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Sample records for long-term pioglitazone treatment

  1. Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial.

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    Cusi, Kenneth; Orsak, Beverly; Bril, Fernando; Lomonaco, Romina; Hecht, Joan; Ortiz-Lopez, Carolina; Tio, Fermin; Hardies, Jean; Darland, Celia; Musi, Nicolas; Webb, Amy; Portillo-Sanchez, Paola

    2016-09-06

    The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone. However, information about its long-term use in this population is limited. To determine the efficacy and safety of long-term pioglitazone treatment in patients with NASH and prediabetes or T2DM. Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT00994682). University hospital. Patients (n = 101) with prediabetes or T2DM and biopsy-proven NASH were recruited from the general population and outpatient clinics. All patients were prescribed a hypocaloric diet (500-kcal/d deficit from weight-maintaining caloric intake) and then randomly assigned to pioglitazone, 45 mg/d, or placebo for 18 months, followed by an 18-month open-label phase with pioglitazone treatment. The primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease activity score in 2 histologic categories without worsening of fibrosis. Secondary outcomes included other histologic outcomes, hepatic triglyceride content measured by magnetic resonance and proton spectroscopy, and metabolic parameters. Among patients randomly assigned to pioglitazone, 58% achieved the primary outcome (treatment difference, 41 percentage points [95% CI, 23 to 59 percentage points]) and 51% had resolution of NASH (treatment difference, 32 percentage points [CI, 13 to 51 percentage points]) (P < 0.001 for each). Pioglitazone treatment also was associated with improvement in individual histologic scores, including the fibrosis score (treatment difference, -0.5 [CI, -0.9 to 0.0]; P = 0.039); reduced hepatic triglyceride content from 19% to 7% (treatment difference, -7 percentage points [CI, -10 to -4 percentage points]; P < 0.001); and improved adipose tissue, hepatic, and muscle insulin sensitivity (P < 0.001 vs. placebo for all). All 18-month metabolic and histologic improvements persisted over 36 months of

  2. Long-term pioglitazone treatment enhances lipolysis in rat adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kazdová, L.; Maxová, M.; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Kurtz, T. W.

    2008-01-01

    Roč. 32, č. 12 (2008), s. 1848-1853 ISSN 0307-0565 R&D Projects: GA MŠk(CZ) 1M0520; GA MŠk(CZ) 1P05ME791; GA AV ČR(CZ) IAA500110604; GA MZd NR9387; GA MZd(CZ) NR9359 Grant - others:EURATools(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Keywords : pioglitazone * adipose tissue * lipolysis Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.640, year: 2008

  3. Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment.

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    Moon, Jae Hoon; Kim, Hae Jin; Kim, Soo Kyung; Kang, Eun Seok; Lee, Byung Wan; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong-Soo

    2011-02-01

    Thiazoledinedione is known to have an anti-inflammatory effect besides a hypoglycemic effect. We investigated changes in high-sensitivity C-reactive protein (hsCRP), a proinflammatory marker, after pioglitazone treatment in association with the resulting changes in various metabolic and anthropometric parameters. A total of 93 type 2 diabetes mellitus patients (47 men and 46 women; mean age, 50.0 ± 10.8 years) who were being treated with a stable dose of sulfonylurea or metformin were enrolled in the study. Pioglitazone (15 mg/d) was added to their treatment regimen for 12 weeks, and metabolic and anthropometric measurements were taken before and after pioglitazone treatment. Pioglitazone treatment for 12 weeks decreased serum hsCRP levels (0.83 [1.14] to 0.52 [0.82] mg/L, P fasting glucose, P benefits of pioglitazone treatment. © 2011 Elsevier Inc. All rights reserved.

  4. Effect of pioglitazone treatment in a patient with secondary multiple sclerosis

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    Pershadsingh Harrihar A

    2004-04-01

    Full Text Available Abstract Background Ligands of the peroxisome proliferator-activated receptor-gamma (PPARγ induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARγ agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. Case presentation The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32% and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. Conclusions In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events

  5. Treatment with pioglitazone induced significant, reversible mitral regurgitation.

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    Dorkhan, Mozhgan; Dencker, Magnus; Frid, Anders

    2008-04-30

    There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

  6. Treatment with pioglitazone induced significant, reversible mitral regurgitation

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    Frid Anders

    2008-04-01

    Full Text Available Abstract There has in recent years been great concern about possible cardiac side effects of thiazolidinediones (TZDs. We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.

  7. Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective

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    Massi-Benedetti Massimo

    2009-05-01

    Full Text Available Abstract Background The aim of this study was to project health-economic outcomes relevant to the German setting for the addition of pioglitazone to existing treatment regimens in patients with type 2 diabetes, evidence of macrovascular disease and at high risk of cardiovascular events. Methods Event rates corresponding to macrovascular outcomes from the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive study of pioglitazone were used with a modified version of the CORE Diabetes Model to simulate outcomes over a 35-year time horizon. Direct medical costs were accounted from a healthcare payer perspective in year 2005 values. Germany specific costs were applied for patient treatment, hospitalization and management. Both costs and clinical benefits were discounted at 5.0% per annum. Results Over patient lifetimes pioglitazone treatment improved undiscounted life expectancy by 0.406 years and improved quality-adjusted life expectancy by 0.120 quality-adjusted life years (QALYs compared to placebo. Direct medical costs (treatment plus complication costs were marginally higher for pioglitazone treatment and calculation of the incremental cost-effectiveness ratio (ICER produced a value of €13,294 per QALY gained with the pioglitazone regimen versus placebo. Acceptability curve analysis showed that there was a 78.2% likelihood that pioglitazone would be considered cost-effective in Germany, using a "good value for money" threshold of €50,000 per QALY gained. Sensitivity analyses showed that the results were most sensitive to changes in the simulation time horizon. After adjustment for the potential stabilization of pancreatic β-cell function with pioglitazone treatment, the ICER was €6,667 per QALY gained for pioglitazone versus placebo. Conclusion The findings of this modelling analysis indicated that, for patients with a history of macrovascular disease, addition of pioglitazone to existing therapy reduces the long-term

  8. Effect of pioglitazone treatment on behavioral symptoms in autistic children

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    Edelson Stephen M

    2007-01-01

    Full Text Available Abstract Introduction Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs are agonists of the peroxisome proliferator activated receptor gamma (PPARγ, a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. Case description The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC, which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. Discussion and evaluation In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity. Improved behaviors were inversely

  9. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

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    Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

    2016-01-01

    Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

  10. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

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    Michael Spencer

    Full Text Available Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily. These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01, and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2 (p = 0.02 in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

  11. Anti-diabetes drug pioglitazone ameliorates synaptic defects in AD transgenic mice by inhibiting cyclin-dependent kinase5 activity.

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    Jinan Chen

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ, which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.

  12. Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice

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    Chunming Jia

    2015-05-01

    Full Text Available Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ, is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD. However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.

  13. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS).

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    Valsamakis, Georgios; Lois, Kostas; Kumar, Sudhesh; Mastorakos, George

    2013-01-01

    Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their "add-on effect" on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metformin-resistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of pioglitazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

  14. Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats

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    Dengfeng Gao

    2012-01-01

    Full Text Available Objective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males were randomly divided into 3 groups (n=8 each for treatment: pioglitazone (10 mg/kg/day, hydralazine (25 mg/kg/day, or saline. Normal male Wistar Kyoto (WKY rats (n=8 served as normal controls. Twelve weeks later, we evaluated the effect of pioglitazone on vascular fibrosis by Masson’s trichrome and immunohistochemical staining of collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA.Vascular expression of PPAR-γ and connective tissue growth factor (CTGF and transforming growth factor-β (TGF-β expression were evaluated by immunohistochemical staining, western blot analysis, and real-time RT-PCR. Results. Pioglitazone and hydralazine treatment significantly decreased systolic blood pressure in SHRs. Masson’s trichrome staining for collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA indicated that pioglitazone significantly inhibited extracellular matrix production in the aorta. Compared with Wistar Kyoto rats, SHRs showed significantly increased vascular CTGF expression. Pioglitazone treatment significantly increased PPAR-γ expression and inhibited CTGF expression but had no effect on TGF-β expression. Conclusions. The results indicate that pioglitazone attenuated vascular fibrosis in SHRs by inhibiting CTGF expression in a TGF-β-independent mechanism.

  15. Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

    DEFF Research Database (Denmark)

    Vigerust, Natalya Filipchuk; Bohov, Pavol; Bjørndal, Bodil

    2012-01-01

    To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS).......To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS)....

  16. Meal fat storage in subcutaneous adipose tissue: comparison of pioglitazone and glipizide treatment of type 2 diabetes.

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    Basu, Ananda; Basu, Rita; Pattan, Vishwanath; Rizza, Robert A; Jensen, Michael D

    2010-10-01

    Treatment of type 2 diabetes (T2DM) with pioglitazone changes abdominal fat in the opposite direction as treatment with glipizide. To determine whether these two medications affect adipose tissue meal fatty acid storage differently we studied 19 T2DM treated with either pioglitazone (n = 8) or glipizide (n = 11) and 11 non-DM control subjects matched for age, BMI, abdominal and leg fat. A breakfast mixed meal containing [1-(14)C]triolein was given and abdominal and femoral subcutaneous (sc) adipose tissue biopsies were collected 6 and 24 h later to measure meal fatty acid storage. The portion of meal fatty acids stored in upper body sc and lower body sc adipose tissue did not differ between non-DM and T2DM subjects either at 6 or 24 h. Likewise, meal fatty acid storage did not differ between the T2DM participants treated with pioglitazone or glipizide. We conclude that meal fatty acid storage in upper body and lower body sc adipose tissue is not abnormal in T2DM patients treated with pioglitazone or glipizide.

  17. Plasma osteoprotegerin is associated with testosterone levels but unaffected by pioglitazone treatment in patients with polycystic ovary syndrome

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    Glintborg, D; Hermann, Pernille; Rasmussen, Lars Melholt

    2013-01-01

    in polycystic ovary syndrome (PCOS). Research design and methods Plasma OPG levels were measured in 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Fourteen age and BMI matched healthy women were included as controls. Clinical and hormonal evaluations......Objective Increased osteoprotegerin (OPG) levels are associated with increased cardiovascular risk and decreased bone resorption. Pioglitazone treatment reduces the inflammatory state but may decrease bone mineral density. OPG levels during pioglitazone treatment have not previously been evaluated...... and whole body DXA-scans were performed in all participants. Results OPG levels were comparable in PCOS patients [12.0 (10.5 - 14.6) ng/ml] and controls [12.9 (11.7 - 14.9) ng/ml]. In PCOS patients (n=30), OPG levels were positively associated with testosterone (r= 0.43), prolactin (r= 0.47), ICTP (r= 0...

  18. Long-term pioglitazone treatment augments insulin sensitivity and PKC-epsilon and PKC-theta activation in skeletal muscles in sucrose fed rats

    Czech Academy of Sciences Publication Activity Database

    Marková, I.; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Mlejnek, Petr; Kazdová, L.; Pravenec, Michal

    2010-01-01

    Roč. 59, č. 4 (2010), s. 509-516 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0520; GA MŠk(CZ) ME08006; GA AV ČR(CZ) IAA500110604; GA MZd(CZ) NR9387; GA MZd(CZ) NR9359; GA MZd(CZ) NS9759 Institutional research plan: CEZ:AV0Z50110509 Keywords : pioglitazone * PKC * insulin resistance Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.646, year: 2010

  19. Association of decrease in liver triglyceride content with increase in plasma adiponectin levels after pioglitazone treatment in Japanese patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Nagasawa, Kan; Kaneko, Yoshihito; Taneichi, Haruhito

    2010-01-01

    Pioglitazone, an insulin-sensitizing thiazolidinedione, has multiple clinical effects including improvement of insulin sensitivity, blood glucose levels and serum lipid profiles, decrease in liver triglyceride (TG) content, and increase in serum adiponectin. However, the correlation and causal relationship between these effects are not fully understood clinically. Therefore, we analyzed these relationships in patients with type 2 diabetes treated with pioglitazone, focusing on changes in liver TG content and serum adiponectin. Thirteen Japanese patients with type 2 diabetes were treated with pioglitazone (15 mg/day) for more than 3 months. Before and after the pioglitazone treatment, liver TG content was measured by magnetic resonance spectroscopy and various clinical variables were also measured. The pioglitazone treatment significantly decreased the liver TG content (-12.9±8.1%, p 2 =0.53, p=0.017), implying increased serum adiponectin may have decreased liver fat content. (author)

  20. [Six-month effectiveness and tolerability of pioglitazone in combination with sulfonylureas or metformin for the treatment of type 2 diabetes mellitus].

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    Rodríguez, Angel; Reviriego, Jesús; Polavieja, Pepa; Mesa, Jordi

    2008-11-29

    Pioglitazone has been reported to improve common cardiovascular risk factors in addition to glycemic control in patients with type 2 diabetes mellitus (T2DM). The changes in cardiovascular risk profile were evaluated comparatively in large cohorts either treated or not with pioglitazone-containing combinations in the current clinical setting within Spain. A nationwide prospective, controlled, observational cohort clinical study was performed in 2294 patients with T2DM who started, at the criterion of the treating physician, oral antihyperglycemic treatment with either pioglitazone plus a sulfonylurea (Pio+SU; n=851), pioglitazone plus metformin (Pio+Met; n=723) or a sulfonylurea plus metformin (SU+Met; n=720) due to inadequate control with previous therapy. Serum cholesterol, blood glucose, hemoglobin A1C, blood pressure and certain anthropometric parameters were measured at baseline and after 6 months of treatment. Serum high density lipoprotein-cholesterol increased in average (mg/dl) 2.08 with Pio+SU, 2.06 with Pio+Met and 0.67 with SU+Met; while triglycerides decreased (mg/dl) 26.6, 30.6 and 17.6 in the same cohorts. Inter-group differences were significant (p<0.001 in both parameters). Total cholesterol decreased significantly more with SU+Met than in the pioglitazone cohorts. Mean fasting plasma glucose and hemoglobin A1C reductions were significantly greater in the pioglitazone cohorts than in the SU+Met cohort: 27.74, 28.94 and 23.46 mg/dl (p=0.012); and 0.80, 0.87 and 0.71% (p=0.016) with Pio+SU, Pio+Met and SU+Met, respectively. Slight, but significant variations of body weight were also registered in the Pio+SU (+1.4 kg) and SU+Met (-0.7 kg) groups. Treatment with pioglitazone was associated with significant improvements of lipid and glycemic parameters that are linked to insulin resistance and cardiovascular risk in patients with T2DM in their routine clinical care. The non-randomised allocation of patients to treatments, inherent to its observational

  1. Fish oil prevents excessive accumulation of subcutaneous fat caused by an adverse effect of pioglitazone treatment and positively changes adipocytes in KK mice

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    Yuzuru Iizuka

    Full Text Available Pioglitazone, a thiazolidinedione (TZD, is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO, safflower oil/low-dose pioglitazone (S/PL, and safflower oil/high-dose pioglitazone (S/PH diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt pioglitazone, respectively. In fish oil (FO, fish oil/low-dose pioglitazone (F/PL, and fish oil/high-dose pioglitazone (F/PH diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups; however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis. Keywords: Fish oil, Pioglitazone, Adverse effect

  2. Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study

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    Sunil Gupta

    2015-01-01

    Full Text Available Aim: To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients. Methods: A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography. Results: Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8% with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5% with pioglitazone therapy. Conclusion: Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control.

  3. Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Chang, Yu-Hung; Hwu, Der-Wei; Chang, Dao-Ming; An, Ling-Wang; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

    2017-06-01

    Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included. A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively. Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

  4. Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment.

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    Newsom, Sean A; Miller, Benjamin F; Hamilton, Karyn L; Ehrlicher, Sarah E; Stierwalt, Harrison D; Robinson, Matthew M

    2017-11-01

    Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10-12 High-resolution respirometry was performed using palmitoyl-l-carnitine, glutamate+malate, and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation were increased in mice consuming a high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H 2 O 2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with a high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance. Copyright © 2017 the

  5. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

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    Hong Yang

    Full Text Available INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR, and glycated hemoglobin (HbA1c% were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3 were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001 whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001. Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001 was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001. CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

  6. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

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    Toba, Junya; Nikkuni, Miyu; Ishizeki, Masato; Yoshii, Aya; Watamura, Naoto; Inoue, Takafumi; Ohshima, Toshio

    2016-01-01

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  7. Pioglitazone Improves Survival In Patients With Cancer: The Hypothesis

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    Banshi Saboo

    2015-12-01

    Full Text Available Pioglitazone is currently the only thiazolidinedione approved by regulatory agencies worldwide for the treatment of type 2 diabetes mellitus (T2DM. The use of pioglitazone in patients with T2DM has been limited because earlier studies showed moderate weight gain and an increased incidence of heart failure, osteoporotic fractures, and bladder cancer. However, new studies have shown that pioglitazone improves both systolic and diastolic left ventricular function and that there is no association between pioglitazone and bladder cancer. Furthermore, pioglitazone is associated with a reduced risk of all-cause mortality in patients with T2DM. Pioglitazone was also found to reduce the incidence of lung, head and neck, breast, colorectal, and hepatocellular cancer. There is tremendous preclinical evidence that links thiazolidinediones with anti-cancer effects. Three possible mechanisms of anti-proliferative effects induced by peroxisome proliferator activated receptor gamma (PPARG agonists emerge: 1 activation of PPARG and epidermal growth factor receptor, which actives several intracellular pathways involved in carcinogenesis; 2 increase in serum adiponectin levels and decrease in serum leptin levels, which are associated with lower cancer risk and more favorable outcomes in patients with cancer; 3 modulate insulin-like growth factor 1 (IGF-1 receptor signaling by decreasing IGF-1 levels and increasing the expression of IGF binding protein 1. To date, there are no prospective, placebo-controlled trials that have analyzed the efficacy of pioglitazone in chemotherapy and chemoprevention. Only one ongoing study has shown that pioglitazone has an excellent capability of eradicating quiescent leukemia stem cells in patients with chronic myeloid leukemia and achieving a complete molecular response. Current evidence supports our theory that future case-control studies examining pioglitazone as chemotherapy, or adjuvant chemotherapy, should be performed in

  8. Current clinical evidence on pioglitazone pharmacogenomics

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    Marina eKawaguchi-Suzuki

    2013-11-01

    Full Text Available Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ. Pioglitazone is approved for use in the management of type 2 diabetes mellitus, but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p=0.018. Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone

  9. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors

    Science.gov (United States)

    Saremi, Aramesh; Schwenke, Dawn C.; Buchanan, Thomas A.; Hodis, Howard N.; Mack, Wendy J.; Banerji, MaryAnn; Bray, George A.; Clement, Stephen C.; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Musi, Nicolas; Tripathy, Devjit; DeFronzo, Ralph A.; Reaven, Peter D.

    2013-01-01

    Objective To determine whether changes in standard and novel risk factors during the ACT NOW trial explained the slower rate of CIMT progression with pioglitazone treatment in persons with prediabetes. Methods and Results CIMT was measured in 382 participants at the beginning and up to three additional times during follow-up of the ACT NOW trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly (P=0.01) lower with pioglitazone treatment (4.76 × 10−3 mm/year, 95% CI, 2.39 × 10−3 – 7.14 × 10−3 mm/year) compared with placebo (9.69 × 10−3 mm/year, 95% CI, 7.24 × 10−3 – 12.15 × 10−3 mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA1c, fasting insulin, Matsuda insulin sensitivity index, adiponectin and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo (P < 0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment. Conclusions Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone. PMID:23175674

  10. Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin.

    Science.gov (United States)

    Kim, Jong Ho; Kim, Sang Soo; Baek, Hong Sun; Lee, In Kyu; Chung, Dong Jin; Sohn, Ho Sang; Bae, Hak Yeon; Kim, Mi Kyung; Park, Jeong Hyun; Choi, Young Sik; Kim, Young Il; Hahm, Jong Ryeal; Lee, Chang Won; Jo, Sung Rae; Park, Mi Kyung; Lee, Kwang Jae; Kim, In Joo

    2016-06-01

    We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes. The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin. The mean changes in HbA1c levels from baseline were -0.94% in the vildagliptin group and -0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were -60.2 mg/dL in the vildagliptin group and -38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was -0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002). As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

  11. Pioglitazone could induce remission in major depression: a meta-analysis

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    Colle R

    2016-12-01

    Full Text Available Romain Colle,1,* Delphine de Larminat,1,* Samuel Rotenberg,1 Franz Hozer,1 Patrick Hardy,1 Céline Verstuyft,2 Bruno Fève,3,* Emmanuelle Corruble1,* 1Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 2Molecular Genetic, Pharmacogenetics and Hormonology Department, Hôpital Bicêtre, INSERM UMR_S1184, Centre IMVA, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 3Endocrinology Department, INSERM UMR_S938, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Paris, France *These authors contributed equally to this work Background: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ, prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates.Methods: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts. It was compared either to placebo (three studies or to metformin (one study. Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment.Results: Pioglitazone could induce higher remission

  12. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

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    Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

    2016-05-13

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  13. Comparison of the effect between pioglitazone and metformin in treating patients with PCOS:a meta-analysis.

    Science.gov (United States)

    Xu, Yifeng; Wu, Yanxiang; Huang, Qin

    2017-10-01

    Pioglitazone was used to treat patients of PCOS in many researches, but the treatment has not been recognized by public or recommended by all the guidelines. We conducted a meta-analysis of the related literatures to objectively evaluate the clinical effectiveness and safety by comparing pioglitazone with metformin administrated by PCOS patients. Searches were performed in Cochrane Library, EMBASE and PubMed (last updated December 2016). Eleven studies among 486 related articles were identified through searches. Fixed effects and random effects models were used to calculate the overall risk estimates. The results of the meta-analysis suggest that improvement of the menstrual cycle and ovulation in pioglitazone treatment group was better than metformin group [OR = 2.31, 95% CI (1.37, 3.91), P treatment group was better than pioglitazone group [SMD = 0.29, 95% CI (0.0, 0.59), P = 0.048, I 2  = 0.0%]. BMI was more elevated in pioglitazone group than in metformin group [SMD = 0.83, 95% CI (0.24, 1.41), P = 0.006, I 2  = 82.8%]. There were no significant differences of the other data between the two groups. This meta-analysis indicated that pioglitazone ameliorated menstrual cycle and ovulation better than metformin and metformin ameliorated BMI and F-G scores better than pioglitazone in treating patients with PCOS. Pioglitazone might be a good choice for the patients with PCOS who were intolerant or invalid to metformin for the treatment.

