.6%) comparison patients without liver disease had anti- HCV. Hepatitis B surface antigen (HBsAg) was found in 23% of...patients with chronic hepatitis, 12% of patients with cirrhosis, and three of seven patients with hepatocellular carcinoma . There was no evidence of chronic

Life events, anxiety, social support, personality, and alexithymia in female patients with chronic pain: A path analysis.

PubMed

Zeng, Fanmin; Sun, Xueli; Yang, Bangxiang; Fu, Xiaoqian

2016-03-01

This study sought to identify a model that explains the relationship between psychosocial factors and chronic pain in female patients, and to explore all of these constructs in a single study and provide a more holistic examination of the overall psychosocial factors that female patients with chronic pain encounter. Female patients with chronic pain (n = 147), aged 20-65 (M = 34.9 years, SD = 11.25), from an outpatient pain clinic completed a cross-sectional self-report questionnaire on anxiety, life events, personality, social support, and alexithymia. Data were analyzed by means of path analysis. The direct effect of anxiety on female patients with chronic pain was greatest among all the paths. Personality and alexithymia led to chronic pain in female patients only indirectly, mediated by life events. The personality factors of neuroticism and extraversion were associated positively with social support, which had an indirect effect on the influence of life events on chronic pain. However, alexithymia was associated negatively with social support, which had an indirect effect on the influence of life events on chronic pain. Our findings provide evidence that life events are a mediator in the relationship between personality, social support, alexithymia, and chronic pain in female patients. © 2015 The Authors. Asia-Pacific Psychiatry published by Wiley Publishing Asia Pty Ltd.

Health-related needs of people with multiple chronic diseases: differences and underlying factors.

PubMed

Hopman, Petra; Schellevis, François G; Rijken, Mieke

2016-03-01

To examine the health-related needs of people with multiple chronic diseases in the Netherlands compared to people with one chronic disease, and to identify different subgroups of multimorbid patients based on differences in their health problems. Participants were 1092 people with one or more chronic diseases of a nationwide prospective panel study on the consequences of chronic illness in the Netherlands. They completed the EQ-6D, a multi-dimensional questionnaire on health problems (October 2013). Chi-square tests and analyses of variance were performed to test for differences between multimorbid patients and patients with one chronic disease. To identify subgroups of multimorbid patients, cluster analysis was performed and differences in EQ-6D scores between clusters were tested with Chi-square tests. Multimorbid patients (51 % of the total sample) experience more problems in most health domains than patients with one chronic disease. Almost half (44 %) of the multimorbid people had many health problems in different domains. These people were more often female, had a smaller household size, had a lower health literacy, and suffered from more chronic diseases. Remarkably, a small subgroup of multimorbid patients (4 %, mostly elderly males) is characterized by all having cognitive problems. Based on the problems they experience, we conclude that patients with multimorbidity have relatively many and diverse health-related needs. Extensive health-related needs among people with multimorbidity may relate not only to the number of chronic diseases they suffer from, but also to their patient characteristics. This should be taken into account, when identifying target groups for comprehensive support programmes.

Does disease management improve clinical and economic outcomes in patients with chronic diseases? A systematic review.

PubMed

Ofman, Joshua J; Badamgarav, Enkhe; Henning, James M; Knight, Kevin; Gano, Anacleto D; Levan, Rebecka K; Gur-Arie, Shoval; Richards, Margaret S; Hasselblad, Vic; Weingarten, Scott R

2004-08-01

To assess the clinical and economic effects of disease management in patients with chronic diseases. Electronic databases were searched for English-language articles from 1987 to 2001. Articles were included if they used a systematic approach to care and evaluated patients with chronic disease, reported objective measurements of the processes or outcomes of care, and employed acceptable experimental or quasi-experimental study designs as defined by the Cochrane Effective Practice and Organization of Care Group. Two reviewers evaluated 16,917 titles and identified 102 studies that met the inclusion criteria. Identified studies represented 11 chronic conditions: depression, diabetes, rheumatoid arthritis, chronic pain, coronary artery disease, asthma, heart failure, back pain, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia. Disease management programs for patients with depression had the highest percentage of comparisons (48% [41/86]) showing substantial improvements in patient care, whereas programs for patients with chronic obstructive pulmonary disease (9% [2/22]) or chronic pain (8% [1/12]) appeared to be the least effective. Of the outcomes more frequently studied, disease management appeared to improve patient satisfaction (71% [12/17]), patient adherence (47% [17/36]), and disease control (45% [33/74]) most commonly and cost-related outcomes least frequently (11% to 16%). Disease management programs were associated with marked improvements in many different processes and outcomes of care. Few studies demonstrated a notable reduction in costs. Further research is needed to understand how disease management can most effectively improve the quality and cost of care for patients with chronic diseases.

Patient-provider relationship as mediator between adult attachment and self-management in primary care patients with multiple chronic conditions.

PubMed

Brenk-Franz, Katja; Strauß, Bernhard; Tiesler, Fabian; Fleischhauer, Christian; Schneider, Nico; Gensichen, Jochen

2017-06-01

The conceptual model of attachment theory has been applied to understand the predispositions of patients in medical care and the patient-provider relationship. In patients with chronic conditions insecure attachment was connected to poorer self-management. The patient-provider relationship is associated with a range of health related outcomes and self-management skills. We determined whether the quality of the patient-provider relationship mediates the link between adult attachment and self-management among primary care patients with multiple chronic diseases. 209 patients with a minimum of three chronic diseases (including type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 from eight general practices were included in the APRICARE cohort study. Adult attachment was measured via self-report (ECR-RD), self-management skills by the FERUS and the patient-provider relationship by the PRA-D. The health status and chronicity were assessed by the GP. Multiple mediation analyses were used to examine whether aspects of the patient-provider relationship (communication, information, affectivity) are a mediators of associations between adult attachment and self-management. The analysis revealed that the quality of the patient-provider relationship mediated the effect of attachment on self-management in patients with multiple chronic conditions. Particularly the quality of communication and information over the course of treatment has a significant mediating influence. A personalized, attachment-related approach that promotes active patient-provider communication and gives information about the treatment to the patient may improve self-management skills in patients. Copyright © 2017 Elsevier Inc. All rights reserved.

[Clinical significance of 2,3-biphosphoglyceric acid content in erythrocytes of patients with chronic pulmonary heart disease].

PubMed

Remennik, O I

2006-01-01

The author gives in the article obtained data reflecting the content of 2,3-biphosphoglyceric acid in erythrocytes of patients with chronic lung heart. A comparative analysis of the content of 2,3-biphosphoglyceric acid in erythrocytes of healthy volunteers and patients with chronic lung heart was carried out. The author detected the correlation of changes of 2,3-biphosphoglyceric acid in erythrocytes and histamines in blood plasma in chronic lung heart patients with chronic lun diseases and it may be used in assessment and diagnostics of severity of secondary metabolic deran gements.

Attitudes of Irish patients with chronic pain towards medicinal cannabis.

PubMed

Rochford, Ciaran; Edgeworth, Deirdre; Hashim, Mohammad; Harmon, Dominic

2018-02-08

Medicinal cannabis use is topical in the media in Ireland. A recent Health Products Regulatory Authority review, however, has recommended against its use for patients with chronic pain. This is despite evidence for its effectiveness in this patient's cohort and the inadequate pain management of these patients. The aim of this study was to evaluate the attitudes of Irish patients with chronic pain towards medicinal cannabis. After institutional ethics committee approval, a 12-item questionnaire (excluding demographics) was randomly assigned to patients attending a chronic pain clinic (University Hospital Limerick). The questionnaire was designed to incorporate patient's attitudes on a variety of medicinal cannabis related topics. Ninety-six adult patients were surveyed. 88.54% agreed that cannabis should be legalised for chronic pain medicinal purposes. 80.21% believed it would have health benefits for them and 73.96% agreed it would be socially acceptable to use cannabis for this purpose. 33.33% perceived cannabis to be addictive while 68.75% would be willing to try it if prescribed by a medical professional. The study highlights the attitudes of chronic pain patients in Ireland towards medicinal cannabis. It shows their desire to have medical cannabis legalised for chronic pain and that they view it as a reasonable pain management option.

Use of transcutaneous electrical nerve stimulation for chronic pruritus.

PubMed

Mohammad Ali, Basma Mourad; Hegab, Doaa Salah; El Saadany, Hanan Mohammad

2015-01-01

Pruritus is a distressing symptom in many dermatological as well as systemic conditions, and it is sometimes very chronic and relapsing. Transcutaneous electrical nerve stimulation (TENS) is an inexpensive form of analgesia that could also ameliorate itching. This study aimed to evaluate TENS efficacy in patients with pruritus due to some types of chronic eczema, and in patients with chronic hepatic disease. Ten patients with atopic dermatitis (AD), 20 patients with lichen simplex chronicus (LSC), and 16 patients with chronic liver disease having chronic distressing pruritus received three sessions of TENS weekly for 12 sessions, and the effect on the visual analogue scale (VAS) scores was recorded after 2 weeks of therapy, at treatment end, and after an additional month for follow up. There was a statistically significant decline in the mean VAS score for studied groups at weeks 2 and 4 of therapy compared to baseline, but the improvement was more significant in patients with AD, and LSC (p < 0.001 for both) than in those with chronic liver disease (p < 0.01) who also showed an early re-elevation of VAS score on follow up. TENS therapy holds promise as a palliative, alternative, safe and inexpensive treatment for patients with some chronic pruritic conditions. © 2015 Wiley Periodicals, Inc.

The protective effect of Lactobacillus and Bifidobacterium as the gut microbiota members against chronic urticaria.

PubMed

Rezazadeh, Akram; Shahabi, Shahram; Bagheri, Morteza; Nabizadeh, Edris; Jazani, Nima Hosseini

2018-06-01

Chronic Urticaria is a common disorder which is defined by recurrent occurrence of wheals and sometimes angioedema. It has a notable influence on the patients' quality of life. Regulation of the immune system is one of the important roles of the gut microbiota. The effect of dysbiosis considering some members of gut microbiota in patients with chronic urticaria has been demonstrated in our previous study. Comparing the frequency and bacterial load of Lactobacillus, Bifidobacterium, and Bacteroides between patients with chronic urticaria and healthy controls. 20 patients with chronic urticaria and 20 age and sex matched healthy individuals were included in the present study. Stool samples were analyzed for determining the frequency and bacterial load of Lactobacillus, Bifidobacterium, and Bacteroides genera. There were no significant differences among the frequencies of detectable Lactobacillus, Bifidobacterium, or Bacteroides in stool samples of patients with chronic urticaria and healthy controls. The relative amounts of Lactobacillus and Bifidobacterium were significantly higher in fecal samples from controls compared to patients with chronic urticaria (P = 0.038 and 0.039, respectively). It is the first study on the implication of Lactobacillus, Bifidobacterium, and Bacteroides genera as gut microbiota members in patients with chronic urticaria. Copyright © 2018 Elsevier B.V. All rights reserved.

Nutritional status, gender and marital status in patients with chronic obstructive pulmonary disease.

PubMed

Odencrants, Sigrid; Bjuström, Tomas; Wiklund, Nils; Blomberg, Karin

2013-10-01

To describe and compare nutritional status, pulmonary function, gender and marital status in patients with chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease is a chronic illness that can lead to poor nutritional status due to an increased energy requirements related to laboured breathing. Inadequate nutritional intake has often been described in this patient group. Nutritional support for patients with chronic obstructive pulmonary disease who suffer from nutritional problems is essential, both for their sense of well-being and for their survival with chronic obstructive pulmonary disease. The study design was descriptive and comparative. Quantitative data collection was carried out among 81 patients with chronic obstructive pulmonary disease (47 women and 34 men) with an average age of 65 years (SD 3·5). The Mini Nutritional Assessment was used to assess nutritional status. Participants who lived alone had worse nutritional status than those who did not live alone, and female participants had worse nutritional status than their male counterparts. No significant correlation was found between pulmonary function and nutritional status. This study contributes knowledge of a potential correlation between nutritional status, gender and marital status in patients with chronic obstructive pulmonary disease. Women with chronic obstructive pulmonary disease may be at an increased risk of malnutrition. Despite the previous results showing malnutrition and underweight to be common, the present study found that many of the participants were overweight, which may reflect a global health trend regardless of disease. Early identification of patients at risk of malnutrition is important. Registered nurses should be aware that patients with chronic obstructive pulmonary disease who are female or who live alone may be at an increased risk of nutritional problems. Patients with chronic obstructive pulmonary disease must be offered information and support for individually adapted measures at an early stage in order to avoid nutritional problems, regardless of under- and overweight. © 2013 John Wiley & Sons Ltd.

Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain? An exploratory study.

PubMed

Bouwense, Stefan A W; Olesen, Søren S; Drewes, Asbjørn M; Frøkjær, Jens B; van Goor, Harry; Wilder-Smith, Oliver H G

2013-01-01

The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study. Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together. The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis.

Association of Interleukin-17 polymorphism (-197G/A) in chronic and localized aggressive periodontitis.

PubMed

Chaudhari, Harshal Liladhar; Warad, Shivaraj; Ashok, Nipun; Baroudi, Kusai; Tarakji, Bassel

2016-01-01

Interleukin 17(IL-17) is a pro-inflammatory cytokine produced mainly by Th17 cells. The present study was undertaken to investigate a possible association between IL-17 A genetic polymorphism at (-197A/G) and susceptibility to chronic and localized aggressive periodontitis (LAgP) in an Indian population. The study was carried out on 105 subjects, which included 35 LAgP patients, 35 chronic periodontitis patients and 35 healthy controls. Blood samples were drawn from the subjects and analyzed for IL-17 genetic polymorphism at (-197A/G), by using the polymerase chain reaction-restriction fragment length polymorphism method. A statistically significant difference was seen in the genotype distribution among chronic periodontitis patients, LAgP patients and healthy subjects. There was a significant difference in the distribution of alleles among chronic periodontitis patients, LAgP patients and healthy subjects. The odds ratio for A allele versus G allele was 5.1 between chronic periodontitis patients and healthy controls, and 5.1 between LAgp patients and healthy controls. Our study concluded that IL-17 A gene polymorphism at (-197A/G) is linked to chronic periodontitis and LAgP in Indian population. The presence of allele A in the IL-17 gene polymorphism (-197A/G) can be considered a risk factor for chronic periodontitis and LAgP.

Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases.

PubMed

Cardoso, Elsa Maria; Reis, Cátia; Manzanares-Céspedes, Maria Cristina

2018-01-01

Periodontal diseases, such as chronic periodontitis, share common inflammatory risk factors with other systemic and chronic inflammatory disorders. Mucosal tissues, such as oral epithelia, are exposed to environmental stressors, such as tobacco and oral bacteria, that might be involved in promoting a systemic inflammatory state. Conversely, chronic disorders can also affect oral health. This review will summarize recent evidence for the interrelationship between chronic periodontitis and other prevalent chronic diseases such as cardiovascular diseases, diabetes, cancer and chronic respiratory diseases. The association with pregnancy is also included due to possible obstetric complications. We will focus on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have been shown to be increased in patients with chronic periodontitis, in patients with chronic systemic diseases, and in patients with both chronic periodontitis and other chronic diseases. Therefore, an imbalance towards a proinflammatory immune response could underline a bidirectional link between chronic periodontitis and other chronic diseases. Finally, we highlight that a close coordination between dental and other health professionals could promote oral health and prevent or ameliorate other chronic diseases.

[Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

PubMed

Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

2016-08-01

To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (P<0.01). Three months after periodontal treatment, CGRP content was significantly higher compared with that before treatment (P<0.05), but no significant difference was found in patients with different degree of periodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

PubMed

da Costa, Marianges Zadrozny Gouvêa; Pires, Júlia Glória Lucatelli; Nasser, Paulo Dominguez; Ferreira, Camila da Silva; Teixeira, Ana Cristina de Sá; Paranaguá-Vezozzo, Denise Cerqueira; Guarita, Dulce Reis; Carrilho, Flair José; Ono, Suzane Kioko

2016-10-01

This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P < 0.01). The difference in smoking frequency was not significant between the patients with idiopathic pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

PubMed

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.

PubMed

Holland-Bill, L; Christiansen, C F; Gammelager, H; Mortensen, R N; Pedersen, L; Sørensen, H T

2015-03-01

Bleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear. To examine the prognostic impact of chronic liver disease on mortality after peptic ulcer bleeding. We used population-based medical registries to conduct a cohort study of all Danish residents hospitalised with incident peptic ulcer bleeding from 2004 through 2011. We identified patients diagnosed with liver cirrhosis or non-cirrhotic chronic liver disease before their admission for peptic ulcer bleeding. We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan-Meier method (1 - survival function) and used a Cox regression model to estimate mortality rate ratios (MRRs), controlling for potential confounders. We identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these, 653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3% and 20.7%, respectively, compared to 18.3% among patients without chronic liver disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95% CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non-cirrhotic chronic liver disease. Patients with chronic liver disease, particularly liver cirrhosis, are at increased risk of death within 90 days after hospitalisation for peptic ulcer bleeding compared to patients without chronic liver disease. © 2015 John Wiley & Sons Ltd.

[Diagnosis and treatment of duodenal dystrophy in patients with chronic pancreatitis].

PubMed

Kriger, A G; Smirnov, A V; Berelavichus, S V; Gorin, D S; Karmazanovskiy, G G; Vetsheva, N N; Nerestyuk, Ya I; Kalinin, D V; Glotov, A V

to define optimal treatment of duodenal dystrophy in patients with chronic pancreatitis. 515 patients with chronic pancreatitis have been treated for the period 2004-2015 in A.V.Vishnevsky Institute of Surgery. Duodenal dystrophy (DD) was diagnosed in 79 (15.3%) of them. The diagnosis was confirmed by sonography, CT, MRI and endosonography. 5 patients are under observation without surgery. 74 patients were operated after previous medical therapy during 39 months on the average. Pancreatoduodenectomy was performed in 36 patients. Organ-sparing interventions were applied in 34 cases including different duodenal resections in 20 patients and pancreatic head resections in different modifications in 14 cases. 4 patients underwent palliative surgery. Chronic pancreatitis and DD were verified by morphological analysis of specimens. Long-term results were estimated in 47 patients. Median follow-up was 49.9 months. X-ray diagnostics showed that DD was combined with chronic pancreatitis in 87.3% of cases while morphological analysis revealed 93.8%. Clinical signs of DD were caused by striated pancreatitis in 69.6% and ectopic pancreatic tissue in 30.4%. Clinical manifestations of DD did not depend on its cause and were presented by symptoms of chronic pancreatitis. Postoperative complications occurred in 25 (34.7%) patients. There were 33.5% of complications after pancreatoduodenectomy and 70% after duodenal resection. 1 patient died. Overall mortality was 1,3%. In long-term period complete regression of symptoms was observed in 66% of cases, significant improvement - in 32%, absence of the effect - in 2%. Medical therapy should be preferred for patients with DD and chronic pancreatitis. Surgery is indicated in case of persistent pain, complicated course of chronic pancreatitis and duodenal obstruction. Pancreatoduodenectomy and pancreatic head resection are preferred.

[Treatment motivation in patients with chronic cardiorenal syndrome].

PubMed

Efremova, E V; Shutov, A M; Borodulina, E O

2015-01-01

To study treatment motivation in patients with chronic heart failure (CHF) and in those with CHF concurrent with chronic kidney disease (CKD). A total of 203 patients (130 men and 73 women; mean age, 61.8±9.6 years) with CHF diagnosed and assessed in accordance with the National Guidelines of the All-Russian Research Society of Cardiology and the Heart Failure Society for the diagnosis and treatment of CHF (third edition, 2009) were examined. CKD was diagnosed according to the 2012 National Guidelines of the Research Nephrology Society of Russia. A group of patients with chronic cardiorenal syndrome (CRS) included those with CHF and CKD with a glomerular filtration rate (GFR) of <60 ml/min/1.73 m2. The clinical course of CHF, personality profile, and motivation for non-drug and drug treatments were assessed in patients with chronic CRS. CFR was 67.7±17.2 ml/min/1.73 m2; chronic CRS was observed in 89 (44%) patients. Psychological functioning assessment showed that the patients with chronic CRS as compared with those with CHF without CKD had high anxiety and maladaptive disease attitudes. CHF treatment motivation (compliance with lifestyle modification and medication) was proved inadequate and detected only in 31 (15.3%) patients with CHF regardless of the presence of CKD. The specific features of psychological functioning, which affected treatment motivation, were seen in patients with chronic CRS: those who were lowly motivated had a euphoric attitude towards their disease (p=0.03); those who were satisfactorily motivated showed an emotive accentuation of character (p=0.002). The presence of CKD aggravates the clinical course of CHF and negatively affects the psychological functioning of patients with CHF. The patients with chronic CRS are characterized by a low level of motivation for both drug and non-drug treatments, which should be taken into account when managing this cohort of patients.

[Chronic pulmonary diseases: point of view of partners and their assessments with regard to the effects of lung sports].

PubMed

Nell, C; Kehr, K; Hildebrandt, O; Sohrabi, K; Cassel, W; Greulich, T; Koehler, K-I; Koehler, U

2011-12-01

Chronic diseases of the respiratory organs have, besides restrictions of lung function, also physical, mental and social consequences. The chronic disease impacts negatively not only the patient's own quality of life but also that of his/her partner and/or relative. As treatment modalities, besides drug therapy, above all outpatient rehabilitation measures have proved to be effective. In this pilot study we sought answers to three questions: (i) How is the quality of life of the patient's partner and/or relative influenced by the disease? How does the partner/relative assess the effect of the disease on the chronically ill patient? How does the partner/relative assess the effect of lung sports on the chronically ill patient? A specially conceived questionnaire was given to the partners/relatives of 25 patients with chronic pulmonary diseases. The patients, 23 with chronic obstructive pulmonary disease and 2 with pulmonary fibrosis, have been participating in lung sports once a week for more than three years. The average age of the patients was 67 years. The patients' illness also negatively influenced the quality of life of the partner to a considerable extent. The impact of the patients' pulmonary disease on the healthy partner was assessed as being rather moderate. Restrictions of social life were essentially influenced by the amount of assistance required by the pulmonary patient. The therapeutic effects of lung sports on the well-being of the patient were aways considered to be positive by the respective partner/relatives. A chronic pulmonary illness also has a negative influence on the partner/relative's quality of life. The necessity for extensive assistance in daily life is accompanied by a considerable negative impact on the partner's quality of life. According to the opinion of the partner/relative, lung sports have positive effects in all of the chronically ill patient's fields of life. © Georg Thieme Verlag KG Stuttgart · New York.

Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

PubMed

Girish, Banavara Narasimhamurthy; Rajesh, Gopalakrishna; Vaidyanathan, Kannan; Balakrishnan, Vallath

2009-11-05

A major role of the pancreas in zinc homeostasis has been suggested. To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; P<0.001), and in tropical chronic pancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, P<0.001). Erythrocyte zinc levels were significantly lower in diabetic patients as compared to non-diabetics (P=0.036). This study demonstrates zinc deficiency in chronic pancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

Teaching and learning about chronic conditions management for undergraduate medical students: utilizing the patient-as-teacher approach.

PubMed

McKinlay, E; McBain, L; Gray, B

2009-09-01

This study was undertaken to evaluate the impact on medical student learning of a revised chronic conditions teaching programme based on the chronic care model utilizing patients-as-teachers. A qualitative questionnaire was completed by students at the start of a primary healthcare rotation to determine existing impressions/understandings about chronic conditions. Following the revised teaching programme, a reflective essay about a home-visit to a person with chronic conditions was completed by students at the end of the rotation. Analysis of the questionnaire at the start of the rotation showed students have some knowledge of the differences between acute and chronic care, have rather negative impressions of what it means to have chronic conditions and know little of overall patient management including the work of an interdisciplinary team. Analysis of the reflective essays completed by students at the end of the rotation showed an increased understanding of chronic conditions, what it means to have a chronic condition and who supports management. A structured chronic conditions teaching programme including patient-as-teacher is an effective way of building knowledge and changing students' impressions of what it means to have a chronic condition.

Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient with chronic urticaria.

PubMed

Wang, Sheng-Huei; Tang, Shih-En; Li, Yu-Huei; Wei, Kuang-Yu; Chang, Chan-Yuan

2017-01-01

Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.

Chronic Colovesical Fistula Leading to Chronic Urinary Tract Infection Resulting in End-Stage Renal Disease in a Chronic Granulomatous Disease Patient.

PubMed

Siddiqui, M R; Sanford, T; Nair, A; Zerbe, C S; Hughes, M S; Folio, L; Agarwal, Piyush K; Brancato, S J

2017-02-01

A 46-year old man with X-linked chronic granulomatous disease (CGD) being followed at the National Institute of Health with uncontrolled CGD colitis who developed chronic colovesical fistula, and end-stage renal disease (ESRD). Despite aggressive medical management of symptoms with immunomodulators and antibiotic prophylaxis, the chronic colovesical fistula led to chronic pyelonephritis, recurrent urinary tract infections, persistent air in the collecting system and bladder, and post-renal obstruction resulting in renal failure. Patient is now hemodialysis dependent and required diverting loop ileostomy placement. This report highlights multiple potential etiologies of rising serum creatinine in patients with CGD.

Salivary TNFα levels in groups of subjects with rheumatoid arthritis and chronic periodontitis.

PubMed

Gamel, Ehsan B; Hashim, Nada T; Satti, Asim; Gismalla, Bakri G

2017-01-07

Rheumatoid arthritis (RA) and chronic periodontitis are the most common chronic inflammatory diseases with significant pathological and clinical similarities. Numerous studies have indicated a relationship between rheumatoid arthritis and periodontal disease. The aim of this study was to compare the TNF-α levels in saliva among patients with Rheumatoid arthritis (RA) and chronic periodontitis as well as healthy subjects. One hundred and seventy-one patients were enrolled in this cross-sectional study. Fifty-seven patients diagnosed of RA, 57 patients with chronic periodontitis and 57 healthy subjects. These patients have been examined with regard to TNF-α level from salivary samples. Their teeth were examined with regard to Plaque Index , Gingival Index, probing depth and clinical attachment level.All patients were non-smokers. The results revealed a significant difference in all periodontal parameters among the three groups. The chronic periodontitis group showed a significantly higher value in all clinical periodontal parameters in comparison to both the RA and healthy groups. No significant difference was found between salivary TNF-α level among the three study groups. Patients with chronic periodontitis had the highest periodontal indices. However there was no significant difference regarding the level of salivary TNF-α. Hence, suppression of proinflammatory cytokines might prove beneficial in suppressing periodontal diseases among RA patients.

Enhanced Cellular Uptake of Short Polyarginine Peptides through Fatty Acylation and Cyclization

PubMed Central

2015-01-01

Many of the reported arginine-rich cell-penetrating peptides (CPPs) for the enhanced delivery of drugs are linear peptides composed of more than seven arginine residues to retain the cell penetration properties. Herein, we synthesized a class of nine polyarginine peptides containing 5 and 6 arginines, namely, R5 and R6. We further explored the effect of acylation with long chain fatty acids (i.e., octanoic acid, dodecanoic acid, and hexadecanoic acid) and cyclization on the cell penetrating properties of the peptides. The fluorescence-labeled acylated cyclic peptide dodecanoyl-[R5] and linear peptide dodecanoyl-(R5) showed approximately 13.7- and 10.2-fold higher cellular uptake than that of control 5,6-carboxyfluorescein, respectively. The mechanism of the peptide internalization into cells was found to be energy-dependent endocytosis. Dodecanoyl-[R5] and dodecanoyl-[R6] enhanced the intracellular uptake of a fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI) in human ovarian cancer cells (SK-OV-3) by 3.4-fold and 5.5-fold, respectively, as shown by flow cytometry. The cellular uptake of F′-GpYEEI in the presence of hexadecanoyl-[R5] was 9.3- and 6.0-fold higher than that in the presence of octanoyl-[R5] and dodecanoyl-[R5], respectively. Dodecanoyl-[R5] enhanced the cellular uptake of the phosphopeptide by 1.4–2.5-fold higher than the corresponding linear peptide dodecanoyl-(R5) and those of representative CPPs, such as hepta-arginine (CR7) and TAT peptide. These results showed that a combination of acylation by long chain fatty acids and cyclization on short arginine-containing peptides can improve their cell-penetrating property, possibly through efficient interaction of rigid positively charged R and hydrophobic dodecanoyl moiety with the corresponding residues in the cell membrane phospholipids. PMID:24978295

Beyond the traditional definition of breakthrough pain: an observational study.

PubMed

Gatti, Antonio; Gentili, Marta; Iorno, Vittorio; Mammucari, Massimo; Tufaro, Giuseppe; Lazzari, Marzia; Sabato, Alessandro Fabrizio

2013-03-01

Breakthrough pain (BTP) is traditionally defined as a transitory pain flare in opioid-treated patients with chronic background pain. This definition has, however, been challenged in recent years. This study aimed to analyze BTP prevalence in different pain conditions. This was a prospective, non-interventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged >18 years with oncological or non-oncological pain were eligible for this study; background pain was acute/ subacute (<3 months) or chronic (>3 months). The characteristics of pain were evaluated by means of a structured interview by physicians, and patients were asked to complete a dedicated clinical study form. The following outcomes were assessed: chronic pain duration (in patients with chronic pain), BTP prevalence, and number and severity of daily BTP episodes. All outcomes were assessed in four populations of patients with: (a) chronic oncological pain; (b) chronic non-oncological pain; (c) non-chronic oncological pain; (d) non-chronic non-oncological pain. The correlation between BTP and gender was also investigated. Of 1,270 patients with chronic pain, 1,086 had non-oncological pain (85.5%). Most patients (68.6%) with non-oncological pain were female (P = 0.001). Pain duration was significantly longer in non-oncological pain versus oncological pain groups (P = 0.002). BTP prevalence was lower in non-oncological patients (P < 0.001). No differences were reported in terms of number and severity of daily BTP episodes. BTP was more frequent in females with non-oncological pain (P = 0.04). Females had a significantly higher pain severity (P = 0.02) than males. BTP is frequently reported in patients who do not have BTP according to the traditional definition. BTP frequency and severity is similar in oncological and non-oncological pain.

