Evaluation of the effectiveness of octreotide in the conservative treatment of postoperative enterocutaneous fistulas.

PubMed

Alivizatos, Vassilos; Felekis, Dimitrios; Zorbalas, Athanasios

2002-01-01

The aim of this study was to evaluate the effectiveness of Octreotide as an adjunct treatment to total parenteral nutrition in the spontaneous closure of postoperative enterocutaneous fistulas. Medical records of 39 patients with postoperative enterocutaneous fistulas treated in our Department between January 1988 and August 2000 were reviewed. Sixteen patients had duodenal fistulas and 23 had jejunal or ileal fistulas. According to the daily output, there were 20 low fistula output and 19 high fistula output. Conservative treatment consisted of nutritional support with total parenteral nutrition in all the patients. Administration of Octreotide (100 micrograms every 8 hours, subcutaneously) was done in 21 consecutive patients until spontaneous closure of the fistulas or their subsequent surgical closure. The occurrence of fistulas closure was compared using the Fisher's exact test. A mean reduction of 50% of fistula output was noted in all the patients who received Octreotide, within 24 hours of its administration. Spontaneous closure was achieved in 13 patients of the Octreotide group (mean closure time: 15.3 days, range: 6-35) and in 12 patients treated only with total parenteral nutrition (mean closure time: 13.9 days, range: 7-25); this difference was not significant (P = 0.5). Also, the fistula closure rate was not influenced by the anatomic site, the high or low output, and the age of the patient. The results of this study suggest that, as an adjunct treatment to total parenteral nutrition, Octreotide reduces rapidly the fistula output without significant influence in the spontaneous closure rate.

Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study

PubMed Central

Kirzinger, Lukas; Boy, Sandra; Marienhagen, Jörg; Schuierer, Gerhard; Neu, Reiner; Ried, Michael; Hofmann, Hans-Stefan; Wiebe, Karsten; Ströbel, Philipp; May, Christoph; Kleylein-Sohn, Julia; Baierlein, Claudia; Bogdahn, Ulrich; Marx, Alexander; Schalke, Berthold

2016-01-01

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%–86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents. PMID:27992479

Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache.

PubMed

Otsuka, Fumio; Mizobuchi, Satoshi; Ogura, Toshio; Sato, Kenji; Yokoyama, Masataka; Makino, Hirofumi

2004-10-01

We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

Redesign of negatively charged 111In-DTPA-octreotide derivative to reduce renal radioactivity.

PubMed

Oshima, Nobuhiro; Akizawa, Hiromichi; Kawashima, Hidekazu; Zhao, Songji; Zhao, Yan; Nishijima, Ken-Ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

2017-05-01

Radiolabeled octreotide derivatives have been studied as diagnostic and therapeutic agents for somatostatin receptor-positive tumors. To prevent unnecessary radiation exposure during their clinical application, the present study aimed to develop radiolabeled peptides which could reduce radioactivity levels in the kidney at both early and late post-injection time points by introducing a negative charge with an acidic amino acid such as L-aspartic acid (Asp) at a suitable position in 111 In-DTPA-conjugated octreotide derivatives. Biodistribution of the radioactivity was evaluated in normal mice after administration of a novel radiolabeled peptide by a counting method. The radiolabeled species remaining in the kidney were identified by comparing their HPLC data with those obtained by alternative synthesis. The designed and synthesized radiolabeled peptide 111 In-DTPA-d-Phe -1 -Asp 0 -d-Phe 1 -octreotide exhibited significantly lower renal radioactivity levels than those of the known 111 In-DTPA-d-Phe 1 -octreotide at 3 and 24h post-injection. The radiolabeled species in the kidney at 24h after the injection of new octreotide derivative represented 111 In-DTPA-d-Phe-OH and 111 In-DTPA-d-Phe-Asp-OH as the metabolites. Their radiometabolites and intact 111 In-DTPA-conjugated octreotide derivative were observed in urine within 24h post-injection. The present study provided a new example of an 111 In-DTPA-conjugated octreotide derivative having the characteristics of both reduced renal uptake and shortened residence time of radioactivity in the kidney. It is considered that this kinetic control was achieved by introducing a negative charge on the octreotide derivative thereby suppressing the reabsorption in the renal tubules and affording the radiometabolites with appropriate lipophilicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome.

PubMed

Gambineri, Alessandra; Patton, Laura; De Iasio, Rosaria; Cantelli, Barbara; Cognini, Graciela Estela; Filicori, Marco; Barreca, Antonina; Diamanti-Kandarakis, Evanthia; Pagotto, Uberto; Pasquali, Renato

2005-07-01

Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. A single-blind, placebo-controlled study was performed, lasting for 7 months. The patients were ambulatory throughout the study. Twenty PCOS subjects were enrolled. Eighteen completed the study. A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.

Continuous subcutaneous octreotide in gastrointestinal cancer patients: pain control and beta-endorphin levels.

PubMed

Befon, S; Mystakidou, K; Lyra, M; Tubanakis, N; Vlahos, L

2000-01-01

Somatostatin is a naturally occurring hormone widely identified in a number of human tissues, with a broad spectrum of physiological actions. Octreotide is a synthetic analogue of somatostatin, which seems to be promising in clinical use. a. to evaluate the efficacy of octreotide in pain control of patients with advanced gastrointestinal cancer, as well as octreotide's outcome in the hepatic function; b. to investigate the relationship between pain intensity and beta-endorphin blood levels in the patients. The study group consisted of 25 patients (age range: 48-89 years, 14 males, 11 females) with far advanced gastrointestinal cancer. All the patients were under s.c. morphine administration using a continuous infusion pump. When pain intensity increased, 0.6 mg/day of octreotide was added to the therapeutic regimen in the same syringe of the continuous infusion pump. Pain intensity and beta-endorphin blood levels were measured five times: Once before octreotide administration and the other four 12, 24, 48 hours and 7 days after. A complete blood count and a biochemical screening profile were taken before the administration of octreotide as well as on the 7th and the 14th day. 24 out of 25 cases showed a reduction in pain intensity (pretreatment x = 5.3, post-treatment x = 0.6). beta-endorphin blood levels increased significantly during the study (an increase of 184.78% was observed on the 7th treatment day). In one patient pain control was achieved by increasing morphine dosage. Statistically significant changes were observed in hepatic function indices (p < 0.02). Significant side-effects were not observed. Octreotide can be used as an adjuvant analgesic in the management of gastrointestinal cancer pain which is managed by continuous s.c. administration. Although fuither research needs to be done, octreotide's administration seemed to improve hepatic function of these patients, therefore, it could potentially have a positive effect in the patient's quality of life.

The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells.

PubMed

Cerovac, Vesna; Monteserin-Garcia, Jose; Rubinfeld, Hadara; Buchfelder, Michael; Losa, Marco; Florio, Tullio; Paez-Pereda, Marcelo; Stalla, Günter K; Theodoropoulou, Marily

2010-01-15

Rapamycin and its analogues have significant antiproliferative action against a variety of tumors. However, sensitivity to rapamycin is reduced by Akt activation that results from the ablative effects of rapamycin on a p70 S6K-induced negative feedback loop that blunts phosphoinositide 3-kinase (PI3K)-mediated support for Akt activity. Thus, sensitivity to rapamycin might be increased by imposing an upstream blockade to the PI3K/Akt pathway. Here, we investigated this model using the somatostatin analogue octreotide as a tool to decrease levels of activated Ser(473)-phosphorylated Akt (pAkt-Ser(473)) in pituitary tumor cells that express somatostatin receptors. Octreotide increased levels of phosphorylated insulin receptor substrate-1 that were suppressed by rapamycin, subsequently decreasing levels of pAkt-Ser(473) through effects on phosphotyrosine phosphatase SHP-1. Octreotide potentiated the antiproliferative effects of rapamycin in immortalized pituitary tumor cells or human nonfunctioning pituitary adenoma cells in primary cell culture, sensitizing tumor cells even to low rapamycin concentrations. Combined treatment of octreotide and rapamycin triggered G(1) cell cycle arrest, decreasing E2F transcriptional activity and cyclin E levels by increasing levels of p27/Kip1. These findings show that adjuvant treatment with a somatostatin analogue can sensitize pituitary tumor cells to the antiproliferative effects of rapamycin.

(131)I-MIBG radionuclide therapy is safe and cost-effective in the control of symptoms of the carcinoid syndrome.

PubMed

Pathirana, A A; Vinjamuri, S; Byrne, C; Ghaneh, P; Vora, J; Poston, G J

2001-06-01

The standard treatment used to control the symptoms of carcinoid syndrome (CS) involves subcutaneous injections of the somatostatin analogue octreotide. This is expensive (US $8000--16,000 per year), and treatment may be for many years. The aim of this study was to evaluate the efficacy and cost-effectiveness of our experience over the last 5 years with 1-131-labelled metaiodobenzylguanidine (MIBG) radionuclide therapy in the palliation of patients with CS. A consecutive series of 20 symptomatic patients (referred between 1994 and 1999) with CS were evaluated. Fifteen of them underwent(123)I-MIBG scanning. Of the 13 patients with significant tracer uptake in metastatic deposits compared to background, 12 underwent a course of therapeutic(131)I-MIBG (one patient refused). Symptoms, biochemical markers, CT scans, follow-up(123)I-MIBG scans, and the requirement for octreotide were used to assess outcome of treatment. Costs of(131)I-MIBG and octreotide treatments were compared. MIBG treatment was well tolerated in all with only transient side-effects. Ten patients showed a measurable clinical improvement. Seven had a complete clinical response. The mean duration of response was 15.4 months. Octreotide was not required or was reduced in eight patients. Treatment with(131)I-MIBG resulted in a saving of US $1000 per patient, with effective symptom control, when compared to octreotide. 1-131 MIBG therapy is a safe and cost-effective therapeutic option to successfully control symptoms in patients with carcinoid syndrome. Copyright Harcourt Publishers Limited.

The somatostatin analogue octreotide inhibits angiogenesis in the earliest, but not in advanced, stages of portal hypertension in rats.

PubMed

Mejias, Marc; Garcia-Pras, Ester; Tiani, Carolina; Bosch, Jaime; Fernandez, Mercedes

2008-01-01

Angiogenesis is an important determinant of the pathophysiology of portal hypertension contributing to the formation of portosystemic collateral vessels and the hyperdynamic splanchnic circulation associated to this syndrome. Somatostatin and its analogues, like octreotide, have been shown to be powerful inhibitors of experimental angiogenesis. To determine whether octreotide has angioinhibitory effects in portal hypertensive rats. Partial portal vein-ligated (PPVL) rats were treated with octreotide or vehicle during 4 or 7 days. Splanchnic neovascularization and VEGF expression were determined by histological analysis and western blotting. Expression of the somatostatin receptor subtype 2 (SSTR2), which mediates the anti-angiogenic effects of octreotide, was also analyzed. Formation of portosystemic collaterals (radioactive microspheres) and hemodynamic parameters were also measured. Octreotide treatment during 4 days markedly and significantly decreased splanchnic neovascularization, VEGF expression by 63% and portal pressure by 15%, whereas portosystemic collateralization and splanchnic blood flow were not modified. After 1 week of octreotide injection, portal pressure was reduced by 20%, but inhibition of angiogenesis escaped from octreotide therapy, a phenomenon that could be related to the finding that expression of SSTR2 receptor decreased progressively (up to 78% reduction) during the evolution of portal hypertension. This study provides the first experimental evidence showing that octreotide may be an effective anti-angiogenic therapy early after induction of portal hypertension, but not in advanced stages most likely due to SSTR2 down-regulation during the progression of portal hypertension in rats. These findings shed light on new mechanisms of action of octreotide in portal hypertension.

Chylous Fistula following Axillary Lymphadenectomy: Benefit of Octreotide Treatment.

PubMed

González-Sánchez-Migallón, Elena; Aguilar-Jiménez, José; García-Marín, José Andrés; Aguayo-Albasini, José Luis

2016-01-01

Chyle leak following axillary lymph node clearance is a rare yet important complication. The treatment of postoperative chyle fistula still remains unclear. Conservative management is the first line of treatment. It includes axillary drains on continuous suction, pressure dressings, bed rest, and nutritional modifications. The use of somatostatin analogue is well documented as a treatment for chylous fistulas after neck surgery. We present a case of chylous fistula after axillary surgery resolved with the use of octreotide.

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

PubMed

Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

2016-10-01

Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

Effects of octreotide and a-tocopherol on bacterial translocation in experimental intestinal obstruction: a microbiological, light and electronmicroscopical study.

PubMed

Reis, E; Kama, N A; Coskun, T; Korkusuz, P; Ors, U; Aksoy, M; Kulaçoglu, S

1997-01-01

Bacterial translocation induced by intestinal obstruction is suggested to be due to increased intestinal luminal volume, leading to intestinal overgrowth with certain enteric microorganisms and intestinal mucosal damage. If this suggestion is true, maintenance of intestinal mucosal integrity by a cytoprotective agent, a-tocopherol, and inhibition of gastrointestinal secretions by octreotide should decrease the incidence of bacterial translocation and extent of mucosal injury due to intestinal obstruction. Complete intestinal obstruction was created in the distal ileum of male Wistar Albino rats by a single 3-0 silk suture. The animals received subcutaneous injections of 1 ml of physiologic saline (group 1) (PS 24) and 1 ml of saline containing octreotide acetate (100 micrograms/kg) (group 2) (OC 24), at 0, 12 and 24 hours of obstruction. In group 3 (PS 48) and group 4 (OC 48), the rats were treated with subcutaneous physiologic saline (1 ml) and octreotide acetate (100 micrograms/kg), respectively, beginning at the time of obstruction and every 12 hours for 48 hours. The rats in group 5 (Toc 24), were pretreated with intramuscular a-tocopherol 500 mg/kg on day 1 and 8, and underwent laparotomy on day 9. A third dose of a-tocopherol was injected at the time of obstruction on day 9 and no treatment was given thereafter. We tested the incidence of bacterial translocation in systemic organs and circulation and evaluated the histopathological changes in all groups. Treatment with octreotide acetate was found to be ineffective in reducing the incidence of translocation, with no histopathological improvement. Mucosal damage scores, on the other hand, in the a-tocopherol group were statistically less than those in the octreotide and control groups (p < 0.05). Additionally, a-tocopherol treatment decreased the incidence of organ invasion with translocating bacteria, although this difference did not reach statistical significance. Octreotide acetate treatment in complete intestinal obstruction has no effect on the incidence of bacterial translocation. a-Tocopherol, on the other hand, has a cytoprotective effect on intestinal mucosa in intestinal obstruction which, in turn, is thought to decrease bacterial translocation when used in physiological doses and prophylactically.

Case study of a 15-year-old boy with McCune-Albright syndrome combined with pituitary gigantism: effect of octreotide-long acting release (LAR) and cabergoline therapy.

PubMed

Tajima, Toshihiro; Tsubaki, Junko; Ishizu, Katsura; Jo, Wakako; Ishi, Nobuaki; Fujieda, Kenji

2008-07-01

The use of octreotide-LAR and cabergoline therapy has shown great promise in adults with acromegaly; however, the experience in pediatric patients has rarely been reported. We described a clinical course of a 15-year-old boy of McCune-Albright syndrome (MAS) with pituitary gigantism. At the age of 8 years, a growth hormone (GH) and prolactin (PRL) producing pituitary adenoma was diagnosed at our hospital. He also had multiple fibrous dysplasia, so that he was diagnosed as having MAS. The tumor was partially resected, and GNAS1 gene mutation (R201C) was identified in affected tissues. We introduced octreotide to suppress GH secretion (100 mug 2/day s.c). During therapy with octreotide, IGF-1 and GH levels could not be suppressed and the patient frequently complained of nausea from octreotide treatment. Therefore, the therapy was changed to monthly injections of octreotide-LAR at the age of 12.3 years and was partially effective. However, as defect of left visual field worsened due to progressive left optic canal stenosis, he underwent second neurological decompression of the left optic nerve at 13.4 years of age. After surgery, in addition to octreotide-LAR, cabergoline (0.25 mg twice a month) was started. This regimen normalized serum levels of GH and IGF-1; however, he showed impaired glucose tolerance and gallstones at 15.7 years of age. Therefore, the dose of octreotide-LAR was reduced to 10 mg and the dose of cabergoline increased. This case demonstrated the difficulty of treating pituitary gigantism due to MAS. The use of octreotide-LAR and cabergoline should be considered even in pediatric patients; however, adverse events due to octreotide-LAR must be carefully examined.

Expression and function of somatostatin receptor subtype 1 in human growth hormone secreting pituitary tumors deriving from patients partially responsive or resistant to long-term treatment with somatostatin analogs.

PubMed

Matrone, C; Pivonello, R; Colao, A; Cappabianca, P; Cavallo, L M; Del Basso De Caro, M L; Taylor, J E; Culler, M D; Lombardi, G; Di Renzo, G F; Annunziato, L

2004-03-01

The role of somatostatin (SS) receptor subtype 1 (SSTR(1)) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR(1) agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR(1) may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo. Copyright 2004 S. Karger AG, Basel

In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5.

PubMed

Gatto, Federico; Barbieri, Federica; Castelletti, Lara; Arvigo, Marica; Pattarozzi, Alessandra; Annunziata, Francesca; Saveanu, Alexandru; Minuto, Francesco; Castellan, Lucio; Zona, Gianluigi; Florio, Tullio; Ferone, Diego

2011-06-01

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of pituitary adenomas. Medical therapy with somatostatin analogues (SSAs) effectively reduces TSH secretion in approximately 80% of patients and induces shrinkage in about 45% of tumors. According with previous data, resistance to SSA treatment might be due to heterogeneity in somatostatin receptors (SSTRs) expression. We report the case of TSHoma in a 41-year-old man treated with octreotide LAR that caused a dramatic decrease of TSH and thyroid hormones and tumor shrinkage already after 3 months of pre-surgical therapy. In search of potential molecular determinants of octreotide effectiveness, we measured, in primary cultures from this tumor, SSTR and dopamine D2 receptor (D2R) expression, and octreotide and/or cabergoline effects on TSH secretion and cell proliferation. SSTR5 and D2R expression was higher than SSTR2. Octreotide significantly inhibited TSH secretion more effectively than cabergoline (P<0.001), whereas the combined treatment was comparable with cabergoline alone. Similarly, octreotide resulted more effective than cabergoline on cell proliferation, while the combination did not show any additive or synergistic effects. In conclusion, the significant antisecretive and antiproliferative effect of octreotide in this patient might be related to the high expression of SSTR5, in the presence of SSTR2. After reviewing the literature, indeed, in line with previous observations, we hypothesize that SSTR5/SSTR2 ratio in TSHomas may represent a useful marker in predicting the outcome of therapy with SSAs. The role of D2R should be further explored considering that the presence of D2R can influence SSTRs functionality. © Springer Science+Business Media, LLC 2010

A prospective study on the role of octreotide in management of chyle fistula neck.

PubMed

Jain, Avani; Singh, Shashank Nath; Singhal, Pawan; Sharma, Man Prakash; Grover, Mohnish

2015-07-01

To study the effectiveness of octreotide in managing chyle fistula neck and its effect on duration of hospitalization. Prospective study. A total of 19 patients with chyle fistula following neck dissection over a period of 10 years were included in the study. All the patients first underwent conservative management of the chyle leak, including suction drainage, pressure dressings, bed rest, and nutritional modifications. In all of the cases, chyle leak persisted despite conservative management. Octreotide was started in a dose of 100 µg subcutaneously every 8 hours for 5 days in cases with low-output leaks and for 7 days in cases with high-output leaks. In all of the cases, the duration of chyle leak after starting treatment with octreotide and the duration of hospitalization was recorded. Chyle leak stopped in all the cases using octreotide. The mean duration of hospitalization was 13.8 days. Chyle leak stopped within 5 days of starting octreotide in the low-output cases and within 7 days in the high-output cases. This permitted early resumption of a regular oral diet and reduced morbidity associated with chyle fistula. The rapid response and minimal side effect profile make octreotide a promising addition to the medical management of a chyle fistula. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Successful Treatment of Protein-Losing Enteropathy Induced by Intestinal Lymphangiectasia in a Liver Cirrhosis Patient with Octreotide: A Case Report

PubMed Central

Lee, Hang Lak; Kim, Jin Bae; Jeon, Yong Chul; Sohn, Joo Hyun; Hahm, Joon Soo

2004-01-01

A 47-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to our hospital with diarrhea and generalized edema and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia by intestinal biopsy and 99mTc albumin scan. During hospitalization, he received subcutaneous octreotide therapy. After 2 weeks of octreotide therapy, follow-up albumin scan showed no albumin leakage, and the serum albumin level was sustained. We speculate that liver cirrhosis can be a cause of intestinal lymphangiectasia and administration of octreotide should be considered for patients with intestinal lymphangiectasia whose clinical and biochemical abnormalities do not respond to a low-fat diet. PMID:15201518

Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.

PubMed

Bronstein, Marcello D; Fleseriu, Maria; Neggers, Sebastian; Colao, Annamaria; Sheppard, Michael; Gu, Feng; Shen, Chiung-Chyi; Gadelha, Mônica; Farrall, Andrew J; Hermosillo Reséndiz, Karina; Ruffin, Matthieu; Chen, YinMiao; Freda, Pamela

2016-04-02

Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension. Patients with inadequate biochemical control (GH ≥2.5 μg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, at month 17 or 20. Twelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide LAR patients achieved GH <2.5 μg/L and normal IGF-1 (main outcome measure); 27.2 and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1, respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients achieved GH <2.5 μg/L, respectively. Mean (±SD) tumor volume further decreased from the end of the core study by 25 % (±25) and 18 % (±28); 54.3 % of pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (≥20 %) tumor volume reduction during the extension. The safety profile of pasireotide LAR was similar to that of octreotide LAR, with the exception of the frequency and degree of hyperglycemia-related adverse events. Pasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR. clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.

Endothelin-converting enzyme-1 degrades internalized somatostatin-14.

PubMed

Roosterman, Dirk; Kempkes, Cordula; Cottrell, Graeme S; Padilla, Benjamin E; Bunnett, Nigel W; Turck, Christoph W; Steinhoff, Martin

2008-05-01

Agonist-induced internalization of somatostatin receptors (ssts) determines subsequent cellular responsiveness to peptide agonists and influences sst receptor scintigraphy. To investigate sst2A trafficking, rat sst2A tagged with epitope was expressed in human embryonic kidney cells and tracked by antibody labeling. Confocal microscopical analysis revealed that stimulation with sst and octreotide induced internalization of sst2A. Internalized sst2A remained sequestrated within early endosomes, and 60 min after stimulation, internalized sst2A still colocalized with beta-arrestin1-enhanced green fluorescence protein (EGFP), endothelin-converting enzyme-1 (ECE-1), and rab5a. Internalized (125)I-Tyr(11)-SST-14 was rapidly hydrolyzed by endosomal endopeptidases, with radioactive metabolites being released from the cell. Internalized (125)I-Tyr(1)-octreotide accumulated as an intact peptide and was released from the cell as an intact peptide ligand. We have identified ECE-1 as one of the endopeptidases responsible for inactivation of internalized SST-14. ECE-1-mediated cleavage of SST-14 was inhibited by the specific ECE-1 inhibitor, SM-19712, and by preventing acidification of endosomes using bafilomycin A(1). ECE-1 cleaved SST-14 but not octreotide in an acidic environment. The metallopeptidases angiotensin-1 converting enzyme and ECE-2 did not hydrolyze SST-14 or octreotide. Our results show for the first time that stimulation with SST-14 and octreotide induced sequestration of sst2A into early endosomes and that endocytosed SST-14 is degraded by endopeptidases located in early endosomes. Furthermore, octreotide was not degraded by endosomal peptidases and was released as an intact peptide. This mechanism may explain functional differences between octreotide and SST-14 after sst2A stimulation. Moreover, further investigation of endopeptidase-regulated trafficking of neuropeptides may result in novel concepts of neuropeptide receptor inactivation in cancer diagnosis.

Successful use of long acting octreotide in two cases with Beckwith-Wiedemann syndrome and severe hypoglycemia.

PubMed

Al-Zubeidi, Hiba; Gottschalk, Michael E; Newfield, Ron S

2014-01-01

Hyperinsulinism associated with Beckwith-Wiedemann syndrome (BWS) can occur in about 50% of cases, causing hypoglycemia of variable severity. Parenteral use of octreotide may be indicated if unresponsive to diazoxide. There is limited data on use of octreotide in BWS. Chart review describing 2 cases with BWS and hypoglycemia treated with long acting Octreotide as a monthly injection. We describe two unrelated females born large for gestational age found to have clinical features consistent with BWS, who developed severe hypoglycemia. Genetic diagnosis of BWS was confirmed. The first patient was born at 37 weeks and developed hypoglycemia shortly after birth. She was initially started on diazoxide but developed pulmonary congestion and was therefore switched to depot octreotide (LAR). She maintained euglycemia with LAR. In the second patient (born at 26-4/7 weeks), onset of hypoglycemia was delayed till 11 weeks of age due to hydrocortisone (indicated hemodynamically) and continuous feeding, and was partially responsive to diazoxide. She was switched to octreotide 4 times daily, treated till at age 18 months. Despite frequent feeds, she required treatment again between ages 4-6.5 years, initially with diazoxide but due to severe hypertrichosis she was switched to LAR with an excellent response. Both patients treated with LAR for over two years achieved euglycemia above 70 mg/dl and had normal height gain, without side effects. Successful treatment of hypoglycemia can be achieved and maintained with LAR in infants and children with BWS who are either resistant or cannot tolerate diazoxide.

Remission of acromegaly after treatment withdrawal in patients controlled by cabergoline alone or in combination with octreotide: results from a multicenter study.

PubMed

Casagrande, A; Bronstein, M D; Jallad, R S; Mota, J I; Tabet, A; Abucham, J

2017-05-01

Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only in case reports of patients controlled by cabergoline alone. To establish the remission rates (normal IGF-1 for age/sex: IGF-1 ≤ 1.00 xULN) after withdrawal of combined treatment with octreotide LAR and cabergoline and of cabergoline alone, we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding 2 years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments. Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n = 12) or cabergoline alone (n = 4). At 8 weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal. Remission of acromegaly after treatment withdrawal seems to be uncommon in patients controlled by cabergoline, either as monotherapy or in combination with octreotide. In the future, larger studies and/or meta-analysis will be necessary to accurately establish the remission rates of acromegaly after withdrawal of cabergoline with or without somatostatin analogs.

[Octreotide treatment for postoperative chylous ascites in an adult].

PubMed

Senosiain Lalastra, Carla; Martínez González, Javier; Mesonero Gismero, Francisco; Moreira Vicente, Víctor

2012-10-01

Chylous ascites is infequent after abdominal surgery. We describe the case of a 43-year-old man with portal cavernomatosis who underwent surgery to insert a splenorenal shunt, which was not placed due to the absence of signs of portal hypertension. On postoperative day 20, the patient developed abdominal distension and mild dyspnea and was diagnosed with chylous ascites, which was related to the surgery. The patient was initially treated with diet and diuretics, with no clinical response, and consequently octreotide therapy was started. Four days later, the ascites was almost resolved and an ultrasound scan at 4 months showed its complete disappearance. This article demonstrates the effectiveness of octreotide in the treatment of postsurgical chylous ascites. Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Comparative inhibition of the GH/IGF-I axis obtained with either the targeted secretion inhibitor SXN101959 or the somatostatin analog octreotide in growing male rats.

PubMed

Somm, Emmanuel; Bonnet, Nicolas; Zizzari, Philippe; Tolle, Virginie; Toulotte, Audrey; Jones, Richard; Epelbaum, Jacques; Martinez, Alberto; Hüppi, Petra S; Aubert, Michel L

2013-11-01

Abnormally high GH/IGF-I levels, most often caused by adenomas arising from pituitary somatotrophs, generate deleterious effects. We recently described a targeted secretion inhibitor (SXN101742) comprising a GHRH domain and the endopeptidase domain of botulinum toxin serotype D (GHRH-light chain endopeptidase type D domain [LC/D] associated to a heavy chain translocation domain [HN]) able to down-regulate the GH/IGF-I axis. In the present study, we compared the effect of a single iv bolus of a related molecule developed for clinical studies (SXN101959, 1 mg/kg) with a sc infusion of the somatostatin analog octreotide (SMS201-995, 10 μg/kg · h) to lower GH/IGF-I activity in growing male rats. Ten days after administration of SXN101959 or initiation of the octreotide infusion, body and pituitary weights, body length, GH peaks, and IGF-I production were reduced by both treatments but to a greater extent with SXN101959. In contrast to unaltered GH gene expression and increased GH storage in pituitaries from octreotide-treated rats, the inhibition of GH secretion was associated with a collapse of both GH mRNA and protein level in pituitaries from SXN101959-treated rats, in line with a specific decrease in hypothalamic GHRH production, not observed with octreotide. SXN101959 did not induce major apoptotic events in anterior pituitary and exhibited a reversible mode of action with full recovery of somatotroph cell functionality 30 days after treatment. Octreotide infusion permanently decreased ghrelin levels, whereas SXN101959 only transiently attenuated ghrelinemia. Both treatments limited bone mass acquisition and altered specifically tissues development. In conclusion, SXN101959 exerts a powerful and reversible inhibitory action on the somatotropic axis. Specific features of SXN101959, including long duration of action coupled to a strong inhibition of pituitary GH synthesis, represent advantages when treating overproduction of GH.

A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR® (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly

PubMed Central

Mercado, Moises; Borges, Fatima; Bouterfa, Hakim; Chang, Tien-Chun; Chervin, Alberto; Farrall, Andrew J; Patocs, Attila; Petersenn, Stephan; Podoba, Jan; Safari, Mitra; Wardlaw, Joanna

2007-01-01

Objective To evaluate the efficacy, safety and tolerability of octreotide LAR® (long-acting repeatable octreotide) in the primary therapy of acromegaly. Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10–30 mg every 4 weeks, and constituted the population used for this analysis. Measurements and results A clinically relevant reduction (i.e. to ≤ 5 µg/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a ‘safe’ GH value (≤ 2·5 µg/l). At week 48, 16 more patients were considered partial GH responders (GH > 2·5 µg/l and ≤ 5 µg/l) and 44% had reached a GH level ≤ 2·5 µg/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14·7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 ± 145 mm3 to 139 ± 94 mm3 after 24 weeks and to 99 ± 70 mm3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 ± 5077 mm3 at baseline and 2723 ± 3435 and 2406 ± 3207 mm3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant (> 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease. PMID:17465997

A rapid hydrolysis method and DABS-Cl derivatization for complete amino acid analysis of octreotide acetate by reversed phase HPLC.

PubMed

Akhlaghi, Yousef; Ghaffari, Solmaz; Attar, Hossein; Alamir Hoor, Amir

2015-11-01

Octreotide as a synthetic cyclic octapeptide is a somatostatin analog with longer half-life and more selectivity for inhibition of the growth hormone. The acetate salt of octreotide is currently used for medical treatment of somatostatin-related disorders such as endocrine and carcinoid tumors, acromegaly, and gigantism. Octreotide contains both cysteine and tryptophan residues which make the hydrolysis part of its amino acid analysis procedure very challenging. The current paper introduces a fast and additive-free method which preserves tryptophan and cysteine residues during the hydrolysis. Using only 6 M HCl, this hydrolysis process is completed in 30 min at 150 °C. This fast hydrolysis method followed by pre-column derivatization of the released amino acids with 4-N,N-dimethylaminoazobenzene-4'-sulfonyl chloride (DABS-Cl) which takes only 20 min, makes it possible to do the complete amino acid analysis of an octreotide sample in a few hours. The highly stable-colored DABS-Cl derivatives can be detected in 436 nm in a reversed phase chromatographic system, which eliminates spectral interferences to a great extent. The amino acid analysis of octreotide acetate including hydrolysis, derivatization, and reversed phase HPLC determination was validated according to International Conference of Harmonization (ICH) guidelines.

Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide.

PubMed

Oberkirchner, Ursula; Linder, Keith E; Zadrozny, Leah; Olivry, Thierry

2010-10-01

Necrolytic migratory erythema (NME; also known as superficial necrolytic dermatitis) is a syndrome most often associated with certain chronic liver diseases or pancreatic glucagonomas. In humans with glucagonoma-associated NME, skin lesions usually respond to octreotide, a somatostatin analogue that inhibits glucagon release. In this report an 11-year-old golden retriever dog with pancreatic glucagonoma and metastasis to the regional lymph nodes, spleen and liver was diagnosed with NME. The dog exhibited erosions, ulcers and crusts on the paws, pressure points, muzzle, periocular area and prepuce. The dog was also anorexic and had difficulty walking. Because metastasis precluded surgery, treatment was initiated with subcutaneous octreotide (2 μg/kg twice daily). Skin lesions and systemic clinical signs improved markedly within 5 days. The dosage was increased to nearly 3 μg/kg twice daily and signs almost completely resolved within 10 days. Anorexia was the major adverse effect observed. During the following month, both dosage (1-3.7 μg/kg) and frequency (two to four times daily) of the octreotide injections were adjusted to permit control of clinical signs while maintaining adequate appetite. Temporary cessation of octreotide administration resulted in the rapid recurrence of skin lesions. Resuming injections led to improvement of clinical signs within 48 h. The dog was later euthanized because of progressive metastatic disease. In conclusion, subcutaneous octreotide injections were beneficial in this dog with glucagonoma-associated NME. This somatostatin analogue could be a valuable option to treat canine patients with non-resectable or relapsing pancreatic glucagonoma-associated NME. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

Efficacy of octreotide in the management of chronic diarrhoea in AIDS.

PubMed

Romeu, J; Miró, J M; Sirera, G; Mallolas, J; Arnal, J; Valls, M E; Tortosa, F; Clotet, B; Foz, M

1991-12-01

Patients with HIV infection were studied to assess the efficacy of octreotide, a somatostatin analogue, in the long-term management of refractory diarrhoea. Dosage of subcutaneous octreotide was increased progressively at 48 h intervals from 150 to 300, 750 and 1500 micrograms/day according to response. Twenty-nine patients, 21 with Cryptosporidium enteritis, one with Isospora belli enteritis and seven with no identifiable pathogen were selected for the study; four of these were excluded from the study because of death during the first month (two cases), abdominal pain and acute pancreatitis (one case each). Twenty-five patients were evaluable for response. Ten patients (four with Cryptosporidium enteritis, five without an identifiable pathogen and one with I. belli enteritis) achieved a complete response (40%) and nine cases (all with cryptosporidial enteritis) had a partial response (36%). Patients with higher weight and Karnofsky performance status and non-cryptosporidial enteritis had a better response to treatment. Mean durations of treatment and response were 4.2 +/- 4.2 and 4.4 +/- 4.5 months, respectively. In the absence of specific agents for cryptosporidial enteritis and HIV enteropathy, octreotide was found to be useful in the management of chronic diarrhoea in AIDS patients.

Endothelin-Converting Enzyme-1 Degrades Internalized Somatostatin-14

PubMed Central

Roosterman, Dirk; Kempkes, Cordula; Cottrell, Graeme S.; Padilla, Benjamin E.; Bunnett, Nigel W.; Turck, Christoph W.; Steinhoff, Martin

2008-01-01

Agonist-induced internalization of somatostatin receptors (ssts) determines subsequent cellular responsiveness to peptide agonists and influences sst receptor scintigraphy. To investigate sst2A trafficking, rat sst2A tagged with epitope was expressed in human embryonic kidney cells and tracked by antibody labeling. Confocal microscopical analysis revealed that stimulation with sst and octreotide induced internalization of sst2A. Internalized sst2A remained sequestrated within early endosomes, and 60 min after stimulation, internalized sst2A still colocalized with β-arrestin1-enhanced green fluorescence protein (EGFP), endothelin-converting enzyme-1 (ECE-1), and rab5a. Internalized 125I-Tyr11-SST-14 was rapidly hydrolyzed by endosomal endopeptidases, with radioactive metabolites being released from the cell. Internalized 125I-Tyr1-octreotide accumulated as an intact peptide and was released from the cell as an intact peptide ligand. We have identified ECE-1 as one of the endopeptidases responsible for inactivation of internalized SST-14. ECE-1-mediated cleavage of SST-14 was inhibited by the specific ECE-1 inhibitor, SM-19712, and by preventing acidification of endosomes using bafilomycin A1. ECE-1 cleaved SST-14 but not octreotide in an acidic environment. The metallopeptidases angiotensin-1 converting enzyme and ECE-2 did not hydrolyze SST-14 or octreotide. Our results show for the first time that stimulation with SST-14 and octreotide induced sequestration of sst2A into early endosomes and that endocytosed SST-14 is degraded by endopeptidases located in early endosomes. Furthermore, octreotide was not degraded by endosomal peptidases and was released as an intact peptide. This mechanism may explain functional differences between octreotide and SST-14 after sst2A stimulation. Moreover, further investigation of endopeptidase-regulated trafficking of neuropeptides may result in novel concepts of neuropeptide receptor inactivation in cancer diagnosis. PMID:18276747

Vascular endothelial growth factor monitoring in advanced hepatocellular carcinoma patients treated with radiofrequency ablation plus octreotide: a single center experience.

PubMed

Montella, L; Addeo, R; Caraglia, M; Faiola, V; Guarrasi, R; Vincenzi, B; Palmeri, A; Capasso, E; Nocera, V; Tarantino, L; Ariete, M; Martorelli, A; Del Prete, S

2008-08-01

Local therapies such as radiofrequency ablation (RFA) represent a valuable choice in limited hepatocellular carcinoma (HCC) and are increasingly used also in advanced tumors. Medical treatments generally gave frustrating results in advanced HCC especially if comorbidities exist. Several biologic non-chemotherapeutic drugs are currently tested in HCC and, among them, octreotide was evaluated in single series of HCC patients reporting conflicting results. We have treated a series of 35 patients affected by advanced HCC (26 M and 9 F; age range: 55-85 years, median: 73 years) with RFA followed by octreotide to primarily evaluate the safety of combined treatment and to give preliminary evaluation on its activity. We have also evaluated serum VEGF changes during the study. Child A and Child B represented 60% and about 34% of the cases, respectively. Only two patients with Child C compensated cirrhosis were included in this study. All patients have multiple liver HCC nodules and one had bone metastases. Two complete responses, 3 partial responses and 23 disease stabilization for at least three months were obtained (overall response rate, 14,2%; clinical benefit, 80%). Mean overall survival was 31.4 months. The combined treatment was well tolerated. Statistically significant correlation was found between serum VEGF and tumor progression. In conclusion, the combination of RFA and octreotide was active in advanced HCC, however, confirmation in a larger series is required.

Carboxyl-terminal multi-site phosphorylation regulates internalization and desensitization of the human sst2 somatostatin receptor.

PubMed

Lehmann, Andreas; Kliewer, Andrea; Schütz, Dagmar; Nagel, Falko; Stumm, Ralf; Schulz, Stefan

2014-04-25

The somatostatin receptor 2 (sst2) is the pharmacological target of somatostatin analogs that are widely used in the diagnosis and treatment of human neuroendocrine tumors. We have recently shown that the stable somatostatin analogs octreotide and pasireotide (SOM230) stimulate distinct patterns of sst2 receptor phosphorylation and internalization. Like somatostatin, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues namely S341, S343, T353, T354, T356 and T359, which in turn leads to a robust receptor endocytosis. Unlike somatostatin, pasireotide stimulates a selective phosphorylation of S341 and S343 of the human sst2 receptor followed by a partial receptor internalization. Here, we show that exchange of S341 and S343 by alanine is sufficient to block pasireotide-driven internalization, whereas mutation of T353, T354, T356 and T359 to alanine is required to strongly inhibited both octreotide- and somatostatin-induced internalization. Yet, combined mutation of T353, T354, T356 and T359 is not sufficient to prevent somatostatin-driven β-arrestin mobilization and receptor desensitization. Replacement of all fourteen carboxyl-terminal serine and threonine residues by alanine completely abrogates sst2 receptor internalization and β-arrestin mobilization in HEK293 cells. Together, our findings demonstrate for the first time that agonist-selective sst2 receptor internalization is regulated by multi-site phosphorylation of its carboxyl-terminal tail. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Localization of Small‐cell Lung Cancer Xenografts with Iodine‐125‐, Indium‐111‐, and Rhenium‐188‐Somatostatin Analogs

PubMed Central

Hosono, Masako N.; Haberberger, Thomas; Zamora, Paul O.; Guhlke, Stefan; Bender, Hans; Russ Knapp, F. F.; Biersack, Hans J.

1996-01-01

We examined the potential of radiolabeled somatostatin analogs, 125I‐Tyr‐3‐octreotide (125I‐octreotide), 111In‐DTPA(diethylenetriaminepentaacetatic acid)‐d‐Phe‐1‐octreotide (111In‐octreotide), and 188Re‐octreotide for targeting small‐cell lung cancer (SCLC) in a mouse model. Tyr‐3‐octreotide was labeled with 125I by the chloramine T method, and 111In‐octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I‐, 111In‐, and 188Re‐octreotides were injected i.v. into athymic mice bearing NCI‐H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5±0.2, 0.3±0.1, 0.3±0.1 %ID/g, and tumor‐to‐blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I‐, 111In‐, and 188Re‐octreotides, respectively. Accumulations of 111In‐octreotide in normal tissues were lower than those of 125I‐ and 188Re‐octreotides. 188Re‐octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In‐octreotide was the most suitable agent to obtain high tumor‐to‐normal tissue contrast for localizing SCLC. PMID:8878464

nRGD modified lycobetaine and octreotide combination delivery system to overcome multiple barriers and enhance anti-glioma efficacy.

PubMed

Chen, Tijia; Song, Xu; Gong, Ting; Fu, Yao; Yang, Liuqing; Zhang, Zhirong; Gong, Tao

2017-08-01

For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs. Lycobetaine (LBT) was adopted to kill glioma cells and octreotide (OCT) was co-delivered to inhibit VM channels and prevent angiogenesis. LBT-OCT liposomes (LPs) showed controlled release profile in vitro, increased uptake efficiency, improved inhibitory effect against glioma cells and VM formation, and enhanced BBB-crossing capability. The median survival time of glioma-bearing mice administered with LBT-OCT LPs-nRGD was significantly longer than LBT-OCT LPs (P<0.01). Besides, nRGD achieved a stronger inhibitory effect against tumor associated macrophages (TAMs) compared to LPs-iRGD treatment groups in vivo. Thus, LPs-nRGD represented a promising versatile delivery platform for combination drug therapy in glioma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Patterns of pharmacologic treatment in US patients with acromegaly.

PubMed

Broder, Michael S; Chang, Eunice; Ludlam, William H; Neary, Maureen P; Carmichael, John D

2016-05-01

To establish a baseline pattern of care across academic and community settings, it is important to examine the contemporary treatment of acromegaly. We characterized medical treatment patterns for acromegaly in the US to develop a basis for tracking concordance with guidelines. Acromegaly patients were identified in two commercial claims databases for this retrospective analysis. Study subjects had ≥2 medical claims with acromegaly (ICD-9-CM code 253.0) and ≥1 claim for pharmacotherapy (bromocriptine, cabergoline, octreotide SA, octreotide LAR, lanreotide, or pegvisomant) in the study timeframe (1 January 2002-31 December 2013). Patients were considered newly treated if they were continuously enrolled for ≥6 months before first observed treatment and had no claim for pharmacologic treatment during that time. Outcomes included various pharmacotherapies, including combination treatments, and differences between lines of therapy. A total of 3150 patients had ≥1 pharmacotherapy (mean age: 46.5 years; 50.1% were female); 1471 were newly treated. Somatostatin receptor ligands (SRLs) were the most common drug class used first line (57.2%); cabergoline (27.8%) was the most common treatment, followed by octreotide LAR (22.3%) and lanreotide (19.7%). SRLs were also the most commonly used second-line (42.8%) and third-line pharmacotherapies (43.9%), with combination therapy (23.2%) and octreotide LAR (19.8%) as the most commonly used treatments, respectively. This study, representing the largest claims-based analysis of acromegaly to date, used two databases across a 12 year period to examine complex treatment patterns in a difficult-to-study disease. Although wide variation in acromegaly treatment patterns exists in US clinical practice, in first-line, second-line, and third-line therapy, SRL was the most commonly used drug class. Drug combinations also varied considerably across lines of therapy. The switching between different monotherapies and varied use of drugs in combination may suggest an unmet need for alternative treatment options. Our claims-based technique of examining treatment patterns may be used for other rare diseases, although high censoring rates may be a challenge.

Hyperthyroidism caused by an ectopic thyrotropin-secreting tumor of the nasopharynx: a case report and review of the literature.

PubMed

Tong, Anli; Xia, Weibo; Qi, Fang; Jin, Zimeng; Yang, Di; Zhang, Zhuhua; Li, Fang; Xing, Xiaoping; Lian, Xiaolan

2013-09-01

Ectopic thyrotropin (TSH)-secreting tumors are extremely rare. To our knowledge, only three cases have previously been reported so far, but the tumors were not studied ultrastructurally and in vitro. We present a case that was extensively examined to gain deeper insights in terms of the histopathological features and hormonal secretion profile of the tumor. A 49-year-old female complained of nasal obstruction for 15 years and thyrotoxicosis for one and a half years. Except for a high basal TSH with concomitantly elevated free tri-iodothyronine (FT3) and free thyroxine (FT4) levels, her pituitary hormone profile yielded normal results. Magnetic resonance imaging revealed a 2 cm × 2 cm mass in the nasopharynx, which showed an increased tracer uptake on octreotide scintigraphy. Preoperative treatment with octreotide effectively reduced serum TSH, FT3, and FT4 to normal levels. The mass was endoscopically removed via an endonasal approach. Immunophenotyping and hormone determination of cultured cells confirmed that the mass was a plurihormonal TSH-/growth hormone (GH)-/prolactin (PRL)-producing adenoma. Co-expression of TSH and GH was found in most cells. Electron microscopy showed that the adenoma was formed by a single cell type, with secretory granules of small size. In vitro studies demonstrated that octreotide reduced both TSH and GH secretion. We report an ectopic TSH-secreting tumor, which had plurihormonal secretion in vitro, including TSH, GH, and PRL. Histologically, it mimicked a TSH-secreting pituitary adenoma. Octreotide was useful in the diagnosis and treatment of this ectopic TSH-secreting tumor. Ectopic TSH-secreting tumors are extremely rare. In terms of hormone secretion profile, histological characteristics, and response to octreotide, they are similar to pituitary TSH-secreting adenomas, suggesting that they are of identical cell origin.

[Effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats].

PubMed

Yu, Tao; Liu, Rui; Li, Mao; Li, Xian; Qiang, Ou; Huang, Wei; Tang, Chengwei

2014-03-01

To investigate effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats. SD rats were divided into control group (n = 14) and high-fat diet group (n = 36). Obese rats from the high-fat diet group were further divided into 2 groups: the obese group (n = 14) and the octreotide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide per 12 h (40 mg/kg BW) for 8 days. Body weight, fasting plasma glucose (FPG), fasting serum insulin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) levels, pancreatic TG and FFA content were measured. Homeostatic model assessment (HOMA) index was calculated. Somatostatin (SST) and the expression of adipose differentiation-related protein (ADFP) in pancrea were measured. Pathological changes of pancreas were examined with light microscopy. Body weight, Lee's index, FPG, fasting serum insulin, TG, TC levels and HOMA index in the obese group were higher than those in the control group (P < 0.05), while the level of HDL-C in the obese group was lower than that in the control group (P < 0.05). Pancreatic TG, FFA contents and expression of ADFP in the obese group were significantly higher than those in the control group (P < 0.05), while pancreatic SST level in the obese group was lower than that in the control group (P < 0.05). Obvious pancreatic intra-lobular fatty infiltration was observed in the obese group. After treatment of octreotide, body weight, HOMA index, as well as other plasma parameters as above showed decrease as compared with those in the obese group (P < 0.05). In addition, pancreatic TG, FFA contents and the expression of ADFP in the octreotide treated group were also significantly decreased compared with those in the obese group (P < 0.05), pancreatic SST level was increased in the octreotide treated group than that in the obese group (P < 0.05), and pancreatic intra-lobular fatty infiltration was alleviated. Octreotide might improve pancreatic fatty infiltration, lipid disorder, insulin resistance and alleviate pancreatic injury by down-regulating the expression of ADFP in pancreas, and lowering the levels of plasma glucose and lipid in the high-fat diet induced obesity rats.

Effectiveness of octreotide in controlling fasting hypergastrinemia and related enterochromaffin-like cell growth.

PubMed

Ferraro, G; Annibale, B; Marignani, M; Azzoni, C; D'Adda, T; D'Ambra, G; Bordi, C; delle Fave, G

1996-02-01

The effects of long term (6-month), high (500-micrograms), once a day administration of octreotide on enterochromaffin-like (ECL) cell proliferation were evaluated in eight patients with hypergastrinemic atrophic gastritis at risk for the development of gastric carcinoids. Fasting gastrin levels were determined during treatment and up to 6 months after the end of treatment. Chromogranin A, hCG alpha, and somatostatin-immunostained cells were morphometrically evaluated in biopsy specimens of corpus mucosa taken before and after treatment. The results showed that gastrin levels significantly decreased from 950 to 238 ng/L (-74.9%; P < 0.01) at the end of treatment, a decrease that persisted 6 months after the end of treatment (450 ng/L; P < 0.05). The volume density of CgA cells (mostly ECL cells) decreased from 3.7% to 2.1% of the epithelial component (-43%; P < 0.014), that of hCG alpha-storing ECL cells decreased by 85% (P < 0.0007), and that of somatostatin-stained cells decreased by 74% (P < 0.04). No clinically significant side-effects were found. It is concluded that octreotide treatment as used in the present study is safe and effective in reducing hypergastrinemia and associated ECL cell changes in patients with atrophic gastritis. The decrease in D cells is consistent with the occurrence of somatostatin receptors and related autocrine regulation in these cells.

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy.

PubMed

de Jong, M; Bakker, W H; Krenning, E P; Breeman, W A; van der Pluijm, M E; Bernard, B F; Visser, T J; Jermann, E; Béhé, M; Powell, P; Mäcke, H R

1997-04-01

In vitro octreotide receptor binding of [111In-DOTA0,d-Phe1, Tyr3]octreotide (111In-DOTATOC) and the in vivo metabolism of 90Y- or 111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]octreotide [111In-DTPAOC). 111In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of 90Y- or 111In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of 111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that 90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that 111In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.

Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia.

PubMed

Dal Monte, Massimo; Latina, Valentina; Cupisti, Elena; Bagnoli, Paola

2012-05-01

In mouse retinal explants, octreotide, a somatostatin [somatotropin release-inhibiting factor (SRIF)] receptor 2 (sst(2)) agonist, prevents the hypoxia-induced vascular endothelial growth factor upregulation. In mice with oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity, either sst(2) overexpression or octreotide have been found to limit hypoxia-induced angiogenic processes. Here, we investigated whether sst(2) influences retinal degeneration in response to hypoxia in wild-type (WT), sst(1)- and sst(2)-knockout (KO) mice. In retinal explants, we determined the role of sst(2) on apoptotic signals. In control condition, caspase-3 activity and the Bax/Bcl-2 ratio were lower in sst(1)-KO than in WT, but higher in sst(2)-KO than in WT retinas. In all strains, a comparable increase in caspase-3 activity and the Bax/Bcl-2 ratio was observed after hypoxia. The hypoxia-induced increase in apoptotic signals was recovered by octreotide in both WT and sst(1)-KO retinas. To investigate the role of sst(2) on retinal function, we recorded electroretinogram (ERG) in response to light flashes in OIR mice. ERG responses did not differ between WT and KO mice with the exception of oscillatory potentials (OPs) which, in sst(1)-KO mice, displayed much larger amplitude. In all strains, hypoxia drastically reduced a-, b-waves and OPs. In both WT and sst(1)-KO mice, octreotide recovered a- and b-waves, but did not recover OPs in sst(1)-KO mice. Neither apoptotic signals nor ERG was affected by octreotide in sst(2)-KO mice. These results show that sst(2) may protect retinal cells from hypoxia, thus implementing the background to establish potential pharmacological targets based on sst(2) pharmacology.

Octreotide exerts different effects in vivo and in vitro in Cushing's disease.

PubMed

Stalla, G K; Brockmeier, S J; Renner, U; Newton, C; Buchfelder, M; Stalla, J; Müller, O A

1994-02-01

The effect of the long-acting somatostatin analog octreotide (SMS 201-995) on adrenocorticotropin (ACTH) secretion was studied in five patients with untreated Cushing's disease in vivo and in six human corticotropic adenoma cell cultures in vitro. For the in vivo study, 100 micrograms of octreotide sc was given 30 and 180 min after cannulation of the cubital vein and 100 micrograms of corticotropin-releasing hormone (CRH) was injected iv at 210 min. Serum ACTH and cortisol levels were measured for 390 min. In vivo, octreotide had no significant effect either on basal or CRH-stimulated ACTH levels and did not influence cortisol levels. The in vitro studies were conducted with corticotropic adenoma cell cultures derived from adenoma tissue obtained from six patients with Cushing's disease. In four of six cell cultures, octreotide (1 nmol/l-1 mumol/l) inhibited basal ACTH secretion in a dose-dependent manner. The inhibition ranged from 70 to 92% for 1 nmol/l octreotide to 14-46% for 1 mumol/l octreotide as compared to controls (100%). In three of three octreotide-responsive adenoma cell cultures investigated. CRH-stimulated ACTH secretion was suppressed by octreotide. Hydrocortisone pretreatment in vitro abolished the inhibitory effect of octreotide on ACTH secretion in one octreotide-responsive corticotropic adenoma cell culture. In conclusion, we showed that octreotide in most cases could inhibit the ACTH release from human corticotropic adenoma cells in vitro but had no suppressive effect on ACTH levels of patients with Cushing's disease in vivo. This discrepancy could be due to a somatostatin receptor down-regulation by cortisol at the hypercortisolemic state in vivo.

Severe hyperkalaemia resulting from octreotide use in a haemodialysis patient.

PubMed

Adabala, Madhuri; Jhaveri, Kenar D; Gitman, Michael

2010-10-01

A 48-year-old man, with end-stage renal disease (ESRD) on haemodialysis, presented to the emergency department with sulphonylurea-induced hypoglycaemia. His hypoglycaemia was persistent despite glucose infusion, so he was treated with octreotide. Octreotide administration reversed the hypoglycaemia but also resulted in severe hyperkalaemia. The patient was urgently dialysed, the octreotide was discontinued and his potassium normalized. We believe that the hyperkalaemia was caused by octreotide-induced insulin suppression and resultant impaired cellular potassium uptake. Although octreotide may be an effective therapy in refractory sulphonylurea-induced hypoglycaemia, it should be used with caution in patients on dialysis.

Effects of Insulin and Octreotide on Memory and Growth Hormone in Alzheimer's Disease

PubMed Central

Watson, G. Stennis; Baker, Laura D.; Cholerton, Brenna A.; Rhoads, Kristoffer W.; Merriam, George R.; Schellenberg, Gerard D.; Asthana, PhD;Sanjay; Cherrier, Monique; Craft, Suzanne

2009-01-01

Both insulin alone and the somatostatin analogue octreotide alone facilitate memory in patients with Alzheimer's disease (AD). Since octreotide inhibits endogenous insulin secretion, the cognitive effects of insulin and octreotide may not be independent. This study tested the individual and interactive effects of insulin and octreotide on memory and plasma growth hormone (GH) levels in older adults. Participants were 16 memory-impaired (AD=7, amnestic mild cognitive impairment=9; apolipoprotein E [APOE] ε4- [no ε4 alleles]=9, ε4+ [1-2 ε4 alleles]=7) and 19 cognitively-intact older adults (APOE ε4-=17, ε4+=1). On separate days, fasting participants received counterbalanced infusions of (1) insulin (1 mU·kg-1·min-1) and dextrose to maintain euglycemia, (2) octreotide (150 μg/h), (3) insulin, dextrose, and octreotide, or (4) saline. Story recall was the principal endpoint. Insulin alone facilitated delayed recall for ε4-patients, relative to ε4+ patients (P=0.0012). Furthermore, ε4- patients with higher Mattis Dementia Rating Scale (DRS) scores had greater octreotide-induced memory facilitation (P=0.0298). For healthy adults, octreotide facilitated memory (P=0.0122). Unexpectedly, hyperinsulinemia with euglycemia increased GH levels in healthy controls (P=0.0299). Thus, insulin and octreotide appear to regulate memory in older adults. APOE ε4 genotype modulates responses to insulin and octreotide. Finally, insulin may regulate GH levels during euglycemia. PMID:19625744

[Monosymptomatic hyperthyroidism and TSH-producing adenoma: successful therapy with octreotide].