  14. Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin

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    Jong Ho Kim

    2016-04-01

    Full Text Available BackgroundWe compared the efficacies of vildagliptin (50 mg twice daily relative to pioglitazone (15 mg once daily as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c levels in Korean patients with type 2 diabetes.MethodsThe present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.ResultsThe mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040. There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL, and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002.ConclusionAs an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

  15. Enhancing pancreatic Beta-cell regeneration in vivo with pioglitazone and alogliptin.

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    Hao Yin

    Full Text Available Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes.In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass.Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery.These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.

  16. Pioglitazone and bladder cancer in human studies: Is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

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    Chin-Hsiao Tseng

    2012-03-01

    pioglitazone and comparators will be helpful. Well-conducted epidemiologic observational studies are probably other options. Because bladder cancer incidence and their risk factors may differ significantly among different ethnicities, a clarification of such a link in different ethnicities is needed, better by using long-term databases with large and representative sample size and appropriate adjustment for confounders. Furthermore, the interactions with other comorbidities and concomitant medications should be addressed.

  17. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Glintborg, D.; Andersen, Mikael; Hagen, C.

    2008-01-01

    OBJECTIVE: Our objective was to investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS). DESIGN AND SETTING: We conducted a randomized, placebo-controlled study at an outpatient clinic at a university hospital. PATIENTS......, sex hormones, and body composition. CONCLUSION: Pioglitazone treatment was followed by decreased lumbar and hip BMD and decreased measures of bone turnover in a premenopausal study population relatively protected from bone mineral loss Udgivelsesdato: 2008/5...

  18. Pioglitazone metabolic effect in metformin-intolerant obese patients treated with sibutramine.

    Science.gov (United States)

    Derosa, Giuseppe; Mereu, Roberto; Salvadeo, Sibilla A T; D'Angelo, Angela; Ciccarelli, Leonardina; Piccinni, Mario N; Ferrari, Ilaria; Gravina, Alessia; Maffioli, Pamela; Cicero, Arrigo F G

    2009-01-01

    Metformin is the drug of choice to treat obese type 2 diabetes patients because it reduces either insulin-resistance and body weight. We aimed to comparatively test the efficacy and tolerability of pioglitazone and sibutramine in metformin-intolerant obese type 2 diabetic patients treated with sibutramine. Five hundred and seventy-six consecutive Caucasian obese type 2 diabetic patients were evaluated during a 12-months period and fifty-two patients were resulted intolerant to metformin at maximum dosage (3,000 mg/day). All intolerant patients to metformin received a treatment with pioglitazone (45 mg/day) and sibutramine (10 mg/day) and they were compared with fifty-three patients treated with metformin (3,000 mg/day) and sibutramine (10 mg/day) for 6 months in a single-blind controlled trial. We assessed body mass index, waist circumference, glycated hemoglobin, Fasting Plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, lipid profile, systolic blood pressure, diastolic blood pressure and heart rate at baseline and after 3, and 6 months. No body mass index change was observed at 3, and 6 months in pioglitazone + sibutramine group, while a significant reduction of body mass index and waist circumference was observed after 6 months in metformin + sibutramine group (psibutramine combination appears to be a short-term equally efficacious and well-tolerated therapeutic alternative respect to metformin-intolerant obese type 2 diabetic patients treated with sibutramine.

  19. Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Frystyk, Jan; Højlund, Kurt

    2008-01-01

    and controls and examined possible mechanisms for increased insulin sensitivity during pioglitazone treatment. STUDY SUBJECTS: Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied. DESIGN: Total and HMW adiponectin levels were...... measured, and euglycaemic hyperinsulinaemic clamps and indirect calorimetry were performed. Delta-values denoted changes during pioglitazone treatment (16 weeks--basal). RESULTS: Pretreatment adiponectin levels were decreased in PCOS patients vs. controls (P ...OBJECTIVE: Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients...

  20. Decreased incidence of gout in diabetic patients using pioglitazone.

    Science.gov (United States)

    Niu, Sheng-Wen; Chang, Kai-Ting; Lin, Hugo You-Hsien; Kuo, I-Ching; Chang, Yu-Han; Chen, Yu-Han; Hung, Chi-Chih; Chiu, Yi-Wen; Hwang, Shang-Jyh

    2018-01-01

    The incidence and prevalence of gout are increasing, but the management is poor. Considering the increased prevalence of gout in the diabetic population, this study evaluated the effects of pioglitazone, an insulin resistance inhibitor, on the incidence of gout in the diabetic population. We used data from the National Health Insurance program in Taiwan. The pioglitazone cohort contained 30 100 patients and each patient was age and sex matched with three non-pioglitazone users who were randomly selected from the diabetic population. Cox proportional hazards regression analysis was conducted to estimate the effects of pioglitazone on the incidence of gout in the diabetic population. The incidence of gout was significantly lower in pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR) 0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)] pioglitazone users than in non-pioglitazone users. An analysis of three age groups (gout in the diabetic population using pioglitazone was less. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  1. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

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    Karoon Shahebrahimi

    2016-01-01

    Full Text Available Introduction: Polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years were treated orally with either metformin (500 mg 3 times daily or pioglitazone (30 mg daily for 3 months. Clinical (body weight, blood pressure [BP], and body mass index and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA] were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008, wrist circle (P = 0.011, weight (P = 0.047, diastolic BP (P = 0.023, and DHEA (P = 0.035. A significant decrease in TG was seen with pioglitazone treatment (P = 0.047. In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin.

  2. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Andersen, Marianne

    2006-01-01

    OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study. ......, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment....

  3. Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Bundhun, Pravesh Kumar; Janoo, Girish; Teeluck, Abhishek Rishikesh; Huang, Feng

    2017-10-23

    vildagliptin and pioglitazone/rosiglitazone are acceptable for the treatment of patients with T2DM on the basis that they are not significantly different in terms of overall adverse drug events. However, weight gain and peripheral edema would have to be re-assessed in further larger randomized controlled trials.

  4. Comparative study of telmisartan with pioglitazone on insulin resistance in type 2 diabetic mice

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    Khan, A.; Qayyum, A.; Khan, B.T.

    2017-01-01

    Objective: To evaluate and compare the effects of telmisartan and pioglitazone on peripheral insulin resistance in diabetic mice. Study Design: Randomized control trail. Place and Duration of Study: National Institute of Health, Islamabad and pharmacology dept, Army Medical College, from 17th March to 17th June 2014. Material and Methods: Twenty four BALB/c mice, both male and female, of 35 to 40 grams were used for this study. Animals were randomly divided into four groups. Two were taken as control groups, one was normal control and the other was diabetic control. Two were taken as interventional groups and received either pioglitazone or telmisartan for four weeks after induction of diabetes. Results: After treatment, pioglitazone reduced all the biochemical parameters significantly when compared with diabetic control. Negative correlation between glucose and insulin was changed into positive correlation (r-value, 0.92) with significant p-value (0.015) in pioglitazone treated group, while telmisartan only managed to convert a negative correlation between insulin and glucose into statistically non-significant positive. Conclusion: Telmisartan although reduces glucose levels and improves beta cell mass but the effect is statistically non-significant as compared to pioglitazone. In hypertensive type 2 diabetics a combination of these two drugs may help in reducing the dose of pioglitazone and consequently the cardiovascular adverse effects of pioglitazone. (author)

  5. Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

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    Yang Ching-Hsiu

    2008-09-01

    Full Text Available Abstract Background Pioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2 and DNA glycosylase (Ogg1, MutY. Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression. Results Our results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration. Conclusion The attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease.

  6. Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

    Science.gov (United States)

    Hsiao, Pi-Jung; Hsieh, Tusty-Jiuan; Kuo, Kung-Kai; Hung, Wei-Wen; Tsai, Kun-Bow; Yang, Ching-Hsiu; Yu, Ming-Lung; Shin, Shyi-Jang

    2008-01-01

    Background Pioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY). Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression. Results Our results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration. Conclusion The attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease. PMID:18822121

  7. Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway

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    Wu, Yuanyuan; Li, Pengfen; Zhang, Dan; Sun, Yingpu

    2018-01-01

    Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance. The potential mechanism for the therapeutic effect of metformin and pioglitazone on POCS was explored through using three inhibitors of the 5′adenosine monophosphate-activated protein kinase (AMPK)/phosphoinositide-3 kinase (PI3K)/c-Jun N-terminal kinase (JNK) pathway (Compound C, Wortmannin and SP600125). The results showed that EV-induced PCOS rats demonstrated hyperandrogenemia, hyperinsulinemia and follicular dysplasia. Metformin or pioglitazone monotherapy significantly suppressed the high level of testosterone, reduced the raised percentage of cystic follicles and primary follicles, promoted the number of early antral follicles, and markedly decreased the high concentration of fasting insulin and homeostatic model assessment for insulin resistance index in PCOS rats. In addition, metformin and pioglitazone combination therapy demonstrated greater efficacy than its individual components. Furthermore, individual or joint treatment with metformin and pioglitazone affected the phosphorylation level of JNK in PCOS rats. Compound C and Wortmannin eliminated the effect of metformin and pioglitazone combination therapy on improving the follicular growth in PCOS rats, whereas SP600125 treatment enhanced this combination therapy effect. These data suggested that metformin and pioglitazone combination therapy

  8. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial.

    Science.gov (United States)

    Umpierrez, Guillermo; Issa, Maher; Vlajnic, Aleksandra

    2006-04-01

    To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy. Multicenter, randomized, parallel-group, open-label, forcedtitration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5-10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C-peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated. Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (p = 0.0001) and FPG (p use of fasting C-peptide concentration > or = 0.27 nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability. In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.

  9. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Mozhgan Dorkhan

    2007-11-01

    Full Text Available Mozhgan Dorkhan, Anders FridDepartment of Clinical Sciences, Division of Diabetes and Endocrinology, Lund University, Malmö University Hospital, SwedenAbstract: Type 2 diabetes (T2D is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/glinides or insulin, biguanides, and thiazolidinediones (TZDs respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.Keywords: pioglitazone, glimepiride, type 2 diabetes, thiazolidinediones, sulfonylureas

  10. Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

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    Weber Mitch

    2008-03-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD, which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a mice, possessing a mutation (Ay in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction. Methods Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4 or an equal volume of vehicle (DMSO; n = 4 for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression. Results Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM, and actin-related protein 6 homolog (ARP6. For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a non-mutant lean mice. Conclusion TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

  11. Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.

    Science.gov (United States)

    Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D; DeFronzo, Ralph A

    2014-06-01

    Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. © 2014 by the American Diabetes Association.

  12. Combination therapy with DPP-4 inhibitors and pioglitazone in type 2 diabetes: theoretical consideration and therapeutic potential

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    Nasser Mikhail

    2008-12-01

    Full Text Available Nasser MikhailEndocrinology Division, Olive View-UCLA Medical Center, David-Geffen School of Medicine, CA, USAAbstract: Sitagliptin and vildagliptin represent a new class of anti-diabetic agents that enhance the action of incretin hormones through inhibition of dipeptidyl peptidase-4 (DPP-4, the enzyme that normally inactivates incretin hormones. Because of their distinct mechanism of action, DPP-4 inhibitors can be used as add-on therapy to other classes of drugs for treatment of type 2 diabetes. The objective of this review is to critically evaluate clinical trials of sitagliptin and vildagliptin in combination with pioglitazone. The addition of either sitagliptin or vildagliptin to ongoing pioglitazone therapy is associated with reduction in average hemoglobin A1c (HbA1c levels of approximately 0.7% compared with placebo and 1% compared with baseline after 24 weeks. When started concomitantly in drug-naïve patients, the combination of pioglitazone 30 mg and vildagliptin 100 mg qd reduces HbA1c by 1.9% after 24 weeks, compared with 1.1% with pioglitazone monotherapy. In general, the addition of DPP-4 inhibitors to pioglitazone was well tolerated, did not increase the incidence of hypoglycemia, and did not substantially worsen the weight-gain induced by pioglitazone. The combination of sitagliptpin or vildagliptin with pioglitazone can be a useful therapeutic approach in patients with type 2 diabetes who cannot tolerate metformin or a sulfonylurea.Keywords: incretins, sitagliptin, vildagliptin, dipeptidyl peptidase inhibitors, pioglitazone, type 2 diabetes

  13. Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents.

    Science.gov (United States)

    de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

    2017-01-01

    Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown. To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats. We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms. Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse. These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

  14. The Preventive Role of Pioglitazone in Glycerol-Induced Acute Kidney Injury in Rats during Two Different Treatment Periods

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    Rama Mousleh

    2018-03-01

    Full Text Available Background: Acute kidney injury is the most life-threatening complication of rhabdomyolysis. Glycerol is commonly used to induce this injury. The aim was to investigate the renoprotective effects of pioglitazone and the possible advantage of administering the drug for a longer period. Methods: Twenty-four male Albino Wistar rats were randomly divided into 4 groups (n=6/group: (A control, (B glycerol (50%, 10 mL/kg intramuscularly, (C glycerol+pioglitazone (10 mg/kg orally for 3 days, and (D glycerol+pioglitazone (for 6 days. Serum urea and creatinine levels were measured to assess the renal function. Reduced glutathione (GSH levels and histological alterations were also measured. Statistical analysis was performed using Prism (version 6. The numerical data were evaluated by ANOVA, followed by the Tukey tests. The categorical data were evaluated by the Mann–Whitney test and the Fisher exact tests. P<0.05 was considered significant. Results: In the glycerol-injected rats, the serum urea and creatinine levels were increased (P<0.001, while the GSH levels were decreased (P<0.001 compared to Group A. The nephrotoxicity showed significant tubular (P=0.01 and glomerular (P=0.02 injuries. In the pioglitazone-treated rats, the changes in the serum biomarkers and in the GSH levels were reversed in Group C (P=0.01 and in Group D (P=0.01. The microscopic examinations of the kidneys also showed some improvement. No obvious statistically significant difference was found between these 2 preventive groups in most studied features. Conclusion: These results indicate that pioglitazone might have nephroprotective effects in this injury model. Pioglitazone succeeded in producing this effect within 3 days. Doubling the drug administration period did not produce any significant superior benefit.

  15. Long-term Morbidity of Testicular Cancer Treatment.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Williams, Annalynn; Travis, Lois B

    2015-08-01

    Second malignant neoplasms, cardiovascular disease, neurotoxicity and ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are potentially life-threatening long-term complications of testicular cancer and its therapy. This article describes the pathogenesis, risks, and management of these late effects experienced by long-term testicular cancer survivors, who are defined as individuals who are disease free 5 years or more after primary treatment. Testicular cancer survivors should follow applicable national guidelines for cancer screening and management of cardiovascular disease risk factors. In addition, health care providers should capitalize on the time of cancer diagnosis as a teachable moment to introduce and promote lifestyle changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

    Science.gov (United States)

    Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

    2016-04-07

    Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; Pischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

  17. Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects.

    Science.gov (United States)

    Rath, Judith J G; Tavy, Dénes L J; Wertenbroek, Agnes A A C M; van Woerkom, Theodoor C A M; de Bruijn, Sebastiaan F T M

    2010-08-01

    To determine the short-term and long-term treatment-effects of botulinum toxin type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with simple motor tics that were treated every 3 months with injections of BTX-A. Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and last 2 (if treated 5 times or more) treatments were recorded, as well as latency of response, changes of premonitory urges (PMUs) and possible side effects. Total number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16 of 18 tics (89%) short-term efficacy was reported successful (good or moderate). Long-term efficacy was reported in 12 tics of which 11 showed similar or even increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A permanent remission of the treated tic was seen in 3 patients with a maximum follow-up of 10 years. BTX-A appears a safe and effective treatment for simple motor tics and retains its efficacy after long-term treatment. BTX may also induce permanent remission of the treated tics and effects of BTX are not restricted to merely motor behaviour.

  18. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

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    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

  19. Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats

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    Uma Bhandari

    2015-01-01

    Full Text Available Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ combined with high fat diet (HFD in rats. Methods: Male Wistar rats (150-200 g were injected with low-dose STZ (45 mg/kg, i.v., single dose and orally fed with a HFD (20 g/day/rat for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o. for a period of 21 days (from 8 th day to 28 th day. On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC and triglycerides (TGs, apoliproprotein-B glycosylated haemoglobin (HbA1c levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

  20. Long-term outcome of neuroparacoccidioidomycosis treatment

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    Fabio Francesconi

    2011-02-01

    Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

  1. Effects of pioglitazone therapy on blood parameters, weight and BMI: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Elena Filipova

    2017-11-01

    Full Text Available Abstract Background Type 2 diabetes mellitus (T2DM is one of the most common diseases worldwide and insulin insufficiency and insulin resistance are two main metabolic issues connected with it. The dyslipidemia associated with insulin resistance and T2DM is characterized by higher triglycerides (TGs, higher very-low-density lipoprotein cholesterol and lower apo A1. Pioglitazone, a member of the thiazolidinedione class, with a proven antihyperglycemic effect, is known to positively influence insulin sensitivity and β-cell function and to have the potential to alter the lipid profile. Methods The aim of our meta-analysis is to summarize and determine the influence of pioglitazone on the glycemic profile and lipoprotein metabolism as well as on weight and BMI in order to highlight the benefit of pioglitazone therapy in patients with T2DM. A comprehensive literature search was conducted through the electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru (from 2000 until February 2016 to identify studies that investigate the effect of pioglitazone on the glycemic and lipid profile and on the weight and BMI. We chose the random-effects method as the primary analysis. Forest plots depict estimated results from the studies included in the analysis and funnel plots are used to evaluate publication bias. Sensitivity analyses were performed in order to evaluate the degree of influence of the consequent elimination of each individual study on the final result. Results Of the 1536 identified sources only 15 randomised trials were included in the meta-analysis. Pioglitazone treatment was associated with improvement in the glycemic profile. It reduced FPG levels by a mean of 1.1–2 mmol/l and HbA1c by a mean of 0.9–1.3%. Our results reaffirmed the hypothesis that pioglitazone has a positive influence on the lipid profile of T2DM patients with increase in TC and HDL, no significant changes in LDL and notable decrease in TGs. Results also showed

  2. Toxicological evaluation of subchronic use of pioglitazone in mice

    Directory of Open Access Journals (Sweden)

    Said Said Elshama

    2016-07-01

    Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  3. Dienogest in long-term treatment of endometriosis

    Directory of Open Access Journals (Sweden)

    Schindler AE

    2011-07-01

    Full Text Available Adolf E SchindlerInstitute for Medical Research and Education, Essen, GermanyAbstract: Endometriosis is a chronic disease primarily affecting women of childbearing age, in which endometriotic lesions form outside the uterus, typically leading to painful symptoms, fatigue, and infertility. The symptoms of endometriosis may cause significant impairment in quality of life and represent a substantial economic burden to patients, families, and society. There is no cure for endometriosis; management consists of alleviating pain and other symptoms, reducing endometriotic lesions, and improving quality of life. Recurrence after surgical intervention is common, while the clinical evidence to support the efficacy and safety of many medications currently used in endometriosis is limited. Dienogest is an oral progestin that has been investigated extensively in the treatment of endometriosis in two clinical programs performed in Europe and Japan, including dose-ranging, placebo-controlled, active comparator-controlled, and long-term (up to 65 weeks studies. These studies demonstrated that dienogest 2 mg daily effectively alleviates the painful symptoms of endometriosis, reduces endometriotic lesions, and improves indices of quality of life. Dienogest showed a favorable safety and tolerability profile in these studies, with predictable adverse effects, high rates of patient compliance, and low withdrawal rates. This review article describes the clinical trial evidence that characterizes the efficacy and safety of dienogest in endometriosis, including two studies characterizing dienogest in long-term use. The relevance of these findings to the management of endometriosis in clinical practice is discussed.Keywords: dienogest, endometriosis, progestins, long-term treatment, quality of life, symptoms, pain

  4. Nanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia.

    Science.gov (United States)

    Nagahama, Ryoji; Matoba, Tetsuya; Nakano, Kaku; Kim-Mitsuyama, Shokei; Sunagawa, Kenji; Egashira, Kensuke

    2012-10-01

    Critical limb ischemia is a severe form of peripheral artery disease (PAD) for which neither surgical revascularization nor endovascular therapy nor current medicinal therapy has sufficient therapeutic effects. Peroxisome proliferator activated receptor-γ agonists present angiogenic activity in vitro; however, systemic administration of peroxisome proliferator-activated receptor-γ agonists is hampered by its side effects, including heart failure. Here, we demonstrate that the nanoparticle (NP)-mediated delivery of the peroxisome proliferator activated receptor-γ agonist pioglitazone enhances its therapeutic efficacy on ischemia-induced neovascularization in a murine model. In a nondiabetic murine model of hindlimb ischemia, a single intramuscular injection of pioglitazone-incorporated NP (1 µg/kg) into ischemic muscles significantly improved the blood flow recovery in the ischemic limbs, significantly increasing the number of CD31-positive capillaries and α-smooth muscle actin-positive arterioles. The therapeutic effects of pioglitazone-incorporated NP were diminished by the peroxisome proliferator activated receptor-γ antagonist GW9662 and were not observed in endothelial NO synthase-deficient mice. Pioglitazone-incorporated NP induced endothelial NO synthase phosphorylation, as demonstrated by Western blot analysis, as well as expression of multiple angiogenic growth factors in vivo, including vascular endothelial growth factor-A, vascular endothelial growth factor-B, and fibroblast growth factor-1, as demonstrated by real-time polymerase chain reaction. Intramuscular injection of pioglitazone (1 µg/kg) was ineffective, and oral administration necessitated a >500 μg/kg per day dose to produce therapeutic effects equivalent to those of pioglitazone-incorporated NP. NP-mediated drug delivery is a novel modality that may enhance the effectiveness of therapeutic neovascularization, surpassing the effectiveness of current treatments for peripheral artery

  5. A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism.

    Science.gov (United States)

    Ghaleiha, Ali; Rasa, Soudeh Mohebbi; Nikoo, Mohammadali; Farokhnia, Mehdi; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

    2015-09-30

    To assess the safety and efficacy of pioglitazone added to risperidone in the treatment of irritability in autistic disorder (AD), we conducted this study. In a 10-week, randomized, double-blind, parallel-group, placebo-controlled clinical trial, 44 outpatients of both genders aged 4-12 years with a diagnosis of AD and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale were included. Mean change of ABC-C irritability subscale score as primary outcome, change in other ABC-C subscale scores and partial and complete responses were compared between two groups. Twenty patients completed the trial in each group. Level of reduction and effect of time×treatment interaction in the treatment group were significant for irritability (P=0.03), lethargy/social withdrawal (P=0.04) and hyperactivity/non-compliance (P=0.03) but not for stereotypic behavior and inappropriate speech subscales compared with the placebo group. Vomiting and headache were the most frequent reported side-effects. Results of this preliminary study indicate positive effects of pioglitazone compared with placebo in improving the behavioral symptoms of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-01-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  7. Multimethod Behavioral Treatment of Long-Term Selective Mutism.