Influence of chronic back pain on kinematic reactions to unpredictable arm pulls.

PubMed

Götze, Martin; Ernst, Michael; Koch, Markus; Blickhan, Reinhard

2015-03-01

There is evidence that muscle reflexes are delayed in patients with chronic low back pain in response to perturbations. It is still unrevealed whether these delays accompanied by an altered kinematic or compensated by adaption of other muscle parameters. The aim of this study was to investigate whether chronic low back pain patients show an altered kinematic reaction and if such data are reliable for the classification of chronic low back pain. In an experiment involving 30 females, sudden lateral perturbations were applied to the arm of a subject in an upright, standing position. Kinematics was used to distinguish between chronic low back pain patients and healthy controls. A calculated model of a stepwise discriminant function analysis correctly predicted 100% of patients and 80% of healthy controls. The estimation of the classification error revealed a constant rate for the classification of the healthy controls and a slightly decreased rate for the patients. Observed reflex delays and identified kinematic differences inside and outside the region of pain during impaired movement indicated that chronic low back pain patients have an altered motor control that is not restricted to the lumbo-pelvic region. This applied paradigm of external perturbations can be used to detect chronic low back pain patients and also persons without chronic low back pain but with an altered motor control. Further investigations are essential to reveal whether healthy persons with changes in motor function have an increased potential to develop chronic back pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

The utility of ambulatory pH monitoring in patients presenting with chronic cough and asthma

PubMed Central

AlHabib, KF; Vedal, S; Champion, P; FitzGerald, JM

2007-01-01

OBJECTIVE: To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough. PATIENTS AND METHODS: The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded. RESULTS: Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0). CONCLUSIONS: The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients. PMID:17377644

Applying a coping with stress questionnaire for cancer patients to patients with non-cancer chronic illnesses.

PubMed

Orive, Miren; Quintana, Jose M; Vrotsou, Kalliopi; Las Hayas, Carlota; Bilbao, Amaia; Barrio, Irantzu; Matellanes, Begoña; Padierna, Jesús A

2013-06-01

One of the few instruments to evaluate coping skills among patients with chronic illnesses is the Cuestionario de Afrontamiento al Estrés para Pacientes Oncológicos (CAEPO), created initially for cancer patients. We evaluate how well CAEPO applies to patients with non-cancer chronic illnesses. A total of 344 patients (115 with chronic hepatitis C, 120 with inflammatory bowel disease and 109 with recurrent vertigo) completed the CAEPO. Exploratory factor analysis and Cronbach's alpha provide only partial support for the seven factors suggested by the original CAEPO. A streamlined version with fewer dimensions and items may be a better solution for identifying coping strategies among these patients.

The prevalence of malnutrition and fat-soluble vitamin deficiencies in chronic pancreatitis.

PubMed

Duggan, Sinead N; Smyth, Niamh D; O'Sullivan, Maria; Feehan, Sinead; Ridgway, Paul F; Conlon, Kevin C

2014-06-01

Patients with chronic pancreatitis are at risk of malnutrition and nutrient deficiency due to malabsorption, pain, and poor diet. We sought to examine fat-soluble vitamin levels and malnutrition parameters in patients with chronic pancreatitis. In a prospective controlled cohort study, 128 subjects (62 chronic pancreatitis patients and 66 age-/sex-matched controls) were recruited. Body mass index (BMI), handgrip strength (measure of functional capacity), fat stores (triceps skin fold), muscle stores (mid-arm muscle circumference), exocrine function, and serum levels of fat-soluble vitamins (A, D, E) were measured. Half of patients in the chronic pancreatitis group were overweight or obese, although the mean BMI was lower in patients than in controls (P = .007). Handgrip strength (P = .048), fat stores (P = .000), and muscle stores (P = .001) were lower in patients than in controls. Of the patients, 14.5% and 24.2% were deficient in vitamins A and E, respectively. Nineteen percent of patients had excess serum vitamin A levels. Despite the prevalence of overweight and obesity, patients had lower muscle stores, strength, and abnormal vitamin levels. Detailed nutrition assessment including anthropometry and vitamin status is warranted in chronic pancreatitis.

Quality of life and health care utilization in patients with chronic respiratory diseases.

PubMed

Kurpas, D; Mroczek, B; Sitko, Z; Helicka, D; Kuchar, E

2015-01-01

High quality of life (QoL) may reduce the costs of medical care of chronically ill patients due to lower health care utilization. The purpose of this study was to establish the influence of the QoL of primary care patients with chronic respiratory diseases on the level of health care utilization and the predictors of hospitalization. The study group consisted of 594 adult patients with chronic respiratory diseases of the mean age 59.8±14.9 years. The highest QoL was observed in the social relationship domain and the lowest in the physical domain. Low QoL was associated with a low level of health care utilization among patients with chronic respiratory diseases. Most patients were hospitalized during the past 3 years. In a group of patients with chronic respiratory diseases, chances for hospitalization were: higher among patients with low QoL and health satisfaction, low QoL levels in the physical and social relationship domains, high QoL levels in the psychological domain, those with higher education, residents of rural areas, patients using frequent consultations over the phone, and those with at least an average index of services.

[Chronic hypoxia and cardiovascular risk : Clinical significance of different forms of hypoxia].

PubMed

Koehler, U; Hildebrandt, O; Krönig, J; Grimm, W; Otto, J; Hildebrandt, W; Kinscherf, R

2018-06-01

It is of fundamental importance to differentiate whether chronic hypoxia occurs intermittently or persistently. While chronic intermittent hypoxia (CIH) is found typically in patients with obstructive sleep apnea (OAS), chronic persistent hypoxia (CPH) is typically diagnosed in patients with chronic lung disease. Cardiovascular risk is markedly increased in patients with CIH compared to patients with CPH. The frequent change between oxygen desaturation and reoxygenation in patients with CIH is associated with increased hypoxic stress, increased systemic inflammation, and enhanced adrenergic activation followed by endothelial dysfunction and increased arteriosclerosis. The pathophysiologic consequences of CPH are less well understood. The relationship between CPH and the development of pulmonary hypertension, pulmonary heart disease as well as polycythemia has been established.

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease.

PubMed

Morren, Mattijn; Rijken, Mieke; Baanders, Arianne N; Bensing, Jozien

2007-02-01

Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition, patients were asked about their preferred source of genetic information. Questionnaires were mailed to participants of a nationwide representative sample of patients with chronic diseases in the Netherlands (n = 1916). The response rate was 82% (n = 1496). Perceived genetic knowledge was low, particularly among older and lower educated patients. Attitudes towards genetics were rather positive, especially among younger and higher educated patients. Some concerns were also documented, mainly about the consequences of genetic testing for employment and taking insurance. Patients who perceived to have little knowledge found it difficult to formulate an opinion about genetic testing. Higher levels of genetic knowledge were associated with a more favourable attitude towards genetics. Chronic patients prefer to receive genetic information from their GP. Chronic patients are ill prepared when they require genetic knowledge to make decisions regarding the treatment of their disease. This seems to result from a knowledge deficiency rather than from disagreement with the genetic developments. When chronic patients are in need of information about genetics or genetic testing, their general practitioner should provide this.

Pain management at the end of life: A comparative study of cancer, dementia, and chronic obstructive pulmonary disease patients.

PubMed

Romem, Anat; Tom, Sarah E; Beauchene, Michelle; Babington, Lynn; Scharf, Steven M; Romem, Ayal

2015-05-01

Limited data exist concerning the unique pain characteristics of patients with non-cancer terminal diseases referred for inpatient hospice care. To define the unique pain characteristics of patients admitted to an acute inpatient hospice setting with end-stage dementia or chronic obstructive lung disease (or chronic obstructive pulmonary disease) and to compare them to patients with end-stage cancer. Retrospective patient chart review. Demographic, physiological, pain parameters, and medication utilization data were extracted. Associations between pain characteristics, medication utilization, and admission diagnoses were assessed. Analyses included descriptive statistics. In total, 146 patients admitted to an acute inpatient hospice between 1 April 2011 and 31 March 2012 with an underlying primary diagnosis of chronic obstructive pulmonary disease (n = 51), dementia (n = 48), or cancer (n = 47). Pain was highly prevalent in all diagnostic groups, with cancer patients experiencing more severe pain on admission. Cancer patients received a significantly higher cumulative opioid dose compared with dementia and chronic obstructive pulmonary disease patients. Pain control within 24 h of pain onset was achieved in less than half of all patient groups with chronic obstructive pulmonary disease patients the least likely to achieve pain control. Despite the fact that pain is the most common complaint at the end of life, pain management may be suboptimal for some primary diagnoses. Admission diagnosis is the strongest predictor of pain control. Patient with cancer achieve the best pain control, and chronic obstructive pulmonary disease patients are the least likely to have their pain adequately treated. © The Author(s) 2015.

Patient-professional partnerships and chronic back pain self-management: a qualitative systematic review and synthesis.

PubMed

Fu, Yu; McNichol, Elaine; Marczewski, Kathryn; Closs, S José

2016-05-01

Chronic back pain is common, and its self-management may be a lifelong task for many patients. While health professionals can provide a service or support for pain, only patients can actually experience it. It is likely that optimum self-management of chronic back pain may only be achieved when patients and professionals develop effective partnerships which integrate their complementary knowledge and skills. However, at present, there is no evidence to explain how such partnerships can influence patients' self-management ability. This review aimed to explore the influence of patient-professional partnerships on patients' ability to self-manage chronic back pain, and to identify key factors within these partnerships that may influence self-management. A systematic review was undertaken, aiming to retrieve relevant studies using any research method. Five databases were searched for papers published between 1980 and 2014, including Cochrane Library, CINAHL, Medline, EMBASE and PsycINFO. Eligible studies were those reporting on patients being supported by professionals to self-manage chronic back pain; patients being actively involved for self-managing chronic back pain; and the influence of patient-professional partnerships on self-management of chronic back pain. Included studies were critically appraised for quality, and findings were extracted and analysed thematically. A total of 738 studies were screened, producing 10 studies for inclusion, all of which happened to use qualitative methods. Seven themes were identified: communication, mutual understanding, roles of health professionals, information delivery, patients' involvement, individualised care and healthcare service. These themes were developed into a model suggesting how factors within patient-professional partnerships influence self-management. Review findings suggest that a partnership between patients and professionals supports patients' self-management ability, and effective communication is a fundamental factor underpinning their partnerships in care. It also calls for the development of individualised healthcare services offering self-referral or telephone consultation to patients with chronic conditions. © 2015 John Wiley & Sons Ltd.

Symptoms of anxiety and depression: A comparison among patients with different chronic conditions.

PubMed

Bayat, Noushin; Alishiri, Gholam Hossein; Salimzadeh, Ahmad; Izadi, Morteza; Saleh, Davoud Kazemi; Lankarani, Maryam Moghani; Assari, Shervin

2011-11-01

Although patients with chronic diseases are at high-risk for symptoms of anxiety and depression, few studies have compared patients with different chronic conditions in this regard. This study aimed to compare patients with different chronic medical conditions in terms of anxiety and depression symptoms after controlling for the effects of socio-demographic and clinical data. This cross-sectional study enrolled 2234 adults, either healthy (n = 362) or patients with chronic medical conditions (n = 1872). Participants were recruited from the outpatient clinic of Baqiyatallah Hospital, Tehran, Iran. Patients had one of the following five medical conditions: coronary artery disease (n = 675), renal transplantation (n = 383), chronic hemodialysis (n = 68), rheumatoid conditions (rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus and ankylosing spondylitis) (n = 666) and viral hepatitis (n = 80). Independent factors included socio-demographic data, pain disability, and somatic comorbidities (Ifudu index). Outcomes included symptoms of anxiety and depression through Hospital Anxiety and Depression Scale (HADS). Two multinomial regression models were used to determine the predictors of anxiety and depression symptoms. After controlling the effect of age, sex, educational level, comorbidities, disability and pain, rheumatoid arthritis and hepatitis were predictors of higher anxiety symptoms, while coronary artery disease and chronic hemodialysis were predictors of depression symptoms. Although all chronic conditions may require psychological consideration; be that as it may, different chronic diseases are dissimilar in terms of their mental health need. Anxiety for rheumatoid arthritis and hepatitis as well as depression for coronary artery disease and chronic hemodialysis is more important.

The presence and meaning of chronic sorrow in patients with multiple sclerosis.

PubMed

Isaksson, Ann-Kristin; Gunnarsson, Lars-Gunnar; Ahlström, Gerd

2007-11-01

The aim of this study was to explore the presence and meaning of chronic sorrow and the presence of depression in a fairly large group of persons with multiple sclerosis (MS). MS is a chronic and progressive neurological disease with a variety of symptoms. The patients have to live with losses of different kinds. A few earlier studies have used the concept of chronic sorrow to illustrate the emotional situation of such patients. Sixty-one patients were interviewed about the occurrence of chronic sorrow and, thereafter, screened for depression. Thirty-eight (62%) of them fulfilled the criteria for chronic sorrow. The interviews were analysed with latent content analysis. Seven themes describe the losses that caused sorrow: loss of hope, loss of control over the body, loss of integrity and dignity, loss of a healthy identity, loss of faith that life is just, loss of social relations and loss of freedom. The sorrow was constantly present or periodically overwhelming. Only four of the 38 patients with chronic sorrow had symptoms of being mildly depressed. Chronic sorrow meant loss of hope, of control over the body, of integrity and of identity. The concept of chronic sorrow complements that of depression in providing important new knowledge relevant to understanding the consequences MS can have for the individual. Knowledge of the meaning of chronic sorrow can contribute to the nurse's ability to give psychological support and promote a sense of hope and control in the MS patient.

Bosutinib: a review of its use in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.

PubMed

Syed, Yahiya Y; McCormack, Paul L; Plosker, Greg L

2014-02-01

Bosutinib (Bosulif®) is an orally administered small molecule tyrosine kinase inhibitor (TKI) of BCR-ABL and SRC family kinases. It is indicated for the treatment of adult patients with chronic-, accelerated-, or blast-phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy (imatinib, dasatinib, or nilotinib) [USA] or for a small subpopulation of these patients for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options (EU). In a multinational pivotal trial (n = 547), bosutinib treatment resulted in a major cytogenetic response (MCyR) at 24 weeks in one-third of all treated patients with imatinib-resistant chronic-phase CML who had no previous exposure to any TKIs other than imatinib (primary endpoint), with similar results observed in chronic-phase CML patients who were intolerant of imatinib and naïve to all other TKIs. MCyRs were also seen in more than one-quarter of evaluable patients with chronic-phase CML previously treated with multiple TKIs. Most of the patients with chronic-phase CML achieved a complete hematologic response with bosutinib and some patients with advanced phases of CML achieved an overall hematologic response. Responses were seen irrespective of the type of BCR-ABL mutation at baseline, except T315I. Bosutinib had a manageable tolerability profile in the pivotal trial, with ≤21 % of patients with chronic-phase CML discontinuing the treatment because of adverse events. Diarrhea was the most common adverse event but was generally manageable, with only few patients discontinuing the treatment because of diarrhea. Therefore, bosutinib is a useful TKI option for patients with Ph+ CML in second-line or greater settings.

The Utility of Diagnostic Laparoscopy in Post-Bariatric Surgery Patients with Chronic Abdominal Pain of Unknown Etiology.

PubMed

Alsulaimy, Mohammad; Punchai, Suriya; Ali, Fouzeyah A; Kroh, Matthew; Schauer, Philip R; Brethauer, Stacy A; Aminian, Ali

2017-08-01

Chronic abdominal pain after bariatric surgery is associated with diagnostic and therapeutic challenges. The aim of this study was to evaluate the yield of laparoscopy as a diagnostic and therapeutic tool in post-bariatric surgery patients with chronic abdominal pain who had negative imaging and endoscopic studies. A retrospective analysis was performed on post-bariatric surgery patients who underwent laparoscopy for diagnosis and treatment of chronic abdominal pain at a single academic center. Only patients with both negative preoperative CT scan and upper endoscopy were included. Total of 35 post-bariatric surgery patients met the inclusion criteria, and all had history of Roux-en-Y gastric bypass. Twenty out of 35 patients (57%) had positive findings on diagnostic laparoscopy including presence of adhesions (n = 12), chronic cholecystitis (n = 4), mesenteric defect (n = 2), internal hernia (n = 1), and necrotic omentum (n = 1). Two patients developed post-operative complications including a pelvic abscess and an abdominal wall abscess. Overall, 15 patients (43%) had symptomatic improvement after laparoscopy; 14 of these patients had positive laparoscopic findings requiring intervention (70% of the patients with positive laparoscopy). Conversely, 20 (57%) patients required long-term medical treatment for management of chronic abdominal pain. Diagnostic laparoscopy, which is a safe procedure, can detect pathological findings in more than half of post-bariatric surgery patients with chronic abdominal pain of unknown etiology. About 40% of patients who undergo diagnostic laparoscopy and 70% of patients with positive findings on laparoscopy experience significant symptom improvement. Patients should be informed that diagnostic laparoscopy is associated with no symptom improvement in about half of cases.

Patient empowerment and choice in chronic pain management.

PubMed

Barrie, Janette

Service provision and access to pain services vary considerably in the UK, with only a small percentage of people with chronic pain accessing specialist services. Government policy supports giving patients more choice and control over their care. Empowerment involves ensuring patients have the knowledge, skills, attitudes and self-awareness to improve the quality of their lives. As most healthcare professionals provide care to people with chronic pain at some point, it is their responsibility to prepare patients to make informed decisions about their treatment. Empowering patients to self-manage their chronic pain can lead to improved person-centred outcomes.

Hepatitis C virus infection can mimic type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis.

PubMed Central

Pawlotsky, J M; Deforges, L; Bretagne, S; André, C; Métreau, J M; Thiers, V; Zafrani, E S; Goossens, M; Duval, J; Mavier, J P

1993-01-01

Hepatitis C virus (HCV) has been shown to induce anti-liver-kidney microsomal-1 (LKM1) antibody positive chronic active hepatitis, simulating type 2 autoimmune chronic active hepatitis. The cases of five patients presenting with features of type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis and extrahepatic autoimmune manifestations, in whom immunosuppressive treatment had no effect on liver disease are presented. In these patients, HCV infection could be shown by the presence in serum of anti-HCV antibodies and HCV-RNA detected by polymerase chain reaction. These cases suggest the following: (a) chronic HCV infection can mimic type 1, as well as type 2, autoimmune chronic active hepatitis; (b) HCV infection might be systematically sought in patients presenting with features of type 1 autoimmune chronic active hepatitis, with special care in patients who are unresponsive to immunosuppressive treatment. Images Figure PMID:7686122

Analysis of electrocardiogram in chronic obstructive pulmonary disease patients.

PubMed

Lazović, Biljana; Svenda, Mirjana Zlatković; Mazić, Sanja; Stajić, Zoran; Delić, Marina

2013-01-01

Chronic obstructive pulmonary disease is the fourth leading cause of mortality worldwide. It is defined as a persistent airflow limitation usually progressive and not fully reversible to treatment. The diagnosis of chronic obstructive pulmonary disease and severity of disease is confirmed by spirometry. Chronic obstructive pulmonary disease produces electrical changes in the heart which shows characteristic electrocardiogram pattern. The aim of this study was to observe and evaluate diagnostic values of electrocardiogram changes in chronic obstructive pulmonary disease patients with no other comorbidity. We analyzed 110 electrocardiogram findings in clinically stable chronic obstructive pulmonary disease patients and evaluated the forced expiratory volume in the first second, ratio of forces expiratory volume in the first second to the fixed vital capacity, chest radiographs and electrocardiogram changes such as p wave height, QRS axis and voltage, right bundle branch block, left bundle branch block, right ventricular hypertrophy, T wave inversion in leads V1-V3, S1S2S3 syndrome, transition zone in praecordial lead and QT interval. We found electrocardiogram changes in 64% patients, while 36% had normal electrocardiogram. The most frequent electrocardiogram changes observed were transition zone (76.36%) low QRS (50%) and p pulmonale (14.54%). Left axis deviation was observed in 27.27% patients. Diagnostic values of electrocardiogram in patients with chronic obstructive pulmonary disease suggest that chronic obstructive pulmonary disease patients should be screened electrocardiographically in addition to other clinical investigations.

An Atypical Presentation of Subacute Encephalopathy with Seizures in Chronic Alcoholism Syndrome.

PubMed

Kim, Tae-Kyoung; Jung, Eui Sung; Park, Jong-Moo; Kang, Kyusik; Lee, Woong-Woo; Lee, Jung-Ju

2016-06-01

Subacute encephalopathy with seizures in chronic alcoholism syndrome is a rare clinical manifestation in patients with chronic alcohol abuse. We report the case of a patient with chronic alcoholism who presented with partial nonconvulsive status epilepticus associated with a thalamic lesion.

Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease.

PubMed Central

Epstein, O; Dick, R; Sherlock, S

1981-01-01

The association of finger clubbing and periostitis has been reported in primary biliary cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and its relationship to finger clubbing is unknown. In this prospective study, we have determined the prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23% in the group of miscellaneous liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscellaneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (P less than 0.01), but this association was uncommon in other forms of chronic liver disease. In all forms of chronic liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third of affected patients. This study indicates that periostitis affecting the lower leg bones is common in patients with chronic liver disease, and its presence should be sought whether or not the patient has finger clubbing. Images Fig. 2 PMID:7227854

Evaluation of anti-inflammatory effect of statins in chronic periodontitis.

PubMed

Suresh, Snophia; Narayana, Satya; Jayakumar, P; Sudhakar, Uma; Pramod, V

2013-01-01

Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. The mean GCF IL-1β levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.

Clinical application of ghrelin for chronic respiratory failure.

PubMed

Matsumoto, Nobuhiro; Tsubouchi, Hironobu; Imazu, Yoshifumi; Arimura, Yasuji; Yanagi, Shigehisa; Iiboshi, Hirotoshi; Nakazato, Masamitsu

2017-01-01

Chronic respiratory failure, which is often caused by chronic obstructive pulmonary disease, chronic lower respiratory tract infection, or interstitial pneumonia, often leads to cachexia with disease progression. Patients who have chronic respiratory failure with cachexia exhibit increased morbidity. Although cachectic status is an important clinical problem, there are no effective therapies for cachexia. Ghrelin has various effects, including increasing food intake, attenuating sympathetic nerve activity, inhibiting inflammation, increasing cardiac output, and controlling fat utilization. These effects of ghrelin are ideal targets for the treatment of severely wasting chronic respiratory disease. In a few clinical studies, including a small randomized controlled trial, ghrelin administration to cachectic patients with chronic respiratory failure improved exercise tolerance, dyspnea, and appetite. The patients in these studies gained muscle mass and weight. In another study of chronic lower respiratory tract infection with cachexia, ghrelin suppressed airway inflammation by decreasing neutrophil accumulation in the airway, resulting in improvements in oxygenation and exercise tolerance. Although further clinical investigations are needed to clarify its usefulness, ghrelin is expected to become a novel therapy for cachectic patients with chronic respiratory failure.

Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease (COPD) Using an Ontario Policy Model

PubMed Central

Chandra, K; Blackhouse, G; McCurdy, BR; Bornstein, M; Campbell, K; Costa, V; Franek, J; Kaulback, K; Levin, L; Sehatzadeh, S; Sikich, N; Thabane, M; Goeree, R

2012-01-01

Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm. For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx. The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact. Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. The inflammation causes repeated cycles of injury and repair in the airway wall— inflammatory cells release a variety of chemicals and lead to cellular damage. The inflammation process also contributes to the loss of elastic recoil pressure in the lung, thereby reducing the driving pressure for expiratory flow through narr

Patient activation in primary healthcare: a comparison between healthier individuals and those with a chronic illness.

PubMed

Wong, Sabrina T; Peterson, Sandra; Black, Charlyn

2011-05-01

Current policy directions place increasing expectations on patients to actively engage in their care, especially in chronic disease management. We examined relationships between patient activation and multiple dimensions of primary healthcare (PHC), including access, utilization, responsiveness, interpersonal communication, and satisfaction for patients with and without chronic illness. Cross-sectional, random digit dial survey conducted in British Columbia (BC), Canada. Stratified sample of adults (n=504), aged 19 to 90 years, who had visited their regular provider within the past 24 months. All data were weighted to represent residents living in BC. Patient activation and PHC experiences include accessibility, continuity, whole-person care, interpersonal communication, responsiveness, chronic disease management, and satisfaction. The multivariate models provide evidence that both quantity of time and quality of interactions with one's regular provider are associated with higher patient activation. Those with no chronic illness had higher activation scores when they spent more time talking with their regular provider, experienced less hurried communication, or if their test results were explained. The more time people with chronic illness are able to spend with their physician, the more activated they were. Chronic illness respondents also had higher activation scores if they reported higher whole-person care or if they were more satisfied. Positive interactions between the patient and the provider can influence the patient's abilities to engage in and be confident in maintaining/improving his/her health. Supporting patients in becoming actively engaged, in ways that work for them, is essential to providing high quality care, especially among those with a chronic condition.

BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

PubMed

Cuellar, Sandra; Vozniak, Michael; Rhodes, Jill; Forcello, Nicholas; Olszta, Daniel

2017-01-01

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Medical Trainees’ Experiences of Treating People With Chronic Pain: A Lost Opportunity for Medical Education

PubMed Central

Rice, Kathleen; Ryu, Jae Eun; Whitehead, Cynthia; Katz, Joel

2018-01-01

Purpose Evidence suggests that physicians’ opinions about patients with chronic pain become progressively negative over the course of medical training, leading to decline in empathy for these patients. Few qualitative studies have focused on this issue, and thus the experiences shaping this process remain unexplored. This study addressed how medical trainees learn about chronic pain management through informal and formal curricula. Method This study adopted a constructive qualitative approach informed by the theoretical lens of the hidden curriculum. Thirteen open-ended interviews were conducted with medical students and residents at various training stages; interviewees had experience treating patients with chronic pain, shadowing the care of these patients, or both. Interviews elicited information about stage of medical training, general descriptions of work, and concrete experiences of managing patients with chronic pain. All interviews were collected in Toronto between June and August 2015. Results Most interviewees described the management of chronic pain as challenging and unrewarding and attributed this at least in part to their perception that pain was subjective. Trainees also recounted that their inability to cure chronic pain left them confused about how to provide care, and voiced a perception that preceptors seemed to view these patients as having little educational value. Conclusions Specifically because chronic pain is subjective and incurable, listening and communication become crucial for patient care. Instead of sheltering trainees, medical educators should be offered the opportunity to reflect on the skills that are required to provide patient-centered care for this population. This approach has the potential to greatly benefit both trainees and patients. PMID:29140917

[Use of decamethoxine in the complex treatment of chronic bronchitis].

PubMed

Iukhimets, V A; Pilipchuk, V N

1990-02-01

Seventy-two patients with chronic bronchitis were examined and divided into 3 groups. Group I consisted of patients with chronic catarrhal bronchitis (CCB) group II of those with chronic purulent bronchitis (CPB), group III of subjects with bronchitis associated with purulent destructive pulmonary diseases. All the patients received combined treatment with decamethoxin as an antibacterial modality. It was found that decamethoxin promotes elimination of the infection of the bronchial secretion in 60% of chronic bronchitis suffers, the incidence of microorganisms resistent to several antibiotics reduced 2-fold. Local use of decamethoxin as an antibacterial and antiinflammatory drug in multimodality treatment of chronic purulent bronchitis proved highly effective.

Transperineal sonographic anal sphincter complex evaluation in chronic anal fissures.

PubMed

Bedair, Elsaid M; El Hennawy, Hany M; Moustafa, Ahmed Abdu; Meki, Gad Youssef; Bosat, Bosat Elwany

2014-11-01

The purpose of this study was to assess the role of transperineal sonography in assessment of pathologic changes to the anal sphincter complex in patients with chronic anal fissures. We conducted a prospective case-control study of 100 consecutive patients of any age and both sexes with chronic anal fissures who presented to a colorectal clinic between January 2012 and August 2013 (group A) and 50 healthy volunteers (group B). The most common patterns of radiologic changes to anal sphincters associated with chronic anal fissures were circumferential thickening of the anal sphincter complex in 5 patients (5%), circumferential thickening of the internal anal sphincter in 3 patients (3%), preferential thickening of the internal anal sphincter at the 6-o'clock position in 80 patients (80%) and the 12-o'clock position in 7 patients (7%), preferential thickening of the internal and external anal sphincters in 3 patients (3%), and thinning of the internal anal sphincter in 2 patients (2%). Chronic anal fissures cause differential thickening of both internal and external anal sphincters, with a trend toward increased thickness in relation to the site of the fissure. Routine preoperative transperineal sonography for patients with chronic anal fissures is recommended, and it is mandatory in high-risk patients. © 2014 by the American Institute of Ultrasound in Medicine.