PubMed

Mayinger, B; Axelos, D; Pavel, M; Hahn, E G; Hensen, J

1999-01-29

Magnetic resonance imaging (MRI) of the central nervous system was performed on a 72-year-old woman who was hyperthyroid without suppression of the thyroid-stimulating hormone (TSH) and had complained of a recent onset of headaches. MRI demonstrated a space-occupying lesion, 1 cm in diameter, in the anterior pituitary. The clinical symptoms were marked by a long-standing monosymptomatic illness of rapidly changing mood swings with depressive and manic phases. Endocrinological-biochemical tests showed hyperthyroidism (fT3 10.55 pmol/l and fT4 39 pmol/l) but no TSH suppression (TSH: 2.9 microU/ml). Octreotide scintigraphy documented an activity-rich area in the anterior pituitary and the upper anterior mediastinum. Mediastinal MRI revealed a 5 cm space-occupying mass lying on the right atrium. 131I scintigraphy identified the mass as a retrosternal goitre. As an operation on the anterior pituitary would have carried a high risk for the patient who was in a poor general condition and she had refused to be operated, treatment with octreotide, a long-acting somatostatin analogue, was initiated. This achieved a euthyroid state with partly suppressed TSH, and the patient's emotional swings ceased. If hyperthyroidism coexists with non-suppressed TSH levels, a TSH-producing hypophyseal adenoma should be considered in the differential diagnosis despite its rarity. Octreotide administration is an effective and safe treatment and is the method of choice, especially when there are contraindications to surgical resection of the anterior pituitary.

Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line Setting for Patients with Neuroendocrine Tumors: A 5-Year Update.

PubMed

Bajetta, Emilio; Catena, Laura; Pusceddu, Sara; Spada, Francesca; Iannacone, Claudio; Sarno, Italo; Di Menna, Giandomenico; Dottorini, Lorenzo; Marte, Anna Maria

2018-01-01

We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of "long responder" patients and of time to progression (TTP) and overall survival (OS) at 5 years. Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term. © 2017 S. Karger AG, Basel.

Biodistribution and pharmacokinetics of recombinant α1-microglobulin and its potential use in radioprotection of kidneys

PubMed Central

Ahlstedt, Jonas; Tran, Thuy A; Strand, Filip; Holmqvist, Bo; Strand, Sven-Erik; Gram, Magnus; Åkerström, Bo

2015-01-01

Peptide-receptor radionuclide therapy (PRRT) is a systemically administrated molecular targeted radiation therapy for treatment of neuroendocrine tumors. Fifteen years of clinical use show that renal toxicity, due to glomerular filtration of the peptides followed by local generation of highly reactive free radicals, is the main side-effect that limits the maximum activity that can be administrated for efficient therapy. α1-microglobulin (A1M) is an endogenous radical scavenger shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. An important feature of A1M is that, following distribution to the blood, it is equilibrated to the extravascular compartments and filtrated in the kidneys. Aiming at developing renal protection against toxic side-effects of PRRT, we have characterized the pharmacokinetics and biodistribution of intravenously (i.v.) injected 125I- and non-labelled recombinant human A1M and the 111In- and fluorescence-labelled somatostatin analogue octreotide. Both molecules were predominantly localized to the kidneys, displaying a prevailing distribution in the cortex. A maximum of 76% of the injected A1M and 46% of the injected octreotide were present per gram kidney tissue at 10 to 20 minutes, respectively, after i.v. injection. Immunohistochemistry and fluorescence microscopy revealed a dominating co-existence of the two substances in proximal tubules, with a cellular co-localization in the epithelial cells. Importantly, analysis of kidney extracts displayed an intact, full-length A1M at least up to 60 minutes post-injection (p.i.). In summary, the results show a highly similar pharmacokinetics and biodistribution of A1M and octreotide, thus enabling the use of A1M to protect the kidneys tissue during PRRT. PMID:26269772

[[111In]-DTPA-D-phenylalanine octreotide SPECT for the scintigraphic imaging of enhanced somatostatin-receptor density in endocrine ophthalmopathy].

PubMed

Cordes, M; Hosten, N; Gräf, K J; Wenzel, K W; Venz, S; Keske, U; Eichstädt, H; Felix, R

1994-01-01

Recently, [111In]-DTPA-D-phenylalanine-octreotide was introduced for clinical use. This radioligand binds specifically to somatostatin receptors and is suitable for SPECT examinations. The aim of this study was to clarify whether an increased somatostatin receptor density can be imaged and quantified in patients with endocrine ophthalmopathy (e.o.). 7 patients between 34 and 55 years with e.o. at stages III to VI and 4 controls between 38 and 63 years were examined. All patients and controls received approximately 200 MBq [111In]-DTPA-D-phenylalanine-octreotide by IV injection. A SPECT examination was performed 4 hours after injection and a normalised tracer uptake (A(n)) was calculated for both orbitae. In patients with e.o. the values of A(n) were significantly higher compared with controls (P = 0.002). There was a correlation between A(n) and exophthalmus stages according to Hertel with r = 0.844 (P = 0.001). These results indicate that [111In]-DTPA-D-phenylalanine-octreotide SPECT might be useful for the in vivo assessment of an increased somatostatin receptor density in e.o. These findings could have an impact on the treatment with somatostatin analogous in e.o.

Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

PubMed

Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P

2016-11-01

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca 2+ signaling ([Ca 2+ ] i ), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca 2+ ] i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca 2+ ] i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

Change in quality of life in patients with acromegaly after treatment with octreotide LAR: first application of AcroQoL in Korea

PubMed Central

Chin, Sang Ouk; Chung, Choon Hee; Chung, Yoon-Sok; Kim, Byung-Joon; Kim, Hee Young; Kim, In-Ju; Kim, Jung Guk; Kim, Min-Seon; Kim, Seong-Yeon; Lee, Eun Jig; Lee, Ki Young; Kim, Sung-Woon

2015-01-01

Objectives This study was designed to investigate changes in health-related quality of life (HRQoL) of patients with acromegaly in Korea after medical treatment with octreotide LAR using the validated Korean version of the acromegaly quality of life questionnaire (AcroQoL). Design A prospective, open-label, single-arm study. Setting 11 tertiary centres in Korea. Participants 58 Korean patients (aged 21–72 years) who were newly diagnosed with acromegaly between 2009 and 2012 were prescribed octreotide LAR 20 mg at the time of enrolment. During 24 weeks of observation, AcroQoL survey questionnaires and measurement of growth hormone insulin-like growth factor 1(GH/IGF-I) were performed at baseline, week 12 and week 24. Main outcome measures We assessed the HRQoL of Korean patients with acromegaly after medical treatment with octreotide LAR using the validated Korean version of the AcroQoL questionnaire. Results Patients had a mean age of 47.2 years (29 males), and GH and IGF-I significantly decreased during the first 12 weeks (GH: 4.8 vs 1.9 μg/L, p<0.001; IGF-I: 497 vs 265 μg/L, p<0.001), but showed insignificant change at week 24 (GH: 2.3 μg/L; IGF-I: 294 μg/L). Only AcroQoL scores for the psychological appearance subdomain showed a significant increase during the entire 24 weeks (p<0.05). The change in the psychological appearance subdomain of AcroQoL scores demonstrated a significant but weak negative correlation with change in IGF-I levels (r=−0.282, p=0.039). When patients were divided into two groups according to their disease activity at week 24 (controlled vs uncontrolled), there was no difference in AcroQoL scores, but the psychological appearance subdomain of the two groups appeared to change differently over the entire 24-week period (p=0.047). Conclusions: Medical treatment with octreotide LAR in patients with acromegaly has a limited contribution to HRQoL as assessed by the AcroQoL. PMID:26063564

A Comprehensive Comparison of the Efficacy and Tolerability of Racecadotril with Other Treatments of Acute Diarrhea in Adults

PubMed Central

Fischbach, Wolfgang; Andresen, Viola; Eberlin, Marion; Mueck, Tobias; Layer, Peter

2016-01-01

Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability, but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain, and meteorism; it was also consistent across countries in Africa, Asia, and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. The seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration, and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea, racecadotril is more efficacious than placebo or S. boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or S. boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together, these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults. PMID:27790616

Effects of octreotide infusion, surgery and estrogen on suppression of height increase and 20K growth hormone ratio in a girl with gigantism due to a growth hormone-secreting macroadenoma.

PubMed

Minagawa, M; Yasuda, T; Someya, T; Kohno, Y; Saeki, N; Hashimoto, Y

2000-01-01

We treated an extremely tall 13-year-old girl with a growth hormone (GH)-secreting macroadenoma and GH levels of 120-495 ng/ml with a combination of preoperative octreotide infusion, surgery and postoperative octreotide infusion plus estrogen, which resulted in reduced tumor size prior to surgery, reduced GH levels and completely suppressed growth after surgery. 20K GH is produced by alternative splicing of 22K GH mRNA and the ratio of 20K GH to 22K GH is within a small range in the normal population and high in a GH-secreting tumor. The 20K/22K GH ratio in this patient was persistently elevated during each phase of the treatment and may serve as a sensitive index of tumor-derived GH secretion. Copyright 2000 S. Karger AG, Basel.

New Combined Medical Treatment With Etilefrine and Octreotide for Chylothorax After Esophagectomy

PubMed Central

Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

2015-01-01

Abstract Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies. Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 μg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to <50 mL/day, we performed pleurodesis with Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing. In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct. PMID:26656358

New Combined Medical Treatment With Etilefrine and Octreotide for Chylothorax After Esophagectomy: A Case Report and Review of the Literature.

PubMed

Ohkura, Yu; Ueno, Masaki; Iizuka, Toshiro; Haruta, Shusuke; Tanaka, Tsuyoshi; Udagawa, Harushi

2015-12-01

Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies.Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 μg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to <50 mL/day, we performed pleurodesis with Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing.In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct.

Experience with indium-111 and yttrium-90-labeled somatostatin analogs.

PubMed

Virgolini, I; Traub, T; Novotny, C; Leimer, M; Füger, B; Li, S R; Patri, P; Pangerl, T; Angelberger, P; Raderer, M; Burggasser, G; Andreae, F; Kurtaran, A; Dudczak, R

2002-01-01

The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell lung cancer ((99m)Tc-depreotide), indicating high diagnostic cabability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. Beneficial results were reported for high-dose treatment with (111)In-DTPA-DPhe(1)-octreotide, based on the emission of Auger electrons. The Phase IIa study "MAURITIUS" (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study) showed in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy / GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the "MAURITIUS" study, cummulative treatment doses up to 200 mCi (90)Y-DOTA-lanreotide were given as short-term infusion. Overall treatment results in 70 patients indicated stable tumor disease in 35% of patients and regressive tumor disease in 10% of tumor patients with different tumor entities expressing hSSTR. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to (90)Y-DOTA-lanreotide treatment, were reported. (90)Y-DOTA-DPhe(1)-Tyr(3)-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore be superior for treatment in patients with neuroendocrine tumors. However, there is only limited excess to long-term and survival data at present. Potential indications for (90Y-DOTA-lanreotide are radioiodine-negative thyroid cancer, hepatocellular cancer and lung cancer. Besides newer approaches and recent developments of 188)Re-labeled radioligands, no clinical results on the treatment response are yet available. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plentitude of preclinical data and clinical studies confirm their potential use in diagnosis as well as "proof-of-principle" for therapy of cancer patients. However, an optimal radiopeptide formulatioents. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy.

Effect of everolimus on the pharmacokinetics of octreotide long-acting repeatable in patients with advanced neuroendocrine tumors: An analysis of the randomized phase III RADIANT-2 trial.

PubMed

Pavel, M E; Becerra, C; Grosch, K; Cheung, W; Hasskarl, J; Yao, J C

2017-04-01

In the RADIANT-2 trial, addition of everolimus to octreotide long-acting repeatable (LAR) exhibited a clinically meaningful 5.1-month improvement in progression-free survival (PFS) in patients with advanced functional neuroendocrine tumors. In this study, we characterized the effects of everolimus co-administration on octreotide LAR pharmacokinetics and its relationship with efficacy and safety. At least one evaluable blood everolimus and plasma octreotide predose minimum concentration (C min ) was available for 182 patients and 294 patients, respectively. Concomitant everolimus administration increased octreotide C min with a geometric mean ratio (everolimus/placebo) of 1.47 (90% confidence interval [CI] = 1.32-1.64). Risk for progression was consistently reduced when everolimus C min was increased twofold, regardless of octreotide exposure (hazard ratio [HR] = 0.74; 95% CI = 0.46-1.18; HR = 0.54; 95% CI = 0.32-0.92 for 6 ng/mL and 4 ng/mL octreotide, respectively). Risk for pulmonary or metabolic events was associated with increased everolimus C min . Co-administration of everolimus plus octreotide LAR increased octreotide C min , which did not impact efficacy. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

PubMed Central

Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

2014-01-01

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2 + AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

[Protein-losing enteropathy with systemic lupus erythematosus effectively treated with octreotide and medium chain triglyceride diet: A case report].

PubMed

Kubo, Makoto; Uchida, Kousuke; Nakashima, Tadaaki; Oda, Seiko; Nakamura, Tomomi; Hashimoto, Shinichi; Watada, Toshiko; Nakamura, Hiroshi; Araki, Jun; Matsuzaki, Masunori; Yano, Masafumi

2015-01-01

In January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed.

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation.

PubMed

Frank, N; Hermida, P; Sanchez-Londoño, A; Singh, R; Gradil, C M; Uricchio, C K

2017-07-01

Octreotide is a somatostatin analog that suppresses insulin secretion. We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Twelve horses, N = 5, ID = 7. Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated. Mean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P < .001) effects were detected for glucose and insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant. Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Antitumor Effects of Somatostatin Analogs in Neuroendocrine Tumors

PubMed Central

Dubé, Pierre; Rinke, Anja

2012-01-01

Background. For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs. Methods. A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts. Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20–0.59; p = .000072). Conclusions. In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs. PMID:22628056

Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures.

PubMed

Mohamed, Amira; Blanchard, Marie-Pierre; Albertelli, Manuela; Barbieri, Federica; Brue, Thierry; Niccoli, Patricia; Delpero, Jean-Robert; Monges, Genevieve; Garcia, Stephane; Ferone, Diego; Florio, Tullio; Enjalbert, Alain; Moutardier, Vincent; Schonbrunn, Agnes; Gerard, Corinne; Barlier, Anne; Saveanu, Alexandru

2014-10-01

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) raise difficult therapeutic problems despite the emergence of targeted therapies. Somatostatin analogs (SSA) remain pivotal therapeutic drugs. However, the tachyphylaxis and the limited antitumoral effects observed with the classical somatostatin 2 (sst2) agonists (octreotide and lanreotide) led to the development of new SSA, such as the pan sst receptor agonist pasireotide. Our aim was to compare the effects of pasireotide and octreotide on cell survival, chromogranin A (CgA) secretion, and sst2 phosphorylation/trafficking in pancreatic NET (pNET) primary cells from 15 tumors. We established and characterized the primary cultures of human pancreatic tumors (pNETs) as powerful preclinical models for understanding the biological effects of SSA. At clinically relevant concentrations (1-10 nM), pasireotide was at least as efficient as octreotide in inhibiting CgA secretion and cell viability through caspase-dependent apoptosis during short treatments, irrespective of the expression levels of the different sst receptors or the WHO grade of the parental tumor. Interestingly, unlike octreotide, which induces a rapid and persistent partial internalization of sst2 associated with its phosphorylation on Ser341/343, pasireotide did not phosphorylate sst2 and induced a rapid and transient internalization of the receptor followed by a persistent recycling at the cell surface. These results provide the first evidence, to our knowledge, of striking differences in the dynamics of sst2 trafficking in pNET cells treated with the two SSAs, but with similar efficiency in the control of CgA secretion and cell viability. © 2014 Society for Endocrinology.

The Treatment of Primary Orthostatic Hypotension.

PubMed

Hale, Genevieve M; Valdes, Jose; Brenner, Michael

2017-05-01

To review the efficacy and safety of pharmacological and nonpharmacological strategies used to treat primary orthostatic hypotension (OH). A literature review using PubMed and MEDLINE databases searching hypotension, non-pharmacological therapy, midodrine, droxidopa, pyridostigmine, fludrocortisone, atomoxetine, pseudoephedrine, and octreotide was performed. Randomized or observational studies, cohorts, case series, or case reports written in English between January 1970 and November 2016 that assessed primary OH treatment in adult patients were evaluated. Based on the chosen criteria, it was found that OH patients make up approximately 15% of all syncope patients, predominantly as a result of cardiovascular or neurological insults, or offending medication. Nonpharmacological strategies are the primary treatment, such as discontinuing offending medications, switching medication administration to bedtime, avoiding large carbohydrate-rich meals, limiting alcohol, maintaining adequate hydration, adding salt to diet, and so on. If these fail, pharmacotherapy can help ameliorate symptoms, including midodrine, droxidopa, fludrocortisone, pyridostigmine, atomoxetine, sympathomimetic agents, and octreotide. Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms. Pyridostigmine and fludrocortisone can be used in patients who fail to respond to these agents. Emerging evidence with low-dose atomoxetine is promising, especially in those with central autonomic failure, and may prove to be a viable alternative treatment option. Data surrounding other therapies such as sympathomimetic agents or octreotide are minimal. Medication management of primary OH should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions.

Pituitary gigantism: a retrospective case series.

PubMed

Creo, Ana L; Lteif, Aida N

2016-05-01

Pituitary gigantism (PG) is a rare pediatric disease with poorly defined long-term outcomes. Our aim is to describe the longitudinal clinical course in PG patients using a single-center, retrospective cohort study. Patients younger than 19 years diagnosed with PG were identified. Thirteen cases were confirmed based on histopathology of a GH secreting adenoma or hyperplasia and a height >2 SD for age and gender. Laboratory studies, initial pathology, and imaging were abstracted. Average age at diagnosis was 13 years with an average initial tumor size of 7.4×3.8 mm. Initial transsphenoidal surgery was curative in 3/12 patients. Four of the nine patients who failed the initial surgery required a repeat procedure. Octreotide successfully normalized GH levels in 1/6 patients with disease refractory to surgery (1/6). Two out of five patients received pegvisomant after failing octreotide but only one patient responded to treatment. Five patients were ultimately treated with radiosurgery or radiation patients were followed for an average of 10 years. PG is difficult to treat. In most patients, the initial transsphenoidal surgery failed to normalize GH levels. If the initial surgery was unsuccessful, repeat surgery was unlikely to control GH secretion. Treatment with octreotide or pegvisomant was successful in less than half the patients failing surgery. Radiosurgery was curative, but is not an optimal treatment for pediatric patients. Despite the small sample, our study suggests that the treatment outcome of pediatric PG may be different than adults.

Eight-year follow-up of a child with a GH/prolactin-secreting adenoma: efficacy of pegvisomant therapy.

PubMed

Bergamaschi, S; Ronchi, C L; Giavoli, C; Ferrante, E; Verrua, E; Ferrari, D I; Lania, A; Rusconi, R; Spada, A; Beck-Peccoz, P

2010-01-01

A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +5.1 SDS) and increased height velocity (16.3 cm/year, +6.1 SDS). Basal hormonal evaluation revealed elevated insulin-like growth factor I (IGF-I) levels (938 ng/ml, nv 40-190), prolactin (PRL) (98.0 ng/ml, nv 1.7-24.0) and mean growth hormone (GH) nocturnal concentration (147 ng/ml). Basal adrenal, gonadal and thyroid functions were normal. Hand-wrist bone age was 3.6 years. Magnetic resonance imaging revealed a macroadenoma with moderate suprasellar invasion. The adenoma was surgically removed and histological characterization confirmed the diagnosis of GH/PRL-secreting adenoma. The patient was admitted to our Endocrine Unit when 7.9 years old, because of the persistence of elevated GH, IGF-I and PRL levels, although there was a slight height velocity reduction and absence of tumor recurrence. Treatment with cabergoline was initiated, but only PRL levels normalized. Afterwards, octreotide long-acting release (LAR) was added without reaching the normalization of GH and IGF-I levels. Thus, treatment with octreotide LAR was discontinued and pegvisomant was added to cabergoline, leading to the normalization of IGF-I levels and height velocity without side effects. Other anterior pituitary functions were always normal. To conclude, treatment of pituitary gigantism with pegvisomant was effective and well tolerated in a young giant unresponsive to combined cabergoline and octreotide treatment.

Multicenter Evaluation of Octreotide as Secondary Prophylaxis in Patients With Left Ventricular Assist Devices and Gastrointestinal Bleeding.

PubMed

Shah, Keyur B; Gunda, Sampath; Emani, Sitaramesh; Kanwar, Manreet K; Uriel, Nir; Colombo, Paolo C; Uber, Patricia A; Sears, Melissa L; Chuang, Joyce; Farrar, David J; Brophy, Donald F; Smallfield, George B

2017-11-01

Gastrointestinal (GI) bleeding is one of the most common complications after continuous-flow left ventricular assist device implantation. More than one third of patients with incident bleed go on to develop recurrent GI bleeding. Octreotide, a somatostatin analog, is proposed to reduce the risk of recurrent GI bleeding in this population. This multicenter, retrospective analysis evaluated 51 continuous-flow left ventricular assist device patients who received secondary prophylaxis with octreotide after their index GI bleed from 2009 to 2015. All patients had a hospitalization for GI bleed and received octreotide after discharge. Patient demographics, medical and medication history, and clinical characteristics of patients who rebled after receiving octreotide were compared with non-rebleeders. These data were also compared with matched historical control patients previously enrolled in the HMII (HeartMate II) clinical trials, none of whom received octreotide, to provide a context for the bleeding rates. Twelve patients (24%) who received secondary octreotide prophylaxis developed another GI bleed, whereas 39 (76%) did not. There were similar intergroup demographics; however, significantly more bleeders had a previous GI bleeding history before left ventricular assist device placement (33% versus 5%; P =0.02) and greater frequency of angiodysplasia confirmed during endoscopy (58% versus 23%; P =0.03). Fewer patients in this study experienced a recurrent GI bleed compared with a matched historical control group that did not receive octreotide (24% versus 43%; P =0.04). Patients with continuous-flow left ventricular assist device receiving secondary prophylaxis with octreotide had a significantly lower GI bleed recurrence compared with historical controls not treated with octreotide. Additional prospective studies are needed to confirm these data. © 2017 American Heart Association, Inc.

[Treatment of acromegaly with octreotide LAR].

PubMed

Sosa, Ernesto; Espinosa-de-los-Monteros, Ana Laura; González, Baldomero; Vargas, Guadalupe; Mier, Fernando; Mercado, Moisés

2008-01-01

Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR. 97 patients, 69 females, 71 with macroadenomas, treated with 20-mg im injections of octreotide LAR every 4 weeks, in 23 as primary therapy. No dose escalation was allowed. Patients were evaluated with GH and IGF-1 levels at 4 weeks after the third injection; thereafter, assessments occurred at 3 to 6 months intervals. In 27 unselected patients, evaluations were also performed 6 weeks after the SA injection. A GH concentration < 2.5 ng/mL was reached by 71%, 75% and 83% of patients at the 3rd , 6th and 12th months of follow up respectively, whereas over 30% achieved an IGF-1 index < or = 1.0 at each of these time points, and both biochemical goals were achieved by 30%, 33% and 32% of patients at the same time points. Biochemical success was the same for those patients treated primarily and those treated secondarily and prior radiation made no difference. A baseline GH level > 10 ng/mL was associated with a poor response. A biochemical control rate comparable with other published series it is feasible to reach with the treatment with a fixed dose of 20 mg.

Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

PubMed Central

Wang, Ji-wen; Li, Ying; Mao, Zhi-gang; Hu, Bin; Jiang, Xiao-bing; Song, Bing-bing; Wang, Xin; Zhu, Yong-hong; Wang, Hai-jun

2014-01-01

Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits. PMID:24421637

Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache.

PubMed

Marina, Djordje; Burman, Pia; Klose, Marianne; Casar-Borota, Olivera; Luque, Raúl M; Castaño, Justo P; Feldt-Rasmussen, Ulla

2015-10-01

Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown. We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas. Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA. Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells. A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enterocutaneous fistula: are treatments improving?

PubMed

Draus, John M; Huss, Sara A; Harty, Niall J; Cheadle, William G; Larson, Gerald M

2006-10-01

We studied the etiology, treatment, and outcome of enterocutaneous fistulas in 106 patients to evaluate our current practice and the impact of newer therapies-octreotide, wound vacuum-assisted closure (VAC), and fibrin glue-on clinical outcomes. Review of the literature and our own 1990 study indicate a mortality rate of 5% to 20% for enterocutaneous fistula, and a healing rate of 75% to 85% after definitive surgery. We reviewed all cases of gastrointestinal-cutaneous fistula from 1997 to 2005 at 2 large teaching hospitals. We identified 106 patients with enterocutaneous fistula; patients with irritable bowel disease and anorectal fistulas were excluded. The origin of the fistula was the small bowel in 67 patients, colon in 26, stomach in 8, and duodenum in 5. The etiology of the fistula was previous operation in 81 patients, trauma in 15, hernia mesh erosion in 6, diverticulitis in 2, and radiation in 2. Of the 106 patients in the study, 31 had a high output fistula (greater than 200 mL/day), 44 had a low output fistula, and, in 31 patients, the fistula output was low but there was no record of volume. Initial treatment was nonoperative except for patients with an abscess who needed urgent drainage. In 24 patients, the effect of octreotide was monitored: in 8 patients, fistula output declined; in 16 patients, octreotide was of no benefit. Fibrin glue was used in 8 patients and was of benefit to 1. The wound VAC was used in 13 patients: 12 patients still required operative repair of the fistula, whereas the fistula was healed in 1 patient. The main benefit of the VAC system was improved wound care in all patients before definitive surgery. Total parenteral nutrition was used in most patients to provide nutritional support. Operative repair was performed in 77 patients and was successful in 69 (89%), failing in 6 patients with persistent cancer or infection. Nonoperative treatment was used in 29 patients and resulted in healing in 60%. Of 106 patients, 7 (7%) died of fistula complications. The cause of death was persistence or recurrence of cancer in 4 patients and persistent sepsis in 3. Enterocutaneous fistula continues to be a serious surgical problem. The wound VAC and fibrin glue had anecdotal successes (n = 2), and one-third of patients responded to octreotide. We believe that octreotide should be tried in most patients and that the wound VAC has a role in selected patients. Although 7% overall mortality is lower than in previous studies, the number managed without operation (27%) remains the same. In addition to early control of sepsis, nutritional support, and wound care, a well-timed operation was the most effective treatment.

Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR.

PubMed

Huynh, Lynn; Totev, Todor; Vekeman, Francis; Neary, Maureen P; Duh, Mei S; Benson, Al B

2017-09-01

To calculate the cost reduction associated with diarrhea/flushing symptom resolution/improvement following treatment with above-standard dose octreotide-LAR from the commercial payor's perspective. Diarrhea and flushing are two major carcinoid syndrome symptoms of neuroendocrine tumor (NET). Previously, a study of NET patients from three US tertiary oncology centers (NET 3-Center Study) demonstrated that dose escalation of octreotide LAR to above-standard dose resolved/improved diarrhea/flushing in 79% of the patients within 1 year. Time course of diarrhea/flushing symptom data were collected from the NET 3-Center Study. Daily healthcare costs were calculated from a commercial claims database analysis. For the patient cohort experiencing any diarrhea/flushing symptom resolution/improvement, their observation period was divided into days of symptom resolution/improvement or no improvement, which were then multiplied by the respective daily healthcare cost and summed over 1 year to yield the blended mean annual cost per patient. For patients who experienced no diarrhea/flushing symptom improvement, mean annual daily healthcare cost of diarrhea/flushing over a 1-year period was calculated. The economic model found that 108 NET patients who experienced diarrhea/flushing symptom resolution/improvement within 1 year had statistically significantly lower mean annual healthcare cost/patient than patients with no symptom improvement, by $14,766 (p = .03). For the sub-set of 85 patients experiencing resolution/improvement of diarrhea, their cost reduction was more pronounced, at $18,740 (p = .01), statistically significantly lower than those with no improvement; outpatient costs accounted for 56% of the cost reduction (p = .02); inpatient costs, emergency department costs, and pharmacy costs accounted for the remaining 44%. The economic model relied on two different sources of data, with some heterogeneity in the prior treatment and disease status of patients. Symptom resolution/improvement of diarrhea/flushing after treatment with an above-standard dose of octreotide-LAR in NET was associated with a statistically significant healthcare cost decrease compared to a scenario of no symptom improvement.

Homologous upregulation of sst2 somatostatin receptor expression in the rat arcuate nucleus in vivo.

PubMed

Tannenbaum, G S; Turner, J; Guo, F; Videau, C; Epelbaum, J; Beaudet, A

2001-07-01

In vitro studies using various cell systems have provided conflicting results regarding homologous regulation of somatostatin (SRIH) receptors, and information on whether SRIH regulates the expression of its own receptors in vivo is lacking. In the present study we examined, by in situ hybridization, the effects of pretreatment with the sst2-preferring SRIH analog, octreotide, in vivo, on mRNA levels of two SRIH receptor subtypes, sst1 and sst2, in rat brain and pituitary. (125)I-[DTrp(8)]-SRIH binding was also measured in these regions. Three hours after the iv injection of 50 microg octreotide to conscious adult male rats, there was a 46% increase (p < 0.01) in the labeling density of sst2 mRNA-expressing cells in the hypothalamic arcuate nucleus compared to normal saline-pretreated controls, but not in any of the other brain regions examined. Computer-assisted image analysis revealed that 3 h exposure to octreotide significantly (p < 0.01) augmented both the number and labeling density of sst2 mRNA-expressing cells in the arcuate nucleus, compared to those in saline-treated controls. By contrast, within the anterior pituitary gland, in vivo exposure to octreotide did not affect the expression of sst2 mRNA. No changes in sst1 mRNA-expressing cells were observed after octreotide treatment in any of the regions measured, indicating that the observed effects were homologous, i.e. specific of the receptor subtype stimulated. Octreotide pretreatment was also without effect on the density of (125)I-[DTrp(8)]-SRIH binding in either the arcuate nucleus or pituitary. These results demonstrate, for the first time, that SRIH preexposure in vivo upregulates the expression of a subtype of its own receptors, sst2, within the central nervous system. They further suggest that pretreatment with SRIH in vivo does not cause sst2 receptor desensitization in arcuate nucleus and pituitary. Such homologous regulatory mechanisms may play an important role in the neuroendocrine control of growth hormone (GH) secretion by the arcuate nucleus. Copyright 2001 S. Karger AG, Basel

Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

PubMed

Tundo, Grazia; Ciaccio, Chiara; Sbardella, Diego; Boraso, Mariaserena; Viviani, Barbara; Coletta, Massimiliano; Marini, Stefano

2012-01-01

The deposition of β-amyloid (Aβ) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

Insulinoma: A Rare Cause of a Common Metabolic Disorder - Hypoglycaemia

PubMed Central

El Shafie, Omayma; Sankhla, Dilip; Al-Kindy, Nayil; Al-Hamadani, Aisha; Grant, Christopher; Woodhouse, Nicholas

2008-01-01

We describe the first patient diagnosed with an insulinoma in Oman and successfully managed with a distal laparoscopic pancreatectomy. The importance of obtaining a good history from the patient and/or his family is stressed. All patients with loss of consciousness must have a Reflow check carried out and, if hypoglycaemic, this should be documented in the laboratory and a simultaneous serum sample stored for measurement of insulin, C-peptide proinsulin and sulphonylurea levels, if subsequently indicated. If magnetic resonance imaging fails to locate the tumour, endoscopic ultrasound of the pancreas, or indium 111 labelled octreotide scanning is indicated if the patient’s hypoglycaemia has previously responded to treatment with octreotide. PMID:21654959

Current and future medical treatments for patients with acromegaly.

PubMed

Maffezzoni, Filippo; Formenti, Anna Maria; Mazziotti, Gherardo; Frara, Stefano; Giustina, Andrea

2016-08-01

Acromegaly is a relatively rare condition of growth hormone (GH) excess associated with significant morbidity and, when left untreated, high mortality. Therapy for acromegaly is targeted at decreasing GH and insulin-like growth hormone 1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant) and radiotherapy. However, despite all these treatments option, approximately 50% of patients are not adequately controlled. In this paper, the authors discuss: 1) efficacy and safety of current medical therapy 2) the efficacy and safety of the new multireceptor-targeted somatostatin ligand pasireotide 3) medical treatments currently under clinical investigation (oral octreotide, ITF2984, ATL1103), and 4) preliminary data on the use of new injectable and transdermal/transmucosal formulations of octreotide. This expert opinion supports the need for new therapeutic agents and modalities for patients with acromegaly.

Effects of the single and combined treatment with dopamine agonist, somatostatin analog and mTOR inhibitors in a human lung carcinoid cell line: an in vitro study.

PubMed

Pivonello, Claudia; Rousaki, Panagoula; Negri, Mariarosaria; Sarnataro, Maddalena; Napolitano, Maria; Marino, Federica Zito; Patalano, Roberta; De Martino, Maria Cristina; Sciammarella, Concetta; Faggiano, Antongiulio; Rocco, Gaetano; Franco, Renato; Kaltsas, Gregory A; Colao, Annamaria; Pivonello, Rosario

2017-06-01

Somatostatin analogues and mTOR inhibitors have been used as medical therapy in lung carcinoids with variable results. No data are available on dopamine agonists as treatment for lung carcinoids. The main aim of the current study was to evaluate the effect of the combined treatment of somatostatin analogue octreotide and the dopamine agonist cabergoline with mTOR inhibitors in an in vitro model of typical lung carcinoids: the NCI-H727 cell line. In NCI-H727 cell line, reverse transcriptase-quantitative polymerase chain reaction and immunofluorescence were assessed to characterize the expression of the somatostatin receptor 2 and 5, dopamine receptor 2 and mTOR pathway components. Fifteen typical lung carcinoids tissue samples have been used for somatostatin receptor 2, dopamine receptor 2, and the main mTOR pathway component p70S6K expression and localization by immunohistochemistry. Cell viability, fluorescence-activated cell sorting analysis and western blot have been assessed to test the pharmacological effects of octreotide, cabergoline and mTOR inhibitors, and to evaluate the activation of specific cell signaling pathways in NCI-H727 cell line. NCI-H727 cell line expressed somatostatin receptor 2, somatostatin receptor 5 and dopamine receptor 2 and all mTOR pathway components at messenger and protein levels. Somatostatin receptor 2, dopamine receptor 2, and p70S6K (non phosphorylated and phosphorylated) proteins were expressed in most typical lung carcinoids tissue samples. Octreotide and cabergoline did not reduce cell viability as single agents but, when combined with mTOR inhibitors, they potentiate mTOR inhibitors effect after long-term exposure, reducing Akt and ERK phosphorylation, mTOR escape mechanisms, and increasing the expression DNA-damage-inducible transcript 4, an mTOR suppressor. In conclusion, the single use of octreotide and cabergoline is not sufficient to block cell viability but the combined approach of these agents with mTOR inhibitors might reduce the mTOR inhibitors-induced escape mechanisms and/or activate the endogenous mTOR suppressor, potentiating the effect of the mTOR inhibitors in an in vitro model of typical lung carcinoids.

Somatostatin Modulates Insulin-Degrading-Enzyme Metabolism: Implications for the Regulation of Microglia Activity in AD

PubMed Central

Tundo, Grazia; Ciaccio, Chiara; Sbardella, Diego; Boraso, Mariaserena; Viviani, Barbara; Coletta, Massimiliano; Marini, Stefano

2012-01-01

The deposition of β-amyloid (Aβ) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity. PMID:22509294

Pasireotide: a novel treatment for patients with acromegaly

PubMed Central

Cuevas-Ramos, Daniel; Fleseriu, Maria

2016-01-01

Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%–70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%–90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be established. Lastly, novel therapies and new potential delivery modalities (oral octreotide) are summarized. PMID:26811671

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.

PubMed

Smith, Tracey L; Yuan, Ziqiang; Cardó-Vila, Marina; Sanchez Claros, Carmen; Adem, Asha; Cui, Min-Hui; Branch, Craig A; Gelovani, Juri G; Libutti, Steven K; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih

2016-03-01

Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct-AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well.

Management of a pregnant woman with thyrotropinoma: a case report and review of the literature.

PubMed

Perdomo, Carolina M; Árabe, Jorge A; Idoate, Miguel Á; Galofré, Juan C

2017-03-01

Pituitary disorders during pregnancy are uncommon. The approach should include a close follow-up in order to reduce maternal and fetal risks associated with physiological changes during pregnancy or treatment side effects. We report a 21-year-old woman with a thyroid-stimulating hormone-secreting pituitary macroadenoma and positive antithyroid antibodies. She was initially treated using transsphenoidal pituitary surgery. The patient relapsed 17-month post-surgery. Somatostatin analog therapy was started which rapidly controlled the hyperthyroidism. Eleven months later, while receiving octreotide, the patient reported to be pregnant and the medication was stopped. Gestation and delivery went well with a healthy full-term newborn. The patient developed a postpartum thyroiditis 15 weeks after giving birth. Twenty-eight months postpartum the patient remains euthyroid without medication. The overall positive outcomes of the four cases reported in literature, including this new case, suggest that pregnancy should not be absolutely contraindicated in women with thyrotropinomas. We emphasize the effectiveness of octreotide to control hyperthyroidism, as well as stopping medication when a patient is found to be pregnant. In our case, close observation following octreotide cessation had a positive outcome.

Octreotide-Associated Neutropenia.

PubMed

Tse, Stacy S; Kish, Troy

2017-06-01

Drug-induced neutropenia and agranulocytosis are rare adverse events but can be fatal. Neutropenia can be induced by a myriad of drugs from almost every pharmacologic class. Octreotide is a somatostatin analog that has been used to treat variceal bleeding, acromegaly, and severe diarrhea associated with metastatic tumors, and to reduce symptoms in the setting of malignant bowel obstruction and pseudoobstruction. The most common adverse effects associated with octreotide include pain at the injection site and gastrointestinal effects such as loose stools, cramping, and nausea; neutropenia is not currently listed as an adverse effect of the drug. We describe the case of an 87-year-old man who developed neutropenia immediately after administration of three doses of subcutaneous octreotide. He presented to the hospital with a history of constipation and straining for 3 days. He was admitted, and laxatives, suppositories, and enemas were administered over the next 3 days to induce a bowel movement; however, they were ineffective. Bowel obstruction secondary to a mass was confirmed by computed tomography; the mass was eventually diagnosed as colon cancer. Octreotide 100 µg subcutaneously every 8 hours was started for the obstruction on the evening of hospital day 4. After the patient had received 3 doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 × 10 3 /mm 3 (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 × 10 3 /mm 3 ) on admission to 1.6 × 10 3 /mm 3 (neutrophils 62%, ANC 0.99 × 10 3 /mm 3 ) on day 5. Given the temporal relationship of octreotide and neutropenia as well as the lack of a reasonable alternative cause, it was suspected that octreotide was the most likely culprit of the patient's neutropenia. Octreotide was subsequently discontinued, and his WBC increased to 4.9 × 10 3 /mm 3 (neutrophils 66.3%, ANC 3.2 × 10 3 /mm 3 ) the next day. The remainder of the patient's hospitalization was not significant for any further hematologic abnormalities. His WBC and ANC (WBC 6.7 × 10 3 /mm 3 , neutrophils 83.2%, ANC 5.6 × 10 3 /mm 3 ) remained stable 30 days after the incident. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient's development of neutropenia and octreotide therapy. To our knowledge, this report highlights the first case of octreotide-associated neutropenia. Although the frequency of drug-induced neutropenia remains rare outside of cytotoxic chemotherapy, the importance of recognizing this adverse effect cannot be understated given the mortality risks for neutropenic patients. © 2017 Pharmacotherapy Publications, Inc.

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

PubMed

Eising, E G; Farahati, J; Bier, D; Knust, E J; Reiners, C

1995-02-01

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

[Injuries of pancreatoduodenal organs].

PubMed

Ivanov, P A; Grishin, A V; Korneev, D A; Ziniakov, S A

2003-01-01

Ten-year experience of treatment of 213 patients with trauma of the pancreas and 56 patients with trauma of the duodenum is analyzed. Combined injury of other organs was seen in 80% patients. Diagnostic policy included intraoperative revision in open abdominal trauma and dynamic observation with US, roentgenography, CT and laboratory tests in closed trauma wich doesn't require urgent surgery. The diagnosis was verified during laparoscopy and contrast duodenography. Surgical treatment results in patients with trauma of the pancreas depending on the variant of surgery are analyzed. The role of drug treatment of traumatic pancreatitis with 5-ftoruracil and octreotid is stressed. It is demonstrated that these principles allowed us to reduce complications rate to 11.7% and lethality to 6.7% from 71.7% and 37.0% respectively. It is established that suturing of duodenal wall on the decompressive nasoduodenal tube is effective within 6 hours after trauma. Later, for prophylaxis of suture insufficiency the duodenum must be switched off. Adequate drainage and depression of secretion with octreotid are very important for success of surgery. In this approach there were no cases of sutures insufficiency among 16 patients in the last 3 years.

Budget impact of somatostatin analogs as treatment for metastatic gastroenteropancreatic neuroendocrine tumors in US hospitals.

PubMed

Ortendahl, Jesse D; Pulgar, Sonia J; Mirakhur, Beloo; Cox, David; Bentley, Tanya Gk; Phan, Alexandria T

2017-01-01

With the introduction of new therapies, hospitals have to plan spending limited resources in a cost-effective manner. To assist in identifying the optimal treatment for patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, budget impact modeling was used to estimate the financial implications of adoption and diffusion of somatostatin analogs (SSAs). A hypothetical cohort of 500 gastroenteropancreatic neuroendocrine tumor patients was assessed in an economic model, with the proportion with metastatic disease treated with an SSA estimated using published data. Drug acquisition, preparation, and administration costs were based on national pricing databases and published literature. Octreotide dosing was based on published estimates of real-world data, whereas for lanreotide, real-world dosing was unavailable and we therefore used the highest indicated dosing. Alternative scenarios reflecting the proportion of patients receiving lanreotide or octreotide were considered to estimate the incremental budget impact to the hospital. In the base case, 313 of the initial 500 gastroenteropancreatic neuroendocrine tumor patients were treated with an SSA. The model-predicted per-patient cost was US$83,473 for lanreotide and US$89,673 for octreotide. With a hypothetical increase in lanreotide utilization from 5% to 30% of this population, the annual model-projected hospital costs decreased by US$488,615. When varying the inputs in one-way sensitivity analyses, the results were most sensitive to changes in dosing assumptions. Results suggest that factors beyond drug acquisition cost can influence the budget impact to a hospital. When considering preparation and administration time, and real-world dosing, use of lanreotide has the potential to reduce health care expenditures associated with metastatic gastroenteropancreatic neuroendocrine tumor treatments.

Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?

PubMed

Mohamed, Amira; Romano, David; Saveanu, Alexandru; Roche, Catherine; Albertelli, Manuela; Barbieri, Federica; Brue, Thierry; Niccoli, Patricia; Delpero, Jean-Robert; Garcia, Stephane; Ferone, Diego; Florio, Tullio; Moutardier, Vincent; Poizat, Flora; Barlier, Anne; Gerard, Corinne

2017-06-20

Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition. Combined inhibition of Akt might then improve everolimus antitumoral effect. In this regard, the somatostatin analog (SSA) octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms caused by peptide release in patients carrying functional GEP-NETs. We have recently established and characterized primary cultures of human pNETs and demonstrated the anti-proliferative effects of both octreotide and pasireotide. In this study, we aim at determining the antitumor efficacy of everolimus alone or in combination with the SSAs octreotide and pasireotide in primary cultures of pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and upregulated Akt activity in single treatment. Its anti-proliferative and anti-secretory efficacy was not improved combined with the SSAs. Both SSAs did not overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent apoptosis induced by SSAs was lost in combined treatments. These molecular events provide the first evidence supporting the lack of marked benefit in patients co-treated with everolimus and SSA.

Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?

PubMed Central

Mohamed, Amira; Romano, David; Saveanu, Alexandru; Roche, Catherine; Albertelli, Manuela; Barbieri, Federica; Brue, Thierry; Niccoli, Patricia; Delpero, Jean-Robert; Garcia, Stephane; Ferone, Diego; Florio, Tullio; Moutardier, Vincent; Gerard, Corinne

2017-01-01

Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition. Combined inhibition of Akt might then improve everolimus antitumoral effect. In this regard, the somatostatin analog (SSA) octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms caused by peptide release in patients carrying functional GEP-NETs. We have recently established and characterized primary cultures of human pNETs and demonstrated the anti-proliferative effects of both octreotide and pasireotide. In this study, we aim at determining the antitumor efficacy of everolimus alone or in combination with the SSAs octreotide and pasireotide in primary cultures of pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and upregulated Akt activity in single treatment. Its anti-proliferative and anti-secretory efficacy was not improved combined with the SSAs. Both SSAs did not overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent apoptosis induced by SSAs was lost in combined treatments. These molecular events provide the first evidence supporting the lack of marked benefit in patients co-treated with everolimus and SSA. PMID:28454119

Therapeutic options in the management of acromegaly: focus on lanreotide Autogel®

PubMed Central

Roelfsema, Ferdinand; Biermasz, Nienke R; Pereira, Alberto M; Romijn, Johannes A

2008-01-01

Background In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients. Objective To delineate the role of lanreotide in the treatment of acromegaly. Methods Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly. Results Treatment with lanreotide slow release and lanreotide Autogel® normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel® on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic β-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel®. When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patients. PMID:19707377

Enhanced Peptide of Prostate Cancer Using Targeted Adenoviral Vectors

DTIC Science & Technology

2005-06-01

receptor subtype 2 has been constructed and evaluated in-human prostate cancer cells with regard to binding: of 64Cu - octreotide. In vivo experiments...of 64CU -octreotide.. The mice wer.e. sacrificed 1. h after peptide injection for biodistribution analysis. In vivo biodistribution studies showed...similar uptake of 64Cu - octreotide in both DU-145 and PC-3 tumors after infection with-AdSSTR2. (2.5. and 2.7% ID/g, respectively). This uptake was

Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2.

PubMed

Ferrante, E; Pellegrini, C; Bondioni, S; Peverelli, E; Locatelli, M; Gelmini, P; Luciani, P; Peri, A; Mantovani, G; Bosari, S; Beck-Peccoz, P; Spada, A; Lania, A

2006-09-01

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160+/-20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172+/-25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.

Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0,Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization?

PubMed

Storch, Daniel; Béhé, Martin; Walter, Martin A; Chen, Jianhua; Powell, Pia; Mikolajczak, Renata; Mäcke, Helmut R

2005-09-01

Radiolabeled somatostatin analogs are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin receptor-positive tumors. The aim of this study was to compare 3 somatostatin analogs designed for the labeling with (99m)Tc (where HYNIC is 6-hydrazinopyridine-3-carboxylic acid): 6-hydrazinopyridine-3-carboxylic acid(0)-octreotide (HYNIC-OC/(99m)Tc-(1)), [HYNIC(0),Tyr(3)]octreotide (HYNIC-TOC/(99m)Tc-(2)), and [HYNIC(0),Tyr(3),Thr(8)]octreotide (HYNIC-TATE/(99m)Tc-(3)), using ethylenediamine-N,N'-diacetic acid (EDDA) as a coligand. In addition, we compared the (99m)Tc-labeled peptides [(111)In-diethylenetriaminepentaacetic acid(0)]octreotide ([(111)In-DTPA]-OC) and [(111)In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(0),Tyr(3),Thr(8)]octreotide ([(111)In-DOTA]-TATE) with regard to the rate of internalization and the biodistribution in AR4-2J (expressing the somatostatin receptor subtype 2) tumor-bearing rats. The main attention was directed toward a potential correlation between the rate of internalization and the tumor or pancreas uptake. Synthesis was performed on solid phase using a standard Fmoc strategy. Internalization was studied in cell culture (AR4-2J) and biodistribution was studied using a Lewis rat tumor model (AR4-2J). The 5 radiopeptides showed a specific internalization into AR4-2J cells in culture (as shown by blocking experiments). The rate of internalization of the 5 radiopeptides differed significantly according to the following order: (99m)Tc-(1) approximately = [(111)In-DTPA]-OC < (99m)Tc-(2) < (99m)Tc-(3) approximately = [(111)In-DOTA]-TATE. All radiopeptides displayed a rapid blood clearance and a fast clearance from all somatostatin receptor-negative tissues predominantly via the kidneys. A receptor-specific uptake of radioactivity was observed for all compounds in somatostatin receptor-positive organs such as the pancreas, the adrenals, and the stomach. After 4 h, the uptake in the AR4-2J tumor was comparable for (99m)Tc-(2) (3.85 +/- 1.0 injected dose per gram tissue (%ID/g)), (99m)Tc-(3) (3.99 +/- 0.58%ID/g), and [(111)In-DOTA]-TATE (4.12 +/- 0.74%ID/g) but much lower for [(111)In-DTPA]-OC (0.99 +/- 0.08%ID/g) and (99m)Tc-(1) (0.70 +/- 0.13%ID/g). The specificity was determined by blocking experiments using a large excess of [Tyr(3)]octreotide. (99m)Tc-(3) displayed the highest tumor-to-kidney ratio (2.5:1), followed by (99m)Tc(2) (1.9:1) and [(111)In-DOTA]-TATE (1.7:1). These data show that the 5 radiopeptides are specific radioligands for the somatostatin receptor subtype 2. The rate of internalization correlates with the uptake in the tumor (R(2) = 0.75; P = 0.026) and pancreas (R(2) = 0.98; P = 7.4.10(-5)). [Tyr(3),Thr(8)]octreotide derivatives show superiority over the corresponding octreotide and [Tyr(3)]octreotide derivatives, indicating that [(111)In-DOTA]-TATE and [(99m)Tc/EDDA/HYNIC]-TATE are suitable candidates for clinical studies.

Combined derivatization and high-performance liquid chromatography with fluorescence and ultraviolet detection for simultaneous analysis of octreotide and gabexate mesylate metabolite in human pancreatic juice samples.

PubMed

Carlucci, Giuseppe; Selvaggi, Federico; Sulpizio, Sara; Bassi, Claudio; Carlucci, Maura; Cotellese, Roberto; Ferrone, Vincenzo; Innocenti, Paolo; Locatelli, Marcello

2015-06-01

A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.1 µg/mL for octreotide and 0.2 µg/mL for gabexate mesylate metabolite, and matrix matched standard curves showed a good linearity up to 15 µg/mL. In the entire analytical range the intra- and inter-day precision (RSD%) values were respectively ≤5.9% and ≤3.1% for octreotide and ≤2.0% and ≤3.9% for gabexate mesylate metabolite. For both analytes the intra- and inter-day accuracy (bias) values ranged respectively from -6.8 to -2.5% and from -4.6 to -5.7%. This method utilizes derivatization with NBD-F and provides adequate sensitivity for both drugs. Copyright © 2014 John Wiley & Sons, Ltd.

Enhanced Peptide Radiotherapy of Prostate Cancer Using Targeted Adenoviral Vectors

DTIC Science & Technology

2004-06-01

regard to binding of 64Cu - octreotide. In vitro experiments were performed with DU-145 and PC-3 human prostate cancer cells. Expression levels of SSTR2...were determined using a 64Cu -octreotide saturation binding assay on cell membrane preparations. In vivo experiments were conducted in scid mice bearing...subcutaneous DU-l45 or PC-3 cells. AdSSTR2 was injected intratumorally followed 48 h later by an i.v. injection of 64Cu -octreotide. The mice were

Polycythemia as rare secondary direct manifestation of acromegaly: management and single-centre epidemiological data.

PubMed

Zoppoli, Gabriele; Bianchi, Federico; Bruzzone, Andrea; Calvia, Alessandro; Oneto, Caterina; Passalia, Caterina; Balleari, Enrico; Bedognetti, Davide; Ponomareva, Elena; Nazzari, Elena; Castelletti, Lara; Castellan, Lucio; Minuto, Francesco; Ghio, Riccardo; Ferone, Diego

2012-06-01

Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy. The medical history of 141 acromegalic patients followed by the Endocrinology Unit of the San Martino University Hospital in Genoa has been also reviewed, together with the literature evidence for similar cases. The diagnostic workflow and 2-years follow-up of a 43-years old acromegalic, polycythemic man with a history of past smoking, moderate hypertension, and mental retardation are described. The hematological parameters of our cohort was retrospectively compared with those of a healthy, age/gender-related control group as well. Therapy with octreotide LAR, 20 mg i.m. q28d was begun soon after diagnosis of acromegaly in the polycythemic patient. Haematocrit level, hormonal setting, as well as pituitary tumor size and visual perimetry during treatment were recorded. Octreotide LAR treatment normalized hormonal alterations, as well as hematological parameters. Polycythemia has not recurred after 2 years of therapy. The median hemoglobin and hematocrit levels of the retrospectively analyzed cohort of acromegalic were significantly lower than normal ranges of a healthy, age/sex- related control population. In conclusions, polycythemia can be a direct, albeit rare, secondary manifestation of acromegaly, that must be considered during the diagnostic work-up of acromegalic patients presenting with such disorder.

[Prevention and treatment of post-traumatic pancreatic necrosis in patients with blunt abdominal trauma].

PubMed

Cherdantsev, D V; Pervova, O V; Vinnik, Iu S; Kurbanov, D Sh

2016-01-01

High incidence of necrotic and suppurative complications is feature of acute post-traumatic pancreatitis. Severe trauma of the pancreas and post-traumatic pancreatitis lead to depressurization of ductal system that requires adequate drainage of damaged area and retroperitoneal fat. 95 patients in group 1 received standardized treatment. The victims of the 2nd group (44 patients) were treated using immunoreactive therapy (roncoleukin) and octreotide (the dose depended on the severity of pancreatitis) at early stages. The efficacy of treatment was assessed based on clinical, laboratory and instrumental parameters. Regardless severity of pancreatic injury overall mortality in groups 1 and 2 was 41% and 20.5% respectively. The main causes of adverse outcomes are severe destructive pancreatitis, postnecrotic suppurative complications. Adequacy rather radicalism of surgery should be preferred for blunt pancreatic trauma management. Minimally invasive surgical techniques and new methods of biological hemostasis may be applied. Timely use of anti-enzymatic and immunoactive therapy reduces the risk of severe post-traumatic pancreatitis, suppurative complications and improves outcomes in patients with blunt pancreatic trauma.

Analysis of accumulation of 99mTc-octreotide and 99mTc-EDDA/HYNIC-Tyr3-octreotide in the rat kidneys.

PubMed

Kopecky, Martin; Semecky, Vladimir; Trejtnar, Frantisek; Laznicek, Milan; Laznickova, Alice; Nachtigal, Petr; Decristoforo, Clemens; Mather, Stephen J; Mäcke, Helmut R

2004-02-01

The aim of this study was to compare renal handling and distribution of (99m)Tc-octreotide and (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide (HYNIC-TOC) in rats. In kidney perfusion experiments, the renal clearance value of (99m)Tc-octreotide was three times lower than that of (99m)Tc-EDDA/HYNIC-TOC. The predominant renal excretion of (99m)Tc-EDDA/HYNIC-TOC was associated with a high and long-term renal accumulation up to 48 hrs. Microautoradiographic results indicated that (99m)Tc-EDDA/HYNIC-TOC was retained mainly in the renal medulla within the cells of the collecting ducts and in the surrounding tissue. Lower positivity was found in the proximal and distal tubular cells. We conclude that the mechanism of renal accumulation of somatostatin analogues renal accumulation is complex and that proximal tubular reabsorption is probably not the main mechanism for uptake of (99m)Tc-EDDA/HYNIC-TOC in the kidneys. The presence of the somatostatin receptors, differences in the tonicity level within kidneys and other possible mechanisms could participate in their renal accumulation.

Acute Variceal Bleeding: Does Octreotide Improve Outcomes in Patients with Different Functional Hepatic Reserve?

PubMed

Monreal-Robles, Roberto; Cortez-Hernández, Carlos A; González-González, José A; Abraldes, Juan G; Bosques-Padilla, Francisco J; Silva-Ramos, Héctor N; García-Flores, Jorge A; Maldonado-Garza, Héctor J

2018-01-01

Current guidelines do not differentiate in the utilization of vasoactive drugs in patients with cirrhosis and acute variceal bleeding (AVB) depending on liver disease severity. In this retrospective study, clinical outcomes in 100 patients receiving octreotide plus endoscopic therapy (ET) and 216 patients with ET alone were compared in terms of failure to control bleeding, in-hospital mortality, and transfusion requirements stratifying the results according to liver disease severity by Child-Pugh (CP) score and MELD. In patients with CP-A or those with MELD < 10 octreotide was not associated with a better outcome compared to ET alone in terms of hospital mortality (CP-A: 0.0 vs. 0.0%; MELD < 10: 0.0 vs. 2.9%, p = 1.00), failure to control bleeding (CP-A: 8.7 vs. 3.7%, p = 0.58; MELD < 10: 5.3 vs. 4.3%, p = 1.00) and need for transfusion (CP-A: 39.1 vs. 61.1%, p = 0.09; MELD < 10: 63.2 vs. 62.9%, p = 1.00). Those with severe liver dysfunction in the octreotide group showed better outcomes compared to the non-octreotide group in terms of hospital mortality (CP-B/C: 3.9 vs. 13.0%, p = 0.04; MELD ≥ 10: 3.9 vs. 13.3%, p = 0.03) and need for transfusion (CP-B/C: 58.4 vs. 71.6%, p = 0.05; MELD ≥ 10: 50.6 vs. 72.7%, p < 0.01). In multivariate analysis, octreotide was independently associated with in-hospital mortality (p = 0.028) and need for transfusion (p = 0.008) only in patients with severe liver dysfunction (CP-B/C or MELD ≥ 10). Patients with cirrhosis and AVB categorized as CP-A or MELD < 10 had similar clinical outcomes during hospitalization whether or not they received octreotide.