    Science.gov (United States)

    Watson, T. Steuart; Kramer, Jack J.

    1992-01-01

    Conducted single-subject, experimental research to examine efficacy of treating severe, long-term selective mutism in nine-year-old male using shaping, multiple reinforcers, natural consequences, stimulus fading, and mild aversives. Implemented different treatment regimens in home and school environments. Home intervention resulted in increase in…

  8. Effect of pioglitazone on plasma ceramides in adults with metabolic syndrome.

    Science.gov (United States)

    Warshauer, Jeremy T; Lopez, Ximena; Gordillo, Ruth; Hicks, Jessica; Holland, William L; Anuwe, Estelle; Blankfard, Martin B; Scherer, Philipp E; Lingvay, Ildiko

    2015-10-01

    Metabolic syndrome (MetS) appears closely linked with ceramide accumulation, inducing insulin resistance and toxicity to multiple cell types. Animal studies demonstrate that thiazolidinediones (TZDs) reduce ceramide concentrations in plasma and skeletal muscle and support lowering of ceramide levels as a potential mediator of TZDs' mechanism of action in reducing insulin resistance; however, studies in humans have yet to be reported. This study investigated the effects of pioglitazone therapy on plasma ceramides to understand the mechanism by which TZDs improve insulin resistance in MetS. Thirty-seven subjects with MetS were studied in a single-centre, randomized, double-blind, placebo-controlled trial comparing pioglitazone to placebo. Data were collected at baseline and after 6 months of therapy. The primary endpoint was the change from baseline in plasma ceramide concentrations. Treatment with pioglitazone for 6 months, compared with placebo, significantly reduced multiple plasma ceramide concentrations: C18:0 (p = 0.001), C20:0 (p = 0.0004), C24 : 1 (p = 0.009), dihydroceramide C18 :0 (p = 0.005), dihydroceramide C24:1 (p = 0.004), lactosylceramide C16:0 (p = 0.02) and the hexosylceramides C16:0 (p = 0.0003), C18 : 0 (p = 0.00001), C22:0 (p = 0.00002) and C24:1 (p = 0.0006). Additionally, significant reductions were found when ceramides were grouped by species: ceramides (p = 0.03), dihydroceramides (p = 0.02), hexosylceramides (p = 0.00001) and lactosylceramides (p = 0.02). The total of all measured ceramides was also significantly reduced (p = 0.001). Following treatment with pioglitazone, the decrease in some ceramide species correlated negatively with the change in insulin sensitivity (dihydroceramide C16:0, r = -0.54; p = 0.02) and positively with total (lactosylceramide C24:0, r = 0.53; p = 0.02) and high molecular weight (lactosylceramide C24:0, r = 0.48; p = 0

  9. Pioglitazone and cause-specific risk of mortality in patients with type 2 diabetes: extended analysis from a European multidatabase cohort study.

    Science.gov (United States)

    Strongman, Helen; Christopher, Solomon; Majak, Maila; Williams, Rachael; Bahmanyar, Shahram; Linder, Marie; Heintjes, Edith M; Bennett, Dimitri; Korhonen, Pasi; Hoti, Fabian

    2018-01-01

    Describe and compare the risk of cardiovascular and non-cardiovascular mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression. This exploratory linked database cohort analysis used pooled health and mortality data from three European countries: Finland, Sweden and the UK. Propensity score together with exact matching was used to match 31 133 patients with type 2 diabetes first prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed pioglitazone. Exact matching variables were treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry. Mean follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality rates were ascertained. Association with pioglitazone use was estimated using Cox proportional hazards models adjusted a priori for country, age, sex, the propensity score quintile and time-dependent variables representing use of antidiabetic drugs. Stepwise testing identified no additional confounders to include in adjusted models. The crude mortality rate was lower in the pioglitazone-exposed group than the non-exposed group for both cardiovascular and non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to 0.68) for cardiovascular and non-cardiovascular mortality, respectively. A protective effect associated with pioglitazone was also found for all specific cardiovascular causes. This analysis suggests that pioglitazone is associated with a decrease in both cardiovascular and non-cardiovascular mortality. Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test

  10. Long-Term Effects of Neurofeedback Treatment in Autism

    Science.gov (United States)

    Kouijzer, Mirjam E. J.; de Moor, Jan M. H.; Gerrits, Berrie J. L.; Buitelaar, Jan K.; van Schie, Hein T.

    2009-01-01

    Previously we demonstrated significant improvement of executive functions and social behavior in children with autism spectrum disorders (ASD) treated with 40 sessions of EEG neurofeedback in a nonrandomized waiting list control group design. In this paper we extend these findings by reporting the long-term results of neurofeedback treatment in…

  11. Evaluation of the PPAR-γ Agonist Pioglitazone in Mild Asthma: A Double-Blind Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    J R Anderson

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPAR-γ is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial.Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1 at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF, scores on the Juniper Asthma Control Questionnaire (ACQ and Asthma Quality of Life Questionnaire (AQLQ, fractional exhaled nitric oxide (FeNO, bronchial hyperresponsiveness (PD20, induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10, vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, and eosinophil cationic protein (ECP levels. Study recruitment was closed early after considering the European Medicines Agency's reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA and 52 in the per-protocol (PP analysis.There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84 or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02.We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma.ClinicalTrials.gov NCT01134835.

  12. Pioglitazone and the risk of cardiovascular events in patients with Type 2 diabetes receiving concomitant treatment with nitrates, renin-angiotensin system blockers, or insulin: results from the PROactive study (PROactive 20).

    Science.gov (United States)

    Erdmann, Erland; Spanheimer, Robert; Charbonnel, Bernard

    2010-09-01

    Patients with Type 2 diabetes mellitus (T2DM) are often treated with multiple glucose-lowering and cardiovascular agents. The concomitant use of nitrates, renin-angiotensin system (RAS) blockers, or insulin has been linked to a potential increase in myocardial ischemic risk with rosiglitazone. The PROactive database provides an opportunity to investigate the effects of these medications on the potential macrovascular benefits reported with pioglitazone. The PROactive study was a randomized double-blind prospective trial that evaluated mortality and cardiovascular morbidity in 5238 patients with T2DM and macrovascular disease. Patients received pioglitazone or placebo in addition to their baseline glucose-lowering and cardiovascular medications. The effect of pioglitazone on composite endpoints was evaluated, including all-cause death, myocardial infarction (MI), and stroke, as well as safety events of edema and serious heart failure, in subgroups using nitrates, RAS blockers, or insulin at baseline. The risk of all-cause death, MI, and stroke for pioglitazone versus placebo was similar regardless of the baseline use of nitrates, RAS blockers, or insulin, with hazard ratios ranging from 0.81 to 0.87. Similar results were obtained for the other composite endpoints analyzed. There were no significant interactions between baseline medication subgroups and treatment. The increased risk of edema and serious heart failure was consistent across the baseline medication subgroups. This post hoc analysis did not reveal an increased risk of macrovascular events with pioglitazone in patients receiving nitrates, RAS blockers, or insulin. Rather, all patients realized the same trend towards benefit with pioglitazone, and adverse events of edema and heart failure were predictable. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  13. Long-term results using LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Trolle, Waldemar; Anthonsen, Kristian

    2017-01-01

    The purpose of the present study was to evaluate the long-term results and patient's satisfaction of a new approach using the LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum (ZD) and to compare with other long-term results using traditional treatment modalities. Between December ...... to traditional endoscopic techniques and is now the standard treatment method for ZD in our departments.......The purpose of the present study was to evaluate the long-term results and patient's satisfaction of a new approach using the LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum (ZD) and to compare with other long-term results using traditional treatment modalities. Between December......%) reported no symptoms at all. Our results suggest that endoscopic management of ZD with the LigaSure™ 5 mm instrument is a minimally invasive, fast and safe method with solid long-term outcome with relief of symptoms and patient satisfaction. This new operative instrument was not found inferior...

  14. [Long-term effectiveness of psychodynamic outpatient treatment of addiction].

    Science.gov (United States)

    Steffen, D V; Werle, L; Steffen, R; Steffen, M; Steffen, S

    2012-07-01

    The aim of this study is to make an evaluation of the effectiveness of long-term outpatient treatment for addiction on the basis of abstinence, cognitive functions, and changes in personality structure. This is a prospective cohort study of 259 patients with registration of the German core data set "addiction", a 12-month follow-up and neuropsychological testing (personality inventory, intelligence and cognitive functions). One year after the end of the long-term treatment we see an abstinence rate (DGSS4) of 57.5 %. The most substantial factors in abstinence are the participation in a self-help-group (β = 0.734, p addiction seem to show its high effectiveness in terms of abstinence and processing of drug structures. The cognitive functions could increase. This could be determinate of a condition for the conservation and restoration of working capacity. Further studies should differentiate the effect of insight into the dependency structure from the abstinence as an specific or unspecific effect. © Georg Thieme Verlag KG Stuttgart · New York.

  15. High prevalence of long-term cardiovascular, neurological and psychosocial morbidity after treatment for craniopharyngioma

    NARCIS (Netherlands)

    Pereira, Alberto M.; Schmid, Eva M.; Schutte, Pieter J.; Voormolen, Joan H. C.; Biermasz, Nienke R.; van Thiel, Sjoerd W.; Corssmit, Eleonora P. M.; Smit, Jan W. A.; Roelfsema, Ferdinand; Romijn, Johannes A.

    2005-01-01

    The treatment of craniopharyngiomas is associated with long-term morbidity. To assess the long-term functional outcome and mortality rates after treatment for craniopharyngiomas, we audited our data with special focus on cardiovascular, neurological and psychosocial morbidity. Between 1965 and 2002,

  16. The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B.

    Science.gov (United States)

    Quinn, L P; Crook, B; Hows, M E; Vidgeon-Hart, M; Chapman, H; Upton, N; Medhurst, A D; Virley, D J

    2008-05-01

    The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease, an effect attributed to its anti-inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse model, not via an anti-inflammatory action, but through inhibition of MAO-B, the enzyme required to biotransform MPTP to its active neurotoxic metabolite 1-methyl-4-phenylpyridinium (MPP+). Mice were treated with pioglitazone (20 mg kg(-1) b.i.d. (twice a day), p.o., for 7 days), prior and post or post-MPTP (30 mg kg(-1) s.c.) treatment. Mice were then assessed for motor impairments on a beam-walking apparatus and for reductions in TH immunoreactivity in the substantia nigra and depletions in striatal dopamine. The effects of pioglitazone on striatal MPP+ levels and MAO-B activity were also assessed. Mice treated with MPTP showed deficits in motor performance, marked depletions in striatal dopamine levels and a concomitant reduction in TH immunoreactivity in the substantia nigra. Pretreatment with pioglitazone completely prevented these effects of MPTP. However, pretreatment with pioglitazone also significantly inhibited the MPTP-induced production of striatal MPP+ and the activity of MAO-B in the striatum. The neuroprotection observed with pioglitazone pretreatment in the MPTP mouse model was due to the blockade of the conversion of MPTP to its active toxic metabolite MPP+, via inhibition of MAO-B.

  17. Long-term effects and quality of life after treatment for rectal cancer

    NARCIS (Netherlands)

    Wiltink, L.M.

    2017-01-01

    In this thesis long-term effects and quality of life after treatment for rectal cancer are evaluated. Long-term data were assessed from the TME trial. In this trial 1530 Dutch patients with rectal cancer were included between 1996 and 1999. These patients were randomly assigned to total mesorectal

  18. Long-term effects of HIV treatment in sub-Saharan Africa: from access to quality

    NARCIS (Netherlands)

    Boender, T.S.

    2016-01-01

    As HIV treatment programs in sub-Saharan Africa mature, there are rising concerns about the long-term sustainability and quality of these programs. Increasing levels of HIV drug resistance have been measured in sub-Saharan Africa, and could jeopardize long-term treatment success. This thesis

  19. The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss.

    Science.gov (United States)

    Shea, M Kyla; Nicklas, Barbara J; Marsh, Anthony P; Houston, Denise K; Miller, Gary D; Isom, Scott; Miller, Michael E; Carr, J Jeffrey; Lyles, Mary F; Harris, Tamara B; Kritchevsky, Stephen B

    2011-08-01

    Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.

  20. Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis

    Science.gov (United States)

    Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

    2014-01-01

    Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (≤1 per cent in clinical trials; metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

  1. Morphometric analysis of long-term dentoskeletal effects induced by treatment with Balters bionator.

    Science.gov (United States)

    Bigliazzi, Renato; Franchi, Lorenzo; Bertoz, André Pinheiro de Magalhães; McNamara, James A; Faltin, Kurt; Bertoz, Francisco Antonio

    2015-09-01

    To evaluate the long-term effects of the standard (Class II) Balters bionator in growing patients with Class II malocclusion with mandibular retrusion by using morphometrics (thin-plate spline [TPS] analysis). Twenty-three Class II patients (8 male, 15 female) were treated consecutively with the Balters bionator (bionator group). The sample was evaluated at T0, start of treatment; T1, end of bionator therapy; and T2, long-term observation (including fixed appliances). Mean age at the start of treatment was 10 years 2 months (T0); at posttreatment, 12 years 3 months (T1); and at long-term follow-up, 18 years 2 months (T2). The control group consisted of 22 subjects (11 male, 11 female) with untreated Class II malocclusion. Lateral cephalograms were analyzed at the three time points for all groups. TPS analysis evaluated statistical differences (permutation tests) in the craniofacial shape and size between the bionator and control groups. TPS analysis showed that treatment with the bionator is able to produce favorable mandibular shape changes (forward and downward displacement) that contribute significantly to the correction of the Class II dentoskeletal imbalance. These results are maintained at a long-term observation after completion of growth. The control group showed no statistically significant differences in the correction of Class II malocclusion. This study suggests that bionator treatment of Class II malocclusion produces favorable results over the long term with a combination of skeletal and dentoalveolar shape changes.

  2. Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2014-01-01

    Full Text Available Background and Aim. Thiazolidinediones (TZDs can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH. Angiotensin (Ang II, the primary effector of renin-angiotensin system (RAS, plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD, pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  3. Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress

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    Mohammad Shokrzadeh

    2017-05-01

    Full Text Available Objective(s: Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN. In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO on the prevention of DN in streptozotocin induced-diabetic mice. Materials and Methods: Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent, diabetic group and four treatment groups which received U. dioica, pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ (200 mg/kg body wt, IP diluted in citrate buffer (pH= 4.6. After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Results: Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO, protein carbonyl in renal supernatant of diabetic mice was inhibited by U. dioica treatment.  Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Conclusion: Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN.

  4. Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress.

    Science.gov (United States)

    Shokrzadeh, Mohammad; Sadat-Hosseini, Sara; Fallah, Marjan; Shaki, Fatemeh

    2017-05-01

    Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U. dioica , pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ) (200 mg/kg body wt, IP) diluted in citrate buffer (pH= 4.6). After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO), protein carbonyl) in renal supernatant of diabetic mice was inhibited by U. dioica treatment. Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN.

  5. Effective Treatment of Intestinal Behçet's Disease with Long-Term, Low-Dose Clarithromycin

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    Yukiya Hakozaki

    2013-03-01

    Full Text Available A 51-year-old man was referred for body weight loss and lower right abdominal pain. Total colonoscopy revealed discrete and round ulceration at the ileocecal valve, and he was diagnosed with intestinal Behçet's disease (BD. By treatment with glucocorticoid, colchicine and salazosulfapyridine, the symptoms and ulceration were improved, but cessation of glucocorticoid resulted in relapse of ulceration at the terminal ileum. Long-term, low-dose treatment with clarithromycin (CAM was implemented for chronic respiratory infections. Furthermore, we expected that this CAM treatment would also be effective in BD. During this long-term, low-dose treatment with CAM, discrete ulceration at the terminal ileum was never revealed by follow-up total colonoscopy once or twice per year for 7 years. No reports have described the effectiveness of this treatment in patients with intestinal BD; however, we confirm that long-term treatment with low-dose CAM might have clinical benefits for patients with intestinal BD.

  6. Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence.

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    Oulis, Panagiotis; Kalogerakou, Stamatina; Anyfandi, Eleni; Konstantakopoulos, George; Papakosta, Vassiliki-Maria; Masdrakis, Vasilios; Tsaltas, Eleftheria

    2014-05-01

    Long-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB. Fourteen patients with long-term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data. Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores. Although preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone.

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    Pareek, Anil; Chandurkar, Nitin; Thomas, Nihal; Viswanathan, Vijay; Deshpande, Alaka; Gupta, O P; Shah, Asha; Kakrani, Arjun; Bhandari, Sudhir; Thulasidharan, N K; Saboo, Banshi; Devaramani, Shashidhar; Vijaykumar, N B; Sharma, Shrikant; Agrawal, Navneet; Mahesh, M; Kothari, Kunal

    2014-07-01

    To compare efficacy and safety of hydroxychloroquine with pioglitazone in type 2 diabetes mellitus (T2DM). This double-blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c ≥7.5% and ≤11.5%), post 3 months' treatment with glimepiride/gliclazide and metformin, to additionally receive hydroxychloroquine 400 mg/day (n = 135) or pioglitazone 15 mg/day (n = 132) for 24 weeks. Efficacy was assessed by changes in HbA1c, fasting (FBG) and post-prandial (PPG) blood glucose at Week 12 and Week 24. At Week 12 and Week 24, HbA1c, FBG and PPG significantly reduced from baseline in both groups. Mean reduction in glycemic parameters at Week 12 (HbA1c: -0.56% vs -0.72%, p = 0.394; FBG: -0.99 mmol/L vs -1.05 mmol/L, p = 0.878; PPG: -1.93 mmol/L vs -1.52 mmol/L, p = 0.423) and Week 24 (HbA1c: -0.87% vs -0.90%, p = 0.909; FBG: -0.79 mmol/L vs -1.02 mmol/L, p = 0.648; PPG: -1.77 mmol/L vs -1.36 mmol/L, p = 0.415) was not significantly different between the hydroxychloroquine and pioglitazone groups. Change in total cholesterol (TC) and LDL-C was significant in favor of hydroxychloroquine (TC: -0.37 mmol/L vs 0.03 mmol/L, p = 0.002; LDL-C: -0.23 mmol/L vs 0.09 mmol/L, p = 0.003). Triglycerides significantly reduced in both groups at Week 24. Mean HDL-C remained unchanged. Study treatments were well tolerated. With favorable effects on glycemic parameters and lipids, hydroxychloroquine may emerge as well tolerated therapeutic option for T2DM. The sample size for this study was small. However, based on the encouraging results of this proof-of-concept study, longer duration studies in larger population can be conducted to further confirm these findings. TRIAL REGISTRATION DETAILS: Clinical Trial Registry-India URL: http://ctri.nic.in, Registration Number: CTRI/2009/091/001036.

  8. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    Science.gov (United States)

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Complete Treatment Versus Residual Lesion - Long-Term Evolution After Acute Coronary Syndrome

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    Alexandre de Matos Soeiro

    Full Text Available Abstract Introduction: A recently published study raised doubts about the need for percutaneous treatment of nonculprit lesions in patients with acute coronary syndromes (ACS. Methods: Retrospective, unicentric, observational study. Objective: To analyze the long-term outcomes in patients undergoing treatment of the culprit artery, comparing those who remained with significant residual lesions in nonculprit arteries (group I versus those without residual lesions in other coronary artery beds (group II. The study included 580 patients (284 in group I and 296 in group II between May 2010 and May 2013. We obtained demographic and clinical data, as well as information regarding the coronary treatment administered to the patients. In the statistical analysis, the primary outcome included combined events (reinfarction/angina, death, heart failure, and need for reintervention. The comparison between groups was performed using the chi-square test and ANOVA. The long-term analysis was conducted with the Kaplan-Meier method, with a mean follow-up of 9.86 months. Results: The mean ages were 63 years in group I and 62 years in group II. On long-term follow-up, there was no significant difference in combined events in groups I and II (31.9% versus 35.6%, respectively, p = 0.76. Conclusion: The strategy of treating the culprit artery alone seems safe. In this study, no long-term differences in combined endpoints were observed between patients who remained with significant lesions compared with those without other obstructions.