Activating patients with chronic disease for self-management: comparison of self-managing patients with those managing by frequent readmissions to hospital.

PubMed

Kirby, Sue E; Dennis, Sarah M; Bazeley, Pat; Harris, Mark F

2013-01-01

Understanding the factors that activate people to self-manage chronic disease is important in improving uptake levels. If the many frequent hospital users who present with acute exacerbations of chronic disease were to self-manage at home, some hospital admissions would be avoided. Patient interview and demographic, psychological, clinical and service utilisation data were compared for two groups of patients with chronic disease: those attending self-management services and those who managed by using hospital services. Data were analysed to see whether there were differences that might explain the two different approaches to managing their conditions. The two groups were similar in terms of comorbidity, age, sex, home services, home support and educational level. Self-managing patients were activated by their clinician, accepted their disease, changed their identity, confronted emotions and learnt the skills to self-manage and avoid hospital. Patients who frequently used hospital services to manage their chronic disease were often in denial about their chronic disease, hung on to their identity and expressed little emotional response. However, they reported a stronger sense of coherence and rated their health more highly than self-managing patients. This study shed light on the process of patient activation for self-management. A better understanding of the process of patient activation would encourage clinicians who come into contact with frequently readmitted chronic disease patients to be more proactive in supporting self-management.

Patient-reported outcomes and health status associated with chronic graft-versus-host disease.

PubMed

Lee, Stephanie J; Onstad, Lynn; Chow, Eric J; Shaw, Bronwen E; Jim, Heather S L; Syrjala, Karen L; Baker, K Scott; Buckley, Sarah; Flowers, Mary E

2018-06-01

Chronic graft-versus-host disease occurs in 20-50% of allogeneic hematopoietic cell transplantation survivors. We surveyed patients about their quality of life, symptoms, health status, comorbid conditions and medication. Instruments included the Short-Form-36 (SF-36), the Patient-Reported Outcomes Measurement Information System (PROMIS) Global and PROMIS-29 scales and the Lee Chronic Graft-versus-Host Disease Symptom Scale. Functional status was measured by self-reported Karnofsky and work status. Of 3027 surveys sent to recipients surviving one or more years after transplantation, 1377 (45%) were returned. Among these, patients reported their chronic graft-versus-host disease was mild (n=257, 18.7%), moderate (n=110, 8.0%) or severe (n=25, 1.8%). Another 377 (27.4%) never had chronic graft-versus-host disease and 280 (20.3%) had chronic graft-versus-host disease but it resolved. We excluded 328 (23.8%) who did not answer the questions about chronic graft-versus-host disease. Patients who reported moderate or severe chronic graft-versus-host disease reported worse quality of life, lower performance status, a higher symptom burden and were more likely to be taking prescription medications for pain, anxiety and depression compared to those with resolved chronic graft-versus-host disease. Self-reported measures were similar between patients with resolved chronic graft-versus-host disease and those who never had it. Our data suggest that the PROMIS measures may be able to replace the SF-36 in chronic graft-versus-host disease assessment. Between 26.7-39.4% of people with active chronic graft-versus-host disease were unable to work due to health reasons, compared with 12.1% whose chronic graft-versus-host disease had resolved and 15.4% who never had chronic graft-versus-host disease. Mouth, eye and nutrition symptoms persisted after resolution of chronic graft-versus-host disease. These results show that better prevention of and treatment for chronic graft-versus-host disease is needed to improve survivorship after allogeneic transplantation. Copyright © 2018, Ferrata Storti Foundation.

Family functioning in families of first-episode psychosis patients as compared to chronic mentally ill patients and healthy controls.

PubMed

Koutra, Katerina; Triliva, Sofia; Roumeliotaki, Theano; Stefanakis, Zacharias; Basta, Maria; Lionis, Christos; Vgontzas, Alexandros N

2014-11-30

The present study aimed to investigate possible differences in family environment among patients experiencing their First Episode of Psychosis (FEP), chronic patients and controls. Family cohesion and flexibility (FACES-IV) and psychological distress (GHQ-28) were evaluated in families of 50 FEP and 50 chronic patients, as well as 50 controls, whereas expressed emotion (FQ) and family burden (FBS) were assessed in families of FEP and chronic patients. Multivariable linear regression analysis, adjusted for confounders, indicated impaired cohesion and flexibility for families of FEP patients compared to controls, and lower scores for families of chronic patients compared to those of FEP patients. Caregivers of chronic patients scored significantly higher in criticism, and reported higher burden and psychological distress than those of FEP patients. Our findings suggest that unbalanced levels of cohesion and flexibility, high criticism and burden appeared to be the outcome of psychosis and not risk factors triggering the onset of the illness. Furthermore, emotional over-involvement both in terms of positive (i.e. concern) and negative behaviors (i.e. overprotection) is prevalent in Greek families. Psychoeducational interventions from the early stages of the illness should be considered to promote caregivers' awareness regarding the patients' illness, which in turn, may ameliorate dysfunctional family interactions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Blood pool scintigraphy of the skull in relation to head-down tilt provocation in patients with chronic tension-type headache and controls.

PubMed

Hannerz, Jan; Schnell, P-O; Larsson, Stig; Jacobsson, Hans

2004-03-01

To investigate the mechanisms behind the increase of chronic tension-type headache during head-down tilt. The pathophysiology of chronic tension-type headache is unknown. Ten patients suffering from chronic tension-type headache and 10 age- and sex-matched controls were studied with respect to pain intensity and alterations in cranial blood volume using planar scintigraphy and radiolabeled autologous erythrocytes before, during, and after head-down tilt, a procedure known to increase chronic tension-type headache. Four of 8 patients with chronic tension-type headache studied had increased cerebrospinal fluid pressure. During head-down tilt, the pain increased significantly in the group with chronic tension-type headache (P <.001) while the procedure did not cause headache in the controls. Blood volume significantly increased extracranially and decreased intracranially in both groups during head-down tilt. The extracranial nasal blood volume was significantly related to the pain experienced by the patients with chronic tension-type headache before and during head-down tilt. Although the changes in blood volume and, presumably, the increase of intracranial pressure were similar in the patients with chronic tension-type headache and the controls, only the patients experienced pain and pain increase during head-down tilt. This indicates that the pre-head-down tilt conditions must be different in the 2 groups and should be related to increased cerebrospinal fluid pressure/intracranial venous pressure in patients with chronic tension-type headache compared with controls. A difference in central mechanisms may, however, also be of importance for the difference in headache provocation in the 2 groups during head-down tilt.

Hospital discharges and patient activity associated with chronic pancreatitis in Ireland 2009-2013.

PubMed

Ní Chonchubhair, Hazel M; Bashir, Yasir; McNaughton, David; Barry, Joseph M; Duggan, Sinead N; Conlon, Kevin C

To investigate trends in acute public hospital patient discharges in Ireland, to analyse hospital discharge activity for geographical variations, aetiological differences, and to estimate a national prevalence for chronic pancreatitis. We performed a nationwide retrospective study of all in-patient discharges from acute public hospitals in Ireland, participating in the Hospital In-Patient Enquiry (HIPE) reporting system. We searched for International Classification of Disease, Tenth Revision, Australian Modification (ICD-10-AM) codes K86.0 alcohol-induced chronic pancreatitis, and K86.1 other chronic pancreatitis, and data were extracted for the years 2009-2013. There were 4098 emergency admissions for any aetiology chronic pancreatitis during the 5 year study period. Total discharges ranged from 753 in 2009 to 999 in 2013. Total patients ranged from 530 in 2009 to 601 in 2013. Prevalence of chronic pancreatitis is estimated at 11.6 per 100,000 to 13.0 per 100,000 over the five years. 'Other aetiology chronic pancreatitis' discharges were almost double that of 'alcohol chronic pancreatitis'. We found notable geographical variation in hospital discharge activity for chronic pancreatitis. We report a prevalence which is similar to those worldwide studies who adopted a similar methodology utilising exact counts of patients. Our data are an underestimated as they are based on in-patient discharges only, excluding those attending primary care, outpatient or emergency room visits without admission. Despite studying this disease in a population with high per capita alcohol consumption, we report almost twice as many discharges for non-alcohol aetiology chronic pancreatitis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

[Retrospective statistical analysis of clinical factors of recurrence in chronic subdural hematoma: correlation between univariate and multivariate analysis].

PubMed

Takayama, Motoharu; Terui, Keita; Oiwa, Yoshitsugu

2012-10-01

Chronic subdural hematoma is common in elderly individuals and surgical procedures are simple. The recurrence rate of chronic subdural hematoma, however, varies from 9.2 to 26.5% after surgery. The authors studied factors of the recurrence using univariate and multivariate analyses in patients with chronic subdural hematoma We retrospectively reviewed 239 consecutive cases of chronic subdural hematoma who received burr-hole surgery with irrigation and closed-system drainage. We analyzed the relationships between recurrence of chronic subdural hematoma and factors such as sex, age, laterality, bleeding tendency, other complicated diseases, density on CT, volume of the hematoma, residual air in the hematoma cavity, use of artificial cerebrospinal fluid. Twenty-one patients (8.8%) experienced a recurrence of chronic subdural hematoma. Multiple logistic regression found that the recurrence rate was higher in patients with a large volume of the residual air, and was lower in patients using artificial cerebrospinal fluid. No statistical differences were found in bleeding tendency. Techniques to reduce the air in the hematoma cavity are important for good outcome in surgery of chronic subdural hematoma. Also, the use of artificial cerebrospinal fluid reduces recurrence of chronic subdural hematoma. The surgical procedures can be the same for patients with bleeding tendencies.

The development of a community and home-based chronic care management program for older adults.

PubMed

Cooper, Jennifer; McCarter, Kathryn A

2014-01-01

The objective of this paper was to evaluate a chronic care management program piloted by a visiting nurses association. Desired outcomes were to increase nurses' knowledge of self-management of chronic conditions and improve patient self-efficacy and clinical measures. The program provided educational development for nurses and piloted encounters with patients with chronic conditions targeting community health nurses for a chronic care professional (CCP) certification and invited 300 faith community nurses to an education program on chronic condition(s). Thirteen patients with chronic condition(s) were enrolled. Chronic care professional modules were used to increase nurses' knowledge and were measured by successful completion of a certification exam. Faith community nurses participated in an education program and completed a posttest to measure knowledge of content. Patient improvement in self-management was measured by pre- and postintervention self-efficacy scores and clinical measures. Seventeen nurses successfully completed the exam, and 38 faith community nurses participated in the program and completed the posttest. Three patients showed improvement in self-efficacy scores and eight in clinical measures. The educational development of community nurses prepared them to provide effective encounters to improve self-efficacy and clinical outcomes for older adults with chronic conditions. © 2013 Wiley Periodicals, Inc.

Health-related quality of life and health care use in cancer survivors compared with patients with chronic diseases.

PubMed

Heins, Marianne J; Korevaar, Joke C; Hopman, Petra E P C; Donker, Gé A; Schellevis, François G; Rijken, Mieke P M

2016-03-15

The number of cancer survivors is steadily increasing and these patients often experience long-lasting health problems. To make care for cancer survivors sustainable for the future, it would be relevant to put the effects of cancer in this phase into perspective. Therefore, the authors compared health-related quality of life (HRQOL) and health care use among cancer survivors with that of patients with chronic diseases. Patients diagnosed at age >18 years with a cancer with a 5-year survival rate > 20% and no distant metastases at the time of diagnosis and patients aged >18 years with physician-diagnosed somatic chronic diseases without cancer were sent a questionnaire. HRQOL was measured with the RAND-36, a measure of HRQOL. Self-reported health care use was measured for general practitioner care, specialist care, rehabilitative care, physical therapy, ambulatory mental health care, and occupational health care. A total of 601 cancer survivors and 1052 patients with chronic diseases without cancer were included in the current study. Multimorbidity was observed in 63% of the cancer survivors and 61% of the patients with chronic diseases. The HRQOL of the cancer survivors was significantly better than that of patients with chronic diseases after adjustment for age and sex. For the mental functioning subscale, no significant differences were found between the 2 groups. Cancer survivors were found to be less likely to have visited a general practitioner or cardiologist compared with patients with chronic diseases. When considering physical HRQOL and health care use, cancer survivors appear to fare better than the average patient with chronic diseases. No difference in mental functioning was observed in the current study. © 2016 American Cancer Society.

Patients, persons or partners? Involving those with chronic disease in their care.

PubMed

McWilliam, Carol L

2009-12-01

Self-care management is essential for effective chronic disease management. Yet prevailing approaches of healthcare practitioners often undermine the efforts of those who require on-going medical attention for chronic conditions, emphasizing their status as patients, failing to consider their larger life experience as people, and most importantly, failing to consider them as people with the potential to be partners in their care. This article explores two approaches for professional-patient interaction in chronic disease management, namely, patient-centred care and empowering partnering, illuminating how professionals might better interact with chronically ill individuals who seek their care. The opportunities, challenges, theory and research evidence associated with each approach are explored. The advantages of moving beyond patient-centred care to the empowering partnering approach are elaborated. For people with chronic disease, having the opportunity to engage in the social construction of their own health as a resource for everyday living, the opportunity to experience interdependence rather than dependence/independence throughout on-going healthcare, and the opportunity to optimize their potential for self-care management of chronic disease are important justifications for being involved in an empowering partnering approach to their chronic disease management.

[Evaluation of a chronic fatigue in patients with moderate-to-severe chronic heart failure].

PubMed

Jasiukeviciene, Lina; Vasiliauskas, Donatas; Kavoliūniene, Ausra; Marcinkeviciene, Jolanta; Grybauskiene, Regina; Grizas, Vytautas; Tumyniene, Vida

2008-01-01

To evaluate the chronic fatigue and its relation to the function of hypothalamus-pituitary-adrenal axis in patients with New York Heart Association (NYHA) functional class III-IV chronic heart failure. A total of 170 patients with NYHA functional class III-IV chronic heart failure completed MFI-20L, DUFS, and DEFS questionnaires assessing chronic fatigue and underwent echocardiography. Blood cortisol concentration was assessed at 8:00 am and 3:00 pm, and plasma N-terminal brain natriuretic pro-peptide (NT-proBNP) concentration was measured at 8:00 am. Neurohumoral investigations were repeated before cardiopulmonary exercise test and after it. The results of all questionnaires showed that 100% of patients with NYHA functional class III-IV heart failure complained of chronic fatigue. The level of overall fatigue was 54.5+/-31.5 points; physical fatigue - 56.8+/-24.6 points. Blood cortisol concentration at 8:00 am was normal (410.1+/-175.1 mmol/L) in majority of patients. Decreased concentration was only in four patients (122.4+/-15.5 mmol/L); one of these patients underwent heart transplantation. In the afternoon, blood cortisol concentration was insufficiently decreased (355.6+/-160.3 mmol/L); reaction to a physical stress was attenuated (Delta 92.9 mmol/L). Plasma NT-proBNP concentration was 2188.9+/-1852.2 pg/L; reaction to a physical stress was diminished (Delta 490.3 pg/L). All patients with NYHA class III-IV heart failure complained of daily chronic fatigue. Insufficiently decreased blood cortisol concentration in the afternoon showed that in the presence of chronic fatigue in long-term cardiovascular organic disease, disorder of a hypothalamus-pituitary-adrenal axis is involved.

Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort.

PubMed

Henkle, Emily; Lu, Mei; Rupp, Lora B; Boscarino, Joseph A; Vijayadeva, Vinutha; Schmidt, Mark A; Gordon, Stuart C

2015-02-15

Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Thermo spectral analysis (TSA) of living human skin by FT-IR -Development of a diagnostic method for the early detection of chronic diseases

NASA Astrophysics Data System (ADS)

Folberth, W.; Heim, G.

1985-12-01

A Fourier spectrometer was used in order to measure the spectral emissivity E(k) of human skin in the FIR region k=190-420 cm-1. Three studies on patient groups with defined chronic diseases have been performed: patients with untreated bronchial carcinoma, patients with rheumatic arthritis and patients with chronic renal insufficiency. In comparison with a symptomfree control group all patient groups show significant differences in E(k). As result of a discriminant analysis a separation of 95.7% between carcinoma patients and control persons is possible. The separation quotes between the other groups indicate that patients with malignant neoplasms can be discriminated from other chronically ill persons.

Low serum uric acid levels in chronic insomnia patients: A case-control study.

PubMed

Zhao, Kai; Luan, Xiaoqian; Liu, Zhihua; Zhu, Zhuoying; Chen, Huijun; Shen, Huiping; Cai, Yan; Qiu, Huihua; Wang, Qiongzhang; Gu, Yingying; Zhu, Lin; He, Jincai

2017-09-14

Recent studies have demonstrated the presence of oxidative stress in insomnia patients. Uric acid (UA) is regarded as one of the most important antioxidants that may attenuate oxidative stress. The aim of our study was to investigate whether there is an alteration of serum UA levels in chronic insomnia patients. The association between sleep quality and serum UA in chronic insomnia patients was also investigated. We recruited 300 chronic insomnia patients and 300 age- and gender-matched normal controls. The uricase-PAP method was used to measure the concentration of UA both in patient and normal control subjects. The Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality of chronic insomniac participants. As a result, significantly lower serum UA levels were observed in patients with chronic insomnia when compared with normal control subjects (279.56±65.80 vs. 299.10±61.17μmol/L, t=-3.991, p<0.001). Low serum UA levels were correlated with high PSQI scores in multiple linear regression models (β=-0.322, p<0.001). Our results suggested that low serum UA levels were associated with the presence and severity of chronic insomnia. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of consumer-centered u-health service for the knowledge, skill, and attitude of the patients with chronic obstructive pulmonary disease.

PubMed

Kim, Jeongeun; Kim, Sukwha; Kim, Hee-Chan; Kim, Kyung-Hwan; Yang, Seok-Chul; Lee, Choon-Taek; Kong, Hyoun-Joong; Lee, Kyungsoon

2012-12-01

Through the use of ubiquitous health, or u-Health, services, medical information can be adapted and made accessible via computer and Internet to provide quality healthcare to anybody, any place, and any time. We developed and implemented u-Health services for patients with chronic obstructive pulmonary disease and studied their experiences with respect to their knowledge of chronic obstructive pulmonary disease and skill and attitude toward the u-Health devices. The u-Health services were composed of telemonitoring and teleconsultation supplemented with home visits. To determine its effectiveness, the u-Health service system was implemented for 2 years with 144 chronic obstructive pulmonary disease patients in a clinical experiment. The subjects were divided into three experimental groups, each provided with different services, compared before and after intervention, and among groups. The analysis of data gathered through the system suggested that u-Health services can support patients with chronic obstructive pulmonary disease, improve patients' knowledge about chronic obstructive pulmonary disease self-management, build u-Health device usage skills, and foster a positive attitude toward u-Health devices. The u-Health services for the chronic obstructive pulmonary disease patients were both feasible and effective from the patients' perspective.

Impact of the Chronic Care Model on medication adherence when patients perceive cost as a barrier.

PubMed

Mackey, Katherine; Parchman, Michael L; Leykum, Luci K; Lanham, Holly J; Noël, Polly H; Zeber, John E

2012-07-01

Cost burdens represent a significant barrier to medication adherence among chronically ill patients, yet financial pressures may be mitigated by clinical or organizational factors, such as treatment aligned with the Chronic Care Model (CCM). This study examines how perceptions of chronic illness care attenuate the relationship between adherence and cost burden. Surveys were administered to patients at 40 small community-based primary care practices. Medication adherence was assessed using the 4-item Morisky scale, while five cost-related items documented recent pharmacy restrictions. CCM experiences were assessed via the 20-item Patient Assessment of Chronic Illness Care (PACIC). Nested random effects models determined if chronic care perceptions modified the association between medication adherence and cost-related burden. Of 1823 respondents reporting diabetes and other chronic diseases, one-quarter endorsed intrapersonal adherence barriers, while 23% restricted medication due of cost. Controlling for age and health status, the relationship between medication cost and CCM with adherence was significant; including PACIC scores attenuated cost-related problems patients with adequate or problematic adherence behavior. Patients experiencing treatment more consistent with the CCM reported better adherence and lower cost-related burden. Fostering highly activated patients and shared clinical decision making may help alleviate medication cost pressures and improve adherence. Published by Elsevier Ltd.

Patient and Disease Characteristics Associated with Activation for Self-Management in Patients with Diabetes, Chronic Obstructive Pulmonary Disease, Chronic Heart Failure and Chronic Renal Disease: A Cross-Sectional Survey Study

PubMed Central

Bos-Touwen, Irene; Schuurmans, Marieke; Monninkhof, Evelyn M.; Korpershoek, Yvonne; Spruit-Bentvelzen, Lotte; Ertugrul-van der Graaf, Inge; de Wit, Niek; Trappenburg, Jaap

2015-01-01

A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions. To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending. A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD). Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants. Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier. In addition, we identified determinants associated with low activation for self-management using logistic regression analysis. We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients. Mean age was 69.6±10.9. Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%. All associations, except for social support, were disease transcending. This study explored factors associated with varying levels of activation for self-management. These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management. Increased scientific efforts are needed to explain the greater part of the factors that contribute to the complex nature of patient activation for self-management. PMID:25950517

Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care.

PubMed

Darbishire, L; Ridsdale, L; Seed, P T

2003-06-01

Chronic fatigue syndrome (CFS) has been defined, but many more patients consult in primary care with chronic fatigue that does not meet the criteria for CFS. General practitioners (GPs) do not generally use the CFS diagnosis, and have some doubt about the validity of CFS as an illness. To describe the proportion of patients consulting their GP for fatigue that met the criteria for CFS, and to describe the social, psychological, and physical differences between patients with CFS and those with non-CFS chronic fatigue in primary care. Baseline data from a trial of complex interventions for fatigue in primary care. Twenty-two general practices located in London and the South Thames region of the United Kingdom recruited patients to the study between 1999 and 2001. One hundred and forty-one patients who presented to their GP with unexplained fatigue lasting six months or more as a main symptom were recruited, and the Centers for Disease Control (CDC) case definition was applied to classify CFS. Approximately two-thirds (69%) of patients had chronic fatigue and not CFS. The duration of fatigue (32 months) and perceived control over fatigue were similar between groups; however, fatigue, functioning, associated symptoms, and psychological distress were more severe in the patients in the CFS group, who also consulted their GP significantly more frequently, were twice as likely to be depressed, and more than twice as likely to be unemployed. About half (CFS = 50%; chronic fatigue = 55%) in each group attributed their fatigue to mainly psychological causes. In primary care, CFS is a more severe illness than chronic fatigue, but non-CFS chronic fatigue is associated with significant fatigue and is reported at least twice as often. That half of patients, irrespective of CFS status, attribute their fatigue to psychological causes, more than is observed in secondary care, indicates an openness to the psychological therapies provided in that setting. More evidence on the natural history of chronic fatigue and CFS in primary care is required, as are trials of complex interventions. The results may help determine the usefulness of differentiating between chronic fatigue and CFS.

Temsirolimus and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

ClinicalTrials.gov

2013-01-11

Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia

[The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study: To better understand chronic kidney disease].

PubMed

Stengel, Bénédicte; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Édouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Pisoni, Ron L; Robinson, Bruce M; Massy, Ziad A

2016-04-01

Preserving kidney function and improving the transition from chronic kidney disease to end stage is a research and healthcare challenge. The national Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort was established to identify the determinants, biomarkers and practice patterns associated with chronic kidney disease outcomes. The study will include more than 3000 adult patients with moderate to advanced chronic kidney disease from a representative sample of 40 nephrology clinics with respect to regions and legal status, public or private. Patients are recruited during a routine visit and followed for 5 years, before and after starting renal replacement therapy. Patient-level clinical, biological, and lifestyle data are collected annually, as well as provider-level data on clinical practices, coordinated with the International Chronic Kidney Disease Outcomes and Practice Pattern Study. Blood and urine samples are stored in a biobank. Major studied outcomes include survival, patient-reported outcomes, disease progression and hospitalizations. More than 13,000 eligible patients with chronic kidney disease were identified, 60% with stage 3 and 40% with stage 4. Their median age is 72 years [interquartile range, 62-80 years], 60% are men and 38% have diabetes. By the end of December 2015, 2885 patients were included. The CKD-REIN cohort will serve to improve our understanding of chronic kidney disease and provide evidence to improve patient survival and quality of life as well as health care system performances. Copyright © 2016 Association Société de néphrologie. All rights reserved.

Mitochondrial DNA deletions in patients with chronic suppurative otitis media.

PubMed

Tatar, Arzu; Tasdemir, Sener; Sahin, Ibrahim; Bozoglu, Ceyda; Erdem, Haktan Bagis; Yoruk, Ozgur; Tatar, Abdulgani

2016-09-01

The aim of this study was to investigate the 4977 and 7400 bp deletions of mitochondrial DNA in patients with chronic suppurative otitis media and to indicate the possible association of mitochondrial DNA deletions with chronic suppurative otitis media. Thirty-six patients with chronic suppurative otitis media were randomly selected to assess the mitochondrial DNA deletions. Tympanomastoidectomy was applied for the treatment of chronic suppurative otitis media, and the curettage materials including middle ear tissues were collected. The 4977 and 7400 bp deletion regions and two control regions of mitochondrial DNA were assessed by using the four pair primers. DNA was extracted from middle ear tissues and peripheral blood samples of the patients, and then polymerase chain reactions (PCRs) were performed. PCR products were separated in 2 % agarose gel. Seventeen of 36 patients had the heterozygote 4977 bp deletion in the middle ear tissue but not in peripheral blood. There wasn't any patient who had the 7400 bp deletion in mtDNA of their middle ear tissue or peripheral blood tissue. The patients with the 4977 bp deletion had a longer duration of chronic suppurative otitis media and a higher level of hearing loss than the others (p < 0.01). Long time chronic suppurative otitis media and the reactive oxygen species can cause the mitochondrial DNA deletions and this may be a predisposing factor to sensorineural hearing loss in chronic suppurative otitis media. An antioxidant drug as a scavenger agent may be used in long-term chronic suppurative otitis media.

Reduction of cervical and respiratory muscle strength in patients with chronic nonspecific neck pain and having moderate to severe disability.

PubMed

López-de-Uralde-Villanueva, Ibai; Sollano-Vallez, Ernesto; Del Corral, Tamara

2017-06-11

To investigate whether patients with chronic nonspecific neck pain and having moderate to severe disability have a greater cervical motor function impairment and respiratory disturbances compared with patients with chronic nonspecific neck pain having mild disability and asymptomatic subjects; and the association between these outcomes in patients with chronic nonspecific neck pain and healthy controls. Cross-sectional study, 44 patients with chronic nonspecific neck pain and 31 healthy subjects participated. The neck disability index was used to divide the patients into 2 groups: 1) mild disability group (scores between 5 and 14 points); and 2) moderate to severe disability group (scores >14 points). Cervical motor function was measured by cervical range of motion, forward head posture, neck flexor, and extensor muscle strength. Respiratory function and maximum respiratory pressures were also measured. Statistically differences were found between the patients with chronic nonspecific neck pain having a moderate to severe disability and the asymptomatic subjects for cervical and respiratory muscle strength. Comparisons between chronic nonspecific neck pain and the asymptomatic groups showed differences for all the variables, except for forward head posture. The regression model determined that strength of cervical flexion explained 36.4 and 45.6% of the variance of maximum inspiratory pressures and maximum expiratory pressures, respectively. Only the chronic nonspecific neck pain group with moderate to severe disability showed differences compared with the healthy subjects. Neck muscle strength could be a good predictor of respiratory muscle function. Implications for rehabilitation Neck pain severity could be closely associated with decreased respiratory pressure in patients with chronic nonspecific neck pain. These findings suggest a new therapeutic approach for patients with moderate to severe disability, such as respiratory muscle training. The regression models show that a simple measurement of neck muscle strength could provide a reasonably accurate prediction for the respiratory function of these patients. Hence, this could provide an easy tool to assess respiratory function to physiotherapists without the need for sophisticated instrumentation.

Effect of Chronic Kidney Diseases on Mortality among Digoxin Users Treated for Non-Valvular Atrial Fibrillation: A Nationwide Register-Based Retrospective Cohort Study.

PubMed

Sessa, Maurizio; Mascolo, Annamaria; Andersen, Mikkel Porsborg; Rosano, Giuseppe; Rossi, Francesco; Capuano, Annalisa; Torp-Pedersen, Christian

2016-01-01

This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin. All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription. We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription. This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation.

The increased risk of globus pharyngeus in patients with chronic thyroiditis: a case control study.