[99mTc-octreotide receptor scintigraphy in NCI-H446 small cell lung cancer nude mice model].

PubMed

Li, Chao; Zuo, Shuyao; Wang, Xufu; Liu, Xinfeng; Wang, Guoming; Wu, Fengyu

2015-01-01

For highly aggressive small cell lung cancer (SCLC), early diagnosis is important for its prognosis, but the current inspection methods are more limited, with poor specificity of the traditional imaging methods, and the high cost of PET/CT, difficult to popularization and application. SCLC is kind of neuroendocrine tumors, high expression of somatostatin receptors, which is the cornerstone of its early molecular imaging diagnosis. The aim of this study is to observe the biodistribution and metabolism of 99mTc-octreotide in normal and the human SCLC bearing nude mice. Dynamic and static scintigraphy at 0.5 h, 2 h, 3 h, 4 h were performed in both normal and tumor bearing nude mice after intravenous injection of 99mTc-octreotide. The technique of drawing region of interest (ROI) was used to obtain the averaged pixel counts and the activity-time (A-T) curve of brain, heart, lung, liver, kidney, tumor, respectively. ① The biodistribution study in normal nude mice showed highest uptake in kidney and liver, lower in lung and heart, lowest in brain. Most 99mTc-octreotide was excreted via kidney. ② All tumors were displayed clearly at 3 h postinjection of 99mTc-octreotide. The averaged T/N ratio at 0.5 h, 2 h, 3 h, 4 h postinjection of 99mTc-octreotide was 1.163 ± 0.03, 2.08 ± 0.12, 3.03 ± 0.23, 2.689 ± 0.31, respectively (F=51.69, P<0.000,1). The radioactivity of tumor was lower than liver, and similar with the lung. The curve of tumor showed a radioactivity peak at 2 min-3 min postinjection. 99mTc-octreotide receptor imaging on nude mice bearing SCLC shares high positive rate, especially at 3 h postinjection.

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives.

PubMed

Decristoforo, C; Mather, S J; Cholewinski, W; Donnemiller, E; Riccabona, G; Moncayo, R

2000-09-01

[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

Adrenocorticotropin-producing pituitary carcinoma with liver metastasis.

PubMed

Lormeau, B; Miossec, P; Sibony, M; Valensi, P; Attali, J R

1997-04-01

We report here the extremely rare case of a twenty-eight year-old woman with a metastatic ACTH-secreting pituitary carcinoma. This is the thirteenth case to be described in the literature. Ten years ago Cushing's disease was diagnosed. After pituitary surgery, then bilateral adrenalectomy, a Nelson's syndrome appeared. The particularly extensive pituitary secondary development led to several pituitary surgical procedures, radiotherapy, and octreotide treatment. Eight years after Cushing's disease was diagnosed, liver tumors were discovered. Pathological examination and ACTH immunostaining demonstrated the secretory nature of these metastases. The lack of ectopic tumor, the LPH/ACTH equimolar ratio and a study of the plasma proopiomelanocortin derivatives by HPLC showed that the ACTH secretion originated in pituitary tissues (in situ and liver metastases). The processing of POMC seems thus to be normal in this kind of tumor and metastases. Intact POMC levels were very high, indicating an aggressive tumor, and ACTH/LPH production was paradoxically stimulated by octreotide. This case is also exceptional because of the slow development of the disease, which may be due to the complementary hepatic chemoembolization treatment.

[Chemotherapy-induced diarrhea].

PubMed

Kobayashi, Kunihiko

2003-06-01

Chemotherapy-induced diarrhea is a well-documented side effect of many cancer treatments and is associated with increased morbidity and mortality. Chemotherapy-induced diarrhea negatively impacts patient quality of life and treatment outcome by requiring dose limitations or treatment interruption. The chemotherapeutic agent CPT-11 (irinotecan) has shown promising results as a single agent and in combination chemotherapy for the treatment of colorectal and small cell lung cancer. However, delayed onset diarrhea is considered to be its major dose-limiting toxicity. In some cases, it can be life threatening. To prevent CPT-11-induced delayed diarrhea, oral alkalization (OA) and control of defecation (CD) [Int J Cancer 92: 269-275, 2001] were developed based on fundamental studies [Int J Cancer 83: 491-496, 1999; Cancer Res 62: 179-187, 2002]. Oral administration of antibiotics [Cancer Res 56: 3752-3757, 1996; Clin Cancer Res 7: 1136-1141, 2001] or kampo medicine [Jpn J Cancer Res 86: 978-984, 1995; Jpn J Cancer Res 86: 985-989, 1995] to decrease beta-glucuronidase activity derived from bacteria in the large intestine was also reported to be successful in preventing delayed diarrhea. When CPT-11-induced delayed diarrhea occurs, the conventional treatment is loperamide [J Natl Cancer Inst 86: 446-449, 1994], and the early recognition and treatment of diarrhea with this opioid has reduced, although not entirely eliminated, patient morbidity. Other therapies are needed to treat patients with loperamide-refractory CPT-11 induced diarrhea, and the successful use of the somatostatin analogue octreotide has been reported [Support Care Cancer 9: 258-260, 2001; Ann Oncol 12: 227-229, 2001; Proc Am Soc Clin Oncol 21: 387a, 2002].

[Experience in the treatment of some complications of portal hypertension in alcoholic liver cirrhosis].

PubMed

Savić, Zeljka; Vracarić, Vladimir; Hadnadjev, Ljiljana; Petrović, Zora; Damjanov, Dragomir

2011-11-01

Portal hypertension (PH) is hemodynamical abnormality associated with the most serious complications of alcoholic liver cirrhosis (ALC): ascites, varices and variceal bleeding. The aim of this study was to determine characteristics of portal hypertension, especially of upper gastrointestinal bleedings in patients with alcoholic liver cirrhosis (ALC). A total of 237 patients with ALC were observed in a 3-year period. A total of 161 patients (68%) were hospitalized because of PH elements: 86 (36.3%) had upper gastrointestinal bleeding, 75 (31.7%) were decompensated. Only 76 (32%) of the patients had icterus. General mortality was 85 (36%). According to the source of bleeding, 61 (71%) patients bled from varices, and 25 (29%) from other sources with existing varices but non-incriminated for bleeding in 16 (64%) of those patients. Active bleeding or stigmata of recent bleeding were found in 63 (73%) cases. Endoscopic treatment of variceal bleeding along with octreotide applied in 20 (32.78%) patients, just octreotide in 32 (52.46%), and octreotid plus balloon tamponade in 9 (14.75%). According to Child-Pugh classification, 25 (29%) of the bleeding patients were in class A, score 5.4; 43 (50%) in class B, score 7.8; and 18 (21%) in class C, score 10.9. Average hemoglobin level was 93 g/L, hematocrit 0.27, AST 71.52 U/L (normal to 37 U/L), ALT 37.74 U/L (normal to 40 U/L). Until this bleeding episode, 41 (47%) of the patients already bled. In the decompensated patients 3 (4%) were in Child Pugh class A, score 6; 42 (56%) in class B, score 8.3; and 30 (40%) in class C, score 10.6. Until this decompensation episode, 7 (9.3%) patients already bled. Patients with ALC need early detection of varices, primary and secondary profilaxis of variceal bleeding and adequate therapy of ascites. When bleeding occurs, patients need urgent upper endoscopy and intensive treatment.

Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy.

PubMed

Inge, Thomas H; Pfluger, Paul; Zeller, Meg; Rose, Susan R; Burget, Lukas; Sundararajan, Sumana; Daniels, Stephen R; Tschöp, Matthias H

2007-08-01

A 14-year-old boy presented with daytime somnolence, intermittent emesis and hypothyroidism. Neuroimaging revealed a calcified suprasellar intracranial mass, suspected to be a craniopharyngioma. Subtotal resection of the tumor confirmed the diagnosis. Extreme obesity (BMI >60 kg/m(2)) and hyperinsulinemia followed tumor resection and cranial irradiation. Dietary interventions were unsuccessful, and pharmacologic intervention (i.e. octreotide) only slowed the rate of weight gain. Radiography documented the suprasellar mass. Following surgical resection and radiotherapy, hypothalamic-pituitary deficiencies were found. Preprandial and postprandial excursions of insulin, active ghrelin and leptin were measured before and after gastric bypass surgery. Panhypopituitarism, hypothalamic obesity and hyperinsulinemia following craniopharyngioma therapy. Severe caloric restriction, octreotide, and pituitary hormone replacement did not produce weight loss. Gastric bypass surgery led to reduced food cravings, significant weight loss, and amelioration of obesity-related comorbidities. Correction of fasting hyperinsulinemia, normalization of postprandial insulin responses, and reductions in active ghrelin and leptin concentrations were also observed.

Role of splanchnic constriction in governing the hemodynamic responses to gravitational stress in conscious dogs

PubMed Central

Wong, Brett J.

2011-01-01

Octreotide is a somatostatin analog that constricts the splanchnic circulation, thereby improving orthostatic tolerance. We tested the hypotheses that octreotide improves orthostatic tolerance by 1)increasing cardiac filling (right atrial) pressure via reductions in vascular capacity; 2) by causing an upward (i.e., cranial) shift of the hydrostatic indifferent point; and 3) by increasing arterial pressure via a reduction in total vascular conductance. Studies were carried out in acepromazine-sedated, hexamethonium-treated atrioventricular-blocked conscious dogs lightly restrained in lateral recumbency. Beat-by-beat cardiac output was held constant via computer-controlled ventricular pacing at rest and during 30 s of 30° head-up tilt. Octreotide (1.5 μg/kg iv) raised right atrial pressure by 0.5 mmHg and raised mean arterial pressure by 11 mmHg by reducing total vascular conductance (all P < 0.05). Right atrial pressure fell by a similar amount in response to tilting before and after octreotide, thus there was no difference in location of the hydrostatic indifferent point. These data indicate that octreotide improves orthostatic tolerance by decreasing total vascular conductance and by increasing cardiac filling pressure via a reduction in unstressed vascular volume and not by eliciting a cranial shift of the location of the hydrostatic indifferent point. PMID:21512154

Suppression of GH secretion in pituitary gigantism by continuous subcutaneous octreotide infusion in a pubertal boy.

PubMed

Näntö-Salonen, K; Koskinen, P; Sonninen, P; Toppari, J

1999-01-01

We describe a 12-y-old boy with excessive growth hormone and prolactin secretion presumably due to diffuse somatotroph hyperplasia. Until mid-puberty, his growth rate was under reasonable control, with high-dose octreotide injections every 8 h combined with a dopamine agonist. As his growth velocity started to increase, the efficacy of continuous s.c. octreotide infusion on GH secretion was tested. Similar total daily doses (600 microg) of octreotide were administered either by incremental s.c. injections at 8 h intervals, or by continuous s.c. infusion, two-thirds of the amount during night-time to control the presumed high nocturnal growth hormone (GH) peaks of the pubertal growth spurt. An overnight GH profile showed inadequate suppression of GH levels by incremental injections, while continuous s.c. infusion efficiently brought down the GH secretion. Another somatostatin analogue, lanreotide as a single depot injection was not effective. A 6-mo trial on the s.c. infusion regimen significantly reduced growth hormone secretion (as judged by IGF-I and IGFBP3 concentrations), and normalized growth velocity overcoming the pubertal growth spurt. It also caused a decrease in the pituitary size in magnetic resonance images. We conclude that the efficacy of octreotide infusion in suppressing GH secretion is superior to incremental injections with the same dose.

Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide

PubMed Central

Lheureux, Philippe ER; Zahir, Soheil; Penaloza, Andrea; Gris, Mireille

2005-01-01

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting. PMID:16356235

Tolerability of continuous subcutaneous octreotide used in combination with other drugs.

PubMed

Mercadante, S

1995-01-01

Continuous subcutaneous infusion of octreotide combined with other drugs has proved to be useful in some circumstances in palliative care setting when theoral route is no longer available. Forty-four patients were administered octreotide alone or in combination with other drugs in the same syringe driver for symptom control in advanced cancer patients. Good tolerability and compatibility were observed without visual drug precipitation for a period of 48 hours at room temperature, the standard clinical situation in patients' homes. Such a combination of drugs administered by the subcutaneous route makes possible the adequate control of symptoms in the final days of life.

Additional Octreotide Therapy to Sirolimus Achieved a Decrease in Sirolimus-refractory Chylous Effusion Complicated with Lymphangioleiomyomatosis.

PubMed

Namba, Masashi; Masuda, Takeshi; Nakamura, Takashi; Horimasu, Yasushi; Miyamoto, Shintaro; Nakashima, Taku; Iwamoto, Hiroshi; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru

2017-12-15

Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control postoperative chylous effusion, in addition to the sirolimus therapy. This combination therapy reduced the chylothorax and chylous ascites. For patients with LAM, octreotide therapy in addition to sirolimus may be effective for treating sirolimus-refractory chylous effusion.

DOTA-derivatives of octreotide dicarba-analogues with high affinity for somatostatin sst2,5 receptors

NASA Astrophysics Data System (ADS)

Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M.; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

2017-02-01

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumours and their metastases. In fact, peptide ligands of somatostatin receptors (sst’s) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogues, which show interesting binding profiles at sst’s. In this context, it was mandatory to explore the possibility that our analogues could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogues of octreotide. Interestingly, two conjugated analogues exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

DOTA-Derivatives of Octreotide Dicarba-Analogs with High Affinity for Somatostatin sst2,5 Receptors.

PubMed

Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

2017-01-01

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumors and their metastases. In fact, peptide ligands of somatostatin receptors (sst's) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogs, which show interesting binding profiles at sst's. In this context, it was mandatory to explore the possibility that our analogs could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogs of octreotide. Interestingly, two conjugated analogs exhibited nanomolar affinities on sst 2 and sst 5 somatostatin receptor subtypes.

Octreotide for left ventricular assist device-related gastrointestinal hemorrhage: can we stop the bleeding?

PubMed

Rennyson, Stephen L; Shah, Keyur B; Tang, Daniel G; Kasirajan, Vigneshwar; Pedram, Sammy; Cahoon, William; Malhotra, Rajiv

2013-01-01

Left ventricular support devices (LVADs) are associated with a propensity toward gastrointestinal bleeding. A postulated mechanism is related to gastrointestinal arteriovenous malformations secondary to nonpulsatile flow. We describe a case of LVAD-related, gastrointestinal bleeding successfully treated with a combination of subcutaneous and intramuscular depot formulations of octreotide.

How to treat an extensive form of primary intestinal lymphangiectasia?

PubMed

Troskot, Rosana; Jurčić, Dragan; Bilić, Ante; Gomerčić Palčić, Marija; Težak, Stanko; Brajković, Ivana

2015-06-21

We report a case of a 42-year-old man with a rare disorder known as primary intestinal lymphangiectasia, which is characterized by dilated intestinal lymphatics that lead to the development of protein-losing enteropathy. The patient presented with a grand mal seizure caused by malabsorption-derived electrolytes and a protein disorder. Signs of the disease, including chronic diarrhea and peripheral edema, manifested 10 years ago, but a diagnosis was never made. The diagnosis was suspected because of the clinical manifestations, laboratory tests, imaging and endoscopic findings. Hyperemic and edematous mucosa of the small intestine corresponded to scattered white spots with dilated intestinal lymphatics and whitish villi in the histological specimen of the biopsied jejunal mucosa. Although numerous therapeutic strategies are available, only octreotide therapy proved to be an effective means of therapeutic resolution in this patient. Although the patient had a partial remission following the use of a slow release formula of octreotide, his prognosis, clinical course, and future treatment challenges are yet to be determined.

How to treat an extensive form of primary intestinal lymphangiectasia?

PubMed Central

Troskot, Rosana; Jurčić, Dragan; Bilić, Ante; Gomerčić Palčić, Marija; Težak, Stanko; Brajković, Ivana

2015-01-01

We report a case of a 42-year-old man with a rare disorder known as primary intestinal lymphangiectasia, which is characterized by dilated intestinal lymphatics that lead to the development of protein-losing enteropathy. The patient presented with a grand mal seizure caused by malabsorption-derived electrolytes and a protein disorder. Signs of the disease, including chronic diarrhea and peripheral edema, manifested 10 years ago, but a diagnosis was never made. The diagnosis was suspected because of the clinical manifestations, laboratory tests, imaging and endoscopic findings. Hyperemic and edematous mucosa of the small intestine corresponded to scattered white spots with dilated intestinal lymphatics and whitish villi in the histological specimen of the biopsied jejunal mucosa. Although numerous therapeutic strategies are available, only octreotide therapy proved to be an effective means of therapeutic resolution in this patient. Although the patient had a partial remission following the use of a slow release formula of octreotide, his prognosis, clinical course, and future treatment challenges are yet to be determined. PMID:26109821

Targeted Delivery of Proteasome Inhibitors to Somatostatin-Receptor-Expressing Cancer Cells by Octreotide Conjugation.

PubMed

Beck, Philipp; Cui, Haissi; Hegemann, Julian D; Marahiel, Mohammed A; Krüger, Achim; Groll, Michael

2015-12-01

Clinical application of proteasome inhibitors (PIs) is so far limited to peripheral blood cancers due to the pronounced cytotoxicity towards all cell types. Targeted delivery of PIs could permit the treatment of other cancers along with decreasing side effects. Herein we describe the first small-molecule proteasome inhibitor conjugate for targeted delivery, created by fusing PIs to a synthetic ligand of somatostatin receptors, which are highly expressed in a variety of tumors. X-ray crystallographic studies and in vitro IC50 measurements demonstrated that addition of the cyclopeptide octreotide as a targeting vehicle does not affect the PI's binding mode. The cytotoxicity of the conjugate against somatostatin-receptor-expressing cells was up to 11-fold higher than that of a non-targeting surrogate. We have therefore established PIs as a new payload for drug conjugates and have shown that targeted delivery thereof could be a promising approach for the broader application of this FDA-approved class of compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hypothesis: proposals for the management of a neonate at risk of hyperammonaemia due to a urea cycle disorder.

PubMed

Leonard, James Vivian; Ward Platt, Martin Peter; Morris, Andrew Alan Myles

2008-03-01

It is difficult to prevent hyperammonaemia in patients with urea cycle disorders that present in the newborn period. This is true, even if treatment is started prospectively because of an affected relative. We propose several additional measures that could be used in conjunction with conventional therapy to improve the metabolic control. Catabolism could be reduced by delivering the babies by elective caesarean section, by starting intravenous glucose immediately after delivery and, possibly, by using beta-blockers or octreotide and insulin. The effectiveness of sodium benzoate and sodium phenylbutyrate might be increased by giving phenobarbital to the mother before delivery and subsequently to the baby to induce the enzymes for conjugation. We would expect the proposed measures to reduce the risk of hyperammonaemia and to improve the outcome for these patients. They have not, however, previously been used in this context, so families would need to be counselled carefully and controlled studies should be undertaken.

[A clinical study using octreotide in relieving gastrointestinal symptoms due to bowel obstruction in a terminally ill cancer patient].

PubMed

Shima, Yasuo; Yamaguchi, Kensei; Miyata, Yoshinori; Hyodo, Ichinosuke; Yagi, Yasuo; Honke, Yoshifumi

2004-09-01

Terminally ill cancer patients with complicated bowel obstructions often have poor quality of life (QOL) due to gastrointestinal symptoms such as nausea and vomiting. Many of these patients are inoperable because of poor general conditions, and half of these patients can't be managed by conventional antiemetics. There are many reports indicating octreotide is effective for these patients. In the present study, 13 patients (5 patients without a nasogastric tube and 8 patients with) were administered octreotide at 300 microg/day by 24 hours continuous subcutaneous infusion. Among the effectively evaluable 10 cases, 6 cases (60.0%) were assessed as effective according to the efficacy criteria based on the JCOG toxicity scale. In the 6 cases who had nasogastric tubes, the nasogastric aspirates decreased from 890 ml (550-1,950) to 480 ml (180-1,790). Vomiting was successfully controlled after the removals of nasogastric tubes in 4 out of 6 cases (66.7%), regarding safety, 2 out of 13 cases (15.4%) showed an excess of liver enzymes but no clinically suspected adverse effect was observed. Octreotide is effective and well tolerated in terminally ill cancer patients with malignant bowel obstruction.

Randomised clinical trial investigating the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction.

PubMed

Zhang, Y; Gao, Y; Ma, Q; Dang, C; Wei, W; De Antoni, F; Rocci, R; Chen, W

2006-03-01

To investigate the effects of combined administration of octreotide and methylglucamine diatrizoate in the older persons with adhesive small bowel obstruction. One hundred and sixty-two consecutive patients who had suffered from adhesive intestinal obstruction without clinical evidence of strangulation or gangrene were randomised into two groups, a control group (treated conservatively, n=82) and a contrast group (treated with combined administration of octreotide and methylglucamine diatrizoate, n=80). A laparotomy was performed in both the two groups if symptoms of strangulation developed or the obstruction did not resolve spontaneously after 72 h. Statistically significant rapid reduction in pain score, lower amount of nasogastric drainage, shorter hospital stay, lower operative rate and lower postoperative morbidity were observed in the contrast group. Among the non-operative patients, earlier passage of stool and gas, earlier first oral intake and shorter duration of nasogastric tube placement were significantly more frequently observed in the contrast group. No difference in the rate of readmission was found between the two groups. Combined administration of octreotide and methylglucamine diatrizoate accelerates resolution of small bowel obstruction by a specific therapeutic effect and is safe for the older persons.

[Effect of different nutritional support on pancreatic secretion in acute pancreatitis].

PubMed

Achkasov, E E; Pugaev, A V; Nabiyeva, Zh G; Kalachev, S V

To develop and justify optimal nutritional support in early phase of acute pancreatitis (AP). 140 AP patients were enrolled. They were divided into groups depending on nutritional support: group I (n=70) - early enteral tube feeding (ETF) with balanced mixtures, group II (n=30) - early ETF with oligopeptide mixture, group III (n=40) - total parenteral nutrition (TPN). The subgroups were also isolated depending on medication: A - Octreotide, B - Quamatel, C - Octreotide + Quamatel. Pancreatic secretion was evaluated by using of course of disease, instrumental methods, APUD-system hormone levels (secretin, cholecystokinin, somatostatin, vasointestinal peptide). ETF was followed by pancreas enlargement despite ongoing therapy, while TPN led to gradual reduction of pancreatic size up to normal values. α-amylase level progressively decreased in all groups, however in patients who underwent ETF (I and II) mean values of the enzyme were significantly higher compared with TPN (group III). Secretin, cholecystokinin and vasointestinal peptide were increasing in most cases, while the level of somatostatin was below normal in all groups. Enteral tube feeding (balanced and oligopeptide mixtures) contributes to pancreatic secretion compared with TPN, but this negative impact is eliminated by antisecretory therapy. Dual medication (Octreotide + Quamatel) is more preferable than monotherapy (Octreotide or Quamatel).

Carcinoid crisis induced by receptor radionuclide therapy with 90Y-DOTATOC in a case of liver metastases from bronchial neuroendocrine tumor (atypical carcinoid).

PubMed

Davì, M V; Bodei, L; Francia, G; Bartolomei, M; Oliani, C; Scilanga, L; Reghellin, D; Falconi, M; Paganelli, G; Lo Cascio, V; Ferdeghini, M

2006-06-01

SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.

Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

PubMed

Erfani, Mostafa; Shafiei, Mohammad; Mazidi, Mohammad; Goudarzi, Mostafa

2013-04-01

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

[Protective effect of octreotide on liver warm ischemia reperfusion injury].

PubMed

Li, Jie-qun; Qi, Hai-zhi; He, Zhi-jun; Hu, Wei; Si, Zhong-zhou; Li, Yi-ning

2006-10-01

To explore the protective effect of octreotide on liver warm ischemia-reperfusion injury and its possible mechanism. Pringle's maneuver liver ischemia-reperfusion models were established. Forty eight male Sprague Daweley rats were randomly divided into a sham operation group (S group, n=16), an ischemia-reperfusion group (I/R group, n=16) and an octreotide preconditioning group (OPC group, n=16). ALT and AST in the serum were measured at 30 min after the ischemia and 120 min after the reperfusion. The histomorphological changes and ultrastructure of hepatocellular were observed by optic and transmission electronic microscope. Hepatic adenine nucleotide levels and energy changes (EC) were determined by high performance liquid chromatography (HPLC). (1) At 30 min after the ischemia and 120 min after the reperfusion, the levels of ALT and AST in the serum of OPC group was lower than those in I/R group, whereas the levels of ATP and EC in the hepatic tissue were higher than those in the I/R group (P<0.01 or P<0.05). Compared with the I/R group, the injury of hepatocellular histomorphology and ultrastructure in the OPC group was abated. (2) At 30, 60, and 120 min after the reperfusion, the levels of ATP and EC in the OPC groups were higher than those in the I/R group. During the ischemia, the levels of ATP and EC in the OPC group dropped more slowly than those in the I/R group, but ATP and EC in the OPC groups rose more quickly than those in the I/R group during the reperfusion. Octreotide precondition can improve the hepatocellular energy reserve, and protect the liver from warm ischemia-reperfusion injury. The protective of octreotide on warm ischemia-reperfusion injury may be related to its influence on endocrine secretion.

A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance

PubMed Central

Florian, J. P.; Curren, M. J.; Pawelczyk, J. A.

2012-01-01

Splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt table tolerance. In randomized, double-blind, crossover trials, hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery. A repeated-measures analysis of variance was used to compare changes from baseline with respect to sex and condition. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance. Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased systemic vascular conductance and non-SpVC. Changes in SpBF and SpVC between supine and HUT were smaller in women (P < 0.05). Tilt table tolerance was increased after administration of octreotide [median tilt time: 15.7 vs. 37.0 min (P < 0.05) and 21.8 vs. 45.0 min (P < 0.05) for women and men, respectively]. A significant relationship existed between change (Δ) in SpBF (placebo-octreotide) and Δtilt time in women (Δtilt time = 2.5–0.0083 ΔSpBF, P < 0.01), but not men (Δtilt time = 3.41–0.0008 ΔSpBF, P = 0.59). In conclusion, administration of octreotide acetate improved tilt table tolerance, which was associated with a decrease in SpVC. In women, but not men, the magnitude of reduction in SpBF was positively associated with improvements in tilt tolerance. PMID:22345429

Management of the hormonal syndrome of neuroendocrine tumors

PubMed Central

Waligórska-Stachura, Joanna; Czarnywojtek, Agata; Sawicka-Gutaj, Nadia; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Woliński, Kosma; Kaznowski, Jarosław; Wrotkowska, Elżbieta; Ruchała, Marek

2016-01-01

Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been cloned and characterized. Somatostatin analogues include octreotide and lanreotide are effective medical tools in the treatment and present selectivity for SSTR2 and SSTR5. During treatment is seen disapperance of flushing, normalization of bowel movements and reduction of serotonin and 5-hydroxyindole acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by specifically inhibiting serotonin synthesis and as such, is a promising potential new treatment for patients with carcinoid syndrome. To pancreatic functionig neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma. Medical management in patients with insulinoma include diazoxide which suppresses insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 – receptor antagonists. In patients with glucagonomas hyperglycaemia can be controlled using insulin and oral blood glucose lowering drugs. In malignant glucagonomas smatostatin analogues are effective in controlling necrolytic migratory erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea. PMID:28507564

Competing risks of death in younger and older postmenopausal breast cancer patients

PubMed Central

Chapman, Judy-Anne W; Pritchard, Kathleen I; Goss, Paul E; Ingle, James N; Muss, Hyman B; Dent, Susan F; Vandenberg, Ted A; Findlay, Brian; Gelmon, Karen A; Wilson, Carolyn F; Shepherd, Lois E; Pollak, Michael N

2014-01-01

AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival (P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival (P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa) and other cause (OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1 (IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-hydroxy vitamin D were associated with (1) all cause mortality, and if so and (2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. RESULTS: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447 (82%) < 70 years and 120 (18%) ≥ 70 years. There were 170 deaths: 106 (62.3%) BrCa; 55 (32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9 (5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrCa and OC deaths were not significantly different by treatment arm (P = 0.40): tamoxifen patients experienced 50 BrCa and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 BrCa and 23 OC deaths. Proportionately more deaths (P = 0.004) were from BrCa for patients < 70 years, where 70% of deaths were due to BrCa, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index (BMI) (P = 0.02). Higher pathologic T and N were associated with more BrCa deaths (P < 0.0001 and 0.002, respectively). The cumulative hazard plot for BrCa and OC mortality indicated the concurrent accrual of both types of death throughout follow-up, that is the existence of competing risks of mortality. MA.14 therapy did not impact mortality (P = 0.77). Three baseline patient and tumor characteristics were differentially associated with cause of death: older patients experienced more OC (P = 0.01) mortality; patients with T1 tumors and hormone receptor positive tumors had less BrCa mortality (respectively, P = 0.01, P = 0.06). Additionally, step-wise cause-specific models indicated that patients with node negative disease experienced less BrCa mortality (P = 0.002); there was weak evidence that, lower C-peptide (P = 0.08) was associated with less BrCa mortality, while higher BMI (P = 0.01) was associated with worse OC mortality. CONCLUSION: We demonstrate here a new paradigm of simultaneous testing of therapeutics directed at multiple diseases for which postmenopausal women are concurrently at risk. Octreotide LAR did not significantly impact breast cancer or other cause mortality, although different baseline factors influenced type of death. PMID:25493245

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy.

PubMed

Pucci, Andrea; Cheung, Wui Hang; Jones, Jenny; Manning, Sean; Kingett, Helen; Adamo, Marco; Elkalaawy, Mohamed; Jenkinson, Andrew; Finer, Nicholas; Doyle, Jacqueline; Hashemi, Majid; Batterham, Rachel L

2015-01-01

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m(2)). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m(2), weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m(2)), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m(2) after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting. Roux-en-Y gastric bypass and SG produce marked sustained weight reduction. However, there is a marked individual variability in this reduction, and post-operative weight loss follows a normal distribution with extremes of 'good' and 'poor' response.Profound anorexia and excessive weight loss post-SG may be associated with markedly elevated circulating fasted PYY and post-meal PYY and GLP1 levels.Octreotide treatment can produce symptomatic relief and weight regain for post-SG patients that have an extreme anorectic and weight loss response.The present case highlights the value of measuring circulating gut hormone levels in patients with post-operative anorexia and extreme weight loss.

Growth hormone used to control intractable bleeding caused by radiation-induced gastritis.

PubMed

Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

2015-08-21

Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis.

Evaluation of (64)Cu-labeled DOTA-D-Phe(1)-Tyr (3)-octreotide ((64)Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors.

PubMed

Hanaoka, Hirofumi; Tominaga, Hideyuki; Yamada, Keiich; Paudyal, Pramila; Iida, Yasuhiko; Watanabe, Shigeki; Paudyal, Bishnuhari; Higuchi, Tetsuya; Oriuchi, Noboru; Endo, Keigo

2009-08-01

In-111 ((111)In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ((64)Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a (64)Cu-labeled octreotide analog, (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D: -Phe(1)-Tyr(3)-octreotide ((64)Cu-DOTA-TOC). (64)Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 degrees C. The stability of (64)Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of (64)Cu-DOTA-TOC and (111)In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of (64)Cu-DOTA-TOC or (64)Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ((64)Cu-TETA-OC). The tumor was imaged using (64)Cu-DOTA-TOC, (64)Cu-TETA-OC, and FDG with an animal PET scanner. (64)Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. (64)Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of (64)Cu was higher than that of (111)In in all organs except kidney. In tumor-bearing mice, (64)Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 +/- 1.17 at 6 h after administration. (64)Cu-DOTA-TOC showed significantly higher accumulation in the tumor than (64)Cu-TETA-OC. (64)Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of (18)F-FDG PET and very similar to that of (64)Cu-TETA-OC. (64)Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.

Parenteral nutrition combined with rice soup can be a safe and effective intervention for congenital chylous ascites.

PubMed

Cao, Yi; Yan, Weihui; Lu, Lina; Tao, Yijing; Lu, Wei; Chen, Yingwei; Tang, Qingya; Cai, Wei

2016-01-01

Congenital chylous ascites in the neonatal period is a rare entity. Total parenteral nutrition (TPN), medium chain triglyceride (MCT)-based diet, octreotide and repeated paracentesis are regarded as appropriate medical treatment for congenital chylous ascites, and surgery is recommended when conservative therapy has failed. We present two cases in which ascites were confirmed via an abdominal sonogram and diagnostic paracentesis. In our clinical experience, rice soup combined with PN can be a safe and effective intervention.

Development of octreotide-conjugated polymeric prodrug of bufalin for targeted delivery to somatostatin receptor 2 overexpressing breast cancer in vitro and in vivo

PubMed Central

Liu, Tao; Jia, Tingting; Yuan, Xia; Liu, Cheng; Sun, Jian; Ni, Zhenhua; Xu, Jian; Wang, Xuhui; Yuan, Yi

2016-01-01

Background Development of polymeric prodrugs of small molecular anticancer drugs has become one of the most promising strategies to overcome the intrinsic shortcomings of small molecular anticancer drugs and improve their anticancer performance. Materials and methods In the current work, we fabricated a novel octreotide (Oct)-modified esterase-sensitive tumor-targeting polymeric prodrug of bufalin (BUF) and explored its anticancer performance against somatostatin receptor 2 overexpressing breast cancer. Results The obtained tumor-targeting polymeric prodrug of BUF, P(oligo[ethylene glycol] monomethyl ether methacrylate [OEGMA]-co-BUF-co-Oct), showed a nanosize dimension and controlled drug release features in the presence of esterase. It was demonstrated by in vitro experiment that P(OEGMA-co-BUF-co-Oct) showed enhanced cytotoxicity, cellular uptake, and apoptosis in comparison with those of free BUF. In vivo experiment further revealed the improved accumulation of drugs in tumor tissues and enhanced anticancer performance of P(OEGMA-co-BUF-co-Oct). Conclusion Taken together, this study indicated that polymeric prodrug of BUF holds promising potential toward the treatment of somatostatin receptor 2 overexpressing breast cancer. PMID:27284243

Development of effective prophylaxis against intraoperative carcinoid crisis.

PubMed

Woltering, Eugene A; Wright, Anne E; Stevens, Melissa A; Wang, Yi-Zarn; Boudreaux, John P; Mamikunian, Gregg; Riopelle, James M; Kaye, Alan D

2016-08-01

The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries. A retrospective study was approved by the institutional review boards at Ochsner Medical Center-Kenner and Louisiana State University Health Sciences Center. Ochsner Medical Center-Kenner operating room and multispecialty NET clinic. One hundred fifty consecutive patients who underwent a total of 179 cytoreductive surgeries for stage IV, small bowel NETs. All patients received a 500-μg/h infusion of octreotide acetate preoperatively, intraoperatively, and postoperatively. Anesthesia and surgical records were reviewed. Carcinoid crisis was defined as a systolic blood pressure of less than 80mm Hg for greater than 10minutes. Patients who experienced intraoperative hypertension or hypotension, profound tachycardia, or a "crisis" according to the operative note were also reviewed. One hundred sixty-nine (169/179; 94%) patients had normal anesthesia courses. The medical records of 10 patients were further investigated for a potential intraoperative crisis using the aforementioned criteria. Upon review, 6 patients were determined to have had a crisis. The final incidence of intraoperative crisis was 3.4% (6/179). A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis. We believe that the low cost and excellent safety profile of octreotide warrant the use of this therapy during extensive surgical procedures for midgut and foregut NETs. Copyright © 2016 Elsevier Inc. All rights reserved.

[Somatostatin and the digestive system. Clinical experiences].

PubMed

Herszényi, László; Mihály, Emese; Tulassay, Zsolt

2013-09-29

The effect of somatostatin on the gastrointestinal tract is complex; it inhibits the release of gastrointestinal hormones, the exocrine function of the stomach, pancreas and bile, decreases motility and influences absorption as well. Based on these diverse effects there was an increased expectation towards the success of somatostatin therapy in various gastrointestinal disorders. The preconditions for somatostatin treatment was created by the development of long acting somatostatin analogues (octreotide, lanreotide). During the last twenty-five years large trials clarified the role of somatostatin analogues in the treatment of various gastrointestinal diseases. This study summarizes shortly these results. Somatostatin analogue treatment could be effective in various pathological conditions of the gastrointestinal tract, however, this therapeutic modality became a part of the clinical routine only in neuroendocrine tumours and adjuvant treatment of oesophageal variceal bleeding and pancreatic fistulas.

Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma

PubMed Central

Norden, Andrew D.; Ligon, Keith L.; Hammond, Samantha N.; Muzikansky, Alona; Reardon, David A.; Kaley, Thomas J.; Batchelor, Tracy T.; Plotkin, Scott R.; Raizer, Jeffrey J.; Wong, Eric T.; Drappatz, Jan; Lesser, Glenn J.; Haidar, Sam; Beroukhim, Rameen; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Gaffey, Sarah C.; Gerard, Mary; Smith, Katrina H.; McCluskey, Christine; Phuphanich, Surasak

2015-01-01

Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Results: Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8–20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12–43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor–1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. Classification of evidence: This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months. PMID:25527270

Agonist-biased trafficking of somatostatin receptor 2A in enteric neurons.

PubMed

Zhao, Peishen; Canals, Meritxell; Murphy, Jane E; Klingler, Diana; Eriksson, Emily M; Pelayo, Juan-Carlos; Hardt, Markus; Bunnett, Nigel W; Poole, Daniel P

2013-09-06

Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions.

Agonist-biased Trafficking of Somatostatin Receptor 2A in Enteric Neurons*

PubMed Central

Zhao, Peishen; Canals, Meritxell; Murphy, Jane E.; Klingler, Diana; Eriksson, Emily M.; Pelayo, Juan-Carlos; Hardt, Markus; Bunnett, Nigel W.; Poole, Daniel P.

2013-01-01

Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions. PMID:23913690

68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT.

PubMed

Breer, Stefan; Brunkhorst, Thomas; Beil, F Timo; Peldschus, Kersten; Heiland, Max; Klutmann, Susanne; Barvencik, Florian; Zustin, Jozef; Gratz, Klaus-Friedrich; Amling, Michael

2014-07-01

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia and low calcitriol levels as well as clinical symptoms like diffuse bone and muscle pain, fatigue fractures or increased fracture risk. Conventional imaging methods, however, often fail to detect the small tumors. Lately, tumor localization clearly improved by somatostatin-receptor (SSTR) imaging, such as octreotide scintigraphy or octreotide SPECT/CT. However, recent studies revealed that still a large number of tumors remained undetected by octreotide imaging. Hence, studies focused on different SSTR imaging methods such as 68Ga DOTA-NOC, 68Ga DOTA-TOC and 68Ga DOTA-TATE PET/CT with promising first results. Studies comparing different SSTR imaging methods for tumor localization in TIO are rare and thus little is known about diagnostic alternatives once a particular method failed to detect a tumor in patients with TIO. Here, we report the data of 5 consecutive patients suffering from TIO, who underwent both 111Indium-octreotide scintigraphy (111In-OCT) SPECT/CT as well as 68Ga DOTA-TATE PET/CT for tumor detection. While 111In-OCT SPECT/CT allowed tumor detection in only 1 of 5 patients, 68Ga DOTA-TATE PET/CT was able to localize the tumor in all patients. Afterwards, anatomical imaging of the region of interest was performed with CT and MRI. Thus, successful surgical resection of the tumor was achieved in all patients. Serum phosphate levels returned to normal and all patients reported relief of symptoms within weeks. Moreover, an iliac crest biopsy was obtained from every patient and revealed marked osteomalacia in all cases. Follow-up DXA revealed an increase in BMD of up to 34.5% 1-year postoperative, indicating remineralization. No recurrence was observed. In conclusion our data indicates that 68Ga DOTA-TATE PET/CT is an effective and promising diagnostic tool in the diagnosis of TIO, even in patients in whom 111In-OCT prior failed to detect a tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

Expression Analysis of Dopamine Receptor Subtypes in Normal Human Pituitaries, Nonfunctioning Pituitary Adenomas and Somatotropinomas, and the Association between Dopamine and Somatostatin Receptors with Clinical Response to Octreotide-LAR in Acromegaly

PubMed Central

Neto, Leonardo Vieira; Machado, Evelyn de O.; Luque, Raul M.; Taboada, Giselle F.; Marcondes, Jorge B.; Chimelli, Leila M. C.; Quintella, Leonardo Pereira; Niemeyer, Paulo; de Carvalho, Denise P.; Kineman, Rhonda D.; Gadelha, Mônica R.

2009-01-01

Context: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies. Objectives: Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1–5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients. Design and Patients: Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients. Results: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T⋙DR4≫DR5>DR1, whereas in NFPAs, DR2T⋙DR4≫DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = −0.67, P = 0.002; and 6 months: r = −0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04). Conclusions: DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5. PMID:19293270

Oral self-nanoemulsifying peptide drug delivery systems: impact of lipase on drug release.

PubMed

Mahjub, Reza; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza; Bernkop Schnürch, Andreas

2015-01-01

It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1 ± 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232 ± 53 nm and 235 ± 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p < 0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.

Doppler waveform study as indicator of change of portal pressure after administration of octreotide

PubMed Central

Haider, Shahbaz; Hussain, Qurban; Tabassum, Sumera; Hussain, Bilal; Durrani, Muhammad Rasheed; Ahmed, Fayyaz

2016-01-01

Objective: To estimate the effect of portal pressure lowering drug ‘octreotide’, by observing the Doppler waveform before and after the administration of intravenous bolus of octreotide and thus to assess indirectly its efficacy to lower the portal pressure. Methods: This quassi experimental study was carried out in Medical Department in collaboration with Radiology Department of Jinnah Postgraduate Medical Center Karachi Pakistan from September 10, 2015 to February 5, 2016. Cases were selected from patients admitted in Medical Wards and those attending Medical OPD. Diagnosis of cirrhosis was confirmed by Clinical Examination and Lab & Imaging investigation in Medical Department. Doppler waveform study was done by experienced radiologist in Radiology Department before and after administration of octreotide. Doppler signals were obtained from the right hepatic vein. Waveform tracings were recorded for five seconds and categorized as ‘monophasic’, ‘biphasic’ and ‘triphasic’. Waveform changes from one waveform to other were noted and analyzed. Results: Significant change i.e. from ‘monophasic’ to ‘biphasic’ or ‘biphasic’ to ‘triphasic’ was seen in 56% cases while ‘monophasic’ to ‘triphasic’ was seen in 20% cases. No change was seen in 24% cases. Improvement in waveform reflects lowering of portal vein pressure. Conclusion: Non invasive Hepatic vein Doppler waveform study showed improvement in Doppler waveform after administration of octreotide in 76% cases. Doppler waveform study has the potential of becoming non invasive ‘follow up tool’ of choice for assessing portal pressure in patients having variceal bleed due to portal hypertension. PMID:27648043

Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome.

PubMed

De Waele, Kathleen; Ishkanian, Stacey L; Bogarin, Roberto; Miranda, Charmaine A; Ghatei, Mohammad A; Bloom, Stephen R; Pacaud, Danièle; Chanoine, Jean-Pierre

2008-10-01

Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS. A 56-week prospective, randomized, cross-over trial. Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score +1.9 (0.6-3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period. Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations (P<0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones. Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study

PubMed Central

2014-01-01

Background We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. Methods This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Results Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. Conclusion The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. Trial registration Trial registration number NCT01203306. PMID:24628963

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery.

PubMed

Besselink, Marc G; van Rijssen, L Bengt; Bassi, Claudio; Dervenis, Christos; Montorsi, Marco; Adham, Mustapha; Asbun, Horacio J; Bockhorn, Maximillian; Strobel, Oliver; Büchler, Markus W; Busch, Olivier R; Charnley, Richard M; Conlon, Kevin C; Fernández-Cruz, Laureano; Fingerhut, Abe; Friess, Helmut; Izbicki, Jakob R; Lillemoe, Keith D; Neoptolemos, John P; Sarr, Michael G; Shrikhande, Shailesh V; Sitarz, Robert; Vollmer, Charles M; Yeo, Charles J; Hartwig, Werner; Wolfgang, Christopher L; Gouma, Dirk J

2017-02-01

Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication. Copyright © 2016 Elsevier Inc. All rights reserved.

Pasireotide in the treatment of neuroendocrine tumors: a review of the literature.

PubMed

Vitale, Giovanni; Dicitore, Alessandra; Sciammarella, Concetta; Di Molfetta, Sergio; Rubino, Manila; Faggiano, Antongiulio; Colao, Annamaria

2018-06-01

Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical relevance and future perspectives for this molecule in the management of NETs. © 2018 Society for Endocrinology.

Update on Modern Management of Pheochromocytoma and Paraganglioma.

PubMed

Lenders, Jacques W M; Eisenhofer, Graeme

2017-06-01

Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as ⁶⁸Ga-DOTATATE (⁶⁸Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace ¹²³I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong. Copyright © 2017 Korean Endocrine Society.

Selective agonists of somatostatin receptor subtype 1 or 2 injected peripherally induce antihyperalgesic effect in two models of visceral hypersensitivity in mice

PubMed Central

Mulak, Agata; Larauche, Muriel; Biraud, Mandy; Million, Mulugeta; Rivier, Jean; Taché, Yvette

2014-01-01

Somatostatin interacts with 5 G-protein-coupled receptor (sst1–5). Octreotide, a stable sst2≫3≥5 agonist, octreotide, exerts a visceral anti-hyperalgesic effect in experimental and clinical studies. Little is known on the receptor subtypes involved. We investigated the influence of the stable sst1–5 agonist, ODT8-SST and selective receptor subtype peptide agonists (3 or 10 μg/mouse) injected intraperitoneally (ip) on visceral hypersensitivity in mice induced by repeated noxious colorectal distensions (4 sets of 3 CRD, each at 55 mmHg) or corticotropin-releasing factor receptor 1 agonist, cortagine given between 2 sets of graded CRD (15, 30, 45, and 60 mmHg, 3 times each pressure). The mean visceromotor response (VMR) was assessed using a non-invasive manometry method and values were expressed as percentage of the VMR to the 1st set of CRD baseline or to the 60 mmHg CRD, respectively. ODT8-SST (10 μg) and the sst2 agonist, S-346-011 (3 and 10 μg) prevented mechanically-induced visceral hypersensitivity in the 3 sets of CRD, the sst1 agonist (10 μg) blocked only the 2nd set and showed a trend at 3 μg while the sst4 agonist had no effect. The selective sst2 antagonist, S-406-028 blocked the sst2 agonist but not the sst1 agonist effect. The sst1 agonist (3 and 10 μg) prevented cortagine-induced hypersensitivity to CRD at each pressure while the sst2 agonist at 10 μg reduced it. These data indicate that in addition to sst2, the sst1 agonist may provide a novel promising target to alleviate visceral hypersensitivity induced by mechanoreceptor sensitization and more prominently, stress-related visceral nociceptive sensitization. PMID:25451334

Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.

PubMed

Goldstone, Anthony P; Miras, Alexander D; Scholtz, Samantha; Jackson, Sabrina; Neff, Karl J; Pénicaud, Luc; Geoghegan, Justin; Chhina, Navpreet; Durighel, Giuliana; Bell, Jimmy D; Meillon, Sophie; le Roux, Carel W

2016-02-01

Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.

PubMed

Fasshauer, Mathias; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen; Paschke, Ralf; Koch, Christian A

2006-04-27

ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

PubMed Central

Fasshauer, Mathias; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen; Paschke, Ralf; Koch, Christian A

2006-01-01

Background ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. Case presentation A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. Conclusion This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using 111In-pentetreotide and a gamma probe. PMID:16643652

99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

PubMed

Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

2004-04-01

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

Radiopharmaceutical development of a freeze-dried kit formulation for the preparation of [99mTc-EDDA-HYNIC-D-Phe1, Tyr3]-octreotide, a somatostatin analog for tumor diagnosis.

PubMed

Guggenberg, Elisabeth Von; Mikolajczak, Renata; Janota, Barbara; Riccabona, Georg; Decristoforo, Clemens

2004-10-01

[(99m)Tc-EDDA-HYNIC-D-Phe(1),Tyr(3)]-Octreotide ((99m)Tc-EDDA/HYNIC-TOC) is a promising new radiopharmaceutical with the potential to replace [(111)In-DTPA-D-Phe(1)]-Octreotide ((111)In-DTPA-OCT) as the radiopharmaceutical for somatostatin receptor scintigraphy due to the advantage of improved image quality, lower radiation dose for the patient, and daily availability. Here we describe the development of a freeze-dried kit formulation based on the Tricine/EDDA exchange labeling approach for the preparation of this radiopharmaceutical in a clinical setting. Three parameters were of major importance to achieve a suitable formulation with a radiochemical purity (RCP) >90%: addition of bulking agent, the pH of the freeze-drying solution, and the content of stannous chloride. The final formulation consisted of 20 mg Tricine, 10 mg EDDA, 50 mg Mannitol, 20 microg SnCl(2). 2H(2)O, and 20 microg [HYNIC-D-Phe(1), Tyr(3)]-Octreotide (HYNIC-TOC). Radiolabeling was performed by addition of 0.2 M Na(2)HPO(4) to adjust the pH to 6-7, followed by 0.5-2 GBq (99m)Tc sodium pertechnetate, in a total volume of 2 mL and incubation for 10 min in a boiling water bath. Mean RCP values of 10 batches showed values >90% over a storage period of up to 1 year, a high stability up to 24 h of the final preparation, and retained biological activity. The developed kit formulation forms the basis for further clinical evaluation of this promising new radiopharmaceutical. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

A thyrotropin-secreting macroadenoma with positive growth hormone and prolactin immunostaining: A case report and literature review.

PubMed

Kuzu, F; Bayraktaroğlu, T; Zor, F; G N, B D; Salihoğlu, Y S; Kalaycı, M

2015-01-01

Thyrotropin (thyroid stimulating hormone [TSH]) secreting pituitary adenomas (TSHoma) are rare adenomas presenting with hyperthyroidism due to impaired negative feedback of thyroid hormone on the pituitary and inappropriate TSH secretion. This article presents a case of TSH-secreting macroadenoma without any clinical hyperthyroidism symptoms accompanying immunoreaction with growth hormone (GH) and prolactin. A 36-year-old female patient was admitted with complaints of irregular menses and blurred vision. On physical exam, she had bitemporal hemianopsia defect. Magnetic resonance imaging (MRI) evaluation showed suprasellar macroadenoma measuring 33 mm × 26 mm × 28 mm was detected on pituitary MRI. She had no hyperthyroidism symptoms clinically. Although free T4 and free T3 levels were elevated, TSH level was inappropriately within the upper limit of normal. Response to T3 suppression and thyrotropin releasing hormone-stimulation test was inadequate. Other pituitary hormones were normal. Transsphenoidal adenomectomy was performed due to parasellar compression findings. Immunohistochemically widespread reaction was observed with TSH, GH and prolactin in the adenoma. The patient underwent a second surgical procedure 2 months later due to macroscopic residual tumor, bitemporal hemianopsia and a suprasellar homogenous uptake with regular borders on indium-111 octreotide scintigraphy. After second surgery; due to ongoing symptoms and residual tumor, she was managed with octreotide and cabergoline treatment. On her follow-up with medical treatment, TSH and free T4 values were within normal limits. Although silent TSHomas are rare, they may arise with compression symptoms as in our case. The differential diagnosis of secondary hyperthyroidism should include TSHomas and thyroid hormone receptor resistance syndrome.

Patient-specific dosimetry calculations using mathematic models of different anatomic sizes during therapy with 111In-DTPA-D-Phe1-octreotide infusions after catheterization of the hepatic artery.

PubMed

Kontogeorgakos, Dimitrios K; Dimitriou, Panagiotis A; Limouris, Georgios S; Vlahos, Lambros J

2006-09-01

The aim of the study was to provide dosimetric data on intrahepatic (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide therapy for neuroendocrine tumors with overexpression of somatostatin receptors. A dosimetric protocol was designed to estimate the absorbed dose to the tumor and healthy tissue in a course of 48 treatments for 12 patients, who received a mean activity of 5.4 +/- 1.7 GBq per session. The patient-specific dosimetry calculations, based on quantitative biplanar whole-body scintigrams, were performed using a Monte Carlo simulation program for 3 male and 3 female mathematic models of different anatomic sizes. Thirty minutes and 2, 6, 24, and 48 h after the radionuclide infusion, blood-sample data were collected for estimation of the red marrow radiation burden. The mean absorbed doses per administered activity (mGy/MBq) by the critical organs liver, spleen, kidneys, bladder wall, and bone marrow were 0.14 +/- 0.04, 1.4 +/- 0.6, 0.41 +/- 0.08, 0.094 +/- 0.013, and (3.5 +/- 0.8) x 10(-3), respectively; the tumor absorbed dose ranged from 2.2 to 19.6 mGy/MBq, strongly depending on the lesion size and tissue type. The results of the present study quantitatively confirm the therapeutic efficacy of transhepatic administration; the tumor-to-healthy-tissue uptake ratio was enhanced, compared with the results after antecubital infusions. Planning of treatment was also optimized by use of the patient-specific dosimetric protocol.

Nutritional support in patients with gastrointestinal fistula.

PubMed

Yanar, F; Yanar, H

2011-06-01

Gastrointestinal fistulas (GIFs) arise as a complication of the surgical treatment of a number of malignant and non-malignant diseases. Fluid loss and electrolyte and nutritional imbalance are related to increased morbidity and mortality in these patients. A multidisciplinary approach under the leadership of the surgeon is essential for successful therapy. Because complication rates are higher in malnourished patients with fistulas, enteral or total parenteral nutritional (TPN) support should be initiated after the patient has been stabilized with respect to fluid loss, acid-base, and sepsis. Pharmacotherapy with somatostatin and octreotide has been shown to reduce fistula output and shorten closure time.

Influence of PET/CT 68Ga somatostatin receptor imaging on proceeding with patients, who were previously diagnosed with 99mTc-EDDA/HYNIC-TOC SPECT.

PubMed

Madrzak, Dorota; Mikołajczak, Renata; Kamiński, Grzegorz

2016-01-01

The aim of this study was the assessment of utility of somatostatin receptor scintigraphy (SRS) by SPECT imaging using 99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-EDDA/HYNIC-TOC) in patients with neuroendocrine neoplasm (NEN) or suspected NEN, referred to Nuclear Medicine Dept. of Voivodship Specialty Center in Rzeszow. The selected group of patients was referred also to 68Ga PET/CT. The posed question was the ratio of patients for whom PET/CT with 68Ga would change their management. The distribution of somatostatin receptors was imaged using 99mTc-EDDA/HYNIC-TOC in 61 planar and SPECT studies between 13/05/2010 and 04/02/2013 in Nuclear Medicine Dept. of Voivodship Specialty Center in Rzeszow. The patient age was within a range of 17-80, with the average age of 57.6. The average age of women (65% of patients over-all) was 55.6 and the average age of men (35% of patients overall) was 61.4. In 46 participants (75% of the study group), that underwent SRS, NEN was documented using pathology tests. Selected patients were referred to PET/CT with 68Ga labeled somatostatin analogs, DOTATATE or DOTANOC. This study group consisted of 14 female and 10 male participants with age range of 35-77 and average age of 55.5 years. Patients were classified into 3 groups, as follows: detection - referral due to clinical symptoms and/or biochemical markers (CgA-Chromogranin A, IAA-indoleacetic acid) with the aim of primary diagnosis, staging - referral with the aim of assessment of tumor spread, and follow-up - assessment of the therapy. Out of 61 patients, 24 underwent both 99mTc-EDDA/HYNIC-Tyr3-octreotide SPECT and 68Ga PET/CT. The result of PET/CT was used as a basis for further evaluation. Therefore, the patients were divided into groups; true positive TP (confirmed presence of tissue somatostatin receptors with 68Ga PET/CT) and TN (68Ga PET/CT did not detect any changes and the results were comparable and had the same influence on treatment protocol). In case of SPECT, the results were assigned as follows: TP, TN (in cases where the results were confirmed by 68Ga PET/CT), FP (patient's scintigraphy demonstrated focal change by SPECT but not PET/CT) and FN (99mTc-EDDA/HYNIC-Tyr3-octreotide SPECT failed to demonstrate any abnormalities; however, the treatment protocol was changed after PET/CT). The accuracy of SPECT diagnosis was found to be as high as 91.6%. Only in 8.4% of patients the additional PET/CT with 68Ga-labeled somatostatin analog changed the treatment protocol.

Acute Kidney Injury: Quoi de Neuf?

PubMed Central

Reichel, Ronald R.