  10. Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats.

    Science.gov (United States)

    Abdelhamid, Amir Mohamed; Abdelaziz, Rania Ramadan; Salem, Hatem Abdelrahman Ali

    2018-03-06

    Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA 1c . It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

  11. A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment

    Directory of Open Access Journals (Sweden)

    Shaw Monica

    2012-09-01

    Full Text Available Abstract Background In childhood, attention deficit/hyperactivity disorder (ADHD is characterized by age-inappropriate levels of inattentiveness/disorganization, hyperactivity/impulsiveness, or a combination thereof. Although the criteria for ADHD are well defined, the long-term consequences in adults and children need to be more comprehensively understood and quantified. We conducted a systematic review evaluating the long-term outcomes (defined as 2 years or more of ADHD with the goal of identifying long-term outcomes and the impact that any treatment (pharmacological, non-pharmacological, or multimodal has on ADHD long-term outcomes. Methods Studies were identified using predefined search criteria and 12 databases. Studies included were peer-reviewed, primary studies of ADHD long-term outcomes published between January 1980 to December 2010. Inclusion was agreed on by two independent researchers on review of abstracts or full text. Published statistical comparison of outcome results were summarized as poorer than, similar to, or improved versus comparators, and quantified as percentage comparisons of these categories. Results Outcomes from 351 studies were grouped into 9 major categories: academic, antisocial behavior, driving, non-medicinal drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. The following broad trends emerged: (1 without treatment, people with ADHD had poorer long-term outcomes in all categories compared with people without ADHD, and (2 treatment for ADHD improved long-term outcomes compared with untreated ADHD, although not usually to normal levels. Only English-language papers were searched and databases may have omitted relevant studies. Conclusions This systematic review provides a synthesis of studies of ADHD long-term outcomes. Current treatments may reduce the negative impact that untreated ADHD has on life functioning, but does not usually 'normalize' the

  12. Pioglitazone Improves In Vitro Viability and Function of Endothelial Progenitor Cells from Individuals with Impaired Glucose Tolerance

    Science.gov (United States)

    Spigoni, Valentina; Picconi, Angela; Cito, Monia; Ridolfi, Valentina; Bonomini, Sabrina; Casali, Chiara; Zavaroni, Ivana; Gnudi, Luigi; Metra, Marco; Dei Cas, Alessandra

    2012-01-01

    Background Evidence suggests that the PPARγ-agonist insulin sensitizer pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC) number is associated with impaired glucose tolerance (IGT) or diabetes, conditions characterised by increased CV risk. Aim To evaluate whether pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects. Materials and Methods Early and late-outgrowth EPCs were obtained from peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of pioglitazone (10 µM) with/without PPARγ-antagonist GW9662 (1 µM) was assessed on EPC viability, apoptosis, ability to form tubular-like structures and pro-inflammatory molecule expression. Results Pioglitazone increased early and late-outgrowth EPC viability, with negligible effects on apoptosis. The capacity of EPCs to form tubular-like structures was improved by pioglitazone in early (mean increase 28%; p = 0.005) and late-outgrowth (mean increase 30%; p = 0.037) EPCs. Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early (p = 0.001 and p = 0.012 respectively) and late-outgrowth (p = 0.047 and p = 0.048, respectively) EPCs. Similarly, pioglitazone reduced TNFα gene and protein expression in both early (p = 0.034;p = 0.022) and late-outgrowth (p = 0.026;p = 0.017) EPCs compared to control. These effects were prevented by incubation with the PPARγ-antagonist GW9662. Conclusion Pioglitazone exerts beneficial effects in vitro on EPCs isolated from IGT subjects, supporting the potential implication of pioglitazone as a CV protective agents. PMID:23139771

  13. Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency.

    Science.gov (United States)

    Lajic, Svetlana; Nordenström, Anna; Hirvikoski, Tatja

    2011-01-01

    Prenatal treatment of congenital adrenal hyperplasia (CAH) with dexamethasone (DEX) has been in use since the mid- 1980s. Its effectiveness for reducing virilization of external genitalia is well established. DEX treatment has to be started in the 6th-7th postmenstrual week and continued until the results of the prenatal diagnosis are available. Hence, the dilemma is that 7 out of 8 fetuses (boys and unaffected girls) are treated unnecessarily. Girls with CAH are treated until term. Accumulating evidence from animal studies and follow-up data has raised concerns regarding the long-term consequences of this controversial treatment. We have previously reported that direct neuropsychological assessment of children exposed to DEX and controls show normal full-scale IQ, learning and longterm memory. However, the children exposed to DEX during the first trimester had an impaired verbal working memory which was significantly associated with low self-perceived scholastic competence. In addition, the children showed increased self-rated social anxiety. The same cohort of children answered questions concerning friends, activities and gender-related behaviors. The results indicate less masculine and more neutral behavior in short-term DEX-exposed boys. These findings indicate that long-term follow-ups of this group of patients are of extreme importance and that future DEX treatment of CAH may be questioned. We therefore encourage additional studies on larger cohorts in order to draw more decisive conclusions about the safety of the treatment. Until then, it is important that the parents are thoroughly informed about the potential risks and uncertainties, as well as the benefits, of this treatment. Copyright © 2011 S. Karger AG, Basel.

  14. Biologically-equivalent dose and long-term survival time in radiation treatments

    International Nuclear Information System (INIS)

    Zaider, Marco; Hanin, Leonid

    2007-01-01

    Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

  15. Fertility treatment: long-term growth and mental development of the children.

    Science.gov (United States)

    Bay, Bjørn

    2014-10-01

    Fertility treatment has been associated with obstetrical and perinatal complications. It is, however, uncertain whether fertility treatment or parental subfertility is associated with long-term development of the children. We aimed to assess the growth and mental health of children and adolescents conceived after fertility treatment compared to spontaneously conceived controls. First, we evaluated all previous studies comparing neurodevelopmental outcomes between children conceived after fertility treatment and spontaneous conceived controls. The systematic review clarified methodological limitations in the existing literature on the long-term development of children conceived after medical assisted reproduction. Although several studies had been published, large, well-controlled studies with long-term follow-up and thorough statistical adjustments were still few. Second, we evaluated the children's mental health by assessing the risk of mental disorders. We studied a population of 555,828 children conceived after spontaneous conception and 33,139 children conceived after fertility treatment with follow-up in 2012 when the children were 8-17 years old. The absolute risk and hazard ratio of overall and specific mental disorders were estimated while adjusting for potential confounding variables. Further, we estimated the association between subtypes of procedures, hormonal treatment, gamete types and cause of infertility on the one hand and the risk of mental disorders on the other. Children conceived after ovulation induction had a low, but significantly increased risks of autism spectrum disorders, hyperkinetic disorders, conduct, emotional, or social disorders, and tic disorders. Children conceived after IVF or ICSI showed no increased risk, except for a small risk of tic disorders. There was no risk systematically related to any specific type of hormone drug treatment. Thus, the increased risks may rely on residual confounding such as unknown parental factors

  16. Considerations on long-term immuno-intervention in the treatment of multiple sclerosis: an expert opinion.

    Science.gov (United States)

    Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L

    2016-10-01

    As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.

  17. The effects of long-term dopaminergic treatment on locomotor behavior in rats.

    Science.gov (United States)

    Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

    2014-12-01

    Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole-PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

  18. The effects of long-term dopaminergic treatment on locomotor behavior in rats

    Science.gov (United States)

    Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

    2014-01-01

    Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole—PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions. PMID:26483930

  19. The effects of long-term dopaminergic treatment on locomotor behavior in rats

    Directory of Open Access Journals (Sweden)

    Welinton Alessandro Oliveira de Almeida

    2014-12-01

    Full Text Available Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL and drug (Pramipexole—PPX groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

  20. A Study of Effects of Pioglitazone and Rosiglitazone on Various Parameters in Patients of Type-2 Diabetes Mellitus with Special Reference to Lipid Profile.

    Science.gov (United States)

    Sharma, S K; Verma, S H

    2016-09-01

    level decreased by 8.62% with pioglitazone but in group B there was no significant decrease in total cholesterol level after 18 weeks of therapy with rosiglitazone. There was no significant reduction in mean LDL cholesterol level in both groups. HDL-c level increased by 17.14% with pioglitazone in group A and decreased by 1.2% with rosiglitazone in group B. Triglycerides levels decreased by 12.33% with pioglitazone in group A and 6.16% with rosiglitazone in group B. Treatment with pioglitazone and rosiglitazone both were associated with reduction in fasting and postprandial blood sugar levels but more with pioglitazone. There was significant reduction in HbA1c with both pioglitazone and rosiglitazone but more with rosiglitazone. The total cholesterol level decreased by pioglitazone significantly but not with rosiglitazone. The LDL levels were not affected much by both drugs, while HDL levels were significantly increased with pioglitazone. Triglycerides levels were decreased with both pioglitazone and rosiglitazone but more with pioglitazone. Both drugs are useful but pioglitazone proved to be more beneficial on deranged lipid profile as compared to rosiglitazone in Type 2 Diabetes mellitus patients on OHA/insulin.

  1. Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction.

    Science.gov (United States)

    Kernan, Walter N; Viscoli, Catherine M; Dearborn, Jennifer L; Kent, David M; Conwit, Robin; Fayad, Pierre; Furie, Karen L; Gorman, Mark; Guarino, Peter D; Inzucchi, Silvio E; Stuart, Amber; Young, Lawrence H

    2017-11-01

    There is growing recognition that patients may respond differently to therapy and that the average treatment effect from a clinical trial may not apply equally to all candidates for a therapy. To determine whether, among patients with an ischemic stroke or transient ischemic attack and insulin resistance, those at higher risk for future stroke or myocardial infarction (MI) derive more benefit from the insulin-sensitizing drug pioglitazone hydrochloride compared with patients at lower risk. A secondary analysis was conducted of the Insulin Resistance Intervention After Stroke trial, a double-blind, placebo-controlled trial of pioglitazone for secondary prevention. Patients were enrolled from 179 research sites in 7 countries from February 7, 2005, to January 15, 2013, and were followed up for a mean of 4.1 years through the study's end on July 28, 2015. Eligible participants had a qualifying ischemic stroke or transient ischemic attack within 180 days of entry and insulin resistance without type 1 or type 2 diabetes. Pioglitazone or matching placebo. A Cox proportional hazards regression model was created using baseline features to stratify patients above or below the median risk for stroke or MI within 5 years. Within each stratum, the efficacy of pioglitazone for preventing stroke or MI was calculated. Safety outcomes were death, heart failure, weight gain, and bone fracture. Among 3876 participants (1338 women and 2538 men; mean [SD] age, 63 [11] years), the 5-year risk for stroke or MI was 6.0% in the pioglitazone group among patients at lower baseline risk compared with 7.9% in the placebo group (absolute risk difference, -1.9% [95% CI, -4.4% to 0.6%]). Among patients at higher risk, the risk was 14.7% in the pioglitazone group vs 19.6% for placebo (absolute risk difference, -4.9% [95% CI, -8.6% to 1.2%]). Hazard ratios were similar for patients below or above the median risk (0.77 vs 0.75; P = .92). Pioglitazone increased weight less among patients at

  2. Treatment of Nonalcoholic Steatohepatitis in Adults: Present and Future

    Directory of Open Access Journals (Sweden)

    S. Gitto

    2015-01-01

    Full Text Available Nonalcoholic steatohepatitis has become one of the most common liver-related health problems. This condition has been linked to an unhealthy diet and weight gain, but it can also be observed in nonobese people. The standard of care is represented by the lifestyle intervention. However, because this approach has several limitations, such as a lack of compliance, the use of many drugs has been proposed. The first-line pharmacological choices are vitamin E and pioglitazone, both showing a positive effect on transaminases, fat accumulation, and inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on long-term morbidity and mortality and pioglitazone has a negative impact on weight. Other drugs have been studied such as metformin, ursodeoxycholic acid, statins, pentoxiphylline, and orlistat with only partially positive results. Among the emerging treatments, telmisartan is particularly interesting as it seems to have an impact on insulin resistance, liver steatosis, inflammation, and fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is determined by different parallel hits; indeed, the association of different drugs that act on various levels has been suggested. In conclusion, lifestyle intervention should be optimised and the associations of different drugs should be tested in large studies with long-term outcomes.

  3. Effects of Pioglitazone on Asymmetric Dimethylarginine and Components of the Metabolic Syndrome in Nondiabetic Patients (EPICAMP Study: A Double-Blind, Randomized Clinical Trial

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    Pedram Shokouh

    2013-01-01

    Full Text Available The present trial aimed to investigate the effects of pioglitazone on the serum level of asymmetric dimethylarginine (ADMA, a marker of endothelial function, and some indices of inflammation and glucose and lipid metabolism in nondiabetic metabolic syndrome patients. 104 eligible participants (57% female; age between 20 and 70 were enrolled in a double-blind placebo-controlled trial and were randomized to receive either pioglitazone (uptitrated to 30 mg/day or matching placebo for 24 weeks. Participants were clinically examined and a blood sample was obtained at baseline and at the end of the trial. Pioglitazone significantly improved C-reactive protein level irrespective of changes in insulin sensitivity. Compared with the placebo group, alanine and aspartate transaminases were decreased and high-density lipoprotein cholesterol was increased after treatment with pioglitazone. A considerably greater weight gain was also recorded in the intervention group. We failed to observe any significant changes in serum ADMA in either group and between groups with and without adjustment for age, sex, and components of the metabolic syndrome. In a nutshell, pioglitazone seems to have positive effects on lipid profile, liver transaminases, and systemic inflammation. However, its previously demonstrated endothelial function-improving properties do not seem to be mediated by ADMA.

  4. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

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    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  5. Changes in the skeleton after long-term treatment with retinoids

    Energy Technology Data Exchange (ETDEWEB)

    Montag, M.; Reiser, M.; Hamm, H.; Traupe, H.; Vogt, H.J.

    1988-07-01

    The synthetic retinoids, the vitamin-A-derivatives ethretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication.

  6. Long-Term Follow-Up after Treatment of Cryptorchidism

    DEFF Research Database (Denmark)

    Thorup, Jorgen; Cortes, Dina

    2016-01-01

    -known knowledge on the field is presented.To some extent a smaller testis in a higher scrotal position than normal must be accepted as a fair cosmetic result after orchidopexy in childhood. The smaller testis size is related to the impaired fertility potential of the testis. In cases with atrophy, testicular......When considering long-term prognosis and results in adult age following treatment of cryptorchidism in childhood there are three main issues to be discussed: cosmetics, fertility, and malignancy. In the present review, the most recent research on the topics related to summaries of well...

  7. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  8. Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.

    Science.gov (United States)

    Ponce-Lopez, Teresa; Liy-Salmeron, Gustavo; Hong, Enrique; Meneses, Alfredo

    2011-12-02

    Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of

  9. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes.

    Science.gov (United States)

    Dorkhan, Mozhgan; Frid, Anders

    2007-01-01

    Type 2 diabetes (T2D) is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c) over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/ glinides) or insulin, biguanides, and thiazolidinediones (TZDs) respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.

  10. Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

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    Keisuke Imafuku

    2017-04-01

    Full Text Available Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs. We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4. We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors.

  11. A conceptual framework for a long-term economic model for the treatment of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Nagy, Balázs; Setyawan, Juliana; Coghill, David; Soroncz-Szabó, Tamás; Kaló, Zoltán; Doshi, Jalpa A

    2017-06-01

    Models incorporating long-term outcomes (LTOs) are not available to assess the health economic impact of attention-deficit/hyperactivity disorder (ADHD). Develop a conceptual modelling framework capable of assessing long-term economic impact of ADHD therapies. Literature was reviewed; a conceptual structure for the long-term model was outlined with attention to disease characteristics and potential impact of treatment strategies. The proposed model has four layers: i) multi-state short-term framework to differentiate between ADHD treatments; ii) multiple states being merged into three core health states associated with LTOs; iii) series of sub-models in which particular LTOs are depicted; iv) outcomes collected to be either used directly for economic analyses or translated into other relevant measures. This conceptual model provides a framework to assess relationships between short- and long-term outcomes of the disease and its treatment, and to estimate the economic impact of ADHD treatments throughout the course of the disease.

  12. Treatment toxicities in long-term survivors of limited small cell lung cancer

    International Nuclear Information System (INIS)

    Frytak, S.; Shaw, J.N.; Lee, R.E.; Eagan, R.T.; Shaw, E.G.; Richardson, R.L.; Creagan, E.T.; Coles, D.T.; Jett, J.R.

    1988-01-01

    A total of 211 patients with limited small cell lung cancer were assessed retrospectively for long-term toxicities, treatment-related deaths, and second primaries. All had received treatment with various combinations of doxorubicin, vincristine, cisplatin, lomustine, cyclophosphamide, and etoposide with or without split-course thoracic radiotherapy (4,000 cGy/10 fractions) and/or split-course prophylactic cranial irradiation (3,600 cGy/10 fractions). Sixty-eight (32%) of the patients survived longer than 1.5 years and formed the basis of this study. Debilitating pulmonary, cardiac, and neurologic toxicity was noted in 12%, 14%, and 15%, respectively, of long-term survivors. These complications were the result of aggressive combined modality therapy. Certain drugs appeared to cause additive toxicity when combined with radiation. Three patients developed new primary tumors of squamous cell origin. Attention must be directed to defining the safest way to employ aggressive combined modality treatment for these patients

  13. Efficacy and acceptability of long-term norethindrone acetate for the treatment of rectovaginal endometriosis.

    Science.gov (United States)

    Morotti, Matteo; Venturini, Pier Luigi; Biscaldi, Ennio; Racca, Annalisa; Calanni, Luana; Vellone, Valerio Gaetano; Stabilini, Cesare; Ferrero, Simone

    2017-06-01

    To study the efficacy of long-term treatment with norethindrone acetate (NETA) in patients with rectovaginal endometriosis. This retrospective cohort study included 103 women with pain symptoms caused by rectovaginal endometriosis. Patients received NETA alone (2.5mg/day up to 5mg/day) for 5 years. Primary outcome was the degree of satisfaction with treatment after 5 years of progestin therapy. Secondary outcomes were the assessment of any variation in pain symptoms and the volumetric assessment of the disease by magnetic resonance imaging (MRI). Sixty-one women completed the 5-year follow-up (61/103, 59.2%) with 16 women withdrawing because of adverse effects (38.1%). Overall, 68.8% (42/61) of the women who completed the study were satisfied or very satisfied of this long term NETA treatment. This represents a 40.8% (42/103) of the patients enrolled. Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (pendometriosis under NETA treatment. Five-year therapy with NETA is safe and well tolerated by women with rectovaginal endometriosis. Due to its low cost and good pharmacological profile, it represents a good candidate for long-term treatment in this setting. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Treatment experience of surgical repair for long-term skull defect

    Directory of Open Access Journals (Sweden)

    Shou-cheng FAN

    2015-12-01

    Full Text Available Retrospective analysis was performed on 30 patients of skull defect who underwent surgical repair. Intraoperative and postoperative curative effect was evaluated on those patients, and the results showed that the incidence rate of intraoperative dura mater defect (P = 0.001, early postoperative complications [new epilepsy (P = 0.035 and effusion (P = 0.021] and late postoperative complications [foreign body sensation (P = 0.035 and dizziness and headache (P = 0.050] in long-term skull defect group were all higher than those in control group. In conclusion, surgical repair of long-term skull defect incurring high risk and various complications will not be an ideal management. Therefore, early surgical treatment for skull defect is suggested. DOI: 10.3969/j.issn.1672-6731.2015.12.016

  15. Long term results of childhood dysphonia treatment.

    Science.gov (United States)

    Mackiewicz-Nartowicz, Hanna; Sinkiewicz, Anna; Bielecka, Arleta; Owczarzak, Hanna; Mackiewicz-Milewska, Magdalena; Winiarski, Piotr

    2014-05-01

    The aim of this study was to assess the long term results of treatment and rehabilitation of childhood dysphonia. This study included a group of adolescents (n=29) aged from 15 to 20 who were treated due to pediatric hyperfunctional dysphonia and soft vocal fold nodules during their pre-mutational period (i.e. between 5 and 12 years of age). The pre-mutational therapy was comprised of proper breathing pattern training, voice exercises and psychological counseling. Laryngostroboscopic examination and perceptual analysis of voice were performed in each patient before treatment and one to four years after mutation was complete. The laryngostroboscopic findings, i.e. symmetry, amplitude, mucosal wave and vocal fold closure, were graded with NAPZ scale, and the GRBAS scale was used for the perceptual voice analysis. Complete regression of the childhood dysphonia was observed in all male patients (n=14). Voice disorders regressed completely also in 8 out of 15 girls, but symptoms of dysphonia documented on perceptual scale persisted in the remaining seven patients. Complex voice therapy implemented in adolescence should be considered as either the treatment or preventive measure of persistent voice strain, especially in girls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  17. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    CONTEXT: Insulin resistance is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). The molecular mechanisms underlying reduced insulin-mediated glycogen synthesis in skeletal muscle of patients with PCOS have not been established. SUBJECTS AND METHODS: We...... metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry. RESULTS: Reduced insulin-mediated glucose disposal (P .... No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P

  18. Treatment timing for functional jaw orthopaedics followed by fixed appliances: a controlled long-term study.

    Science.gov (United States)

    Pavoni, Chiara; Lombardo, Elisabetta Cretella; Lione, Roberta; Faltin, Kurt; McNamara, James A; Cozza, Paola; Franchi, Lorenzo

    2017-11-01

    To evaluate the role of treatment timing on long-term dentoskeletal effects of Class II treatment with removable functional appliances followed by full-fixed appliance therapy. A group of 46 patients (23 females and 23 males) with Class II malocclusion treated consecutively with either Bionator or Activator, followed by fixed appliances was compared with a matched control group of 31 subjects (16 females and 15 males) with untreated Class II malocclusion. The treated sample was evaluated at T1, start of treatment (mean age: 9.9 ± 1.3 years); T2, end of functional treatment and prior to fixed appliances (mean age: 11.9 ± 1.3 years); and T3, long-term observation (mean age: 18.3 ± 2.1 years). The treated and the control samples were divided into pre-pubertal and pubertal groups according to skeletal maturity observed at the start of treatment. Statistical comparisons were performed with independent sample t-tests. When treatment was initiated before puberty, Class II correction was mostly confined to the dentoalveolar changes, with significant improvements of both overjet and molar relationships. On the other hand, treatment with the outset at puberty produced significant long-term improvement of sagittal skeletal relationships, which were mainly sustained by mandibular changes. Treatment with removable functional appliances (Bionator or Activator) followed by full-fixed appliances produced significant skeletal long-term changes when it begins at puberty. Prepubertal Class II treatment results primarily in dentoalveolar changes. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

  19. Very long-term sequelae of craniopharyngioma.

    Science.gov (United States)

    Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

    2017-06-01

    Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

  20. Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.