PubMed

Karahatay, S; Ayan, A; Aydin, U; Ince, S; Emer, O; Alagoz, E

2015-12-01

A correlation between globus pharyngeus and thyroid gland inflammation has been mentioned in previous studies. However, the potential risk of globus pharyngeus in chronic thyroiditis patients has not been shown so far. The aim of this study is to investigate a possible association between chronic thyroiditis and globus pharyngeus. The study was performed in an ultrasound (US) center of a tertiary health care institution. Ninety-two patients who were under examination for suspected thyroid pathologies or undergoing follow-up for a previously diagnosed thyroid disease were enrolled in the study. The patients were divided into two groups according to the existence of globus symptoms. Subsequently, all patients underwent high-resolution thyroid ultrasounds. The patients whose ultrasound findings were suggestive of chronic thyroiditis constituted the second subgroup. The demographic data of the patients and other ultrasound findings including the volume of the thyroid glands and nodules, if any, were noted as well. Sixty-seven female (73%) and 25 male (27%) patients were enrolled in the study. Thirty-two (35%) of the 92 patients constituted the globus pharyngeus group according to their responses to the questionnaire and the US findings were concordant with chronic thyroiditis in 36 (39%) patients. The correlation between chronic thyroiditis and globus sensation was significant (p = 0.004), and the odds ratio was calculated as 3.7 (95% CI = 1.5-9.11). Other parameters including age, sex, thyroid volume and nodule status were not significantly related to globus pharyngeus in this particular patient series. In the presented study, the risk of globus pharyngeus occurrence was calculated as 3.7-fold higher in patients with chronic thyroiditis. Being a preliminary report, it is necessary to confirm this finding and understand the pathophysiological mechanism via further investigations with a larger patient series.

Risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patient with component of metabolic syndrome.

PubMed

Cai, Shaohang; Ou, Zejin; Liu, Duan; Liu, Lili; Liu, Ying; Wu, Xiaolu; Yu, Tao; Peng, Jie

2018-05-01

We investigated whether metabolic syndrome exacerbated the risk of liver fibrosis among chronic hepatitis B patients and risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patients with components of metabolic syndrome. This study included 1236 chronic hepatitis B patients with at least one component of metabolic syndrome. The controlled attenuation parameter and liver stiffness, patient information and relevant laboratory data were recorded. Controlled attenuation parameter was increased progressively with the number of metabolic syndrome components ( p  < 0.001). Multivariate analysis indicated younger age, high gamma-glutamyltransferase level, high waist-hip ratio, and high body mass index were independent risk factors associated with nonalcoholic fatty liver disease among chronic hepatitis B patients with metabolic syndrome. In the fibrosis and non-fibrosis groups, most of blood lipid was relatively lower in fibrosis group. An increased proportion of chronic hepatitis B patients with liver fibrosis was found concomitant with an increasing number of components of metabolic syndrome. Male gender, older age, smoking, aspartate aminotransferase levels, high body mass index, and low platelet level were identified as independent risk factors associated with liver fibrosis. For chronic hepatitis B patients with coexisting components of metabolic syndrome, stratification by independent risk factors for nonalcoholic fatty liver disease and fibrosis can help with management of their disease.

Using an electronic self-management tool to support patients with chronic kidney disease (CKD): a CKD clinic self-care model.

PubMed

Ong, Stephanie W; Jassal, Sarbjit V; Porter, Eveline; Logan, Alexander G; Miller, Judith A

2013-01-01

New healthcare delivery models are needed to enhance the patient experience and improve quality of care for individuals with chronic conditions such as kidney disease. One potential avenue is to implement self-management strategies. There is growing evidence that self-management interventions help optimize various aspects of chronic disease management. With the increasing use of information technology (IT) in health care, chronic disease management programs are incorporating IT solutions to support patient self-management practices. IT solutions have the ability to promote key principles of self-management, namely education, empowerment, and collaboration. Positive clinical outcomes have been demonstrated for a number of chronic conditions when IT solutions were incorporated into self-management programs. There is a paucity of evidence for self-management in chronic kidney disease (CKD) patients. Furthermore, IT strategies have not been tested in this patient population to the same extent as other chronic conditions (e.g., diabetes, hypertension). Therefore, it is currently unknown if IT strategies will promote self-management behaviors and lead to improvements in overall patient care. We designed and developed an IT solution called My KidneyCare Centre to support self-management strategies for patients with CKD. In this review, we discuss the rationale and vision of incorporating an electronic self-management tool to support the care of patients with CKD. © 2013 Wiley Periodicals, Inc.

Beyond fighting fires and chasing tails? Chronic illness care plans in Ontario, Canada.

PubMed

Russell, Grant; Thille, Patricia; Hogg, William; Lemelin, Jacques

2008-01-01

Recent work has conceptualized new models for the primary care management of patients with chronic illness. This study investigated the experience of family physicians and patients with a chronic illness management initiative that involved the joint formulation of comprehensive individual patient care plans. A qualitative evaluation, framed by phenomenology, immediately followed a randomized controlled trial examining the effect of external facilitators in enhancing the delivery of chronic condition care planning in primary care. The study, set in Ontario family practices, used semistructured in-depth interviews with a purposive sample of 13 family physicians, 20 patients, and all 3 study facilitators. Analysis used independent transcript review and constant comparative methods. Despite the intervention being grounded in patient-centered principles, family physicians generally viewed chronic illness management from a predominantly biomedical perspective. Only a few enthusiasts viewed systematic care planning as a new approach to managing patients with chronic illness. Most family physicians found the strategy to be difficult to implement within existing organizational and financial constraints. For these participants, care planning conflicted with preexisting concepts of their role and of their patient's abilities to become partners in care. The few patients who noticed the process spoke favorably about their experience. Although the experiences of the enthusiastic family physicians were encouraging, we found important individual-level barriers to chronic illness management in primary care. These issues seemed to transcend existing organizational and resource constraints.

Chronic pain and difficulty in relaxing postural muscles in patients with fibromyalgia and chronic whiplash associated disorders.

PubMed

Elert, J; Kendall, S A; Larsson, B; Månsson, B; Gerdle, B

2001-06-01

To investigate if muscle tension according to the surface electromyogram (EMG) of the shoulder flexors is increased in consecutive patients with fibromyalgia (FM) or chronic whiplash associated disorders (WAD). A total of 59 consecutive patients with FM (n = 36) or chronic WAD (n = 23) performed 100 maximal isokinetic contractions combined with surface electromyography of the trapezius and infraspinatus. A randomized group of pain-free female (n = 27) subjects served as control group. Peak torque initially (Pti) and absolute and relative peak torque at endurance level (PTe, PTer) were registered as output variables, together with the EMG level of unnecessary muscle tension, i.e., the signal amplitude ratio (SAR). The patient groups had a higher level of unnecessary tension initially and at the endurance level. The patients had lower absolute output (PTi and PTe), but the relative levels (PTer) did not differ comparing all 3 groups. Subjects with FM had significantly higher body mass index (BMI) than the other groups. BMI did not influence the SAR but correlated positively with PTi. The results confirmed earlier findings that groups of patients with chronic pain have increased muscle tension and decreased output during dynamic activity compared to pain-free controls. However, the results indicated there is heterogeneity within groups of patients with the same chronic pain disorder and that not all patients with chronic pain have increased muscle tension.

Hospital readmissions for COPD: a retrospective longitudinal study.

PubMed

Harries, Timothy H; Thornton, Hannah; Crichton, Siobhan; Schofield, Peter; Gilkes, Alexander; White, Patrick T

2017-04-27

Prevention of chronic obstructive pulmonary disease hospital readmissions is an international priority aimed to slow disease progression and limit costs. Evidence of the risk of readmission and of interventions that might prevent it is lacking. We aimed to determine readmission risk for chronic obstructive pulmonary disease, factors influencing that risk, and variation in readmission risk between hospitals across 7.5 million people in London. This retrospective longitudinal observational study included all chronic obstructive pulmonary disease admissions to any hospital in the United Kingdom among patients registered at London general practices who had emergency National Health Service chronic obstructive pulmonary disease hospital admissions between April 2006 and March 2010. Influence of patient characteristics, geographical deprivation score, length of stay, day of week of admission or of discharge, and admitting hospital, were assessed using multiple logistic regression. 38,894 chronic obstructive pulmonary disease admissions of 20,932 patients aged ≥ 45 years registered with London general practices were recorded. 6295 patients (32.2%) had at least one chronic obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%) were readmitted within 30 days and 3471 patients (17.8%) were readmitted within 90 days. Age and patient geographical deprivation score were very weak predictors of readmission. Rates of chronic obstructive pulmonary disease readmissions within 30 days and within 90 days did not vary among the majority of hospitals. The finding of lower chronic obstructive pulmonary disease readmission rates than was previously estimated and the limited variation in these rates between hospitals suggests that the opportunity to reduce chronic obstructive pulmonary disease readmission risk is small. LOWER RISK OF READMISSION FOR LONDON-BASED PATIENTS: A managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed. Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs. However, few data are available to determine and ultimately reduce the risk of readmission. Timothy Harries at King's College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010. They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days. Neither age nor geographical deprivation were useful predictors of readmission. These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further.

CXCL9, a promising biomarker in the diagnosis of chronic Q fever.

PubMed

Jansen, Anne F M; Schoffelen, Teske; Textoris, Julien; Mege, Jean-Louis; Nabuurs-Franssen, Marrigje; Raijmakers, Ruud P H; Netea, Mihai G; Joosten, Leo A B; Bleeker-Rovers, Chantal P; van Deuren, Marcel

2017-08-09

In the aftermath of the largest Q fever outbreak in the world, diagnosing the potentially lethal complication chronic Q fever remains challenging. PCR, Coxiella burnetii IgG phase I antibodies, CRP and 18 F-FDG-PET/CT scan are used for diagnosis and monitoring in clinical practice. We aimed to identify and test biomarkers in order to improve discriminative power of the diagnostic tests and monitoring of chronic Q fever. We performed a transcriptome analysis on C. burnetii stimulated PBMCs of 4 healthy controls and 6 chronic Q fever patients and identified genes that were most differentially expressed. The gene products were determined using Luminex technology in whole blood samples stimulated with heat-killed C. burnetii and serum samples from chronic Q fever patients and control subjects. Gene expression of the chemokines CXCL9, CXCL10, CXCL11 and CCL8 was strongly up-regulated in C. burnetii stimulated PBMCs of chronic Q fever patients, in contrast to healthy controls. In whole blood cultures of chronic Q fever patients, production of all four chemokines was increased upon C. burnetii stimulation, but also healthy controls and past Q fever individuals showed increased production of CXCL9, CXCL10 and CCL8. However, CXCL9 and CXCL11 production was significantly higher for chronic Q fever patients compared to past Q fever individuals. In addition, CXCL9 serum concentrations in chronic Q fever patients were higher than in past Q fever individuals. CXCL9 protein, measured in serum or as C. burnetii stimulated production, is a promising biomarker for the diagnosis of chronic Q fever.

Assessing the effect of chronic oedema with associated ulceration.

PubMed

Hunter, Megan

2015-10-01

Chronic oedema is a common problem in the UK and, given the country's ageing population, the numbers are predicted to rise. In an epidemiological study carried out in Derby, England, researchers found the prevalence of chronic oedema to be 3.99 in every 1000 people, with the prevalence increasing to 10.31 in those aged 65-74 years. Often, patients with untreated chronic oedema will develop an ulceration that can lead to further costs and hospital admissions. The cost of treating chronic wounds has been estimated at £2.3 billion-£3.1 billion a year. It is therefore surprising that given the number of patients living with these problems, there is still a lack of knowledge and skill among nurses when assessing patients with chronic oedema and associated ulceration. This article offers advice for nurses when assessing leg ulcers in patients with chronic oedema, detailing the visual skin changes most frequently seen in these patients. The article also discusses some of the treatment options available, briefly covering the advantages and disadvantages of each option.

Giving patients responsibility or fostering mutual response-ability: family physicians' constructions of effective chronic illness management.

PubMed

Thille, Patricia H; Russell, Grant M

2010-10-01

Current visions of family medicine and models of chronic illness management integrate evidence-based medicine with collaborative, patient-centered care, despite critiques that these constructs conflict with each other. With this potential conflict in mind, we applied a critical discursive psychology methodology to present discursive patterns articulated by 13 family physicians in Ontario, Canada, regarding care of patients living with multiple chronic illnesses. Physicians constructed competing versions of the terms "effective chronic illness management" and "patient involvement." One construction integrated individual responsibility for health with primacy of "evidence," resulting in a conceptualization consistent with paternalistic care. The second constructed effective care as involving active partnership of physician and patient, implying a need to foster the ability of both practitioners and patients to respond to complex challenges as they arose. The former pattern is inconsistent with visions of family medicine and chronic illness management, whereas the latter embodies it.

Psychogenic nonepileptic seizures and chronic pain: a retrospective case-controlled study.

PubMed

Gazzola, Deana M; Carlson, Chad; Rugino, Angela; Hirsch, Scott; Starner, Karen; Devinsky, Orrin

2012-12-01

Psychogenic nonepileptic seizures (PNES) can be challenging to diagnose, but certain clinical features can help to distinguish PNES from epileptic seizures. The purpose of this study is to assess chronic pain and prescribed pain medication use in PNES patients. A case-controlled, retrospective analysis was performed examining pain medication use in 85 PNES patients versus an active control group of 85 patients with idiopathic generalized epilepsy (IGE). Chronic pain was more frequent among PNES patients (N=40) than active controls (N=10) (p<0.0001). Reported use of prescription pain medication was higher among PNES patients (N=20) versus active controls (N=6) (p=0.0048). The Positive Predictive Value of prescription pain medications for PNES patients was 76.9%. Opioid use in the PNES population was higher compared with active controls (p=0.0096). When excluding patients with a dual diagnosis of PNES and epilepsy from the latter two analyses and comparing these results to those that included this patient population, no statistically significant difference in results was found. Patients with PNES are more likely than those with IGE to report chronic pain disorders. A history of chronic pain and opioid use among patients with seizures raises the possibility of PNES. Among patients with PNES and chronic pain, a psychogenic etiology for pain and non-opiate pain management strategies should be considered. Copyright © 2012 Elsevier Inc. All rights reserved.

Cell Penetrating Peptides and Cationic Antibacterial Peptides

PubMed Central

Rodriguez Plaza, Jonathan G.; Morales-Nava, Rosmarbel; Diener, Christian; Schreiber, Gabriele; Gonzalez, Zyanya D.; Lara Ortiz, Maria Teresa; Ortega Blake, Ivan; Pantoja, Omar; Volkmer, Rudolf; Klipp, Edda; Herrmann, Andreas; Del Rio, Gabriel

2014-01-01

Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs. PMID:24706763

The role of disease management programs in the health behavior of chronically ill patients.

PubMed

Cramm, Jane Murray; Adams, Samantha A; Walters, Bethany Hipple; Tsiachristas, Apostolos; Bal, Roland; Huijsman, Robbert; Rutten-Van Mölken, Maureen P M H; Nieboer, Anna Petra

2014-04-01

Investigate the effects of disease management program (DMP) implementation on physical activity, smoking, and physical quality of life among chronically ill patients. This study used a mixed-methods approach involving qualitative (35 interviews with project managers) and quantitative (survey of patients from 18 DMPs) data collection. Questionnaire response rates were 51% (2010; 2619/5108) at T0 and 47% (2011; 2191/4693) at T1. Physical activity and the percentage of smokers improved significantly over time, whereas physical quality of life declined. After adjusting for patients' physical quality of life at T0, age, educational level, marital status, and gender, physical activity at T0 (p<0.01), changes in physical activity (p<0.001), and percentage of smokers at T0 (p<0.05) predicted physical quality of life at T1. Project managers reported that DMPs improved patient-professional interaction. The ability to set more concrete targets improved patients' health behaviors. DMPs appear to improve physical activity among chronically ill patients over time. Furthermore, (changes in) health behavior are important for the physical quality of life of chronically ill patients. Redesigning care systems and implementing DMPs based on the chronic care model may improve health behavior among chronically ill patients. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Muscle strengthening activity associates with reduced all-cause mortality in COPD.

PubMed

Loprinzi, Paul D; Sng, Eveleen; Walker, Jerome F

2017-06-01

Objective Emerging research suggests that aerobic-based physical activity may help to promote survival among chronic obstructive pulmonary disease patients. However, the extent to which engagement in resistance training on survival among chronic obstructive pulmonary disease patients is relatively unknown. Therefore, the purpose of this study was to examine the independent associations of muscle strengthening activities on all-cause mortality among a national sample of U.S. adults with chronic obstructive pulmonary disease. We hypothesize that muscle strengthening activities will be inversely associated with all-cause mortality. Methods Data from the 2003-2006 NHANES were employed, with follow-up through 2011. Aerobic-based physical activity was objectively measured via accelerometry, muscle strengthening activities engagement was assessed via self-report, and chronic obstructive pulmonary disease was assessed via physician-diagnosis. Results Analysis included 385 adults (20 + yrs) with chronic obstructive pulmonary disease, who represent 13.3 million chronic obstructive pulmonary disease patients in the USA. The median follow-up period was 78 months (IQR=64-90), with 82 chronic obstructive pulmonary disease patients dying during this period. For a two muscle strengthening activity sessions/week increase (consistent with national guidelines), chronic obstructive pulmonary disease patients had a 29% reduced risk of all-cause mortality (HR=0.71; 95% CI: 0.51-0.99; P = 0.04). Conclusion Participation in muscle strengthening activities, independent of aerobic-based physical activity and other potential confounders, is associated with greater survival among chronic obstructive pulmonary disease patients.

Modified Puestow procedure for the management of chronic pancreatitis in children.

PubMed

Laje, Pablo; Adzick, N Scott

2013-11-01

To present our experience with the modified Puestow procedure in the management of children with chronic pancreatitis. Retrospective chart review of patients treated between 2003 and 2012. Six patients underwent a modified Puestow procedure (lateral pancreaticojejunostomy) for the management of chronic pancreatitis, three females and three males. Four patients had hereditary pancreatitis (three with confirmed N34S mutation in the SPINK1 gene), one patient had chronic pancreatitis of unknown etiology, and one patient with annular pancreas developed obstructive chronic pancreatitis. The pancreatic duct was dilated in all cases, with a maximum diameter of 5 to 10mm. Median time between onset of pain and surgery was 4 years (range: 1-9). Median age at surgery was 7.5 years (range: 5-15). Median hospital stay was 12 days (range: 9-28). Median follow up was 4.5 years (range: 5 months to 9 years). All patients had temporary postoperative improvement of their abdominal pain. In two patients the pain recurred at 6 months and 2 years postoperatively and eventually required total pancreatectomy to treat intractable pain, 3 and 8 years after surgery. Two patients were pain free for two years and subsequently developed occasional episodes of pain. The two most recent patients are pain free at 1 year (obstructive chronic pancreatitis) and 5 months (hereditary pancreatitis) follow-up. Two patients developed type I diabetes mellitus 10 and 12 months postoperatively (one with hereditary and one with idiopathic chronic pancreatitis). We conclude that the modified Puestow procedure in children is feasible and safe. It seems to provide definitive pain control and prevent further damage to the pancreas in patients with obstructive chronic pancreatitis. However, in patients with hereditary pancreatitis, pain control outcomes are variable and the operation may not abrogate the progression of disease to pancreatic insufficiency. Copyright © 2013 Elsevier Inc. All rights reserved.

[Deficient lactose digestion and intolerance in a group of patients with chronic nonspecific ulcerative colitis: a controlled, double-blind, cross-over clinical trial].

PubMed

Cabrera-Acosta, G A; Milke-García, M P; Ramírez-Iglesias, M T; Uscanga, L

2012-01-01

Despite the fact that the frequency of hypolactasia and lactose intolerance is similar in both chronic idiopathic ulcerative colitis patients and the general population, the elimination of dairy products from the patient's diet is a habitual recommendation. Hypolactasia is common in Mexico, but its relation to chronic idiopathic ulcerative colitis has not been established. To evaluate lactose digestion and lactose intolerance in persons with chronic idiopathic ulcerative colitis. Thirty-nine patients with confirmed chronic idiopathic ulcerative colitis diagnosis were included in the study (mean: 31 years, range: 15 to 38). Twenty-two patients presented with rectosigmoid involvement and the remaining patients with pancolitis. No patient showed inflammatory activity according to the Truelove-Witts criteria and all consumed dairy products before diagnosis. A prospective, controlled, double-blind, cross-over study was designed. Patients randomly received 12.5 g of lactose or maltose in 250 cc water- each test 72 hours apart - and ydrogen was measured in exhaled air before disaccharide ingestion and then every 30 minutes for 3 hours. Digestion was considered deficient when there was an increase in hydrogen of at least 20 ppm. Symptom intensities were evaluated by Visual Analog Scales before, during, and after the hydrogen test. Differences between the groups were contrasted with the Mann-Whitney U and the Wilcoxon tests. Eighteen patients (46%) presented with deficient lactose digestion. No significant differences were found in the symptoms, extension, or progression of chronic idiopathic ulcerative colitis between patients that could digest and those that could not digest lactose. No patient had symptom exacerbation with the disaccharides used. Lactose digestion deficiency frequency is similar in subjects with chronic idiopathic ulcerative colitis and in healthy individuals in Mexico. We do not know whether higher doses could have some effect, but symptoms in patients with inactive chronic idiopathic ulcerative colitis were not modified using 12.5 g of lactose/day.

Inhaled corticosteroids (ICS) and risk of mycobacterium in patients with chronic respiratory diseases: a meta-analysis.

PubMed

Ni, Songshi; Fu, Zhenxue; Zhao, Jing; Liu, Hua

2014-07-01

Studies have indicated that therapy with inhaled corticosteroids (ICS) can be associated with a higher risk of pneumonia. However, it is not known whether ICS increases the risk of mycobacterium. Most of these published studies were small, and the conclusions were inconsistent. A meta-analysis was conducted into whether ICS increases the risk of mycobacterium in patients with chronic respiratory diseases. PubMed, OVID, EMBASE and Cochrane Library databases were searched. Five studies involving 4,851 cases and 28,477 controls were considered in the meta-analysis. From the pooled analyses, there was significant association between ICS and risk of mycobacterium in all patients with chronic respiratory diseases [risk ratio (RR) =1.81; 95% confidence interval (CI), 1.23-2.68; P=0.003]. Among patients with chronic respiratory diseases, the relationship between ICS and risk of tuberculosis (TB) was also significant (RR =1.34; 95% CI, 1.15-1.55; P=0.0001). And meta-analysis of four studies in patients with chronic obstructive pulmonary disease (COPD) (RR =1.42; 95% CI, 1.18-1.72; P=0.0003) or two studies in patients who have prior pulmonary TB (RR =1.61; 95% CI, 1.35-1.92; P<0.00001) or three studies in patients with high-dose ICS (RR =1.60; 95% CI, 1.28-1.99; P<0.0001) showed a relationship between ICS and risk of mycobacterium. Significant relationship has been shown between ICS use and risk of mycobacterium in all patients with chronic respiratory diseases. ICS use also increases the risk of TB among the patients with chronic respiratory diseases. Use of ICS increases the risk of mycobacterium in patients with COPD or patients with prior pulmonary TB or patients inhaling high-dose corticosteroids. Further research is required to establish the potential adverse effect of ICS as a therapy for chronic respiratory diseases.

Patient-Clinician Communication About End-of-Life Care in Patients With Advanced Chronic Organ Failure During One Year.

PubMed

Houben, Carmen H M; Spruit, Martijn A; Schols, Jos M G A; Wouters, Emiel F M; Janssen, Daisy J A

2015-06-01

Patient-clinician communication is an important prerequisite to delivering high-quality end-of-life care. However, discussions about end-of-life care are uncommon in patients with advanced chronic organ failure. The aim was to examine the quality of end-of-life care communication during one year follow-up of patients with advanced chronic organ failure. In addition, we aimed to explore whether and to what extent quality of communication about end-of-life care changes toward the end of life and whether end-of-life care communication is related to patient-perceived quality of medical care. Clinically stable outpatients (n = 265) with advanced chronic obstructive pulmonary disease, chronic heart failure, or chronic renal failure were visited at home at baseline and four, eight, and 12 months after baseline to assess quality of end-of-life care communication (Quality of Communication questionnaire). Two years after baseline, survival status was assessed, and if patients died during the study period, a bereavement interview was done with the closest relative. One year follow-up was completed by 77.7% of the patients. Quality of end-of-life care communication was rated low at baseline and did not change over one year. Quality of end-of-life care communication was comparable for patients who completed two year follow-up and patients who died during the study. The correlation between quality of end-of-life care communication and satisfaction with medical treatment was weak. End-of-life care communication is poor in patients with chronic organ failure and does not change toward the end of life. Future studies should develop an intervention aiming at initiating high-quality end-of-life care communication between patients with advanced chronic organ failure and their clinicians. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Care Coordination for the Chronically Ill: Understanding the Patient's Perspective

PubMed Central

Maeng, Daniel D; Martsolf, Grant R; Scanlon, Dennis P; Christianson, Jon B

2012-01-01

Objective To identify factors associated with perception of care coordination problems among chronically ill patients. Methods Patient-level data were obtained from a random-digit dial telephone survey of adults with chronic conditions. The survey measured respondents' self-report of care coordination problems and level of patient activation, using the Patient Activation Measure (PAM-13). Logistic regression was used to assess association between respondents' self-report of care coordination problems and a set of patient characteristics. Results Respondents in the highest activation stage had roughly 30–40 percent lower odds of reporting care coordination problems compared to those in the lowest stage (p < .01). Respondents with multiple chronic conditions were significantly more likely to report coordination problems than those with hypertension only. Respondents' race/ethnicity, employment, insurance status, income, and length of illness were not significantly associated with self-reported care coordination problems. Conclusion We conclude that patient activation and complexity of chronic illness are strongly associated with patients' self-report of care coordination problems. Developing targeted strategies to improve care coordination around these patient characteristics may be an effective way to address the issue. PMID:22985032

Effect of free radical scavenger, edaravone, for patients with carbon monoxide poisoning.

PubMed

Mori, Kiyofumi; Beppu, Takaaki; Fujisawa, Yutaka; Onodera, Makoto; Ogasawara, Kuniaki; Sasaki, Makoto; Ehara, Shigeru; Sakai, Akio; Endo, Shigeatsu

2015-12-01

Chronic neurological symptoms after carbon monoxide (CO) poisoning are caused by various biological processes in the damaged brain, with free radicals playing roles as mediators in establishing pathological processes leading to chronic neurological symptoms under CO poisoning. This study aimed to clarify the effects of a free radical scavenger, edaravone, in patients with CO poisoning. We retrospectively compared two groups comprising patients treated with hyperbaric oxygenation alone (Group A, n=25) or edaravone in addition to hyperbaric oxygenation (Group B, n=25). Edaravone was administrated intravenously at 30 mg every 12h for 7 days. Patient characteristics, general conditions on admission, and frequency of chronic neurological symptoms were compared between groups. Among patients showing chronic neurological symptoms, cognitive function and daily activity were also compared between groups. No significant differences in characteristics or general conditions on admission were identified between groups. In Group B, no patients presented with marked complications caused by edaravone. Although chronic persisting symptoms were less frequent in Group B (n=1, 0.04%) than in Group A (n=5, 20%), this difference was not significant. In the 11 patients showing chronic symptoms, scores for cognitive function and daily activity in the chronic phase were better in Group B than in Group A, but no significant differences were apparent. The present results suggest that edaravone represents a tolerable and feasible treatment for CO-poisoned patients. Further studies are needed to clarify whether edaravone can favorably influence chronic neurological symptoms caused by CO poisoning. Copyright © 2015 Elsevier B.V. All rights reserved.

Incidence and predictors of 30-day readmissions in patients hospitalized with chronic pancreatitis: A nationwide analysis.

PubMed

Shah, Rushikesh; Haydek, Christopher; Mulki, Ramzi; Qayed, Emad

2018-06-01

Patients with chronic pancreatitis are prone to frequent readmissions. The aim of this study is to evaluate the rate and predictors of 30-day readmissions in patients with chronic pancreatitis using the Nationwide Readmission Database (NRD). We performed a retrospective analysis of all adult patients with the principal discharge diagnosis of chronic pancreatitis from 2010 through 2014. We excluded patients who died during the hospitalization. Multivariate Cox proportional hazard regression was performed to identify demographic, clinical, and hospital factors that associated with 30-day unplanned readmissions. During the study period, 25,259 patients had the principal discharge diagnosis of chronic pancreatitis and survived the index hospitalization. Of these, 6477 (26.7%) were readmitted within 30 days. Younger age group, males, length of stay >5 days, admission to a large, metropolitan hospital, and several comorbidities (renal failure, rheumatic disease, chronic anemia, heart failure, depression, drug abuse, psychosis, and diabetes) were independently associated with increased risk of 30-day readmission. ERCP, pancreatic surgery, and obesity were associated with lower risk. The most common reasons for readmissions were acute pancreatitis (30%), chronic pancreatitis (17%), pseudocyst (2%), and abdominal pain (6%). One in four patients with chronic pancreatitis is readmitted within 30 days (26.7%). Pancreatic disease accounts for at least half of all readmissions. Several baseline comorbidities and characteristics are associated with 30-day readmission risk after index admission. Knowledge of these predictors can help design interventions to target high-risk patients and reduce readmissions and costs of care. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo- controlled treatment with rupatadine 10 and 20 mg.

PubMed

Giménez-Arnau, A; Izquierdo, I; Maurer, M

2009-09-01

According to the EAACI/GA(2)LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed. This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS). A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than rupatadine 10 mg. Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.

Managing multimorbidity in primary care in patients with chronic respiratory conditions.

PubMed

Morrison, Deborah; Agur, Karolina; Mercer, Stewart; Eiras, Andreia; González-Montalvo, Juan I; Gruffydd-Jones, Kevin

2016-09-15

The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions. Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs. Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety. Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease. This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age. The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy. The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions. The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy. Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams.

Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis.

PubMed

Hu, Shenlin; Shang, Wei; Yue, Haitao; Chen, Ruini; Dong, Zheng; Hu, Jinhua; Mao, Zhao; Yang, Jian

2015-04-01

To evaluate the DEC1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis. 20 non-smoking patients with chronic periodontitis and 20 healthy individuals were enrolled. Periodontal ligament tissue and gingival tissue samples from healthy subjects were collected during teeth extraction for orthodontic reason or the third molar extraction. The parallel samples from patients with chronic periodontitis were obtained during periodontal flap operations or teeth extraction as part of periodontal treatment. The DEC1 expression and the alkaline phosphatase (ALP) activity of both the periodontal ligament tissue and gingival tissue were determined by Western blot, Immunohistochemistry and ALP Detection Kit. The DEC1 expression of periodontal ligament tissue in the patients with chronic periodontitis decreased significantly along with the decreased ALP activity. On the contrary, the DEC1 expression of gingival tissue in the patients with chronic periodontitis increased significantly. Further study found that the DEC1 expression of gingival tissue increased mainly in the suprabasal layer of gingival epithelial cells but decreased in the gingival connective tissue of the patients with chronic periodontitis. The DEC1 expression decreases in the periodontal ligament tissue which is related to the osteogenic capacity, whereas the DEC1 expression increases in the suprabasal layer of gingival epithelial cells which are involved in immune inflammatory response in the patients with chronic periodontitis. The findings provide a new target to explore the pathology and the therapy of periodontitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

High satisfaction and low decisional conflict with advance care planning among chronically ill patients with advanced chronic obstructive pulmonary disease or heart failure using an online decision aid: A pilot study.

PubMed

Van Scoy, Lauren J; Green, Michael J; Dimmock, Anne Ef; Bascom, Rebecca; Boehmer, John P; Hensel, Jessica K; Hozella, Joshua B; Lehman, Erik B; Schubart, Jane R; Farace, Elana; Stewart, Renee R; Levi, Benjamin H

2016-09-01

Many patients with chronic illnesses report a desire for increased involvement in medical decision-making. This pilot study aimed to explore how patients with exacerbation-prone disease trajectories such as advanced heart failure or chronic obstructive pulmonary disease experience advance care planning using an online decision aid and to compare whether patients with different types of exacerbation-prone illnesses had varied experiences using the tool. Pre-intervention questionnaires measured advance care planning knowledge. Post-intervention questionnaires measured: (1) advance care planning knowledge; (2) satisfaction with tool; (3) decisional conflict; and (4) accuracy of the resultant advance directive. Comparisons were made between patients with heart failure and chronic obstructive pulmonary disease. Over 90% of the patients with heart failure (n = 24) or chronic obstructive pulmonary disease (n = 25) reported being "satisfied" or "highly satisfied" with the tool across all satisfaction domains; over 90% of participants rated the resultant advance directive as "very accurate." Participants reported low decisional conflict. Advance care planning knowledge scores rose by 18% (p < 0.001) post-intervention. There were no significant differences between participants with heart failure and chronic obstructive pulmonary disease. Patients with advanced heart failure and chronic obstructive pulmonary disease were highly satisfied after using an online advance care planning decision aid and had increased knowledge of advance care planning. This tool can be a useful resource for time-constrained clinicians whose patients wish to engage in advance care planning. © The Author(s) 2016.

The Efficacy of a Perceptive Rehabilitation on Postural Control in Patients with Chronic Nonspecific Low Back Pain

ERIC Educational Resources Information Center

Paolucci, Teresa; Fusco, Augusto; Iosa, Marco; Grasso, Maria R.; Spadini, Ennio; Paolucci, Stefano; Saraceni, Vincenzo M.; Morone, Giovanni

2012-01-01

Patients with chronic low back pain have a worse posture, probably related to poor control of the back muscles and altered perception of the trunk midline. The aim of this study was to evaluate the efficacy of a perceptive rehabilitation in terms of stability and pain relief in patients with chronic nonspecific low back pain. Thirty patients were…

Effect of exercise on cognitive function in chronic disease patients: a meta-analysis and systematic review of randomized controlled trials.

PubMed

Cai, Hong; Li, Guichen; Hua, Shanshan; Liu, Yufei; Chen, Li

2017-01-01

The purpose of this study was to conduct a meta-analysis and systematic review to assess the effect of exercise on cognitive function in people with chronic diseases. PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, PsycINFO, and three Chinese databases were electronically searched for papers that were published until September 2016. This meta-analysis and systematic review included randomized controlled trials that evaluated the effect of exercise on cognitive function compared with control group for people with chronic diseases. Totally, 35 studies met the inclusion criteria, with 3,113 participants. The main analysis revealed a positive overall random effect of exercise intervention on cognitive function in patients with chronic diseases. The secondary analysis revealed that aerobic exercise interventions and aerobic included exercise interventions had a positive effect on cognition in patients with chronic diseases. The intervention offering low frequency had a positive effect on cognitive function in patients with chronic diseases. Finally, we found that interventions offered at both low exercise intensity and moderate exercise intensity had a positive effect on cognitive function in patients with chronic diseases. The secondary analysis also revealed that exercise interventions were beneficial in Alzheimer's disease patients when grouped by disease type. This meta-analysis and systematic review suggests that exercise interventions positively influence cognitive function in patients with chronic diseases. Beneficial effect was independent of the type of disease, type of exercise, frequency, and the intensity of the exercise intervention.

The relationship between self-management abilities, quality of chronic care delivery, and wellbeing among patients with chronic obstructive pulmonary disease in The Netherlands

PubMed Central

Cramm, Jane Murray; Nieboer, Anna Petra

2013-01-01

Background This cross-sectional study aimed to identify the relationship between quality of chronic care delivery, self-management abilities, and wellbeing among patients with chronic obstructive pulmonary disease (COPD). Methods The study was conducted in 2012 and included 548 (out of 1303; 42% response rate) patients with COPD enrolled in a COPD care program in the region of Noord-Kennemerland in The Netherlands. We employed a multilevel random-effects model (548 patients nested in 47 healthcare practices) to investigate the relationship between quality of chronic care delivery, self-management abilities, and patients’ wellbeing. In the multilevel analyses we controlled for patients’ background characteristics and health behaviors. Results Multilevel analyses clearly showed a significant relationship between quality of chronic care delivery and wellbeing of patients with COPD (P ≤ 0.001). When self-management abilities were included in the equation while controlling for background characteristics, health behaviors, and quality of chronic care delivery, these abilities were found to have a strong positive relationship with patients’ wellbeing (P ≤ 0.001). Low educational level, single marital status, and physical exercise were not significantly associated with wellbeing when self-management abilities were included in the equation. Conclusion Self-management abilities and the quality of chronic care delivery are important for the wellbeing of patients with COPD. Furthermore, self-management abilities acted as mediators between wellbeing and low educational level, single status, and physical exercise among these patients. PMID:23641152

Effect of Smoking on Peripheral Blood Lymphocyte Subsets of Patients With Chronic Renal Failure.

PubMed

Düvenci Birben, Özlem; Akçay, Şule; Sezer, Siren; Şirvan, Şale; Haberal, Mehmet

2016-11-01

Smoking is known to suppress the immune system. It is also known that chronic renal failure affects the immune system. However, the number of studies investigating the effects of chronic renal failure and smoking together is limited. In our study, we examined whether smoking affects the diminished response of the immune system in patients with chronic renal failure. We compared peripheral blood lymphocyte subsets in smoking and nonsmoking patients with chronic renal failure. We also used the Fagerström Test for Nicotine Dependence to evaluate its correlation with the lymphocyte subset count in patients who are current smokers. Our study included 126 patients with chronic renal failure. According to their smoking habits, patients were divided into 2 groups: smokers and nonsmokers. The average age of patients who were smokers was 53.2 ± 1.5 years, with average age of nonsmokers being 59.2 ± 2.2 years. The average duration of smoking in smokers was 30.7 ± 2.7 packyears. We found that the percentage of cluster of differentiation 16-56 cells (natural killer cells) and lymphocyte percentage were significantly lower among smokers in our study (P < .05). We compared the lymphocyte subset panel to pack-years and found that the rate of cluster of differentiation 16-56 cells decreased as smoking duration increased. Our study revealed that smoking suppresses the immune system, as measured by lymphocyte subsets, in patients with chronic renal failure, similar to that shown in healthy smokers. According to our findings, patients with chronic renal failure, where infection is the primary reason for mortality and morbidity, must be questioned for smoking and referred to smoking cessation clinics. Because of its immunosuppressive effects, smoking behaviors must be solved preoperatively in transplant candidates.

Burnout in Patients with Chronic Whiplash-Associated Disorders

ERIC Educational Resources Information Center

Clementz, Gunilla; Borsbo, Bjorn; Norrbrink, Cecilia

2012-01-01

This study sought to assess burnout and its relation to pain, disability, mood and health-related quality of life in a group of patients with chronic whiplash-associated disorders (WAD). Forty-five patients with chronic WAD ([greater than or equal to] 3 months) referred to a multidisciplinary rehabilitation centre were included. A questionnaire…

[Capillaroscopy in patients with chronic alcoholic pancreatitis].

PubMed

Teixeira, G P; de Alencar, R; Fonseca, M de O; Bernardini, E M

1996-01-01

The aim of this study was verify frequency and morphological presentations of microangiopathy in patients with alcoholic chronic pancreatitis, using nailfold capillaroscopy. All patients showed morphological and functional capillary abnormalities. None of them had a normal capillaroscopy. Our findings may suggest an important role of microcirculation in Alcoholic Chronic Pancreatitis pathogenesis and/or its course.

Metastatic pancreatic adenocarcinoma associated with chronic calcific pancreatitis and a heterozygous SPINK1 N34S mutation.

PubMed

Moran, Robert A; Klapheke, Robert; Jalaly, Niloofar Y; Makary, Martin A; Hirose, Kenzo; Goggins, Michael; Wood, Laura; Laheru, Daniel A; Lennon, Anne Marie; Khashab, Mouen A; Singh, Vikesh K

2016-01-01

Contrary to patients with a cationic trypsinogen gene (PRSS1) mutations, Serine protease inhibitor Kazal-type 1 (SPINK1) heterozygote gene mutation carriers have a very low penetrance for acute, acute recurrent and/or chronic pancreatitis. Despite this, heterozygote SPINK 1 gene mutation patients have a similar age of onset of pancreatitis as PRSS 1 gene mutation patients. While the substantially elevated risk of pancreatic cancer in patients with PRSS1 gene mutations with chronic pancreatitis has been well established, little is known about the risk of pancreatic cancer in SPINK 1 gene mutation carriers with pancreatitis. We describe a case of malignant pancreatic cancer diagnosed in a young patient with chronic pancreatitis who is a SPINK 1 heterozygote gene mutation carrier. The risk of pancreatic cancer in gene mutation patients with chronic pancreatitis, in addition to screening options and management options for these patients is discussed. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction.

PubMed

Belotti, Silvia; Rossi, Alessandra; Colombo, Paolo; Bettini, Ruggero; Rekkas, Dimitrios; Politis, Stavros; Colombo, Gaia; Balducci, Anna Giulia; Buttini, Francesca

2014-08-25

An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement. Copyright © 2014 Elsevier B.V. All rights reserved.

Percutaneous endoscopic colostomy for adults with chronic constipation: Retrospective case series of 12 patients.

PubMed

Strijbos, D; Keszthelyi, D; Masclee, A A M; Gilissen, L P L

2018-05-01

Percutaneous endoscopic colostomy (PEC) is a technique derived from percutaneous endoscopic gastrostomy. When conservative treatment of chronic obstipation fails, colon irrigation via PEC seems less invasive than surgical interventions. However, previous studies have noted high complication rates of PEC, mostly related to infections. Our aim was to report our experiences with PEC in patients with chronic refractory constipation. Retrospective analysis of all patients who underwent PEC for refractory constipation in our secondary referral hospital between 2009 and 2016. Twelve patients received a PEC for chronic, refractory constipation. Short-term efficacy for relief of constipation symptoms was good in 8 patients and moderate in 4 patients. Two patients had the PEC removed because of spontaneous improvement of constipation. Three patients, who initially noticed a positive effect, preferred an ileostomy over PEC after 1-5 years. One PEC was removed because of an abscess. Long-term efficacy is 50%: 6 patients still use their PEC after 3.3 years of follow-up. No mortality occurred. PEC offers a technically easily feasible and safe treatment option for patients with chronic constipation not responding to conventional therapy. Long-term efficacy of PEC in our patients is 50%. © 2017 John Wiley & Sons Ltd.

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

PubMed

Samson, C M; Waheed, N; Baltatzis, S; Foster, C S

2001-06-01

To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Retrospective noncomparative interventional case series. All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

Risk factors and nomogram for pancreatic pseudocysts in chronic pancreatitis: A cohort of 1998 patients.

PubMed

Hao, Lu; Pan, Jun; Wang, Dan; Bi, Ya-Wei; Ji, Jun-Tao; Xin, Lei; Liao, Zhuan; Du, Ting-Ting; Lin, Jin-Huan; Zhang, Di; Zeng, Xiang-Peng; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Xie, Ting; Li, Bai-Rong; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2017-07-01

Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts. Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. With a total of 1998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these five factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves. The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

The primary-specialty care interface in chronic diseases: patient and practice characteristics associated with co-management.

PubMed

Larochelle, Jean-Louis; Feldman, Debbie Ehrmann; Levesque, Jean-Frederic

2014-11-01

Specialist physicians may act either as consultants or co-managers for patients with chronic diseases along with their primary healthcare (PHC) physician. We assessed factors associated with specialist involvement. We used questionnaire and administrative data to measure co-management and patient and PHC practice characteristics in 702 primary care patients with common chronic diseases. Analysis included multilevel logistic regressions. In all, 27% of the participants were co-managed. Persons with more severe chronic diseases and lower health-related quality of life were more likely to be co-managed. Persons who were older, had a lower socioeconomic status, resided in rural regions and who were followed in a PHC practice with an advanced practice nurse were less likely to be co-managed. Co-management of patients with chronic diseases by a specialist is associated with higher clinical needs but demonstrates social inequalities. PHC practices more adapted to chronic care may help optimize specialist resources utilization. Copyright © 2014 Longwoods Publishing.

The Primary-Specialty Care Interface in Chronic Diseases: Patient and Practice Characteristics Associated with Co-Management

PubMed Central

Larochelle, Jean-Louis; Feldman, Debbie Ehrmann; Levesque, Jean-Frederic

2014-01-01

Objective: Specialist physicians may act either as consultants or co-managers for patients with chronic diseases along with their primary healthcare (PHC) physician. We assessed factors associated with specialist involvement. Methods: We used questionnaire and administrative data to measure co-management and patient and PHC practice characteristics in 702 primary care patients with common chronic diseases. Analysis included multilevel logistic regressions. Results In all, 27% of the participants were co-managed. Persons with more severe chronic diseases and lower health-related quality of life were more likely to be co-managed. Persons who were older, had a lower socioeconomic status, resided in rural regions and who were followed in a PHC practice with an advanced practice nurse were less likely to be co-managed. Discussion: Co-management of patients with chronic diseases by a specialist is associated with higher clinical needs but demonstrates social inequalities. PHC practices more adapted to chronic care may help optimize specialist resources utilization. PMID:25617515

Evaluating the impact of a switch to nilotinib on imatinib-related chronic low-grade adverse events in patients with CML-CP: the ENRICH study

PubMed Central

Cortes, Jorge E.; Lipton, Jeffrey H.; Miller, Carole B.; Busque, Lambert; Akard, Luke P.; Pinilla-Ibarz, Javier; Keir, Christopher; Warsi, Ghulam; Lin, Felice P.; Mauro, Michael J.

2016-01-01

Background Many patients with chronic myeloid leukemia in chronic phase (CML-CP) experience chronic treatment-related adverse events (AEs) on imatinib therapy. These AEs can impair quality of life (QOL) and lead to reduced treatment adherence, which is associated with poor clinical outcomes. Patients and Methods In the phase 2 Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events (ENRICH) study (N = 52), the impact of switching patients with imatinib-related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated. Results Three months after switching to nilotinib, 84.6% of patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% resolved within 3 months of switching to nilotinib. Among evaluable patients, most had improvements in overall QOL after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of MMR was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported on nilotinib were typically grade 1/2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib due to new or worsening AEs. Conclusions Overall, results from ENRICH demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with CML-CP in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018. PMID:26993758

Readmission patterns in patients with chronic obstructive pulmonary disease, chronic heart failure and diabetes mellitus: an administrative dataset analysis.

PubMed

Brand, C; Sundararajan, V; Jones, C; Hutchinson, A; Campbell, D

2005-05-01

Comprehensive disease management programmes for chronic disease aim to improve patient outcomes and reduce health-care utilization. Readmission rates are often used as an outcome measure of effectiveness. This study aimed to document readmission rates, and risk for early and late readmission, for patients discharged from the Royal Melbourne Hospital with a disease diagnosis of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus compared to those with other general medical conditions. Eighty five (8.6%) of patients were readmitted within 28 days and 183 (20.8%) were readmitted between 29 and 180 days. No risk factors for early readmission were identified. Patients with a primary disease diagnosis of CHF and COPD are at increased risk of late readmissions (29-180 days).

Twist drill craniostomy with closed drainage for chronic subdural haematoma in the elderly: an effective method.

PubMed

Ramnarayan, R; Arulmurugan, B; Wilson, Paul M; Nayar, Rani

2008-09-01

Chronic subdural haematoma is a disease of the elderly and surgery in these patients carries a much higher risk. The common surgical procedures for chronic subdural haematoma include twist drill craniostomy, burr hole evacuation or craniotomy. The aim of this study was to analyse the results of twist drill craniostomy with drainage in elderly patients with chronic subdural haematoma. Forty-two elderly patients (>65 years) with radiologically proven chronic subdural haematoma were analysed. All the patients underwent twist drill craniostomy and continuous drainage of the haematoma under local anaesthesia and total intravenous anaesthesia (TIVA). There were 24 males and 18 females. Headache and cognitive decline was seen in 50% and weakness of limbs in 60% of patients. CT scan was done in all cases. All patients underwent twist drill 2-3 cm in front of the parietal eminence under local anaesthesia. The drain was left for 24-72 h depending on the drainage. At 1 week, 88% of patients had a good outcome. Twist drill craniostomy with drainage under local anaesthesia is a safe and effective procedure for chronic subdural haematoma in the elderly and could be used as the first and only option in these people.

Model construction for the intention to use telecare in patients with chronic diseases.

PubMed

Huang, Jui-Chen; Lee, Yii-Ching

2013-01-01

Objective. This study chose patients with chronic diseases as study subjects to investigate their intention to use telecare. Methods. A large medical institute in Taiwan was used as the sample unit. Patients older than 20 years, who had chronic diseases, were sampled by convenience sampling and surveyed with a structural questionnaire, and a total of 500 valid questionnaires were collected. Model construction was based on the Health Belief Model. The reliability and validity of the measurement model were tested using confirmatory factor analysis (CFA), and the causal model was explained by structural equation modeling (SEM). Results. The priority should be on promoting the perceived benefits of telecare, with a secondary focus on the external cues to action, such as promoting the influences of important people on the patients. Conclusion. The findings demonstrated that patients with chronic diseases use telecare differently from the general public. To promote the use and acceptance of telecare in patients with chronic diseases, technology developers should prioritize the promotion of the usefulness of telecare. In addition, policy makers can strengthen the marketing from media and medical personnel, in order to increase the acceptance of telecare by patients with chronic diseases.

Pneumococcal vaccination and chronic respiratory diseases.

PubMed

Froes, Filipe; Roche, Nicolas; Blasi, Francesco

2017-01-01

Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.

[Radionuclide evaluation of the mucociliary function of the mucosa of the nasal cavity in chronic lung diseases].

PubMed

Kasatkin, Iu N; Kaganov, S Iu; Vyrenkova, N Iu; Kramer, E F; Rozinova, N N

1987-02-01

The authors presented their first experience of radionuclide assessment of the nasal mucosal transport (NMT) in 39 patients with chronic bronchopulmonary pathology (14 adults and 25 children) to detect patients among them with suspected syndrome of primary ciliary dyskinesia (SPCD). In 18 patients the test was positive excluding SPCD as a cause of a chronic inflammatory pulmonary process. In 21 patients NMT was absent, 2 of these patients had Kartagener's triad serving as a kind of model confirming the data on NMT. The authors proposed the method as a screening test due to its non-invasiveness and simplicity in patients with chronic inflammatory pulmonary diseases in order to detect among them patients with suspected SPCD for further examination using invasive methods.

Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: real-world data from a nationwide cohort study in Taiwan.

PubMed

Tang, Kuo-Tung; Chen, Yi-Ming; Chang, Shih-Ni; Lin, Ching-Heng; Chen, Der-Yuan

2018-05-09

Methotrexate (MTX) is commonly used in the treatment of patients with moderate to severe psoriasis. We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 MTX non-users) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 MTX non-users) from January 1, 2000 to December 31, 2010. After a mean follow-up of more than 9 years since the diagnosis of chronic viral hepatitis, a total of 125 (5%) CHB patients and 120 (11%) CHC patients developed liver cirrhosis. A comparable proportion of MTX users and MTX non-users developed liver cirrhosis (4% vs. 5% in CHB patients and 11% and vs. 11% in CHC patients, both p < 0.05). There is possibly selection bias and medication nonadherence. Our real-world data show that long-term MTX use may not be associated with an increased risk of liver cirrhosis among psoriatic patients with chronic viral hepatitis. Copyright © 2018. Published by Elsevier Inc.

A qualitative study on the experiences and perspectives of public sector patients in Cape Town in managing the workload of demands of HIV and type 2 diabetes multimorbidity.

PubMed

Matima, Rangarirai; Murphy, Katherine; Levitt, Naomi S; BeLue, Rhonda; Oni, Tolu

2018-01-01

Current South African health policy for chronic disease management proposes integration of chronic services for better outcomes for chronic conditions; that is based on the Integrated Chronic Disease Model (ICDM). However, scant data exist on how patients with chronic multimorbidities currently experience the (re)-organisation of health services and what their perceived needs are in order to enhance the management of their conditions. A qualitative study was conducted in a community health centre treating both HIV and diabetes patients in Cape Town. The study was grounded in the Shippee's Cumulative Complexity Model (CCM) and explored "patient workload" and "patient capacity" to manage chronic conditions. Individual interviews were conducted with 10 adult patient-participants with HIV and type two diabetes (T2D) multimorbidity and 6 healthcare workers who provided health services to these patient-participants. Patient-participants in this study experienced clinic-related workload such as: two separate clinics for HIV and T2D and perceived and experienced power mismatch between patients and healthcare workers. Self-care related workloads were largely around nutritional requirements, pill burden, and stigma. Burden of these demands varied in difficulty among patient-participants due to capacity factors such as: positive attitudes, optimal health literacy, social support and availability of economic resources. Strategies mentioned by participants for improved continuity of care and self-management of multi-morbidities included integration of chronic services, consolidated guidelines for healthcare workers, educational materials for patients, improved information systems and income for patients. Using the CCM to explore multimorbidity captured most of the themes around "patient workload" and "patient capacity", and was thus a suitable framework to explore multimorbidity in this high HIV/T2D burden setting. Integration of chronic services and addressing social determinants of health may be the first steps towards alleviating patient burden and improving their access and utilisation of these services. Further studies are necessary to explore multimorbidity beyond the context of HIV/T2D.

A qualitative study on the experiences and perspectives of public sector patients in Cape Town in managing the workload of demands of HIV and type 2 diabetes multimorbidity

PubMed Central

Murphy, Katherine; Levitt, Naomi S.; BeLue, Rhonda; Oni, Tolu

2018-01-01

Background Current South African health policy for chronic disease management proposes integration of chronic services for better outcomes for chronic conditions; that is based on the Integrated Chronic Disease Model (ICDM). However, scant data exist on how patients with chronic multimorbidities currently experience the (re)-organisation of health services and what their perceived needs are in order to enhance the management of their conditions. Methods A qualitative study was conducted in a community health centre treating both HIV and diabetes patients in Cape Town. The study was grounded in the Shippee's Cumulative Complexity Model (CCM) and explored “patient workload” and “patient capacity” to manage chronic conditions. Individual interviews were conducted with 10 adult patient-participants with HIV and type two diabetes (T2D) multimorbidity and 6 healthcare workers who provided health services to these patient-participants. Results Patient-participants in this study experienced clinic-related workload such as: two separate clinics for HIV and T2D and perceived and experienced power mismatch between patients and healthcare workers. Self-care related workloads were largely around nutritional requirements, pill burden, and stigma. Burden of these demands varied in difficulty among patient-participants due to capacity factors such as: positive attitudes, optimal health literacy, social support and availability of economic resources. Strategies mentioned by participants for improved continuity of care and self-management of multi-morbidities included integration of chronic services, consolidated guidelines for healthcare workers, educational materials for patients, improved information systems and income for patients. Conclusion Using the CCM to explore multimorbidity captured most of the themes around "patient workload" and "patient capacity”, and was thus a suitable framework to explore multimorbidity in this high HIV/T2D burden setting. Integration of chronic services and addressing social determinants of health may be the first steps towards alleviating patient burden and improving their access and utilisation of these services. Further studies are necessary to explore multimorbidity beyond the context of HIV/T2D. PMID:29538415

Chronic pancreatitis.

PubMed

DiMagno, Matthew J; DiMagno, Eugene P

2012-09-01

We review important new clinical observations in chronic pancreatitis reported in 2011. Smoking increases the risk of nongallstone acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. Binge drinking during Oktoberfest did not associate with increased hospital admissions for acute pancreatitis. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in chronic pancreatitis is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90 000 United States Pharmacopeia units of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared with endoscopic treatment in patients advanced chronic pancreatitis with a dilated main duct ± pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with chronic pancreatitis but approximately 30% of patients have significant side effects. Patients with nongallstone-related acute pancreatitis or chronic pancreatitis of any cause should cease smoking. Results of this year's investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in chronic pancreatitis, and the mechanisms and treatment of neuropathic pain in chronic pancreatitis.

Chronic pancreatitis.

PubMed

Gupte, Anand R; Forsmark, Chris E

2014-09-01

We review selected important clinical observations in chronic pancreatitis reported in 2013. Early diagnosis of chronic pancreatitis remains difficult, although newer techniques utilizing endoscopic ultrasonography-elastography and MRI hold promise. Patients with chronic pancreatitis are at risk of nutritional deficiencies. Osteoporosis, osteopenia, and bone fracture are particularly common in these patients, and require active intervention and treatment. Diabetes caused by chronic pancreatitis, type 3c diabetes, has specific characteristics and requires careful management. Antioxidants and neuromodulators may decrease pain in some patients with chronic pancreatitis. Endoscopic treatment is effective and can be utilized in patients with painful chronic pancreatitis, although randomized trials demonstrate that surgical therapy is somewhat more durable and effective. Although surgery has typically been a last resort, some advocate early surgical intervention but the optimal time remains unknown. Early diagnosis of pancreatitis may be improved by newer techniques associated with endoscopic ultrasonography imaging. Treatment of nutritional deficiencies and diabetes is an important aspect of treating chronic pancreatitis. Pain relief with adjunct means of pain modulation should be tried before starting narcotics for pain control. Endoscopic therapy is appropriate for treating chronic pancreatitis and its local complications and surgical intervention can be considered early in carefully selected individuals.

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH).

PubMed

Gandaglia, Giorgio; Briganti, Alberto; Gontero, Paolo; Mondaini, Nicola; Novara, Giacomo; Salonia, Andrea; Sciarra, Alessandro; Montorsi, Francesco

2013-08-01

Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation. © 2013 BJU International.

Bacteriological profile of pancreatic juice in patients with chronic pancreatitis.

PubMed

Parida, Salil Kumar; Pottakkat, Biju; Raja, Kalayarasan; Vijayahari, Ranjit; Lakshmi, Chandrasekharan Padma

2014-09-28

Information regarding the association of bacteria in the pancreatic fluid in patients with chronic pancreatitis is limited. This study was designed to analyze the prevalence of bacteria in pancreatic juice in patients with chronic pancreatitis and the association of positive pancreatic fluid culture with pre-operative and post-operative parameters. All patients with chronic pancreatitis who underwent operation from November 2011 to October 2013 were prospectively included in the study. Intra-operatively pancreatic duct fluid was collected and sent for culture sensitivity in all patients. The bacteriology of the fluid was analyzed and was correlated with preoperative, intraoperative and postoperative parameters. A total of 26 patients were analyzed. Two patients underwent endoscopic retrograde cholangio-pancreatography (ERCP) preoperatively. Bacteria was present in pancreatic duct fluid in 11 (42%) patients. Both patients who underwent ERCP had positive cultures. Most common organism observed was Escherichia coli (6/11, 55%) followed by Klebsiella pneumonia (3/11, 27%). Five patients with positive culture developed wound infection. Bacteria isolated from the wound were similar to pancreatic fluid. Bacteria is commonly present in the pancreatic juice in patients with chronic pancreatitis and its presence may have an effect on the post-operative infections following operations. Based on the pancreatic fluid culture results appropriate antibiotic can be given to the patients who will develop septic complications following surgery. Role of bacteria in the pathogenesis of the chronic calcific pancreatitis needs to be investigated in future studies.

Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

PubMed Central

2014-01-01

Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis. PMID:24964956

Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

PubMed

Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

2014-09-01

MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. © 2014 Wiley Periodicals, Inc.

The contribution of the SPINK1 c.194+2T>C mutation to the clinical course of idiopathic chronic pancreatitis in Chinese patients.

PubMed

Sun, Chang; Liao, Zhuan; Jiang, Lili; Yang, Fu; Xue, Geng; Zhou, Qi; Chen, Ruiwen; Sun, Shuhan; Li, Zhaoshen

2013-01-01

Recent data suggest that the serine protease inhibitor Kazal type 1 (SPINK1) gene mutation is associated with idiopathic chronic pancreatitis. However, few studies have focused on the serine protease inhibitor Kazal type 1 c.194+2T>C mutation. Therefore, our goal was to study the prevalence and impact of serine protease inhibitor Kazal type 1 mutations on the clinical profile of idiopathic chronic pancreatitis patients in China. A retrospective-cohort study of 118 Chinese patients with idiopathic chronic pancreatitis was performed, and genetic tests were carried out to detect SPINK1 mutations. Subjects without pancreatitis were used as controls. In total, 118 idiopathic chronic pancreatitis patients and 100 control subjects were evaluated. The serine protease inhibitor Kazal type 1 c.194+2T>C variant was present in 44.9% of patients with idiopathic chronic pancreatitis. The frequency of diabetes in idiopathic chronic pancreatitis patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (39.6%) was higher than that of patients without the mutation (9.2%). The time to occurrence of diabetes mellitus after idiopathic chronic pancreatitis symptom onset is significantly influenced by the c.194+2T>C mutation (p<0.001). In addition, the mean age of diabetes onset in patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (38.33 ± 9.50) was significantly younger than that of patients without this mutation (49.67 ± 6.74). The presence of the serine protease inhibitor Kazal type 1 c.194+2T>C mutation seems to be associated with idiopathic chronic pancreatitis and could predispose individuals to pancreatic diabetes onset at an earlier age. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Urological symptoms in a subset of patients with urological chronic pelvic pain syndrome and a polysymptomatic, polysyndromic pattern of presentation.

PubMed

Lai, H Henry; North, Carol S; Andriole, Gerald L; Cupps, Lori; Song, David; Ness, Timothy J; Hong, Barry A

2014-06-01

We characterized urological symptoms in a subset of patients with urological chronic pelvic pain syndrome who have a high somatic symptom burden and a wide symptom distribution fitting a polysymptomatic, polysyndromic presentation pattern. A total of 81 patients with urological chronic pelvic pain syndrome enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases MAPP Research Network Study at Washington University in St. Louis and University of Alabama at Birmingham sites. They completed a symptom questionnaire to assess the somatic symptom burden and its distribution, and GUPI (Genitourinary Pain Index) to assess urological chronic pelvic pain syndrome symptoms, impact on quality of life and self-reported treatment seeking behaviors for urological chronic pelvic pain symptoms. The polysymptomatic, polysyndromic symptom pattern was defined by self-report of numerous painful and nonpainful somatic symptoms across many organ systems and by symptom categories on the polysymptomatic, polysyndromic questionnaire. Patients with urological chronic pelvic pain syndrome and the symptom pattern reported more severe genitourinary pain on a Likert scale, more frequent pain in the last week and more widespread pain distribution in the genital and pelvic areas than patients with urological chronic pelvic pain syndrome without the pattern. Patients with the symptom pattern also had significantly higher scores on the GUPI pain subscale, quality of life subscale (worse) and total questionnaire scores than patients without the pattern. Patients with the pattern reported significantly more treatment seeking behavior than others. The polysymptomatic, polysyndromic pattern might be an important phenotypic factor to assess in the evaluation of urological chronic pelvic pain syndrome with clinical and research implications. This may be a distinct clinical subgroup among patients with urological chronic pelvic pain syndrome. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Evaluation of patients with chronic thromboembolic pulmonary hypertension for pulmonary endarterectomy

PubMed Central

Auger, William R.; Kerr, Kim M.; Kim, Nick H.; Fedullo, Peter F.

2012-01-01

Pulmonary hypertension as a result of chronic thromboembolic disease (CTEPH) is potentially curable with pulmonary endarterectomy surgery. Consequently, correctly diagnosing patients with this type of pulmonary hypertension and evaluating these patients with the goal of establishing their candidacy for surgical intervention is of utmost importance. And as advancements in surgical techniques have allowed successful resection of segmental-level chronic thromboembolic disease, the number of CTEPH patients that are deemed suitable surgical candidates has expanded, making it even more important that the evaluation be conducted with greater precision. This article will review a diagnostic approach to patients with suspected chronic thromboembolic disease with an emphasis on the criteria considered in selecting patients for pulmonary endarterectomy surgery. PMID:22837856

[Specifications of motivational interviewing within a cognitive-behavioral therapy of chronic pain].

PubMed

Aguerre, C; Bridou, M; Laroche, F; Csillik, A; Jensen, M

2015-12-01

Cognitive and behavioral approach of chronic pain presents encouraging results by improving physical, functional and psychological states of chronic pain patients. This specific treatment is partially based on the acquisition of new adaptive strategies to help the patients to manage more effectively chronic pain and to improve subsequently their subjective well-being. This requires in parallel to give up noxious emotional, cognitive and behavioral attitudes towards pain. Now, we have to admit that numerous therapeutic failures are directly imputable to difficulties introducing and making the indispensable changes continue in pursuit of the fixed therapeutic objectives. Readiness to change could play a considerable role in the success or not of chronic pain treatment. The main objective of this article is to present the data of the current literature concerning the specificities of the process of change in the field of the chronic pain. We present a review of the literature describing at first, the psychological progress made by chronic pain patients longing to manage their suffering better via the trans-theoretical model of intentional change. Secondly, we develop the contributions of the technique of motivational interviewing in the improvement of chronic pain treatment. The identification of the motivational profile of chronic pain patients will determine how motivational interviewing can be conducted to improve their readiness for change. There are several strategies used with chronic pain patients in pre-contemplative and contemplative stages. Therapists may facilitate the problem recognition (help chronic pain patients to become aware of and identify the nature of the difficulties they face when trying to cope with their physical suffering); increase the personal concern (empowering chronic pain patients so that they feel fully involved in what they offer and invest in the therapy); develop the intention of change (ensure that the change becomes truly intentional); cultivate optimism (to help chronic pain patients to consider the present situation as being less desperate than it seems); ask open-ended questions (the direct questioning can be used to specify a request or reveal ambivalence about change); present personal feedback (the therapist provides the patient with a maximum of information that may help to appreciate the true value of the effectiveness of their current management of pain); review consequences of change versus non-change (to review the plausible positive (pros) and negative (cons) consequences of change); and summarizing (to summarize the key points discussed during the interview). In the active stage, therapists may use other strategies like: developing a plan for change (to suggest the adoption of certain coping strategies with pain); providing information advice (provide information advice in order to help chronic pain patients to determine how they will take concrete steps to initiate change); and using a change plan worksheet (help chronic pain patients to develop a synthetic view of the change process they will undertake). The various strategies discussed in this article are intended to accompany chronic pain patients to a process of change to help them consider a fundamental change in their ways of managing pain, when they are insufficient, ineffective and/or unintentionally aggravating their situation. It is important to help chronic pain patients to become aware of the nature of the adaptive problems they face, but also opportunities for change that are offered in order to encourage them to manage more efficiently and more autonomously their physical and mental suffering. In this context of openness to change, motivational interviewing can be an invaluable help to build a good therapeutic alliance in order to maximize the impact of supported global and multidimensional chronic pain by including a cognitive-behavioral approach for example. Copyright © 2014 L’Encéphale, Paris, 2007. All rights reserved.

Systematic review of the effects of chronic disease management on quality-of-life in people with chronic obstructive pulmonary disease.

PubMed

Niesink, A; Trappenburg, J C A; de Weert-van Oene, G H; Lammers, J W J; Verheij, T J M; Schrijvers, A J P

2007-11-01

Chronic disease management for patients with chronic obstructive pulmonary disease (COPD) may improve quality, outcomes and access to care. To investigate effectiveness of chronic disease management programmes on the quality-of-life of people with COPD. Medline and Embase (1995-2005) were searched for relevant articles, and reference lists and abstracts were searched for controlled trials of chronic disease management programmes for patients with COPD. Quality-of-life was assessed as an outcome parameter. Two reviewers independently reviewed each paper for methodological quality and extracted the data. We found 10 randomized-controlled trials comparing chronic disease management with routine care. Patient populations, health-care professionals, intensity, and content of the intervention were heterogeneous. Different instruments were used to assess quality of life. Five out of 10 studies showed statistically significant positive outcomes on one or more domains of the quality of life instruments. Three studies, partly located in primary care, showed positive results. All chronic disease management projects for people with COPD involving primary care improved quality of life. In most of the studies, aspects of chronic disease management were applied to a limited extent. Quality of randomized-controlled trials was not optimal. More research is needed on chronic disease management programmes in patients with COPD across primary and secondary care.

Surgical Management of Chronic Pancreatitis.

PubMed

Parekh, Dilip; Natarajan, Sathima

2015-10-01

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

Obstructive sleep apnoea in adults: a common chronic condition in need of a comprehensive chronic condition management approach.

PubMed

Heatley, Emer M; Harris, Melanie; Battersby, Malcolm; McEvoy, R Doug; Chai-Coetzer, Ching Li; Antic, Nicholas A

2013-10-01

Obstructive sleep apnoea (OSA) is a common disorder that has all the characteristics of a chronic condition. As with other chronic conditions, OSA requires ongoing management of treatments and problems, such as residual symptoms, deficits and co-morbidities. Also, many OSA patients have modifiable lifestyle factors that contribute to their disease, which could be improved with intervention. As health systems are in the process of developing more comprehensive chronic care structures and supports, tools such as chronic condition management programs are available to enable OSA patients and their health care providers to further engage and collaborate in health management. This review explains why the OSA patient group requires a more comprehensive approach to disease management, describes the chronic care model as a platform for management of chronic conditions, and assesses the suitability of particular chronic disease management programs in relation to the needs of the OSA population. Implementation of an evidence-based health-professional-led chronic condition management program into OSA patient care is likely to provide a context in which health risks are properly acknowledged and addressed. Such programs present an important opportunity to enable more optimal health outcomes than is possible by device-focused management alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

How Clinicians Feel about Working with Spouses of the Chronically Ill.

PubMed

Ingram, Douglas H

2015-09-01

Clinicians who provide psychotherapy to spouses or partners of the chronically ill were solicited through listserves of psychodynamic and other organizations. The current report excluded those therapists working with spouses of dementia patients. Interviews were conducted with clinicians who responded. The interviews highlight the challenges commonly encountered by psychotherapeutic work with this cohort of therapy patients. A comparison is drawn that shows both overlap and distinctions between the experiences of those therapists engaging with spouses of chronically ill patients without a dementing process and those working with spouses of chronically ill patients who do suffer from a dementing process.

Simultaneous Bilateral Quadriceps Tendon Rupture in Patient with Chronic Renal Failure

PubMed Central

Lee, Yunseok; Kim, Byounggook; Chung, Ju-Hwan

2011-01-01

Simultaneous bilateral spontaneous rupture of the quadriceps tendon is a very rare condition and only a few cases have been reported in the literature. The etiology is not clear yet. But it occurs infrequently in patients with chronic metabolic disorders. A 30-year-old female patient with simultaneous bilateral spontaneous quadriceps tendon rupture visited our hospital. She had chronic renal failure and her parathyroid hormone level was elevated due to parathyroid adenoma. We report a surgical repair of both quadriceps tendons of a patient with chronic renal failure as well as management of hyperparathyroidism. PMID:22570843

The patient with a complex chronic respiratory disease: a specialist of his own life?

PubMed

Houben-Wilke, Sarah; Augustin, Ingrid Ml; Wouters, Birgit Bref; Stevens, Rosita Ah; Janssen, Daisy Ja; Spruit, Martijn A; Vanfleteren, Lowie Egw; Franssen, Frits Me; Wouters, Emiel Fm

2017-12-01

The independent and central role of the patient with a complex chronic respiratory disease in targeted, personalized disease management strategies is becoming increasingly important. Patients are the ones living with the disease and are finally responsible for their lives underlining their role as essential members of the interdisciplinary treatment team. Areas covered: The present paper narratively reviews existing research and discusses the special, as well as specialized, role of the patient with a complex chronic respiratory disease in the healthcare system and highlights fundamental elements of the (future) relationship between patient and healthcare professionals. Expert commentary: Since the chronic respiratory disease at hand is part of the patient's entire life, we need holistic, personalized approaches optimizing patients' quality of life by not only treating the disease but considering the patients' whole environment and where healthcare professionals and patients are co-creating value care.

Overgeneral autobiographical memory in patients with chronic pain.

PubMed

Liu, Xianhua; Liu, Yanling; Li, Li; Hu, Yiqiu; Wu, Siwei; Yao, Shuqiao

2014-03-01

Overgenerality and delay of the retrieval of autobiographical memory (AM) are well documented in a range of clinical conditions, particularly in patients with emotional disorder. The present study extended the investigation to chronic pain, attempting to identify whether the retrieval of AM in patients with chronic pain tends to be overgeneral or delayed. With an observational cross-sectional design, we evaluated the AM both in patients with chronic pain and healthy controls by Autobiographical Memory Test. Pain conditions were assessed using the pain diagnostic protocol, the short-form McGill Pain Questionnaire (SF-MPQ), and the Pain Self-Efficacy Questionnaire (PSEQ). Emotion was assessed using the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory. Subjects included 176 outpatients with chronic pain lasting for at least 6 months and 170 healthy controls. 1) Compared with the healthy group, the chronic pain group had more overgeneral memories (OGMs) (F = 29.061, P < 0.01) and longer latency (F = 13.602, P < 0.01). 2) In the chronic pain group, the stepwise multiple regression models for variables predicting OGM were significant (P < 0.01). Specifically, the variance in OGM scores could be predicted by the BDI score (9.7%), pain chronicity (4.3%), PSEQ score (7.1%), and Affective Index (of SF-MPQ) score (2.7%). 3) In the chronic pain group, the stepwise multiple regression models for variables predicting latency were significant (P < 0.05). Specifically, the variance in latency could be predicted by age (3.1%), pain chronicity (2.7%), pain duration (4.3%), and PSEQ score (2.0%). The retrieval of AM in patients with chronic pain tends to be overgeneral and delayed, and the retrieval style of AM may be contributed to negative emotions and chronic pain conditions. Wiley Periodicals, Inc.

A longitudinal study to identify the influence of quality of chronic care delivery on productive interactions between patients and (teams of) healthcare professionals within disease management programmes

PubMed Central

Cramm, Jane Murray; Nieboer, Anna Petra

2014-01-01

Objective The chronic care model is an increasingly used approach to improve the quality of care through system changes in care delivery. While theoretically these system changes are expected to increase productive patient–professional interaction empirical evidence is lacking. This study aims to identify the influence of quality of care on productive patient–professional interaction. Setting Longitudinal study in 18 Dutch regions. Participants Questionnaires were sent to all 5076 patients participating in 18 Disease Management Programmes (DMPs) in 2010 (2676 (53%) respondents). One year later (T1), 4693 patients still participating in the DMPs received a questionnaire (2191 (47%) respondents) and 2 years later (in 2012; T2) 1722 patients responded (out of 4350; 40% response). Interventions DMPs Primary outcome measure Patients’ perceptions of the productivity of interactions (measured as relational coordination/coproduction of care) with professionals. Patients were asked about communication dimensions (frequent, accurate, and problem-solving communication) and relationship dimensions (shared goals and mutual respect). Findings After controlling for background characteristics these results clearly show that quality of chronic care (T0), first-year changes in quality of chronic care (T1—T0) and second-year changes in quality of chronic care (T2—T1) predicted productive interactions between patients and professionals at T2 (all at p≤0.001). Furthermore, we found a negative relationship between lower educational level and productive interactions between patients and professionals 2 years later. Conclusions We can conclude that successfully dealing with the consequences of chronic illnesses requires proactive patients who are able to make productive decisions together with their healthcare providers. Since patients and professionals share responsibility for management of the chronic illness, they must also share control of interactions and decisions. The importance of patient-centeredness is growing and this study reports a first example of how quality of chronic care stimulates productive interactions between patients and professionals. PMID:25239294

The effect of combined mechanism ankle support on postural control of patients with chronic ankle instability.

PubMed

Hadadi, Mohammad; Ebrahimi, Ismaeil; Mousavi, Mohammad Ebrahim; Aminian, Gholamreza; Esteki, Ali; Rahgozar, Mehdi

2017-02-01

Chronic ankle instability is associated with neuromechanical changes and poor postural stability. Despite variety of mechanisms of foot and ankle orthoses, almost none apply comprehensive mechanisms to improve postural control in all subgroups of chronic ankle instability patients. The purpose of this study was to investigate the effect of an ankle support implementing combined mechanisms to improve postural control in chronic ankle instability patients. Cross-sectional study. An ankle support with combined mechanism was designed based on most effective action mechanisms of foot and ankle orthoses. The effect of this orthosis on postural control was evaluated in 20 participants with chronic ankle instability and 20 matched healthy participants. The single-limb stance balance test was measured in both groups with and without the new orthosis using a force platform. The results showed that application of combined mechanism ankle support significantly improved all postural sway parameters in chronic ankle instability patients. There were no differences in means of investigated parameters with and without the orthosis in the healthy group. No statistically significant differences were found in postural sway between chronic ankle instability patients and healthy participants after applying the combined mechanism ankle support. The combined mechanism ankle support is effective in improving static postural control of chronic ankle instability patients to close to the postural sway of healthy individual. the orthosis had no adverse effects on balance performance of healthy individuals. Clinical relevance Application of the combined mechanism ankle support for patients with chronic ankle instability is effective in improving static balance. This may be helpful in reduction of recurrence of ankle sprain although further research about dynamic conditions is needed.

Is Traumatic and Non-Traumatic Neck Pain Associated with Brain Alterations? - A Systematic Review.

PubMed

DePauw, Robby; Coppieters, Iris; Meeus, Mira; Caeyenberghs, Karen; Danneels, Lieven; Cagnie, Barbara

2017-05-01

Chronic neck pain affects 50% - 85% of people who have experienced an acute episode. This transition and the persistence of chronic complaints are believed to be mediated by brain alterations among different central mechanisms. This study aimed to systematically review and critically appraise the current existing evidence regarding structural and functional brain alterations in patients with whiplash associated disorders (WAD) and idiopathic neck pain (INP). Additionally, associations between brain alterations and clinical symptoms reported in neck pain patients were evaluated. Systematic review. The present systematic review was performed according to the PRISMA guidelines. PubMed, Web of Science, and Cochrane databases were searched. First, the obtained articles were screened based on title and abstract. Secondly, the screening was based on the full text. Risk of bias in included studies was investigated. Twelve studies met the inclusion criteria. Alterations in brain morphology and function, including perfusion, neurotransmission, and blood oxygenation level dependent-signal, were demonstrated in chronic neck pain patients. There is some to moderate evidence for both structural and functional brain alterations in patients with chronic neck pain. In contrast, no evidence for structural brain alterations in acute neck pain patients was found. Only 12 articles were included, which allows only cautious conclusions to be drawn. Brain alterations were observed in both patients with chronic WAD and chronic INP. Furthermore, more evidence exists for brain alterations in chronic WAD, and different underlying mechanisms might be present in both pathologies. In addition, pain and disability were correlated with the observed brain alterations. Accordingly, morphological and functional brain alterations should be further investigated in patients with chronic WAD and chronic INP with newer and more sensitive techniques, and associative clinical measurements seem indispensable in future research.

Survival of macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking in patients with type 2 diabetes: BioBank Japan cohort.

PubMed

Yokomichi, Hiroshi; Nagai, Akiko; Hirata, Makoto; Kiyohara, Yutaka; Muto, Kaori; Ninomiya, Toshiharu; Matsuda, Koichi; Kamatani, Yoichiro; Tamakoshi, Akiko; Kubo, Michiaki; Nakamura, Yusuke; Yamagata, Zentaro

2017-03-01

The number of patients with diabetes is increasing worldwide. Macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking frequently accompany type 2 diabetes. Few data are available related to mortality of Asians with diabetes associated with these serious comorbidities. The present study aimed to quantify the excess mortality risks of type 2 diabetic patients with comorbidities. We analysed the available records of 30,834 Japanese patients with type 2 diabetes from the BioBank Japan Project between 2003 and 2007. Men and women were followed up for median 8.03 and 8.30 years, respectively. We applied Cox proportional hazard model and Kaplan-Meier estimates for survival curves to evaluate mortality in diabetic patients with or without macrovascular disease, chronic respiratory disease, chronic kidney disease, cancer and smoking. Adjusted hazard ratios (HRs) for mortality were 1.39 (95% CI, 1.09-1.78) for male sex, 2.01 (95% CI, 1.78-2.26) per 10-year increment of age. Adjusted HRs of primary interest were 1.77 (95% CI, 1.42-2.22), macrovascular disease; 1.58 (95% CI, 1.08-2.31), chronic respiratory disease; 2.03 (95% CI, 1.67-2.47), chronic kidney disease; 1.16 (95% CI, 0.86-1.56), cancer; and 1.74 (95% CI, 1.30-2.31), current smoking. Diabetic patients with a past or current history of chronic kidney, macrovascular or respiratory diseases or smoking habit have exhibited the highest risk of mortality. Data were limited to those of survivors of comorbidities but we propose the need to improve comorbidities and terminate cigarette smoking for better prognosis in patients with diabetes. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

[The clinical study of IgA nephropathy with severe chronic periodontitis and aggressive periodontitis].

PubMed

Cao, Y L; Qiao, M; Xu, Z H; Zou, G M; Ma, L L; Li, W G; Xu, B H

2016-01-05

To explore the clinical characteristics of IgA nephropathy (IgAN) with severe chronic periodontitis and aggressive periodontitis. A total of 436 hospitalized patients who underwent renal needle biopsy in the department of nephrology of China-Japan Friendship Hospital from November 2013 to December 2014 were recruited in the study and blindly had periodontal examination. The patients were divided into IgAN group and non-IgAN group according to the renal pathology. The patients with IgAN were further categorized as non-periodontitis, chronic periodontitis and aggressive peridontitis group by Haas classification. The chronic periodontitis group was continually divided into mild, moderate and severe periodontitis group. The levels of interleukin (IL)-1β and IL-6 in gingival crevicular fluid were analyzed by enzyme-linked immunosorbent assays. The prevalence of periodontitis in the study was 88.3% (385/436). The prevalence of chronic periodontitis and aggressive periodontitis were higher in patients with IgAN than those with non-IgAN (P<0.05). Degree of chronic periodontitis was correlated with pathologic grading of IgAN (r=0.48, P<0.001). Compared with IgAN patients with other types of periodontitis, those with severe chronic and aggressive periodontitis had more severe pathology, more frequent recurrent gross hematuria, higher levels of 24 h proteinuria, serum triglyceride and uric acid, higher periodontal probing depth and clinical attatchment level, as well as higer levels of IL-1β and IL-6, but had lower creatinine clearance rate (all P<0.05). The prevalence of severe chronic and aggressive periodontitis was higher in patients with IgAN. Chronic periodontitis is correlated with the onset and development of IgAN. Patients with IgAN have worse condition with the aggravation of periodontitis.

Influence of Postoperative Thrombosis Prophylaxis on the Recurrence of Chronic Subdural Hematoma After Burr-Hole Drainage.

PubMed

Licci, Maria; Kamenova, Maria; Guzman, Raphael; Mariani, Luigi; Soleman, Jehuda

2018-01-01

Chronic subdural hematoma is a commonly encountered disease in neurosurgic practice, whereas its increasing prevalence is compatible with the ageing population. Recommendations concerning postoperative thrombosis prophylaxis after burr-hole drainage of chronic subdural hematoma are lacking. The aim of this study was to analyze the correlation between recurrence of chronic subdural hematoma and postoperative application of thrombosis prophylaxis. Retrospective, consecutive sample of patients undergoing burr-hole drainage for chronic subdural hematoma over 3 years. Single, academic medical center. All patients undergoing surgical evacuation of a chronic subdural hematoma with burr-hole drainage. Exclusion: patients under the age of 18 years, who presented with an acute subdural hematoma and those who underwent a craniotomy. We compared patients receiving thrombosis prophylaxis treatment after burr-hole drainage of chronic subdural hematoma with those who were not treated. Primary outcome measure was reoperation of chronic subdural hematoma due to recurrence. Secondary outcome measures were thromboembolic and cardiovascular events, hematologic findings, morbidity, and mortality. In addition, a subanalysis comparing recurrence rate dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) was undertaken. Overall recurrence rate of chronic subdural hematoma was 12.7%. Out of the 234 analyzed patients, 135 (57.3%) received postoperative thrombosis prophylaxis (low-molecular-weight heparin) applied subcutaneously. Recurrence of chronic subdural hematoma occurred in the thrombosis prophylaxis group and control group in 12 patients (8.9%) and 17 patients (17.2%), respectively, showing no significant difference (odds ratio, 0.47 [95% CI, 0.21 - 1.04]). A subanalysis comparing recurrence rate of chronic subdural hematoma dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) showed no significant difference either (odds ratio, 2.80 [95% CI, 0.83-9.36]). Higher dosage of thrombosis prophylaxis correlated with recurrence rates of chronic subdural hematoma, both in univariate and multivariate analyses. Our data suggest that the application of postoperative thrombosis prophylaxis after burr-hole drainage for chronic subdural hematoma does not result in higher recurrence rates of chronic subdural hematoma. In addition, it seems that early administration of thrombosis prophylaxis (< 48 hr) has no influence on recurrence rates; however, high dosage seems to increase recurrence rates.

Therapeutic-diagnostic Evaluation of Chronic Cough Amongst Adults: Causes, Symptoms and Management at the Primary Care Level, Malaysia.

PubMed

Nantha, Yogarabindranath Swarna

2014-07-01

Patients presenting with chronic cough pose a common diagnostic dilemma during routine consultations at public primary care clinics in Malaysia. To date, there has been little attempt at designing a standardized model or algorithm to facilitate an accurate diagnosis of chronic cough. This study proposes a clinical method to detect the causes of chronic cough in a primary care setting in Malaysia. A total of 117 patients aged above 18 at an urban primary care clinic were tracked over a span of 5 months to diagnose the cause of chronic cough. A therapeutic-diagnostic method was employed to help identify the causes of chronic cough. Subsequently, the demographic details of patients, the prevalence of the different causes of chronic cough and the relationship between history and diagnosis were analyzed statistically. Chronic cough had a slightly higher male preponderance (51.3% vs. 48.7%). Patients within the 'above 60' age category had the highest frequency of chronic cough. The most common cause of chronic cough was post-infectious cough (n = 42, 35.9%), followed closely by angiotensin-converting enzyme-inhibitor related cough (n = 14, 12%). Majority of patients had the symptom of phlegm production (n = 41, 54%). 33 patients (29.2%) had recent upper respiratory tract infection (<2 weeks ago) prior to the diagnosis of chronic cough. There were poor association between symptoms and the various entities comprising chronic cough. The exceptions were the following associations: (1) Bronchial asthma and itchiness of throat (P = 0021), (2) gastroesophageal reflux disease and heartburn (P < 0.001), (3) upper airway cough syndrome and running nose (P = 0.016) and (4) pulmonary tuberculosis and absence of weight loss (P = 0.004). This study demonstrates that the effectiveness of a therapeutic-diagnostic technique in the diagnosis of chronic cough. Consistent with previous studies, there was poor association between most symptoms and the causes of chronic cough. A study involving a larger primary care population is required to confirm the findings found in this analysis.

Older people's experiences of patient-centered treatment for chronic pain: a qualitative study.

PubMed

Teh, Carrie F; Karp, Jordan F; Kleinman, Arthur; Reynolds Iii, Charles F; Weiner, Debra K; Cleary, Paul D

2009-04-01

Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed. To explore the experiences of older adults seeking treatment for chronic pain, with respect to patient-directed care and the patient-provider relationship. In-depth interviews with 15 Caucasian older adults with chronic pain who had been evaluated at a university-based pain clinic. All interviews were audiotaped and the transcripts were analyzed using a grounded theory based approach. Older adults with chronic pain vary in their willingness to be involved in their treatment decisions. Many frequently participate in decisions about their pain treatment by asking for or refusing specific treatments, demanding quality care, or operating outside of the patient-provider relationship to manage pain on their own. However, others prefer to let their provider make the decisions. In either case, having a mutually respectful patient-provider relationship is important to this population. Specifically, participants described the importance of "being heard" and "being understood" by providers. As some providers switch from a patriarchal model of care toward a model of care that emphasizes patient activation and patient-centeredness, the development and cultivation of valued patient-provider relationships may change. While it is important to encourage patient involvement in treatment decisions, high-quality, patient-centered care for older adults with chronic pain should include efforts to strengthen the patient-provider relationship by attending to differences in patients' willingness to engage in patient-directed care and emphasizing shared decision-making.

Healthcare model with use of information and communication technology for patients with chronic disease.