2014-01-01

Background Acute kidney injury (AKI) is frequently encountered in the nephrology practice. Serum creatinine, with its many shortcomings, is still the main biomarker used to detect AKI. Methods This review focuses on recent advances in definition, diagnosis, risk factors, and molecular mechanisms of AKI. In addition, specific AKI syndromes such as contrast-induced AKI, hepatorenal syndrome, and acute decompensated heart failure are discussed. The connection between AKI and subsequent chronic kidney disease and recent developments in renal replacement therapy are also covered. Results Novel biomarkers such as cystatin C and neutrophil gelatinase–associated lipocalin (NGAL) are being investigated to replace serum creatinine in the detection of AKI. Recent studies suggest that intravenous (IV) fluid use is beneficial for the prevention of contrast-induced AKI, while N-acetylcysteine use is not as well established. Diuretics are clearly beneficial in the treatment of acute decompensated heart failure. Ultrafiltration is less promising and can lead to adverse side effects. Although terlipressin use in hepatorenal syndrome is associated with reduced mortality, it is not available in the United States; combination therapy with midodrine, octreotide, and albumin provides an alternative. Fluid resuscitation is frequently used in critically ill patients with AKI; however, overly aggressive fluid resuscitation is frequently associated with an increased risk of mortality. A 3-step approach that combines guided fluid resuscitation, establishment of an even fluid balance, and an appropriate rate of fluid removal may be beneficial. If fluid resuscitation is needed, crystalloid solutions are preferred over hetastarch solutions. Renal replacement therapy is the last resort in AKI treatment, and timing, modality, and dosing are discussed. Research suggests that AKI leads to an increased incidence of subsequent chronic kidney disease. However, this relationship has not been fully established and additional studies are needed for clarification. Conclusion Despite major advances in AKI research, serum creatinine remains the major biomarker for the detection of AKI. The following interventions have shown to be beneficial: IV fluids for contrast-induced AKI; diuretics for acute decompensated heart failure/cardiorenal syndrome; and combination therapy with midodrine, octreotide, and albumin for hepatorenal syndrome. Fluid resuscitation in a patient with AKI should be used with caution because too liberal use of fluids can be associated with increased mortality. AKI appears to be related to increased rates of subsequent chronic kidney disease, and patients with AKI should therefore be monitored closely. Recent studies on renal replacement therapy have neither revealed an optimal timing for initiation of dialysis nor a clear advantage for a specific dialysis modality. PMID:25249802

Hyperthyroidism due to inappropriate secretion of thyroid-stimulating hormone: diagnosis and management.

PubMed

Hermus, A; Ross, H; van Liessum, P; Naber, A; Smals, A; Kloppenborg, P

1991-06-01

The case histories of three patients with hyperthyroidism due to overproduction of thyroid-stimulating hormone (TSH) by the pituitary gland are described. In the first patient treatment with the T3-metabolite 3,5,3'-triiodothyroacetic acid (TRIAC) led to complete clinical and biochemical normalization. In the second patient treatment with the dopaminergic agonist bromocriptine led to a temporal amelioration of hyperthyroidism. In the third patient, who was the only one with a proven pituitary adenoma, hypersecretion of TSH could be controlled by administration of the somatostatin analogue octreotide. It is emphasized that patients with this disorder should preferably not be treated with thyrostatic drugs, radioactive iodine or thyroid surgery. The success rate of these treatment modalities is lower than normal, they may lead to an increase of goiter size, and they potentially may promote growth or development of a TSH-producing adenoma. Treatment should be aimed at diminishing TSH hypersecretion.

High-dose octreotide acetate for management of gastroenteropancreatic neuroendocrine tumors.

PubMed

Chadha, Manpreet K; Lombardo, Jeffrey; Mashtare, Terry; Wilding, Gregory E; Litwin, Alan; Raczyk, Cheryl; Gibbs, John F; Kuvshinoff, Boris; Javle, Milind M; Iyer, Renuka V

2009-10-01

Long-acting sandostatin (S-LAR; octreotide acetate) is well tolerated and effective for symptom control and possibly disease control in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We undertook a retrospective analysis to study the efficacy and tolerability of higher doses (more than 20-30 mg/month) of S-LAR in GEP-NETs. With IRB approval, charts of all patients with GEP-NET who received S-LAR between June 2002 to September 2007 at Roswell Park Cancer Institute were reviewed and their data analyzed. Fifty-four patients with GEP-NET received S-LAR; thirty required dose escalation. Patients received a median of 5 doses of S-LAR at conventional dose followed by up-titration of the dose for symptom control (20) and radiological progression (17). Median high dose of S-LAR was 40 mg (range: 40-90 mg) with a median of 8.5 high doses received. No treatment related toxicities were seen. The estimated 1-year survival for patients on conventional dose alone was 0.77 (95% CI of 0.50 to 0.91) and those on high-dose was 0.88 (95% CI of 0.68 to 0.96) (p=0.4777) while median time to any other intervention was 2.9 months versus 17.7 months (p=0.12). Dose escalation of S-LAR is well tolerated and may provide longer disease control.

Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial.

PubMed

Strosberg, Jonathan; Wolin, Edward; Chasen, Beth; Kulke, Matthew; Bushnell, David; Caplin, Martyn; Baum, Richard P; Kunz, Pamela; Hobday, Timothy; Hendifar, Andrew; Oberg, Kjell; Sierra, Maribel Lopera; Thevenet, Thomas; Margalet, Ines; Ruszniewski, Philippe; Krenning, Eric

2018-06-07

Purpose Neuroendocrine tumor (NET) progression is associated with deterioration in quality of life (QoL). We assessed the impact of 177 Lu-Dotatate treatment on time to deterioration in health-related QoL. Methods The NETTER-1 trial is an international phase III study in patients with midgut NETs. Patients were randomly assigned to treatment with 177 Lu-Dotatate versus high-dose octreotide. European Organisation for Research and Treatment of Cancer quality-of-life questionnaires QLQ C-30 and G.I.NET-21 were assessed during the trial to determine the impact of treatment on health-related QoL. Patients completed the questionnaires at baseline and every 12 weeks until tumor progression. QoL scores were converted to a 100-point scale according to European Organisation for Research and Treatment of Cancer instructions, and individual changes from baseline scores were assessed. Time to QoL deterioration (TTD) was defined as the time from random assignment to the first QoL deterioration ≥ 10 points for each patient in the corresponding domain scale. All analyses were conducted on the intention-to-treat population. Patients with no deterioration were censored at the last QoL assessment date. Results TTD was significantly longer in the 177 Lu-Dotatate arm (n = 117) versus the control arm (n = 114) for the following domains: global health status (hazard ratio [HR], 0.406), physical functioning (HR, 0.518), role functioning (HR, 0.580), fatigue (HR, 0.621), pain (HR, 0.566), diarrhea (HR, 0.473), disease-related worries (HR, 0.572), and body image (HR, 0.425). Differences in median TTD were clinically significant in several domains: 28.8 months versus 6.1 months for global health status, and 25.2 months versus 11.5 months for physical functioning. Conclusion This analysis from the NETTER-1 phase III study demonstrates that, in addition to improving progression-free survival, 177 Lu-Dotatate provides a significant QoL benefit for patients with progressive midgut NETs compared with high-dose octreotide.

A Case of Acromegaly in which a Pituitary Gland Tumor was Reduced Significantly by Administering Octreotide Long Acting Release (LAR) and Could Be Removed Surgically.

PubMed

Arao, Tadashi; Okada, Yosuke; Uemura, Fumi; Nishizawa, Shigeru; Tanaka, Yoshiya

A 54-year-old woman was admitted to our hospital for detailed examination of acromegaly because she noticed bilateral hand and finger swelling at the age of 43 and plantar thickening, facial changes and unclear articulation at the age of 49. She had prominent brow ridges, mandibular protrusion, and enlargement of the hands, feet, nasal wings, lips and tongue. Her growth hormone (GH) level was 39.8 ng/ml, insulin-like growth factor-1 (IGF-1) level was 717 ng/ml, GH level was not suppressed (22.9 ng/ml) during a 75-g oral glucose tolerance test (OGTT). Radiography showed cauliflower-like enlargement of the distal phalanx of the fingers, thickening/enlargement of the plantar soft tissues, and increased antero-posterior diameter of the sella turcica. Magnetic resonance imaging showed a mass (21×17 mm) growing towards the right suprasellar region and invading the cavernous sinus. She was diagnosed with acromegaly based on the characteristic physical findings, GH excess, high IGF-1, lack of GH suppression during the 75-g OGTT, and the presence of a pituitary tumor. She was started on octreotide long acting release (Oct-LAR) 20 mg/4w for tumor shrinkage. After three doses, her GH and IGF-1 levels decreased to 2.19 ng/ml (1.69 during the 75-g OGTT) and 205 ng/ml, respectively, meeting cure criteria for acromegaly. In this case, a decrease in GH and IGF-1 levels, tumor shrinkage, and resolution of cavernous sinus invasion allowed the patient to undergo surgery with curative intent (the first-line treatment for acromegaly) without postoperative complications. Thus, preoperative Oct-LAR administration has the potential to improve treatment outcomes of acromegaly.

Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients.

PubMed

Faggiano, Antongiulio; Tavares, Lidice Brandao; Tauchmanova, Libuse; Milone, Francesco; Mansueto, Gelsomina; Ramundo, Valeria; De Caro, Maria Laura Del Basso; Lombardi, Gaetano; De Rosa, Gaetano; Colao, Annamaria

2008-11-01

In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

Thymic pathologies in myasthenia gravis: a preoperative assessment of CAT scan and nuclear based imaging.

PubMed

Jordan, Berit; Kellner, Juliane; Jordan, Karin; Bähre, Manfred; Behrmann, Curd; Zierz, Stephan

2016-04-01

Precise diagnostic work up of a suspected thymic pathology in patients with myasthenia gravis (MG) is very important for potential surgical implications and further disease course. In this study the diagnostic value of combined preoperative radiological (CAT scan) and nuclear based imaging (octreotide and thallium scintigraphy) in patients with MG was evaluated. Twenty four patients were included. Histopathology revealed thymoma in nine patients, thymic carcinoma (TC) in one patient, lymphofollicular hyperplasia in seven patients, and involuted thymus in another seven patients. Diagnostic sensitivity for detecting thymoma/TC was 80 % in CAT scan as well as in somatostatin scintigraphy; the combination of both procedures reached 90 %. However, the diagnostic specifity to exclude thymoma in CAT scan was 100 % and in octreotide scintigraphy 85.7 %. Semiquantitative octreotide uptake significantly correlated with histological grading of thymoma/TC (r = 0.764) and histological proliferation rate Ki67 (r = 0.894). Thallium scintigraphy was positive only in one out of four thymoma cases. In this study, somatostatin scintigraphy has been shown to be a useful additional diagnostic technique in detecting thymic malignancies in patients with MG. These results might be especially helpful in patients with late onset MG as these patients are in general no candidates for thymectomy.

[Pancreatic fistula after left pancreatectomy. Risk factors analysis on 68 patients].

PubMed

Pericoli Ridolfini, M; Alfieri, S; Gourgiotis, S; Di Miceli, D; Quero, G; Rotondi, F; Caprino, P; Sofo, L; Doglietto, B G

2008-06-01

The aim of this study was to identify risk factors related to pancreatic fistula after left pancreatectomy, considering the difference between the use of mechanical suture and the manual suture to close the pancreatic stump. Sixty-eight patients, undergoing left pancreatectomy, were included in this study during a 10-year period. Eight possible risk factors related to pancreatic fistula were examined, such as demographic data (age and sex), pathology (pancreatic and extrapancreatic), technical characteristics (stump closure, concomitant splenectomy, additional procedures), texture of pancreatic parenchyma, octreotide therapy. Fourty-one patients (60%) underwent left pancreatectomy for primary pancreatic disease and 27 (40%) for extrapancreatic malignancy. Postoperative mortality and morbidity rates were 1.5% and 35%, respectively. Fourteen patients (20%) developed pancreatic fistula: 4 of them were classified as Grade A, 9 as Grade B and only one as Grade C. Three factors have been significantly associated to the incidence of pancreatic fistula: none prophylactic octreotide therapy, spleen preserving and soft pancreatic texture. It's still unclear the influence of pancreatic stump closure (stapler vs hand closure) in the onset of pancreatic fistula. In this study the incidence of pancreatic fistula after left pancreatectomy has been 20%. This rate is lower for patients with fibrotic pancreatic tissue, concomitant splenectomy and postoperative prophylactic octreotide therapy.

Investigation into the efficacy and safety of octreotide LAR in Japanese patients with acromegaly: Shizuoka study.

PubMed

Oki, Yutaka; Inoue, Tatsuhide; Imura, Mitsuo; Tanaka, Tokutaro; Genma, Rieko; Iwabuchi, Masayasu; Hataya, Yuji; Matsuzawa, Yuji; Iino, Kazumi; Nishizawa, Shigeru; Nakamura, Hirotoshi

2009-01-01

The efficacy and safety of the long-acting repeatable formulation of octreotide (OCT-LAR) treatment in patients suffering from acromegaly was investigated retrospectively in Shizuoka prefecture, Japan. Thirty patients (11 male, 19 female; average age, 48.9 years old), 29 of whom had undergone transsphenoidal surgery previously, were treated with OCT-LAR. OCT-LAR was injected i.m. every 4 weeks with an intended protocol of 20 mg over 24 months, however, 46.7% of patients required the dose of OCT-LAR to be increased. The final average dose of OCT-LAR was 25.0 +/- 6.8 mg. Administering OCT-LAR significantly decreased serum GH and insulin-like growth factor 1 (IGF-1) levels (from 13.7 +/- 11.9 to 5.8 +/- 7.3 microg/L and from 585 +/- 263 to 339 +/- 193.7 microg/L after 3 months, respectively). Among patients treated with OCT-LAR, 56.7% expressed

Use of somatostatin analogues to treat chylothorax in a child with Generalised Lymphatic Dysplasia

PubMed Central

Brodlie, Malcolm; Abdelgalil, Sara; Mansour, Sahar; Spencer, David A.

2011-01-01

Generalised Lymphatic Dysplasia is a rare condition that may be associated with significant chylothoraces. The management of such effusions is often challenging. We present the case of a 15-year-old girl with bilateral chylothoraces and lymphoedema of her limbs. A clinical diagnosis of Generalised Lymphatic Dysplasia was made and long-term treatment with somatostatin analogues (somatostatin initially followed by monthly octreotide) was initiated. Over 12 months there was symptomatic benefit with some objective improvement in lung function and no adverse effects. After a year of treatment there was some reaccumulation of fluid, however this did not require any intervention. This is the first paediatric report of the use of somatostatin analogues to manage chylothorax in Generalised Lymphatic Dysplasia and we conclude that they represent a potentially useful treatment modality. Experience is only anecdotal however and further studies are required to establish an evidence base with regard to efficacy and safety. PMID:26056769

Comparison of different methods for radiochemical purity testing of [99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide.

PubMed

von Guggenberg, Elisabeth; Penz, Barbara; Kemmler, Georg; Virgolini, Irene; Decristoforo, Clemens

2006-02-01

[99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide (99mTc-EDDA-HYNIC-TOC) is an alternative radioligand for somatostatin receptor (SSTR) scintigraphy of neuroendocrine tumours. In order to allow a rapid and accurate determination of the quality in the clinical routine the aim of this study was to evaluate different methods of radiochemical purity (RCP) testing. Three different methods of RCP testing were compared: high-performance liquid chromatography (HPLC), thin layer chromatography (TLC) and minicolumn (Sep-Pak purification = SPE). HPLC was shown to be the most effective method for the quality control. The use of TLC and SPE is only recommended after sufficient practical labelling experience.

Recurrent Glioblastoma Multiforme (grade IV - WHO 2007): a case of complete objective response - concomitant administration of Somatostatin / Octreotide, Retinoids, Vit E, Vit D3, Vit C, Melatonin, D2 R agonists (Di Bella Method.

PubMed

Di Bella, Giuseppe; Leci, Jovan; Ricchi, Alessandro; Toscano, Rosilde

2015-01-01

In a 41 year old man, with Glioblastoma Multiforme (Grade IV - WHO 2007) and loco-regional recurrence, treated conventionally with surgery, radio-therapy and Temolozomide, a complete objective response was subsequently achieved by means of the well-tolerated concomitant administration of Somatostatin + slow-release Octreotide, Melatonin, Retinoids solubilized in Vitamin E, Vit D3, Vit C, D2 R agonists, and Temolozomide. In addition to the positive and previously unreported therapeutic finding, this result allowed the patient to avoid further surgical trauma and the correlated risks, achieving an excellent quality of life and working capacity.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

PubMed

Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

2017-01-01

To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

Anemia and neutropenic fever with high dose diazoxide treatment in a case with hyperinsulinism due to Munchausen by proxy.

PubMed

Ozon, A; Demirbilek, H; Ertugrul, A; Unal, S; Gumruk, F; Kandemir, N

2010-07-01

The etiology of hyperinsulinemic hypoglycemia in adolescents is similar to that of adults. Patients resistant to medical treatment may undergo pancreatectomy. Diazoxide is the mainstay of medical treatment. Rarely bone marrow suppression is reported due to diazoxide. An adolescent with severe hyperinsulinemic hypoglycemia was referred for pancreatectomy after she was treated with high doses of diazoxide, octreotide and glucose. She developed anemia and febrile neutropenia in the course of diazoxide treatment that resolved with cessation of medication. The cause of the hyperinsulinemia proved to be classical Munchausen by proxy. This is the first report of bone marrow suppression involving erythroid series by diazoxide. Follow-up of blood count may be considered in patients on high dosages since anemia may be dose dependent. Munchausen by proxy poses a serious threat to children with significant morbidity and mortality. Awareness and a high index of suspicion in clinical settings with unusual causes are the mainstay for the diagnosis.

Octreotide Injection

MedlinePlus

... to decrease the amount of growth hormone (a natural substance) produced by people with acromegaly (condition in ... by carcinoid tumors (slow-growing tumors that release natural substances that can cause symptoms) and vasoactive intestinal ...

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

PubMed

Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

2011-01-01

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

Comparison of 99mTc-HYNIC-TOC and HYNIC-TATE octreotide scintigraphy with FDG PET and 99mTc-MIBI in local recurrent or distant metastatic thyroid cancers.

PubMed

Sager, Sait; Kabasakal, Levent; Halac, Metin; Maecke, Helmut; Uslu, Lebriz; Önsel, Çetin; Kanmaz, Bedii

2013-05-01

There have been various studies for early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study is to evaluate the clinical utility of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, octreotide derivatives, to detect recurrences or distant metastases in 131I-negative thyroglobulin positive thyroid cancer patients and to compare the lesions with FDG PET and 99mTc-MIBI studies in the same patient group. Twenty differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 ± 15.3 (range 13-78 years), were included in this study. Eighteen patients had papillary thyroid cancer and 2 had follicular thyroid cancer. Fifteen patients received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical. All patients underwent whole-body scan 1 and 4 hours after injection of octreotide derivatives and SPECT imagings were performed from the suspicious sites. The lesions that were seen in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE studies were compared with 99mTc-MIBI and FDG-PET studies. Among 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE scintigraphies, 15 patient studies were evaluated as true positive (75%) and 5 were false negative (25%). The total number of lesions in octreotide scintigraphy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET study, 15 of them were evaluated as true positive (78.9%), and 4 them were evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74. 99mTc-MIBI study was positive in 11 patients (55%) and negative in 9 patients (45%). Total number of lesions in 99mTc-MIBI was 25. Technetium-labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are useful imaging alternatives in somatostatin receptor expressing thyroid cancer patients. Radiolabeling is easy and they are readily available for routine use.

Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine.

PubMed

Kroiss, Alexander; Putzer, Daniel; Uprimny, Christian; Decristoforo, Clemens; Gabriel, Michael; Santner, Wolfram; Kranewitter, Christof; Warwitz, Boris; Waitz, Dietmar; Kendler, Dorota; Virgolini, Irene Johanna

2011-05-01

(68)Ga-DOTA-Tyr(3)-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) has proven to be superior to (111)In-DTPA-D-Phe(1)-octreotide ((111)In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard. Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with (68)Ga-DOTA-TOC PET and (123)I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis. On a per-patient basis, both (68)Ga-DOTA-TOC and (123)I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 91.7% and that of (123)I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 97.2% and that of (123)I-MIBG was 90.7%. Overall, in this patient cohort, (68)Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and (123)I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of (68)Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of (123)I-MIBG was 76.9% (McNemar p<0.0001). Our analysis in this relatively small patient cohort indicates that (68)Ga-DOTA-TOC PET may be superior to (123)I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma.

Ranitidine: forgotten drug of delayed gastric emptying.

PubMed

Veevers, Abbie E; Oxberry, Stephen G

2017-09-01

Delayed gastric emptying in the presence or absence of mechanical bowel obstruction can cause distressing symptoms in palliative care patients. We present two patients, both with vomiting due to delayed gastric emptying and gastric outlet obstruction secondary to pancreatic cancer, treated with subcutaneous ranitidine resulting in a symptomatic response. We hypothesise that ranitidine is a useful adjunct to standard treatment with prokinetic agents or octreotide in such patients and potentially those with proximal mechanical bowel obstruction from other malignancies with associated delayed gastric emptying. 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/.

Development and Evaluation of User-Friendly Single Vial DOTA-Peptide Kit Formulations, Specifically Designed for Radiolabelling with 68Ga from a Tin Dioxide 68Ge/68Ga Generator.

PubMed

Prince, Deidré; Rossouw, Daniel; Davids, Claudia; Rubow, Sietske

2017-12-01

This study was aimed to develop single vial 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptide kits to be used with fractionated eluates from a SnO 2 -based 68 Ge/ 68 Ga generator. Kits were formulated with 35 μg DOTA-Tyr 3 -Thre 8 -octreotide, DOTA-[Tyr 3 ]-octreotide and DOTA-[NaI 3 ]-octreotide (DOTATATE, DOTATOC and DOTANOC) and sodium acetate powder, vacuum-dried and stored at -20 °C for up to 12 months. Labelling of the kits was carried out with 2 ml 68 Ga eluate. Comparative labelling was carried out using aqueous DOTA-peptide stock solutions kept frozen at -20 °C for up to 12 months. The quality of the kits was found to be suitable over a 1-year storage period (pH, sterility, endotoxin content, radiolabelling efficiency and radiochemical yields of 68 Ga-labelled DOTA-peptides). Radiochemical yields ranged from 73 to 83 %, while those obtained from stock solutions from 64 to 79 %. No significant decline in kit labelling yields was observed over a 12-month storage period. The single vial kit formulations met the quality release specifications for human administration and appear to be highly advantageous over using peptide stock solutions in terms of stability and user-friendliness.

Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases

PubMed Central

Patel, Sulabh P.; Vaishya, Ravi; Patel, Ashaben; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K.

2016-01-01

This manuscript is focused on the development of pentablock (PB) copolymer based sustained release formulation for the treatment of posterior segment ocular diseases. We have successfully synthesized biodegradable and biocompatible PB copolymers for the preparation of nanoparticles (NPs) and thermosensitive gel. Achieving high drug loading with hydrophilic biotherapeutics (peptides /proteins) is a challenging task. Moreover, small intravitreal injection volume (≤100 μL) requires high loading to develop a long term (6 months) sustained release formulation. We have successfully investigated various formulation parameters to achieve maximum peptide/protein (octreotide, insulin, lysozyme, IgG-Fab, IgG, and catalase) loading in PB NPs. Improvement in drug loading can facilitate delivery of larger doses of therapeutic proteins via limited injection volume. A composite formulation comprised of NPs in gel system exhibited sustained release (without burst effect) of peptides and proteins, may serve as a platform technology for the treatment of posterior segment ocular diseases. PMID:26964498

[Surgical therapy of segmental jejunal, primary intestinal lymphangiectasia].

PubMed

Kneist, W; Drescher, D G; Hansen, T; Kreitner, K F; Lang, H

2013-06-01

Primary intestinal lymphangiectasia (PIL) is a protein-losing, exsudative gastroenteropathy causing lymphatic obstruction. Diagnosis depends on clinical examination and histological findings. Conservative treatment modalities include a low-fat diet and enteral nutritional therapy in order to reduce enteric protein loss and to improve fat metabolism. Other treatment options consist of administration of antiplasmin or octreotide to lower lymph flow and secretion. We report on a 58-year-old patient who underwent exploratory laparotomy due to a worsening physical status, recurrent chylaskos and leg oedema under conservative dietary therapy. Intraoperative findings showed a typical PIL of the jejunum about 20 cm distal to the Treitz's ligament. Histological examinations confirmed this diagnosis. One year after segmental small bowel resection (105 cm) with end-to-end anastomosis the patient is healthy, free of symptoms, has gained weight and his serum protein level has increased. Intraabdominal ascites and leg oedema have not reoccurred since.

Tumour-induced osteomalacia: An emergent paraneoplastic syndrome.

PubMed

Alonso, Guillermo; Varsavsky, Mariela

2016-04-01

Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

ClinicalTrials.gov

2014-11-21

Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone-secreting adrenal phaeochromocytoma: review of the literature and report of a case

PubMed Central

Ruggeri, R.M.; Ferraù, F.; Campennì, A.; Simone, A.; Barresi, V.; Giuffrè, G.; Tuccari, G.; Baldari, S.; Trimarchi, F.

2009-01-01

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochromocytoma, causing ectopic Cushing’s syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous, 9-cm mass in the right adrenal gland, and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region, corresponding to the adrenal mass. The patient underwent laparoscopic surgery and formalin-fixed and paraffin-embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed. Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma, which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing’s disease was dependent on CRH overproduction by the pheochromocytoma, in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas, and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas, suggesting that these tumours may represent potential target for octreotide treatment.

Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone- secreting adrenal phaeochromocytoma: review of the literature and report of a case.

PubMed

Ruggeri, Rosaria M; Ferraù, F; Campennì, A; Simone, A; Barresi, V; Giuffrè, G; Tuccari, G; Baldari, S; Trimarchi, F

2009-01-01

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochro-mocytoma,causing ectopic Cushing's syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous,9-cm mass in the right adrenal gland,and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region,corresponding to the adrenal mass.The patient underwent laparoscopic surgery and formalin-fixed and paraffin embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed.Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma,which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing's disease was dependent on CRH overproduction by the pheochromocytoma,in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas,and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas,suggesting that these tumours may represent potential target for octreotide treatment.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

PubMed Central

Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

2017-01-01

Objective To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 (67Ga) citrate scintigraphy. Materials and Methods We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. PMID:29307928

Hypoglycaemia begets hypoglycaemia

PubMed Central

Arora, Alok

2013-01-01

Drug-induced (insulin/insulin secretagogue) hypoglycaemia is the most common cause of hypoglycaemia particularly in the elderly. It is estimated that hypoglycaemia of any severity occurs annually in 5–20% of patients taking antihyperglycaemic agents. Although these hypoglycaemic episodes are rarely fatal, they can be associated with serious clinical sequelae. The half-life for most sulfonylurea medications is 14–16 h; they can cause severe, prolonged hypoglycaemia. It is important to recognise, prevent and treat hypoglycaemic episodes secondary to the use of antihyperglycaemic agents. Patient education has become focused on minimising hyperglycaemia but emphasis must be placed on minimising even minor subclinical hypoglycaemia because it will contribute to a vicious cycle of hypoglycaemia begetting hypoglycaemia. Ten per cent dextrose is recommended for the reversal of all hypoglycaemic episodes rather than the conventional 50% dextrose. Octreotide can be an option for recurrent and relapsing hypoglycaemia in an acute setting. PMID:23814226

Pediatric obesity: Causes, symptoms, prevention and treatment.

PubMed

Xu, Shumei; Xue, Ying

2016-01-01

Pediatric or childhood obesity is the most prevalent nutritional disorder among children and adolescents worldwide. Approximately 43 million individuals are obese, 21-24% children and adolescents are overweight, and 16-18% of individuals have abdominal obesity. The prevalence of obesity is highest among specific ethnic groups. Obesity increases the risk of heart diseases in children and adults. Childhood obesity predisposes the individual to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and kidney diseases and causes reproductive dysfunction in adults. Obesity in children is a major health concern of the developed world. The National Health and Nutrition Examination Survey has reported that the prevalence of obesity is on the increase in all the pediatric age groups, in males and females, and in various ethnic and racial groups. Factors, such as eating habits, genetics, environment, metabolism, and lifestyle play an important role in the development of obesity. Over 90% of obesity cases are idiopathic and less than 10% are associated with genetic and hormonal causes. Obesity occurs when the body consumes more calories than it burns, through overeating and underexercising. The symptoms of obesity include breathing disorders, sleep apnea, chronic obstructive pulmonary disease, certain types of cancer such as prostate, bowel, breast and uterine, coronary heart disease, diabetes (type 2 in children), depression, liver and gallbladder problems, gastro-esophageal reflux disease, high blood pressure, high cholesterol, stroke, and joint diseases such as osteoarthritis, pain in knees and lower back. Environmental, behavioral such as consumption of convenience foods, genetic, and family factors contribute to pediatric obesity. Obesity can be countered through lower calorie consumption, weight loss and diet programs, as well as increased physical activity. A number of endogenous molecules including leptin, hypothalamic melanocortin 4 receptor, and mitochondrial uncoupling proteins, are known to affect body weight. These molecules serve as potential targets for the pharmacological manipulation of obesity. Sibutramine and orlistat are primariliy used for the treatment of adult obesity, which produces modest weight loss, of 3-8% compared to placebo. For children and obese adolescents, metformin is used in the case of insulin resistance and hyperinsulinemia. Octreotide is used for hypothalamic obesity. Bariatric surgery is performed for the treatment of severe childhood obesity. The causes, symptoms, prevention and treatment of pediatric obesity are described in the present review.

Octreotide as Palliative Therapy for Cancer-Related Bowel Obstruction That Cannot Be Removed by Surgery

ClinicalTrials.gov

2012-05-31

Colorectal Cancer; Constipation, Impaction, and Bowel Obstruction; Extrahepatic Bile Duct Cancer; Gastric Cancer; Gastrointestinal Stromal Tumor; Nausea and Vomiting; Ovarian Cancer; Pancreatic Cancer; Peritoneal Cavity Cancer; Small Intestine Cancer

Localization and postoperative follow-up of a bronchial carcinoid tumor causing Cushing's syndrome by 111In-DTPA labelled octreotide scintigraphy.

PubMed

Fernandez-Fernandez, F; Halperin, I; Manzanares, J M; Flores, L; Lomeña, F; Vilardell, E

1997-06-01

Bronchial carcinoid tumor is the most frequent occult source of ectopic ACTH-dependent Cushing's syndrome, but its initial localization may be very difficult, as well as its postoperative follow-up. We here present the case of a 21-year-old man with Cushing's syndrome and biochemical findings suggesting an ectopic source of ACTH (lack of inhibition of cortisol after overnight 8-mg dexamethasone suppression test, and lack of response to h-CRH challenge). Chest CT-scan showed a node adjacent to the left lung hilium whose nature was confirmed by uptake of 111Indium-DTPA labelled octreotide scintigraphy. Surgical resection of the tumor consisted in an upper lobectomy of the left lung. Microscopic examination identified a typical carcinoid tumor. After surgery pituitary-adrenal function normalized and a second scintigraphy offered additional data on the absence of tumor remnants.

A freeze-dried kit formulation for the preparation of Lys(27)(99mTc-EDDA/HYNIC)-Exendin(9-39)/99mTc-EDDA/HYNIC-Tyr3-Octreotide to detect benign and malignant insulinomas.

PubMed

Medina-García, Veronica; Ocampo-García, Blanca E; Ferro-Flores, Guillermina; Santos-Cuevas, Clara L; Aranda-Lara, Liliana; García-Becerra, Rocio; Ordaz-Rosado, David; Melendez-Alafort, Laura

2015-12-01

About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys(27)((99m)Tc-EDDA/HYNIC)-Exendin(9-39)/(99m)Tc-EDDA/HYNIC-Tyr(3)Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97±1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

Ectopic Cushing's syndrome and pulmonary carcinoid tumour identified by [111In-DTPA-D-Phe1]octreotide.

PubMed Central

Matte, J.; Roufosse, F.; Rocmans, P.; Schoutens, A.; Jacobovitz, D.; Mockel, J.

1998-01-01

The differential diagnosis and management of Cushing's syndrome remain difficult, particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from small bronchial carcinoids. We report the case of a 41-year-old man with ectopic ACTH-dependent Cushing's syndrome. Two computed tomography scans of the thorax were normal and magnetic resonance imaging of the chest showed a 6-mm hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide scintigraphy scan demonstrated a positive image for somatostatin receptors in exactly the same location and surgery confirmed the presence of a small ACTH-secreting carcinoid tumour in the upper left lung lobe which was resected. Surgery cured the hypercorticism of the patient. The differential diagnosis of Cushing's syndrome and the procedure for localisation of an ACTH source are discussed. Images Figure PMID:9616493

Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer.

PubMed

Brom, Maarten; Joosten, Lieke; Oyen, Wim Jg; Gotthardt, Martin; Boerman, Otto C

2012-01-27

In single photon emission computed tomography [SPECT], high specific activity of 111In-labelled tracers will allow administration of low amounts of tracer to prevent receptor saturation and/or side effects. To increase the specific activity, we studied the effect of the buffer used during the labelling procedure: NaAc, NH4Ac, HEPES and MES buffer. The effect of the ageing of the 111InCl3 stock and cadmium contamination, the decay product of 111In, was also examined in these buffers. Escalating amounts of 111InCl3 were added to 1 μg of the diethylene triamine pentaacetic acid [DTPA]- and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA]-conjugated compounds (exendin-3, octreotide and anti-carbonic anhydrase IX [CAIX] antibody). Five volumes of 2-(N-morpholino)ethanesulfonic acid [MES], 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [HEPES], NH4Ac or NaAc (0.1 M, pH 5.5) were added. After 20 min at 20°C (DTPA-conjugated compounds), at 95°C (DOTA-exendin-3 and DOTA-octreotide) or at 45°C (DOTA-anti-CAIX antibody), the labelling efficiency was determined by instant thin layer chromatography. The effect of the ageing of the 111InCl3 stock on the labelling efficiency of DTPA-exendin-3 as well as the effect of increasing concentrations of Cd2+ (the decay product of 111In) were also examined. Specific activities obtained for DTPA-octreotide and DOTA-anti-CAIX antibody were five times higher in MES and HEPES buffer. Radiolabelling of DTPA-exendin-3, DOTA-exendin-3 and DTPA-anti-CAIX antibody in MES and HEPES buffer resulted in twofold higher specific activities than that in NaAc and NH4Ac. Labelling of DTPA-exendin-3 decreased with 66% and 73% for NaAc and NH4Ac, respectively, at day 11 after the production date of 111InCl3, while for MES and HEPES, the maximal decrease in the specific activity was 10% and 4% at day 11, respectively. The presence of 1 pM Cd2+ in the labelling mixture of DTPA-exendin-3 in NaAc and NH4Ac markedly reduced the labelling efficiency, whereas Cd2+ concentrations up to 0.1 nM did not affect the labelling efficiency in MES and HEPES buffer. We showed improved labelling of DTPA- and DOTA-conjugated compounds with 111In in HEPES and MES buffer. The enhanced labelling efficiency appears to be due to the reduced competitive chelation of cadmium. The enhanced labelling efficiency will allow more sensitive imaging of the biomarkers with SPECT.

Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy.

PubMed

Nguyen, Sheila; Hojjati, Mehrnaz

2011-01-01

Hypertrophic osteoarthropathy (HOA) is a disabling condition that may occur secondarily to primary lung cancer. It is characterized by digital clubbing, arthralgia/arthritis, and periostosis of the tubular bones. The pain associated with HOA can be disabling and often refractory to conventional analgesics. We performed a comprehensive review of the literature using the PubMed database on treatment modalities available for HOA. We found 52 relevant articles-40 case reports, six case series, two review papers, and four combined case series and review papers. There were no randomized controlled trials reported. We then classified treatments used for HOA into two categories: (1) treatment of primary cause (i.e., resection of tumor, chemotherapy, radiotherapy, treatment of infection, etc.) and (2) symptomatic treatments (i.e., bisphosphonates, octreotide, NSAIDs, vagotomy, etc.). Subsequently, we summarized the main findings for each treatment. Although the clinical diagnosis of HOA has existed for over 100 years, the pathogenesis mechanism has not yet been elucidated, and treatment options for this condition remain experimental. Primary treatment is the most widely reported modality to be efficacious. In cases which primary therapy is not possible, several symptomatic treatment modalities are suggested, with various degree of success. Further research is needed to clarify the pathophysiological mechanism of HOA as to appropriately direct therapy.

Lanreotide in the treatment of patients with thyroid eye disease.

PubMed

Krassas, G E; Kaltsas, T; Dumas, A; Pontikides, N; Tolis, G

1997-04-01

Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Five patients, three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using 111 In DTPA-D-Phe1-octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The five patients who comprised the treatment group received 0.04 g LRT i.m. once every 2 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for 3 months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to be given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results.

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.

PubMed

Strosberg, Jonathan; El-Haddad, Ghassan; Wolin, Edward; Hendifar, Andrew; Yao, James; Chasen, Beth; Mittra, Erik; Kunz, Pamela L; Kulke, Matthew H; Jacene, Heather; Bushnell, David; O'Dorisio, Thomas M; Baum, Richard P; Kulkarni, Harshad R; Caplin, Martyn; Lebtahi, Rachida; Hobday, Timothy; Delpassand, Ebrahim; Van Cutsem, Eric; Benson, Al; Srirajaskanthan, Rajaventhan; Pavel, Marianne; Mora, Jaime; Berlin, Jordan; Grande, Enrique; Reed, Nicholas; Seregni, Ettore; Öberg, Kjell; Lopera Sierra, Maribel; Santoro, Paola; Thevenet, Thomas; Erion, Jack L; Ruszniewski, Philippe; Kwekkeboom, Dik; Krenning, Eric

2017-01-12

Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ( 177 Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177 Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) ( 177 Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177 Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177 Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177 Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177 Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Treatment with 177 Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177 Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

PubMed

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

[External pancreatic fistulas management].

PubMed

Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

Clinical indications to the use of (99m)Tc-EDDA/HYNIC-TOC to detect somatostatin receptor-positive neuroendocrine tumors.

PubMed

Parisella, M G; Chianelli, M; D'Alessandria, C; Todino, V; Mikolajczak, R; Papini, E; Dierckx, R A; Scopinaro, F; Signore, A

2012-02-01

The aim of this study was to define, retrospectively, the utility to perform (99m)Tc-EDDA/HYNIC-Tyr3-octreotide ((99m)Tc-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which (99m)Tc-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of (99m)Tc-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 (99m)Tc-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, (99m)Tc-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

Prescription patterns of long-acting somatostatin analogues

PubMed Central

Machado-Alba, Jorge Enrique; Machado-Duque, Manuel Enrique

2017-01-01

Background: Acromegaly and endocrine tumors are uncommon morbidities that are currently treated with different drugs. Objective: To determine the prescription patterns of somatostatin analogues in patients affiliated with the Health System of Colombia. Methods: Retrospective cohort study of patients of any age and sex treated with octreotide or lanreotide between January 2011 and August 2015. Socio-demographic, clinical (indications) and pharmacological (comedications) variables were considered. Multivariate analysis was performed with SPSS 23.0. Results: We identified 289 patients, with a mean age of 56.6 ± 14.0 years and female predominance (59.5%), who underwent treatment during the 56 months of monitoring. Octreotide was used in 56.1% of cases, followed by lanreotide (43.9%), both at approved doses. We found that 4.5% of subjects changed from one drug to another over the course of therapy, which was associated with being diabetic and receiving insulin (odds ratio: 4.27; 95% confidence interval: 1.23–14.84; p = 0.014). The most common indications were acromegaly (52.2% of cases) followed by neuroendocrine tumors (15.9%). The most common comorbidities were hypertension (39.4% of cases), depression (27.3%), dyslipidemia (23.3%), diabetes mellitus (23.5%) and hypothyroidism (23.5%). Being male (odds ratio: 0.57; 95% confidence interval: 0.35–0.94; p = 0.029) and belonging to the age group between 45 and 65 years (odds ratio: 0.44; 95% confidence interval: 0.21–0.90; p = 0.024) were significantly associated with a lower risk of receiving comedications. Conclusion: Somatostatin analogues are being used at recommended doses, especially in patients with acromegaly and neuroendocrine tumors. Variables associated with change in therapy were identified. PMID:28540043

Prescription patterns of long-acting somatostatin analogues.

PubMed

Machado-Alba, Jorge Enrique; Machado-Duque, Manuel Enrique

2017-01-01

Acromegaly and endocrine tumors are uncommon morbidities that are currently treated with different drugs. To determine the prescription patterns of somatostatin analogues in patients affiliated with the Health System of Colombia. Retrospective cohort study of patients of any age and sex treated with octreotide or lanreotide between January 2011 and August 2015. Socio-demographic, clinical (indications) and pharmacological (comedications) variables were considered. Multivariate analysis was performed with SPSS 23.0. We identified 289 patients, with a mean age of 56.6 ± 14.0 years and female predominance (59.5%), who underwent treatment during the 56 months of monitoring. Octreotide was used in 56.1% of cases, followed by lanreotide (43.9%), both at approved doses. We found that 4.5% of subjects changed from one drug to another over the course of therapy, which was associated with being diabetic and receiving insulin (odds ratio: 4.27; 95% confidence interval: 1.23-14.84; p = 0.014). The most common indications were acromegaly (52.2% of cases) followed by neuroendocrine tumors (15.9%). The most common comorbidities were hypertension (39.4% of cases), depression (27.3%), dyslipidemia (23.3%), diabetes mellitus (23.5%) and hypothyroidism (23.5%). Being male (odds ratio: 0.57; 95% confidence interval: 0.35-0.94; p = 0.029) and belonging to the age group between 45 and 65 years (odds ratio: 0.44; 95% confidence interval: 0.21-0.90; p = 0.024) were significantly associated with a lower risk of receiving comedications. Somatostatin analogues are being used at recommended doses, especially in patients with acromegaly and neuroendocrine tumors. Variables associated with change in therapy were identified.

Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyr-octreotide: the experience of the European Institute of Oncology Group.

PubMed

Chinol, Marco; Bodei, Lisa; Cremonesi, Marta; Paganelli, Giovanni

2002-04-01

High concentrations of subtype 2 somatostatin tumor receptors (sst(2)) are expressed in numerous tumors, enabling primary and metastatic masses to be localized by scintigraphy after injecting (111)In-labeled somatostatin analogue octreotide. In addition to neuroendocrine tumors, somatostatin receptors have been identified on cancers of the central nervous system, breast, lung, and lymphatic tissue, and the use of radionuclide-labeled somatostatin analogues appeared promising for therapy as well as for diagnosis of such malignancies. The somatostatin analogue [DOTA-(D)Phe(1)-Tyr(3)] octreotide (DOTATOC) possesses favorable characteristics for its potential therapeutic use in that it shows high affinity for sst(2), moderately high affinity for sst(5), and intermediate affinity for sst(3), high hydrophilicity, stable and facile labeling with (111)In and (90)Y. We began to investigate the potential therapeutic applications of (90)Y DOTATOC in 1997 by performing a thorough dosimetric study in 18 patients who were administered (111)In DOTATOC to estimate the absorbed doses during(90)Y-DOTATOC therapy. Then, we moved on and treated an overall number of 256 patients, mostly recruited in 2 distinct protocols with and without the administration of kidney protecting agents, with (90)Y DOTATOC. No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The MTD per cycle was defined as 5.18 GBq. Objective therapeutic responses were documented in more than 20% of patients in terms of partial and complete responses. The present article reports in details our clinical experience (still ongoing) and outcomes with the use of (90)Y DOTATOC. Copyright 2002, Elsevier Science (USA). All rights reserved.

Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

PubMed

Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

2008-07-01

The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin.

PubMed

Vegt, Erik; Wetzels, Jack F M; Russel, Frans G M; Masereeuw, Rosalinde; Boerman, Otto C; van Eerd, Juliette E; Corstens, Frans H M; Oyen, Wim J G

2006-03-01

Peptide receptor-mediated radiotherapy of neuroendocrine and other somatostatin receptor-positive tumors with radiolabeled somatostatin analogs has been applied in several experimental settings. The kidneys are the organs responsible for dose-limiting toxicity attributable to the retention of radiolabeled octreotide in the renal cortex, leading to a relatively high radiation dose that may result in irreversible loss of kidney function. The administration of basic amino acids reduces renal uptake but does have significant side effects. We observed that gelatin-based plasma expanders induced tubular low-molecular-weight proteinuria in healthy volunteers, suggesting that components in these solutions can interfere with the tubular reabsorption of proteins and peptides. Here, we studied the effects of infusion of low doses of the plasma expander succinylated gelatin (GELO) on the renal uptake of 111In-labeled octreotide (111In-OCT). Five healthy volunteers were given 111In-OCT, first in combination with normal saline and 2 wk later in combination with GELO. Scintigraphic images of the kidneys as well as blood and urine samples were analyzed. To exclude a nonspecific hemodynamic effect of the plasma expander, the procedure was repeated with 5 other volunteers who received the carbohydrate-based plasma expander hydroxyethyl starch (HES). Low doses of GELO were able to effectively reduce the kidney retention of 111In-OCT. The renal radiation dose was significantly reduced by 45% +/- 10% (mean +/- SD) (P = 0.006), whereas HES showed no significant effect (0% +/- 12%). The infusion of GELO did not cause any side effects. GELO effectively reduces the renal uptake of 111In-OCT. In contrast to currently used mixtures of amino acids, GELO does not cause any side effects.

Congenital hyperinsulinism: current trends in diagnosis and therapy

PubMed Central

2011-01-01

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable. PMID:21967988

McCune Albright syndrome in association with excessive GH secretion: case report.

PubMed

Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

2015-06-01

McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease.

PubMed

Santoro, Domenico; Pellicanò, Vincenzo; Visconti, Luca; Trifirò, Gianluca; Buemi, Michele; Cernaro, Valeria

2015-01-01

At present, treatment of autosomal dominant polycystic kidney disease (ADPKD) is essentially supportive as there is still no specific therapy. However, recent advances with ADPKD pathophysiology have stimulated research for new therapeutic strategies. The aim of this systematic review is to analyze the experimental and early investigational therapies currently under evaluation in this field. Data from completed clinical trials were retrieved from the currently available scientific literature and from the ClinicalTrials.gov website. Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

Carcinoid Tumor: Frequently Asked Questions

MedlinePlus

... There are more, but these are the initial ones that come to mind plus the 2009 published study. Feel free to print this article and show it to any physician who doubts the efficacy of octreotide (in this case Sandostatin): The reference published in 2009: New Study ...

Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients.

PubMed

Zuo, Qing-Yao; Wang, Hong; Li, Wei; Niu, Xiao-Hui; Huang, Yan-Hong; Chen, Jia; You, Yu-Hua; Liu, Bao-Yue; Cui, Ai-Min; Deng, Wei

2017-09-21

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. Nonspecific symptoms make the diagnosis elusive. In addition, locating the responsible tumor(s) is challenging. The aim of this study was to investigate the clinical management and outcomes of TIO. The clinical features, diagnostic procedures, treatment, and outcomes of 12 patients were reviewed retrospectively. The cohort comprised six men and six women (mean age 45.5 ± 9.9 years, range 23-61 years). The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12 mmol/L). Technetium-99m octreotide scintigraphy was performed in 11 patients and showed lesions in the right distal femur, left femoral head, and right tibial plateau, respectively, in three patients. Magnetic resonance imaging (MRI) was negative for lesions in one patient. Two patients underwent biopsies that showed negative histopathology. Two patients, at 2 years and 8 months, respectively, after having negative technetium-99m octreotide studies, underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (CT), which revealed lesions in the sacrum and soft tissue of the left palm, respectively. One tumor was detected by CT and MRI. Overall, lesion sites were the head (two patients, 16.7%), thoracic and lumbar region (two, 16.7%), pelvis (three, 25%), lower limbs (four, 33.3%), and upper limbs (one, 8.3%). All patients underwent surgery, and histopathology showed phosphaturic mesenchymal tumors in each. Postoperatively, serum phosphorus concentrations normalized within 2-7 days in 11 patients. With follow-ups of 1-41 months, surgery was effective in 10 patients. One patient developed local recurrence and another had metastases. Locating tumors responsible for tumor-induced osteomalacia is often challenging. Although complete tumor resection confers a good prognosis in most patients, surveillance for recurrence and metastasis is necessary. Before surgery or when surgery is not indicated, oral phosphate can alleviate symptoms and metabolic imbalance.

Primary intestinal lymphangiectasia (Waldmann's disease).

PubMed

Vignes, Stéphane; Bellanger, Jérôme

2008-02-22

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool alpha1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur.

Primary intestinal lymphangiectasia (Waldmann's disease)

PubMed Central

Vignes, Stéphane; Bellanger, Jérôme

2008-01-01

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur. PMID:18294365

The role of the neuropeptide somatostatin on methamphetamine and glutamate-induced neurotoxicity in the striatum of mice.

PubMed

Afanador, Lauriaselle; Mexhitaj, Ina; Diaz, Carolyn; Ordonez, Dalila; Baker, Lisa; Angulo, Jesus A

2013-05-13

A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

The Role of the Neuropeptide Somatostatin on Methamphetamine and Glutamate-Induced Neurotoxicity in the Striatum of Mice

PubMed Central

Afanador, Lauriaselle; Mexhitaj, Ina; Diaz, Carolyn; Ordonez, Dalila; Baker, Lisa; Angulo, Jesus A.

2014-01-01

A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30 mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms. PMID:23524190

[Surgical tactics in duodenal trauma].

PubMed

Ivanov, P A; Grishin, A V

2004-01-01

Results of surgical treatment of 61 patients with injuries of the duodenum are analyzed. The causes of injuries were stab-incised wounds in 24 patients, missile wound -- in 7, closed abdominal trauma -- in 26, trauma of the duodenum during endoscopic papillosphincterotomy -- in 4. All the patients underwent surgery. Complications were seen in 32 (52.5%) patients, 21 patients died, lethality was 34.4%. Within the first 24 hours since the trauma 7 patients died due to severe combined trauma, blood loss, 54 patients survived acute period of trauma, including 28 patients after open trauma, 26 -- after closed and 4 -- after trauma of the duodenum during endoscopic papillosphincterotomy. Diagnostic and surgical policies are discussed. Results of treatment depending on kind and time of surgery are regarded. It is demonstrated that purulent complications due to retroperitoneal phlegmona, traumatic pancreatitis, pneumonia are the causes of significant number of unfavorable outcomes. Therefore, it is important to adequately incise and drainage infected parts of retroperitoneal fat tissue with two-lumen drainages. Decompression through duodenal tube is the effective procedure for prophylaxis of suture insufficiency and traumatic pancreatitis. Suppression of pancreatic and duodenal secretion with octreotid improves significantly surgical treatment results.

Enterocutaneous fistula: a review of 82 cases.

PubMed

Njeze, G E; Achebe, U J

2013-01-01

Enterocutaneous fistula is an unpleasant and troublesome complication of abdominal operations. The objective was to review the outcome of treatment of patients treated for enterocutaneous fistula. This is a retrospective study of 82 teenage and adult patients, who suffered from enterocutaneous fistula, seen over an 11 year period, in the University of Nigeria Teaching Hospital, Enugu. Patients' charts were reviewed for biodata, etiology of the fistula, volume of the fistula output, and result of treatment. Majority of the fistulas occurred after abdominal operations; many by general practitioners. After treatment for correction of fluid and electrolyte deficits, they were all tried on conservative therapy with enteral nutritional support as the main stay of management. Those, whose fistulas did not close, underwent surgical treatment. Total parenteral nutrition, octreotide, fibrin glue, and wound vacuum assisted closure (VAC) were not used for treating these patients. Spontaneous healing of fistulas occurred in 26 patients (31.7%), whereas 42 patients out of 50 (84%) healed after definitive operation. Fourteen patients (17%) in this study, died. Proper management of fluid and electrolyte imbalances, enteral nutritional support, control of sepsis and correctly timed surgical therapy, resulted in this good healing rate and acceptable mortality, without the use of parenteral nutrition, biologic fibrin glue injection or VAC. Suggestions are offered about steps that may help in eradicating some of these enterocutaneous fistulas.

[Portal hypertension. Evidence-based guide].

PubMed

Mercado, Miguel Angel; Orozco Zepeda, Héctor; Plata-Muñoz, Juan José

2004-01-01

Treatment of portal hypertension has evolved widely during the last decades. Advances in physiopathology have allowed better application of therapeutic options and also have permitted to know the natural history of varices and variceal bleeding, predicting which patients have a higher risk of bleeding. It also permits probability of designing patient treatment. According to liver function and subadjacent liver disease, it is possible to offer different alternatives within the three possible scenarios (primary prophylaxis, acute bleeding episode, and secondary prophylaxis). For primary prophylaxis, pharmacotherapy offers the best choice. Endoscopic banding is also growing in these scenarios and probably will be accepted in the near future. For the acute bleeding episode, endoscopic therapy (sclerosis and/or bands) and/or pharmacologic therapy (octreotide, terlipresin) represent best choice, considering TIPS as a rescue option. Surgery is not used routinely in this scenario in most centers. For secondary prophylaxis, pharmaco- and endoscopic therapy are first-line treatments, while TIPS and surgery as second-line treatments. TIPS is mainly used in patients on a waiting list for liver transplantation. Surgery offers good results for low-risk patients, with good liver function and with portal blood-flow preserving procedures (selective shunts, extensive devascularizations). Liver transplantation is recommended for patients with poor liver function because together with portal hypertension, it treats subadjacent liver disease.

Variceal bleeding and portal hypertension: new lights on old horizon.

PubMed

Bhasin, D K; Siyad, I

2004-02-01

New clinical, endoscopic, and imaging modalities for diagnosing varices and predicting bleeding are being investigated. Transnasal endoscopy and ultrathin battery-powered esophagoscopes are being used to improve patient comfort and compliance. Patients who respond to portal pressure-reducing drugs not only have a reduced risk of bleeding, but also a reduced risk of developing other complications, with improved survival. Nitrates have been shown to have no definite role in primary prophylaxis against variceal bleeding. The hemodynamic response to treatment has an independent prognostic value for the risk of variceal bleeding. Newer drugs have been investigated for reducing the hepatic venous pressure gradient, but with little success. Survival after bleeding has increased due to improved patient care and technological advances. Combined radiographic and endoscopic management of gastric varices is evolving and appears to be promising. Nonvariceal bleeding from portal hypertensive gastropathy is increasingly being recognized as a potential cause of bleeding in patients with portal hypertension, and pharmacotherapy with octreotide appears to be promising for the treatment of this condition. Variceal band ligation in children has been found to be as safe and effective as in adults.

Treatment of nausea and vomiting in terminally ill cancer patients.

PubMed

Glare, Paul A; Dunwoodie, David; Clark, Katherine; Ward, Alicia; Yates, Patsy; Ryan, Sharon; Hardy, Janet R

2008-01-01

Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

PubMed Central

Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

2018-01-01

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients.

PubMed

Putzer, D; Gabriel, M; Kendler, D; Henninger, B; Knoflach, M; Kroiss, A; Vonguggenberg, E; Warwitz, B; Virgolini, I J

2010-02-01

(68)Ga-DOTA-Tyr3-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) and (18)F-fluoro-L-dihydroxyphenylalanine PET ((18)F-DOPA PET) are emerging modalities for imaging of neuroendocrine tumors. This study reports our initial experiences with these two PET modalities on initial diagnosis, staging and restaging in NET patients. Fifteen patients with NET underwent both (68)Ga-DOTA-TOC and (18)F-DOPA PET as well as computed tomography (CT). Image findings were compared on a patient-basis (pathological uptake: yes/no) as well as on a lesion-basis. Contrast-enhanced CT and histological follow-up served as gold standard. Furthermore, imaging results were matched with tumor marker levels and quantitative tracer uptake by the tumor lesions. When comparing (68)Ga-DOTA-TOC and (18)F-DOPA PET, each modality showed a sensitivity of 64% and a specificity of 100% on a patient-based analysis. (68)Ga-DOTA-TOC PET and (18)F-DOPA PET showed equal findings in 7 out of 15 patients and disagreement in 8 patients. (68)Ga-DOTA-TOC revealed more metastases than (18)F-DOPA PET in 6 patients, while (18)F-DOPA PET detected more metastases than (68)Ga-DOTA-TOC in 4 patients. By (68)Ga-DOTA-TOC PET, 208 malignant lesions were detected, while by (18)F-DOPA only 86 lesions were found, and in CT 124, respectively. (68)Ga-DOTA-TOC and (18)F-DOPA PET are useful tools in the detection and staging of NET lesions. Our initial results allow the conclusion that (68)Ga-DOTA-TOC PET may have a stronger clinical impact in NET patients, as it does not only offer diagnostic information, but is decisive for the further treatment management, i. e. PRRT, as well.

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

PubMed

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Carcinoid syndrome.