    Science.gov (United States)

    Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S

    2013-01-01

    The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02). CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  1. Impact of the CYP2C8 *3 polymorphism on the drug–drug interaction between gemfibrozil and pioglitazone

    Science.gov (United States)

    Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S

    2013-01-01

    AIM The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug–drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). METHODS In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. RESULTS Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P= 0.02). CONCLUSION CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil–pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug–drug interactions. PMID:22625877

  2. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes.

    Science.gov (United States)

    Bi, Yan; Zhang, Bing; Xu, Wen; Yang, Huijie; Feng, Wenhuan; Li, Cuiliu; Tong, Guoyu; Li, Ming; Wang, Xin; Shen, Shanmei; Zhu, Bin; Weng, Jianping; Zhu, Dalong

    2014-10-01

    Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

  3. Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by neurostimulation

    NARCIS (Netherlands)

    Staal, M. J.; Holm, A. F.; Mooij, J. J. A.; Albers, F. W. J.; Bartels, H.

    2007-01-01

    Objective: Long-term evaluation of treatment of chronic, therapeutically refractory tinnitus by means of chronic electrical stimulation of the vestibulocochlear nerve. Patients: Inclusion criteria were severe, chronic, therapeutically refractory, unilateral tinnitus and severe hearing loss at the

  4. Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

    DEFF Research Database (Denmark)

    Connor, Kathryn M; Aurora, Sheena K; Loeys, Tom

    2011-01-01

    To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine....

  5. Long-term results after Boston brace treatment in adolescent idiopathic scoliosis

    Directory of Open Access Journals (Sweden)

    Steen Harald

    2009-08-01

    Full Text Available Abstract Background Few studies have evaluated long-term outcome after bracing using validated health related quality of life outcome measures. The aim of the present study was to evaluate the long-term outcome in adolescent idiopathic scoliosis (AIS 12 years or more after treatment with the Boston brace. Methods 109 (80% of 135 patients (7 men with AIS treated with the Boston brace at a mean of 19.2 (range 12–28 years previously responded to long-term follow-up examination. All patients (n = 109 answered a standardised questionnaire including demographics, work status, treatment, Global Back Disability Question, Oswestry Disability Index (ODI (100-worst possible, General Function Score (GFS (100 – worst possible, EuroQol (EQ-5D (1 – best possible, EQ-VAS (100 – best possible and Scoliosis Research Society -22 (SRS – 22 (5 – best possible. Clinical and radiological examination was obtained in 86 patients. Results The magnitude of the primary prebrace major curve was in average 33.4° (range 20 – 52. At weaning and at the last follow-up the corresponding values were 28.3° (9–56 and 34.2° (8 – 87, respectively. The mean age at follow-up was 35 (27 – 46 years. Work status was: full time (80%, on sick-leave (3%, on rehabilitation (4%, disability pension (4%, homemaker (7%, students (2%, 7% had changed their job because of back pain. 88% had had delivered a baby, 55% of them had pain in pregnancy. Global back status was excellent or good in 81%. The mean (standard deviation ODI was 6.4 (9.8, GFS 5.4 (10.5, EQ-5D 0.84 (0.2, SRS-22: pain 4.2 (0.8, mental health 4.2 (0.7, self-image 3.9 (0.7, function 4.1 (0.6, satisfaction with treatment 3.7 (1.0. 28% had taken physiotherapy for back pain the last year and 12% had visited a doctor. Conclusion Long-term results were satisfactory in most patients with AIS treated with the Boston brace.

  6. Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study

    Directory of Open Access Journals (Sweden)

    Nam Hoon Kim

    2017-06-01

    Full Text Available BackgroundGlycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes.MethodsIn this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17 or pioglitazone (15 mg once daily, n=14 treatment groups for 16 weeks. Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions (MAGE, which was obtained from continuous glucose monitoring. Urinary 8-iso prostaglandin F2α, serum oxidised low density lipoprotein, and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation.ResultsBoth vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL, P=0.046, and mean standard deviation of 24 hours glucose (from 38±17.3 to 27.7±6.9, P=0.026; however, pioglitazone did not, although the magnitude of decline was similar in both groups. Markers of oxidative stress or inflammation including urinary 8-iso prostaglandin F2α did not change after treatment in both groups.ConclusionIn this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.

  7. Psychosexual Development in Men with Congenital Hypogonadotropic Hypogonadism on Long-Term Treatment: A Mixed Methods Study

    Directory of Open Access Journals (Sweden)

    Andrew A. Dwyer, MSN, FNP-BC

    2015-03-01

    Conclusions: CHH men frequently experience psychosexual problems that pose barriers to intimate relationships and initiating sexual activity. These lingering effects cause significant distress and are not ameliorated by long-term treatment. Psychosexual assessment in CHH men with appropriate psychological support and treatment should be warranted in these patients. Dwyer AA, Quinton R, Pitteloud N, and Morin D. Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: A mixed methods study. Sex Med 2015;3:32–41.

  8. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsson, H.; Jernberg, C.; Andersson, A.F.; Sjolund-Karlsson, M.; Jansson, J.K.; Engstrand, L.

    2010-01-15

    Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.

  9. Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

    DEFF Research Database (Denmark)

    Hauerslev, Marie; Mørk, Sivagowry Rasalingam; Pryds, Kasper

    2018-01-01

    Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Due to overlapping mechanisms this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term ...

  10. Long-term effects of stimulant treatment on ADHD symptoms, social-emotional functioning, and cognition.

    Science.gov (United States)

    Schweren, Lizanne; Hoekstra, Pieter; van Lieshout, Marloes; Oosterlaan, Jaap; Lambregts-Rommelse, Nanda; Buitelaar, Jan; Franke, Barbara; Hartman, Catharina

    2018-03-13

    Methodological and ethical constraints have hampered studies into long-term lasting outcomes of stimulant treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). Lasting effects may be beneficial (i.e. improved functioning even when treatment is temporarily ceased) or detrimental (i.e. worse functioning while off medication), but both hypotheses currently lack empirical support. Here we investigate whether stimulant treatment history predicts long-term development of ADHD symptoms, social-emotional functioning or cognition, measured after medication wash-out. ADHD symptoms, social-emotional functioning and cognitive test performance were measured twice, 6 years apart, in two ADHD groups (stimulant-treated versus not stimulant-treated between baseline and follow-up). Groups were closely matched on baseline clinical and demographic variables (n = 148, 58% male, age = 11.1). A matched healthy control group was included for reference. All but two outcome measures (emotional problems and prosocial behaviour) improved between baseline and follow-up. Improvement over time in the stimulant-treated group did not differ from improvement in the not stimulant-treated group on any outcome measure. Stimulant treatment is not associated with the long-term developmental course of ADHD symptoms, social-emotional functioning, motor control, timing or verbal working memory. Adolescence is characterised by clinical improvement regardless of stimulant treatment during that time. These findings are an important source to inform the scientific and public debate.

  11. Long-term skeletal effects of high-pull headgear followed by fixed appliances for the treatment of Class II malocclusions.

    Science.gov (United States)

    Bilbo, E Erin; Marshall, Steven D; Southard, Karin A; Allareddy, Verrasathpurush; Holton, Nathan; Thames, Allyn M; Otsby, Marlene S; Southard, Thomas E

    2018-04-18

    The long-term skeletal effects of Class II treatment in growing individuals using high-pull facebow headgear and fixed edgewise appliances have not been reported. The purpose of this study was to evaluate the long-term skeletal effects of treatment using high-pull headgear followed by fixed orthodontic appliances compared to an untreated control group. Changes in anteroposterior and vertical cephalometric measurements of 42 Class II subjects (n = 21, mean age = 10.7 years) before treatment, after headgear correction to Class I molar relationship, after treatment with fixed appliances, and after long-term retention (mean 4.1 years), were compared to similar changes in a matched control group (n = 21, mean age = 10.9 years) by multivariable linear regression models. Compared to control, the study group displayed significant long-term horizontal restriction of A-point (SNA = -1.925°, P appliances resulted in correction to Class I molar through restriction of horizontal maxillary growth with continued horizontal mandibular growth and vertical skeletal changes unaffected. The anteroposterior molar correction and skeletal effects of this treatment were stable long term.

  12. Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment

    NARCIS (Netherlands)

    Mothapo, K.M.; Schellekens, A.F.A.; Crevel, R. van; Keuter, M.; Grintjes-Huisman, K.; Koopmans, P.; Ven, A. van der

    2015-01-01

    Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to

  13. Influences on the start, selection and duration of treatment with antibiotics in long-term care facilities.

    Science.gov (United States)

    Daneman, Nick; Campitelli, Michael A; Giannakeas, Vasily; Morris, Andrew M; Bell, Chaim M; Maxwell, Colleen J; Jeffs, Lianne; Austin, Peter C; Bronskill, Susan E

    2017-06-26

    Understanding the extent to which current antibiotic prescribing behaviour is influenced by clinicians' historical patterns of practice will help target interventions to optimize antibiotic use in long-term care. Our objective was to evaluate whether clinicians' historical prescribing behaviours influence the start, prolongation and class selection for treatment with antibiotics in residents of long-term care facilities. We conducted a retrospective cohort study of all physicians who prescribed to residents in long-term care facilities in Ontario between Jan. 1 and Dec. 31, 2014. We examined variability in antibiotic prescribing among physicians for 3 measures: start of treatment with antibiotics, use of prolonged durations exceeding 7 days and selection of fluoroquinolones. Funnel plots with control limits were used to determine the extent of variation and characterize physicians as extreme low, low, average, high and extreme high prescribers for each tendency. Multivariable logistic regression was used to assess whether a clinician's prescribing tendency in the previous year predicted current prescribing patterns, after accounting for residents' demographics, comorbidity, functional status and indwelling devices. Among 1695 long-term care physicians, who prescribed for 93 132 residents, there was wide variability in the start of antibiotic treatment (median 45% of patients, interquartile range [IQR] 32%-55%), use of prolonged treatment durations (median 30% of antibiotic prescriptions, IQR 19%-46%) and selection of fluoroquinolones (median 27% of antibiotic prescriptions, IQR 18%-37%). Prescribing tendencies for antibiotics by physicians in 2014 correlated strongly with tendencies in the previous year. After controlling for individual resident characteristics, prior prescribing tendency was a significant predictor of current practice. Physicians prescribing antibiotics exhibited individual, measurable and historical tendencies toward start of antibiotic treatment

  14. Seminar on long term research into liquid effluent treatment,

    International Nuclear Information System (INIS)

    Hooper, E.W.

    1987-02-01

    A one-day Seminar on Long Term Research into Liquid Waste Treatment was held at Harwell on 30th January 1986. The Seminar was sponsored by the Department of the Environment and was attended by ninety-five delegates representing industry, universities, DoE, CEGB and the AEA. The purpose of the meeting was to provide an opportunity for people working in the field of liquid effluent treatment to obtain up-to-date information on the nature and status of research being carried out in the United Kingdom. Nine presentations on research activity described work being undertaken on ultrafiltration and associated techniques, electrical processes and ion exchange. The presenters were from BNF plc, CEGB, Imperial College, University of Salford, University of Reading and from Harwell. (author)

  15. Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism.

    Science.gov (United States)

    Zimmermann, E; Wassmer, S; Steudle, V

    1996-01-01

    Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

  16. Pioglitazone reverses down-regulation of cardiac PPARγ expression in Zucker diabetic fatty rats

    International Nuclear Information System (INIS)

    Pelzer, Theo; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

    2005-01-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARγ in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARγ agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARγ, glucose transporter-4 and α-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARγ, glut-4, and α-MHC expression levels in diabetic ZDF rats. Cardiac [ 18 F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARγ agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARγ expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin

  17. Are long-term bisphosphonate users a reality?

    DEFF Research Database (Denmark)

    Abrahamsen, B

    2012-01-01

    The prevalence of long-term bisphosphonate use may be low due to low refill compliance and gaps in treatment. An analysis of the prescription history of 58,674 bisphosphonate users in Denmark found that only 2.8 % had received ten dose years of treatment or above. INTRODUCTION: This study aims...... to describe the demographics of present bisphosphonate (BP) users, to determine the prevalence of long-term BP use, and to establish if long-term use (a 10-year history of osteoporosis treatment) translated to ten dose years of bisphosphonate prescriptions filled, given the propensity for treatment gaps...... more than ten dose years of a BP. For any osteoporosis drug, 3.0 % had received ten dose years or more, while 23.2 % had received between 5 and 10 years of treatment. CONCLUSION: Long-term users with ten dose years or more of a BP are rare due to periods of low compliance and gaps, with a discrepancy...

  18. Acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage in neonatal rats.

    Science.gov (United States)

    Klebe, Damon; Krafft, Paul R; Hoffmann, Clotilde; Lekic, Tim; Flores, Jerry J; Rolland, William; Zhang, John H

    2014-08-01

    This study investigated if acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH). Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals received either deferoxamine or vehicle twice a day for 7 consecutive days. Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH. At 28 days post-GMH, brain morphology was assessed and extracellular matrix protein (fibronectin and vitronectin) expression was determined. Acute and delayed deferoxamine treatment improved long-term motor and cognitive function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with improved overall brain morphology at 28 days post-GMH, reducing white matter loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical loss. GMH resulted in significantly increased expression of fibronectin and vitronectin, which was reversed by acute and delayed deferoxamine treatment. Acute and delayed deferoxamine administration ameliorated long-term sequelae after GMH. © 2014 American Heart Association, Inc.

  19. Long-term treatment of severe hypertension with minoxidil.

    Science.gov (United States)

    Nawar, T.; Nolin, L.; Plante, G. E.; Caron, C.; Montambault, P.

    1977-01-01

    Minoxidil, a new potent hypotensive agent, was used as the primary antihypertensive agent in 11 patients--10 men and 1 woman aged 35 to 54 years with severe hypertension that was refractory to treatment with maximal (or maximally tolerated) doses of conventional antihypertensive agents. Six patients had severely impaired renal function and three of them were undergoing long-term hemodialysis. The patients were given 2.5 to 40 mg/d of minoxidil for periods of 2 to 29 months. All except one who was almost anuric received propranolol and diuretics. Blood pressure was controlled satisfactorily in all patients. In two patients the hypertension became partially resistant after 1 year of treatment. The main side effects were sodium retention, tachycardia and hirsutism. Renal function remained stable or improved and hemodialysis was discontinued in two patients. Minoxidil is a remarkably potent hypotensive with relatively few side effects and seems particularly advantageous in patients with chronic renal failure. PMID:603847

  20. Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome.

    Science.gov (United States)

    Colas, Damien; Chuluun, Bayarsaikhan; Garner, Craig C; Heller, H Craig

    2017-04-01

    Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABA A receptor (GABA A R) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABA A R antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS. Copyright © 2017. Published by Elsevier Inc.

  1. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    Science.gov (United States)

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

  2. Lenalidomide in relapsed and refractory multiple myeloma disease: feasibility and benefits of long-term treatment.

    Science.gov (United States)

    Zago, Manola; Oehrlein, Katharina; Rendl, Corinna; Hahn-Ast, Corinna; Kanz, Lothar; Weisel, Katja

    2014-12-01

    Lenalidomide in combination with dexamethasone is an effective and well-established treatment of relapsed or refractory multiple myeloma (rrMM) disease. Due to the scarcity of reports assessing benefit and risk of long-term lenalidomide treatment in non-selected rrMM patients, we retrospectively analysed the long-term outcome in patients with rrMM treated with lenalidomide and dexamethasone. Sixty-seven patients (pts) who were treated with lenalidomide/dexamethasone for rrMM in the approved indication from 2007 to 2011 were included in this retrospective, single-centre analysis. Kaplan-Meier survival estimates were compared between total population, patients on lenalidomide for more than 12 months (mo) and patients discontinuing therapy earlier than 12 months. Median overall survival (OS) of the total patient population was 33.2 mo. OS of pts treated beyond 12 mo was 42.9 mo compared to 20.2 mo (p = 0.027) for pts stopping lenalidomide earlier than 12 mo for other reasons than progression disease (PD). OS of pts >12 mo on lenalidomide treatment did not significantly differ between pts who had received previous autologous transplantation, allogeneic transplantation or conventional therapy. Main non-hematologic toxicities were infections of grade 3/4 in 25 % and thrombembolic events of all grades in 18 % of patients. To the best of our knowledge, this is the first report on feasibility and efficacy of long-term lenalidomide treatment in a non-selected patient cohort. OS of pts >12 mo on lenalidomide is superior when compared to pts discontinued earlier for reasons other than PD. Our data confirm the current use of lenalidomide as a continuous long-term treatment strategy.

  3. Additive effects of glucagon-like peptide 1 and pioglitazone in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, Mette; Christiansen, Allan; Madsbad, Sten

    2004-01-01

    plasma levels of glucose, insulin, glucagon, free fatty acids (FFAs), and sensation of appetite. RESULTS: Fasting plasma glucose decreased from 13.5 +/- 1.2 mmol/l (saline) to 11.7 +/- 1.2 (GLP-1) and 11.5 +/- 1.2 (pioglitazone) and further decreased to 9.9 +/- 1.0 (combination) (P ...-hour mean plasma glucose levels were reduced from 13.7 +/- 1.1 mmol/l (saline) to 10.6 +/- 1.0 (GLP-1) and 12.0 +/- 1.2 (pioglitazone) and were further reduced to 9.5 +/- 0.8 (combination) (P ....01). Glucagon levels were reduced in GLP-1 and combination therapy compared with saline and monotherapy with pioglitazone (P Sensation of appetite was reduced during monotherapy...

  4. Long term surgical treatment outcome of talar body fracture

    Directory of Open Access Journals (Sweden)

    Sen Ramesh Kumar

    2012-02-01

    Full Text Available 【Abstract】Objective: Talar body fractures are rare and have poor treatment outcome. The purpose of this study is to report the long term surgical treatment outcome of closed talar dome fractures. Methods: Eight closed talar body fractures, treated by open reduction and internal fixation with small fragment cancellous screws and/or Herbert screws in our level I trauma centre were retrospectively analyzed. Preoperative and postoperative radiographs of the foot (antero-posterior, lateral and oblique views and ankle (antero-posterior, lateral and mortise views were obtained. The patients were followed up both radiologically and functionally (foot function index, FFI after 3 weeks, 6 weeks, 3 months, 6 months and then annually. Results: There were five crush fractures and three shear fractures (two sagittal shear and one coronal shear, with average follow-up of 5 years. No early complications were noticed in these patients. Late complications included osteoarthrosis of subtalar/ankle joints in six patients and osteonecrosis of talar body in four patients. On functional assessment, mean FFI after 5 years was 104.63 points and worse outcome was noticed in crush injury and coronal shear fractures. Sagittal shear fractures had a good functional and radiological outcome. Conclusions: Late complications subsequent to surgically treated talar body fractures are inevitable, even though exact reduction and rigid fixation are achieved, thus patients are supposed to be counseled about the adverse outcome. Although crush and coronal shear fractures have poor outcome, sagittal injuries have good prognosis on long term evaluation. Key words: Fractures, bone; Talus; Fracture fixation, internal

  5. Fecal Transplantation Treatment of Antibiotic-Induced, Noninfectious Colitis and Long-Term Microbiota Follow-Up

    NARCIS (Netherlands)

    Satokari, R.; Fuentes, S.; Mattila, E.; Jalanka, J.; Vos, de W.M.; Arkkila, P.

    2014-01-01

    Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) and is considered as a treatment for other gastrointestinal (GI) diseases. We followed up the relief of symptoms and long-term, over-a-year microbiota stabilization in a 46-year-old

  6. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

    Directory of Open Access Journals (Sweden)

    Todd D. Levine

    2012-01-01

    Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

  7. Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis.

    Science.gov (United States)

    Kang, Young Ae; Kim, Song Yee; Jo, Kyung-Wook; Kim, Hee Jin; Park, Seung-Kyu; Kim, Tae-Hyung; Kim, Eun Kyung; Lee, Ki Man; Lee, Sung Soon; Park, Jae Seuk; Koh, Won-Jung; Kim, Dae Yun; Shim, Tae Sun

    2013-01-01

    Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death. Copyright © 2013 S. Karger AG, Basel.

  8. The effects of long- and short-term interdisciplinary treatment approaches in women with fibromyalgia: a randomized controlled trial.