PubMed

Lisiecka-Biełanowicz, Mira; Wawrzyniak, Zbigniew

2016-07-15

The healthcare system is positioned in the patient's environment and works with other determinants of the treatment. Patient care requires a whole system compatible to the needs of organizational and technical solutions. The purpose of this study is to present a new model of patient-oriented care, in which the use of information and communication technology (ICT) can improve the effectiveness of healthcare for patients with chronic diseases. The study material is the process of healthcare for chronically ill patients. Knowledge of the circumstances surrounding ecosystem and of the patients' needs, taking into account the fundamental healthcare goals allows us to build a new models of care, starting with the economic assumptions. The method used is modeling the construction of efficient healthcare system with the patient-centered model using ICT tools. We present a new systemic concept of building patient's environment in which he is the central figure of the healthcare organization - so called patient centered system. The use of ICT in the model of chronic patient's healthcare can improve the effectiveness of this kind of care. The concept is a vision to making wide platform of information management in chronic disease in a real environment ecosystem of patient using ICT tools. On the basis of a systematic approach to the model of chronic disease, and the knowledge of the patient itself, a model of the ecosystem impacts and interactions through information feedback and the provision of services can be constructed. ICT assisted techniques will increase the effectiveness of patient care, in which nowadays information exchange plays a key role.

[Manegement and countermeasures against tuberculous patients with chronic positive sputum].

PubMed

Sato, K

1996-01-01

We studied measures for the prevention and treatment of chronic positive-sputum tuberculosis. Most physicians treating chronic intractable pulmonary tuberculosis are concerned about treatment and control measures. However, both the medical and social aspects of the disease must be dealt with. The study of the medical aspects of tuberculosis used data on patients at the Tokyo National Chest Hospital and other sanitoria in Japan. The socioeconomic study employed data from a health center in Tokyo. Recently, new cases of tuberculosis are concentrated in socioeconomically high risk groups, such as the homeless and illegal aliens, in a few large cities. Patients in these groups often have multidrug-resistant tuberculosis (MDRTB), including many patients with relapsing tuberculosis. However, it is dificult to keep such patients under treatment because of poor compliance and patient dropout. The results of our study are summarized as follows: 1. Prevention and treatment of chronic intractable tuberculosis should involve both the medical and socioeconomic aspects of the disease. 2. Surgical treatment offers benefits for patients with chronically positive sputum. Therefore, surgery should be recommended to patients with chronic intractable MDRTB. 3. If resistance to both isoniazid and rifampin is demonstrated, it is better to replace all ineffective drugs with a new effective regimen than to add a single drug to a failing regimen.

The nursing contribution to chronic disease management: a case of public expectation? Qualitative findings from a multiple case study design in England and Wales.

PubMed

Wilson, Patricia Mary; Brooks, Fiona; Procter, Susan; Kendall, Sally

2012-01-01

The global response to the rise in prevalence of chronic disease is a focus on the way services are managed and delivered, in which nurses are seen as central in shaping patient experience. However, there is relatively little known on how patients perceive the changes to service delivery envisaged by chronic care models. The PEARLE project aimed to explore, identify and characterise the origins, processes and outcomes of effective chronic disease management models and the nursing contributions to the models. Design, settings and participants Case study design of seven sites in England and Wales ensuring a range of chronic disease management models. Participants included over ninety patients and family carers ranging in age from children to older people with conditions such as diabetes, respiratory disease, epilepsy, or coronary heart disease. Semi-structured interviews with patients and family carers. Focus groups were conducted with adolescents and children. A whole systems approach guided data collection and data were thematically analysed. Despite nurses' role and skill development and the shift away from the acute care model, the results suggested that patients had a persisting belief in the monopoly of expertise continuing to exist in the acute care setting. Patients were more satisfied if they saw the nurse as diagnostician, prescriber and medical manager of the condition. Patients were less satisfied when they had been transferred from an established doctor-led to nurse-led service. While nurses within the study were highly skilled, patient perception was guided by the familiar rather than most appropriate service delivery. Most patients saw chronic disease management as a medicalised approach and the nursing contribution was most valued when emulating it. Patients' preferences and expectations of chronic disease management were framed by a strongly biomedical discourse. Perceptions of nurse-led chronic disease management were often shaped by what was previously familiar to the patient. At a strategic level, autonomous nursing practice requires support and further promotion to wider society if there is to be a shift in societal expectation and trust in the nurse's role in chronic disease management. Copyright © 2011 Elsevier Ltd. All rights reserved.

Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer.

PubMed

Martínez-Carrillo, D N; Atrisco-Morales, J; Hernández-Pando, R; Reyes-Navarrete, S; Betancourt-Linares, R; Cruz-del Carmen, I; Illades Aguiar, B; Román-Román, A; Fernández-Tilapa, G

2014-01-01

Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.

Coeliac disease and C virus-related chronic hepatitis: a non association.

PubMed

Gravina, Antonietta Gerarda; Federico, Alessandro; Masarone, Mario; Cuomo, Antonio; Tuccillo, Concetta; Loguercio, Carmelina; Persico, Marcello; Romano, Marco

2012-09-26

A higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C. Two hundred-ten consecutive patients (M/F = 140/70, range of age 35-58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18-74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent. 1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological. 1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Prevalence and associated factors of anxiety and depression among patients with chronic respiratory diseases in eight general hospitals in Jiangsu Province of China: A cross-sectional study.

PubMed

Zhou, Xianmei; Li, Jiashu; Gu, Wei; Wang, Jian; Zhu, Yimin; Zhang, Guicai; Ding, Yuanhua; Tang, Yanfen

2017-05-01

Anxiety and depression are two common psychological disorders with high morbidity worldwide. Understanding of their prevalence of patients with chronic respiratory diseases is becoming more and more important for clinicians. The current study aims at investigation of the prevalence and potential risk factors of anxiety and depression among patients with chronic respiratory diseases. The psychological status, anxiety and depression, and the relevant risk factors of 1713 patients with chronic respiratory diseases from 8 general hospitals in Jiangsu Province of China were evaluated. The results showed that the patients with chronic respiratory diseases experiencing depression and anxiety accounted for 46.00% and 25.34%, respectively. Multivariate logistic regression analysis revealed that lower body mass index (BMI), sleep disorders, limitation of physical activity, and negative life events were significantly associated with an increased risk of both depressive and anxiety symptoms. Poor marital status including divorce, separation and widowerhood was markedly correlated with an increased risk of depression, and chronic pain was with anxiety symptoms, respectively. Collectively, the data demonstrated that depression and anxiety were highly prevalent among the patients with chronic respiratory diseases. It is greatly significant to take specific psychological measures to lower the incidence of depression and anxiety in these patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Quantitative Evaluation of MMP-9 and TIMP-1 Promoter Methylation in Chronic Periodontitis.

PubMed

Li, Xiting; Lu, Jiaxuan; Teng, Wei; Zhao, Chuanjiang; Ye, Xiaolei

2018-03-01

In this study, we investigated the promoter DNA methylation (DNAm) status of the MMP-9 and TIMP-1 genes in patients with chronic periodontitis to evaluate disease progression. Using pyrosequencing technology, DNAm levels of MMP-9 and TIMP-1 CpG islands were measured in 88 chronic periodontitis patients and 15 healthy controls. We found a positive correlation between methylation levels of MMP-9 CpG islands and the severity of chronic periodontitis. Methylated CpG islands were also closely associated with the duration of chronic periodontitis. Moreover, female patients exhibited lower methylation levels of MMP-9 but higher methylation levels of TIMP-1 compared with male patients, and the methylation levels of TIMP-1 gradually decreased with age. The findings of gender disparity in the DNAm of MMP-9 and TIMP-1 genes provide novel insights into chronic periodontitis.

Candida albicans chronic colonisation in cystic fibrosis may be associated with inhaled antibiotics.

PubMed

Noni, Maria; Katelari, Anna; Kaditis, Athanasios; Theochari, Ioanna; Lympari, Ioulia; Alexandrou-Athanassoulis, Helen; Doudounakis, Stavros-Eleftherios; Dimopoulos, George

2015-07-01

Candida albicans is increasingly recognised as a coloniser of the respiratory tract in cystic fibrosis (CF) patients. Yet, the potential role, if any, of the micro-organism in the progress of the disease remains unclear. In this study, we investigated the association between inhaled antibiotics and C. albicans chronic colonisation in patients with CF. A cohort of 121 CF patients born from 1988 to 1996 was, respectively, studied. The medical records of each patient were reviewed from the first time they attended the CF Centre until the occurrence of C. albicans chronic colonisation or their last visit for the year 2010. Chronic colonisation was defined as the presence of C. albicans in more than 50% of cultures in a given year. A number of possible confounders were included in the multivariate logistic regression analysis to identify an independent association between inhaled antibiotics and C. albicans chronic colonisation. Fifty-four (44.6%) of the 121 patients enrolled in the study developed chronic colonisation by the micro-organism. Multivariate logistic regression analysis determined the independent effect of inhaled antibiotic treatment on the odds of chronic colonisation (OR 1.112, 95% CI [1.007-1.229], P = 0.036). Candida albicans chronic colonisation may be associated with the duration of inhaled antibiotic treatment. © 2015 Blackwell Verlag GmbH.

INCIDENCE AND RISK FACTORS FOR CHRONIC PELVIC PAIN AFTER HYSTEROSCOPIC STERILIZATION

PubMed Central

YUNKER, Amanda C.; RITCH, Jessica M. B.; ROBINSON, Erica F.; GOLISH, Cara T.

2014-01-01

Objective To investigate the incidence and pre-operative risk factors for developing pelvic pain after hysteroscopic sterilization using the Essure™ micro-inserts Design Retrospective cohort study (Canadian Task Force classification II-2). Setting University Medical Center Patients A total of 458 patients who underwent hysteroscopic sterilization with Essure™ between January 1, 2005 and June 30, 2012. Results The incidence of acute pelvic pain after hysteroscopic sterilization was 8.1%, and the incidence of persistent pain after 3 months post-procedure was 4.2%. The range of presentation with pain was 1 to 469 days, with a mean time of 56 days. Of the patients that developed chronic pelvic pain after the procedure, 75% presented within 130 days of the procedure. Patients with previous diagnoses of any chronic pain (chronic pelvic pain, chronic low back pain, chronic headache, and fibromyalgia) were more likely to report both acute pain (OR 6.81, 95% CI 2.95,15.73) and chronic pain (OR 6.15, 95% CI 2.10,18.10) after hysteroscopic sterilization. Conclusions Pelvic pain may develop after hysteroscopic sterilization. Patients with preexisting chronic pain diagnoses may be at increased risk of developing pelvic pain after the procedure. Fifty percent of new pelvic pain after Essure™ placement will resolve by 3 months. PMID:24952343

Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes.

PubMed

Liu, Bo-Nan; Zhang, Tai-Ping; Zhao, Yu-Pei; Liao, Quan; Dai, Meng-Hua; Zhan, Han-Xiang

2010-08-01

Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

[Disease management for chronic heart failure patient].

PubMed

Bläuer, Cornelia; Pfister, Otmar; Bächtold, Christa; Junker, Therese; Spirig, Rebecca

2011-02-01

Patients with chronic heart failure (HF) are limited in their quality of life, have a poor prognosis and face frequent hospitalisations. Patient self-management was shown to improve quality of life, reduce rehospitalisations and costs in patients with chronic HF. Comprehensive disease management programmes are critical to foster patient self-management. The chronic care model developed by the WHO serves as the basis of such programmes. In order to develop self-management skills a needs orientated training concept is mandatory, as patients need both knowledge of the illness and the ability to use the information to make appropriate decisions according to their individual situation. Switzerland has no established system for the care of patients with chronic diseases in particular those with HF. For this reason a group of Swiss experts for HF designed a model for disease management for HF patients in Switzerland. Since 2009 the Swiss Heart Foundation offers an education programme based on this model. The aim of this programme is to offer education and support for practitioners, patients and families. An initial pilot evaluation of the program showed mixed acceptance by practitioners, whereas patient assessed the program as supportive and in line with their requirements.

Consequences of dextropropoxyphene market withdrawal in elderly patients with chronic pain.

PubMed

Becquemont, Laurent; Delespierre, Tiba; Bauduceau, Bernard; Benattar-Zibi, Linda; Berrut, Gilles; Corruble, Emmanuelle; Danchin, Nicolas; Derumeaux, Geneviève; Doucet, Jean; Falissard, Bruno; Forette, Francoise; Hanon, Olivier; Pasquier, Florence; Pinget, Michel; Ourabah, Rissane; Bucher, Sophie; Lazkani, Aida; Piedvache, Celine; Bertin, Philippe

2014-10-01

Describe the consequences of dextropropoxyphene (DXP) market withdrawal on analgesic prescriptions and on the quality of therapeutic management of chronic pain. From a cohort of non-institutionalised elderly patients with chronic pain recruited by general practitioners, we selected patients who were treated with DXP daily for at least 6 months just prior to DXP market withdrawal and who had an evaluation of pain and its impact on daily activities before and after DXP withdrawal. One hundred three patients took DXP daily for chronic pain. Immediately after DXP market withdrawal, 42 (40.8%), 55 (53.4%) and 3 (2.9%) patients were treated with step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9%) were no longer receiving any analgesic medication. Among the 55 patients who continued on step 2 analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain intensity and the impact of pain on daily activities remained stable. DXP market withdrawal had no consequences on the intensity or impact of chronic pain in elderly patients.

Time to gain trust and change—Experiences of attachment and mindfulness-based cognitive therapy among patients with chronic pain and psychiatric co-morbidity

PubMed Central

Peilot, Birgitta; Andréll, Paulin; Samuelsson, Anita; Mannheimer, Clas; Frodi, Ann; Sundler, Annelie J.

2014-01-01

The treatment of patients with chronic pain disorders is complex. In the rehabilitation of these patients, coping with chronic pain is seen as important. The aim of this study was to explore the meaning of attachment and mindfulness-based cognitive therapy (CT) among patients with chronic pain and psychiatric co-morbidity. A phenomenological approach within a lifeworld perspective was used. In total, 10 patients were interviewed after completion of 7- to 13-month therapy. The findings reveal that the therapy and the process of interaction with the therapist were meaningful for the patients’ well-being and for a better management of pain. During the therapy, the patients were able to initiate a movement of change. Thus, CT with focus on attachment and mindfulness seems to be of value for these patients. The therapy used in this study was adjusted to the patients’ special needs, and a trained psychotherapist with a special knowledge of patients with chronic pain might be required. PMID:25138653

Discriminative ability of reflex receptive fields to distinguish patients with acute and chronic low back pain.

PubMed

Müller, Monika; Biurrun Manresa, José A; Treichel, Fabienne; Agten, Christoph A; Heini, Paul; Andersen, Ole K; Curatolo, Michele; Jüni, Peter

2016-12-01

Low back pain has a life time prevalence of 70% to 85%. Approximately 10% to 20% of all patients experience recurrent episodes or develop chronic low back pain. Sociodemographic, clinical, and psychological characteristics explain the transition from acute to chronic low back pain only to a limited extent. Altered central pain processing may be a contributing mechanism. The measurement of reflex receptive fields (RRF) is a novel method to assess altered central pain processing. The RRF area denotes the area of the foot sole from which spinal nociceptive reflexes can be elicited. It was shown to be enlarged in patients with acute and chronic low back pain compared with pain-free individuals. The aim of the study was to explore the discriminative ability of the RRF to distinguish patients with acute and chronic low back pain with the hypothesis that enlarged RRF are associated with chronic low back pain. We included 214 patients with either acute or chronic low back pain and compared RRF between groups in both univariable and multivariable analyses adjusted for different sociodemographic and clinical characteristics possibly associated with the transition to chronic pain. We found a mean difference between patients with acute and chronic low back pain of -0.01 (95% confidence interval [CI], -0.06 to 0.04) in the crude, -0.02 (95% CI, -0.08 to 0.04) in the age and sex adjusted, and -0.02 (95% CI, -0.09 to 0.05) in the fully adjusted model. Our results suggest that the enlargement of RRF area may not be associated with the transition from acute to chronic low back pain.

Natural course of new-onset urticaria: Results of a 10-year follow-up, nationwide, population-based study.

PubMed

Eun, Sang Jun; Lee, Jin Yong; Kim, Do-Yeop; Yoon, Hyun-Sun

2018-06-23

Previous epidemiologic studies of the natural course of urticaria mainly focused on chronic spontaneous urticaria and were conducted at hospitals. The natural course of new-onset urticaria in the general population is unknown. Patients with new-onset urticaria were identified from the National Health Insurance Service-National Sample Cohort data. Patients who had at least one visit for urticaria in 2002 and 2003 were excluded and the study cohort consisted of 1,027,620 subjects with no history of urticaria. We analyzed cumulative incidences of urticaria, chronic urticaria, and chronic urticaria remission using the life table estimation method from 2004 to 2013. Their association with related factors was analyzed using the Cox proportional hazards analysis. From 2004 to 2013, a total of 49,129 patients with new-onset urticaria were identified. The 10-year cumulative incidence rate of urticaria for the general population was 4.9% and that of chronic urticaria among patients with new-onset urticaria was 7.8%. Remission rates of chronic urticaria were 52.6% at 1 year and 88.9% at 5 years. Age, sex, residential area, and autoimmune thyroid disease were significantly associated with urticaria or chronic urticaria, but not with chronic urticaria remission, after adjusting for covariates. Female individuals were more likely to have new-onset urticaria but less likely to develop chronic urticaria compared with male individuals. During the 10-year follow-up period, only a small proportion of patients with new-onset urticaria developed chronic urticaria. Remission was achieved in the majority of patients with chronic urticaria regardless of demographic characteristics or accompanying thyroid disease. Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Psychometric evaluation of a new instrument to measure disease self-management of the early stage chronic kidney disease patients.

PubMed

Lin, Chiu-Chu; Wu, Chia-Chen; Wu, Li-Min; Chen, Hsing-Mei; Chang, Shu-Chen

2013-04-01

This study aims to develop a valid and reliable chronic kidney disease self-management instrument (CKD-SM) for assessing early stage chronic kidney disease patients' self-management behaviours. Enhancing early stage chronic kidney disease patients' self-management plays a key role in delaying the progression of chronic kidney disease. Healthcare provider understanding of early stage chronic kidney disease patients' self-management behaviours can help develop effective interventions. A valid and reliable instrument for measuring chronic kidney disease patients' self-management behaviours is needed. A cross-sectional descriptive study collected data for principal components analysis with oblique rotation. Mandarin- or Taiwanese-speaking adults with chronic kidney disease (n=252) from two medical centres and one regional hospital in Southern Taiwan completed the CKD-SM. Construct validity was evaluated by exploratory factor analysis. Internal consistency and test-retest reliability were estimated by Cronbach's alpha and Pearson correlation coefficients. Four factors were extracted and labelled self-integration, problem-solving, seeking social support and adherence to recommended regimen. The four factors accounted for 60.51% of the total variance. Each factor showed acceptable internal reliability with Cronbach's alpha from 0.77-0.92. The test-retest correlations for the CKD-SM was 0.72. The psychometric quality of the CKD-SM instrument was satisfactory. Research to conduct a confirmatory factor analysis to further validate this new instrument's construct validity is recommended. The CKD-SM instrument is useful for clinicians who wish to identify the problems with self-management among chronic kidney disease patients early. Self-management assessment will be helpful to develop intervention tailored to the needs of the chronic kidney disease population. © 2013 Blackwell Publishing Ltd.

Outcomes of greater occipital nerve injections in pediatric patients with chronic primary headache disorders.

PubMed

Gelfand, Amy A; Reider, Amanda C; Goadsby, Peter J

2014-02-01

Chronic migraine is common in pediatrics and generally disabling. In adults, infiltration of the area around the greater occipital nerve can provide short- to medium-term benefit in some patients. This study reports the efficacy of greater occipital nerve infiltrations in pediatric patients with chronic primary headache disorders. Retrospective chart review of patients <18 years with a chronic primary headache disorder undergoing a first-time injection. Infiltrations were unilateral and consisted of a mixture of methylprednisolone acetate, adjusted for weight, and lidocaine 2%. Forty-six patients were treated. Thirty-five (76%) had chronic migraine, 9 (20%) new daily persistent headache (NDPH), and 2 (4%) a chronic trigeminal autonomic cephalalgia. Medication overuse was present in 26%. Ages ranged from 7 to 17 years. Follow-up data were available for 40 (87%). Overall, 53% (21/40) benefitted, and 52% (11/21) benefitted significantly. Benefit onset ranged from 0 to 14 days, mean 4.7 (SD 4.3), with mean benefit duration of 5.4 (SD 4.9) weeks. In chronic migraine, 62% (18/29) benefitted, and 56% (10/18) significantly benefitted. In NDPH, 33% (3/9) benefitted; 33% (n = 1) significantly. Neither child with a chronic trigeminal autonomic cephalalgia benefitted. In logistic regression modeling, medication overuse, age, sex, and sensory change in the distribution of the infiltrated nerve did not predict outcome. There were no serious side effects. Greater occipital nerve injections benefitted 53% of pediatric patients with chronic primary headache disorders. Efficacy appeared greater in chronic migraine than NDPH. Given the benign side effect profile, a greater occipital nerve infiltration seems appropriate before more aggressive approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

Outcomes of Greater Occipital Nerve Injections in Pediatric Patients with Chronic Primary Headache Disorders

PubMed Central

Gelfand, Amy A.; Reider, Amanda C.; Goadsby, Peter J.

2014-01-01

Background Chronic migraine is common in pediatrics and generally disabling. In adults, infiltration of the area around the greater occipital nerve can provide short to medium term benefit in some patients. This study reports the efficacy of greater occipital nerve infiltrations in pediatric patients with chronic primary headache disorders. Methods Retrospective chart review of patients <18 years with a chronic primary headache disorder undergoing a first-time injection. Infiltrations were unilateral and consisted of a mixture of methylprednisolone acetate, adjusted for weight, and lidocaine 2%. Results Forty-six patients were treated. Thirty-five (76%) had chronic migraine, nine (20%) New Daily Persistent Headache (NDPH), and two (4%) a chronic trigeminal autonomic cephalalgia. Medication overuse was present in 26%. Ages ranged from 7–17 years. Follow-up data were available for 40 (87%). Overall, 53% (21/40) benefitted, 52% (11/21) significantly. Benefit onset ranged from 0–14 days, mean 4.7(SD 4.3), with mean benefit duration of 5.4(SD 4.9) weeks. In chronic migraine, 62% (18/29) benefitted, 56% (10/18) significantly. In NDPH, 33% (3/9) benefitted; 33% (n=1) significantly. Neither child with a chronic trigeminal autonomic cephalalgia benefitted. In logistic regression modeling, medication overuse, age, sex, and sensory change in the distribution of the infiltrated nerve did not predict outcome. There were no serious side effects. Conclusions Greater occipital nerve injections benefitted 53% of pediatric patients with chronic primary headache disorders. Efficacy appeared higher in chronic migraine than NDPH. Given the benign side effect profile, a greater occipital nerve infiltration prior to more aggressive approaches seems appropriate. PMID:24268688

Prior history of non-melanoma skin cancer is associated with increased mortality in patients with chronic lymphocytic leukemia

PubMed Central

Toro, Jorge R.; Blake, Patrick W.; Björkholm, Magnus; Kristinsson, Sigurdur Y.; Wang, Zhuoqiao; Landgren, Ola

2009-01-01

We investigated whether a previous diagnosis of non-melanoma skin cancer among chronic lymphocytic leukemia patients is a predictor of poor outcome. Using the Swedish Cancer Registry, we conducted a population-based study to evaluate the survival patterns among chronic lymphocytic leukemia patients with and without non-melanoma skin cancer. Cox proportional hazards regression models were used and Kaplan-Meier curves were constructed. Of a total of 12,041 chronic lymphocytic leukemia cases identified, 236 cases, including 111 squamous cell cancer, had a prior history of non-melanoma skin cancer. Chronic lymphocytic leukemia patients with a prior history of non-melanoma skin cancer had a 1.29-fold (95% CI 1.10–1.52; p=0.0024) increased risk of dying; and those with a history of squamous cell cancer had a further elevated 1.86-fold (95% CI 1.46–2.36; p<0.0001) risk of dying. Kaplan-Meier plots showed that patients with a history of non-melanoma skin cancer, particularly those with squamous cell cancer, had significantly poorer survival than chronic lymphocytic leukemia patients without non-melanoma skin cancer (p<0.0001; log-rank test). Non-melanoma skin cancer may be a novel clinical predictor of worse chronic lymphocytic leukemia outcome. PMID:19794092

Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double-blind randomized clinical trial.

PubMed

Baughman, Robert P; Judson, Marc A; Lower, Elyse E; Drent, Marjolein; Costabel, Ulrich; Flavin, Susan; Lo, Kim Hung; Barnathan, Elliot S

2016-01-15

Limited evidence exists demonstrating an effective treatment for chronic cutaneous sarcoidosis. To determine infliximab's effectiveness in sarcoidosis. We conducted a subset analysis from a randomized, double-blind, placebo-controlled trial for chronic pulmonary sarcoidosis to determine infliximab's effectiveness. Patients with chronic cutaneous sarcoidosis received infliximab (3 or 5 mg/kg) or placebo over 24 weeks. Of 138 patients, the subset analysis evaluated 17 patients with chronic facial and another 9 patients with nonfacial skin involvement. The SASI evaluated lesions for degree of erythema, desquamation, induration, and percentage of area involved. Facial and nonfacial lesions were scored in a blinded manner. Among 5 placebo-treated and 12 infliximab-treated patients, an improvement was observed with infliximab versus placebo in change from baseline to weeks 12 and 24 in desquamation (P<0.005) and induration (P<0.01) at week 24. Erythema, percentage of area involved and the evaluation of paired photographs did not reveal significant differences. Sample size; more extensive disease in placebo patients; chronic therapy upon enrollment; lung as primary organ of sarcoidosis involvement; limited investigator experience with SASI. Infliximab appears to be a beneficial treatment for chronic cutaneous sarcoidosis. The SASI scoring system demonstrated significant improvement versus placebo in lesion desquamation and induration.

Development of a profile scoring system for assessing the psychosocial situation of patients with chronic musculoskeletal pain.

PubMed

Nikaido, Takuya; Fukuma, Shingo; Wakita, Takafumi; Sekiguchi, Miho; Yabuki, Shoji; Onishi, Yoshihiro; Fukuhara, Shunichi; Konno, Shin-Ichi

2017-01-01

Chronic pain is a manifestation of interactions among physical, psychological, and social conditions, but the latter two, that is, the nonphysical correlates of chronic pain, are only rarely measured. This study aimed to develop a profile scoring system for assessing the psychosocial situation of patients with chronic musculoskeletal pain. An expert panel chose social and psychological domains considered to be relevant to patients with chronic pain and wrote questions asking about each of those domains. The questionnaire was completed by 252 patients with chronic musculoskeletal pain. Factor analysis was used to select questionnaire items for each domain. Associations and interactions of pain severity and each domain score with pain-related quality of life (PRQOL) were examined using linear regression models. Five domains were chosen: work, family, sleep, mental health, and PRQOL. Then, a total of 17 questions were created for the work, family, and sleep domains. Using the likelihood-ratio test, we found significant interactions with PRQOL in four pairs: severity-family, severity-mental, family-sleep, and work-mental. The association between pain severity and PRQOL was related to each patient's social and psychological situation. These results suggest that interventions for patients with chronic pain may be personalized to account for each individual's psychosocial situation.

Measuring financial protection for health in families with chronic conditions in Rural China.

PubMed

Jiang, Chunhong; Ma, Jingdong; Zhang, Xiang; Luo, Wujin

2012-11-16

As the world's largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures. We used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient. An additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks. There is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods.

Measuring financial protection for health in families with chronic conditions in Rural China

PubMed Central

2012-01-01

Background As the world’s largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures. Methods We used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient. Results An additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks. Conclusions There is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods. PMID:23158260

Incidence of gastroesophageal reflux disease and positive maxillary antral cultures in children with symptoms of chronic rhinosinusitis.

PubMed

Nation, Javan; Kaufman, Michael; Allen, Meredith; Sheyn, Anthony; Coticchia, James

2014-02-01

Studies have shown that gastroesophageal reflux disease occurs more frequently than expected in children with chronic rhinosinusitis. The objective of this study is to further understand the relationship of pediatric chronic rhinosinusitis and gastroesophageal reflux disease in children with symptoms of rhinorrhea, nasal congestion, and chronic cough. A retrospective chart review of 63 children, ages 6 months to 10 years old with rhinorrhea, nasal congestion, and chronic cough. The patients underwent maxillary cultures, adenoidectomy, and distal third esophageal biopsies. Children with esophageal biopsies showing esophagitis were classified as positive for gastroesophageal reflux disease, and maxillary antral swabs growing a high density of bacteria were classified as positive for chronic rhinosinusitis. Six months to 5 years old children (n=43), 6 (14%) had simultaneous positive maxillary antral cultures and positive esophageal biopsies, 11 (26%) had positive esophageal biopsies alone, 23 (53%) had positive maxillary antral cultures alone, and 3 (7%) had neither. Six to 10 years old children (n=20), 9 (45%) had simultaneous positive maxillary antral cultures and positive esophageal biopsies, 1 (5%) patient had positive esophageal biopsies alone, 3 (15%) patients had positive maxillary antral cultures alone, and 7 (35%) patients had neither. Twenty-seven (42%) of the patients from the whole study had gastroesophageal reflux positive biopsies. The younger children were statistically likely to have chronic rhinosinusitis and gastroesophageal reflux disease independently of each other (p=0.0002). A direct group comparison found the younger group to have independent chronic rhinosinusitis and gastroesophageal reflux disease and the older group to have simultaneous chronic rhinosinusitis and gastroesophageal reflux disease (p=0.0006). In children with the presenting symptoms of rhinorrhea, nasal congestion, and chronic cough, younger children tend to have either chronic rhinosinusitis or gastroesophageal reflux disease, whereas older children tend to have a more complicated etiology of chronic rhinosinusitis and gastroesophageal reflux disease or other. In all of these patients gastroesophageal reflux disease plays an important role, as over 40% of all patients had gastroesophageal positive biopsies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-fungus-associated chronic cough (FACC).