PubMed

Zambrzycki, J K; Elliott, C G

1993-12-01

Carcinoid tumors stimulate the release of specific hormones that lead to flushing, diarrhea, and bronchospasm. Serotonin is the most significant of these substances. Recently, a somatostatin analogue as well as the longer acting octreotide have been used to inhibit tumor secretions and reduce their untoward actions. This is a case report in which somatostatin was used perioperatively for removal of carcinoid tumors with an uneventful course.

Reflections on the theory of "silver bullet" octreotide tracers: implications for ligand-receptor interactions in the age of peptides, heterodimers, receptor mosaics, truncated receptors, and multifractal analysis

PubMed Central

2011-01-01

The classical attitude of Nuclear Medicine practitioners on matters of peptide-receptor interactions has maintained an intrinsic monogamic character since many years. New advances in the field of biochemistry and even in clinical Nuclear Medicine have challenged this type of thinking, which prompted me to work on this review. The central issue of this paper will be the use of somatostatin analogs, i.e., octreotide, in clinical imaging procedures as well as in relation to neuroendocirne tumors. Newly described characteristics of G-protein coupled receptors such as the formation of receptor mosaics will be discussed. A small section will enumerate the regulatory processes found in the cell membrane. Possible new interpretations, other than tumor detection, based on imaging procedures with somatostatin analogs will be presented. The readers will be taken to situations such as inflammation, nociception, mechanosensing, chemosensing, fibrosis, taste, and vascularity where somatostatin is involved. Thyroid-associated orbitopathy will be used as a model for the development of multi-agent therapeutics. The final graphical summary depicts the multifactorial properties of ligand binding. PMID:22214590

Quantitative determination and validation of octreotide acetate using 1 H-NMR spectroscopy with internal standard method.

PubMed

Yu, Chen; Zhang, Qian; Xu, Peng-Yao; Bai, Yin; Shen, Wen-Bin; Di, Bin; Su, Meng-Xiang

2018-01-01

Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards. Copyright © 2017 John Wiley & Sons, Ltd.

BRD4 inhibitor IBET upregulates p27kip/cip protein stability in neuroendocrine tumor cells.

PubMed

Wang, Lei; Matkar, Smita; Xie, Gengchen; An, Chiying; He, Xin; Kong, Xiangchen; Liu, Xiuheng; Hua, Xianxin

2017-04-03

The prevalence of neuroendocrine tumors (NETs) has recently been increasing. Although various drugs such as Octreotide and its analogs show certain efficacy, NETs in many patients progress and metastasize. It is desirable to develop new interventions to improve the therapy. Here we show that human neuroendocrine tumor BON cells are resistant to several drugs commonly used for NET therapy, including Octreotide that activates somatostatin receptor-induced anti-proliferation, and Capecitabine and Temozolimide that damage DNA. In contrast, an inhibitor (IBET) to an epigenetic regulator, Brd4 that binds acetylated histones and upregulates transcription of multiple genes including protooncogene c-Myc, potently inhibited the NET cells. We found that IBET increased the protein levels of cyclin-dependent kinase (CDK) inhibitor p27 kip/cip (or p27), but not its mRNA levels. Moreover, the p27 induction at protein level by IBET was at least partly through increasing the protein stability of p27. The increased protein stability of p27 likely resulted from IBET-mediated suppression of Skp2, an E3 ligase that can mediate p27 degradation by increasing its ubiquitinylation. These findings unravel a new mechanism whereby the IBET-induced repression of proliferation of neuroendocrine cells.

Biokinetics and dosimetry of several radiolabelled peptides in cancer cells

NASA Astrophysics Data System (ADS)

Rodríguez-Cortés, J.; Ferro-Flores, G.; de Murphy, C. Arteaga; Pedraza-López, M.; Ramírez-Iglesias, M. A. T.

Radiolabelled peptides have been used as target-specific radiopharmaceuticals. The goal of this research was the in vitro assessment of the uptake, internalization, externalization, and efflux of five radiolabelled peptides in cancer cells to estimate radiation-absorbed doses from experimental biokinetic data. 177Lu-DOTA-octreotate, 188Re-lanreotide, and 99mTc-HYNIC-octreotide were studied in the AR42J cell line. The PC3 and NCIH69 cells were used for 99mTc-HYNIC-bombesin and 177Lu-DOTA-minigastrin, respectively. The cumulated activities in the membrane and cytoplasm were calculated by integration of the experimental time-activity curves and used for dosimetry calculations according to the Medical Internal Radiation Dose (MIRD) cellular methodology. The mean absorbed dose to the cell nucleus were 0.69±0.09, 0.11±0.08, 0.55±0.09, 3.45±0.48, and 3.30±0.65 Gy/Bq for 99mTc-HYNIC-bombesin, 99mTc-HYNIC-octreotide, 177Lu-DOTA-minigastrin, 177Lu-DOTA-octreotate, and 188Re-lanreotide, respectively. If radiopharmaceutical cell kinetics were not used and only uptake data were considered, the calculated doses would be overestimated up to 25 times.

Stability of peptide drugs in the colon.

PubMed

Wang, Jie; Yadav, Vipul; Smart, Alice L; Tajiri, Shinichiro; Basit, Abdul W

2015-10-12

This study was the first to investigate the colonic stability of 17 peptide molecules (insulin, calcitonin, glucagon, secretin, somatostatin, desmopressin, oxytocin, Arg-vasopressin, octreotide, ciclosporin, leuprolide, nafarelin, buserelin, histrelin, [D-Ser(4)]-gonadorelin, deslorelin, and goserelin) in a model of the large intestine using mixed human faecal bacteria. Of these, the larger peptides - insulin, calcitonin, somatostatin, glucagon and secretin - were metabolized rapidly, with complete degradation observed within 5 min. In contrast, a number of the smaller peptides - Arg-vasopressin, desmopressin, oxytocin, gonadorelin, goserelin, buserelin, leuprolide, nafarelin and deslorelin - degraded more slowly, while octreotide, histrelin and ciclosporin were seen to be more stable as compared to the other small peptides under the same conditions. Peptide degradation rate was directly correlated to peptide lipophilicity (logP); those peptides with a higher logP were more stable in the colonic model (R(2)=0.94). In the absence of human faecal bacteria, all peptides were stable. This study highlights the impact of the colonic environment - in particular, the gut microbiota - on the metabolism of peptide drugs, and identifies potential peptide candidates for drug delivery to the colon. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel facile method of labeling octreotide with (18)F-fluorine.

PubMed

Laverman, Peter; McBride, William J; Sharkey, Robert M; Eek, Annemarie; Joosten, Lieke; Oyen, Wim J G; Goldenberg, David M; Boerman, Otto C

2010-03-01

Several methods have been developed to label peptides with (18)F. However, in general these are laborious and require a multistep synthesis. We present a facile method based on the chelation of (18)F-aluminum fluoride (Al(18)F) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The method is characterized by the labeling of NOTA-octreotide (NOTA-d-Phe-cyclo[Cys-Phe-d-Trp-Lys-Thr-Cys]-Throl (MH(+) 1305) [IMP466]) with (18)F. Octreotide was conjugated with the NOTA chelate and labeled with (18)F in a 2-step, 1-pot method. The labeling procedure was optimized with regard to the labeling buffer, peptide, and aluminum concentration. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in AR42J tumor-bearing mice and compared with that of (68)Ga-labeled IMP466. In addition, small-animal PET/CT images were acquired. IMP466 was labeled with Al(18)F in a single step with 50% yield. The labeled product was purified by high-performance liquid chromatography to remove unbound Al(18)F and unlabeled peptide. The radiolabeling, including purification, was performed in 45 min. The specific activity was 45,000 GBq/mmol, and the peptide was stable in serum for 4 h at 37 degrees C. Labeling was performed at pH 4.1 in sodium citrate, sodium acetate, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, and 2-(N-morpholino)ethanesulfonic acid buffer and was optimal in sodium acetate buffer. The apparent 50% inhibitory concentration of the (19)F-labeled IMP466 determined on AR42J cells was 3.6 nM. Biodistribution studies at 2 h after injection showed a high tumor uptake of (18)F-IMP466 (28.3 +/- 5.2 percentage injected dose per gram [%ID/g]; tumor-to-blood ratio, 300 +/- 90), which could be blocked by an excess of unlabeled peptide (8.6 +/- 0.7 %ID/g), indicating that the accumulation in the tumor was receptor-mediated. Biodistribution of (68)Ga-IMP466 was similar to that of (18)F-IMP466. (18)F-IMP466 was stable in vivo, because bone uptake was only 0.4 +/- 0.2 %ID/g, whereas free Al(18)F accumulated rapidly in the bone (36.9 +/- 5.0 %ID/g at 2 h after injection). Small-animal PET/CT scans showed excellent tumor delineation and high preferential accumulation in the tumor. NOTA-octreotide could be labeled rapidly and efficiently with (18)F using a 2-step, 1-pot method. The compound was stable in vivo and showed rapid accretion in somatostatin receptor subtype 2-expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds with (18)F.

Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

PubMed

Satpati, Drishty; Shinto, Ajit; Kamaleshwaran, K K; Sarma, Haladhar Dev; Dash, Ashutosh

2017-12-01

Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([ 68 Ga]DOTAGA, Tyr 3 , Thr 8 ) octreotide ([ 68 Ga]DOTAGA-TATE) and ([ 68 Ga]DOTAGA, Tyr 3 ) octreotide ([ 68 Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [ 68 Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1 h post-injection (p.i.). [ 68 Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170 MBq, 1 h p.i.) with histologically confirmed well-differentiated NETs. [ 68 Ga]DOTAGA-TATE exhibited hydrophilicity similar to [ 68 Ga]DOTA-TATE (log P = -3.51 vs -3.69) whereas [ 68 Ga]DOTAGA-TOC was more hydrophilic than [ 68 Ga]DOTA-TOC (log P = -3.27 vs -2.93). [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p < 0.05) of [ 68 Ga]DOTAGA-TATE was observed from other non-specific organs (liver, lungs, spleen, intestine). [ 68 Ga]DOTAGA-TOC also demonstrated rapid clearance from blood and kidneys (p < 0.05) in comparison to [ 68 Ga]DOTA-TOC. The metastatic lesions in NET patients were well identified by [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTAGA-TOC. The phenomenal analogy was observed between [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE as well as between [ 68 Ga]DOTAGA-TOC and [ 68 Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.

Interventions for the treatment of craniopharyngioma-related hypothalamic obesity: a systematic review.

PubMed

Ni, Weimin; Shi, Xiang'en

2018-06-23

Craniopharyngiomas (CPs) and their treatment are associated with hypothalamic damage that causes hypothalamic obesity (HO) in 30-70% of cases. Thus, there is ongoing research regarding tangible solutions for HO, as these patients have unrelenting resistance to basic weight-loss interventions. This review aims to summarize the interventions that are currently used to treat CP-related HO (CP-HO), including pharmacotherapy and bariatric surgery. The Cochrane Library, EMBASE, and PubMed databases were searched up to June 2017 for relevant reports. Two reviewers conducted independent evaluations of the identified studies. Eighteen publications were included in the systematic review, with three reports describing pharmacotherapy in randomized controlled trials and 15 reports describing bariatric surgery. Although several studies described effective interventions for treating CP-HO, the evidence base was limited by its low quality and our inability to perform a meta-analysis, which was related to a lack of adequate or integrated data. Octreotide appears to be a preferred treatment for CP-HO patients, based on currently limited data. Gastric bypass surgery may also be suitable for select CP-HO patients, based on a review of various procedures in this setting. Microsurgical preservation of the hypothalamic structures is mandatory to decrease CP-HO-related morbidity and mortality. Further studies with adequate analytical power and sufficient follow-up are needed to identify effective strategies for CP-HO treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

ClinicalTrials.gov

2016-07-14

Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

(68)Ga-DOTA (0)-Tyr (3)-octreotide positron emission tomography in nasopharyngeal carcinoma.

PubMed

Schartinger, Volker H; Dudás, József; Url, Christoph; Reinold, Susanne; Virgolini, Irene J; Kroiss, Alexander; Riechelmann, Herbert; Uprimny, Christian

2015-01-01

PET/CT with (68)Ga-labelled [DOTA(0),Tyr(3)]-octreotide ((68)Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased (68)Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for (68)Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. (68)Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC.

Treatment of solitary gastric carcinoid tumor by endoscopic polypectomy in a patient with pernicious anemia

PubMed Central

Kadikoylu, Gurhan; Yavasoglu, Irfan; Yukselen, Vahit; Ozkara, Esra; Bolaman, Zahit

2006-01-01

Type I gastric carcinoid tumors result from hypergastrinemia in 1%-7% of patients with pernicious anemia. We diagnosed pernicious anemia in a 48-year-old female patient with complaint of fatigue for three months. She had no gastrointestinal symptoms. Endoscopic examination ot the upper gastrointestinal tract revealed atrophic gastritis and a polypoid lesion in the corpus of 3-4 mm in size. Endoscopic polypectomy was performed. Histopathological examination of the specimen revealed positive chromogranin A and synaptophysin stainings compatible with the diagnosis of a carcinoid tumor. Serum gastrin level was increased, urinary 5-hydroxyindoleacetic acid was within the normal range. There was no other symptom, sign, or laboratory finding of a carcinoid syndrome in the patient. No metastasis was found with indium-111 octreotide scan, computed tomographies of abdomen and thorax. Type I gastric carcinoid tumors are only rarely solitary and patients with tumors < 1 cm in size may benefit from endoscopic polypectomy. PMID:16830392

Lung Shunt Fraction prior to Yttrium-90 Radioembolization Predicts Survival in Patients with Neuroendocrine Liver Metastases: Single-Center Prospective Analysis

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

Ludwig, Johannes M.; Ambinder, Emily McIntosh; Ghodadra, Anish

ObjectiveTo investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival.MethodsA single-center, prospective study of 44 consecutive patients (median age: 58.5 years, 29.5 % male) diagnosed with pancreatic (52.3 %) or carcinoid (47.7 %) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients’ baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10 %) and low (<10 %) LSF. Baseline comparisons were performed usingmore » Fisher’s exact tests for categorical and Mann–Whitney U test for continuous variables. Survival was calculated using the Kaplan–Meier method. Univariate (Wilcoxon rank-sum test) and multivariate analyses (Cox Proportional Hazard Model) for risk factor analysis were performed.ResultsThere was no statistically significant difference in age, gender, race, tumor properties, or previous treatments between patients with high (n = 15) and low (n = 29) LSF. The median OS was 27.4 months (95 %CI 12.73–55.23), with 4.77 months (95 %CI 2.87–26.73) for high and 42.77 months (95 %CI 18.47–59.73) for low LSF (p = 0.003). Multivariate analysis identified high LSF (p = 0.001), total serum bilirubin >1.2 mg (p = 0.016), and lack of pretreatment with octreotide (p = 0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival.ConclusionsLSF ≥10 %, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.« less

Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

PubMed Central

Ahlstedt, Jonas; Tran, Thuy A.; Strand, Sven-Erik; Gram, Magnus; Åkerström, Bo

2015-01-01

Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies. PMID:26694383

HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens.

PubMed

Gao, Jennifer J; Tan, Ming; Pohlmann, Paula R; Swain, Sandra M

2017-02-01

Approximately 40% to 80% of patients receiving pertuzumab-directed therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer will develop chemotherapy-induced diarrhea (CID). Loperamide and octreotide are frequently used to treat CID after diarrhea occurs, but neither is used prophylactically or targets the underlying mechanism. Previous studies suggest blocking epidermal growth factor receptor may cause excess chloride secretion, resulting in diarrhea. Crofelemer is derived from the red latex of the Croton lechleri tree, blocks gastrointestinal cystic fibrosis transmembrane regulator and calcium-activated chloride channels, and is U.S. Food and Drug Administration approved for relief of diarrhea in HIV/AIDS patients on anti-retroviral therapy. Crofelemer is not systemically absorbed, has relatively few side effects, and presents a targeted approach at preventing CID in patients receiving pertuzumab-based therapy. HALT-D (DiarrHeA Prevention and ProphyLaxis with Crofelemer in HER2-Positive Breast Cancer Patients Receiving Trastuzumab, Pertuzumab, and Docetaxel or Paclitaxel with or without Carboplatin, NCT02910219) is a phase II, randomized, open-label trial that aims to recruit 46 patients from 3 MedStar sites. Adults with HER2-positive breast cancer being treated with trastuzumab, pertuzumab, and docetaxel or paclitaxel (THP) or trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) will be randomized to receive crofelemer or no medication for diarrhea prophylaxis. The primary endpoint is incidence of all grade diarrhea for ≥ 2 consecutive days during cycles 1 to 2 of THP or TCHP. Secondary endpoints include overall incidence, duration, and severity of diarrhea; time to onset of diarrhea; use of other anti-diarrheal medications; stool frequency and consistency; and quality of life. HALT-D will provide important information about the feasibility and tolerability of crofelemer in preventing diarrhea for patients receiving THP or TCHP. Copyright © 2016 Elsevier Inc. All rights reserved.

[Clinical experience in image-guided ultra-conformal hypofractionated radiotherapy in case of metastatic diseases at the University of Pécs].

PubMed

László, Zoltán; Boronkai, Árpád; Lõcsei, Zoltán; Kalincsák, Judit; Szappanos, Szabolcs; Farkas, Róbert; Al Farhat, Yousuf; Sebestyén, Zsolt; Sebestyén, Klára; Kovács, Péter; Csapó, László; Mangel, László

2015-06-01

With the development of radiation therapy technology, the utilization of more accurate patient fixation, inclusion of PET/CT image fusion into treatment planning, 3D image-guided radiotherapy, and intensity-modulated dynamic arc irradiation, the application of hypofractionated stereotactic radiotherapy can be extended to specified extracranial target volumes, and so even to the treatment of various metastases. Between October 2012 and August 2014 in our institute we performed extracranial, hypofractionated, image-többguided radiotherapy with RapidArc system for six cases, and 3D conformal multifield technique for one patient with Novalis TX system in case of different few-numbered and slow-growing metastases. For the precise definition of the target volumes we employed PET/CT during the treatment planning procedure. Octreotid scan was applied in one carcinoid tumour patient. Considering the localisation of the metastases and the predictable motion of the organs, we applied 5 to 20 mm safety margin during the contouring procedure. The average treatment volume was 312 cm3. With 2.5-3 Gy fraction doses we delivered 39-45 Gy total dose, and the treatment duration was 2.5 to 3 weeks. The image guidance was carried out via ExacTrac, and kV-Cone Beam CT equipment based on an online protocol, therefore localisation differences were corrected before every single treatment. The patients tolerated the treatments well without major (Gr>2) side effects. Total or near total regression of the metastases was observed at subsequent control examinations in all cases (the median follow-up time was 5 months). According to our first experience, extracranial, imageguided hypofractionated radiotherapy is well-tolerated by patients and can be effectively applied in the treatment of slow-growing and few-numbered metastases.

Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study.

PubMed

Sgroi, Dennis C; Chapman, Judy-Anne W; Badovinac-Crnjevic, T; Zarella, Elizabeth; Binns, Shemeica; Zhang, Yi; Schnabel, Catherine A; Erlander, Mark G; Pritchard, Kathleen I; Han, Lei; Shepherd, Lois E; Goss, Paul E; Pollak, Michael

2016-01-04

Biomarkers that can be used to accurately assess the residual risk of disease recurrence in women with hormone receptor-positive breast cancer are clinically valuable. We evaluated the prognostic value of the Breast Cancer Index (BCI), a continuous risk index based on a combination of HOXB13:IL17BR and molecular grade index, in women with early breast cancer treated with either tamoxifen alone or tamoxifen plus octreotide in the NCIC MA.14 phase III clinical trial (ClinicalTrials.gov Identifier NCT00002864; registered 1 November 1999). Gene expression analysis of BCI by real-time polymerase chain reaction was performed blinded to outcome on RNA extracted from archived formalin-fixed, paraffin-embedded tumor samples of 299 patients with both lymph node-negative (LN-) and lymph node-positive (LN+) disease enrolled in the MA.14 trial. Our primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS). MA.14 patients experienced similar RFS on both treatment arms. Association of gene expression data with RFS was evaluated in univariate analysis with a stratified log-rank test statistic, depicted with a Kaplan-Meier plot and an adjusted Cox survivor plot. In the multivariate assessment, we used stratified Cox regression. The prognostic performance of an emerging, optimized linear BCI model was also assessed in a post hoc analysis. Of 299 samples, 292 were assessed successfully for BCI for 146 patients accrued in each MA.14 treatment arm. BCI risk groups had a significant univariate association with RFS (stratified log-rank p = 0.005, unstratified log-rank p = 0.007). Adjusted 10-year RFS in BCI low-, intermediate-, and high-risk groups was 87.5 %, 83.9 %, and 74.7 %, respectively. BCI had a significant prognostic effect [hazard ratio (HR) 2.34, 95 % confidence interval (CI) 1.33-4.11; p = 0.004], although not a predictive effect, on RFS in stratified multivariate analysis, adjusted for pathological tumor stage (HR 2.22, 95 % CI 1.22-4.07; p = 0.01). In the post hoc multivariate analysis, higher linear BCI was associated with shorter RFS (p = 0.002). BCI had a strong prognostic effect on RFS in patients with early-stage breast cancer treated with tamoxifen alone or with tamoxifen and octreotide. BCI was prognostic in both LN- and LN+ patients. This retrospective study is an independent validation of the prognostic performance of BCI in a prospective trial.

Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on 68Ga-DOTANOC PET/CT.

PubMed

Tripathy, Sarthak; Mukherjee, Anirban; Singh, Chirom A; Jat, Bhinyaram; Bal, Chandrasekhar; Shamim, Shamim Ahmed

2017-01-01

Paragangliomas are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by overproduction of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a baseline 68 Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide.

Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on 68Ga-DOTANOC PET/CT

PubMed Central

Tripathy, Sarthak; Mukherjee, Anirban; Singh, Chirom A; Jat, Bhinyaram; Bal, Chandrasekhar; Shamim, Shamim Ahmed

2017-01-01

Paragangliomas are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by overproduction of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a baseline 68 Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide PMID:28680217

Epidermal Growth Factor Receptor, C-kit, and Her2/neu Immunostaining in Advanced or Recurrent Thymic Epithelial Neoplasms Staged According to the 2004 World Health Organization in Patients Treated with Octreotide and Prednisone

PubMed Central

Aisner, Seena C.; Dahlberg, Suzanne; Hameed, Meera R.; Ettinger, David S.; Schiller, Joan H.; Johnson, David H.; Aisner, Joseph; Loehrer, Patrick J.

2011-01-01

Background Advanced or recurrent nonresectable thymic epithelial tumors show only a modest response to standard chemotherapy. A recent study using octreotide and prednisone in thymic tumors, Eastern Cooperative Oncology Group study E1C97, was conducted to verify the activity of octreotide for thymic tumors. The aim of this study was to determine whether epidermal growth factor receptor (EGFR) immunoreactivity correlated with outcomes and to identify new biologic markers for potential targeted therapy. Three markers, EGFR, C-kit, and Her2/neu, were selected for evaluation in patients with advanced thymic epithelial tumors treated on E1C97. Methods Of the 42 patients entered onto E1C97, 34 patients (World Health Organization [WHO] categories: type A = 1, type AB = 1, type B1 = 10, type B2 = 11 type B3 = 8, and type C = 3) had sufficient tissue available for immunohistologic study. Each tumor was assessed to have 0, 1+, 2+, or 3+ immunore-activity in the cytoplasm or membranes of the neoplastic cells for Her2/neu and EGFR and for the presence or absence of C-kit immunoreactivity. Results EGFR immunoreactivity of 2+ or 3+ was associated with more aggressive thymic tumors (WHO types B2 and B3). However, strong EGFR immunoreactivity was not consistently seen with thymic carcinoma. The presence of EGFR within cells was associated with a significantly improved progression-free survival (PFS) and a trend for overall survival (OS). Twelve patients demonstrated C-kit immunoreactivity; the lack of C-kit immunoreactivity was significantly associated with superior PFS but not OS. Her2/neu immunoreactivity was uniformly negative for all tumors evaluated. There was no association between response and biomarker status. Conclusions High EGFR immunoreactivity is seen in more aggressive thymic neoplasms as classified according to the 2004 WHO, but regardless of classification, the presence of EGFR in tumor cells (1+, 2+, and 3+) is associated with improved performance free survival (PFS) and a trend for better OS. In contrast, the absence of C-kit immunoreactivity was associated with improved PFS. These data suggest that EGFR and C-kit may be prognostic, and further studies of these markers in subcategories of thymic malignancies is warranted. PMID:20421818

Specificity and sensitivity of ⁹⁹mTc-EDDA/HYNIC-Tyr³-octreotide (⁹⁹mTc-TOC) for imaging neuroendocrine tumors.

PubMed

Sepúlveda-Méndez, Jesús; de Murphy, Consuelo Arteaga; Pedraza-López, Martha; Murphy-Stack, Eduardo; Rojas-Bautista, Juan Carlos; González-Treviño, Ofelia

2012-01-01

Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the ⁹⁹mTc-EDDA-HYNIC-Tyr³octreotide (⁹⁹mTc-TOC) to image and localize NETs and their metastases. Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with ⁹⁹mTc-TOC. The patients were injected with 500-600 MBq ⁹⁹mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the ⁹⁹mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. The validity of ⁹⁹mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76.8% (64-87%). Because of these high values, we strongly recommend scintigraphy with the Mexican-produced ⁹⁹mTc-TOC for the localization of NETs and their metastases, and we conclude that it is a good tool for detecting neuroendocrine disease in a Mexican population.

Toward oral delivery of biopharmaceuticals: an assessment of the gastrointestinal stability of 17 peptide drugs.

PubMed

Wang, Jie; Yadav, Vipul; Smart, Alice L; Tajiri, Shinichiro; Basit, Abdul W

2015-03-02

A major barrier to successful oral delivery of peptide and protein molecules is their inherent instability in the lumen of the gastrointestinal tract. The aim of this study was to determine the stability of 17 disparate peptide drugs (insulin, calcitonin, glucagon, secretin, somatostatin, desmopressin, oxytocin, [Arg(8)]-vasopressin, octreotide, ciclosporin, leuprolide, nafarelin, buserelin, histrelin, [d-Ser](4)-gonadorelin, deslorelin, and goserelin) in gastric and small intestinal fluids from both humans and pigs, and in simulated gastric and intestinal fluids. In human gastric fluid, the larger peptides including somatostatin, calcitonin, secretin, glucagon, and insulin were metabolized rapidly, while the smaller peptides showed good stability. In human small intestinal fluid, however, both small and large peptides degraded rapidly with the exception of the cyclic peptide ciclosporin and the disulfide-bridge containing peptides octreotide and desmopressin, which showed good stability. The stability of peptides in both simulated gastric fluid and pig gastric fluid correlated well with stability in human gastric fluid. However, it was not possible to establish such a correlation with the small intestinal fluids because of the rapid rate of peptide degradation. This work has identified the molecular features in the structure of a wide range of peptides that influence their stability in the environment of the gastrointestinal tract, which in turn will allow for better selection of peptide candidates for oral delivery.

[Latest advances in acute pancreatitis].

PubMed

de-Madaria, Enrique

2013-10-01

The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

NASA Astrophysics Data System (ADS)

Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

2013-09-01

Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

Tumor-induced osteomalacia

PubMed Central

Chong, William H; Molinolo, Alfredo A; Chen, Clara C; Collins, Michael T

2012-01-01

Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed. PMID:21490240

Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide.

PubMed

Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Traub-Weidinger, Tatjana; Uprimny, Christian; von Guggenberg, Elisabeth; Decristoforo, Clemens; Warwitz, Boris; Widmann, Gerlig; Virgolini, Irene Johanna

2013-02-01

The aim of this study was to evaluate the impact of (68)Ga-labelled DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)-octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or (68)Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga-DOTA-LAN (106 vs 53). The tumour to background ratios for tumour and liver calculated from SUV(max) measurements were significantly higher for (68)Ga-DOTA-TOC than (68)Ga-DOTA-LAN (p < 0.02). (68)Ga-DOTA-TOC PET imaging is an established imaging procedure for accurate staging of NET patients. (68)Ga-DOTA-LAN should only be considered as a PET tracer of second choice in patients with no pathologic tracer uptake on (68)Ga-DOTA-TOC PET. In these patients, (68)Ga-DOTA-LAN PET can provide valuable information when evaluating PRRT as the treatment option, as a broader spectrum of human SSTR subtypes can be detected.

McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

PubMed

Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

2006-05-01

McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.

PubMed

Fujio, Shingo; Ashari; Habu, Mika; Yamahata, Hitoshi; Moinuddin, F M; Bohara, Manoj; Arimura, Hiroshi; Nishijima, Yui; Arita, Kazunori

2014-01-01

Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year-old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 μ U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions.

Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl.

PubMed

Rix, M; Laurberg, P; Hoejberg, A S; Brock-Jacobsen, B

2005-08-01

The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation.

PubMed

Vieira, Teresa C; Bergamin, Carla S; Gurgel, Lucimary C; Moisés, Regina S

2010-11-01

Congenital hyperinsulinism of infancy (CHI) is the most common cause of hypoglycemia in newborns and infants. Several molecular mechanisms are involved in the development of CHI, but the most common genetic defects are inactivating mutations of the ABCC8 or KCNJ11 genes. The classical treatment for CHI has been pancreatectomy that eventually leads to diabetes. More recently, conservative treatment has been attempted in some cases, with encouraging results. Whether or not the patients with heterozygous ABCC8 mutations submitted to conservative treatment may spontaneously develop type 2 diabetes in the long run, is a controversial issue. Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood. The mutation occurred as a de novo germ line mutation in the mother of the index patient. Her hypoglycemic symptoms as a child occurred after the fourth year of life and were very mild, but she developed glucose metabolism impairment in adulthood. On the other hand, in her daughter, the clinical manifestations of the disease occurred in the neonatal period and were more severe, leading to episodes of tonic-clonic seizures that were well controlled with octreotide or diazoxide. Our data corroborate the hypothesis that the dominant E1506K ABCC8 mutation, responsible for CHI, predisposes to the development of glucose intolerance and diabetes later in life. © 2009 John Wiley & Sons A/S.

Gallium-68 DOTA-NOC PET/CT as an alternate predictor of disease activity in sarcoidosis.

PubMed

Sharma, Sanchit; Singh, Achintya D; Sharma, Surendra K; Tripathi, Madhavi; Das, Chandan J; Kumar, Rajeev

2018-05-30

We evaluated the role of gallium-68-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (Ga-DOTA-NOC) PET/CT in assessing sarcoidosis disease activity. Patients diagnosed with sarcoidosis underwent Ga-DOTA-NOC-PET/CT. The maximum standardized uptake value (SUVmax) at the pathological site and in the descending thoracic aorta (reference standard, SUVmed) were assessed. A SUVmax/SUVmed ratio (disease activity score) of more than one was considered a marker of active disease and was compared with the clinical symptoms and serum angiotensin-converting enzyme and computed tomography (CT) scan. The primary outcome was to assess the efficacy of the scan in estimating disease activity. Of the 39 patients enrolled in the study, 27 patients were symptomatic and the rest were asymptomatic at enrollment. Increased disease activity was present in 25 (92%) of the 27 symptomatic patients and two (16%) of the 12 asymptomatic patients. The sensitivity and specificity of the test were 92.5% (95% confidence interval=75.7-99.0) and 83.3% (95% confidence interval=51.5-97.9), respectively. Seven out of nine patients who became asymptomatic after treatment showed a significant decrease in the mean disease activity score in post-treatment scans (3.38±1.05 vs 1.20±0.82, P<0.001). Ga-DOTA-NOC PET/CT emerged as a useful tool to assess the disease activity and treatment response in patients with sarcoidosis with thoracic involvement.

[(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial.

PubMed

Iten, Fabienne; Muller, Beat; Schindler, Christian; Rasch, Helmut; Rochlitz, Christoph; Oertli, Daniel; Maecke, Helmut R; Muller-Brand, Jan; Walter, Martin A

2009-05-15

The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N'''-tetraacetic acid [(90)Y-DOTA]-Tyr(3)-octreotide (TOC) in advanced iodine-refractory thyroid cancer. In a phase 2 trial, the authors investigated biochemical response (assessed by serum thyroglobulin levels), survival, and the long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized iodine-refractory thyroid cancer. Adverse events were assessed according to the National Cancer Institute criteria. Survival analyses were performed by using multiple regression models. A total of 24 patients were enrolled. A median cumulative activity of 13.0 GBq (range, 1.7-30.3 GBq) was administered. Response was found in 7 (29.2%) patients. Eight (33.3%) patients developed hematologic toxicity grade 1-3, and 4 (16.7%) patients developed renal toxicity grade 1-4. The median survival was 33.4 months (range, 3.6-126.8 months) from time of diagnosis and 16.8 months (range, 1.8-99.1 months) from time of first [(90)Y-DOTA]-TOC treatment. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.03-0.92; P = .04) and from time of first [(90)Y-DOTA]-TOC therapy (HR, 0.20; 95% CI, 0.04-0.94; P = .04). The visual grade of scintigraphic tumor uptake was not associated with treatment response (odds ratio [OR], 0.98; 95% CI, 0.26-3.14; P = 1.00). Response to [(90)Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles.

Palliative surgery versus medical management for bowel obstruction in ovarian cancer

PubMed Central

Kucukmetin, Ali; Naik, Raj; Galaal, Khadra; Bryant, Andrew; Dickinson, Heather O

2014-01-01

Background Ovarian cancer is the sixth most common cancer among women and is usually diagnosed at an advanced stage. Bowel obstruction is a common feature of advanced or recurrent ovarian cancer. Patients with bowel obstruction are generally in poor physical condition with a limited life expectancy. Therefore, maintaining their QoL with effective symptom control is the main purpose of the management of bowel obstruction. Objectives To compare the effectiveness and safety of palliative surgery (surgery performed to control the cancer, reduce symptoms and improve quality of life for those whose cancer is not able to be entirely removed) and medical management for bowel obstruction in women with ovarian cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled trials (CENTRAL), Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Studies that compared palliative surgery and medical interventions, in adult women diagnosed with ovarian cancer who had either full or partial obstruction of the bowel. Randomised controlled trials (RCTs) and non-RCTs that used multivariable statistical adjustment for baseline case mix were eligible. Data collection and analysis Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed risk of bias. One non-randomised study was identified so no meta-analyses were performed. Main results The search strategy identified 183 unique references of which 22 were identified as being potentially eligible on the basis of title and abstract. Only one study met our inclusion criteria and was included in the review. It analysed retrospective data for 47 women who received either palliative surgery (n = 27) or medical management with Octreotide (n = 20) and reported overall survival and perioperative mortality and morbidity. Women with poor performance status were excluded from surgery. Although six (22%) women who received surgery had serious complications of the operation and three (11%) died of complications, multivariable analysis found that women who received surgery had significantly (p < 0.001) better survival than women who received Octreotide, after adjustment for important prognostic factors. However, the magnitude of this effect was not reported. Quality of life (QoL) was not reported and adverse events were incompletely documented. Authors’ conclusions We found only low quality evidence comparing palliative surgery and medical management for bowel obstruction in ovarian cancer. Therefore we are unable to reach definite conclusions about the relative benefits and harms of the two forms of treatment, or to identify sub-groups of women who are likely to benefit from one treatment or the other. However, there is weak evidence in support of surgical management to prolong survival. PMID:20614464

Intestinal Lymphangiectasia: Insights on Management and Literature Review

PubMed Central

Alshikho, Mohamad J.; Talas, Joud M.; Noureldine, Salem I.; Zazou, Saf; Addas, Aladdin; Kurabi, Haitham; Nasser, Mahmoud

2016-01-01

Patient: Male, 24 Final Diagnosis: Intestinal lymphangiectasia Symptoms: Frequent episodes of diarrhea • recurrent infections • swelling in the lower limbs Medication: Octreotide • MCT oils Clinical Procedure: Endoscopic exam • Doppler ultrasound study • abdominal CT scan Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Intestinal lymphangiectasia (IL) is a rare disease characterized by a dilatation of the intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract leading to hypoproteinemia, edema, lymphocytopenia, hypogammaglobinemia, and immunological abnormalities. Iron, calcium, and other serum components (e.g., lipids, fat soluble vitamins) may also be depleted. A literature search revealed more than 200 reported cases of IL. Herein, we report our observations of a patient diagnosed with IL; we also present our conclusion for our review of the published literature. Case Report: A 24-year-old male was admitted to Aleppo University Hospital with the complaints of abdominal pain, headache, arthralgia, fever, and rigors. His past medical history was remarkable for frequent episodes of diarrhea, recurrent infections, and swelling in the lower limbs. In addition, he had been hospitalized several times in non-academic hospitals due to edema in his legs, cellulitis, and recurrent infections. In the emergency department, a physical examination revealed a patient in distress. He was weak, dehydrated, pale, and had a high-grade fever. His lower extremities were edematous, swollen, and extremely tender to touch. The overlying skin was erythematous and warm. Moreover, the patient was tachycardic, tacypneic, and moderately hypotensive. The patient was resuscitated with IV fluids, and Tylenol was administered to bring the temperature down. Blood tests showed anemia and high levels of inflammatory markers. The patient’s white blood cell count was elevated with an obvious left shift. However, subsequent investigations showed that the patient had IL. Suitable diet modification plans were applied as a long-term management plan. Conclusions: IL is a rare disease of challenging nature due to its systematic effects and lack of comprehensive studies that can evaluate the effectiveness of specific treatments in a large cohort of patients. Medium-chain triglyceride (MCT) oils and diet modification strategies are effective in reducing the loss of body proteins and in maintaining near-normal blood levels of immunoglobulins. However, octreotide and MCT oils had no proven role in reducing lymphedema in our patient. PMID:27440277

An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors.

PubMed

Gabriel, Michael; Decristoforo, Clemens; Donnemiller, Eveline; Ulmer, Hanno; Watfah Rychlinski, Christine; Mather, Stephen J; Moncayo, Roy

2003-05-01

The aim of this study was to compare the imaging abilities of the recently developed somatostatin analog, (99m)Tc-hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC [(99m)Tc-TOC]), with (111)In-diethylenediaminepentaacetic acid-D-Phe(1)-octreotide ((111)In-OCT [Octreoscan]) in patients undergoing routine somatostatin receptor (SSTR) scintigraphy. Forty-one patients (20 men, 21 women; age range, 29-75 y; mean age, 56.7 y) with either histologically proven or biologically and clinically suspected endocrine tumors were enrolled in the study. Four groups were distinguished: (a) patients being evaluated for the detection and localization of neuroendocrine tumors (n = 6), (b) tumor staging (n = 19), (c) patients being investigated to determine the SSTR status of tumor lesions (n = 11), and (d) patient follow-up studies (n = 5). Each patient received a mean activity of 150 MBq (111)In-OCT and 350-400 MBq (99m)Tc-TOC. Scintigraphy with (99m)Tc-TOC was performed 4 h after injection and scintigraphy with (111)In-OCT was performed 4 and 24 h after injection. SPECT studies of areas of interest were performed 4 h after injection for both tracers as well as at 24 h after injection for (111)In-OCT. The time interval between the studies using each tracer ranged from 2 to 22 d (mean interval, 9.3 d). (111)In-OCT and (99m)Tc-TOC showed an equivalent scan result in 32 patients (78%), 9 cases showed discrepancies (22%), false-negative results with (111)In-OCT were seen in 6 cases (14.6%), whereas (99m)Tc-TOC was false-positive in 2 cases (4.9%). (111)In-OCT was true-negative in both cases. The false-positive findings of the (99m)Tc-TOC studies were caused by nonspecific uptake in the bowel. In 1 case, (99m)Tc-TOC correctly identified a metastasis in the lumbar spine but both scan results were false-positive because of an inflammatory process. In 21 patients with SSTR-expressing tumors, the semiquantitative region-of-interest analysis showed that (99m)Tc-TOC achieved higher tumor-to-normal tissue ratios than (111)In-OCT. This study revealed a higher sensitivity of (99m)Tc-TOC as compared with (111)In-OCT as an imaging agent for the localization of SSTR-expressing tumors. To avoid false-positive findings with (99m)Tc-OCT due to nonspecific tracer accumulation, additional scanning at 1-2 h after injection should be done.

Anemia Due to Inflammation in an Anti-Coagulated Patient with Blue Rubber Bleb Nevus Syndrome.

PubMed

Bonaventura, Aldo; Liberale, Luca; Hussein El-Dib, Nadia; Montecucco, Fabrizio; Dallegri, Franco

2016-01-01

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by vascular malformations mostly involving skin and gastrointestinal tract. This disease is often associated with sideropenic anemia and occult bleeding. We report the case of chronic severe anemia in an old patient under oral anticoagulation treatment for chronic atrial fibrillation. At admission, the patient also presented fever and increased laboratory parameters of systemic inflammation (ferritin 308 mcg/L, C-reactive protein (CRP) 244 mg/L). A small bluish-colored lesion over the left ear lobe was observed. Fecal occult blood test was negative as well as other signs of active bleeding. Lower gastrointestinal endoscopy revealed internal hemorrhoids and multiple teleangiectasias that were treated with argon plasma coagulation. Videocapsule endoscopy demonstrated multiple bluish nodular lesions in the small intestine. Unexpectedly, chronic severe anemia due to systemic inflammation was diagnosed in an old anticoagulated patient with BRNBS. The patient was treated with blood transfusions, hydration, antibiotic treatment, and long-acting octreotide acetate, without stopping warfarin. Fever and inflammation disappeared without any acute gastrointestinal bleeding and improvement of hemoglobin levels at three-month follow up. This is the oldest patient presenting with chronic anemia, in which BRNBS was also diagnosed. Surprisingly, anemia was mainly caused by systemic inflammation instead of chronic gastrointestinal bleeding. However, we would recommend investigating this disease also in old subjects with mild signs and symptoms.

Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors

PubMed Central

Kjaer, Andreas; Knigge, Ulrich

2015-01-01

Abstract Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when treatment is targeted at the somatostatin receptors as with the use of somatostatin analogues or PRRT. SRI with gamma camera technique using the tracer 111In-DTPA-octreotide has for many years been the backbone of nuclear imaging of NETs. However, increasingly PET tracers for SRI are now used. 68Ga-DOTATATE, 68Ga-DOTATOC and 68Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also 11C-5-HTP, 18F-DOPA and 123I-MIBG may be used in NET. However, with FDG-PET and somatostatin receptor PET at hand we see limited necessity of other tracers. PRRT is an important tool in the treatment of advanced NETs causing complete or partial response in 20% and minor response or tumor stabilization in 60% with response duration of up to 3 years. Grade 3–4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. 177Lu-DOTATATE seems to have less toxicity than 90Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed and the role of PRRT in treatment of NETs remains to be established. PMID:25959100

Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors.

PubMed

Kjaer, Andreas; Knigge, Ulrich

2015-06-01

Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when treatment is targeted at the somatostatin receptors as with the use of somatostatin analogues or PRRT. SRI with gamma camera technique using the tracer (111)In-DTPA-octreotide has for many years been the backbone of nuclear imaging of NETs. However, increasingly PET tracers for SRI are now used. (68)Ga-DOTATATE, (68)Ga-DOTATOC and (68)Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also (11)C-5-HTP, (18)F-DOPA and (123)I-MIBG may be used in NET. However, with FDG-PET and somatostatin receptor PET at hand we see limited necessity of other tracers. PRRT is an important tool in the treatment of advanced NETs causing complete or partial response in 20% and minor response or tumor stabilization in 60% with response duration of up to 3 years. Grade 3-4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. (177)Lu-DOTATATE seems to have less toxicity than (90)Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed and the role of PRRT in treatment of NETs remains to be established.

Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma

PubMed Central

2012-01-01

Background External beam radiotherapy (EBRT) is the treatment of choice for irresectable meningioma. Due to the strong expression of somatostatin receptors, peptide receptor radionuclide therapy (PRRT) has been used in advanced cases. We assessed the feasibility and tolerability of a combination of both treatment modalities in advanced symptomatic meningioma. Methods 10 patients with irresectable meningioma were treated with PRRT (177Lu-DOTA0,Tyr3 octreotate or - DOTA0,Tyr3 octreotide) followed by external beam radiotherapy (EBRT). EBRT performed after PRRT was continued over 5–6 weeks in IMRT technique (median dose: 53.0 Gy). All patients were assessed morphologically and by positron emission tomography (PET) before therapy and were restaged after 3–6 months. Side effects were evaluated according to CTCAE 4.0. Results Median tumor dose achieved by PRRT was 7.2 Gy. During PRRT and EBRT, no side effects > CTCAE grade 2 were noted. All patients reported stabilization or improvement of tumor-associated symptoms, no morphologic tumor progression was observed in MR-imaging (median follow-up: 13.4 months). The median pre-therapeutic SUVmax in the meningiomas was 14.2 (range: 4.3–68.7). All patients with a second PET after combined PRRT + EBRT showed an increase in SUVmax (median: 37%; range: 15%–46%) to a median value of 23.7 (range: 8.0–119.0; 7 patients) while PET-estimated volume generally decreased to 81 ± 21% of the initial volume. Conclusions The combination of PRRT and EBRT is feasible and well tolerated. This approach represents an attractive strategy for the treatment of recurring or progressive symptomatic meningioma, which should be further evaluated. PMID:22720902

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Obeticholic acid for severe bile acid diarrhea with intestinal failure: A case report and review of the literature

PubMed Central

Hvas, Christian Lodberg; Ott, Peter; Paine, Peter; Lal, Simon; Jørgensen, Søren Peter; Dahlerup, Jens Frederik

2018-01-01

Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn’s disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24 h and improved the patient’s quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea. PMID:29881241

Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

PubMed

Schwartz, Laurent; Guais, Adeline; Israël, Maurice; Junod, Bernard; Steyaert, Jean-Marc; Crespi, Elisabetta; Baronzio, Gianfranco; Abolhassani, Mohammad

2013-04-01

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

PubMed Central

Song, Xiao-li; Ju, Rui-jun; Xiao, Yao; Wang, Xin; Liu, Shuang; Fu, Min; Liu, Jing-jing; Gu, Li-yan; Li, Xue-tao; Cheng, Lan

2017-01-01

Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC. PMID:29066893

Everolimus induces rapid plasma glucose normalization in insulinoma patients by effects on tumor as well as normal tissues.

PubMed

Fiebrich, Helle-Brit; Siemerink, Ester J M; Brouwers, Adrienne H; Links, Thera P; Remkes, Wouter S; Hospers, Geke A P; de Vries, Elisabeth G E

2011-01-01

Mammalian target of rapamycin inhibitor everolimus administered to four insulinoma patients rapidly controlled hypoglycemia (Kulke et al., N Engl J Med 2009;360:195-197). We wanted to identify the kinetics of everolimus effects on controlling hypoglycemia and understand underlying mechanisms. Three consecutive patients with a metastasized symptomatic insulinoma were started on 100 μg of octreotide subcutaneously three times daily. Because of persisting hypoglycemias, treatment with daily 10 mg of oral everolimus was initiated. Serial plasma glucose levels and serum insulin levels were measured. Computer tomography (CT) scans were performed before and after 2 and 5 months of treatment. [¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) scans, to visualize glucose metabolism, were made before and after 2 weeks, 5 weeks, and 5 months of treatment. The ¹⁸F-FDG uptake was quantified as the maximum standardized uptake value. All patients achieved control of hypoglycemia on everolimus within 14 days. Insulin levels were 2.5- to 6.3-fold elevated before start of treatment and declined 14%-64% after 4 weeks of treatment. CT scans showed stable disease at 2 months in all patients, with progressive disease after 5 months in one. Before treatment, both the tumor lesions and the muscles and myocardium showed high ¹⁸F-FDG uptake. Everolimus reduced tumor and muscle ¹⁸F-FDG uptake after 2 weeks by 26% ± 14% and 19% ± 41%, and after 5 months by 31% ± 13% and 27% ± 41%. Everolimus normalizes plasma glucose levels in metastatic insulinoma within 14 days, coinciding with a lower glucose uptake in tumor and muscles and declining (pro)insulin levels. This effect on tumor as well as normal tissues explains the rapid controlling of hypoglycemia.

Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.

PubMed

Salerno, Francesco; Navickis, Roberta J; Wilkes, Mahlon M

2015-11-25

Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes. Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose. Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period. This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.

Osteomalacia-inducing renal clear cell carcinoma uncovered by 99mTc-Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) scintigraphy.

PubMed

Jin, Xiaona; Jing, Hongli; Li, Fang; Zhuang, Hongming

2013-11-01

Most osteomalacia-causing tumors are small, benign mesenchymal neoplasms, which are commonly located in the extremities or craniofacial regions. An 18-year-old male patient with suspicion of tumor-induced osteomalacia underwent (99m)Tc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed a large activity in the region of the left kidney. The lesion was resected and a clear cell renal cell carcinoma was found. One year after the left nephrectomy, the patient was tumor-free without symptoms of osteomalacia.

Highly Increased 125I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst2 Targeting in Human Cancers.

PubMed

Reubi, Jean Claude; Waser, Beatrice; Mäcke, Helmut; Rivier, Jean

2017-02-01

There is recent in vitro and in vivo evidence that somatostatin receptor subtype 2 (sst 2 ) antagonists are better tools to target neuroendocrine tumors (NETs) than sst 2 agonists. Indeed, antagonists bind to a greater number of sst 2 sites than agonists. Whether sst 2 antagonists could be used successfully to target non-NETs, expressing low sst 2 density, is unknown. Here, we compare quantitatively 125 I-JR11 sst 2 antagonist binding in vitro with that of the sst 2 agonist 125 I-Tyr 3 -octreotide in large varieties of non-NET and NET. In vitro receptor autoradiography was performed with 125 I-JR11 and 125 I-Tyr 3 -octreotide in cancers from prostate, breast, colon, kidney, thyroid, and lymphoid tissues as well as NETs as reference. In general, 125 I-JR11 binds to many more sst 2 sites than 125 I-Tyr 3 -octreotide. In 13 breast cancers, 8 had a low binding (mean density, 844 ± 168 dpm/mg of tissue) with the agonist whereas 12 had a high binding (mean density, 4,447 ± 1,128 dpm/mg of tissue) with the antagonist. All 12 renal cell cancers showed a low binding of sst 2 with the agonist (mean density, 348 ± 49 dpm/mg of tissue) whereas all cases had a high sst 2 binding with the antagonist (mean density, 3,777 ± 582 dpm/mg of tissue). One of 5 medullary thyroid cancers was positive with the agonist, whereas 5 of 5 were positive with the antagonist. In 15 non-Hodgkin lymphomas, many more sst 2 sites were labeled with the antagonist than with the agonist. In 14 prostate cancers, none had sst 2 binding with the agonist and only 4 had a weak binding with the antagonist. None of 17 colon cancers showed sst 2 sites with the agonist, and only 3 cases were weakly positive with the antagonist. In the various tumor types, adjacent sst 2 -expressing tissues such as vessels, lymphocytes, nerves, mucosa, or stroma were more strongly labeled with the antagonist than with the agonist. The reference NET cases, incubated with a smaller amount of tracer, were also found to have many more sst 2 sites measured with the antagonist. All renal cell cancers and most breast cancers, non-Hodgkin lymphomas, and medullary thyroid cancers represent novel indications for the in vivo radiopeptide targeting of sst 2 by sst 2 antagonists, comparable to NET radiotargeting with sst 2 agonists. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Pancreas-preserving segmental duodenectomy for gastrointestinal stromal tumor of the duodenum and splenectomy for splenic angiosarcoma.

PubMed

Muroni, Mirko; Ravaioli, Matteo; Del Gaudio, Massimo; Nigri, Giuseppe; D'Angelo, Francesco; Uccini, Stefania; Ramacciato, Giovanni

2012-06-01

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. (111)In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes. We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence.

Relative Bioavailability of a Single 4-mg Dose of Somatropin Administered by Subcutaneous Injection or by Needle-free Device and Coadministered With the Growth Hormone Inhibitor Octreotide Acetate in Healthy Adult Subjects.

PubMed

Brimhall, Darin B; Petri, Niclas; D'Angelo, Pina

2018-05-01

Somatropin, used to treat growth hormone deficiency, has been traditionally administered by subcutaneous (SC) injection with needle and syringe. Needle-free devices offer ease of administration and may improve adherence and outcomes. This study evaluated the relative bioavailability of somatropin delivered with a needle-free device compared with traditional SC injection. In this randomized, single-dose, crossover study, healthy adults aged 18 to 35 years received single 4-mg doses of somatropin via a needle-free device or SC injection, along with octreotide to suppress endogenous growth hormone production. Blood samples were analyzed for serum somatropin and insulin-like growth factor-1 (IGF-1) concentrations over 24 hours after somatropin dosing. Pharmacokinetic and pharmacodynamic parameters were evaluated by using noncompartmental methods, and bioequivalence was determined based on ln transformation of the AUC 0-24 , AUC 0-∞ , C max , area under the effect-time curve from time 0 to 24 hours (AUEC 0-24 ), and maximum effect concentration (E max ). Bioequivalence was concluded if the 90% CIs of the needle-free device compared with the SC injection, constructed by using the two 1-sided hypotheses at the α = 0.05 level, for these pharmacokinetic/pharmacodynamic parameters fell within the 80.00% to125.00% regulatory acceptance range. A total of 57 subjects completed both study periods and were included in the pharmacokinetic analyses. Point estimates (90% CIs) of the geometric mean ratio (needle-free device/SC injection) based on serum somatropin were 1.013 (0.987-1.040) for AUC 0-24 , 1.012 (0.986-1.038) for AUC 0-∞ , and 1.200 (1.137-1.267) for C max . For IGF-1, baseline-corrected point estimates (90% CIs) were 0.901 (0.818-0.993) for AUEC 0-24 and 0.867 (0.795-0.946) for E max . Non-baseline-corrected values were 0.978 (0.953-1.004) for AUEC 0-24 and 0.953 (0.923-0.984) for E max . Both treatments were well tolerated; blood glucose levels increased in nearly all subjects (98.3%). All adverse events were mild and resolved spontaneously within 24 hours. Bioequivalence was shown for a single 4-mg dose of somatropin delivered by using a needle-free device compared with SC injection based on ln-transformed AUC 0-24 and AUC 0-∞ but not ln-transformed C max . Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours.

PubMed

Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene

2008-10-01

Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

Effective detection of the tumors causing osteomalacia using [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan.

PubMed

Jing, Hongli; Li, Fang; Zhuang, Hongming; Wang, Zhenghua; Tian, Jian; Xing, Xiaoping; Jin, Jin; Zhong, Dingrong; Zhang, Jingjing

2013-11-01

Tumor-induced osteomalacia (TIO) is an endocrine disorder caused by tumors producing excessive fibroblast growth factor-23 (FGF-23). The causative tumors are generally small, slow-growing benign mesenchymal tumors. The only cure of the disease depends on resection of the tumors, which are extremely difficult to localize due to their small sizes and rare locations. Since these tumors are known to express somatostatin receptors, this research was undertaken to evaluate efficacy of [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body imaging in this clinical setting Images of 99mTc-HYNIC-TOC scans and clinical chart from 183 patients with hypophosphatemia and clinically suspected TIO were retrospectively reviewed. The scan findings were compared to the results of histopathological examinations and clinical follow-ups. Among 183 patients, 72 were confirmed to have TIO while 103 patients were found to have other causes of hypophosphatemia. The possibility of TIO could not be either diagnosed or excluded in the remaining 8 patients. For analytical purposes, these 8 patients who could neither be diagnosed nor excluded as having TIO were regarded as having the disease, bringing the total of TIO patients to 80. The 99mTc-HYNIC-TOC scan identified 69 tumors in 80 patients with TIO, which rendered a sensitivity of 86.3% (69/80). 99mTc-HYNIC-TOC scintigraphy excluded 102 patients without TIO with a specificity of 99.1% (102/103). The overall accuracy of 99mTc-HYNIC-TOC whole body scan in the localization of tumors responsible for osteomalacia is 93.4% (171/183). Whole body 99mTc-HYNIC-TOC imaging is effective in the localization of occult tumors causing TIO. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in Patients With Hepatic Metastases of Neuroendocrine Tumors.

PubMed

Sänger, Philipp Wilhelm; Freesmeyer, Martin

2016-06-01

Whole-body PET with Ga-DOTA-D-Phe-Tyr-octreotide (Ga-DOTATOC) and contrast-enhanced CT (ceCT) are considered a standard for the staging of neuroendocrine tumors (NETs). This study sought to verify whether early dynamic (ed) Ga-DOTATOC PET/CT can reliably detect liver metastases of NETs (hypervascular, nonhypervascular; positive or negative for somatostatin receptors) and to verify if the receptor positivity has a significant impact on the detection of tumor hypervascularization. Twenty-seven patients with NET were studied by ceCT and standard whole-body PET according to established Ga-DOTATOC protocols. In addition, edPET data were obtained by continuous scanning during the first 300 seconds after bolus injections of the radiotracer. Early dynamic PET required an additional low-dose, native CT image of the liver for the purpose of attenuation correction. Time-activity and time-contrast curves were obtained, the latter being calculated by the difference between tumor and reference regions. Early dynamic PET/CT proved comparable with ceCT in readily identifying hypervascular lesions, irrespective of the receptor status, with activities rising within 16 to 40 seconds. Early dynamic PET/CT also readily identified nonhypervascular, receptor-positive lesions. Positive image contrasts were obtained for hypervascular, receptor-positive lesions, whereas early negative contrasts were obtained for nonhypervascular, receptor-negative lesions. The high image contrast of hypervascular NET metastases in early arterial phases suggests that edPET/CT can become a useful alternative in patients with contraindications to ceCT. The high density of somatostatin receptors did not seem to interfere with the detection of the lesion's hypervascularization.