    Science.gov (United States)

    Saral, Ilknur; Sindel, Dilsad; Esmaeilzadeh, Sina; Sertel-Berk, Hanife Ozlem; Oral, Aydan

    2016-10-01

    We investigated the effects of long- and short-term interdisciplinary treatment approaches for reducing symptoms and improving health-related quality of life (HRQoL) and physical functions of patients with fibromyalgia and compared the effects of two different interdisciplinary treatment approaches. We conducted a prospective, randomized, controlled trial involving 66 women with fibromyalgia eligible for the study at a university hospital setting. The patients were randomized into three groups (allocation ratio 1:1:1) using a computer-generated random numbers: a long-term interdisciplinary treatment group (LG, n = 22) that participated in 10 sessions (3-h once-weekly session for 10 weeks) of cognitive behavioral therapy (CBT) together with exercise training and other fibromyalgia related educational programs (two full days); a short-term interdisciplinary treatment group (SG, n = 22) that received two full days of educational, exercise, and CBT programs; and a control group (CG, n = 22). The patients were evaluated at baseline and 6 months after treatment using the visual analog scale (pain, fatigue, and sleep), Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Short Form-36, tender point numbers, and pressure algometry as primary outcomes. The statistical analysis was confined to the 'per-protocol' set. No blinding was performed. The number of patients analyzed was 21 in the LG, 19 in the SG, and 19 in the CG. The intensity of pain (p treatment approaches when compared with controls; the long-term treatment was found more effective in reducing pain than the short-term. Both, long- and short-term interdisciplinary treatments were effective in reducing the severity of some symptoms and disease activity in patients with fibromyalgia. The short-term program well meets the needs of women with fibromyalgia particularly in relation to pain and health status as measured using FIQ; however, a long-term program may be beneficial in reducing fatigue and

  9. Long-term results of combined ESWL and ERCP treatment of chronic calcific pancreatitis.

    Science.gov (United States)

    Korpela, Taija; Udd, Marianne; Tenca, Andrea; Lindström, Outi; Halttunen, Jorma; Myrskysalo, Sanna; Mikkola, Arto; Kylänpää, Leena

    2016-07-01

    Extracorporeal shock wave lithotripsy (ESWL) combined with endotherapy (ET) is the standard treatment for pancreatic duct stones (PDS) in chronic pancreatitis (CP). Our aim was to report the short- and long-term results of ESWL and ET. Consecutively treated 83 patients with symptomatic PDS using ESWL and ET. Success was defined (i) technically: PDS fragmentation and clearance obtained and (ii) clinically: improvement/resolution of pain. To get information on quality of life, we conducted a phone survey whereby we contacted 64 (89%) patients. The long-term results are presented in those patients with ≥2 years follow-up. Treated PDS with median size of 10 (5-25) mm were located in the head, body, or the tail of the pancreas in 78, 4, and 1 patients, respectively. The primary results were that technical success was achieved in 69 patients (83%) and clinical success in 66 patients (80%). Fourteen patients had technical failure, but eight of them became free of pain. Thus, clinical success can be considered to have been achieved in 74 of 83 patients (89%). In patients with persistent pseudocyst (PC) at the time of ESWL (n = 19), the PC disappeared in a year in 14 patients (74%). The long-term results were obtained from 61 (73%) ESWL- and ET-treated patients. The median follow-up for them was 53 months (range: 24-124) and 57 patients (93%) became pain-free or had less pain. For patients with CP and PDS ESWL combined with ET is an effective and safe treatment giving favorable long-term results.

  10. Differences in health status between long-term and short-term benzodiazepine users.

    NARCIS (Netherlands)

    Zandstra, S.M.; Furer, J.W.; Lisdonk, E.H. van de; Bor, J.H.J.; Zitman, F.G.; Weel, C. van

    2002-01-01

    BACKGROUND: Despite generally accepted advice to keep treatment short, benzodiazepines are often prescibed for more than six months. Prevention of long-term benzodiazepine use could be facilitated by the utilisation of risk indicators for long-term use. However, the characteristics of long-term

  11. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  12. Cardiac damage after treatment of childhood cancer: A long-term follow-up

    International Nuclear Information System (INIS)

    Velensek, Veronika; Mazic, Uros; Krzisnik, Ciril; Demšar, Damjan; Jazbec, Janez; Jereb, Berta

    2008-01-01

    With improved childhood cancer cure rate, long term sequelae are becoming an important factor of quality of life. Signs of cardiovascular disease are frequently found in long term survivors of cancer. Cardiac damage may be related to irradiation and chemotherapy. We have evaluated simultaneous influence of a series of independent variables on the late cardiac damage in childhood cancer survivors in Slovenia and identified groups at the highest risk. 211 long-term survivors of different childhood cancers, at least five years after treatment were included in the study. The evaluation included history, physical examination, electrocardiograpy, exercise testing and echocardiograpy. For analysis of risk factors, beside univariate analysis, multivariate classification tree analysis statistical method was used. Patients treated latest, from 1989–98 are at highest risk for any injury to the heart (73%). Among those treated earlier are at the highest risk those with Hodgkin's disease treated with irradiation above 30 Gy and those treated for sarcoma. Among specific forms of injury, patients treated with radiation to the heart area are at highest risk of injury to the valves. Patients treated with large doses of anthracyclines or concomitantly with anthracyclines and alkylating agents are at highest risk of systolic function defect and enlarged heart chambers. Those treated with anthracyclines are at highest risk of diastolic function defect. The time period of the patient's treatment is emerged as an important risk factor for injury of the heart

  13. Long-Term Quality of Life Improvement in Subjects with Healed Erosive Esophagitis: Treatment with Lansoprazole

    Science.gov (United States)

    Freston, James W.; Haber, Marian M.; Atkinson, Stuart; Hunt, Barbara; Peura, David A.

    2009-01-01

    Background Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. Aims To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. Methods Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. Results During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P ≤ 0.05) greater improvements than ranitidine-treated patients in the frequency, severity, and ‘bothersomeness’ of heartburn, the symptom index, problems of activity limitation, eating and drinking problems, symptom problems, health distress, and social functioning. During dose-titrated, open-label treatment (n = 195), all disease-specific QOL scales except sleep improved significantly (P lansoprazole for 12 months in healed EE subjects produced significantly greater improvements in QOL indicators than ranitidine. These improvements were sustained during dose-titrated, open-label lansoprazole treatment. PMID:19582579

  14. Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

    Science.gov (United States)

    Fox, Henrik; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf; Gutleben, Klaus-Jürgen

    2017-05-01

    Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remedē® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remedē® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. We performed remedē® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. Novel remedē® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting. © 2017 Wiley Periodicals, Inc.

  15. Follow-up of Long-term Treatment with Clean Intermittent Catheterization for Neurogenic Bladder in Children

    Directory of Open Access Journals (Sweden)

    Panuwat Lertsithichai

    2004-04-01

    Conclusions: For most patients and with close long-term follow-up, early treatment of neurogenic bladder using CIC in children born with myelomeningocele yields better results than late treatment. In our experience, treatment is recommended as soon as possible, especially during the first year of life.

  16. Comparative Study on Adding Pioglitazone or Sitagliptin to Patients with Type 2 Diabetes Mellitus Insufficiently Controlled With Metformin

    Directory of Open Access Journals (Sweden)

    Maryam Jameshorani

    2017-12-01

    CONCLUSION: Sitagliptin and Pioglitazone demonstrated similar improvements in glycemic control in type 2 diabetes mellitus patients whose diabetes had been inadequately controlled with metformin. Nevertheless, sitagliptin was more effective than pioglitazone regarding lipid and body weight change.

  17. Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial.

    LENUS (Irish Health Repository)

    Bonati, Leo H

    2009-10-01

    In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), early recurrent carotid stenosis was more common in patients assigned to endovascular treatment than it was in patients assigned to endarterectomy (CEA), raising concerns about the long-term effectiveness of endovascular treatment. We aimed to investigate the long-term risks of restenosis in patients included in CAVATAS.

  18. Neoadjuvant twice daily chemoradiotherapy for esophageal cancer: Treatment-related mortality and long-term outcomes

    Directory of Open Access Journals (Sweden)

    Stuart E. Samuels, MD, PhD

    2017-07-01

    Conclusion: Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

  19. Long-term outcomes of Class III treatment with mandibular cervical headgear followed by fixed appliances.

    Science.gov (United States)

    Baccetti, Tiziano; Rey, Diego; Oberti, Giovanni; Stahl, Franka; McNamara, James A

    2009-09-01

    To evaluate the stability of the outcomes of mandibular cervical headgear (MCH) and fixed appliance-treated Class III patients at a long-term posttreatment (5 years) observation, compared with well-matched untreated Class III controls, following a previous report on the short-term outcomes of this protocol. The treated group consisted of 20 patients with dentoskeletal Class III malocclusions treated with a two-phase protocol consisting of MCH and fixed appliances, while the control group comprised 18 untreated subjects with similar dentoskeletal Class III malocclusion. Lateral cephalograms of both patients and controls were analyzed at two time points: posttreatment (PT), after two-phase treatment; and long term (LT). All patients were at a postpubertal stage of skeletal maturity at PT, and they showed CS6 at LT, thus revealing completion of pubertal craniofacial growth. In the long term, the treatment group showed significantly smaller values for mandibular length (Co-Gn), SNB angle, maxillomandibular differential, and molar relation. When compared with the controls, the treated patients exhibited also greater values for ANB angle, Wits appraisal, and overjet at LT. No significant difference between the two groups was found for the changes occurring from PT to LT. Favorable dentoskeletal outcomes induced by MCH and fixed appliances remained stable in the long term; untreated Class III malocclusion did not show any tendency toward self-improvement during the postpubertal interval.

  20. Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Madsen, Jan Kyst; Grande, Peer

    2010-01-01

    Abstract Objectives. The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. Design. Patients (N=751) with post-thrombolytic Q-wave myo......Abstract Objectives. The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. Design. Patients (N=751) with post-thrombolytic Q...

  1. Age at treatment and long-term performance results in medulloblastoma

    International Nuclear Information System (INIS)

    Chin, H.W.; Maruyama, Y.

    1984-01-01

    Medulloblastoma is highly radioresponsive, and recent treatment results have improved greatly since the introduction of megavoltage machine in 1960s. There is increasing evidence for the potential cure of medulloblastoma if properly treated in its early stages. The curable group represents approximately 75% of diagnosed patients. Long-term treatment effects were examined in this study. The study reveals age-dependent late effects in learning ability; the patients less than 4-years-old at treatment had major learning problems; patients of 5 to 7 years old performed at satisfactory-to-low passing levels in school work; patients older than 8 years old had no major intellectual impairment. Short stature was common when growth potential was present at the time of therapy, but endocrine tests were generally negative. These observations indicate special educational requirement needs, especially for children treated at a young age

  2. Chronic treatment with pioglitazone does not protect obese patients with diabetes mellitus type II from free fatty acid-induced insulin resistance

    NARCIS (Netherlands)

    Serlie, Mireille J.; Allick, Gideon; Groener, Johanna E.; Ackermans, Mariette T.; Heijligenberg, Rik; Voermans, Barbara C.; Aerts, Johannes M.; Meijer, Alfred J.; Sauerwein, Hans P.

    2007-01-01

    CONTEXT: Thiazolidinediones increase peripheral insulin sensitivity and decrease plasma free fatty acids (FFA). However, their exact mechanism of action has not been fully elucidated. OBJECTIVE: We studied the protective effect of pioglitazone on FFA-induced insulin resistance and the effects on

  3. Neural Rhythms of Change: Long-Term Improvement after Successful Treatment in Children with Disruptive Behavior Problems

    Directory of Open Access Journals (Sweden)

    Steven Woltering

    2015-01-01

    Full Text Available Neural changes were investigated for children with disruptive behavior problems one year after a treatment program ended. Thirty-nine children and their parents visited the research lab before, after, and a year after treatment ended. During those lab visits, electroencephalography (EEG was recorded during a challenging Go/No-go task. Treatment consisted of intensive 14-week combined cognitive behavioral therapy and parent management training sessions. For the analysis, participants were divided into long-term improvers (IMPs and long-term nonimprovers (NIMPs based on changes in their externalizing problem scores. The results showed early no-go theta power (4–8 Hz, 100–250 ms decreased for long-term IMPs compared to NIMPs. When participants were divided based on changes in their comorbid internalizing symptoms, effects were stronger and reductions in theta power were found for early as well as later phases (250–650 ms. We provided preliminary evidence that theta power is a useful neural measure to trace behavioral change linked to improved self-regulation even up to a year after treatment ended. Results may have implications for the characterization of children with disruptive behavior problems and may lead to the development of novel markers of treatment success.

  4. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Glintborg, D.; Andersen, Mikael; Hagen, C.

    2008-01-01

    OBJECTIVE: Our objective was to investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS). DESIGN AND SETTING: We conducted a randomized, placebo-controlled study at an outpatient clinic at a university hospital. PATIENTS......: Thirty premenopausal patients with PCOS and 14 age- and weight-matched healthy females participated. INTERVENTIONS: Pioglitazone (30 mg/d) or placebo was given for 16 wk. MAIN OUTCOME MEASURES: Measurements of BMD [hip (neck and total) and lumbar spine (L2-L4)], bone metabolic parameters [alkaline...... phosphatase (ALP), 25-hydroxyvitamin D, C-telopeptide of type I collagen (ICTP), osteocalcin, and PTH], endocrine profiles (testosterone, estradiol, and insulin), and body composition (waist to hip ratio, body mass index, and whole-body dual-energy x-ray absorptiometry scans) were performed. RESULTS: Patients...

  5. Long-term treatment effect of trauma-affected refugees with flexible cognitive behavioural therapy and antidepressants.

    Science.gov (United States)

    Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

    2018-04-04

    Few studies exist on the long-term effect of treatment of trauma-affected refugees. The purpose of this study was to estimate the long-term treatment effects of cognitive behavioural therapy and antidepressants (sertraline and mianserin) in trauma-affected refugees. Follow-ups were conducted 6 and 18 months after a randomised controlled clinical trial. The included patients were refugees with war-related traumatic experiences, PTSD and without psychotic disorders. We found a small improvement over time in PTSD, depression and anxiety symptoms and level of functioning, but the improvement was not associated with any specific treatment. Personality change after catastrophic experiences and life events influenced the symptom level at all follow-ups while depression at completion of treatment was associated with a steeper decline in symptom load at the follow-ups. In spite of the limited decline in symptom scores and treatment effects immediately after treatment, the condition of the treated trauma-affected refugees was significantly improved 6 and 18 months after treatment although the improvement was small. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2008-01-01

    indicate that pioglitazone therapy restores insulin sensitivity, in part, by a coordinated upregulation of genes involved in mitochondrial OXPHOS and ribosomal protein biosynthesis in muscle in PCOS. These transcriptional effects of pioglitazone may contribute to prevent the onset of type 2 diabetes...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp...... Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes representing mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome degradation in PCOS after...

  7. Pioglitazone modulates vascular inflammation in atherosclerotic rabbits : noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging

    NARCIS (Netherlands)

    Vucic, E.; Dickson, S.D.; Calcagno, C.; Rudd, J.H.F.; Moshier, E.; Hayashi, K.; Mounessa, J.S.; Roytman, M.; Moon, M.J.; Lin, J.; Tsimikas, S.; Fisher, E.A.; Nicolay, K.; Fuster, V.; Fayad, Z.A.

    2011-01-01

    Objectives We sought to determine the antiatherosclerotic properties of pioglitazone using multimethod noninvasive imaging techniques. Background Inflammation is an essential component of vulnerable or high-risk atheromas. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist,

  8. The ε3 and ε4 alleles of human APOE differentially affect tau phosphorylation in hyperinsulinemic and pioglitazone treated mice.

    Directory of Open Access Journals (Sweden)

    Alvina W M To

    2011-02-01

    Full Text Available Impaired insulin signalling is increasingly thought to contribute to Alzheimer's disease (AD. The ε4 isoform of the APOE gene is the greatest genetic risk factor for sporadic, late onset AD, and is also associated with risk for type 2 diabetes mellitus (T2DM. Neuropathological studies reported the highest number of AD lesions in brain tissue of ε4 diabetic patients. However other studies assessing AD pathology amongst the diabetic population have produced conflicting reports and have failed to show an increase in AD-related pathology in diabetic brain. The thiazolidinediones (TZDs, peroxisome proliferator-activated receptor gamma agonists, are peripheral insulin sensitisers used to treat T2DM. The TZD, pioglitazone, improved memory and cognitive functions in mild to moderate AD patients. Since it is not yet clear how apoE isoforms influence the development of T2DM and its progression to AD, we investigated amyloid beta and tau pathology in APOE knockout mice, carrying human APOEε3 or ε4 transgenes after diet-induced insulin resistance with and without pioglitazone treatment.Male APOE knockout, APOEε3-transgenic and APOEε4-transgenic mice, together with background strain C57BL6 mice were kept on a high fat diet (HFD or low fat diet (LFD for 32 weeks, or were all fed HFD for 32 weeks and during the final 3 weeks animals were treated with pioglitazone or vehicle.All HFD animals developed hyperglycaemia with elevated plasma insulin. Tau phosphorylation was reduced at 3 epitopes (Ser396, Ser202/Thr205 and Thr231 in all HFD, compared to LFD, animals independent of APOE genotype. The introduction of pioglitazone to HFD animals led to a significant reduction in tau phosphorylation at the Ser202/Thr205 epitope in APOEε3 animals only. We found no changes in APP processing however the levels of soluble amyloid beta 40 was reduced in APOE knockout animals treated with pioglitazone.

  9. Long-term skeletal and dental effects and treatment timing for functional appliances in Class II malocclusion.

    Science.gov (United States)

    Franchi, Lorenzo; Pavoni, Chiara; Faltin, Kurt; McNamara, James A; Cozza, Paola

    2013-03-01

    To analyze the long-term skeletal and dentoalveolar effects and to evaluate treatment timing of Class II treatment with functional appliances followed by fixed appliances. A group of 40 patients (22 females and 18 males) with Class II malocclusion consecutively treated either with a Bionator or an Activator followed by fixed appliances was compared with a control group of 20 subjects (9 females and 11 males) with untreated Class II malocclusion. Lateral cephalograms were available at the start of treatment (mean age 10 years), end of treatment with functional appliances (mean age 12 years), and long-term observation (mean age 18.6 years). The treated sample also was divided into two groups according to skeletal maturity. The early-treatment group was composed of 20 subjects (12 females and 8 males) treated before puberty, while the late-treatment group included 20 subjects (10 females and 10 males) treated at puberty. Statistical comparisons were performed with analysis of variance followed by Tukey's post hoc tests. Significant long-term mandibular changes (Co-Gn) in the treated group (3.6 mm over the controls) were associated with improvements in the skeletal sagittal intermaxillary relationship, overjet, and molar relationship (∼3.0-3.5 mm). Treatment during the pubertal peak was able to produce significantly greater increases in total mandibular length (4.3 mm) and mandibular ramus height (3.1 mm) associated with a significant advancement of the bony chin (3.9 mm) when compared with treatment before puberty. Treatment of Class II malocclusion with functional appliances appears to be more effective at puberty.

  10. Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Huan [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Gao, Zhangfeng [Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410008 (China); Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Li, Zhi, E-mail: lizhi489@163.com [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China)

    2015-08-07

    The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST.

  11. Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

    International Nuclear Information System (INIS)

    Ren, Huan; Gao, Zhangfeng; Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng; Li, Zhi

    2015-01-01

    The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST

  12. Impact of long-term and short-term therapies on seminal parameters

    Directory of Open Access Journals (Sweden)

    Jlenia Elia

    2013-04-01

    Full Text Available Aim: The aim of this work was: i to evaluate the prevalence of male partners of subfertile couples being treated with long/short term therapies for non andrological diseases; ii to study their seminal profile for the possible effects of their treatments on spermatogenesis and/or epididymal maturation. Methods: The study group was made up of 723 subjects, aged between 25 and 47 years. Semen analysis was performed according to World Health Organization (WHO guidelines (1999. The Superimposed Image Analysis System (SIAS, which is based on the computerized superimposition of spermatozoa images, was used to assess sperm motility parameters. Results: The prevalence of subjects taking pharmacological treatments was 22.7% (164/723. The prevalence was 3.7% (27/723 for the Short-Term Group and 18.9% (137/723 for the Long-Term Group. The subjects of each group were also subdivided into subgroups according to the treatments being received. Regarding the seminal profile, we did not observe a significant difference between the Long-Term, Short-Term or the Control Group. However, regarding the subgroups, we found a significant decrease in sperm number and progressive motility percentage in the subjects receiving treatment with antihypertensive drugs compared with the other subgroups and the Control Group. Conclusions: In the management of infertile couples, the potential negative impact on seminal parameters of any drugs being taken as Long-Term Therapy should be considered. The pathogenic mechanism needs to be clarified.

  13. Evaluation of the long-term efficacy of CT-guided epidural steroid injection for the treatment of sciatica

    International Nuclear Information System (INIS)

    Tong Guohai; Wang Wei; Chen Wei; Chen Kemin

    2005-01-01

    Objective: To evaluate the long-term efficacy of CT-guided epidural steroid injection for the treatment of sciatica. Methods: CT-guided epidural steroid injection was performed in 180 patients with sciatica from May 1998 to March 2004, and all patients had failure to previous conservative treatment. Visual analogue scale was used to evaluate the pain of the patient before and after the treatment. Results: Follow-up was taken for 112 cases during 1-6 years after the treatment, 89 patients (79.5%) had successful long-term outcome and 80 patients (71.4%) were satisfied. Conclusions: CT-guided epidural steroid injection can reduce low back pain and radical pain. It should be preferentially considered as the first choice when conservative treatments are failed. (authors)

  14. Systematic review of long-term Xingnao Kaiqiao needling effcacy in ischemic stroke treatment

    Directory of Open Access Journals (Sweden)

    Zhi-xin Yang

    2015-01-01

    CONCLUSION: The Xingnao Kaiqiao needling method has a better effect than control treatment in reducing disability rate. The long-term effect of Xingnao Kaiqiao needling against ischemic stroke is better than that of control treatment. However, the limitations of this study limit the strength of the conclusions. Randomized controlled trials with a strict, reasonable design, and multi-center, large-scale samples and follow-up are necessary to draw conclusions about Xingnao Kaiqiao needling.