PubMed

Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

2009-05-01

This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi. Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging. The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p < 0.001) when compared with that of the placebo. Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

Long-term occipital nerve stimulation for drug-resistant chronic cluster headache.

PubMed

Leone, Massimo; Proietti Cecchini, Alberto; Messina, Giuseppe; Franzini, Angelo

2017-07-01

Introduction Chronic cluster headache is rare and some of these patients become drug-resistant. Occipital nerve stimulation has been successfully employed in open studies to treat chronic drug-resistant cluster headache. Data from large group of occipital nerve stimulation-treated chronic cluster headache patients with long duration follow-up are advantageous. Patients and methods Efficacy of occipital nerve stimulation has been evaluated in an experimental monocentric open-label study including 35 chronic drug-resistant cluster headache patients (mean age 42 years; 30 men; mean illness duration: 6.7 years). The primary end-point was a reduction in number of daily attacks. Results After a median follow-up of 6.1 years (range 1.6-10.7), 20 (66.7%) patients were responders (≥50% reduction in headache number per day): 12 (40%) responders showed a stable condition characterized by sporadic attacks, five responders had a 60-80% reduction in headache number per day and in the remaining three responders chronic cluster headache was transformed in episodic cluster headache. Ten (33.3%) patients were non-responders; half of these have been responders for a long period (mean 14.6 months; range 2-48 months). Battery depletion (21 patients 70%) and electrode migration (six patients - 20%) were the most frequent adverse events. Conclusions Occipital nerve stimulation efficacy is confirmed in chronic drug-resistant cluster headaches even after an exceptional long-term follow-up. Tolerance can occur years after improvement.

Expanded indications for bariatric surgery: should patients on chronic steroids be offered bariatric procedures?

PubMed

Kaplan, Jennifer A; Schecter, Samuel C; Rogers, Stanley J; Lin, Matthew Y C; Posselt, Andrew M; Carter, Jonathan T

2017-01-01

Patients who take chronic corticosteroids are increasingly referred for bariatric surgery. Little is known about their clinical outcomes. Determine whether chronic steroid use is associated with increased morbidity and mortality after stapled bariatric procedures. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. All patients who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass and were reported to the ACS-NSQIP from 2011 to 2013 were reviewed. Patients were grouped based on type of surgery and history of chronic steroid use. Primary outcome measures were mortality and serious morbidity in the first 30 days. Regression analyses were used to determine predictors of outcome. Of 23,798 patients who underwent laparoscopic sleeve gastrectomy and 38,184 who underwent Roux-en-Y gastric bypass, 385 (1.6%) and 430 (1.1%), respectively, were on chronic steroids. Patients on chronic steroids had a 3.4 times increased likelihood of dying within 30 days (95% confidence interval 1.4-8.1, P = .007), and 2-fold increased odds of serious complications (95% confidence interval 1.2-2.3, P = .008), regardless of surgery type. In multivariate regression, steroid usage remained an independent predictor of mortality and serious complications. In a large, nationally representative patient database, steroid use independently predicted mortality and serious postoperative complications after stapled bariatric procedures. Surgeons should be cautious about offering stapled bariatric procedures to patients on chronic steroids. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Expanded Indications for Bariatric Surgery: Should Patients on Chronic Steroids Be Offered Bariatric Procedures?

PubMed Central

Kaplan, Jennifer A.; Schecter, Samuel C.; Rogers, Stanley J.; Lin, Matthew Y.C.; Posselt, Andrew M.; Carter, Jonathan T.

2015-01-01

Background Patients who take chronic corticosteroids are increasingly referred for bariatric surgery. Little is known about their clinical outcomes. Objective Determine whether chronic steroid use is associated with increased morbidity and mortality after stapled bariatric procedures. Setting American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Methods We reviewed all patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (RYGB) and were reported to the ACS-NSQIP from 2011 to 2013. Patients were grouped based on type of surgery and history of chronic steroid use. Primary outcome measures were mortality and serious morbidity in the first 30 days. Regression analyses were used to determine predictors of outcome. Results Of 23,798 patients who underwent LSG and 38,184 who underwent RYGB, 385 (1.6%) and 430 (1.1%), respectively, were on chronic steroids. Patients on chronic steroids had a 3.4 times increased likelihood of dying within 30 days (95% CI 1.4–8.1, p=0.007), and two-fold increased odds of serious complications (95% CI 1.2–2.3, p=0.008), regardless of surgery type. In multivariate regression, steroid usage remained an independent predictor of mortality and serious complications. Conclusions In a large, nationally-representative patient database, steroid use independently predicted mortality and serious postoperative complications after stapled bariatric procedures. Surgeons should be cautious about offering stapled bariatric procedures to patients on chronic steroids. PMID:26823088

Abnormal brain processing of affective and sensory pain descriptors in chronic pain patients.

PubMed

Sitges, Carolina; García-Herrera, Manuel; Pericás, Miquel; Collado, Dolores; Truyols, Magdalena; Montoya, Pedro

2007-12-01

Previous research has suggested that chronic pain patients might be particularly vulnerable to the effects of negative mood during information processing. However, there is little evidence for abnormal brain processing of affective and sensory pain-related information in chronic pain. Behavioral and brain responses, to pain descriptors and pleasant words, were examined in chronic pain patients and healthy controls during a self-endorsement task. Eighteen patients with fibromyalgia (FM), 18 patients with chronic musculoskeletal pain due to identifiable physical injury (MSK), and 16 healthy controls were asked to decide whether word targets described their current or past experience of pain. The number of self-endorsed words, elapsed time to endorse the words, and event-related potentials (ERPs) elicited by words, were recorded. Data revealed that chronic pain patients used more affective and sensory pain descriptors, and were slower in responding to self-endorsed pain descriptors than to pleasant words. In addition, it was found that affective pain descriptors elicited significantly more enhanced positive ERP amplitudes than pleasant words in MSK pain patients; whereas sensory pain descriptors elicited greater positive ERP amplitudes than affective pain words in healthy controls. These data support the notion of abnormal information processing in chronic pain patients, which might be characterized by a lack of dissociation between sensory and affective components of pain-related information, and by an exaggerated rumination over word meaning during the encoding of self-referent information about pain.

Multimorbidity and patterns of chronic conditions in a primary care population in Switzerland: a cross-sectional study

PubMed Central

Déruaz-Luyet, Anouk; N'Goran, A Alexandra; Senn, Nicolas; Bodenmann, Patrick; Pasquier, Jérôme; Widmer, Daniel; Tandjung, Ryan; Rosemann, Thomas; Frey, Peter; Streit, Sven; Zeller, Andreas; Excoffier, Sophie; Burnand, Bernard; Herzig, Lilli

2017-01-01

Objective To characterise in details a random sample of multimorbid patients in Switzerland and to evaluate the clustering of chronic conditions in that sample. Methods 100 general practitioners (GPs) each enrolled 10 randomly selected multimorbid patients aged ≥18 years old and suffering from at least three chronic conditions. The prevalence of 75 separate chronic conditions from the International Classification of Primary Care-2 (ICPC-2) was evaluated in these patients. Clusters of chronic conditions were studied in parallel. Results The final database included 888 patients. Mean (SD) patient age was 73.0 (12.0) years old. They suffered from 5.5 (2.2) chronic conditions and were prescribed 7.7 (3.5) drugs; 25.7% suffered from depression. Psychological conditions were more prevalent among younger individuals (≤66 years old). Cluster analysis of chronic conditions with a prevalence ≥5% in the sample revealed four main groups of conditions: (1) cardiovascular risk factors and conditions, (2) general age-related and metabolic conditions, (3) tobacco and alcohol dependencies, and (4) pain, musculoskeletal and psychological conditions. Conclusion Given the emerging epidemic of multimorbidity in industrialised countries, accurately depicting the multiple expressions of multimorbidity in family practices’ patients is a high priority. Indeed, even in a setting where patients have direct access to medical specialists, GPs nevertheless retain a key role as coordinators and often as the sole medical reference for multimorbid patients. PMID:28674127

A longitudinal study to identify the influence of quality of chronic care delivery on productive interactions between patients and (teams of) healthcare professionals within disease management programmes.

PubMed

Cramm, Jane Murray; Nieboer, Anna Petra

2014-09-19

The chronic care model is an increasingly used approach to improve the quality of care through system changes in care delivery. While theoretically these system changes are expected to increase productive patient-professional interaction empirical evidence is lacking. This study aims to identify the influence of quality of care on productive patient-professional interaction. Longitudinal study in 18 Dutch regions. Questionnaires were sent to all 5076 patients participating in 18 Disease Management Programmes (DMPs) in 2010 (2676 (53%) respondents). One year later (T1), 4693 patients still participating in the DMPs received a questionnaire (2191 (47%) respondents) and 2 years later (in 2012; T2) 1722 patients responded (out of 4350; 40% response). DMPs Patients' perceptions of the productivity of interactions (measured as relational coordination/coproduction of care) with professionals. Patients were asked about communication dimensions (frequent, accurate, and problem-solving communication) and relationship dimensions (shared goals and mutual respect). After controlling for background characteristics these results clearly show that quality of chronic care (T0), first-year changes in quality of chronic care (T1-T0) and second-year changes in quality of chronic care (T2-T1) predicted productive interactions between patients and professionals at T2 (all at p≤0.001). Furthermore, we found a negative relationship between lower educational level and productive interactions between patients and professionals 2 years later. We can conclude that successfully dealing with the consequences of chronic illnesses requires proactive patients who are able to make productive decisions together with their healthcare providers. Since patients and professionals share responsibility for management of the chronic illness, they must also share control of interactions and decisions. The importance of patient-centeredness is growing and this study reports a first example of how quality of chronic care stimulates productive interactions between patients and professionals. 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.

International recognition of the Chronic Otitis Media Questionnaire 12.

PubMed

Kosyakov, S I; Minavnina, J V; Phillips, J S; Yung, M W

2017-06-01

The Chronic Otitis Media Questionnaire 12 was developed initially in the UK to assess patient-reported health-related quality of life associated with chronic otitis media. This study aimed to determine whether this tool is applicable to the Russian population, which has a materially different healthcare system. A total of 108 patients with different forms of chronic otitis media completed the Russian Chronic Otitis Media Questionnaire 12. The average Russian Chronic Otitis Media Questionnaire 12 score was 19.4 (standard deviation = 8.3). The internal consistency of the Russian Chronic Otitis Media Questionnaire 12 was high, with a Cronbach's alpha value of 0.860. The Russian version of the Chronic Otitis Media Questionnaire 12 was found to be a reliable tool for the assessment of health-related quality of life in patients with chronic otitis media. This sets the scene for international collaboration, using this tool to assess the effectiveness of surgical treatments even amongst countries with different healthcare systems.

Enhancing the Safe and Effective Management of Chronic Pain in Accountable Care Organization Primary Care Practices in Kentucky.

PubMed

Wubu, Selam; Hall, Laura Lee; Straub, Paula; Bair, Matthew J; Marsteller, Jill A; Hsu, Yea-Jen; Schneider, Doron; Hood, Gregory A

Chronic pain is a prevalent chronic condition with significant burden and economic impact in the United States. Chronic pain is particularly abundant in primary care, with an estimated 52% of chronic pain patients obtaining care from primary care physicians (PCPs). However, PCPs often lack adequate training and have limited time and resources to effectively manage chronic pain. Chronic pain management is complex in nature because of high co-occurrence of psychiatric disorders and other medical comorbidities in patients. This article describes a quality improvement initiative conducted by the American College of Physicians (ACP), in collaboration with the Kentucky ACP Chapter, and the Center for Health Services and Outcomes Research at the Johns Hopkins Bloomberg School of Public Health, to enhance chronic pain management in 8 primary care practices participating in Accountable Care Organizations in Kentucky, with a goal of enhancing the screening, diagnosis, and treatment of patients with chronic pain.

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2013-09-27

B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

Nilotinib induced avascular necrosis of femoral head in an adult chronic myeloid leukemia patient.

PubMed

Thekkudan, Shinto Francis; Nityanand, Soniya

2018-06-01

We report a rare case of avascular necrosis of femoral head (AVNFH) in an adult chronic myeloid leukemia - chronic phase (CML-CP) patient during due course of therapy with second line Tyrosine Kinase Inhibitor (TKI), Nilotinib. A high index of clinical suspicion should be kept in any symptomatic CML patient on TKI's.

[Development and application of WEB-based information management system for chronic schistosomiasis patients].

PubMed

Wei, Hua; Fei, Yang; Guo-Hua, Peng

2017-01-16

To improve the management level of patients' information of schistosomiasis control stations in Nanchang City, the B/S three-layer architecture and ASP+SQL technology were applied to formulate the WEB-based management system of chronic schistosomiasis patients' information, so as to achieve the information sharing of chronic schistosomiasis among schistosomiasis control stations.

Determination of glycated hemoglobin in patients with advanced liver disease

PubMed Central

Lahousen, Theresa; Hegenbarth, Karin; Ille, Rottraut; Lipp, Rainer W.; Krause, Robert; Little, Randie R.; Schnedl, Wolfgang J.

2004-01-01

AIM: To evaluate the glycated hemoglobin (HbA 1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA1c results below the non -diabetic reference range by at least one HbA1c method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA1c results were below the non-diabetic reference using at least one of the HbA1c methods. CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA 1c results should be used in patients with advanced liver disease. HbA 1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment. PMID:15259084

Differentiating early-onset chronic depression from episodic depression in terms of cognitive-behavioral and emotional avoidance.

PubMed

Brockmeyer, Timo; Kulessa, Dominika; Hautzinger, Martin; Bents, Hinrich; Backenstrass, Matthias

2015-04-01

Although chronic depression is associated with lower global functioning and poorer treatment response than episodic depression, little is known about the differences between these two forms of depression in terms of psychological factors. Thus, the present study aimed at differentiating chronic and episodic depression regarding cognitive-behavioral and emotional avoidance that have been proposed as important risk factors for depression and promising targets for the treatment of depression. Thirty patients with early onset chronic depression were compared with 30 patients with episodic depression and 30 healthy, never-depressed controls in terms of self-reported cognitive-behavioral (social and non-social) and emotional avoidance. Chronically depressed patients reported more avoidance than healthy controls in each of the measures. Moreover, they reported more cognitive-nonsocial and behavioral-nonsocial as well as behavioral-social and emotional avoidance (in the form of restricted emotional expression to others) than patients with episodic depression. This kind of emotional avoidance also separated best between chronically and episodically depressed patients. Furthermore, general emotion avoidance and behavioral-social avoidance were positively correlated with levels of depression in chronically depressed patients. The results are based on self-report data and should thus be interpreted with caution. Additionally, the cross-sectional design limits any causal conclusions. The findings underscore the relevance of cognitive-behavioral and emotional avoidance in differentiating chronic from episodic depression and healthy controls and advocate a stronger focus on maladaptive avoidance processes in the treatment of chronic depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Long-term outcome of patients with chronic pancreatitis treated with micronutrient antioxidant therapy.

PubMed

Rupasinghe, Sukitha Namal; Siriwardena, Ajith K

2017-04-01

Micronutrient antioxidant therapy did not relieve pain in a European randomized trial of patients with chronic pancreatitis without malnutrition. However, intervention was undertaken only for 6 months leaving unanswered the question of whether long-term antioxidant therapy may modulate chronic pancreatitis. The aim of this study is to assess the outcome of long-term use of micronutrient antioxidant therapy in patients with chronic pancreatitis. This is a single center clinical cohort report of patients with chronic pancreatitis prescribed micronutrient antioxidant therapy and followed for up to 10 years. Data were collected on demographic detail, clinic pain assessment, insulin requirements, interventions and outcome. A group of 30 patients with a diagnosis of chronic pancreatitis constitute the study population. Median age at time of diagnosis was 40 years (range 14-66); 19 (63%) were male and the median duration of symptoms was 2 years (range 0-18). Alcohol was the dominant cause in 22 (73%) patients and 16 (53%) patients were Cambridge stage 1. Twenty-four (80%) patients had pain at presentation. During antioxidant treatment of 4 years (range 1-10), pain decreased but the proportion with abdominal pain compared to those who were pain-free remained constant (P=0.16; two-way ANOVA with Bonferroni correction). There was a significant increase in requirement for insulin (P=0.028) with time together with use of both endoscopic and surgical interventions. This is the first study to report long-term disease-specific outcome in patients with chronic pancreatitis prescribed micronutrient antioxidant therapy. There appears to be no effect of intervention on outcome.

A Chronic Disease Management Student-Faculty Collaborative Practice: Educating Students on Innovation in Health Care Delivery.

PubMed

Remus, Kristin E; Honigberg, Michael; Tummalapalli, Sri Lekha; Cohen, Laura P; Fazio, Sara; Weinstein, Amy R

2016-07-01

In the current transformative health care landscape, it is imperative that clinician educators inspire future clinicians to practice primary care in a dynamic environment. A focus on patient-centered, goal-oriented care for patients with chronic conditions is critical. In 2009, Harvard Medical School founded the Crimson Care Collaborative, a student-faculty collaborative practice (SFCP) network. With the aim of expanding clinical and educational opportunities for medical students and improving patient control of chronic disease (i.e., hypertension, obesity, and diabetes) in an innovative learning environment, in 2012, the authors developed a novel SFCP at their hospital-based academic primary care practice. In this SFCP, students learn to explore patient priorities, provide focused counseling and education, and assist patients with self-management goals during clinical visits. From 2012 to 2014, 250 student volunteers participated in the SFCP as clinicians, innovators, educators, and leaders, with between 80 and 95 medical students engaging each semester. Between January 2012 and March 2014, there were 476 urgent care or chronic disease management visits. Patients with chronic diseases were seen at least twice on average, and by 2014, chronic disease management visits accounted for approximately 74% of visits. Work is under way to create assessment tools to evaluate the practice's educa tional impact and student understanding of the current health care system, develop interdisciplinary care teams, expand efforts in registry management and broaden the patient recruitment scope, further emphasize patient engage ment and retention, and evaluate chronic disease management and patient satisfaction effectiveness.

Congruence or discrepancy? Comparing patients' health valuations and physicians' treatment goals for rehabilitation for patients with chronic conditions.

PubMed

Nagl, Michaela; Farin, Erik

2012-03-01

The aim of this study was to test the congruence of patients' health valuations and physicians' treatment goals for the rehabilitation of chronically ill patients. In addition, patient characteristics associated with greater or less congruence were to be determined. In a questionnaire study, patients' health valuations and physicians' goals were assessed in three chronic conditions [breast cancer (BC), chronic ischemic heart disease (CIHD), and chronic back pain (CBP)] using a ranking method. Sociodemographic variables and health-related quality of life were assessed as patient-related factors that influence congruence. Congruence was determined at the group (Spearman's ρ) and individual levels (percentage of congruence). Patient-related influencing factors were calculated after a simple imputation using multiple logistic regression analysis. At the group level, there were often only low correlations. The mean percentage of congruence was 34.7% (BC), 48.5% (CIHD), and 31.9% (CBP). Patients with BC or CIHD who have a higher level of education showed greater congruence. Our results indicate some high discrepancy rates between physicians' treatment goals and patients' health valuations. It is possible that patients have preferences that do not correspond well with realistic rehabilitation goals or that physicians do not take patients' individual health valuations sufficiently into consideration when setting goals.

Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective.

PubMed

Alric, Laurent; Ollivier-Hourmand, Isabelle; Bérard, Emilie; Hillaire, Sophie; Guillaume, Maeva; Vallet-Pichard, Anais; Bernard-Chabert, Brigitte; Loustaud-Ratti, Veronique; Bourlière, Marc; de Ledinghen, Victor; Fouchard-Hubert, Isabelle; Canva, Valerie; Minello, Anne; Nguyen-Khac, Eric; Leroy, Vincent; Saadoun, David; Trias, Dominique; Pol, Stanislas; Kamar, Nassim

2018-07-01

Patients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily. All patients had severe chronic kidney disease with 70 patients stage G5, including patients on hemodialysis (74.2%), and 23 were stage G4 chronic kidney disease. Severe liver disease (Metavir F3/F4) was found in 33 patients. A sustained virologic response 12 weeks after the end of therapy was achieved in 87 of 90 patients. Two patients had a virologic breakthrough and one had a relapse after treatment withdrawal. Most patients received many concomitant medications (mean 7.7) related to comorbid conditions. Serious adverse events occurred in six patients, including three deaths while on grazoprevir plus elbasvir, not related to this therapy. Thus, once-daily grazoprevir plus elbasvir was highly effective with a low rate of adverse events in this advanced chronic kidney disease difficult-to-treat population with an HCV genotype 1 or 4 infection. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of extracorporeal shock wave lithotripsy for chronic pancreatitis.

PubMed

Vaysse, Thibaut; Boytchev, Isabelle; Antoni, Guillemette; Croix, Damien Sainte; Choury, André Daniel; Laurent, Valérie; Pelletier, Gilles; Buffet, Catherine; Bou-Farah, Rita; Carbonnel, Franck

2016-11-01

There is still uncertainty regarding the efficacy and optimal modalities of extracorporeal shock wave lithotripsy (ESWL) in the treatment of chronic pancreatitis. The aims of the present study were to assess the safety and the efficacy of ESWL, either alone or followed by therapeutic endoscopic retrograde cholangiopancreatography (adjuvant ERCP) and to determine predictive factors of efficacy, in a real-life setting. This study included all consecutive patients who underwent an ESWL in a single University Hospital between 2001 and 2012. The indication for ESWL was obstructive stone(s) of the main pancreatic duct resulting in either painful chronic pancreatitis or recurrent acute pancreatitis. Success was defined by resolution of pain, no analgesic treatment, no acute pancreatitis and no surgical treatment for chronic pancreatitis 6 months after the ESWL. One hundred and forty-six patients were studied; 6/146 (4%) had a complication of ESWL. Among the 132 patients in whom follow-up was completed, 91 (69%) had an adjuvant ERCP. After 6 months of follow-up, 100/132 (76%) patients achieved success. In multivariate analysis, the single significant predictive factor of the success of the ESWL treatment was chronic pain (p = 0.03). Patients who had chronic pain and needed opioid treatment had less chance of success than patients without chronic pain (OR 95%CI 0.31 [0.07-1.14]). We found no difference in the success rates between patients who underwent adjuvant ERCP and those who had ESWL only (p = 0.93). This study shows that the ESWL is a safe and effective treatment for patients with chronic pancreatitis and obstructive stones within the main pancreatic duct. Systematic association with therapeutic ERCP appears to provide no additional benefit and is therefore not recommended.

Predictors of osteodystrophy in patients with chronic nonalcoholic pancreatitis with or without diabetes.

PubMed

Sudeep, Krishna; Chacko, Ashok; Thomas, Nihal; Selvakumar, Ratnasamy; George, Biju; Paul, Thomas Vizhalil; Seshadri, Mandalam S

2011-01-01

To study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables. Thirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated. In patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D. Pancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC.

Use of the UPOINT Classification in Turkish Chronic Prostatitis or Chronic Pelvic Pain Syndrome Patients.

PubMed

Arda, Ersan; Cakiroglu, Basri; Tas, Tuncay; Ekici, Sinan; Uyanik, Bekir Sami

2016-11-01

To determine the positive subdomain numbers and distribution of the UPOINT classification in chronic prostatitis and to compare the erectile dysfunction (ED) pattern. From 2008 to 2013, 839 patients with symptomatic chronic prostatitis or chronic pelvic pain syndrome were included in this study. The correlation between UPOINT domains and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) total score, subscores, and the 5-item International Index of Erectile Function scores were evaluated retrospectively. The mean patient age was calculated as 37.7 ± 7.4 (range 21-65). The average total NIH-CPSI score was determined as 9.07 (range 1-40) and the average positive UPOINT subdomain number was determined as 2.87 ± 0.32 (range 1-6). Subdomain patient numbers and rates were calculated as 529 urinary (63%), 462 psychosocial (55%), 382 organ specific (45%), 290 infection (34%), 288 neurological or systemic (34%), and 418 tenderness (skeletal muscle) (50%), respectively. It was determined that ED, determining the subdomain of sexual dysfunction in patients, was positive in a total of 326 (39.9%) patients, with 220 patients having mild (26.2%), 76 mild to moderate (9.1%), 19 moderate (2.3%), and 5 with severe (0.6%) ED. A statistically significant correlation was not determined between the 5-item International Index of Erectile Function score and UPOINT subdomain number and NIH-CPSI score. It has been determined that although there is a strong and significant correlation between UPOINT classification and NIH-CPSI score in Turkish patients with chronic prostatitis or chronic pelvic pain syndrome, the inclusion of ED as an independent subdomain to the UPOINT classification is not statistically significant. Copyright © 2016 Elsevier Inc. All rights reserved.

Substitution scenario in follow-up of chronic cancer patients in primary care: prevalence, disease duration and estimated extra consultation time.

PubMed

van Dipten, C; Olde Hartman, T C; Biermans, M C J; Assendelft, W J J

2016-02-01

The incidence of cancer as well as survival rates for it are increasing. It is debated whether care in the chronic phase of cancer can be positioned in primary care due to doubts about capacity and workload. To estimate GPs' extra consultation time if they assume responsibility for the care in the chronic phase of cancer. Retrospective cohort study. Estimation of extra consultation time by quantifying prevalence, incidence, survival, number of chronic cancer patients, current practice contacts and registration of risk factors in patients with all types of cancers. The most prevalent types of cancer (with 5-year survival rates) are as follows: breast cancer (91.5%), colorectal cancer (63.8%), prostate cancer (78.3%), melanoma (91.9%) and bladder and urinary tract cancer (77.3%). Primary care practices include ~32 chronic cancer patients, with a potential extra consultation time of ~19 hours per year per 1000 patients. One-third (35%) are already in a chronic disease management programme and 57% were diagnosed >5 years ago. Registration of risk factors for cancer is incomplete, but of better quality when comorbidity is present. Numbers of chronic cancer patients and possible time investment by primary care professionals in the case of a substitution scenario should not be a limiting factor for transition of follow-up from secondary to primary care, as most of the patients were diagnosed >5 years ago and a large proportion of these patients are already monitored in an existing chronic care programme. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Knowledge of hypertension and its management among hypertensive patients on chronic medicines at primary health care public sector facilities in South Africa; findings and implications.

PubMed

Rampamba, Enos M; Meyer, Johanna C; Helberg, Elvera; Godman, Brian

2017-08-01

There are high growing prevalence rates of hypertension in South Africa. Consequently, there is a need to assess knowledge and management among hypertensive patients receiving chronic medication from primary health care (PHC) facilities in South Africa as a basis for improving future management. This is important as South Africa seeks to improve its management of chronic diseases. Descriptive, quantitative study amongst chronic hypertensive patients in the chronic disease programme. Patients were interviewed face-to-face by trained pharmacists using a structured questionnaire. Data analysis included descriptive and inferential statistics. Half (53.7%) of the patients had uncontrolled blood pressure (BP). Less than a third of patients (27.7%) knew what hypertension is, the meaning of recorded BP numbers (4.5%), and what normal BP should be (19.9%). All patients who knew the meaning of BP numbers had formal education (p = 0.047). Only 15.6% of the 56.0% patients, who received hypertension information, received it on antihypertensive medicines specifically. The majority of the patients lacked hypertension specific knowledge and only half had controlled BP. Interventions to improve the control of high BP should be targeted at closing knowledge gaps as part of the current chronic treatment initiatives in South Africa to ensure the benefits of increased access to care are realized.

Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

PubMed

Si, Tianmei; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson; Feng, Yu

2017-12-01

The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

A prospective study of acceptance of pain and patient functioning with chronic pain.

PubMed

McCracken, Lance M; Eccleston, Christopher

2005-11-01

Acceptance of chronic pain is emerging as an important concept in understanding ways that chronic pain sufferers can remain engaged with valued aspects of life. Recent studies have relied heavily on cross-sectional investigations at a single time point. The present study sought to prospectively investigate relations between acceptance of chronic pain and patient functioning. A sample of adults referred for interdisciplinary treatment of severe and disabling chronic pain was assessed twice, an average of 3.9 months apart. Results showed that pain and acceptance were largely unrelated. Pain at Time 2 was weakly related to measures of functioning at Time 2. On the other hand, acceptance at Time 1 was consistently related to patient functioning at Time 2. Those patients who reported greater acceptance at Time 1 reported better emotional, social, and physical functioning, less medication consumption, and better work status at Time 2. These data suggest that willingness to have pain, and to engage in activity regardless of pain, can lead to healthy functioning for patients with chronic pain. Treatment outcome and process studies may demonstrate the potential for acceptance-based clinical methods for chronic pain management.

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476