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

PubMed

Gandomkar, Mostafa; Najafi, Reza; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, Sayed Esmaeil Sadat

2007-08-01

Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors.

PubMed

Gabriel, M; Muehllechner, P; Decristoforo, C; von Guggenberg, E; Kendler, D; Prommegger, R; Profanter, C; Moncayo, R; Virgolini, I

2005-09-01

To evaluate the use of 99mTc-EDDA-hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC) for staging and follow-up of neuroendocrine gastro-entero-pancreatic (GEP) tumors with special focus on the acquisition protocol including single photon emission computed tomography (SPECT). Eighty-eight patients (37 female, 51 male; age range: 16 to 81 years; mean age: 56.3 years) were studied: 42 patients for staging after initial histological confirmation and 46 patients during post-therapy follow-up. An average activity of 400 MBq of the radiopharmaceutical was injected. All tumors originated from neuroendocrine tissue of the gastroenteropancreatic tract. Whole body scintigrams at 4 h postinjection and SPECT of the abdomen were obtained in all patients. Additional planar images of the abdomen were acquired at 2 h after injection in 68 patients. The Tc-TOC scan result was true-positive in 56 patients, true-negative in 17, false-negative in 14, and false-positive in 1 patient. The false-positive finding was caused by a colonic adenoma. Overall, a scan sensitivity of 80% (56/70 patients), specificity of 94.4% (17/18 patients) and accuracy of 82.9% (73/88 patients) were calculated on patient basis. In total, Tc-TOC detected 357 foci in 69 patients. In 7 patients equivocal findings were observed in the bowel at 4 h postinjection without corresponding tracer uptake in the scan 2 h earlier, meaning that these abnormal findings were correctly classified as non-malignant. In addition to planar views, SPECT revealed further 62 lesions. Tc-TOC with one-day, dual-time acquisition protocol is an accurate staging procedure in patients with neuroendocrine GEP tumors. SPECT shows high sensitivity for detection of abdominal lesions, while earlier images improve the reliability of abnormal abdominal findings.

Biokinetics and dosimetry in patients of 99mTc-EDDA/HYNIC-Tyr3-octreotide prepared from lyophilized kits.

PubMed

González-Vázquez, Armando; Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Gutiérrez-García, Zohar

2006-07-01

99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for 99mTc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after 99mTc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all eight scans and the count per minute (cpm) of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99mTc-HYNIC-TOC time-activity curves in each organ, to adjust a biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed an average tumor/blood (heart) ratio of 4.3+/-0.7 in receptor-positive tumors at 1 h. The mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers.

PubMed

Villard, Linda; Romer, Anna; Marincek, Nicolas; Brunner, Philippe; Koller, Michael T; Schindler, Christian; Ng, Quinn K T; Mäcke, Helmut R; Müller-Brand, Jan; Rochlitz, Christoph; Briel, Matthias; Walter, Martin A

2012-04-01

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. A total of 486 patients completed three or more treatment cycles; 237 patients received [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC. Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response.

PubMed

Helseth, R; Carlsen, S M; Bollerslev, J; Svartberg, J; Øksnes, M; Skeie, S; Fougner, S L

2016-02-01

In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p < 0.03). HbA1c, fasting glucose, and AUC-G increased significantly during SSA pretreatment in patients not achieving hormonal control (all p < 0.05) but did not change significantly in patients with normalized hormone levels. At 3 months postoperative, HbA1c, fasting glucose, and AUC-G were significantly reduced in both cured and not cured patients (all p < 0.05). To conclude, in de novo patients with acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

PubMed

Jadhav, Swati; Kasaliwal, Rajeev; Shetty, Nitin S; Kulkarni, Suyash; Rathod, Krantikumar; Popat, Bhavesh; Kakade, Harshal; Bukan, Amol; Khare, Shruti; Budyal, Sweta; Jagtap, Varsha S; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S

2014-09-01

Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized. We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA. The response was documented in terms of symptomatic improvement, phosphorus normalization, and follow-up (99m)Technitium-labelled hydrazinonicotinyl-Tyr3-octreotide ((99m)Tc HYNIC TOC) scan. Two of the three individuals, patient A (with a 1.5 × 1.2-cm lesion in the head of the right femur) and patient B (with a 1.3 × 1.2-cm lesion on the endosteal surface of the shaft of the left femur), achieved complete remission with single sessions of RFA. Three months after the procedure, (99m)Tc HYNIC TOC scans revealed the absence of uptake at the previous sites, corroborating with the clinical improvement and phosphorus normalization. Patient C had a large 5.6 × 6.5-cm complex lesion in the lower end of the left femur with irregular margins, loculations, and bone grafts placed in previous surgery. He failed to achieve remission after multiple sessions of RFA due to the complex nature of the lesion, although the tumor burden was reduced significantly as documented on serial (99m)Tc HYNIC TOC scans. Although surgery remains the treatment of choice, RFA could be an effective, less invasive, and safe modality of treatment in judiciously selected patients.

Nuclear oncology, a fast growing field of nuclear medicine

NASA Astrophysics Data System (ADS)

Olivier, Pierre

2004-07-01

Nuclear Medicine in oncology has been for a long time synonymous with bone scintigraphy, the first ever whole body imaging modality, and with treatment of thyroid cancer with iodine-131. More recently, somatostatin receptor scintigraphy (SRS) using peptides such as 111In-labelled octreotide became a reference imaging method in the detection and staging of neuroendocrine tumors while 131I- and 123I-MIBG remain the tracers of reference for pheochromocytomas and neuroblastomas. Lymphoscintigraphic imaging based on peritumoral injection of 99mTc-labelled colloids supports, in combination with per operative detection, the procedure of sentinel node identification in breast cancers and melanomas. Positron Emission Tomography (PET) is currently experiencing a considerable growth in oncology based on the use of 18F-FDG (fluorodeoxyglucose), a very sensitive, although non-specific, tumor tracer. Development of instrumentation is crucial in this expansion of PET imaging with new crystals being more sensitive and hybrid imagers that permit to reduce the acquisition time and offer fused PET-CT images. Current developments in therapy can be classified into three categories. Radioimmunotherapy (RIT) based on monoclonal antibodies (or fragments) labelled with beta-emitters. This technique has recently made its entrance in clinical practice with a 90Y-labelled anti-CD20 antibody ( 90Y-ibritumomab tiuxetan (Zevalin ®)) approved in US for the treatment of some subtypes of non-Hodgkin's lymphoma. Radionuclide-bone pain palliation has experienced developments with 153Sm-EDTMP, 186Re-HEDP or 89Sr, efficient in patients with widespread disease. Last, the same peptides, as those used in SRS, are being developed for therapy, labelled with 90Y, 111In or 177Lu in patients who failed to respond to other treatments. Overall, nuclear oncology is currently a fast growing field thanks to the combined developments of radiopharmaceuticals and instrumentation.

Quantitative magnetic resonance imaging assessments of autosomal recessive polycystic kidney disease progression and response to therapy in an animal model.

PubMed

Erokwu, Bernadette O; Anderson, Christian E; Flask, Chris A; Dell, Katherine M

2018-05-01

BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is associated with significant mortality and morbidity, and currently, there are no disease-specific treatments available for ARPKD patients. One major limitation in establishing new therapies for ARPKD is a lack of sensitive measures of kidney disease progression. Magnetic resonance imaging (MRI) can provide multiple quantitative assessments of the disease.MethodsWe applied quantitative image analysis of high-resolution (noncontrast) T2-weighted MRI techniques to study cystic kidney disease progression and response to therapy in the PCK rat model of ARPKD.ResultsSerial imaging over a 2-month period demonstrated that renal cystic burden (RCB, %)=[total cyst volume (TCV)/total kidney volume (TKV) × 100], TCV, and, to a lesser extent, TKV detected cystic kidney disease progression, as well as the therapeutic effect of octreotide, a clinically available medication shown previously to slow both kidney and liver disease progression in this model. All three MRI measures correlated significantly with histologic measures of renal cystic area, although the correlation of RCB and TCV was stronger than that of TKV.ConclusionThese preclinical MRI results provide a basis for applying these quantitative MRI techniques in clinical studies, to stage and measure progression in human ARPKD kidney disease.

Molecular targeted therapy in enteropancreatic neuroendocrine tumors: from biology to clinical practice.

PubMed

Fazio, N; Scarpa, A; Falconi, M

2014-01-01

Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies, including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy: somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation are addressed.

Selective agonists of somatostatin receptor subtype 1 or 2 injected peripherally induce antihyperalgesic effect in two models of visceral hypersensitivity in mice.

PubMed

Mulak, Agata; Larauche, Muriel; Biraud, Mandy; Million, Mulugeta; Rivier, Jean; Taché, Yvette

2015-01-01

Somatostatin interacts with five G-protein-coupled receptor (sst1-5). Octreotide, a stable sst2≫3≥5 agonist, exerts a visceral anti-hyperalgesic effect in experimental and clinical studies. Little is known on the receptor subtypes involved. We investigated the influence of the stable sst1-5 agonist, ODT8-SST and selective receptor subtype peptide agonists (3 or 10μg/mouse) injected intraperitoneally (ip) on visceral hypersensitivity in mice induced by repeated noxious colorectal distensions (four sets of three CRD, each at 55mmHg) or corticotropin-releasing factor receptor 1 agonist, cortagine given between two sets of graded CRD (15, 30, 45, and 60mmHg, three times each pressure). The mean visceromotor response (VMR) was assessed using a non-invasive manometry method and values were expressed as percentage of the VMR to the 1st set of CRD baseline or to the 60mmHg CRD, respectively. ODT8-SST (10μg) and the sst2 agonist, S-346-011 (3 and 10μg) prevented mechanically induced visceral hypersensitivity in the three sets of CRD, the sst1 agonist (10μg) blocked only the 2nd set and showed a trend at 3μg while the sst4 agonist had no effect. The selective sst2 antagonist, S-406-028 blocked the sst2 agonist but not the sst1 agonist effect. The sst1 agonist (3 and 10μg) prevented cortagine-induced hypersensitivity to CRD at each pressure while the sst2 agonist at 10μg reduced it. These data indicate that in addition to sst2, the sst1 agonist may provide a novel promising target to alleviate visceral hypersensitivity induced by mechanoreceptor sensitization and more prominently, stress-related visceral nociceptive sensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

Management of neuroendocrine tumors.

PubMed

Chung, Clement

2016-11-01

Current strategies for managing neuroendocrine tumors (NETs) in adult patients are reviewed, with a focus on medication safety concerns. NETs usually originate in the gastrointestinal or bronchopulmonary tract. Symptoms due to hormonal hypersecretion often occur in patients with foregut or midgut NETs or liver metastases. Surgical resection is recommended for most localized NETs, while systemic cytotoxic chemotherapy is typically used for high-grade and pancreatic tumors. The standard of care for metastatic NETs is somatostatin analog therapy with octreotide (available in both short- and long-acting formulations) or a depot formulation of lanreotide. Everolimus and sunitinib are targeted therapies with approved indications for use in treating advanced pancreatic NETs. Some patients with liver-predominant disease or liver metastases may undergo regional chemoembolization procedures. Pharmacists should be cognizant of differences between newer and older chemoembolization agents and procedures, as well as differences between somatostatin analog products used as medications and the radiolabelled forms used in diagnostic scintigraphy. Other medication safety issues in NET management arise during perioperative supportive care, patient education, compliance counseling, and management of adverse effects of targeted therapies and chemotherapy, including stomatitis, hyperthyroidism, and hand-foot skin reaction. Somatostatin analog therapy is the mainstay for management of locally advanced or metastatic NETs. Liver-directed therapy is an option for localized unresectable disease; platinum-based chemotherapy is the first-line treatment for poorly differentiated tumors. Optimal sequencing of these treatments and targeted therapies such as everolimus and tyrosine kinase inhibitors remains to be elucidated. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

En bloc resection for treatment of tumor-induced osteomalacia: a case presentation and a systematic review.

PubMed

Meng, Tong; Zhou, Wang; Li, Bo; Yin, Huabin; Li, Zhenxi; Zhou, Lei; Kong, Jinhai; Yan, Wangjun; Yang, Xinghai; Liu, Tielong; Song, Dianwen; Xiao, Jianru

2015-05-08

Tumor-induced osteomalacia (TIO) is a rare disorder, which is commonly found in craniofacial locations and in the extremities. To the best of our knowledge, only 16 cases have been described in the spine, and this is the first report to describe a case of patient with TIO in the thoracic spine combined with a mesenchymal hamartoma which had confused the therapeutic strategies to date. We report the case of a 60-year-old patient with hypophosphatemia and presented with limb weakness. Treating with phosphate did not correct the hypophosphatemia and an (111)In pentetreotide scintigraphy (octreotide scan) revealed an increased uptake at the right forearm. The tumor was resected totally, and the histopathology revealed a mesenchymal hamartoma, but we noticed that hypophosphatemia was not corrected after the tumor resection. Then a whole-body magnetic resonance imaging (WB-MRI) was performed and the results revealed tumorous tissues at the right T1 vertebral pedicle. The tumor was removed with an en bloc method, and the pathology showed phosphaturic mesenchymal tumor. Follow-up at 1 year after surgery revealed no recurrence, and the serum phosphorus level of the patient was normal. Tumor-induced osteomalacia is exceedingly rare with only 16 cases in spine published in the literature. It is difficult to find and leads to years of suffering debilitating complications. In this regard, the WB-MRI is a better method to locate the real tumor. Treating with phosphate can only relieve symptoms, and a complete surgical removal remains the gold standard treatment.

Pharmacological interventions for acute pancreatitis.

PubMed

Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-21

In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials. seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

Prevention praised, cure preferred: results of between-subjects experimental studies comparing (monetary) appreciation for preventive and curative interventions

PubMed Central

2013-01-01

Background 'An ounce of prevention is worth a pound of cure’ is a common saying, and indeed, most health economic studies conclude that people are more willing to pay for preventive measures than for treatment activities. This may be because most health economic studies ask respondents to compare preventive measures with treatment, and thus prompt respondents to consider other uses of resources. However, psychological theorizing suggests that, when methods do not challenge subjects to consider other uses of resources, curative treatment is favored over prevention. Could it be that while prevention is praised, cure is preferred? Methods In two experimental studies, we investigated, from a psychological perspective and using a between-subjects design, whether prevention or treatment is preferred and why. In both studies, participants first read a lung cancer prevention or treatment intervention scenario that varied on the prevention-treatment dimension, but that were the same on factors like 'costs per saved life’ and kind of disease. Then participants completed a survey measuring appreciation (general and monetary) as well as a number of potential mediating variables. Results Both studies clearly demonstrated that, when the design was between-subjects, participants had greater (general and monetary) appreciation for treatment interventions than for preventive interventions with perceived urgency of the intervention quite consistently mediating this effect. Differences in appreciation of treatment over preventive treatment were shown to be .59 (Study 1) and .45 (Study 2) on a 5-point scale. Furthermore, participants thought that health insurance should compensate more for the treatment than for preventive measures, differences of 16% (Study 1), and 22% (Study 2). When participants were asked to directly compare both interventions on the basis of a short description, they preferred the preventive intervention. Conclusion It appears that people claim to prefer prevention when they are asked to consider other use of resources, but otherwise they prefer treatment. This preference is related to perceived urgency. The preference for treatment may be related to the prevention-treatment dimension itself, but also to variations on other dimensions that are inherently linked to prevention and treatment (like different efficacy rates and costs per treatment). PMID:24344779

Rapidly progressing malignant insulinoma presented with multiple liver metastases: a case report.

PubMed

Erdogan, Askin; Askin, Erdogan; Kose, Fatih; Fatih, Kose; Akkaya, Hampar; Hampar, Akkaya; Bascil Tutuncu, Neslihan; Tutuncu, Neslihan Bascil; Ozyilkan, Ozgur; Ozgur, Ozyilkan

2010-12-01

A 51-year-old female was admitted to emergency unit with sudden loss of consciousness. Her blood glucose level from fingertip was 33 mg/dl, and insulin level was 55 (normal range, 4-17 IU). Abdominal ultrasonography revealed pancreatic mass with diffuse liver metastases. Biopsy of liver metastases showed differentiated neuroendocrine carcinoma. Diazoxide and chemotherapy stabilized her glucose level for more than 4 months. However, the disease showed progression, and death occurred 8 months later. In conclusion, this case may suggest that biologic behavior may differ from histological behavior in insulinoma and platin-based systemic chemotherapy may provide some benefit in patients those who had diazoxide- and octreotide-resistant tumors.

Motilin-induced gastric contractions signal hunger in man.

PubMed

Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I

2016-02-01

Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. 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/

Synthesis, Characterization, and In Vitro Evaluation of New (99m)Tc/Re(V)-Cyclized Octreotide Analogues: An Experimental and Computational Approach.

PubMed

Li, Yawen; Ma, Lixin; Gaddam, Vikram; Gallazzi, Fabio; Hennkens, Heather M; Harmata, Michael; Lewis, Michael R; Deakyne, Carol A; Jurisson, Silvia S

2016-02-01

Radiolabeled proteolytic degradation-resistant somatostatin analogues have been of long-standing interest as cancer imaging and radiotherapy agents for targeting somatostatin receptor-positive tumors. Our interest in developing (186)Re- and (188)Re-based therapeutic radiopharmaceuticals led to investigation of a new Re(V)-cyclized octreotide analogue, Re(V)-cyclized, thiolated-DPhe(1)-Cys(2)-Tyr(3)-DTrp(4)-Lys(5)-Thr(6)-Cys(7)-Thr(OH)(8) (Re-SDPhe-TATE) using both experimental and quantum chemical methods. The metal is directly coordinated to SDPhe-TATE through cyclization of the peptide around the [ReO](3+) core. Upon complexation, four isomers were observed; the isolated/semi-isolated isomers exhibited different somatostatin receptor (sstr) binding affinities, 0.13 to 1.5 μM, in rat pancreatic tumor cells. Two-dimensional NMR experiments and electronic structure calculations were employed to elucidate the structural differences among the different isomers. According to NMR studies, the metal is coordinated to three thiolates and the backbone amide of Cys(2) in isomers 1 and 4, whereas the metal is coordinated to three thiolates and the backbone amide of Tyr(3) in isomer 2. Quantum chemical methods clarified the stereochemistry of Re-SDPhe-TATE and the possible peptide arrangements around the [ReO](3+) core. The re-cyclization reaction was translated to the (99m)Tc radiotracer level with four isomers observed on complexation with comparable HPLC retention times as the Re-SDPhe-TATE isomers. About 85% total (99m)Tc labeling yield was achieved by ligand exchange from (99m)Tc-glucoheptonate at 60 °C for an hour. About 100% and 51% of (99m)Tc(V)-cyclized SDPhe-TATE remained intact in phosphate buffered saline and 1 mM cysteine solution under physiological conditions at 6 h, respectively.

Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

PubMed

Kagna, Olga; Pirmisashvili, Natalia; Tshori, Sagi; Freedman, Nanette; Israel, Ora; Krausz, Yodphat

2014-12-01

Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

Somatostatin sst2 receptor-mediated inhibition of parietal cell function in rat isolated gastric mucosa.

PubMed Central

Wyatt, M. A.; Jarvie, E.; Feniuk, W.; Humphrey, P. P.

1996-01-01

1. The aim of this study was to determine the location and functional characteristics of the somatostatin (SRIF) receptor type(s) which mediate inhibition of acid secretion in rat isolated gastric mucosa. 2. Gastrin (1 nM-1 microM), dimaprit (10 microM-300 microM) and isobutyl methylxanthine (IBMX, 1 microM-100 microM) all caused concentration-dependent increases in acid output. Responses to gastrin were almost completely inhibited by ranitidine (10 microM) at a concentration which abolished the secretory response to dimaprit. In contrast, responses to IBMX were not changed by ranitidine suggesting that IBMX acts directly on the parietal cell and not indirectly by releasing histamine from enterochromaffin-like (ECL) cells. 3. SRIF-14 (1 nM-1 microM) had no effect on basal acid output, but inhibited acid output produced by gastrin, dimaprit and IBMX in a concentration-dependent manner with respective EC50 values of 46, 54 and 167 nM. The peptidase inhibitors, amastatin (10 microM) and phosphoramidon (1 microM), had no effect on SRIF-induced inhibition of dimaprit stimulated gastric acid secretion. 4. The inhibitory effect of a range of SRIF analogues on gastrin-, dimaprit- and IBMX-induced acid secretion was also studied. Irrespective of the secretagogue used to increase acid output, the rank order of potencies was similar (BIM-23027 = seglitide = octreotide > SRIF-14 = SRIF-28 > L-362,855). The linear peptide BIM-23056 was devoid of agonist or antagonist activity in concentrations up to 1 microM. 5. The sst2 receptor selective peptides, BIM-23027, seglitide and octreotide were the most potent inhibitors of gastrin-, dimaprit- and IBMX-induced acid secretion suggesting that SRIF receptors resembling the recombinant sst2 receptors are involved. Furthermore, since dimaprit and IBMX stimulate gastric acid secretion independently of histamine release, sst2 receptor-mediated inhibition must occur at the level of the parietal cell itself. PMID:8922739

Somatostatin sst2 receptor-mediated inhibition of parietal cell function in rat isolated gastric mucosa.

PubMed

Wyatt, M A; Jarvie, E; Feniuk, W; Humphrey, P P

1996-11-01

1. The aim of this study was to determine the location and functional characteristics of the somatostatin (SRIF) receptor type(s) which mediate inhibition of acid secretion in rat isolated gastric mucosa. 2. Gastrin (1 nM-1 microM), dimaprit (10 microM-300 microM) and isobutyl methylxanthine (IBMX, 1 microM-100 microM) all caused concentration-dependent increases in acid output. Responses to gastrin were almost completely inhibited by ranitidine (10 microM) at a concentration which abolished the secretory response to dimaprit. In contrast, responses to IBMX were not changed by ranitidine suggesting that IBMX acts directly on the parietal cell and not indirectly by releasing histamine from enterochromaffin-like (ECL) cells. 3. SRIF-14 (1 nM-1 microM) had no effect on basal acid output, but inhibited acid output produced by gastrin, dimaprit and IBMX in a concentration-dependent manner with respective EC50 values of 46, 54 and 167 nM. The peptidase inhibitors, amastatin (10 microM) and phosphoramidon (1 microM), had no effect on SRIF-induced inhibition of dimaprit stimulated gastric acid secretion. 4. The inhibitory effect of a range of SRIF analogues on gastrin-, dimaprit- and IBMX-induced acid secretion was also studied. Irrespective of the secretagogue used to increase acid output, the rank order of potencies was similar (BIM-23027 = seglitide = octreotide > SRIF-14 = SRIF-28 > L-362,855). The linear peptide BIM-23056 was devoid of agonist or antagonist activity in concentrations up to 1 microM. 5. The sst2 receptor selective peptides, BIM-23027, seglitide and octreotide were the most potent inhibitors of gastrin-, dimaprit- and IBMX-induced acid secretion suggesting that SRIF receptors resembling the recombinant sst2 receptors are involved. Furthermore, since dimaprit and IBMX stimulate gastric acid secretion independently of histamine release, sst2 receptor-mediated inhibition must occur at the level of the parietal cell itself.

SiRNA-Mediated Down-Regulation of CLIC4 Gene Inhibits Cell Proliferation and Accelerates Cell Apoptosis of Mouse Liver Cancer Hca-F and Hca-P Cells.

PubMed

Yu, Qiu-Yun; Zhou, Xin-Feng; Xia, Qing; Shen, Jia; Yan, Jia; Zhu, Jiu-Ting; Li, Xiang; Shu, Ming

2018-01-01

This study explored the effects involved in silencing CLIC4 on apoptosis and proliferation of mouse liver cancer Hca-F and Hca-P cells. A CLIC4-target small interfering RNA (siRNA) was designed to compound into two individual complementary oligonucleotide chains. A process of annealing and connection to a pSilencer vector was followed by transfection with Hca-F and Hca-P cells. Quantitative real-time polymerase chain reaction and Western blotting techniques were used to determine CLIC4 mRNA and protein expressions. CCK8 assay and flow cytometry were employed for analysis of the survival and apoptosis rate as well as the cell cycle in an octreotide-induced apoptosis model. Expressions of caspase 3, caspase 9, and cleaved PARP were measured using Western blotting. The CLIC4 mRNA and protein expressions in Hca-F and Hca-P cells transfected by pSilencer-CLIC4 siRNA plasmid in the blank group displayed remarkably decreased levels of expression, when compared with both the control and negative control (NC) groups. Decreased survival rates and cleaved PARP expression, increased cell apoptosis rate,expressions of caspase 3 and caspase 9 in Hca-F and Hca-P cells were detected in groups that had been cultured in a medium containing octreotide. The pSilencer-CLIC4 siRNA-2 group when compared with the control and NC groups exhibited decreased survival rates, cleaved PARP expression, increased cell apoptosis rates, and increased expressions of caspase 3 and caspase 9 of Hca-F and Hca-P cells. The results demonstrated that siRNA-induced down-regulation of CLIC4 could proliferation, while in turn promoting apoptosis of mouse liver cancer Hca-F and Hca-P cells. J. Cell. Biochem. 119: 659-668, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Acromegaly Presenting With Bilateral Vocal Fold Immobility: Case Report and Review of the Literature.

PubMed

Cooper, Timothy; Dziegielewski, Peter T; Singh, Praby; Seemann, Robert

2016-11-01

To present a case of bilateral vocal fold immobility (BVCI) in a patient with acromegaly and review the current literature describing this presentation. Case report and literature review. Academic tertiary care center. English language literature search of online journal databases. A 56-year-old man presented with 3 months of progressive stridor and shortness of breath. Transnasal flexible endoscopy revealed BVCI. A tracheostomy was performed to secure his airway. Further history was suggestive of acromegaly and imaging demonstrated a pituitary macroadenoma. The diagnosis of acromegaly was made. The patient was treated with octreotide followed by an endoscopic trans sphenoidal resection of the pituitary adenoma. Sixteen months after his initial presentation, a right laser arytenoidectomy was performed and the patient was subsequently decannulated. In the literature to date, 11 cases of BVCI in acromegaly have been reported. These patients often present with stridor and require a tracheostomy. With treatment of their acromegaly, these patients may regain vocal fold mobility and may be decannulated. Acromegaly with BVCI is a rare presentation. Acute management of the airway of patients with acromegaly presenting with BVCI typically requires a tracheostomy. A period of 15 months should be allowed for restoration of vocal fold mobility before airway opening procedures are considered. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Novel Somatostatin Receptor Ligands Therapies for Acromegaly

PubMed Central

Paragliola, Rosa Maria; Salvatori, Roberto

2018-01-01

Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs) octreotide (OCT), lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed. These include both new formulation of older molecules and new molecules. Novel OCT formulations are aimed in particular to improve patients’ compliance and to reduce injection discomfort. They include an investigational ready-to-use subcutaneous depot OCT formulation (CAM2029), delivered via prefilled syringes and oral OCT that uses a “transient permeability enhancer” technology, which allows for OCT oral absorption. Another new delivery system is a long-lasting OCT implant (VP-003), which provide stable doses of OCT throughout a period of several months. Finally, a new SRL DG3173 (somatoprim) seems to be more selective for GH secretion, suggesting possible advantages in the presence of hyperglycemia or diabetes. How much these innovations will actually be beneficial to acromegaly patients in real clinical practice remains to be seen. PMID:29563895

Palliative Management of Malignant Bowel Obstruction in Terminally Ill Patient

PubMed Central

Thaker, Darshit A; Stafford, Bruce C; Gaffney, Luke S

2010-01-01

Mr. P was a 57-year-old man who presented with symptoms of bowel obstruction in the setting of a known metastatic pancreatic cancer. Diagnosis of malignant bowel obstruction was made clinically and radiologically and he was treated conservatively (non-operatively)with octreotide, metoclopromide and dexamethasone, which provided good control over symptoms and allowed him to have quality time with family until he died few weeks later with liver failure. Bowel obstruction in patients with abdominal malignancy requires careful assessment. The patient and family should always be involved in decision making. The ultimate goals of palliative care (symptom management, quality of life and dignity of death) should never be forgotten during decision making for any patient. PMID:21811356

(99m)Tc-HYNIC-TOC scintigraphy in evaluation of active Graves' ophthalmopathy (GO).

PubMed

Sun, Hua; Jiang, Xu-Feng; Wang, Shu; Chen, Hao-Yan; Sun, Jiao; Li, Pei-Yong; Ning, Guang; Zhao, Yong-Ju

2007-06-01

A promising radiopharmaceutical (99m)Tc-HYNIC-TOC ((99m)Tc-HYNIC-Octreotide) can be applied for somatostatin receptor scintigraphy with the potential to replace Indium-111 labeled somatostatin analogus. Here we evaluate whether orbital (99m)Tc-HYNIC-TOC scintigraphy can be used as a Graves' ophthalmopathy (GO) activity parameter to predict the retrobulbar irradiation response. Orbital (99m)Tc-HYNIC-TOC scintigraphy was performed on 14 consecutive patients demonstrating moderated to severe Graves' ophthalmopathy. The patients were treated with retrobulbar irradiation following the octreoscan and the response to this therapy was assessed at 3 months after the start of treatment. The orbital (99m)Tc-HYNIC-TOC uptake was calculated to assess the effects of treatment. Among the 14 GO patients, eight (57.1%) responded to retrobulbar radiotherapy; six (42.9%) showed no change. We compared the eight responders and six non-responders in terms of orbital (99m)Tc-HYNIC-TOC uptake, using the orbital/occipital ratio. On the 4-h (99m)Tc-HYNIC-TOC scintigraphy, responders had a higher orbital/occipital uptake ratio than the no-responders (P = 0.001). A significant correlation was found between the orbital/occipital ratio and the clinical activity score (CAS) (P = 0.034). The Receiving-Operator-Characteristic curve showed the best threshold for discriminating active and inactive disease was 1.40 (sensitivity, 100%; specificity, 83.3%). In the responders group, all these eight patients had positive scintigraphy. While there were five patients who had negative scintigraphy in the non-responders group. Orbital (99m)Tc-HYNIC-TOC scintigraphy can be a useful method for the estimation of disease activity and prediction the response to subsequent radiotherapy in GO patient. And the patients with positive octreoscan were more likely to respond to irradiation.

Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms.

PubMed

Baum, Richard P; Kulkarni, Harshad R; Carreras, Cecilia

2012-05-01

Theranostics of neuroendocrine neoplasms (NENs) based on molecular imaging using receptor positron emission tomography/computed tomography (PET/CT) with (68)Ga-labeled somatostatin (SMS) analogs and molecular radiotherapy applying peptide receptor radionuclide therapy (PRRNT) with (90)Y- and/or (177)Lu-labeled peptides has paved the way to personalized medicine. SMS receptor PET/CT enables very accurate detection of NENs and their metastases with high diagnostic sensitivity and specificity and provides quantitative, reproducible data that can be used for selecting patients for PRRNT and evaluation of therapy response. Among other advantages are the fast imaging protocol (total study time, 60-90 minutes), low radiation burden (10-12 mSv), flexibility in daily use, and lower cost than octreotide scintigraphy. As we move toward personalized medicine, the diagnostic information obtained from PET/CT must be improved, that is, by fast routine quantification of lesions. PRRNT is highly effective for the treatment of NENs, even in very advanced cases, and lends a benefit in overall survival of several years. In addition, significant improvement in clinical symptoms and excellent palliation can be achieved. In patients with progressive NENs, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period (Bad Berka Concept) results in good therapeutic responses. By this concept, severe hematologic and/or renal toxicity can be reduced or completely avoided, and the quality of life can be improved. Sequential (DUO-PRRNT) and concurrent (TANDEM-PRRNT) administrations of radiopeptides are more effective in progressive NEN than using either radionuclide alone. PRRNT should only be performed at specialized centers, as NEN patients need highly individualized interdisciplinary treatment and long-term care. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of a Framework Based on Reflective MCDA to Support Patient-Clinician Shared Decision-Making: The Case of the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the United States.

PubMed

Wagner, Monika; Samaha, Dima; Khoury, Hanane; O'Neil, William M; Lavoie, Louis; Bennetts, Liga; Badgley, Danielle; Gabriel, Sylvie; Berthon, Anthony; Dolan, James; Kulke, Matthew H; Goetghebeur, Mireille

2018-01-01

Well- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making. The framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing. The framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option. Patients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives. Ipsen Pharma.

20 CFR 10.313 - Will OWCP pay for preventive treatment?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Will OWCP pay for preventive treatment? 10..., AS AMENDED Medical and Related Benefits Medical Treatment and Related Issues § 10.313 Will OWCP pay for preventive treatment? The FECA does not authorize payment for preventive measures such as vaccines...

20 CFR 10.313 - Will OWCP pay for preventive treatment?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Will OWCP pay for preventive treatment? 10.313... AMENDED Medical and Related Benefits Medical Treatment and Related Issues § 10.313 Will OWCP pay for preventive treatment? The FECA does not authorize payment for preventive measures such as vaccines and...

20 CFR 10.313 - Will OWCP pay for preventive treatment?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Will OWCP pay for preventive treatment? 10.313... AMENDED Medical and Related Benefits Medical Treatment and Related Issues § 10.313 Will OWCP pay for preventive treatment? The FECA does not authorize payment for preventive measures such as vaccines and...

Position of nuclear medicine techniques in the diagnostic work-up of neuroendocrine tumors.

PubMed

Bombardieri, E; Seregni, E; Villano, C; Chiti, A; Bajetta, E

2004-06-01

In recent years nuclear medicine has contributed to the impressive development of the knowledge of neuroendocrine tumors in terms of biology (receptor scintigraphy), pharmacology (development of new tracers), and therapy (radiometabolic therapy). At present, it is impossible to plan the management of a patient affected by a neuroendocrine tumor without performing nuclear medicine examinations. The contribution of nuclear medicine had affected and improved the management of these patients by offering various important options that are part of the modern diagnosis and treatment protocols. The clinical experience and the literature confirm that, among the wide variety of tracers and nuclear medicine modalities available today, metaiodobenzylguanidine (MIBG) and DTPA-D-Phe-octreotide (pentetreotide) are the radiopharmaceuticals of current clinical use. Several new somatostatin analogues are under investigation. Positron emission tomography (PET) supplies a range of labelled compounds to be used for the visualization of tumor biochemistry. In addition to the first routinely used PET tracer in oncology, 18F-labelled deoxyglucose (FDG), a number of radiopharmaceuticals based on different precursors such as fluorodopamine and 5-hydroxytryptophan (5-HTP) are going to gain a clinical role. Of course, the diagnosis of neuroendocrine tumors has to be based on integrated information derived from different examinations including nuclear medicine studies. The clinical presentation of neuroendocrine tumors is highly variable: sometimes they manifest typical or atypical symptoms but they may also be detected by chance during an X-ray or ultrasound examination carried out for other reasons. At disease presentation nuclear medicine modalities are sometimes able to direct physicians towards the clinical diagnosis thanks to the specificity of their imaging mechanisms. They also play a role in disease staging and restaging, patient follow-up and treatment monitoring. In addition, the biological characterisation of neuroendocrine tissues (receptor status, glucose metabolism, differentiation, etc.) allows the interpretation of radiopharmaceutical uptake as a prognostic parameter and sometimes as a predictor of the response to treatment.

Somatostatin and its 2A receptor in dorsal root ganglia and dorsal horn of mouse and human: expression, trafficking and possible role in pain

PubMed Central

2014-01-01

Background Somatostatin (SST) and some of its receptor subtypes have been implicated in pain signaling at the spinal level. In this study we have investigated the role of SST and its sst2A receptor (sst2A) in dorsal root ganglia (DRGs) and spinal cord. Results SST and sst2A protein and sst2 transcript were found in both mouse and human DRGs, sst2A-immunoreactive (IR) cell bodies and processes in lamina II in mouse and human spinal dorsal horn, and sst2A-IR nerve terminals in mouse skin. The receptor protein was associated with the cell membrane. Following peripheral nerve injury sst2A-like immunoreactivity (LI) was decreased, and SST-LI increased in DRGs. sst2A-LI accumulated on the proximal and, more strongly, on the distal side of a sciatic nerve ligation. Fluorescence-labeled SST administered to a hind paw was internalized and retrogradely transported, indicating that a SST-sst2A complex may represent a retrograde signal. Internalization of sst2A was seen in DRG neurons after systemic treatment with the sst2 agonist octreotide (Oct), and in dorsal horn and DRG neurons after intrathecal administration. Some DRG neurons co-expressed sst2A and the neuropeptide Y Y1 receptor on the cell membrane, and systemic Oct caused co-internalization, hypothetically a sign of receptor heterodimerization. Oct treatment attenuated the reduction of pain threshold in a neuropathic pain model, in parallel suppressing the activation of p38 MAPK in the DRGs Conclusions The findings highlight a significant and complex role of the SST system in pain signaling. The fact that the sst2A system is found also in human DRGs and spinal cord, suggests that sst2A may represent a potential pharmacologic target for treatment of neuropathic pain. PMID:24521084

Cancer treatment - preventing infection

MedlinePlus

... preventing infection; Bone marrow transplant - preventing infection; Cancer treatment - immunosuppression ... types of cancer, such as leukemia, and some treatments including bone marrow transplant and chemotherapy affect your ...

Probiotics: their role in the treatment and prevention of disease.

PubMed

Doron, Shira; Gorbach, Sherwood L

2006-04-01

A probiotic is a "live microbial food ingredients that, when ingested in sufficient quantities, exerts health benefits on the consumer". Probiotics exert their benefits through several mechanisms; they prevent colonization, cellular adhesion and invasion by pathogenic organisms, they have direct antimicrobial activity and they modulate the host immune response. The strongest evidence for the clinical effectiveness of probiotics has been in their use for the prevention of symptoms of lactose intolerance, treatment of acute diarrhea, attenuation of antibiotic-associated gastrointestinal side effects and the prevention and treatment of allergy manifestations. More research needs to be carried out to clarify conflicting findings on the use of probiotics for prevention of travelers' diarrhea, infections in children in daycare and dental caries, and elimination of nasal colonization with potentially pathogenic bacteria. Promising ongoing research is being conducted on the use of probiotics for the treatment of Clostridium difficile colitis, treatment of Helicobacter pylori infection, treatment of inflammatory bowel disease and prevention of relapse, treatment of irritable bowel syndrome, treatment of intestinal inflammation in cystic fibrosis patients, and prevention of necrotizing enterocolitis in premature infants. Finally, areas of future research include the use of probiotics for the treatment of rheumatoid arthritis, prevention of cancer and the treatment of graft-versus-host disease in bone marrow transplant recipients.

Preventive Migraine Treatment

PubMed Central

Silberstein, Stephen D.

2015-01-01

Purpose of Review: This article reviews the evidence base for the preventive treatment of migraine. Recent Findings: Evidence-based guidelines for the preventive treatment of migraine have recently been published by the American Academy of Neurology (AAN) and the Canadian Headache Society (CHS), providing valuable guidance for clinicians. Strong evidence exists to support the use of metoprolol, timolol, propranolol, divalproex sodium, sodium valproate, and topiramate for migraine prevention, according to the AAN. Based on best available evidence, adverse event profile, and expert consensus, topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan, Petasites (butterbur), riboflavin, coenzyme Q10, and magnesium citrate received a strong recommendation for use from the CHS. Summary: Migraine preventive drug treatments are underutilized in clinical practice. Principles of preventive treatment are important to improve compliance, minimize side effects, and improve patient outcomes. Choice of preventive treatment of migraine should be based on the presence of comorbid and coexistent illness, patient preference, reproductive potential and planning, and best available evidence. PMID:26252585

HIV Treatment as Prevention: Natural Experiments Highlight Limits of Antiretroviral Treatment as HIV Prevention

PubMed Central

Wilson, David P.

2012-01-01

There is growing enthusiasm for increasing coverage of antiretroviral treatment among HIV-infected people for the purposes of preventing ongoing transmission. Treatment as prevention will face a number of barriers when implemented in real world populations, which will likely lead to the effectiveness of this strategy being lower than proposed by optimistic modelling scenarios or ideal clinical trial settings. Some settings, as part of their prevention and treatment strategies, have already attained rates of HIV testing and use of antiretroviral therapy—with high levels of viral suppression—that many countries would aspire to as targets for a treatment-as-prevention strategy. This review examines a number of these “natural experiments”, namely, British Columbia, San Francisco, France, and Australia, to provide commentary on whether treatment as prevention has worked in real world populations. This review suggests that the population-level impact of this strategy is likely to be considerably less than as inferred from ideal conditions. PMID:22807656

Exposure Plus Response-Prevention Treatment of Bulimia Nervosa.

ERIC Educational Resources Information Center

Leitenberg, Harold; And Others

1988-01-01

Evaluated exposure plus response-prevention treatment of bulimia nervosa among 47 women. Subjects were assigned to either exposure plus response-prevention in one setting, exposure plus response-prevention in multiple settings, cognitive-behavioral therapy, or waiting-list control conditions. Found three treatment groups improved significantly on…

Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

PubMed

Havermans, Remco C; Jansen, Anita T M

2003-07-01

Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjögren's syndrome treated with Infliximab: a pilot study.

PubMed

Anzola-Fuentes, L K; Chianelli, M; Galli, F; Glaudemans, A W J M; Martin Martin, L; Todino, V; Migliore, A; Signore, A

2016-12-01

Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue ((99m)Tc-EDDA/tricine-HYNIC-tyr(3)-octreotide ((99m)Tc-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjögren's syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment. Eighteen patients with rheumatoid arthritis and secondary Sjögren's syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-α. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer's test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3-6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of (99m)Tc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively. All patients showed uptake of (99m)Tc-EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands. SRS using (99m)Tc-EDDA/HYNIC-TOC may be a useful imaging tool to assess disease activity and extent in patients with rheumatoid arthritis and may help to detect secondary Sjögren's syndrome. It may also aid therapy decision-making with anti-TNFα antibodies in the joints but not in salivary glands.

Social Justice and HIV Vaccine Research in the Age of Pre-Exposure Prophylaxis and Treatment as Prevention

PubMed Central

Bailey, Theodore C.; Sugarman, Jeremy

2014-01-01

The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297

45 CFR 96.46 - Substance abuse prevention and treatment services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Substance abuse prevention and treatment services... BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.46 Substance abuse prevention... organizations under the substance abuse prevention and treatment Block Grant. (b) For the purpose of determining...

45 CFR 96.46 - Substance abuse prevention and treatment services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Substance abuse prevention and treatment services... BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.46 Substance abuse prevention... organizations under the substance abuse prevention and treatment Block Grant. (b) For the purpose of determining...

45 CFR 96.46 - Substance abuse prevention and treatment services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Substance abuse prevention and treatment services... BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.46 Substance abuse prevention... organizations under the substance abuse prevention and treatment Block Grant. (b) For the purpose of determining...

45 CFR 96.46 - Substance abuse prevention and treatment services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Substance abuse prevention and treatment services... BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.46 Substance abuse prevention... organizations under the substance abuse prevention and treatment Block Grant. (b) For the purpose of determining...

45 CFR 96.46 - Substance abuse prevention and treatment services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Substance abuse prevention and treatment services... BLOCK GRANTS Direct Funding of Indian Tribes and Tribal Organizations § 96.46 Substance abuse prevention... organizations under the substance abuse prevention and treatment Block Grant. (b) For the purpose of determining...

Prevention and Treatment of Esophageal Stenosis after Endoscopic Submucosal Dissection for Early Esophageal Cancer

PubMed Central

Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

2014-01-01

Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward. PMID:25386186

Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

PubMed

MacLean, Joanna E; Cohen, Eyal; Weinstein, Michael

2002-06-01

Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

Severe Refractory Anemia in Primary Intestinal Lymphangiectasia. A Case Report.

PubMed

Balaban, Vasile Daniel; Popp, Alina; Grasu, Mugur; Vasilescu, Florina; Jinga, Mariana

2015-09-01

Primary intestinal lymphangiectasia (Waldmann's disease) is a rare disease characterized by dilated lymphatics in the small bowel leading to an exudative enteropathy with lymphopenia, hypoalbuminemia and hypogammaglobulinemia. We report the case of a 23 year-old male who presented with chronic anemia and in whom primary intestinal lymphangiectasia was diagnosed. A low-fat diet along with nutritional therapy with medium-chain triglyceride supplementation improved the protein-losing enteropathy, but did not solve the anemia. Octreotide was also unsuccessful, and after attempting angiographic embolization therapy, limited small bowel resection together with antiplasmin therapy managed to correct the anemia and control the exudative enteropathy. Although primary intestinal lymphangiectasia is usually adequately managed by nutritional therapy, complications such as anemia can occur and can prove to be a therapeutic challenge.

Limitations and pitfalls of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) scintigraphy.

PubMed

Garai, Ildikó; Barna, Sandor; Nagy, Gabor; Forgacs, Attila

2016-01-01

Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005, 99mTc-EDDA/HYNIC-Tyr3-Octreotide has been used in clinical imaging and achieved high impact in management of patients with neuroendocrine tumors. Knowing the limitations and pitfalls is essential to provide ac-curate diagnosis. Therefore, the potential pitfalls associated with the use of 99mTc-EDDA/HYNIC-TOC are reviewed on the basis of own experience. Data were analyzed of 310 patients who underwent somatostatin receptor scintigraphy with 99mTc-Tektrotyd. Pitfalls during radiolabeling process or acquisition can worsen the sensitivity of SRS (somatostatin receptor scintigraphy). Recognizing physi-ological and clinical pitfalls, the diagnostic accuracy will improve.

Co-delivery of doxorubicin and siRNA using octreotide-conjugated gold nanorods for targeted neuroendocrine cancer therapy

NASA Astrophysics Data System (ADS)

Xiao, Yuling; Jaskula-Sztul, Renata; Javadi, Alireza; Xu, Wenjin; Eide, Jacob; Dammalapati, Ajitha; Kunnimalaiyaan, Muthusamy; Chen, Herbert; Gong, Shaoqin

2012-10-01

A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers.A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers. Electronic supplementary information (ESI) available: Additional flow cytometry histogram profiles of DOX fluorescence and ASCL1 knockdown results. See DOI: 10.1039/c2nr31853a

Prevention literacy: community-based advocacy for access and ownership of the HIV prevention toolkit.

PubMed

Parker, Richard G; Perez-Brumer, Amaya; Garcia, Jonathan; Gavigan, Kelly; Ramirez, Ana; Milnor, Jack; Terto, Veriano

2016-01-01

Critical technological advances have yielded a toolkit of HIV prevention strategies. This literature review sought to provide contextual and historical reflection needed to bridge the conceptual gap between clinical efficacy and community effectiveness (i.e. knowledge and usage) of existing HIV prevention options, especially in resource-poor settings. Between January 2015 and October 2015, we reviewed scholarly and grey literatures to define treatment literacy and health literacy and assess the current need for literacy related to HIV prevention. The review included searches in electronic databases including MEDLINE, PsycINFO, PubMed, and Google Scholar. Permutations of the following search terms were used: "treatment literacy," "treatment education," "health literacy," and "prevention literacy." Through an iterative process of analyses and searches, titles and/or abstracts and reference lists of retrieved articles were reviewed for additional articles, and historical content analyses of grey literature and websites were additionally conducted. Treatment literacy was a well-established concept developed in the global South, which was later partially adopted by international agencies such as the World Health Organization. Treatment literacy emerged as more effective antiretroviral therapies became available. Developed from popular pedagogy and grassroots efforts during an intense struggle for treatment access, treatment literacy addressed the need to extend access to underserved communities and low-income settings that might otherwise be excluded from access. In contrast, prevention literacy is absent in the recent surge of new biomedical prevention strategies; prevention literacy was scarcely referenced and undertheorized in the available literature. Prevention efforts today include multimodal techniques, which jointly comprise a toolkit of biomedical, behavioural, and structural/environmental approaches. However, linkages to community advocacy and mobilization efforts are limited and unsustainable. Success of prevention efforts depends on equity of access, community-based ownership, and multilevel support structures to enable usage and sustainability. For existing HIV prevention efforts to be effective in "real-world" settings, with limited resources, reflection on historical lessons and contextual realities (i.e. policies, financial constraints, and biomedical patents) indicated the need to extend principles developed for treatment access and treatment literacy, to support prevention literacy and prevention access as an integral part of the global response to HIV.

75 FR 78997 - Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

... on HIV and STD Prevention and Treatment: Notice of Charter Renewal This gives notice under the... on HIV and STD Prevention and Treatment, Department of Health and Human Services, has been renewed...., PhD, Designated Federal Officer, CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment...

64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients.

PubMed

Pfeifer, Andreas; Knigge, Ulrich; Binderup, Tina; Mortensen, Jann; Oturai, Peter; Loft, Annika; Berthelsen, Anne Kiil; Langer, Seppo W; Rasmussen, Palle; Elema, Dennis; von Benzon, Eric; Højgaard, Liselotte; Kjaer, Andreas

2015-06-01

Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of (64)Cu-DOTATATE and (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide ((111)In-DTPA-OC) as a basis for implementing (64)Cu-DOTATATE as a routine. We prospectively enrolled 112 patients with pathologically confirmed NETs of gastroenteropancreatic or pulmonary origin. All patients underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with (111)In-DTPA-OC within 60 d. PET scans were acquired 1 h after injection of 202 MBq (range, 183-232 MBq) of (64)Cu-DOTATATE after a diagnostic contrast-enhanced CT scan. Patients were followed for 42-60 mo for evaluation of discrepant imaging findings. The McNemar test was used to compare the diagnostic performance. Eighty-seven patients were congruently PET- and SPECT-positive. No SPECT-positive cases were PET-negative, whereas 10 false-negative SPECT cases were identified using PET. The diagnostic sensitivity and accuracy of (64)Cu-DOTATATE (97% for both) were significantly better than those of (111)In-DTPA-OC (87% and 88%, respectively, P = 0.017). In 84 patients (75%), (64)Cu-DOTATATE identified more lesions than (111)In-DTPA-OC and always at least as many. In total, twice as many lesions were detected with (64)Cu-DOTATATE than with (111)In-DTPA-OC. Moreover, in 40 of 112 cases (36%) lesions were detected by (64)Cu-DOTATATE in organs not identified as disease-involved by (111)In-DTPA-OC. With these results, we demonstrate that (64)Cu-DOTATATE is far superior to (111)In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of (64)Cu-DOTATATE as a replacement for (111)In-DTPA-OC. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy.

PubMed

Kiviniemi, Aida; Gardberg, Maria; Frantzén, Janek; Pesola, Marko; Vuorinen, Ville; Parkkola, Riitta; Tolvanen, Tuula; Suilamo, Sami; Johansson, Jarkko; Luoto, Pauliina; Kemppainen, Jukka; Roivainen, Anne; Minn, Heikki

2015-01-01

High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our purpose was to evaluate the potential of (68)Ga-DOTA-1-Nal(3)-octreotide ((68)Ga-DOTANOC) or (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTATOC) to target SSTR subtype 2 (SSTR2) in HGGs, and to study the association between SSTR2 expression and established biomarkers. Twenty-seven patients (mean age 52 years) with primary or recurrent HGG prospectively underwent (68)Ga-DOTA-peptide positron emission tomography/computed tomography (PET/CT) before resection. Maximum standardized uptake values (SUVmax) and receptor binding potential (BP) were calculated on PET/CT and disruption of blood-brain barrier (BBB) from contrast-enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume concordance between PET and MRI-T1-Gad was assessed by Dice similarity coefficient (DC) and correlation by Spearman's rank. Immunohistochemically determined SSTR2 status was compared to receptor imaging findings, prognostic biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and multivariate Cox regression, respectively. All 19 HGGs with disrupted BBB demonstrated tracer uptake. Tumor SUVmax (2.25 ± 1.33) correlated with MRI-T1-Gad (r = 0.713, P = 0.001) although DC 0.41 ± 0.19 suggested limited concordance. SSTR2 immunohistochemistry was regarded as positive in nine HGGs (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR2 expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P = 0.015). In HGGs, uptake of (68)Ga-DOTA-peptides is associated with disrupted BBB and cannot be predicted by SSTR2 immunohistochemistry. Thus, PET/CT shows limited value to detect HGGs suitable for PRRT. However, high SSTR2 expression portends favorable outcome along with established biomarkers such as IDH1 mutation. ClinicalTrials.gov NCT01460706.

E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors.

PubMed

Lubner, Sam; Feng, Yang; Mulcahy, Mary; O'Dwyer, Peter; Giang, Guang-Yu; Louis Hinshaw, J; Deming, Dustin; Klein, Leonard; Teitelbaum, Ursina; Payne, Jennifer; Engstrom, Paul; Stella, Philip; Meropol, Neal; Benson, Al

2018-05-31

Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial.Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints. Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively). This was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%-2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS). Forty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1-2. Median PFS was 8.7 months, and overall survival was 27.5 months. Motesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3-4 toxicities were encountered. The progression-free survival of 8.7 months in all NETs merits further study. The Oncologist 2018. © AlphaMed Press 2018.

An unusual case of ectopic ACTH syndrome.

PubMed

Willhauck, M J; Pöpperl, G; Rachinger, W; Giese, A; Auernhammer, C J; Spitzweg, C

2012-02-01

Ectopic ACTH-syndrome is a rare cause of Cushing's disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult. This case describes a 45-year old woman with an ectopic Cushing's syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion. In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing's syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms. During follow-up a [(68)Ga-DOTA-dPhe(1), Tyr(3)]-octreotate ([(68)Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor. This case report demonstrates the management of ectopic ACTH-syndrome by molecularly -targeted therapy with dopamine receptor -agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [(68)Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver.

PubMed

Ando, Hitoshi; Ushijima, Kentaro; Shimba, Shigeki; Fujimura, Akio

2016-02-01

Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production-related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon.

Imaging features of carcinoid tumors metastatic to the breast.

PubMed

Glazebrook, Katrina N; Jones, Katie N; Dilaveri, Christina A; Perry, Kyle; Reynolds, Carol

2011-06-29

The objective of this study was to describe the imaging findings of carcinoid tumors metastatic to the breast, with pathologic and clinical correlations. We searched our surgical database for cases of pathologically proven carcinoid tumors metastatic to the breast from October 1, 2000, to May 31, 2010. Of the approximate 10,000 breast biopsies identified, 7000 had malignant findings. Ten cases of metastatic carcinoid (0.1% of all malignancies), all with imaging studies available for review, were included in the study. All patients were women and had their primary carcinoid in the gastrointestinal tract (n=9) or lung (n = 1). One patient presented with a palpable breast mass and no history of carcinoid tumor; an ileal carcinoid was discovered after the pathologic diagnosis of metastatic carcinoid was established. In the breast, tumors presented as solitary lesions in half the cases. Metastases to the breast typically presented as circumscribed masses mammographically and as hypoechoic circumscribed masses ultrasonographically; some showed increased through-transmission and increased vascularity with color Doppler evaluation. Five patients had octreotide scans; of these, 4 had increased focal activity in the region of metastasis within the breast. Six patients underwent computed tomography. Without contrast, nodular masses were observed; with contrast, the masses showed rapid enhancement during arterial phase imaging. Magnetic resonance imaging (n = 4) also showed rapid enhancement and washout kinetics after contrast administration. Recognition of carcinoid metastases to the breast in patients with known or occult primary carcinoid tumors is important to avoid unnecessary treatment for primary breast cancer.

Dual tracer functional imaging of gastroenteropancreatic neuroendocrine tumors using 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT: competitive or complimentary?

PubMed

Naswa, Niraj; Sharma, Punit; Gupta, Santosh Kumar; Karunanithi, Sellam; Reddy, Rama Mohan; Patnecha, Manish; Lata, Sneh; Kumar, Rakesh; Malhotra, Arun; Bal, Chandrasekhar

2014-01-01

This study aimed to compare the diagnostic performance of Ga-DOTANOC PET/CT with F-FDG PET/CT in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Data of 51 patients with definite histological diagnosis of GEP-NET who underwent both Ga-DOTA-NOC PET-CT and F-FDG PET-CT within a span of 15 days were selected for this retrospective analysis. Sensitivity, specificity, and predictive values were calculated for Ga-DOTA-NOC PET-CT and F-FDG PET-CT, and results were compared both on patientwise and regionwise analysis. Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT on patientwise analysis (P < 0.0001). On regionwise analysis, Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT only for lymph node metastases (P < 0.003). Although Ga-DOTA-NOC PET-CT detected more liver and skeletal lesions compared with F-FDG PET-CT, the difference was not statistically significant. In addition, the results of combined imaging helped in selecting candidates who would undergo the appropriate mode of treatment, whether octreotide therapy or conventional chemotherapy Ga-DOTA-NOC PET-CT seems to be superior to F-FDG PET-CT for imaging GEP-NETs. However, their role seems to be complementary because combination of Ga-DOTA-NOC PET-CT and F-FDG PET-CT in such patients helps demonstrate the total disease burden and segregate them to proper therapeutic groups.

Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

PubMed

Zimmerman, D; Young, W F; Ebersold, M J; Scheithauer, B W; Kovacs, K; Horvath, E; Whitaker, M D; Eberhardt, N L; Downs, T R; Frohman, L A

1993-01-01

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.

78 FR 64221 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment; Notice of Meeting In... Hepatitis and STD Prevention and Treatment Dates and Times: November 13, 2013, 10:00 a.m.-4:30 p.m. November... Administrator, HRSA, regarding activities related to prevention and control of HIV/AIDS, Viral Hepatitis and...

Pressure ulcer prevention and treatment knowledge of Jordanian nurses.

PubMed

Saleh, Mohammad Y N; Al-Hussami, Mahmoud; Anthony, Denis

2013-02-01

The aims of the study were to determine: (1) Jordanian nurses' level of knowledge of pressure ulcer prevention and treatment of hospitalized patients based on guidelines for pressure ulcer prevention and treatment. (2) Frequency of utilization of pressure ulcer prevention and treatment interventions in clinical practice. (3) Variables that are associated with nurses' utilization of pressure ulcer prevention and treatment interventions. Pressure ulcers are common and previous studies have shown education, knowledge and attitude affect implementation of interventions. A cross-sectional survey design was used to collect data from 460 nurses between June 2010 and November 2010. We used a questionnaire, which was informed by earlier work and guidelines, to collect data about nurses' knowledge and practice of pressure ulcer prevention and treatment. Knowledge and education show an association with implementation of prevention, and demographic variables do not. Similarly knowledge and type of hospital showed an association with implementing treatment. Of concern the use of "donuts" and massage are reported in use. Although pressure ulcer care is well known by nurses, inappropriate pressure ulcer interventions were reported in use. Copyright © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Dental treatment and caries prevention preceding treatment under general anaesthesia in healthy children and adolescents: a retrospective cohort study.

PubMed

Grindefjord, M; Persson, J; Jansson, L; Tsilingaridis, G

2018-04-01

This was to examine healthy children and adolescents treated under general anaesthesia (GA) and a matched control group not receiving GA to compare treatment and preventive care received prior to GA treatment. This retrospective cohort study included 71 healthy subjects and 213 age- and gender-matched control subjects. The treatment group had been consecutively referred from the Public Dental Health Service (PDS) in Stockholm to the Department of Paediatric Dentistry, Eastman Institute, Stockholm during 2006-2007. Data was extracted from the patient records at the PDS, including variables such as number of dental visits, treatment/prophylaxis prior to GA, number of missed and cancelled appointments, and number of decayed teeth. On average, the treatment group had significantly more decayed teeth (p < 0.001) than the control group. Furthermore, the treatment group had significantly more restorations (p < 0.01), had visited the dentist significantly more often (p < 0.001), and had undergone significantly more behaviour management treatment and preventive treatment (p < 0.001). In the treatment group 65% of the children and adolescents, had received no behaviour management treatment and 48%, no preventive treatment. In the Stockholm PDS, over half of the children and adolescents referred by general dentists to paediatric specialists had no behaviour management treatment and nearly half, no preventive treatment, despite receiving significantly more operative treatment compared with matched controls. General dentists should target high caries-risk patients for additional behaviour management and preventive care to reduce the need for treatment under GA.

Monitoring latent tuberculosis infection diagnosis and management in the Netherlands.

PubMed

Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; de Vries, Gerard; Cobelens, Frank; van den Hof, Susan

2016-05-01

Targeted diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) among persons with a high risk of exposure to TB or of developing TB when infected has been performed and monitored routinely in the Netherlands since 1993. We describe trends in target groups, diagnostic methods and treatment regimens, and explore determinants for treatment initiation, treatment completion and adverse events.In total, 37 729 persons were registered with LTBI from 1993 to 2013, of whom 28 931 (77%) started preventive treatment; 82% of those completed preventive treatment and 8% stopped preventive treatment due to adverse events. Two-thirds of the notified cases were detected through contact investigation.Increasing numbers of persons with immunosuppressive disorders, elderly persons and foreign-born persons were notified in recent years, due to policy changes and the introduction of the interferon-γ release assay. Children (96%) and the immunosuppressed (95%) were more likely to start preventive treatment. Children (93%) were also more likely to complete preventive treatment, as were persons treated with rifampicin or rifampicin/isoniazid regimens (91% and 92%, respectively). The latter groups were also 40% less likely to stop preventive treatment due to adverse events.Under these operational conditions, the estimated risk reduction on incident TB in the target population for LTBI management is 40-60%. Copyright ©ERS 2016.

45 CFR 1340.14 - Eligibility requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States... child abuse or neglect. (h) Prevention and treatment services. The State must demonstrate that it has...

45 CFR 1340.14 - Eligibility requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States... child abuse or neglect. (h) Prevention and treatment services. The State must demonstrate that it has...

45 CFR 1340.14 - Eligibility requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States... child abuse or neglect. (h) Prevention and treatment services. The State must demonstrate that it has...

45 CFR 1340.14 - Eligibility requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States... child abuse or neglect. (h) Prevention and treatment services. The State must demonstrate that it has...

45 CFR 1340.14 - Eligibility requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States... child abuse or neglect. (h) Prevention and treatment services. The State must demonstrate that it has...

Prevention literacy: community-based advocacy for access and ownership of the HIV prevention toolkit

PubMed Central

Parker, Richard G; Perez-Brumer, Amaya; Garcia, Jonathan; Gavigan, Kelly; Ramirez, Ana; Milnor, Jack; Terto, Veriano

2016-01-01

Introduction Critical technological advances have yielded a toolkit of HIV prevention strategies. This literature review sought to provide contextual and historical reflection needed to bridge the conceptual gap between clinical efficacy and community effectiveness (i.e. knowledge and usage) of existing HIV prevention options, especially in resource-poor settings. Methods Between January 2015 and October 2015, we reviewed scholarly and grey literatures to define treatment literacy and health literacy and assess the current need for literacy related to HIV prevention. The review included searches in electronic databases including MEDLINE, PsycINFO, PubMed, and Google Scholar. Permutations of the following search terms were used: “treatment literacy,” “treatment education,” “health literacy,” and “prevention literacy.” Through an iterative process of analyses and searches, titles and/or abstracts and reference lists of retrieved articles were reviewed for additional articles, and historical content analyses of grey literature and websites were additionally conducted. Results and discussion Treatment literacy was a well-established concept developed in the global South, which was later partially adopted by international agencies such as the World Health Organization. Treatment literacy emerged as more effective antiretroviral therapies became available. Developed from popular pedagogy and grassroots efforts during an intense struggle for treatment access, treatment literacy addressed the need to extend access to underserved communities and low-income settings that might otherwise be excluded from access. In contrast, prevention literacy is absent in the recent surge of new biomedical prevention strategies; prevention literacy was scarcely referenced and undertheorized in the available literature. Prevention efforts today include multimodal techniques, which jointly comprise a toolkit of biomedical, behavioural, and structural/environmental approaches. However, linkages to community advocacy and mobilization efforts are limited and unsustainable. Success of prevention efforts depends on equity of access, community-based ownership, and multilevel support structures to enable usage and sustainability. Conclusions For existing HIV prevention efforts to be effective in “real-world” settings, with limited resources, reflection on historical lessons and contextual realities (i.e. policies, financial constraints, and biomedical patents) indicated the need to extend principles developed for treatment access and treatment literacy, to support prevention literacy and prevention access as an integral part of the global response to HIV. PMID:27702430

The cost of pressure ulcer prevention and treatment in hospitals and nursing homes in Flanders: A cost-of-illness study.

PubMed

Demarré, Liesbet; Verhaeghe, Sofie; Annemans, Lieven; Van Hecke, Ann; Grypdonck, Maria; Beeckman, Dimitri

2015-07-01

The economic impact of pressure ulcer prevention and treatment is high. The results of cost-of-illness studies can assist the planning, allocation, and priority setting of healthcare expenditures to improve the implementation of preventive measures. Data on the cost of current practice of pressure ulcer prevention or treatment in Flanders, a region of Belgium, is lacking. To examine the cost of pressure ulcer prevention and treatment in an adult population in hospitals and nursing homes from the healthcare payer perspective. A cost-of-illness study was performed using a bottom-up approach. Hospitals and nursing homes in Flanders, a region of Belgium. Data were collected in a series of prospective multicentre cross-sectional studies between 2008 and 2013. Data collection included data on risk assessment, pressure ulcer prevalence, preventive measures, unit cost of materials for prevention and treatment, nursing time measurements for activities related to pressure ulcer prevention and treatment, and nursing wages. The cost of pressure ulcer prevention and treatment in hospitals and nursing homes was calculated as annual cost for Flanders, per patient, and per patient per day. The mean (SD) cost for pressure ulcer prevention was €7.88 (8.21) per hospitalised patient at risk per day and €2.15 (3.10) per nursing home resident at risk per day. The mean (SD) cost of pressure ulcer prevention for patients and residents identified as not at risk for pressure ulcer development was €1.44 (4.26) per day in hospitals and €0.50 (1.61) per day in nursing homes. The main cost driver was the cost of labour, responsible for 79-85% of the cost of prevention. The mean (SD) cost of local treatment per patient per day varied between €2.34 (1.14) and €77.36 (35.95) in hospitals, and between €2.42 (1.15) and €16.18 (4.93) in nursing homes. Related to methodological differences between studies, the cost of pressure ulcer prevention and treatment in hospitals and nursing homes in Flanders was found to be low compared to other international studies. Recommendations specific to pressure ulcer prevention are needed as part of methodological guidelines to conduct cost-of-illness studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

An institutional analysis of HIV prevention efforts by the nation's outpatient drug abuse treatment units.

PubMed

D'Aunno, T; Vaughn, T E; McElroy, P

1999-06-01

Drawing from an institutional-theory perspective on innovations in organizations, this paper examines the use of human immunodeficiency virus (HIV) prevention practices by the nation's outpatient substance abuse treatment units during a critical period from 1988 to 1995. An institutional perspective argues that organizations adopt new practices not only for technical reasons, but also because external actors actively promote or model the use of particular practices. We examine the extent to which treatment units use several practices to prevent HIV infection among their clients and among drug-users not in treatment. Results from random-effects regression analyses of national survey data show that treatment units significantly increased their use of HIV prevention practices from 1988 to 1995. Further, the results show that treatment units' use of prevention practices was related to clients' risk for HIV infection, unit resources available to support these practices, and organizational support for the practices. Implications are discussed for an institutional view of organizational innovation as well as for research on HIV prevention.

Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial.

PubMed

Desai, Meghna; Gutman, Julie; L'lanziva, Anne; Otieno, Kephas; Juma, Elizabeth; Kariuki, Simon; Ouma, Peter; Were, Vincent; Laserson, Kayla; Katana, Abraham; Williamson, John; ter Kuile, Feiko O

2015-12-19

Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine. We did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941. Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine (n=515); 1368 (88%) women comprised the intention-to-treat population for the primary endpoint. Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15 [3%] of 457 women vs 47 [10%] of 459 women; relative risk 0·32, 95% CI 0·18-0·56; p<0·0001), but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1·23, 0·86-1·77; p=0·26). Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine, intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy (192·0 vs 54·4 events per 100 person-years; incidence rate ratio [IRR] 0·28, 95% CI 0·22-0·36; p<0·0001) and clinical malaria during pregnancy (37·9 vs 6·1 events; 0·16, 0·08-0·33; p<0·0001), whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection (232·0 events; 1·21, 1·03-1·41; p=0·0177) and clinical malaria (53·4 events; 1·41, 1·00-1·98; p=0·0475). We recorded 303 maternal and infant serious adverse events, which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group. At current levels of rapid diagnostic test sensitivity, intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission. However, dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies should investigate the efficacy, safety, operational feasibility, and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine. The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Head Lice: Treatment

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Body Lice Treatment

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Evidence of effectiveness of preventive dental care in reducing dental treatment use and related expenditures.

PubMed

Pourat, Nadereh; Choi, Moonkyung Kate; Chen, Xiao

2018-02-06

Preventive dental health services are intended to reduce the likelihood of development of tooth decay and the need for more intensive treatment overtime. The evidence on the effectiveness of preventive dental care in reducing treatment services and expenditures is lagging for adults, particularly those with lower incomes and chronic conditions. We assessed the impact of preventive dental services on dental treatment service use and expenditures overall and by category of service. We calculated the annual numbers of preventive (periodic diagnostic and prophylactic procedures) and treatment (restorative, surgery, prosthodontic, endodontic, and periodontic) services per beneficiary using Medicaid enrollment and claims data for beneficiaries with three categories of conditions (diabetes, heart disease, and respiratory disease) from 10 largest California counties. We used Cragg hurdle exponential regression models controlling for past service use, demographics, length of enrollment, and county. We found that using preventive services in 2005-2007 was associated with higher likelihood and number of treatment dental services used, but associated with lower treatment expenditures in 2008. The reduction in expenditures was noted only in restorative, prosthodontics, and periodontic services. The findings provide much needed evidence of the contribution of preventive dental care in maintaining oral health of low-income adults with chronic conditions and potential for savings to the Medicaid program. Providing lower cost preventive dental care to the individuals with chronic conditions would achieve better oral health and lower treatment expenditures. © 2018 American Association of Public Health Dentistry.

21 CFR 310.547 - Drug products containing quinine offered over-the-counter (OTC) for the treatment and/or...

Code of Federal Regulations, 2014 CFR

2014-04-01

...-counter (OTC) for the treatment and/or prevention of malaria. 310.547 Section 310.547 Food and Drugs FOOD... over-the-counter (OTC) for the treatment and/or prevention of malaria. (a) Quinine and quinine salts have been used OTC for the treatment and/or prevention of malaria, a serious and potentially life...

21 CFR 310.547 - Drug products containing quinine offered over-the-counter (OTC) for the treatment and/or...

Code of Federal Regulations, 2013 CFR

2013-04-01

...-counter (OTC) for the treatment and/or prevention of malaria. 310.547 Section 310.547 Food and Drugs FOOD... over-the-counter (OTC) for the treatment and/or prevention of malaria. (a) Quinine and quinine salts have been used OTC for the treatment and/or prevention of malaria, a serious and potentially life...

21 CFR 310.547 - Drug products containing quinine offered over-the-counter (OTC) for the treatment and/or...

Code of Federal Regulations, 2012 CFR

2012-04-01

...-counter (OTC) for the treatment and/or prevention of malaria. 310.547 Section 310.547 Food and Drugs FOOD... over-the-counter (OTC) for the treatment and/or prevention of malaria. (a) Quinine and quinine salts have been used OTC for the treatment and/or prevention of malaria, a serious and potentially life...

21 CFR 310.547 - Drug products containing quinine offered over-the-counter (OTC) for the treatment and/or...

Code of Federal Regulations, 2011 CFR

2011-04-01

...-counter (OTC) for the treatment and/or prevention of malaria. 310.547 Section 310.547 Food and Drugs FOOD... over-the-counter (OTC) for the treatment and/or prevention of malaria. (a) Quinine and quinine salts have been used OTC for the treatment and/or prevention of malaria, a serious and potentially life...

21 CFR 310.547 - Drug products containing quinine offered over-the-counter (OTC) for the treatment and/or...

Code of Federal Regulations, 2010 CFR

2010-04-01

...-counter (OTC) for the treatment and/or prevention of malaria. 310.547 Section 310.547 Food and Drugs FOOD... over-the-counter (OTC) for the treatment and/or prevention of malaria. (a) Quinine and quinine salts have been used OTC for the treatment and/or prevention of malaria, a serious and potentially life...

45 CFR 1340.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.1 Purpose and scope. (a) This part implements the Child Abuse Prevention and Treatment Act...

45 CFR 1340.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.1 Purpose and scope. (a) This part implements the Child Abuse Prevention and Treatment Act...

45 CFR 1340.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.1 Purpose and scope. (a) This part implements the Child Abuse Prevention and Treatment Act...

45 CFR 1340.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.1 Purpose and scope. (a) This part implements the Child Abuse Prevention and Treatment Act...

45 CFR 1340.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.1 Purpose and scope. (a) This part implements the Child Abuse Prevention and Treatment Act...

Pubic "Crab" Lice Treatment

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Outcomes Associated With Early Preventive Dental Care Among Medicaid-Enrolled Children in Alabama

PubMed Central

Morrisey, Michael A.; Sen, Bisakha

2017-01-01

Importance There is a recommendation for children to have a dental home by 6 months of age, but there is limited evidence supporting the effectiveness of early preventive dental care or whether primary care providers (PCPs) can deliver it. Objective To investigate the effectiveness of preventive dental care in reducing caries-related treatment visits among Medicaid enrollees. Design, Setting, and Participants High-dimensional propensity scores were used to address selection bias for a retrospective cohort study of children continuously enrolled in coverage from the Alabama Medicaid Agency from birth between 2008 and 2012, adjusting for demographics, access to care, and general health service use. Exposures Children receiving preventive dental care prior to age 2 years from PCPs or dentists vs no preventive dental care. Main Outcome and Measures Two-part models estimated caries-related treatment and expenditures. Results Among 19 658 eligible children, 25.8% (n = 3658) received early preventive dental care, of whom 44% were black, 37.6% were white, and 16.3% were Hispanic. Compared with matched children without early preventive dental care, children with dentist-delivered preventive dental care more frequently had a subsequent caries-related treatment (20.6% vs 11.3%, P < .001), higher rate of visits (0.29 vs 0.15 per child-year, P < .001), and greater dental expenditures ($168 vs $87 per year, P < .001). Dentist-delivered preventive dental care was associated with an increase in the expected number of caries-related treatment visits by 0.14 per child per year (95% CI, 0.11-0.16) and caries-related treatment expenditures by $40.77 per child per year (95% CI, $30.48-$51.07). Primary care provider–delivered preventive dental care did not significantly affect caries-related treatment use or expenditures. Conclusions and Relevance Children with early preventive care visits from dentists were more likely to have subsequent dental care, including caries-related treatment, and greater expenditures than children without preventive dental care. There was no association with subsequent caries-related treatment and preventive dental care from PCPs. We observed no evidence of a benefit of early preventive dental care, regardless of the provider. Additional research beyond administrative data may be necessary to elucidate any benefits of early preventive dental care. PMID:28241184

An incidentally found inflamed uterine myoma causing low abdominal pain, using Tc-99m-tektrotyd single photon emission computed tomography-CT hybrid imaging.

PubMed

Zandieh, Shahin; Schütz, Matthias; Bernt, Reinhard; Zwerina, Jochen; Haller, Joerg

2013-01-01

We report the case of a 50-year-old woman presented with a history of right hemicolectomy due to an ileocecal neuroendocrine tumor and left breast metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal pain, single photon emission computed tomography-computer tomography (SPECT-CT) was performed. There were no signs of recurrence on the SPECT-CT scan, but the patient was incidentally found to have an inflamed intramural myoma. We believe that the slightly elevated chromogranin A-level was caused by the hypertension that the patient presented. In the clinical context, this is a report of an inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging.

45 CFR 96.133 - Submission to Secretary of Statewide assessment of needs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.133 Submission to Secretary... description on current substance abuse prevention and treatment activities: (i) For fiscal year 1993, the... goals and objectives for improving substance abuse treatment and prevention activities and shall report...

45 CFR 96.133 - Submission to Secretary of Statewide assessment of needs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.133 Submission to Secretary... description on current substance abuse prevention and treatment activities: (i) For fiscal year 1993, the... goals and objectives for improving substance abuse treatment and prevention activities and shall report...

45 CFR 96.133 - Submission to Secretary of Statewide assessment of needs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.133 Submission to Secretary... description on current substance abuse prevention and treatment activities: (i) For fiscal year 1993, the... goals and objectives for improving substance abuse treatment and prevention activities and shall report...

42 CFR 54.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... TO STATES RECEIVING SUBSTANCE ABUSE PREVENTION AND TREATMENT BLOCK GRANTS AND/OR PROJECTS FOR... programs authorized under: (1) The Substance Abuse Prevention and Treatment (SAPT) Block Grant, 42 U.S.C... Grants, 42 U.S.C. 290cc-21 to 290cc-35 insofar as they fund substance abuse prevention and/or treatment...

45 CFR 96.133 - Submission to Secretary of Statewide assessment of needs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.133 Submission to Secretary... description on current substance abuse prevention and treatment activities: (i) For fiscal year 1993, the... goals and objectives for improving substance abuse treatment and prevention activities and shall report...

42 CFR 54.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... TO STATES RECEIVING SUBSTANCE ABUSE PREVENTION AND TREATMENT BLOCK GRANTS AND/OR PROJECTS FOR... programs authorized under: (1) The Substance Abuse Prevention and Treatment (SAPT) Block Grant, 42 U.S.C... Grants, 42 U.S.C. 290cc-21 to 290cc-35 insofar as they fund substance abuse prevention and/or treatment...

42 CFR 54.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... TO STATES RECEIVING SUBSTANCE ABUSE PREVENTION AND TREATMENT BLOCK GRANTS AND/OR PROJECTS FOR... programs authorized under: (1) The Substance Abuse Prevention and Treatment (SAPT) Block Grant, 42 U.S.C... Grants, 42 U.S.C. 290cc-21 to 290cc-35 insofar as they fund substance abuse prevention and/or treatment...

42 CFR 54.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... TO STATES RECEIVING SUBSTANCE ABUSE PREVENTION AND TREATMENT BLOCK GRANTS AND/OR PROJECTS FOR... programs authorized under: (1) The Substance Abuse Prevention and Treatment (SAPT) Block Grant, 42 U.S.C... Grants, 42 U.S.C. 290cc-21 to 290cc-35 insofar as they fund substance abuse prevention and/or treatment...

42 CFR 54.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... TO STATES RECEIVING SUBSTANCE ABUSE PREVENTION AND TREATMENT BLOCK GRANTS AND/OR PROJECTS FOR... programs authorized under: (1) The Substance Abuse Prevention and Treatment (SAPT) Block Grant, 42 U.S.C... Grants, 42 U.S.C. 290cc-21 to 290cc-35 insofar as they fund substance abuse prevention and/or treatment...

75 FR 10485 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... programs (programs that pay for substance abuse treatment and prevention services, not for certain... the services. The provisions apply to the Substance Abuse Prevention and Treatment Block Grant (SAPT... (OMB) as part of the Substance Abuse Prevention and Treatment Block Grant FY 2008-2010 annual...

Head Lice: Treatment Frequently Asked Questions (FAQs)

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Given Resource Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention

PubMed Central

Macklin, Ruth; Cowan, Ethan

2013-01-01

Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies preexposure prophylaxis and treatment as prevention—use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention. PMID:22778343

Health and Economic Implications of National Treatment Coverage for Cardiovascular Disease in India: Cost-Effectiveness Analysis.

PubMed

Basu, Sanjay; Bendavid, Eran; Sood, Neeraj

2015-11-01

Whether to cover cardiovascular disease costs is an increasingly pressing question for low- and middle-income countries. We sought to identify the impact of expanding national insurance to cover primary prevention, secondary prevention, and tertiary treatment for cardiovascular disease in India. We incorporated data from coverage experiments into a validated microsimulation model of myocardial infarction and stroke in India to evaluate the cost-effectiveness of alternate coverage strategies. Coverage of primary prevention alone saved 3.6 million disability-adjusted life-years (DALY) per annum at an incremental cost-effectiveness ratio of $469 per DALY averted when compared with the status quo of no coverage. Coverage of primary and secondary preventions was dominated by a strategy of covering primary prevention and tertiary treatment, which prevented 6.6 million DALYs at an incremental cost-effectiveness ratio of $2241 per DALY averted, when compared with that of primary prevention alone. The combination of all 3 categories yielded the greatest impact at an incremental cost per DALY averted of $5588 when compared with coverage of primary prevention plus tertiary treatment. When compared with the status quo of no coverage, coverage of all 3 categories of prevention/treatment yielded an incremental cost-effectiveness ratio of $1331 per DALY averted. In sensitivity analyses, coverage of primary preventive treatments remained cost-effective even if adherence and access to therapy were low, but tertiary coverage would require avoiding unnecessary procedures to remain cost-effective. Coverage of all 3 major types of cardiovascular treatment would be expected to have high impact and reasonable cost-effectiveness in India across a broad spectrum of access and adherence levels. © 2015 American Heart Association, Inc.

Overdose prevention in injecting opioid users: the role of substance abuse treatment and training programs.

PubMed

Sarasa-Renedo, Ana; Espelt, Albert; Folch, Cinta; Vecino, Carmen; Majó, Xavier; Castellano, Yolanda; Casabona, Jordi; Brugal, M Teresa

2014-01-01

Opioid overdose is still the first cause of preventable death among young men in Barcelona. Sound knowledge of opioid overdose prevention is important to avoid complications and deaths. This study aimed to identify the factors associated with limited knowledge of overdose prevention and to assess the possible effect of treatment and overdose prevention training programs on this variable. From October 2008 to March 2009, current injecting opioid users attending harm reduction centers in Catalonia (Spain) were interviewed. Crude and adjusted prevalence ratios of limited knowledge about overdose prevention were calculated by adjusting Poisson regression models with a robust variance. In this sample, 28.7% of clients had limited knowledge of overdose prevention. Factors associated with limited knowledge were country of origin, never having received treatment for drug dependency, having a low educational level, and never having experienced an overdose. In contrast, treatment at the time of the interview was not associated with a lower prevalence of limited knowledge about overdose prevention. These findings suggest that preventive programs would benefit from accounting for linguistic and educational limitations and from participation in every treatment episode. Comprehensiveness and broad coverage of such programs could help to maximize their impact. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Treatment and Prevention of Acute Diarrhoea. Guidelines for the Trainers of Health Workers.

ERIC Educational Resources Information Center

World Health Organization, Geneva (Switzerland).

This booklet, intended primarily for the trainers of middle-level community health workers in underdeveloped countries, is designed to help such workers present the topic of diarrhea treatment and prevention in training courses. Divided into five sections, the booklet gives guidelines on treatment and prevention, with particular emphasis on the…

76 FR 49500 - Privacy Act of 1974; Department of Homeland Security United States Coast Guard-020 Substance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

... system of records titled, ``DHS/USCG-020 Substance Abuse Prevention and Treatment Program System of.../United States Coast Guard--020 Substance Abuse Prevention and Treatment Program System of Records. In... Substance Abuse Prevention and Treatment program, including to identify alcohol and drug abusers within the...

[The international communication and cooperation of prevention and treatment of epidemics in the Republican period of China].

PubMed

Zhang, Tai-shan

2008-07-01

During the Republican period of China, either the Northern Warlords Government or the National Government at Nanking, to different extent, all conducted international communication and cooperation in the prevention and treatment of epidemics. Firstly, they communicated and cooperated with International League in epidemic information, establishment of new health organization, health investigation and prevention and treatment of epidemics. Secondly, with WHO in epidemic information, live prevention and treatment of epidemics and personnel training. In addition, with international medical academic society by the initiative means of selecting and sending returned students abroad, dispatching overseas staff to study and attend international academic meeting. These communications and cooperations not only created good circumstances of international society for the prevention and treatment of epidemics in the Republican period of China, but also open a special window for the mutual understanding between China and the world, at the same time, promoted and reinforced independent research and development forces of prevention and treatment technology of infectious disease of our nation. Unfortunately, the inherent defects of the society of Republic of China greatly detracted from the effects of these endeavor.

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

PubMed Central

Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

2010-01-01

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

Reauthorization of the Child Abuse Prevention and Treatment and Adoption Reform Act. Hearings before the Subcommittee on Select Education of the Committee on Education and Labor, House of Representatives, 97th Congress, First Session on H.R. 2318 to Reauthorize the Child Abuse Prevention and Treatment and Adoption Reform Act (Washington, DC, March 9 and 12, 1981).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The document contains the transcript of the congressional hearings on H.R. 2318 to extend authorizations of appropriations for programs established in the Child Abuse Prevention and Treatment Act and the Child Abuse Prevention and Treatment and Adoption Reform Act of 1978. Among the individuals presenting statements are the following: A. Cohn on…

Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm.

PubMed

Vijay, Anantha; Santhanam, R; Katusic, Zvonimir S

2006-10-01

Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.

The Roles of Behavioral and Social Science Research in the Fight Against HIV/AIDS: A Functional Framework.

PubMed

Gaist, Paul; Stirratt, Michael J

2017-08-01

Landmark advances have been made in HIV/AIDS prevention and treatment. These include proof-of-concept and public health implementation of preexposure prophylaxis and "treatment as prevention" to reduce HIV transmission as well as definitive evidence of the clinical gain from early antiretroviral treatment initiation. Significant progress has been made in understanding and addressing the social contexts and behavioral factors that impact HIV prevention, care, and treatment interventions. These include facilitating uptake of testing and counseling, developing technology-based interventions that increase viral suppression, reducing HIV/AIDS-related stigma, and addressing other sociobehavioral and structural barriers to care and treatment. This evolving landscape provides an important juncture to assess current and future directions for HIV/AIDS behavioral and social science research (BSSR). We propose a functional framework for HIV/AIDS-related BSSR, highlighting 4 primary BSSR domains: (1) understanding vulnerable populations and contexts of risk ("Basic BSSR"); (2) improving behavioral and social factor approaches to risk reduction, prevention, and care ("Elemental BSSR"); (3) strengthening the design and outcomes of biomedically focused research in HIV/AIDS treatment and prevention ("Supportive BSSR"); and (4) contributing building blocks to integrated HIV/AIDS prevention and treatment approaches ("Integrative BSSR"). These domains and their resulting confluence at the highest level underscore how fundamental and essential BSSR is to current and future efforts to prevent, treat, and cure HIV/AIDS.

Cognitive-Behavioral and Response-Prevention Treatments for Bulimia Nervosa.

ERIC Educational Resources Information Center

Agras, W. Stewart; And Others

1989-01-01

Assessed treatment for bulimia nervosa among 77 female patients assigned to wait-list control, self-monitoring of caloric intake and purging behaviors, cognitive-behavioral treatment, and cognitive-behavioral treatment plus response prevention of vomiting. All treatment groups showed significant improvement; control group did not.…

Can DCE-MRI Explain the Heterogeneity in Radiopeptide Uptake Imaged by SPECT in a Pancreatic Neuroendocrine Tumor Model?

PubMed Central

Groen, Harald C.; Niessen, Wiro J.; Bernsen, Monique R.; de Jong, Marion; Veenland, Jifke F.

2013-01-01

Although efficient delivery and distribution of treatment agents over the whole tumor is essential for successful tumor treatment, the distribution of most of these agents cannot be visualized. However, with single-photon emission computed tomography (SPECT), both delivery and uptake of radiolabeled peptides can be visualized in a neuroendocrine tumor model overexpressing somatostatin receptors. A heterogeneous peptide uptake is often observed in these tumors. We hypothesized that peptide distribution in the tumor is spatially related to tumor perfusion, vessel density and permeability, as imaged and quantified by DCE-MRI in a neuroendocrine tumor model. Four subcutaneous CA20948 tumor-bearing Lewis rats were injected with the somatostatin-analog 111In-DTPA-Octreotide (50 MBq). SPECT-CT and MRI scans were acquired and MRI was spatially registered to SPECT-CT. DCE-MRI was analyzed using semi-quantitative and quantitative methods. Correlation between SPECT and DCE-MRI was investigated with 1) Spearman’s rank correlation coefficient; 2) SPECT uptake values grouped into deciles with corresponding median DCE-MRI parametric values and vice versa; and 3) linear regression analysis for median parameter values in combined datasets. In all tumors, areas with low peptide uptake correlated with low perfusion/density/ /permeability for all DCE-MRI-derived parameters. Combining all datasets, highest linear regression was found between peptide uptake and semi-quantitative parameters (R2>0.7). The average correlation coefficient between SPECT and DCE-MRI-derived parameters ranged from 0.52-0.56 (p<0.05) for parameters primarily associated with exchange between blood and extracellular extravascular space. For these parameters a linear relation with peptide uptake was observed. In conclusion, the ‘exchange-related’ DCE-MRI-derived parameters seemed to predict peptide uptake better than the ‘contrast amount- related’ parameters. Consequently, fast and efficient diffusion through the vessel wall into tissue is an important factor for peptide delivery. DCE-MRI helps to elucidate the relation between vascular characteristics, peptide delivery and treatment efficacy, and may form a basis to predict targeting efficiency. PMID:24116203

77 FR 64809 - Announcement of the Award of a Single-Source Replacement Grant to the University of Colorado...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... Denver, Kempe Center for the Prevention and Treatment of Child Abuse & Neglect AGENCY: Children's Bureau... Colorado Denver, Kempe Center for the Prevention and Treatment of Child Abuse & Neglect. SUMMARY: The..., Kempe Center for the Prevention and Treatment of Child Abuse & Neglect (Kempe Center), Denver, CO, an...

75 FR 26258 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

... approved vaccines or antiviral drugs for the treatment or prevention of B19V infection. The subject... infectious B19V virus. Applications: VLPs based vaccines for the prevention and/or treatment of B19V infection DNA based vaccines for the prevention and/or treatment of B19V infection B19V diagnostics Viral...

Folliculitis keloidalis nuchae and pseudofolliculitis barbae: are prevention and effective treatment within reach?

PubMed

Alexis, Andrew; Heath, Candrice R; Halder, Rebat M

2014-04-01

Pseudofolliculitis barbae and folliculitis keloidalis nuchae are chronic follicular disorders disproportionately affecting men of African ancestry. This article explores the etiology, pathogenesis, treatment, and prevention strategies of these conditions. Effective treatment and prevention of these disorders involves pharmacologic and procedural interventions as well as behavioral modifications. Copyright © 2014 Elsevier Inc. All rights reserved.

77 FR 66469 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-05

... Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment In accordance with section 10(a...--Treatment as Prevention; (2) Ryan White HIV/AIDS Program Client Level Data Update; (3) Viral Hepatitis... Person for More Information: Margie Scott-Cseh, National Center for HIV/AIDS, Viral Hepatitis, STD, and...

Integrated prevention services for HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use drugs illicitly: summary guidance from CDC and the U.S. Department of Health and Human Services.

PubMed

2012-11-09

This report summarizes current (as of 2011) guidelines or recommendations published by multiple agencies of the U.S. Department of Health and Human Services (DHHS) for prevention and control of human immunodeficiency virus (HIV) infection, viral hepatitis, sexually transmitted diseases (STDs), and tuberculosis (TB) for persons who use drugs illicitly. It also summarizes existing evidence of effectiveness for practices to support delivery of integrated prevention services. Implementing integrated services for prevention of HIV infection, viral hepatitis, STDs, and TB is intended to provide persons who use drugs illicitly with increased access to services, to improve timeliness of service delivery, and to increase effectiveness of efforts to prevent infectious diseases that share common risk factors, behaviors, and social determinants. This guidance is intended for use by decision makers (e.g., local and federal agencies and leaders and managers of prevention and treatment services), health-care providers, social service providers, and prevention and treatment support groups. Consolidated guidance can strengthen efforts of health-care providers and public health providers to prevent and treat infectious diseases and substance use and mental disorders, use resources efficiently, and improve health-care services and outcomes in persons who use drugs illicitly. An integrated approach to service delivery for persons who use drugs incorporates recommended science-based public health strategies, including 1) prevention and treatment of substance use and mental disorders; 2) outreach programs; 3) risk assessment for illicit use of drugs; 4) risk assessment for infectious diseases; 5) screening, diagnosis, and counseling for infectious diseases; 6) vaccination; 7) prevention of mother-to-child transmission of infectious diseases; 8) interventions for reduction of risk behaviors; 9) partner services and contact follow-up; 10) referrals and linkage to care; 11) medical treatment for infectious diseases; and 12) delivery of integrated prevention services. These strategies are science-based, public health strategies to prevent and treat infectious diseases, substance use disorders, and mental disorders. Treatment of infectious diseases and treatment of substance use and mental disorders contribute to prevention of transmission of infectious diseases. Integrating prevention services can increase access to and timeliness of prevention and treatment.

Head Lice: Diagnosis

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Body Lice Diagnosis

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

HIV treatment as prevention: how scientific discovery occurred and translated rapidly into policy for the global response.

PubMed

Cohen, Myron S; Holmes, Charles; Padian, Nancy; Wolf, Megan; Hirnschall, Gottfried; Lo, Ying-Ru; Goosby, Eric

2012-07-01

In 2011 interim results of HIV Prevention Trials Network study 052, a National Institutes of Health study designed to test the effectiveness of antiretroviral treatment against the spread of HIV, were reported. These results showed that in a stable relationship in which one member of the couple was infected with HIV, treatment of the infected partner with antiretroviral drugs, combined with couples counseling and condom use, resulted in a 96 percent reduction in sexual transmission of HIV-1. This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention. Independent advisory committees of the President's Emergency Plan for AIDS Relief (PEPFAR) and the World Health Organization (WHO) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention. This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospective new trials to test how best to maximize the benefits of early treatment for prevention.

Clinical utility of apixaban in the prevention and treatment of venous thromboembolism: current evidence

PubMed Central

Zalpour, Ali; Oo, Thein Hlaing

2014-01-01

Anticoagulation with heparin and vitamin K antagonist has been the mainstay of prevention and treatment of venous thromboembolism (VTE) for many years. In recent years, novel oral anticoagulants such as dabigatran etexilate (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (a direct factor Xa inhibitor) have emerged for the prevention and treatment of VTE. Novel oral anticoagulants have been shown to be noninferior to vitamin K antagonist or heparin in the prevention and treatment of VTE. This review specifically examines the role of apixaban in the prevention and treatment of VTE based on the available literature. The management of apixaban in the perioperative setting is also explored because some patients on apixaban may require surgical intervention. Finally, we discuss the management of apixaban-induced major bleeding complications, the relevance of drug–drug interactions, and patient education. PMID:25395835

Pubic "Crab" Lice Diagnosis

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... announced below concerns Epidemiology, Prevention, and Treatment of Influenza and Other Respiratory..., Prevention, and Treatment of Influenza and Other Respiratory Infections in a Malaria-Endemic Area of Malawi...

77 FR 23733 - CDC/HRSA Advisory Committee on HIV and STD Prevention and Treatment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... Discussed: Agenda items include: (1) Enhancing Hepatitis Prevention Treatment and Care in the United States... Information: Margie Scott-Cseh, CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention...

Prevention of myopia by partial correction of hyperopia: a twins study.

PubMed

Medina, Antonio

2018-04-01

To confirm the prediction of emmetropization feedback theory that myopia can be prevented by correcting the hyperopia of a child at risk of becoming myopic. We conducted such myopia prevention treatment with twins at risk. Their hyperopia was partially corrected by one half at age 7 and in subsequent years until age 16. Hyperopia progressively decreased in all eyes as expected. None of the twins developed myopia. The spherical equivalent refractions of the followed eyes were +1 and +1.25 D at age 16. Feedback theory accurately predicted these values. The treatment of the twins with partial correction of their hyperopia was successful. Prevention of myopia with this technique is relatively simple and powerful. The use of this myopia prevention treatment has no adverse effects. This prevention treatment is indicated in children with a hyperopic reserve at risk of developing myopia.

Episodic migraines in children: limited evidence on preventive pharmacological treatments.

PubMed

Shamliyan, Tatyana A; Kane, Robert L; Ramakrishnan, Rema; Taylor, Frederick R

2013-10-01

The authors conducted a systematic literature review of preventive pharmacological treatments for episodic childhood migraines searching several databases through May 20, 2012. Episodic migraine prevention was examined in 24 publications of randomized controlled trials that enrolled 1578 children in 16 nonrandomized studies. Single randomized controlled trials provided low-strength evidence that propranolol would result in complete cessation of migraine attacks in 713 per 1000 children treated (95% confidence interval, 452-974); trazodone and nimodipine decreased migraine days, while topiramate, divalproex, and clonidine were no more effective than placebo in preventing migraines. Migraine prevention with multidisciplinary drug management was not sustained at 6 months. Divalproex resulted in treatment discontinuation due to adverse effects, and topiramate increased the risk of paresthesia, upper respiratory tract infection, and weight loss. Long-term preventive benefits and improvement in disability and quality of life are unknown. No studies examined quality of life or provided evidence for individualized treatment decisions.

Growth hormone-Insulin-like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune-Albright Syndrome.

PubMed

Tessaris, Daniele; Boyce, Alison M; Zacharin, Margaret; Matarazzo, Patrizia; Lala, Roberto; De Sanctis, Luisa; Collins, Michael T

2018-04-19

In fibrous dysplasia (BFD), normal bone and bone marrow are replaced by fibro-osseous tissue, leading to fracture, deformity and pain. BFD may be isolated, or in association with cutaneous hyperpigmentation and/or hyperfunctioning endocrinopathies, termed McCune-Albright syndrome (MAS). GH hypersecretion has been described in 10%-20% of MAS-BFD patients. Aim of the study was to determine the impact of GH-insulin like growth factor 1 (IGF1) axis hyperactivity on MAS-BFD morbidities and the efficacy of GH excess therapy. A multicentric cross-sectional analysis was conducted on three different MAS cohorts. From 195 MAS patients, 37 subjects (19%) with GH excess were identified and compared with 34 MAS controls without GH hypersecretion. Mean head circumference SDS was significantly higher in GH excess: 4.025 SDS vs 0.683 SDS (P < .0001). The risk of optic neuropathy (Odds ratio 4.231; P = .039), hearing deficit (Odds ratio 2.961; P = .0481), facial asymmetry (Odds ratio 6.563; P = .0192), malignancies (Odds ratio 15.24; P = .0173) were higher in GH excess group. Overall, pharmacotherapy (octreotide alone 10-30 mg/mo or with pegvisomant 10-20 mg/d) was effective in IGF1 normalization (IGF1 Z-score between -2 and +2 SDS) in 21/29 patients (72.4%) with good compliance to the regimen. Late diagnosis and GH excess treatment after 16 years old of age was associated with an increased risk of optic neuropathy (Odds ratio 4.500; P = .0491) and growth of pituitary adenomas (Odds ratio 7.846; P = .050). GH-IGF1 hyperactivity increases risk of morbidities in MAS. Medical therapy is effective in normalizing IGF1 in most patients, and early treatment during paediatric age is associated with a decreased risk of optic neuropathy and GH-secreting adenomas growth. © 2018 John Wiley & Sons Ltd.

Insights from a national survey into why substance abuse treatment units add prevention and outreach services

PubMed Central

Wells, Rebecca; Lemak, Christy Harris; D'Aunno, Thomas A

2006-01-01

Background Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. Results A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Conclusion Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of supervisor graduate education on likelihood of adding new prevention and outreach programs suggests that leaders' education can affect organizational strategy. Foundation and government officials may encourage prevention and outreach by funding curricular enhancements to graduate degree programs demonstrating the importance of public goods. Overall, these findings suggest that both money and professional education affect substance abuse treatment unit additions of prevention and outreach services, as well as other factors less amenable to policy intervention. PMID:16887037

Insights from a national survey into why substance abuse treatment units add prevention and outreach services.

PubMed

Wells, Rebecca; Lemak, Christy Harris; D'Aunno, Thomas A

2006-08-03

Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of supervisor graduate education on likelihood of adding new prevention and outreach programs suggests that leaders' education can affect organizational strategy. Foundation and government officials may encourage prevention and outreach by funding curricular enhancements to graduate degree programs demonstrating the importance of public goods. Overall, these findings suggest that both money and professional education affect substance abuse treatment unit additions of prevention and outreach services, as well as other factors less amenable to policy intervention.

Scabies: Treatment

MedlinePlus

... Information Scabies FAQs Workplace FAQs Epidemiology & Risk Factors Biology Disease Diagnosis Treatment Prevention & Control Resources for Health Professionals Medications Institutional Settings Prevention ...

Prevention of Portal Hypertension: from Variceal Development to Clinical Decompensation

PubMed Central

Vorobioff, Julio D.; Groszmann, Roberto J

2015-01-01

Pharmacological treatment of portal hypertension (PH) has been exclusively devoted to gastro-esophageal varices related events at different frameworks including prophylactic, emergency or preventive therapy. The goals of treatment are to avoid the first bleeding episode, stop active bleeding and prevent bleeding recurrence, respectively. The objective of pre-primary prophylaxis (PPP) is to avoid variceal development and therefore, it necessarily deals with cirrhotic patients at earlier stages of the disease. At these earlier stages, nonselective beta blocker (NSBB) have been ineffective in preventing the development of varices and other complications of PH. Therefore, treatment should not rely on NSBB. It is possible, that at these earlier stages, etiological treatment of liver disease itself could prevent the progression of PH. This review will focus mainly on early treatment of PH, because if successful, it may translate into histological-hemodynamic improvements, avoiding not only variceal development but also other PH related complications, such as ascites and porto-systemic encephalopathy (PSE). Moreover, the advent of new therapies may allow not only the prevention of the complications of PH, but also the chance of a substantial degree of regression in the cirrhotic process with the possible prevention of hepatocellular carcinoma (HCC). PMID:24913395

Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination.

PubMed

Lim, Aaron G; Qureshi, Huma; Mahmood, Hassan; Hamid, Saeed; Davies, Charlotte F; Trickey, Adam; Glass, Nancy; Saeed, Quaid; Fraser, Hannah; Walker, Josephine G; Mukandavire, Christinah; Hickman, Matthew; Martin, Natasha K; May, Margaret T; Averhoff, Francisco; Vickerman, Peter

2018-04-01

The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. With no further treatment (currently ∼150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan's HCV burden will increase markedly.

Head Lice: Malathion Frequently Asked Questions

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Head Lice: Frequently Asked Questions (FAQs)

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Body Lice Frequently Asked Questions (FAQs)

MedlinePlus

... Treatment FAQs Malathion FAQs Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ... Frequently Asked Questions (FAQs) Epidemiology & Risk Factors Disease Biology Diagnosis Treatment Prevention & Control Resources for Health Professionals ...

Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases.

PubMed

Koutsilieris, Michael; Mitsiades, Constantine S; Bogdanos, John; Dimopoulos, Theodoros; Karamanolakis, Dimitrios; Milathianakis, Constantine; Tsintavis, Athanassios

2004-07-01

Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy). Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days). Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse. The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.

Metastatic Neuroendocrine Tumour in a Renal Transplant Recipient: Dual-Tracer PET-CT with (18)F-FDG and (68)Ga-DOTANOC in This Rare Setting.

PubMed

Karunanithi, Sellam; Roy, Shambo Guha; Sharma, Punit; Yadav, Rajni; Bal, Chandrasekhar; Kumar, Rakesh

2015-03-01

Recipients of renal transplant are at increased risk of developing various malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and skin cancers. Neuroendocrine tumours (NET) of the gastrointestinal tract have not been reported in this setting. Here we describe the case of a 75-year-old male who had undergone renal transplant 8 years back and now presented with significant weight loss and backache, clinically suspected as PTLD. (18)F-Fluordeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) showed hypermetabolic lesions in the liver and rectum, raising the suspicion of PTLD. However, biopsy from the liver lesion showed poorly differentiated NET. (68)Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-octreotide ((68)Ga-DOTANOC) PET-CT was then done, which confirmed the primary lesion in the rectum with liver metastases.

The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.

PubMed Central

Tormey, W. P.; FitzGerald, R. J.

1995-01-01

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested. PMID:7479466

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

PubMed

Sampaziotis, Fotios; de Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh; Soares, Filipa A C; Schrumpf, Elisabeth; Melum, Espen; Karlsen, Tom H; Bradley, J Andrew; Gelson, William Th; Davies, Susan; Baker, Alastair; Kaser, Arthur; Alexander, Graeme J; Hannan, Nicholas R F; Vallier, Ludovic

2015-08-01

The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.

Recurrent malignant pheochromocytoma with unusual omental metastasis: 68Ga-DOTANOC PET/CT and 131I-MIBG SPECT/CT scintigraphy findings

PubMed Central

Arora, Saurabh; Agarwal, Krishan Kant; Karunanithi, Sellam; Tripathi, Madhavi; Kumar, Rakesh

2014-01-01

Pheochromocytomas are rare catecholamine-secreting tumors derived from the sympathetic nervous system. The most common sites of metastasis for pheochromocytoma or extra-adrenal paraganglioma are lymph nodes, bones, lungs, and liver. Patients with known or suspected malignancy should undergo staging with computed tomography (CT) or magnetic resonance imaging as well as functional imaging (e.g. with 123I/131I-MIBG (131I-metaiodobenzylguanidine) and 68Ga-DOTANOC (68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide) positron emission tomography (PET)/CT) to determine the extent and location of disease. We present a case of recurrent malignant pheochromocytoma with unusual site of metastasis in omentum, which was positive on 68Ga-DOTANOC PET/CT and 131I-MIBG single-photon emission computed tomography (SPECT/)/CT scintigraphy. PMID:25400380

Recurrent malignant pheochromocytoma with unusual omental metastasis: (68)Ga-DOTANOC PET/CT and (131)I-MIBG SPECT/CT scintigraphy findings.

PubMed

Arora, Saurabh; Agarwal, Krishan Kant; Karunanithi, Sellam; Tripathi, Madhavi; Kumar, Rakesh

2014-10-01

Pheochromocytomas are rare catecholamine-secreting tumors derived from the sympathetic nervous system. The most common sites of metastasis for pheochromocytoma or extra-adrenal paraganglioma are lymph nodes, bones, lungs, and liver. Patients with known or suspected malignancy should undergo staging with computed tomography (CT) or magnetic resonance imaging as well as functional imaging (e.g. with (123)I/(131)I-MIBG ((131)I-metaiodobenzylguanidine) and (68)Ga-DOTANOC ((68)Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide) positron emission tomography (PET)/CT) to determine the extent and location of disease. We present a case of recurrent malignant pheochromocytoma with unusual site of metastasis in omentum, which was positive on (68)Ga-DOTANOC PET/CT and (131)I-MIBG single-photon emission computed tomography (SPECT/)/CT scintigraphy.

Nanotechnology for the Prevention and Treatment of Cataract.

PubMed

Cetinel, Sibel; Montemagno, Carlo

2015-01-01

The purpose of this article was to review recent advances in the applications of nanotechnology in cataract treatment and prevention strategies. A literature review on the use of nanotechnology for the prevention and treatment of cataract was done. Research articles about nanotechnology-based treatments and prevention technologies for cataract were searched on Web of Science, and the most recent advances were reported. Nonsteroid anti-inflammatory drugs, natural antioxidants, biologic and chemical chaperones, and chaperones such as molecules have found great application in preventing and treating cataracts. Current scientific research on new treatment strategies, which focuses on the biochemical basis of the disease, will likely result in new anticataract agents. However, none of the drug formulations will be approved for use unless efficient delivery is promised. Nanoparticle engineering together with biomimetic strategies enable the development of next-generation, more efficient, less complex, and personalized treatments. The only currently available treatment for cataracts, surgical replacement of the opacified lens, is not an easily accessible option in developing countries. New treatment strategies based on topical drugs would enable treatment to reach massive populations facing the threat of blindness and more effectively deal with the postsurgical complications. Nanotechnology plays a key role in improving drug delivery systems with enhanced controlled release, targeted delivery, and bioavailability to overcome diffusion limitations in the eye.

Incorporating primary and secondary prevention approaches to address childhood obesity prevention and treatment in a low-income, ethnically diverse population

USDA-ARS?s Scientific Manuscript database

There is consensus that development and evaluation of a systems-oriented approach for child obesity prevention and treatment that includes both primary and secondary prevention efforts is needed. This article describes the study design and baseline data from the Texas Childhood Obesity Research Demo...

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

PubMed

Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Principled Missing Data Treatments.

PubMed

Lang, Kyle M; Little, Todd D

2018-04-01

We review a number of issues regarding missing data treatments for intervention and prevention researchers. Many of the common missing data practices in prevention research are still, unfortunately, ill-advised (e.g., use of listwise and pairwise deletion, insufficient use of auxiliary variables). Our goal is to promote better practice in the handling of missing data. We review the current state of missing data methodology and recent missing data reporting in prevention research. We describe antiquated, ad hoc missing data treatments and discuss their limitations. We discuss two modern, principled missing data treatments: multiple imputation and full information maximum likelihood, and we offer practical tips on how to best employ these methods in prevention research. The principled missing data treatments that we discuss are couched in terms of how they improve causal and statistical inference in the prevention sciences. Our recommendations are firmly grounded in missing data theory and well-validated statistical principles for handling the missing data issues that are ubiquitous in biosocial and prevention research. We augment our broad survey of missing data analysis with references to more exhaustive resources.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

PubMed

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-11-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

VEGF as a Survival Factor in Ex Vivo Models of Early Diabetic Retinopathy.

PubMed

Amato, Rosario; Biagioni, Martina; Cammalleri, Maurizio; Dal Monte, Massimo; Casini, Giovanni

2016-06-01

Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR. Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants. Data were obtained with real-time RT-PCR, Western blot, ELISA, and immunohistochemistry. Apoptosis was induced in the retinal explants by HG, OS, or AGE treatments. At the same time, explants also showed increased VEGF expression and release. The data revealed that VEGF is released shortly after exposure of the explants to stressors and before the level of cell death reaches its maximum. Retinal cell apoptosis was inhibited by OCT and PACAP. At the same time, OCT and PACAP also reduced VEGF expression and release. Vascular endothelial growth factor turned out to be a protective factor for the stressed retinal explants, because inhibiting VEGF with a VEGF trap further increased cell death. These data show that protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. These observations suggest that the retina in early DR releases VEGF as a prosurvival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.

ENERGY PRODUCTION AND POLLUTION PREVENTION AT SEWAGE TREATMENT PLANTS USING FUEL CELL POWER PLANTS

EPA Science Inventory

The paper discusses energy production and pollution prevention at sewage treatment plants using fuel cell power plants. Anaerobic digester gas (ADG) is produced at waste water treatment plants during the anaerobic treatment of sewage to reduce solids. The major constituents are...

Selecting a preventive maintenance treatment for flexible pavements

DOT National Transportation Integrated Search

2000-06-14

Maintenance engineers have been applying treatments to both flexible and rigid pavements for as long as such pavements have existed. The types and application of various treatments for both corrective and preventive maintenance have been the subject ...

TBI Symptoms, Diagnosis, Treatment, Prevention

MedlinePlus

... Bar Home Current Issue Past Issues Cover Story: Traumatic Brain Injury TBI Symptoms, Diagnosis, Treatment, Prevention Past Issues / Fall ... very lucky in my ongoing recovery from the traumatic brain injury I suffered in Iraq." —Bob Woodruff Treatment Immediate ...

Butterbur extract: prophylactic treatment for childhood migraines.

PubMed

Utterback, Gretchann; Zacharias, Rayna; Timraz, Shahrazad; Mershman, Denay

2014-02-01

The incidence of migraine headaches in childhood is increasing. Migraines are often difficult to diagnose in pediatrics and even more difficult to treat and prevent. In order to decrease the impact of the condition on the child and the family, prophylactic treatment is recommended if the child is experiencing disabling migraines. The medications currently prescribed for the prevention of pediatric migraines often have significant side effects and are of questionable therapeutic value. For those patients and parents who are interested in alternative therapies and natural remedies for preventive treatment of pediatric migraines, butterbur extract derived from the butterbur plant, Petasites hybridus, has emerged as a promising treatment. This paper discusses the impact of migraines among pediatric patients, the rationale for the preventative treatment of pediatric migraines, the current therapies and the relevance of butterbur extract as a prophylactic treatment for migraines in this patient population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Treatment of vascular dementia. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

PubMed Central

Brucki, Sonia Maria Dozzi; Ferraz, Ana Cláudia; de Freitas, Gabriel R.; Massaro, Ayrton Roberto; Radanovic, Márcia; Schultz, Rodrigo Rizek

2011-01-01

Scientific Department of Cognitive Neurology and Aging of ABN had a consensus meeting to write recommendations on treatment of vascular dementia, there was no previous issue. This disease has numerous particularities and can be considered a preventable dementia. Prevention treatment is primary care of vascular risk factors or a secondary prevention of factors that could cause recurrence of ischemic or hemorrhagic brain modifications. In these guidelines we suggested only symptomatic treatment, pharmacologic or non-pharmacologic. We have reviewed current publications on MEDLINE (PubMed), LILACS e Cochrane Library databases. Recommendations are concern to the following factors and their prevention evidences, association, or treatment of vascular dementia: physical activity, tobacco use, diet and food supplements, arterial hypertension, diabetes mellitus, obesity, statins, cardiac failure, atrial fibrillation, antithrombotics, sleep apnea, carotid revascularization, symptomatic pharmacological treatment. PMID:29213754

[Advances in the research of mechanism in prevention and treatment of scar with botulinum toxin type A and its clinical application].