  15. Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation

    International Nuclear Information System (INIS)

    Hirakata, Masao; Tozawa, Ryuichi; Imura, Yoshimi; Sugiyama, Yasuo

    2004-01-01

    In order to elucidate the antiatherogenic effects of pioglitazone (a peroxisome proliferator-activated receptor [PPAR]γ agonist with PPARα agonistic activity) and rosiglitazone (a more selective PPARγ agonist), we examined gene expression and cholesteryl ester accumulation in THP-1-derived macrophages. Pioglitazone enhanced the mRNA expression of the proatherogenic factors CD36 and adipophilin, but was approximately 10 times less potent than rosiglitazone. The potencies of the two agents appeared to correspond to their PPARγ agonistic activities in this respect. However, both agents were similarly potent in enhancing the mRNA expression of the antiatherogenic factors liver X receptor α and ATP-binding cassette-transporter A1. Furthermore, both agents enhanced cholesteryl ester hydrolase mRNA expression and inhibited acyl-CoA cholesterol acyltransferase-1 mRNA expression and cholesteryl ester accumulation in macrophages. In this respect, their potencies appeared to correspond to their PPARα agonistic activities. These results suggest that pioglitazone has an equally beneficial effect on antiatherogenic events to rosiglitazone, despite being almost 10 times less potent than a PPARγ agonist

  16. Studies of long-term noopept and afobazol treatment in rats with learned helplessness neurosis.

    Science.gov (United States)

    Uyanaev, A A; Fisenko, V P

    2006-08-01

    Long-lasting effects of new Russian psychotropic drugs Noopept and Afobazol on active avoidance conditioning and formation of learned helplessness neurosis were studied on an original experimental model in rats. Noopept eliminated the manifestations of learned helplessness after long-term (21-day) treatment by increasing the percent of trained animals. Afobazol was low effective in preventing manifestations of learned helplessness, but if used for a long time, it reduced the incidence of learned helplessness development by increasing the percent of untrained animals.

  17. Long-term course of opioid addiction.

    Science.gov (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  18. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    Science.gov (United States)

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm 2 ). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  19. Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR

    Directory of Open Access Journals (Sweden)

    Zhongxia Wang

    2016-01-01

    Full Text Available The inflammatory response after polymer-based drug-eluting stent (DES placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ activators thiazolidinedione (TZD remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO on circulating peripheral blood mononuclear cells (MNCs in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO or placebo (control; Con treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and matrix metalloproteinase-9 (MMP-9 were significantly decreased in PIO group compared to the Con group (P=0.035, 0.011, 0.008, and 0.012, resp.. DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P=0.031, 0.012, and 0.007, resp.. In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γ activity. Mechanically, DES induced PPAR-γ ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era.

  20. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

    NARCIS (Netherlands)

    Bonati, Leo H.; Dobson, Joanna; Featherstone, Roland L.; Ederle, Jörg; van der Worp, H. Bart; de Borst, Gert J.; Mali, Willem P. Th M.; Beard, Jonathan D.; Cleveland, Trevor; Engelter, Stefan T.; Lyrer, Philippe A.; Ford, Gary A.; Dorman, Paul J.; Brown, Martin M.; Bamford, J.; Beard, J.; Bland, M.; Bradbury, A. W.; Brown, M. M.; Hacke, W.; Halliday, A.; Malik, I.; Mas, J. L.; McGuire, A. J.; Sidhu, P.; Venables, G.; Clifton, A.; Gaines, P.; Collins, R.; Molyneux, A.; Naylor, R.; Warlow, C.; Ferro, J. M.; Thomas, D.; Coward, L.; Dobson, J.; Doig, D.; Ederle, J.; Featherstone, R. F.; Kennedy, F.; Tindall, H.; Turner, E.; McCabe, D. J. H.; Wallis, A.; Brooks, M.; Chambers, B.; Koelemay, M. J. W.; Nederkoorn, P. J.; Reekers, J. A. A.; Roos, Y. B. W. E. M.

    2015-01-01

    Background Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. Methods Patients with symptomatic carotid stenosis

  1. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

    NARCIS (Netherlands)

    Bonati, L.H.; Dobson, J.; Featherstone, R.L.; Ederle, J.; Worp, H.B. van der; Borst, G.J. de; Mali, W.P.; Beard, J.D.; Cleveland, T.; Engelter, S.T.; Lyrer, P.A.; Ford, G.A.; Dorman, P.J.; Brown, M.M.; Leeuw, F.E. de; et al.,

    2015-01-01

    BACKGROUND: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. METHODS: Patients with symptomatic carotid

  2. FP7 project LONGLIFE: Treatment of long-term irradiation embrittlement effects in RPV safety assessment

    International Nuclear Information System (INIS)

    May, J.; Hein, H.; Altstadt, E.; Bergner, F.; Viehrig, H.W.; Ulbricht, A.; Chaouadi, R.; Radiguet, B.; Cammelli, S.; Huang, H.; Wilford, K.

    2012-01-01

    The increasing age of European Nuclear Power Plants (NPPs) and envisaged extensions of plant lifetimes from 40 up to 80 years require an improved understanding of ageing phenomena of RPV components. The Network of Excellence NULIFE (Nuclear Plant Life Prediction) has been established to advance the safe and economic long-term operation (LTO) of NPPs by facilitating increased co-operation for applied R and D amongst members of the European nuclear community. The accurate prediction and management of RPV neutron irradiation embrittlement connected with long-term operation is an important aspect of this co-operation. Phenomena that might become important at high neutron fluences (such as flux effects and late blooming effects) have to be considered adequately in safety assessments. However, the surveillance database for prolonged irradiation times and low neutron fluxes is sparse. Consequently, there are significant uncertainties in the treatment of long-term irradiation effects. Therefore, the project LONGLIFE (Treatment of long-term irradiation embrittlement effects in RPV safety assessment) was initiated under the Euratom 7th Framework Programme of the European Commission as an umbrella project of NULIFE. LONGLIFE aims at 1) improved understanding of long-term irradiation phenomena that might compromise RPV integrity, and thereby the LTO of European NPPs, and 2) assessment of the adequacy of current prediction tools, codes, standards and surveillance guidelines for supporting long-term RPV operation. The scope of the work comprises the analysis of LTO boundary conditions; microstructural investigations and supplementary mechanical tests on RPV steels, including RPV steels from decommissioned plants; training activities; and elaboration of recommendations for RPV materials assessment and embrittlement surveillance under LTO conditions. A key part of the technical work is the selection of relevant materials for examination, e.g. which contain different weld and base

  3. Long-term experience on surgical treatment of alveolar echinococcosis.

    Science.gov (United States)

    Buttenschoen, Klaus; Carli Buttenschoen, Daniela; Gruener, Beate; Kern, Peter; Beger, Hans G; Henne-Bruns, Doris; Reuter, Stefan

    2009-07-01

    Alveolar echinococcosis (AE) is life-threatening and reports on surgical procedures and results are rare, but essential. Longitudinal surveillance and long-term follow-up of patients surgically treated for AE during the periods 1982-1999 (group A) and 2000-2006 (group B). University hospital within an endemic area. The median (min-max) follow-up period was 141 (5-417) months. Forty-eight surgical procedures were performed in 36 patients with AE: 63% were partial resections of the liver (additional extrahepatic resection in ten of them), 17% just extrahepatic resections, 10% biliodigestive anastomosis, and 10% exploratory laparotomies. Seventy-five percent of the operations were first-time procedures, 25% done due to a relapse. Forty-two percent of the operations were estimated to be curative (R0), whereas 58% were palliative (R1, R2). All patients had additional medical treatment and periodical follow-up. Two out of 18 (11%) patients, estimated to have had curative surgery, developed a relapse 42 and 54 months later. R0-resection rates depended on the primary, neighboring, metastasis stage of AE (S1, 100%; S2, 100%; S3a, 33%; S3b, 27%; S4, 11%). During the period 2000-2006 elective radical surgery for AE was done only if a safe distance of at least 2 cm was attainable. This concept was associated with an increased R0-resection rate of 87% for group B compared to 24% for group A. Operative procedures done to control complicated courses of AE (jaundice, cholangitis, vascular compression, bacterial superinfection) have not been curative (R2) in 82% because the disease had spread into irresectable structures. Morbidity was 19%. All patients with curative resections are alive. Fifty-six percent of the patients with palliative treatment are alive as long as 14-237 months, 28% died from AE 164-338 months after diagnosis (late lethality), and 17% died due to others diseases 96-417 months after diagnosis of AE. One out of seven (14%) patients suffering from suppurative

  4. Long-term psychosocial consequences of surgical congenital malformations.

    Science.gov (United States)

    Diseth, Trond H; Emblem, Ragnhild

    2017-10-01

    Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

  5. Acupuncture treatment of a male patient suffering from long-term schizophrenia and sleep disorders

    NARCIS (Netherlands)

    Bosch, M.P.C.; Staudte, H.; Yeo, S.; Lee, S.H.; Lim, S.; Noort, M.W.M.L. van den

    2017-01-01

    Objective: To investigate the effectiveness of acupuncture in the treatment of chronic schizophrenia and co-morbid sleep disorders. Methods: A 42-year-old German male outpatient, suffering from long-term schizophrenia and sleep disorders, entered the study. Acupuncture was used as a

  6. Long-term outcome of a multidisciplinary concept of spinal dural arteriovenous fistulae treatment

    International Nuclear Information System (INIS)

    Sherif, Camillo; Gruber, Andreas; Bavinzski, Gerhard; Standhardt, Harald; Widhalm, Georg; Knosp, Engelbert; Gibson, Daniel; Richling, Bernd

    2008-01-01

    The optimal treatment of spinal dural arteriovenous fistulae (SDAVF) remains controversial and long-term follow-up data, especially data from multidisciplinary treatment, are rarely available. Thus, long-term outcomes following a multidisciplinary approach to the treatment of SDAVF were investigated. The investigation included 26 patients with SDAVF treated at the authors' department over a 15-year period including a follow-up of more than 2 years. The treatment strategy when occlusion of the draining vein could be achieved was to embolize the fistula with Histoacryl, with surgery reserved for those patients unsuitable for embolization. Posttreatment angiography followed by MRI was performed in all patients. Clinical follow-up was performed using the gait and micturition Aminoff-Logue scale scores and the modified Rankin scale score. Embolization was performed in 19 patients (73.1%), and direct surgery in 7 patients (26.9%). Follow-up angiography (at a mean of 21.7 months) showed occlusion of the SDAVF in 24 patients (92.3%). Of the 19 embolized patients, 2 (10.5%) developed recurrence secondary to insufficient occlusion of the SDAVF draining vein, and one of these two patients underwent re-embolization and one re-operation. No negative effects of SDAVF recurrence on the final clinical outcome were identified in either patient. MRI after angiography (at a mean of 91.5 months) demonstrated occlusion of all SDAVFs. After a mean clinical follow-up of 103.4 months there was a statistically significant improvement in both the modified Rankin scale score and the Aminoff-Logue gait scale score (P < 0.05). The present multidisciplinary study showed for the first time that embolization leads to stable neuroradiological results and favourable clinical outcomes even for very long follow-up times of more than 100 months. Microsurgery remains the treatment of choice when safe embolization of the draining vein cannot be achieved. (orig.)

  7. Restoration treatments in urban park forests drive long-term changes in vegetation trajectories.

    Science.gov (United States)

    Johnson, Lea R; Handel, Steven N

    2016-04-01

    Municipalities are turning to ecological restoration of urban forests as a measure to improve air quality, ameliorate urban heat island effects, improve storm water infiltration, and provide other social and ecological benefits. However, community dynamics following urban forest restoration treatments are poorly documented. This study examines the long-term effects of ecological restoration undertaken in New York City, New York, USA, to restore native forest in urban park natural areas invaded by woody non-native plants that are regional problems. In 2009 and 2010, we sampled vegetation in 30 invaded sites in three large public parks that were restored 1988-1993, and 30 sites in three large parks that were similarly invaded but had not been restored. Data from these matched plots reveal that the restoration treatment achieved its central goals. After 15-20 years, invasive species removal followed by native tree planting resulted in persistent structural and compositional shifts, significantly lower invasive species abundance, a more complex forest structure, and greater native tree recruitment. Together, these findings indicate that successional trajectories of vegetation dynamics have diverged between restored forests and invaded forests that were not restored. In addition, the data suggest that future composition of these urban forest patches will be novel assemblages. Restored and untreated sites shared a suite of shade-intolerant, quickly-growing tree species that colonize disturbed sites, indicating that restoration treatments created sites hospitable for germination and growth of species adapted to high light conditions and disturbed soils. These findings yield an urban perspective on the use of succession theory in ecological restoration. Models of ecological restoration developed in more pristine environments must be modified for use in cities. By anticipating both urban disturbances and ecological succession, management of urban forest patches can be

  8. Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1997-01-01

    Purpose: To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection. Methods and Materials: Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years. Results: The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort. Conclusion: TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not

  9. The long-term prognosis for live birth in couples initiating fertility treatments

    DEFF Research Database (Denmark)

    Malchau, S. S.; Henningsen, A. A.; Loft, A.

    2017-01-01

    -26% in women ≥40 years, overall, 14% of couples conceived naturally and one-third of couples starting treatments with intrauterine insemination delivered from that treatment. WHAT IS KNOWN ALREADY: Few studies report success rates in fertility treatments across a couple's complete fertility treatment history......STUDY QUESTION: What are the long-term chances of having a child for couples starting fertility treatments and how many conceive with ART, IUI and without treatment? SUMMARY ANSWER: Total 5-year live birthrates were strongly influenced by female age and ranged from 80% in women under 35...... years (N = 3553), 35-39 years (N = 1156) and ≥40 years (N = 451), a total of 64%, 49% and 16% had a live birth due to treatment, respectively. Additionally, in women aged years, 35-39 years and ≥40 years, 16%, 11% and 10% delivered after natural conception, yielding total 5-year birthrates of 80...

  10. Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

    Science.gov (United States)

    Zanin, M P; Hellström, M; Shepherd, R K; Harvey, A R; Gillespie, L N

    2014-09-26

    Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Long-term outcome of sports injuries : results after inpatient treatment

    NARCIS (Netherlands)

    Dekker, R; van der Sluis, CK; Groothoff, JW; Eisma, WH; ten Duis, HJ

    Objective: To investigate whether sports injuries result in long-term disabilities and handicaps and to establish variables with a prognostic value for the occurrence of these long-term consequences. Materials and methods: All patients older than 17 years of age and admitted to the University

  12. Long-term Outcomes of Operative and Nonoperative Treatment of Congenital Coxa Vara.

    Science.gov (United States)

    Roberts, David W; Saglam, Yavuz; De La Rocha, Adriana; Frasquillo, Brigid N; Tulchin-Francis, Kirsten; Kim, Harry K W

    2018-04-01

    Congenital coxa vara (CCV) is a rare hip condition with few long-term studies. The purpose of this study was to assess clinical, radiographic, and functional outcomes after operative and nonoperative treatment of CCV, assess reliability of radiographic parameters, and investigate risk factors for recurrence after surgery. Retrospective review was performed of all CCV patients treated at 1 institution from 1980 to 2010. In addition, patients were recalled for additional follow-up x-rays, modified Harris Hip Score (mHHS), and gait analysis. Radiographic measurements [neck-shaft angle (NSA), head-shaft angle (HSA), Hilgenreiner-epiphyseal angle (HEA), and femoral neck length (FNL)] were assessed for reliability using intraclass correlation coefficients. Multivariate analysis was performed to identify risk factors for recurrence after surgery. Forty-six hips in 32 patients were reviewed. Mean age at presentation was 5.4±4.9 years. Mean follow-up was 11.8±5.8 years. Valgus proximal femoral osteotomy was performed in 27 hips (20 patients). Initial deformity was greater in the operative group (NSA 90±17 degrees, HEA 68±19 degrees) versus nonoperative patients (NSA 122±19 degrees, HEA 34±14 degrees) (PNSA occurred in only 21%. In contrast, 56% of operative hips showed decreased FNL growth rates. Interobserver reliability was excellent for HEA (0.98), NSA (0.90), and FNL (0.89), and good for HSA (0.79). Repeat osteotomy was performed in 6 cases (22%). No significant predictors for recurrence were identified. At long-term follow-up for recalled patients, 72% had significantly abnormal gait, and 50% had fair-poor functional outcomes (mHHSNSA are the most reliable radiographic measurements of proximal femoral deformity in CCV. Recurrence is not uncommon, but no predictors were identified. Many patients have persistent gait abnormalities and functional impairment at long-term follow-up, regardless of prior treatment. Level III-retrospective cohort.

  13. Medulloblastoma in childhood: long-term results of treatment

    International Nuclear Information System (INIS)

    Broadbent, V.A.; Barnes, N.D.; Wheeler, T.K.

    1981-01-01

    Thirty-one children under the age of 15 years with verified medulloblastoma were treated at Addenbrookes Hospital from 1940 to 1976. In addition to surgical treatment, all received high dose irradiation to the whole neuraxis. Nine were still alive in 1979, of whom eight were examined. All these patients showed some residual problems, but five were leading active lives and had only minor physical disability. There was evidence of disturbance in growth, with shortening of the spine in relation to the limbs, in all the children. The height centile was lower than expected from parental height in four and one was severely dwarfed. Growth hormone secretion in response to exercise was, however, normal in five of six patients tested. Three children also showed failure of growth of the jaw sufficiently severe to be a cosmetic problem. Frank mental retardation was present in three children. A raised resting TSH level was found in two children, one of whom had a multinodular goiter. Of the three children with severe problems, two had been treated when under two years of age. Long-term follow-up of children who survive medulloblastoma is clearly necessary and consideration should perhaps be given to revision of current treatment regimes in very young children

  14. Long-term efficacy of reverse pull headgear therapy.

    Science.gov (United States)

    Wells, Andrew P; Sarver, David M; Proffit, William R

    2006-11-01

    To add to the data for long-term reverse pull headgear (RPHG) outcomes and further explore possible variables that could be predictors of long-term failure. Cephalometric radiographs of 41 Class III malocclusion children treated with RPHG (face mask) were evaluated before and immediately after treatment; at 5 years posttreatment; and, for 18 patients, at 10 years posttreatment. Patients were assigned to success or failure groups according to positive or negative overjet at the longest available recall. Seventy-five percent of the patients maintained positive overjet, whereas 25% outgrew the correction. In a stepwise discriminant analysis, a large mandible and vertical positioning of the maxilla and mandible so that mandibular growth would be projected more horizontally were the major indicators of unfavorable later mandibular growth. Patients who experienced downward-backward rotation of the mandible during RPHG treatment were more likely to be categorized in the failure group. The age at which treatment began had no effect on long-term success and failure for patients younger than 10 years, but the percentage of successful treatment decreased after that age. When RPHG treatment is used for all but the most obviously prognathic children to correct anterior cross-bite in the early mixed dentition, positive overjet is maintained long-term in 70%-75% of cases, whereas 25%-30% of cases relapse into reverse overjet mainly because of increased horizontally directed and often late mandibular growth. Up to age 10, the time at which RPHG treatment began does not appear to be a major factor in long-term success in maintaining positive overjet.

  15. Long and short term effects of plasma treatment on meristematic plant cells

    Science.gov (United States)

    Puač, N.; Živković, S.; Selaković, N.; Milutinović, M.; Boljević, J.; Malović, G.; Petrović, Z. Lj.

    2014-05-01

    In this paper, we will present results of plasma treatments of meristematic cells of Daucus carota. Plasma needle was used as an atmospheric pressure/gas composition source of non-equilibrium plasma in all treatments. Activity of antioxidant enzymes superoxide dismutase and catalase was measured immediately after plasma treatment and after two weeks following the treatment. Superoxide dismutase activity was increased in samples immediately after the plasma treatment. On the other hand, catalase activity was much higher in treated samples when measured two weeks after plasma treatment. These results show that there is a direct proof of the triggering of signal transduction in the cells by two reactive oxygen species H2O2 and O2-, causing enzyme activity and short and long term effects even during the growth of calli, where the information is passed to newborn cells over the period of two weeks.

  16. Patient factors associated with hemoglobin A1C change with pioglitazone as adjunctive therapy in type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Tran MT

    2008-06-01

    Full Text Available Objective: To identify patient factors associated with change in hemoglobin A1C (A1C with adjunct pioglitazone therapy in routine clinical practice. Methods: This was a retrospective analysis of adult type 2 diabetes mellitus patients in a health maintenance organization setting who were newly-initiated on pioglitazone between January 2002 and December 2005. Eligible patients were receiving at least one other oral antihyperglycemic medication prior to initiating pioglitazone and maintained a stable dose of pioglitazone for 90 days. Data on eligible patients’ characteristics, pharmacy purchases, comorbidities, and A1C measurement 90 days prior to the pioglitazone purchase date (baseline and 90 days after achieving a stable dose (follow-up were obtained from electronic records. Multivariate regression modeling was used to assess factors independently associated with: 1 absolute change in A1C, 2 achieving a ≥1 percentage point decrease in A1C, and 3 achieving an A1C8%. At follow-up, the mean A1C change was -1.2 percentage points (interquartile range= -0.4, -2.1, 59% achieved a ≥1 unit decrease in A1C, and 44% achieved an A1C<7%. Independent predictors in all models were baseline A1C and time (in days between baseline and follow-up A1C measurements (p<0.05. Conclusions: Adjunct pioglitazone therapy in routine clinical practice was associated with clinically meaningful reductions in A1C levels. Patients with higher baseline A1C achieved the greatest absolute reduction in A1C but were less likely to achieve levels <7%.