PubMed

Li, Y H; Liu, J Q; Xiao, D; Zhang, W; Hu, D H

2017-04-20

Scar is a common complication in wound healing process, and how to effectively prevent and treat it is a hot and difficult problem in burns and plastic surgery field. Botulinum toxin type A is a neurotoxin that has been widely and effectively used in the cosmetic surgery field such as anti-wrinkle and thin face. In recent years, botulinum toxin type A has been applied in prevention and treatment of scar, which causes a great concern. Nowadays, the relevant reports have gradually increased, and the mechanisms have been explored more deeply. This article aims to summarize the possible mechanisms and clinical reports on the prevention and treatment of scar by botulinum toxin type A to provide a new way for the prevention and treatment of scar after surgery.

Diapause Prevention Effect of Bombyx mori by Dimethyl Sulfoxide

PubMed Central

Yamamoto, Takayuki; Mase, Keisuke; Sawada, Hiroshi

2013-01-01

HCl treatment has been, for about 80 years, the primary method for the prevention of entry into embryonic diapauses of Bombyx mori. This is because no method is as effective as the HCl treatment. In this study, we discovered that dimethyl sulfoxide (DMSO) prevented entry into the diapause of the silkworm, Bombyx mori. The effect of diapause prevention was 78% as a result of treatment with 100% DMSO concentration, and the effect was comparable to that of the HCl treatment. In contrast, in the case of non-diapause eggs, hatchability was decreased by DMSO in a concentration-dependent manner. The effect of DMSO was restricted within 24 hours after oviposition of diapause eggs, and the critical period was slightly shorter than the effective period of the HCl treatment. DMSO analogs, such as dimethyl formamide (DMF) and dimethyl sulfide (DMS), did little preventive effect against the diapause. Furthermore, we also investigated the permeation effects of chemical compounds by DMSO. When treated with an inhibitor of protein kinase CK2 (CK2) dissolved in DMSO, the prevention rate of the diapause was less than 40%. This means that the inhibition effect by the CK2 inhibitor was the inhibition of embryonic development after diapause prevention by DMSO. These data suggest that DMSO has the effects of preventing from entering into the diapause and permeation of chemicals into diapause eggs. PMID:23675522

Good Health and Moral Responsibility: Key Concepts Underlying the Interpretation of Treatment as Prevention in South Africa and Zambia Before Rolling Out Universal HIV Testing and Treatment.

PubMed

Bond, Virginia; Hoddinott, Graeme; Viljoen, Lario; Simuyaba, Melvin; Musheke, Maurice; Seeley, Janet

2016-09-01

Gauging community responses to the WHO 2015 recommendation to provide antiretroviral treatment (ART) to all people living with HIV (PLHIV) is critical. There is limited qualitative evidence on the acceptability of this Universal Test and Treat (UTT) strategy or community understanding of the impact of ART on reducing HIV transmission, promoted as Treatment as Prevention (TasP). This article explores early understanding of UTT and TasP in 21 urban communities in South Africa and Zambia in 2013 before a community randomized trial of combination prevention-HPTN 071 (PopART). It draws on participatory research conducted in each community, which carried out group discussions and interviews with 1202 respondents and 203 structured observations. Participants were largely unfamiliar with the concepts of UTT and TasP. They were concerned about an accompanying de-emphasis on sexual behavior change. Treatment and prevention seemed, at first glance, to be experienced separately. With the exception of the prevention of mother-to-child transmission, prevention seldom came into discussions about ART. This was partly because this science had not yet been explained to many and also because it was not an easy fit. Contemplating the link between treatment and prevention, participants emphasized both PLHIV taking care of themselves through good health and preventing disease progression and the moral responsibility of PLHIV to prevent HIV transmission. To avoid igniting moralizing and blaming when introducing UTT and TasP, we should capitalize on the "taking care of yourself" legacy while boosting public responsibility through broad antistigma education and patient empowerment efforts.

Technology Use and Preferences for Mobile Phone–Based HIV Prevention and Treatment Among Black Young Men Who Have Sex With Men: Exploratory Research

PubMed Central

Winder, Terrell JA; Lea III, Charles Herbert; Tan, Diane; Boyd, Donte; Novak, David

2017-01-01

Background Black young men who have sex with men (BYMSM) experience higher human immunodeficiency virus (HIV) incidence than their white and Latino counterparts. Objective The aim of our study was to understand BYMSM’s preferences for mobile phone–based HIV prevention and treatment in order to inform culturally tailored interventions to reduce the spread of HIV and improve HIV treatment outcomes in this population. Methods Qualitative focus groups (N=6) with BYMSM aged 18-29 years (N=41; 46%, 19/41 HIV-positive) were conducted to elucidate their preferences for the design and delivery of mobile phone–based HIV prevention and treatment interventions. A modified grounded theory approach to data analysis was undertaken using ATLAS.ti textual analysis software. Results Participants preferred holistic health interventions that did not focus exclusively on HIV prevention and treatment. Issues of privacy and confidentiality were paramount. Participants preferred functionality that enables discreet connections to culturally competent health educators and treatment providers who can address the range of health and psychosocial concerns faced by BYMSM. Conclusions Mobile phone–based HIV prevention has the potential to increase engagement with HIV prevention and treatment resources among BYMSM. For these approaches to be successful, researchers must include BYMSM in the design and creation of these interventions. PMID:28408360

Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

NASA Astrophysics Data System (ADS)

Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

2004-03-01

Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

[Relapse prevention in drug addicts].

PubMed

Rácz, József

2013-12-01

The literature review deals with methods of relapse prevention. Relapse prevention is the key in the treatment of clients with drug addictions according to the transtheoretical model of change. If relapse prevention is more effective then not only the relapse would be prevented, but the client would leave the circulus vitiosus of relapses. Among psychotherapies cognitive behavioural methods are proven effective. Shorter forms of cognitive therapies are also available: for example, cognitive bias modification. Pharmacotherapy partly decreases craving of the clients or ceases the effects of psychoactive substances. Specific pharmacotherapeutic methods prevent relapses in a non-abstinent treatment design. Here the goal is not the abstinence in a short time, but the reduction of harms associated with drug use. In this way, a new target group of drug users can be involved in treatment.

Novel Nanotechnology Strategies for the Treatment and Prevention of HIV Infection

NASA Astrophysics Data System (ADS)

Tan, Jian Jun; Sun, Xiao Hui; Ma, Xue Ting; Guan, Jian Qing; Wang, Cun Xin

2013-09-01

It is a hard work to develop an hightly effective cure and prevention of HIV/AIDS. The widespread used of some therapy approaches such as highly active anti retroviral therapy (HAART) has improved life quality and span of infected individuals. However, some limitations of these approaches prevent them achieving further advancement. Recent research on drug delivery approaches indicates that engineered nanosystems may bring positive effect on the improvement of current antiretroviral therapy. Furthermore, the basic researches of nanotechnology- based systems which prevent HIV transmission have been started. Therefore, nanotechnology may become a potential approach in the field of HIV/AIDS treatment and prevention. This chapter reviews the latest advancement in the field of nanotechnology-based systems which improve the fields of HIV/AIDS treatment and prevention.

Prediabetes Screening and Treatment in Diabetes Prevention: The Impact of Physician Attitudes.

PubMed

Mainous, Arch G; Tanner, Rebecca J; Scuderi, Christopher B; Porter, Maribeth; Carek, Peter J

Detection and treatment of prediabetes is an effective strategy in diabetes prevention. However, most patients with prediabetes are not identified. Our objective was to evaluate the relationship between attitudes toward prediabetes as a clinical construct and screening/treatment behaviors for diabetes prevention among US family physicians. An electronic survey of a national sample of academic family physicians (n 1248) was conducted in 2016. Attitude toward prediabetes was calculated using a summated scale assessing agreement with statements regarding prediabetes as a clinical construct. Perceived barriers to diabetes prevention, current strategies for diabetes prevention, and perceptions of peers were also examined. Physicians who have a positive attitude toward prediabetes as a clinical construct are more likely to follow national guidelines for screening (58.4% vs 44.4; P < .0001) and recommend metformin to their patients for prediabetes (36.4% vs 20.9%; P < .0001). Physicians perceived a number of barriers to treatment, including a patient's economic resources (71.9%), sustaining patient motivation (83.2%), a patient's ability to modify his or her lifestyle (75.3%), and time to educate patient (75.3%) as barriers to diabetes prevention. How physicians view prediabetes varies significantly, and this variation is related to treatment/screening behaviors for diabetes prevention. © Copyright 2016 by the American Board of Family Medicine.

Factors affecting compliance with preventive treatment for tuberculosis at Mistassini Lake, Quebec, Canada.

PubMed

Rideout, M; Menzies, R

1994-02-01

Non-compliance is the most important cause of failure of anti-tuberculous therapy throughout the world. In 1990 and 1991, an outbreak of tuberculosis occurred on the Mistassini Cree territory in Northern Quebec, Canada, and a number of cases of active tuberculosis occurred among known tuberculin-positive contacts who were non-compliant with preventive therapy. To better understand the factors affecting compliance with preventive treatment, a review of patients prescribed preventive treatment over the past 10 y was conducted. A freely-translated, interviewer-administered questionnaire was used to measure personal/lifestyle factors and knowledge/attitudes about tuberculosis. Clinic dossiers were reviewed to assess compliance. One hundred and two (102) subjects prescribed preventive treatment between 1981 and 1991 were interviewed, of whom 33.7% were judged to have been compliant. The most significant factor associated with compliance with preventive therapy was year of therapy. Between 1981 and 1985, 78% completed treatment, compared to less than 20% since 1986 (p < .0001). The major factor identified as associated with this sudden change was a shift in responsibility for tuberculosis treatment follow-up from native community health workers to non-native nurses in 1985/86. We conclude that tuberculosis control programs must be tailored to take into account the importance of cultural factors in promoting compliance with therapy.

Preventive treatment of migraine.

PubMed

Silberstein, Steven D

2005-01-01

Migraine preventive therapy, even in the absence of a headache, is given in an attempt to reduce the frequency, duration, or severity of attacks. Circumstances that might warrant preventive treatment include disabling migraine attacks, the overuse of acute medications or failure of or contraindication to acute medications, troublesome side effects from medication, hemiplegic migraine, or very frequent headaches (more than 2 a week). The major medication groups for preventive treatment include anticonvulsants, antidepressants, b-adrenergic blockers, calcium channel antagonists, serotonin antagonists, neurotoxins, nonsteroidal anti-inflammatory drugs, and others. If preventive medication is indicated, the agent preferentially should be chosen from one of the first-line categories, based on the drug's side-effect profile and the patient's coexistent and comorbid conditions.

Direct costs of preventive headache treatments: comparison of behavioral and pharmacologic approaches.

PubMed

Schafer, Allison M; Rains, Jeanetta C; Penzien, Donald B; Groban, Leanne; Smitherman, Todd A; Houle, Timothy T

2011-06-01

This study provides preliminary data and a framework to facilitate cost comparisons for pharmacologic vs behavioral approaches to headache prophylactic treatment. There are few empirical demonstrations of cumulative costs for pharmacologic and behavioral headache treatments, and there are no direct comparisons of short- and long-range (5-year) costs for pharmacologic vs behavioral headache treatments. Two separate pilot surveys were distributed to a convenience sample of behavioral specialists and physicians identified from the membership of the American Headache Society. Costs of prototypical regimens for preventive pharmacologic treatment (PPT), clinic-based behavioral treatment (CBBT), minimal contact behavioral treatment (MCBT), and group behavioral treatment were assessed. Each survey addressed total cost accumulated during treatment (ie, intake, professional fees) excluding costs of acute medications. The total costs of preventive headache therapy by type of treatment were then evaluated and compared over time. During the initial months of treatment, PPT with inexpensive mediations (<0.75 $/day) represents the least costly regimen and is comparable to MCBT in expense until 6 months. After 6 months, PPT is expected to become more costly, particularly when medication cost exceeds 0.75$ a day. When using an expensive medication (>3 $/day), preventive drug treatment becomes more expensive than CBBT after the first year. Long-term, and within year 1, MCBT was found to be the least costly approach to migraine prevention. Through year 1 of treatment, inexpensive prophylactic medications (such as generically available beta-blocker or tricyclic antidepressant medications) and behavioral interventions utilizing limited delivery formats (MCBT) are the least costly of the empirically validated interventions. This analysis suggests that, relative to pharmacologic options, limited format behavioral interventions are cost-competitive in the early phases of treatment and become more cost-efficient as the years of treatment accrue. © 2011 American Headache Society.

Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

PubMed

Hubalewska-Hola, Alicja; Fröss, Katarzyna; Kostecka-Matyja, Marta; Sowa-Staszczak, Anna; Szybiński, Zbigniew; Huszno, Bohdan; Ptak, Marzena

2003-01-01

Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma (histopathologically a chromophobic adenoma). The example of presented patients suggests that clinical course of the pituitary tumor producing TSH and the rate of the tumor growth may differ significantly. Surgical resection of TSH producing adenoma is the most effective therapy. It should be proceeded by octreotide administration in patients with macroadenoma.

A case-control study of HIV-associated pancreatic abnormalities during HAART era. Focus on emerging risk factors and specific management.

PubMed

Manfredi, Roberto; Calza, L; Chiodo, F

2004-12-22

The epidemiological and clinical features of HIV-associated pancreatic abnormalities are expected to change after HAART introduction. The frequency, risk factors, and clinical and therapeutic features of pancreatic alterations were assessed in an observational case-control study. Nine hundred and 20 were evaluated for pancreatic abnormalities in a case-control study including the whole follow-up period of each considered patient; 128 subjects with high and prolonged laboratory anomalies were assessed, to outline the profile of pancreatic disease before and during the HAART era. Compared with controls, the 334 patients (36.3%) who experienced at least one episode of confirmed pancreatic laboratory abnormality had a longer duration of seropositivity, exposure to protease inhibitors, a more frequent immunodeficiency, AIDS diagnosis, liver or biliary disease, and hypertriglyceridemia, while no relation was found with antiretroviral administration, and the duration of nucleoside analogue use. Among these 334 patients, high and prolonged laboratory alterations eventually associated with signs of organ involvement occurred in 128 cases, and were related to the administration of didanosine, stavudine, lamivudine, pentamidine, cotrimoxazole, or anti-tubercular therapy, substance or alcohol abuse, opportunistic infections, liver or biliary disease, a protease inhibitor-based HAART, and hypertriglyceridemia. However, no difference was noticed between the 32 patients with clinical and/or imaging evidence of pancreatic involvement and the remaining 96 asymptomatic cases, as to the same risk factors. Although recurrences of enzyme alterations involved >70% of patients, in only 33.8% of cases a change of antiretroviral or antimicrobial therapy was necessary. An acute but uncomplicated pancreatitis occurred in 7 patients of 26 overall symptomatic subjects. A 2-4-week gabexate and/or octreotide administration (performed in 59 cases of 128), attained a significant laboratory, clinical, and imaging cure or improvement in 71.2% of cases, with a better success rate of combined versus single therapy; a reduced tendency to disease recurrences, and a better tolerability of antiretrovirals were also noticed. Epidemiological and pathogenetic studies are needed to assess pancreatic abnormalities especially in the HAART era, and their consequences on continued antiretroviral and antimicrobial therapy. The antiretroviral management and the indication to gabexate and/or octreotide administration in the different clinical and laboratory situations, warrant controlled investigation.

77 FR 14806 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... announced below concerns Epidemiology, Prevention and Treatment of Influenza and Other Respiratory... Vietnam, The Incidence of Community Associated Influenza and Other Respiratory Infections in the United States, and Epidemiology, Prevention and Treatment of Influenza and Other Respiratory Infections in...

Quantitative PCR monitoring of the effect of azoxystrobin treatments on Mycosphaerella graminicola epidemics in the field.

PubMed

Rohel, Eric A; Laurent, Paul; Fraaije, Bart A; Cavelier, Nadine; Hollomon, Derek W

2002-03-01

Quantitative PCR and visual monitoring of Mycosphaerella graminicola epidemics were performed to investigate the effect of curative and preventative applications of azoxystrobin in wheat field crops. A non-systemic protectant and a systemic curative fungicide, chlorothalonil and epoxiconazole, respectively, were used as references. PCR diagnosis detected leaf infection by M graminicola 3 weeks before symptom appearance, thereby allowing a clear distinction between curative and preventative treatments. When applied 1 week after the beginning of infection, azoxystrobin curative activity was intermediate between chlorothalonil (low effect) and epoxiconazole. When applied preventatively, none of the fungicides completely prevented leaf infection. There was some indication that azoxystrobin preventative treatments may delay fungal DNA increase more than epoxiconazole at the beginning of leaf infection. Both curative and preventative treatments increased the time lapse between the earliest PCR detection and the measurement of a 10% necrotic leaf area. Azoxystrobin only slightly decreased the speed of necrotic area increase compared with epoxiconazole. Hence, azoxystrobin activity toward M graminicola mainly resides in lengthening the time lapse between the earliest PCR detection and the measurement of a 10% necrotic leaf area. Information generated in this way is useful for optimal positioning of azoxystrobin treatments on M graminicola.

[Prevention of pressure ulcer (bedsore)].

PubMed

Sedmak, Dijana; Vrhovec, Marina; Huljev, Dubravko

2013-10-01

Although progress in many fields of science, medicine and technology is evident, we are still witnessing the appearance of bedsores and its consequences. However, in the last fifty years there has been considerable progress in the understanding of its causes, prevention and treatment. Prevention and treatment of pressure ulcers are complicated by the many misconceptions. However, with due knowledge of the process of healing of acute and chronic wounds and of the pathophysiological processes, in many cases chronic wounds, like pressure ulcers, can now be prevented and cured, and thus reduce the cost of treatment, as well as the mortality rate.

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2015-04-01

AWARD NUMBER: W81XWH-14-1-0073 TITLE: Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath...Annual 3. DATES COVERED 1 Apr 2014 - 31 Mar 2015 4. TITLE AND SUBTITLE Prevention and Treatment of Neurofibromatosis Type 1- 5a. CONTRACT NUMBER...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is

Low-Dose Nocturnal Tegaserod or Erythromycin Delays Symptom Recurrence After Treatment of Irritable Bowel Syndrome Based on Presumed Bacterial Overgrowth

PubMed Central

Morales, Walter; Lezcano, Sheila; Sun-Chuan, Dai; Low, Kimberly; Yang, Janet

2009-01-01

Our group previously demonstrated a deficiency of migrating motor complexes in irritable bowel syndrome (IBS) patients with small intestinal bacterial overgrowth (SIBO). Based on disturbed fasting motility, we tested whether low-dose nocturnal erythromycin or tegaserod can prevent the recurrence of IBS symptoms after successful antibiotic treatment. Methods: 203 patient charts were reviewed to find IBS patients with SIBO, and treatment cycles were assessed to identify subjects with clinical and breath test resolution. The charts of those who met the inclusion criteria were reviewed to determine the method of prevention of symptom recurrence and the length of remission. The two preventive agents used were erythromycin (50 mg) or tegaserod (2–6 mg) orally at bedtime. Results: 64 patients met the inclusion criteria. Subjects receiving no prevention (n=6) after successful antibiotic treatment experienced symptom recurrence after 59.7±47.4 days. Prevention using erythromycin (n=42) demonstrated 138.5±132.2 symptom-free days (P=.08 vs no prevention) compared to 241.6±162.2 days with tegaserod (n=16; P=.003 vs no prevention; P=.004 vs erythromycin). Switching from erythromycin to tegaserod (n=20) extended resolution from 105.8±73.3 days to 199.7±162.9 days (P=.04). Changing from no therapy to erythromycin or tegaserod (n=6) extended recurrence from 41.0±44.8 days to 195.6±153.5 days (P=.06). Conclusion: Tegaserod significantly prevents the recurrence of IBS symptoms after antibiotic treatment compared to erythromycin or no prevention. PMID:20574504

Sunburn: Treatment and Prevention

MedlinePlus

... Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & Prevention Safety & Prevention Safety and Prevention Immunizations ...

Technology Use and Preferences for Mobile Phone-Based HIV Prevention and Treatment Among Black Young Men Who Have Sex With Men: Exploratory Research.

PubMed

Holloway, Ian W; Winder, Terrell Ja; Lea, Charles Herbert; Tan, Diane; Boyd, Donte; Novak, David

2017-04-13

Black young men who have sex with men (BYMSM) experience higher human immunodeficiency virus (HIV) incidence than their white and Latino counterparts. The aim of our study was to understand BYMSM's preferences for mobile phone-based HIV prevention and treatment in order to inform culturally tailored interventions to reduce the spread of HIV and improve HIV treatment outcomes in this population. Qualitative focus groups (N=6) with BYMSM aged 18-29 years (N=41; 46%, 19/41 HIV-positive) were conducted to elucidate their preferences for the design and delivery of mobile phone-based HIV prevention and treatment interventions. A modified grounded theory approach to data analysis was undertaken using ATLAS.ti textual analysis software. Participants preferred holistic health interventions that did not focus exclusively on HIV prevention and treatment. Issues of privacy and confidentiality were paramount. Participants preferred functionality that enables discreet connections to culturally competent health educators and treatment providers who can address the range of health and psychosocial concerns faced by BYMSM. Mobile phone-based HIV prevention has the potential to increase engagement with HIV prevention and treatment resources among BYMSM. For these approaches to be successful, researchers must include BYMSM in the design and creation of these interventions. ©Ian W Holloway, Terrell JA Winder, Charles Herbert Lea III, Diane Tan, Donte Boyd, David Novak. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 13.04.2017.

HIV epidemic control-a model for optimal allocation of prevention and treatment resources.

PubMed

Alistar, Sabina S; Long, Elisa F; Brandeau, Margaret L; Beck, Eduard J

2014-06-01

With 33 million people living with human immunodeficiency virus (HIV) worldwide and 2.7 million new infections occurring annually, additional HIV prevention and treatment efforts are urgently needed. However, available resources for HIV control are limited and must be used efficiently to minimize the future spread of the epidemic. We develop a model to determine the appropriate resource allocation between expanded HIV prevention and treatment services. We create an epidemic model that incorporates multiple key populations with different transmission modes, as well as production functions that relate investment in prevention and treatment programs to changes in transmission and treatment rates. The goal is to allocate resources to minimize R 0, the reproductive rate of infection. We first develop a single-population model and determine the optimal resource allocation between HIV prevention and treatment. We extend the analysis to multiple independent populations, with resource allocation among interventions and populations. We then include the effects of HIV transmission between key populations. We apply our model to examine HIV epidemic control in two different settings, Uganda and Russia. As part of these applications, we develop a novel approach for estimating empirical HIV program production functions. Our study provides insights into the important question of resource allocation for a country's optimal response to its HIV epidemic and provides a practical approach for decision makers. Better decisions about allocating limited HIV resources can improve response to the epidemic and increase access to HIV prevention and treatment services for millions of people worldwide.

Effectiveness of secondary prevention and treatment interventions for crack-cocaine abuse: a comprehensive narrative overview of English-language studies.

PubMed

Fischer, Benedikt; Blanken, Peter; Da Silveira, Dartiu; Gallassi, Andrea; Goldner, Elliot M; Rehm, Jürgen; Tyndall, Mark; Wood, Evan

2015-04-01

There are an estimated several million crack-cocaine users globally; use is highest in the Americas. Most crack users are socio-economically marginalized (e.g., homeless), and feature elevated risks for morbidity (e.g., blood-borne viruses), mortality and crime/violence involvement, resulting in extensive burdens. No comprehensive reviews of evidence-based prevention and/or treatment interventions specifically for crack use exist. We conducted a comprehensive narrative overview of English-language studies on the efficacy of secondary prevention and treatment interventions for crack (cocaine) abuse/dependence. Literature searches (1990-2014) using pertinent keywords were conducted in main scientific databases. Titles/abstracts were reviewed for relevance, and full studies were included in the review if involving a primary prevention/treatment intervention study comprising a substantive crack user sample. Intervention outcomes considered included drug use, health risks/status (e.g., HIV or sexual risks) and select social outcome indicators. Targeted (e.g., behavioral/community-based) prevention measures show mixed and short-term effects on crack use/HIV risk outcomes. Material (e.g., safer crack use kit distribution) interventions also document modest efficacy in risk reduction; empirical assessments of environmental (e.g., drug consumption facilities) for crack smokers are not available. Diverse psycho-social treatment (including contingency management) interventions for crack abuse/dependence show some positive but also limited/short-term efficacy, yet likely constitute best currently available treatment options. Ancillary treatments show little effects but are understudied. Despite ample studies, pharmaco-therapeutic/immunotherapy treatment agents have not produced convincing evidence; select agents may hold potential combined with personalized approaches and/or psycho-social strategies. No comprehensively effective 'gold-standard' prevention/treatment interventions for crack abuse exist; concerted research towards improved interventions is urgently needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Conceptualizing a Human Right to Prevention in Global HIV/AIDS Policy

PubMed Central

Meier, Benjamin Mason; Brugh, Kristen Nichole; Halima, Yasmin

2012-01-01

Given current constraints on universal treatment campaigns, recent advances in public health prevention initiatives have revitalized efforts to stem the tide of HIV transmission. Yet, despite a growing imperative for prevention—supported by the promise of behavioral, structural and biomedical approaches to lower the incidence of HIV—human rights frameworks remain limited in addressing collective prevention policy through global health governance. Assessing the evolution of rights-based approaches to global HIV/AIDS policy, this review finds that human rights have shifted from collective public health to individual treatment access. While the advent of the HIV/AIDS pandemic gave meaning to rights in framing global health policy, the application of rights in treatment access litigation came at the expense of public health prevention efforts. Where the human rights framework remains limited to individual rights enforced against a state duty bearer, such rights have faced constrained application in framing population-level policy to realize the public good of HIV prevention. Concluding that human rights frameworks must be developed to reflect the complementarity of individual treatment and collective prevention, this article conceptualizes collective rights to public health, structuring collective combination prevention to alleviate limitations on individual rights frameworks and frame rights-based global HIV/AIDS policy to assure research expansion, prevention access and health system integration. PMID:23226723

Prevention of β Thalassemia in Northern Israel - a Cost-Benefit Analysis

PubMed Central

Koren, Ariel; Profeta, Lora; Zalman, Luci; Palmor, Haya; Levin, Carina; Zamir, Ronit Bril; Shalev, Stavit; Blondheim, Orna

2014-01-01

Background β Thalassemia major is characterized by hemolytic anemia, ineffective erythropoiesis and hemosiderosis. About 4% of the world population carries a Thalassemia gene. Management includes blood transfusions and iron chelation. However, this treatment is costly, and population screening may be significantly more cost beneficial. Purpose The purpose of the current study is to analyze the cost of running a prevention program for β Thalassemia in Israel and to compare it to the actual expenses incurred by treating Thalassemia patients. Methods Three cost parameters were analyzed and compared: the prevention program, routine treatment of patients and treatment of complications. An estimation of the expenses needed to treat patients who present with complications was calculated based on our ongoing experience in treating deteriorating patients. Results and Conclusions The cost of preventing one affected newborn was $63,660 compared to $1,971,380 for treatment of a patient during 50 years (mean annual cost: $39,427). Thus, the prevention of 45 affected newborns over a ten year period represents a net saving of $88.5 million to the health budget. Even after deducting the cost of the prevention program ($413.795/year), the program still represents a benefit of $76 million over ten years. Each prevented case could pay the screening and prevention program for 4.6 years. PMID:24678389

Gender and racial/ethnic disparities in the impact of HIV prevention programming in substance abuse treatment.

PubMed

Cao, Dingcai; Marsh, Jeanne C; Shin, Hee-Choon

2008-01-01

The objective of the study was to evaluate the capacity of HIV prevention programs offered in substance abuse treatment to reduce HIV-related risk behavior for women and men and for Black, Latino, and White groups. Prospective data was collected at intake, discharage, and 12 months post-treatment from 1992 to 1997 for the National Treatment Improvement Evaluation Study with a sample consisting of 3,142 clients from 59 service delivery units: 972 females, 1,870 males, 1,812 Blacks, 486 Latinos, and 844 Whites. Study findings show that receipt of HIV prevention programming as part of substance abuse treatment services resulted in reductions in HIV-related risk behavior for the sample overall and for women as well as men. However, although Blacks received more prevention services than Latinos and Whites, the significant positive effect of HIV services on reduced HIVrisk behavior held only for Whites. Racial/ethnic disparities exist in the capacity for HIV prevention programming offered as part of substance abuse treatment to reduce HIV-risk behavior. The findings highlight the need for the development of culturally competent service delivery strategies to enhance the impact of these services for all groups.

45 CFR 1340.20 - Confidentiality.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Discretionary...

45 CFR 1340.20 - Confidentiality.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Discretionary...

45 CFR 1340.20 - Confidentiality.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Discretionary...

45 CFR 1340.20 - Confidentiality.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Discretionary...

45 CFR 1340.20 - Confidentiality.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Discretionary...

Good Health and Moral Responsibility: Key Concepts Underlying the Interpretation of Treatment as Prevention in South Africa and Zambia Before Rolling Out Universal HIV Testing and Treatment

PubMed Central

Hoddinott, Graeme; Viljoen, Lario; Simuyaba, Melvin; Musheke, Maurice; Seeley, Janet

2016-01-01

Abstract Gauging community responses to the WHO 2015 recommendation to provide antiretroviral treatment (ART) to all people living with HIV (PLHIV) is critical. There is limited qualitative evidence on the acceptability of this Universal Test and Treat (UTT) strategy or community understanding of the impact of ART on reducing HIV transmission, promoted as Treatment as Prevention (TasP). This article explores early understanding of UTT and TasP in 21 urban communities in South Africa and Zambia in 2013 before a community randomized trial of combination prevention—HPTN 071 (PopART). It draws on participatory research conducted in each community, which carried out group discussions and interviews with 1202 respondents and 203 structured observations. Participants were largely unfamiliar with the concepts of UTT and TasP. They were concerned about an accompanying de-emphasis on sexual behavior change. Treatment and prevention seemed, at first glance, to be experienced separately. With the exception of the prevention of mother-to-child transmission, prevention seldom came into discussions about ART. This was partly because this science had not yet been explained to many and also because it was not an easy fit. Contemplating the link between treatment and prevention, participants emphasized both PLHIV taking care of themselves through good health and preventing disease progression and the moral responsibility of PLHIV to prevent HIV transmission. To avoid igniting moralizing and blaming when introducing UTT and TasP, we should capitalize on the “taking care of yourself” legacy while boosting public responsibility through broad antistigma education and patient empowerment efforts. PMID:27610464

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Sterne, Jonathan Ac; Bodalia, Pritesh N; Bryden, Peter A; Davies, Philippa A; López-López, Jose A; Okoli, George N; Thom, Howard Hz; Caldwell, Deborah M; Dias, Sofia; Eaton, Diane; Higgins, Julian Pt; Hollingworth, Will; Salisbury, Chris; Savović, Jelena; Sofat, Reecha; Stephens-Boal, Annya; Welton, Nicky J; Hingorani, Aroon D

2017-03-01

Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. Efficacy  Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety  Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. Apixaban (Eliquis ® , Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana ® , Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330. The National Institute for Health Research Health Technology Assessment programme.

Measures of Effective Military Public Health Interventions in Stability Operations

DTIC Science & Technology

2011-06-10

treatment of acute watery diarrhea ( nutritional support and oral rehydration therapy). 5. Prevention/treatment of endemic diseases, targeting...age of 5, targeting immunizations and treatment of acute watery diarrhea ( nutritional support and oral rehydration therapy). -Prevention...Improve care for children under-five targeting immunizations and treatment of acute watery diarrhea ( nutritional support and oral rehydration

About Supportive and Palliative Care Research | Division of Cancer Prevention

Cancer.gov

The program supports research in three areas: prevention or treatment of acute or chronic symptoms and morbidities related to cancer, its treatment and caregiving (symptom management research); effects on quality of life from cancer, its treatment and caregiving (quality of life research); and end-of-life psychosocial issues, caregiving and treatment strategies (end-of-life

Integrating Motivational Interviewing and Self-Determination Theory with Cognitive Behavioral Therapy to Prevent Suicide

ERIC Educational Resources Information Center

Britton, Peter C.; Patrick, Heather; Wenzel, Amy; Williams, Geoffrey C.

2011-01-01

Cognitive behavioral therapy (CBT) has been found to be effective in preventing suicide-related behavior. However, it is often difficult to engage patients who are at-risk in treatment. Motivational Interviewing (MI) has been shown to increase treatment engagement and improve treatment outcomes when it is used to complement other treatments. As a…

Effects of alpha-tocopherol treatment on newborn rat lung development and injury in hyperoxia.

PubMed

Bucher, J R; Roberts, R J

1982-01-01

The efficacy of alpha-tocopherol treatment to influence the pattern or extent of lung injury resulting during exposure of newborn rats to hyperoxia was assessed following six-day exposures to FIO2 0.21, 0.4, and greater than 0.95. Alpha-Tocopherol treatment was found incapable of preventing the developmental arrest of the lung that occurs during hyperoxic exposure, shown by assessments of wet lung weights, lung DNA, lung volumes, and the progress of secondary septal and capillary development. However alpha-tocopherol treatment was found effective in preventing the hyperoxic-induced lessening of lung compliance and in preventing the deterioration of gas exchange capacity in the lung of the hyperoxic-exposed newborn rat. These findings suggest alpha-tocopherol treatment may not be capable of preventing major alterations in lung morphology in infants with chronic lung disease may be lessened by preserving gas exchange capabilities.

[Prevention and treatment of obesity in children].

PubMed

Togashi, Kenji; Iguchi, Kosei; Masuda, Hidenari

2013-02-01

The prevalence of childhood obesity and its comorbidities is high in Japan. Increasing prevalence of obesity among children emphasizes the importance of focusing on primary prevention to avoid health complications later in life. We emphasize the prevention of obesity by recommending breast-feeding of infants for at least 6 months and advocating that schools provide for 60 min of moderate to vigorous daily exercise in all grades. Treatment interventions include behavioral therapy, reduction in sedentary behavior, and dietary and exercise education. After dietary treatment combined with exercise treatment, the areas of subcutaneous and visceral fat decreased significantly. These data suggest that dietary treatment combined with exercise treatment in obese children normalizes the distribution of abdominal fat and reduces the risk factors for chronic disease.

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2016-04-01

Page 1 AWARD NUMBER: W81XWH-14-1-0073 TITLE: Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral...COVERED 04/01/2015 to 03/31/2016 4. TITLE AND SUBTITLE Prevention and Treatment of Neurofibromatosis Type 1- 5a. CONTRACT NUMBER W81XWH-14-1-0073...ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is malignant peripheral nerve sheath tumor (MPNST). MPNSTs are

Treatment and prevention of pediatric heat-related illnesses at mass gatherings and special events.

PubMed

Bernardo, Lisa Marie; Crane, Patricia A; Veenema, Tener Goodwin

2006-01-01

Pediatric heat-related illnesses are likely to occur during mass gatherings and special events. Because critical care nurses may be called upon to provide care during such events, education in the recognition, treatment, and prevention of these illnesses is essential. This article describes the pathophysiology of heat-related illnesses and their recognition and treatment at mass gatherings and special events. Interventions to prevent heat-related illnesses at these events are discussed.

Situational analysis: regional review of the substance use Atlas 2015.

PubMed

Gehring, Elise; Saeed, Khalid

2017-05-01

The Atlas project on substance use is a global WHO project that aims to collect and disseminate data on resources for the prevention and treatment of substance use disorders. Information on resources available in the WHO Eastern Mediterranean Region was first published in 2012. The Atlas questionnaire was updated in 2014 and data were collected in all WHO Member States. All countries of the Region submitted the Atlas questionnaire. This report presents the latest key information on resources for the prevention and treatment of substance use disorders in the Eastern Mediterranean Region based on the responses of the countries to the questionnaire. Current estimates show that the burden attributable to drug use disorders in the Region is high. Health system resources for the prevention and treatment of substance use disorders vary across countries, but are generally still insufficient to provide adequate care and treatment for people with these disorders. Countries need to strengthen prevention and treatment of substance use disorders, particularly by increasing coverage of treatment interventions.

Preemptive mechanical ventilation can block progressive acute lung injury.

PubMed

Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

2016-02-04

Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.

Preemptive mechanical ventilation can block progressive acute lung injury

PubMed Central

Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

2016-01-01

Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

Cost-effectiveness analysis of annual Trichomonas vaginalis screening and treatment in HIV-positive women to prevent HIV transmission.

PubMed

Lazenby, Gweneth Bratton; Unal, Elizabeth Ramsey; Andrews, Annie Lintzenich; Simpson, Kit

2014-06-01

Because of a high incidence of Trichomonas infection among HIV-positive women, annual screening and treatment are recommended. Trichomonas infection is associated with a 2-fold risk of HIV transmission. The objective of this study was to determine if annual screening is cost-effective for the prevention of new HIV cases in susceptible male partners secondary to Trichomonas infection in HIV-positive women. A decision tree analysis was constructed to model the costs of Trichomonas screening, treatment, and follow-up. 200 women cycled through the model for a period of 12 months. One hundred women were unscreened and 100 were screened and treated per recommendations. Annual Trichomonas screening and treatment saves US $553 (US $475- US $645) per woman in the prevention of HIV transmission to male partners. The cost-effectiveness of this strategy was maintained across all assumptions in a sensitivity analysis. Trichomonas screening and treatment for the purpose of decreasing new HIV infections is not only cost-effective but also cost saving in HIV-positive women. If Centers for Disease Control and Prevention treatment guidelines were followed in all HIV-positive women living in the United States, the lifetime cost of new HIV infections prevented would approximate US $159,264,000 and could potentially prevent new HIV cases secondary to female-to-male transmissions.

Risk of developing tuberculosis disease among persons diagnosed with latent tuberculosis infection in the Netherlands.

PubMed

Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; Cobelens, Frank; van den Hof, Susan

2016-11-01

Diagnosis and preventive treatment of latent tuberculosis infection (LTBI) among high-risk groups is recommended to achieve tuberculosis (TB) elimination in low-incidence countries.We studied TB incidence rates among those notified with LTBI in the Netherlands from 2005 to 2013 and analysed associated risk factors. We stratified analyses by target group for screening, and by initiation and completion of preventive treatment.The incidence for those completing, stopping and not receiving preventive treatment was 187, 436 and 355 per 100 000 person-years for contacts of TB patients, respectively, and 63, 96 and 110 per 100 000 person-years for other target groups. The rate ratio for TB development among contacts compared to other target groups was 3.1 (95% CI 2.0-4.9). In both groups, incidence was highest in the first year after diagnosis. Independent factors associated with progression to TB among contacts were age <5 years and stopping preventive treatment within 28 days compared to those not receiving preventive treatment. Among other target groups, being foreign born was the only risk factor associated with the risk of developing TB.We conclude that the epidemiological impact of preventive treatment is highest in contacts of TB patients and limited in other target groups for LTBI management in the Netherlands. Copyright ©ERS 2016.

Optimal control of vancomycin-resistant enterococci using preventive care and treatment of infections.

PubMed

Lowden, Jonathan; Miller Neilan, Rachael; Yahdi, Mohammed

2014-03-01

The rising prevalence of vancomycin-resistant enterococci (VRE) is a major health problem in intensive care units (ICU) because of its association with increased mortality and high health care costs. We present a mathematical framework for determining cost-effective strategies for prevention and treatment of VRE in the ICU. A system of five ordinary differential equations describes the movement of ICU patients in and out of five VRE-related states. Two control variables representing the prevention and treatment of VRE are incorporated into the system. The basic reproductive number is derived and calculated for different levels of the two controls. An optimal control problem is formulated to minimize VRE-related deaths and costs associated with prevention and treatment controls over a finite time period. Numerical solutions illustrate optimal single and dual allocations of the controls for various cost values. Results show that preventive care has the greatest impact in reducing the basic reproductive number, while treatment of VRE infections has the most impact on reducing VRE-related deaths. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevention and treatment of relapse after stem cell transplantation by cellular therapies.

PubMed

Falkenburg, Fred; Ruggiero, Eliana; Bonini, Chaira; Porter, David; Miller, Jeff; Malard, Floran; Mohty, Mohamad; Kröger, Nicolaus; Kolb, Hans Jochem

2018-05-24

Despite recent advances in reducing therapy-related mortality after allogeneic stem cell transplantation (alloSCT) relapse remains the major cause of treatment failure and little progress has been achieved in the last decades. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg/Germany in November 2016 international experts presented and discussed recent developments in the field. Here, the potential of cellular therapies including unspecific and specific T cells, genetically modified T cells, CAR-T cells, NK-cells, and second allografting in prevention and treatment of relapse after alloSCT are summarized.

Women as Child Abusers: Indicators, Treatment, and Policy Directions.

ERIC Educational Resources Information Center

Kemp, Donna R.; And Others

Child abuse is a major problem in the United States. Policy concerning child abuse involves a criminal justice approach, a treatment approach, and a prevention approach. Prevention programs have focused on identifying and serving high-risk groups and on preventive education. A study was conducted to examine issues related to child abuse. Four…

Preventing and Treating Substance Abuse among Adolescents

ERIC Educational Resources Information Center

Sussman, Steve

2011-01-01

Substance misuse is one of the most prevalent causes of adolescent injury and death. Additionally, 5-8% of adolescents in the U.S. qualify for a diagnosis of substance abuse disorder. This article discusses formal prevention and treatment program models, focusing on a continuum of care which extends from prevention to treatment alternatives.…

Innovations in Protective Services. Annual Report, September 1, 1982 through August 31, 1983.

ERIC Educational Resources Information Center

Texas State Dept. of Human Resources, Austin.

The Child Abuse Prevention and Treatment Act (Public Law 93-247 as amended) provides financial assistance for, among other purposes, demonstration programs aimed at prevention and treatment of child abuse and neglect. To encourage innovative approaches to identifying, treating, and preventing child abuse at the community level, the Texas…

Probiotics for Treatment and Prevention of Urogenital Infections in Women: A Systematic Review.

PubMed

Hanson, Lisa; VandeVusse, Leona; Jermé, Martha; Abad, Cybéle L; Safdar, Nasia

2016-05-01

Probiotics are a complementary and integrative therapy useful in the treatment and prevention of urogenital infections in women. This study extends the work of researchers who systematically investigated the scientific literature on probiotics to prevent or treat urogenital infections. A systematic review was conducted to determine the efficacy of probiotics for prevention and/or treatment of urogenital infections in adult women from January 1, 2008, through June 30, 2015. We searched in CINAHL, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Dissertations and Theses, and Alt-HealthWatch. After removing duplicates and studies that did not meet inclusion criteria, 20 studies were reviewed. All included at least one species of Lactobacillus probiotic as an intervention for treatment or prevention of urogenital infections. Data extracted included samples, settings, study designs, intervention types, reported outcomes, follow-up periods, and results. We evaluated all randomized controlled trials for risk of bias and made quality appraisals on all studies. Fourteen of the studies focused on bacterial vaginosis (BV), 3 on urinary tract infections (UTIs), 2 on vulvovaginal candidiasis, and one on human papillomavirus (HPV) as identified on Papanicolaou test. Studies were heterogeneous in terms of design, intervention, and outcomes. Four studies were of good quality, 9 of fair, and 7 poor. Probiotic interventions were effective for treatment and prevention of BV, prevention of recurrences of candidiasis and UTIs, and clearing HPV lesions. No study reported significant adverse events related to the probiotic intervention. The quality of the studies in this systematic review varied. Although clinical practice recommendations were limited by the strength of evidence, probiotic interventions were effective in treatment and prevention of urogenital infections as alternatives or co-treatments. More good quality research is needed to strengthen the body of evidence needed for application by clinicians. © 2016 by the American College of Nurse-Midwives.

Joubert Syndrome

MedlinePlus

... developing methods of treatment and prevention. NINDS, in conjunction with the NIH Office of Rare Disorders, sponsored ... developing methods of treatment and prevention. NINDS, in conjunction with the NIH Office of Rare Disorders, sponsored ...

Nanotechnology and HIV: potential applications for treatment and prevention.

PubMed

Kim, Peter S; Read, Sarah W

2010-01-01

HIV/AIDS is a global pandemic and is the leading infectious cause of death among adults. Although antiretroviral (ARV) therapy has dramatically improved the quality of life and increased the life expectancy of those infected with HIV, life-long suppressive treatment is required and a cure for HIV infection remains elusive; frequency of dosing and drug toxicity as well as the development of viral resistance pose additional limitations. Furthermore, preventative measures such as a vaccine or microbicide are urgently needed to curb the rate of new infections. The capabilities inherent to nanotechnology hold much potential for impact in the field of HIV treatment and prevention. This article reviews the potential for the multidisciplinary field of nanotechnology to advance the fields of HIV treatment and prevention. © 2010 John Wiley & Sons, Inc.

Wilderness Medical Society practice guidelines for the prevention and treatment of lightning injuries: 2014 update.

PubMed

Davis, Chris; Engeln, Anna; Johnson, Eric L; McIntosh, Scott E; Zafren, Ken; Islas, Arthur A; McStay, Christopher; Smith, William R; Cushing, Tracy

2014-12-01

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the treatment and prevention of lightning injuries. These guidelines include a review of the epidemiology of lightning and recommendations for the prevention of lightning strikes, along with treatment recommendations organized by organ system. Recommendations are graded on the basis of the quality of supporting evidence according to criteria put forth by the American College of Chest Physicians. This is an updated version of the original WMS Practice Guidelines for Prevention and Treatment of Lightning Injuries published in Wilderness & Environmental Medicine 2012;23(3):260-269. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Zoledronic Acid for the Treatment and Prevention of Primary and Secondary Osteoporosis

PubMed Central

Rizzoli, René

2010-01-01

There is increasing interest in therapies that can be administered less frequently and/or avoid gastrointestinal irritation. The efficacy of once-yearly zoledronic acid (5 mg) in the treatment and prevention of osteoporosis has been evaluated in different patient populations. In the 3-year HORIZON-Pivotal Fracture Trial in postmenopausal women with osteoporosis, zoledronic acid reduced the risk of vertebral and hip fracture by 70% and 41%, respectively, versus placebo. The efficacy of zoledronic acid in preventing subsequent fracture in patients with a hip fracture was evaluated in the HORIZON-Recurrent Fracture Trial. New vertebral and nonvertebral fractures were significantly reduced by treatment initiated within 90 days of incident hip fracture, without evidence of delayed fracture healing. Data from a 1-year study show that a single zoledronic acid 5-mg infusion is superior to oral risedronate 5 mg/day for treatment and prevention of glucocorticoid-induced osteoporosis. Increases in bone mineral density and decreases in bone turnover markers were significantly greater with zoledronic acid than with risedronate. Two different treatment regimens of zoledronic acid were found to be more effective than placebo for prevention of bone loss in postmenopausal women and reducing markers of bone turnover after 2 years. In conclusion, zoledronic acid 5 mg once-yearly infusion has demonstrated marked efficacy in the treatment and prevention of primary and secondary osteoporosis, with a combination of fracture risk reduction and prevention of bone loss at key sites. It is the only agent shown to reduce the incidence of fracture and mortality in patients with a previous low-trauma hip fracture. PMID:22870433

Menstrual Migraine and Treatment Options: Review.

PubMed

Maasumi, Kasra; Tepper, Stewart J; Kriegler, Jennifer S

2017-02-01

A review of treatment options for menstrual migraine. Migraine affects ∼30 million people in the US. A subset of female migraineurs have migraines that are mainly associated with menstruation. Menstrual migraine (MM) is divided into pure MM and menstrually related migraine. Pure MM attacks occur only with menstruation and have a prevalence of 1%. Menstrually related migraine has a prevalence of 6-7%, and occurs both during menstruation as well as during the rest of the cycle. MM is usually without aura and is more severe, longer lasting, and more resistant to treatment due to the effects of ovarian hormones, specifically estrogen. MM treatment is divided into acute, short-term prophylaxis, and daily prevention. The best-studied acute treatments are triptans. For short-term prophylaxis, triptans, non-triptans, or combinations are used. Some preventive medications may be used daily to prevent MM. Many anti-epileptic medications used in migraine prevention can affect the efficacy of oral contraceptives and hormonal treatments, so caution is indicated when these are used. PubMed, Scopus, Cochrane, and Embase were searched for MM and treatments. Many randomized, placebo-controlled, prospective studies have evaluated the efficacy of sumatriptan, rizatriptan, naratriptan, zolmitriptan, and almotriptan in MM. Reviewing numerous studies with statistically significant results, rizatriptan has the best overall evidence for acute treatment of MM, ranging from pain-free responses of 33-73% at 2 hours. Sumatriptan and rizatriptan have shown similar efficacies of 61-63% in terms of 2 hour pain freedom. Rizatriptan showed sustained pain relief between 2 and 24 hours with an efficacy of 63% and sustained pain freedom for MM between 2 and 24 hours with an efficacy of 32%. For short-term prevention of MM, there were four randomized controlled trials for frovatriptan taken twice daily, one trial for zolmitriptan taken three times daily, and two studies for naratriptan taken twice daily, all of which showed statistically significant results. Among studies on non-triptans for short-term prevention of MM, magnesium, estrogen, naproxen sodium, and dihydroergotamine all had statistically significant results. Many antiepileptic medications taken for prevention of MM can cause enzyme induction affecting oral contraceptives (OCs) and hormonal treatments to different degrees. Topiramate has the least effect on OCs at doses below 200 mg/day. Lamotrigine noticeably decreases oral contraceptive levels; however, the evidence for it as a preventive medication is not strong. MM can be very difficult to treat. For acute treatments, rizatriptan has the best overall evidence. For short-term prevention, frovatriptan, zolmitriptan, or naratriptan, as well as magnesium, estrogen, naproxen sodium, or dihydroergotamine may be useful. © 2016 American Headache Society.

Consensus Document on Prevention and Treatment of Tuberculosis in Patients for Biological Treatment.

PubMed

Mir Viladrich, Isabel; Daudén Tello, Esteban; Solano-López, Guillermo; López Longo, Francisco Javier; Taxonera Samso, Carlos; Sánchez Martínez, Paquita; Martínez Lacasa, Xavier; García Gasalla, Mercedes; Dorca Sargatal, Jordi; Arias-Guillén, Miguel; García García, José Maria

2016-01-01

Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to TB is mandatory in these patients. This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

[Investigation and strategy research of eye disease prevention resources in community health service centers in Shanghai].

PubMed

He, Jiangnan; Zou, Haidong; Zhu, Jianfeng; He, Xiangui; Lu, Lina

2015-07-01

To investigate the status of eye disease prevention resources in community health service centers, to understand the distribution of ophthalmology service resources in each community, and to understand the main problems existing in the work of blindness prevention and treatment in Shanghai, so as to strengthen the prevention of blindness and improve the primary eye care level. Using the survey method, we carried out the investigation of disease control and prevention resources in all community health service centers to obtain the data of eye disease prevention and treatment resources. Using the descriptive statistics, we described the distribution of resources of eye disease prevention and treatment in different districts. There were 244 communities in 17 districts and counties in Shanghai, of which 236 (96.72%) communities participated in the survey and completed the questionnaires. Forty-nine (20.8%) communities had independent outpatient departments of ophthalmology, 96 (40.7%) had departments of ophthalmology and otorhinolaryngology, 33 (14%) had ophthalmology doctor visits from secondary or tertiary medical institutions, and 87 (36.9%) had no outpatient department of ophthalmology. There were 82 oculists, 129 general or otorhinolaryngology doctors treating eye disease, 9 ophthalmic nurses, and 1 optometrist. There were 36 specialized personnel for public health of eye protection and 217 part-time personnel. Moreover, there were a total of 1 103 pieces of ophthalmic equipment in all communities with the use rate of 91%. Uneven ophthalmology resources and eye care professional ability in community health service centers, lack of technical and public health personnel for prevention of eye disease, backward eye disease screening equipment, and inadequate investment in prevention and treatment of eye disease are major problems. More government supports for prevention and treatment of eye disease in communities and continuous improvement in three-level blindness prevention network systems and information construction are needed.

Cost-effectiveness model for prevention of early childhood caries.

PubMed

Ramos-Gomez, F J; Shepard, D S

1999-07-01

This study presents and illustrates a model that determines the cost-effectiveness of three successively more complete levels of preventive intervention (minimal, intermediate, and comprehensive) in treating dental caries in disadvantaged children up to 6 years of age. Using existing data on the costs of early childhood caries (ECC), the authors estimated the probable cost-effectiveness of each of the three preventive intervention levels by comparing treatment costs to prevention costs as applied to a typical low-income California child for five years. They found that, in general, prevention becomes cost-saving if at least 59 percent of carious lesions receive restorative treatment. Assuming an average restoration cost of $112 per surface, the model predicts cost savings of $66 to $73 in preventing a one-surface, carious lesion. Thus, all three levels of preventive intervention should be relatively cost-effective. Comprehensive intervention would provide the greatest oral health benefit; however, because more children would receive reparative care, overall program costs would rise even as per-child treatment costs decline.

Flu Prevention and Treatment Tips

MedlinePlus

Flu Prevention and Treatment Tips Expert Information from Healthcare Professionals Who Specialize in the Care of Older Adults Influenza, or the “flu,” is a contagious respiratory illness. It can cause ...

Genetics, Disease Prevention and Treatment

MedlinePlus

Skip to main content FAQ About Genetics, Disease Prevention and Treatment Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News ...

Articulating A Rights-Based Approach to HIV Treatment and Prevention Interventions

PubMed Central

Barr, David; Amon, Joseph J; Clayton, Michaela

2011-01-01

Since the beginning of the epidemic, the protection of human rights has been an integral component in the response to Human Immunodeficiency Virus (HIV). The high degree of stigma and discrimination associated with acquired immune deficiency syndrome (AIDS) has made human rights protection not only a priority to ensure the rights of people living with and at-risk for HIV, but to address public health goals as well. Advances in understanding the impact of antiretroviral treatment on HIV prevention provide exciting opportunities and even a paradigm shift in terms of AIDS prevention. However, this potential cannot be reached unless the advancement of human rights is a primary component of treatment and prevention programme and policy development. The use of antiretroviral treatment as prevention reinforces the value of basic principles related to the dignity and agency of people living with HIV to participate in the design and implementation of programmes, to be informed and to make informed decisions about their health and lives, to be protected from harm, and to have opportunities to seek redress and accountability for abuses. The possibility of using HIV treatment as a prevention tool means that now, more than ever, legal reform and community empowerment and mobilisation are necessary to realize the rights and health of people affected by HIV. PMID:21999775

Articulating a rights-based approach to HIV treatment and prevention interventions.

PubMed

Barr, David; Amon, Joseph J; Clayton, Michaela

2011-09-01

Since the beginning of the epidemic, the protection of human rights has been an integral component in the response to Human Immunodeficiency Virus (HIV). The high degree of stigma and discrimination associated with acquired immune deficiency syndrome (AIDS) has made human rights protection not only a priority to ensure the rights of people living with and at-risk for HIV, but to address public health goals as well. Advances in understanding the impact of antiretroviral treatment on HIV prevention provide exciting opportunities and even a paradigm shift in terms of AIDS prevention. However, this potential cannot be reached unless the advancement of human rights is a primary component of treatment and prevention programme and policy development. The use of antiretroviral treatment as prevention reinforces the value of basic principles related to the dignity and agency of people living with HIV to participate in the design and implementation of programmes, to be informed and to make informed decisions about their health and lives, to be protected from harm, and to have opportunities to seek redress and accountability for abuses. The possibility of using HIV treatment as a prevention tool means that now, more than ever, legal reform and community empowerment and mobilisation are necessary to realize the rights and health of people affected by HIV.

An Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer, Based on Epidermal Growth Factor Receptor Variant, Type III

DTIC Science & Technology

1999-05-01

H. (1996). Pulmonary metastases neutralization and tumor rejection by in vivo administration of B glucan and bispecific antibody. Int. J. Cancer 65...AD GRANT NUMBER DAMD17-96-1-6016 Title: An Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer , Based on Epidermal Growth...Leave blank) 2. REPORT DATE May 1999 4. TITLE AND SUBTITLE An Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer

Acute and Delayed Systemic Treatment with Cannabinoid Receptor 2 Agonists to Prevent or Treat/Reverse Osteoporosis in a Mouse Model of SCI

DTIC Science & Technology

2017-08-01

AWARD NUMBER: W81XWH-16-1-0349 TITLE: Acute and Delayed Systemic Treatment with Cannabinoid Receptor 2 Agonists to Prevent or Treat/Reverse...REPORT TYPE Annual 3. DATES COVERED 1 Aug 2016 - 31 Jul 2017 4. TITLE AND SUBTITLE Acute and Delayed Systemic Treatment with Cannabinoid Receptor 2...for the cannabinoid-2 receptor, when systemically delivered, can prevent the onset of osteoporosis in mice when delivered during the acute phase of

The role of antibiotics in the prevention of preterm birth

PubMed Central

2009-01-01

There are multiple uses for antibiotics during pregnancy: treatment of intercurrent bacterial infections such as urinary or respiratory tract infections, maternal treatment to prevent fetal or neonatal disease, prophylactic treatment for surgical procedures, and treatment of puerperal infections. This report will summarize the current recommendations for the use of antibiotics specifically to reduce the risk of preterm birth. PMID:20948759