  17. Treatment of anorexia nervosa with long-term risperidone in an outpatient setting: case study.

    Science.gov (United States)

    Kracke, Elsa J; Tosh, Aneesh K

    2014-01-01

    There are currently few studies focusing on the efficacy of long-term atypical antipsychotics to treat anorexia nervosa in the pediatric population. This case report follows the treatment of a 17 year-old female with anorexia nervosa over her four-year undergraduate career. After two years of multidisciplinary treatment, low-dose risperidone was initiated due to persistence of her disease. She expressed decreased rigidity around meal times, her weight improved and she had resumption of menses. She was compliant with treatment through graduation and maintained her weight gain. Atypical antipsychotics are a treatment option in the management of anorexia nervosa. Risperidone has not been studied as frequently as olanzapine for eating disorders. Risperidone was chosen for its more favorable side effect profile and decreased cost to the patient. Previous studies on anorexia nervosa treatment have occurred during inpatient treatment and have limited follow-up due to patients' refusal to initiate or maintain medication compliance. This case presents 17 months of outpatient data. The efficacy of risperidone therapy was evaluated with frequent weight checks, subjective decrease in rigidity, serial complete metabolic panels, and restoration of menses. In this case report, an adolescent female treated with low-dose risperidone had decreased rigid thinking, weight gain and resolution of secondary amenorrhea without medication side effects. Therefore, the atypical antipsychotic risperidone may be an effective long-term outpatient treatment option for patients with anorexia nervosa.

  18. A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Nielsen, Rasmus H

    2009-01-01

    : vehicle, pioglitazone 10 mg/kg, pioglitazone 30 mg/kg, balaglitazone 5 mg/kg, balaglitazone 10 mg/kg. At day -7, 21 and 42 fasting serum samples were collected and whole body tissue composition was evaluated by MR scanning. Food intake and bodyweights were monitored during the study period. At day 42...

  19. Efficacy and safety of the partial PPARγ agonist balaglitazone compared with pioglitazone and placebo: A phase III, randomised, parallel-group study in patients with type 2 diabetes on stable insulin therapy

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Qvist, Per

    2011-01-01

    Treatment of patients with full PPARγ agonists is associated with weight gain, heart failure, peripheral oedema and bone loss. However, the safety of partial PPARγ agonists has not been established in a clinical trial. The BALLET trial aimed to establish the glucose-lowering effects and safety...... in all treatment arms. DXA analyses showed balaglitazone 10mg led to less fat and fluid accumulation and no change in bone mineral density, when compared to pioglitazone. In the balaglitazone 10mg treated group clinically relevant reductions in HbA(1c) and glucose levels were observed, although...... it appeared to be a little less potent that pioglitazone 45mg. On the other hand significantly less fluid and fat accumulation were observed, highlighting this treatment regimen for further studies....

  20. Long-term evaluation of Class II subdivision treatment with unilateral maxillary first molar extraction

    NARCIS (Netherlands)

    Livas, Christos; Pandis, Nikolaos; Booij, Johan Willem; Katsaros, Christos; Ren, Yijin

    Objective: To evaluate the long-term effects of asymmetrical maxillary first molar (M1) extraction in Class II subdivision treatment. Materials and Methods: Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0 years; SD, 1.7 years) consecutively treated with the Begg technique

  1. Long term results of 125I for treatment of hyperthyroidism

    International Nuclear Information System (INIS)

    Bremner, W.F.; McDougall, I.R.; Greig, W.R.; Ratcliffe, J.G.

    1976-01-01

    125 I emits very low energy conversion and Auger electrons. This radionuclide has been used in place of 131 I with the hope of reducing the incidence of post treatment hypothyroidism. 303 of 360 patients treated have been reviewed. Originally very large doses of 125 I were prescribed (751-1,600 μCi/g) but 9 out of 15 patients (60%) became hypothyroid, therefore 4 smaller therapeutic regimes were employed. (1) 55 patients received doses of 200 μCi or less/g thyroid, 69% are euthyroid and 24% hypothyroid after an average of 33 months from treatment. (2) 87 patients received doses of 201-350 μCi/g thyroid, 67% are euthyroid and 21% hypothyroid after an average follow up of 30 months. (3) 70 patients received doses of 351-500 μCi/g thyroid, 77% are euthyroid and 18% hypothyroid 36 months after treatment and (4) 76 patients received doses of 501-750 μCi/g, 41% are euthyroid and 56% hypothyroid 49 months after therapy. No long term complications such as thyroid cancer or leukaemia have occurred but because 125 I does not eliminate or reduce the incidence of post treatment hypothyroidism it probably should not be used in preference to 131 I for the routine treatment of hyperthyroidism

  2. PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double-blind randomized controlled pilot trial.

    Science.gov (United States)

    Schmitz, Joy M; Green, Charles E; Hasan, Khader M; Vincent, Jessica; Suchting, Robert; Weaver, Michael F; Moeller, F Gerard; Narayana, Ponnada A; Cunningham, Kathryn A; Dineley, Kelly T; Lane, Scott D

    2017-10-01

    Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance and tolerability were evaluated. Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). Single-site out-patient treatment research clinic in Houston, TX, USA. Thirty treatment-seeking adults, 18 to 60 years old, with CUD. Eighteen participants (8 = PIO; 10 = PLC) completed diffusion tensor imaging (DTI) of WM integrity at pre-/post-treatment. Study medication was dispensed at thrice weekly visits along with once-weekly cognitive behavioral therapy for 12 weeks. Measures of target engagement mechanisms of interest included cocaine craving assessed by the Brief Substance Craving Scale (BSCS), the Obsessive Compulsive Drug Use Scale (OCDUS), a visual analog scale (VAS) and change in WM integrity. Feasibility measures included number completing treatment, medication compliance (riboflavin detection) and tolerability (side effects, serious adverse events). Target engagement change in mechanisms of interest, defined as a ≥ 0.75 Bayesian posterior probability of an interaction existing favoring PIO over PLC, was demonstrated on measures of craving (BSCS, VAS) and WM integrity indexed by fractional anisotropy (FA) values. Outcomes indicated greater decrease in craving and greater increase in FA values in the PIO group. Feasibility was demonstrated by high completion rates among those starting treatment (21/26 = 80%) and medication compliance (≥ 80%). There were no reported serious adverse events for PIO. Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine

  3. Long-term benzodiazepine treatment in patients with psychotic disorders attending a mental health service in rural Greece

    Directory of Open Access Journals (Sweden)

    Vaios Peritogiannis

    2016-01-01

    Full Text Available Introduction: Long-term benzodiazepine (BZD treatment in patients with mental disorders is widespread in clinical practice, and this is also the case of patients with schizophrenia, although the evidence is weak and BZD prescription is discouraged by guidelines and medical authorities. Data on BZD prescription are usually derived from national or regional databases whereas information on the use of BZD by patients with schizophrenia and related psychoses in general population-based samples is limited. Materials and Methods: Information for 77 patients with psychotic disorders who were regularly attending follow-up appointments with the multidisciplinary Mobile Mental Health Unit of the prefectures of Ioannina and Thesprotia, Northwest Greece, during 1-year period (2015 was obtained from our database. Results: From the total of 77 engaged patients, 30 (39% were regularly prescribed BZDs in the long term, as part of their treatment regimen. Prescribed BZDs were mostly diazepam and lorazepam, in 43.3% of cases each. The mean daily dose of these compounds was 13 mg and 3.77 mg, respectively. Statistical analysis showed a correlation of long-term BZD use with the history of alcohol/substance abuse. Most patients were receiving BZD continuously for several years, and the mean dose was steady within this interval. Conclusions: A large proportion of patients with psychotic disorders were regularly prescribed BZD in long term. It appears that when BZDs are prescribed for some period in the course of a psychotic disorder, their use commonly exceeds the recommended interval and then becomes a regular part of the chronic treatment regimen. Future research should address the factors that may be related to the long-term BZD use by patients with psychotic disorders. Interventions for the reduction of regular BZD prescription should target the primary care setting and all those who treat first episode patients.

  4. Long-term outcomes of treatment of hyperthyroidism in Ireland.

    LENUS (Irish Health Repository)

    Leary, A C

    2012-02-03

    We investigated the long-term outcome of treatment in 159 patients with hyperthyroidism first seen between 1979 and 1992. Median duration of follow-up was 10 1\\/2 years. We also inquired into current practice for the follow-up of hyperthyroidism by other endocrinologists in Ireland. Seven cases of unrecognised hyperthyroidism (4 per cent) and one of unrecognised hypothyroidism were identified. Among patients with Graves\\' disease, of those treated with an antithyroid drug, 28 per cent were in remission, 68 per cent had relapsed and 4 per cent had become hypothyroid. Of those treated by sub-total thyroidectomy, 31 per cent were in remission, 19 per cent had relapsed, 19 per cent were hypothyroid and 31 per cent were sub-clinically hypothyroid. Among patients treated with radioiodine, 19 per cent were euthyroid, 3 per cent were still hyperthyroid and three-quarters had become hypothyroid. In contrast, after radioiodine for toxic nodular goitre, 63 per cent were euthyroid and only 32 per cent had become hypothyroid (Chi Squared v. Graves\\' disease, P = 0.001). Of 73 patients receiving thyroxine replacement, plasma TSH was normal in only 41 per cent, although 82 per cent of patients had been seen by the family doctor within the previous 12 months. Seven of 17 other endocrinologists undertook long-term follow-up of hyperthyroid patients in their specialist clinics but none was using a computerised system to co-ordinate this. The findings confirm that careful follow-up is required for all hyperthyroid patients. The family doctor is well positioned to undertake this, but education and auditing are required.

  5. Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice.

    Directory of Open Access Journals (Sweden)

    Bilal Haider Shamsi

    Full Text Available OBJECTIVE: Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ on the relationship of Cell death-inducing DFFA-like effector C (CIDEC with obesity related changes in mice. METHODS: Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND while Group 2 mice were given high fat diet (HFD, and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P. Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT. RESULTS: Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity. CONCLUSION: It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

  6. Long-term functional outcome after type A3 spinal fractures : operative versus non-operative treatment

    NARCIS (Netherlands)

    Post, Richard B.; van der Sluis, Corry K.; Leferink, Vincent J. M.; ten Duis, Henk-Jan

    The authors retrospectively studied, by questionnaires, the long-term (5 years) functional outcome after operative (posterior instrumentation : 38 cases) and non-operative treatment (25 cases) for type A3 spinal fractures (Comprehensive Classification) without neurological deficit. A possible bias

  7. Long-term adherence to follow-up after treatment of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Barken, Sidsel S; Lynge, Elsebeth; Andersen, Erik S.

    2013-01-01

    OBJECTIVE: To measure adherence to annual follow-up among women treated for cervical intraepithelial neoplasia. DESIGN: Prospective, population-based, register study. SETTING: Denmark, 1996-2007. POPULATION: All women treated for cervical intraepithelial neoplasia with conization. METHODS: Treated...... was poor in Denmark. Our findings suggest that because of this poor adherence, recommendations for long-term annual follow-up after treatment of cervical intraepithelial neoplasia may not be highly effective. Shorter follow-up schedules using highly sensitive tests appear attractive....

  8. Associations between treatment, scoliosis, pulmonary function, and physical performance in long-term survivors of sarcoma.

    Science.gov (United States)

    Interiano, Rodrigo B; Kaste, Sue C; Li, Chenghong; Srivastava, Deo Kumar; Rao, Bhaskar N; Warner, William C; Green, Daniel M; Krasin, Matthew J; Robison, Leslie L; Davidoff, Andrew M; Hudson, Melissa M; Fernandez-Pineda, Israel; Ness, Kirsten K

    2017-10-01

    Longer survival for children with sarcoma has led to the recognition of chronic health conditions related to prior therapy. We sought to study the association of sarcoma therapy with the development of scoliosis. We reviewed patient demographics, treatment exposures, and functional outcomes for patients surviving >10 years after treatment for sarcoma between 1964 and 2002 at our institution. The diagnosis of scoliosis was determined by imaging. Functional performance and standardized questionnaires were completed in a long-term follow-up clinic. We identified 367 patients, with median age at follow-up of 33.1 years. Scoliosis was identified in 100 (27.2%) patients. Chest radiation (relative risk (RR), 1.88 (95% confidence interval (CI), 1.21-2.92), p sarcoma are at risk of developing scoliosis when treatment regimens include chest radiation or rib resection. Identification of these risk factors may allow for early intervention designed to prevent adverse long-term outcomes. Cancer survivors at risk of developing scoliosis may benefit from monitoring of pulmonary status and early physical therapy.

  9. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment

    NARCIS (Netherlands)

    Weinreb, Neal J.; Goldblatt, Jack; Villalobos, Jacobo; Charrow, Joel; Cole, J. Alexander; Kerstenetzky, Marcelo; vom Dahl, Stephan; Hollak, Carla

    2013-01-01

    We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1). The International Collaborative Gaucher Group (ICGG) Gaucher Registry

  10. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

    Science.gov (United States)

    Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

    2017-05-16

    Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P =0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P =0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P =0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P =0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus

  11. Long-term outcome of craniopharyngioma in children. A review

    International Nuclear Information System (INIS)

    Tamiya, Takashi; Okada, Masaki; Miyake, Keisuke; Kawai, Nobuyuki

    2011-01-01

    The treatment for pediatric craniopharyngioma remains challenging and controversial. Although this tumor is histologically benign, the treatments include radical surgery, conservative surgery, radiotherapy, intracystic chemotherapy and multimodality approaches. In addition, the long-term functional outcomes including visual function, endocrine function, cognitive function, hypothalamic function, and quality of life are complex and major problems among survivors. In this paper, we reviewed the recent treatments for pediatric craniopharyngioma and the long-term outcomes after treatment in literatures. (author)

  12. Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Chiba T

    2013-07-01

    Full Text Available Toshimi Chiba, Kazunari Yamamoto, Shoko Sato, Kazuyuki Suzuki Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan Abstract: Irritable bowel syndrome (IBS is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT] plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 µg and 10 µg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 µg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001. Furthermore, the responder rate was increased in the oral administration of 5 µg of ramosetron for at least 28 weeks (up to 52 weeks, and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in ramosetron treatment. No serious adverse events, eg, severe constipation or ischemic colitis, were reported for long-term treatment with ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of ramosetron are warranted in the form of randomized controlled trials. Keywords: long-term

  13. Successful treatment of dwarfism secondary to long-term steroid therapy in steroid-dependent nephrotic syndrome.

    Science.gov (United States)

    Sun, Linlin; Chen, Dongping; Zhao, Xuezhi; Xu, Chenggang; Mei, Changlin

    2010-01-01

    Prolonged steroid therapy is generally used for steroid-dependent nephrotic syndrome in pediatric patients. However, dwarfism secondary to a long-term regimen and its successful reverse is rarely reported. The underlying mechanism of dwarfism is still poorly understood, as both long-term steroid use and nephrotic syndrome may interact or independently interfere with the process of growth. Here, we present a 17-year-old patient with dwarfism and steroid-dependent nephrotic syndrome and the successful treatment by recombinant human growth factor and cyclosporine A with withdrawal of steroid. We also briefly review the current understanding and the management of dwarfism in pediatric patients with nephrotic syndrome.

  14. Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study.

    Science.gov (United States)

    Seong, Jong-Mi; Choi, Nam-Kyong; Shin, Ju-Young; Chang, Yoosoo; Kim, Ye-Jee; Lee, Joongyub; Kim, Ju-Young; Park, Byung-Joo

    2015-01-01

    Data on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin. We conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score. During follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively. Compared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.

  15. Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Jong-Mi Seong

    Full Text Available Data on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD exists for the combination of a dipeptidyl peptidase-4 (DPP-4 inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin.We conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI, heart failure (HF, and ischemic stroke (IS were assessed using the hazard ratios (HRs estimated from a Cox proportional-hazards model weighted for a propensity score.During follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32 for total CVD; 1.14 (1.04-1.91 for MI; 1.07 (0.71-1.62 for HF; and 1.51 (1.28-1.79 for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99, 1.05 (0.76-1.46, 4.81 (3.53-6.56, and 0.81 (0.67-0.99, respectively.Compared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.

  16. OK-432 sclerotherapy in head and neck lymphangiomas: long-term follow-up result.

    Science.gov (United States)

    Yoo, Jae Chul; Ahn, Youngjin; Lim, Yune Syung; Hah, J Hun; Kwon, Tack-Kyun; Sung, Myung-Whun; Kim, Kwang Hyun

    2009-01-01

    Nonsurgical treatments, such as sclerotherapy have been attempted for head and neck lymphagiomas. Of the available sclerosing agents, picibanil has shown satisfactory short-term treatment results in many studies, but no study has presented long-term treatment results. Accordingly, in the present study, the authors retrospectively reviewed the long-term treatment results of picibanil sclerotherapy. Fifty-five lymphangioma patients who underwent picibanil sclerotherapy were enrolled. Data about initial and long-term response, recurrence, and excision rate were collected. Initial response rates were 83.5 percent and long-term response rates were 76.3 percent. Initial and the long-term response rate were equally good for lymphangioma.

  17. Periodontal and periimplant maintenance: a critical factor in long-term treatment success.

    Science.gov (United States)

    Shumaker, Nicholas D; Metcalf, Brett T; Toscano, Nicholas T; Holtzclaw, Dan J

    2009-09-01

    Periodontal maintenance (PM) is a critical factor in the long-term success of both periodontal and dental implant therapy. Studies have shown both modern periodontal and dental implant therapies are effective in maintaining natural teeth and replacing lost teeth, respectively. However, without a regular program of clinical reevaluation, plaque control, oral hygiene instruction, and reassessment of biomechanical factors, the benefits of treatment often are lost and inflammatory disease in the form of recurrent periodontitis or periimplantitis may result. This article reviews the goals, types, and appropriate frequency of PM in periodontal and dental implant therapy, as well as the incidence and etiology of periimplant disease and strategies for management when recurrent disease develops during the maintenance phase of treatment.

  18. Long-term use of short- and long-acting nitrates in stable angina pectoris.

    Science.gov (United States)

    Kosmicki, Marek Antoni

    2009-05-01

    Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

  19. Strategies to meet the need for long-term data.

    Science.gov (United States)

    Chalmers, John; Woodward, Mark; Borghi, Claudio; Manolis, Athanasios; Mancia, Giuseppe

    2016-08-01

    Chronic diseases afflict patients for many years, often to the end of life, and there is increasing need for estimating lifelong risk and for evaluating the effects of treatment in the long term. Yet recommendations for lifelong treatment are most frequently based on findings from randomized clinical trials lasting only a few years. There is therefore a clear need for much longer term data, and here we present the advantages and disadvantages of many strategies, including the use of long-term posttrial follow-up, of long-term prospective cohort studies, registry databases, and of administrative databases. We also emphasize the need for long-term cost-effectiveness studies. One of the most promising strategies comes from linkage of data gathered through the ever-expanding pool of administrative databases worldwide with data from other sources, including randomized trials and the many forms of observational study.

  20. Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients: A systematic review & comparison with European Medicines Agency Assessment Report.

    Science.gov (United States)

    Pai, Sarayu A; Kshirsagar, Nilima A

    2016-11-01

    With pioglitazone ban and subsequent revoking in India along with varying regulatory decisions in other countries, it was decided to carry out a systematic review on its safety, efficacy and drug utilization in patients with type 2 diabetes mellitus (T2DM) in India and compare with the data from the European Medicines Agency Assessment Report (EMA-AR). Systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching Medline/PubMed, Google Scholar and Science Direct databases using 'pioglitazone AND India AND human' and 'pioglitazone AND India AND human AND patient' and compared with EMA-AR. Spontaneous reports in World Health Organization VigiBase from India were compared with VigiBase data from other countries. Sixty six publications, 26 (efficacy), 32 (drug utilization) and eight (safety), were retrieved. In India, pioglitazone was used at 15-30 mg/day mostly with metformin and sulphonylurea, being prescribed to 26.7 and 8.4 per cent patients in north and south, respectively. The efficacy in clinical trials (CTs) was similar to those in EMA-AR. Incidence of bladder cancer in pioglitazone exposed and non-exposed patients was not significantly different in an Indian retrospective cohort study. There were two cases and a series of eight cases of bladder cancer published but none reported in VigiBase. In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

  1. Long-term use of Bonviva for the treatment of postmenopausal osteoporosis: new evidence

    Directory of Open Access Journals (Sweden)

    Olga Borisovna Yershova

    2012-01-01

    Full Text Available Osteoporosis is a disease of great social importance. Its treatment is a complicated problem and it is associated with low compliance and a risk for adverse reactions. Ibandronate belongs to a group of bisphosphonates. The performed trials have proven the efficacy of its two formulations (a tablet once monthly and intravenous injection once every 3 months in reducing the risk of bone fractures. At present there are data of trials of long-term therapy with this drug, which demonstrate its positive effect on bone mineral density and bone metabolism markers. The agent has been also shown to be highly safe when used long.

  2. Net sulfur mineralization potential in Swedish arable soils in relation to long-term treatment history and soil properties

    DEFF Research Database (Denmark)

    Boye, Kristin; Nilsson, S Ingvar; Eriksen, Jørgen

    2009-01-01

    accumulated net S mineralization (SAccMin) and a number of soil physical and chemical properties were determined. Treatments and soil differences in SAccMin, as well as correlations with soil variables, were tested with single and multivariate analyses. Long-term FYM application resulted in a significantly (p......The long-term treatment effect (since 1957-1966) of farmyard manure (FYM) application compared with crop residue incorporation was investigated in five soils (sandy loam to silty clay) with regards to the net sulfur (S) mineralization potential. An open incubation technique was used to determine...... = 0.012) higher net S mineralization potential, although total amounts of C, N, and S were not significantly (p soils within this treatment. The measured soil variables were not significantly correlated...

  3. Pioglitazone Confers Neuroprotection Against Ischemia-Induced Pyroptosis due to its Inhibitory Effects on HMGB-1/RAGE and Rac1/ROS Pathway by Activating PPAR-ɤ

    Directory of Open Access Journals (Sweden)

    Pingping Xia

    2018-03-01

    Full Text Available Background/Aims: Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. Methods: The cerebral injury was established by middle cerebral artery occlusion (MCAO. in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD. ELISA and Western Blot analysis were employed to the levels of PPAR-γ, pyroptosis-related biomarkers and cytoplasmic translocation of HMGB-1 and RAGE expression as well as Rac1 activity, respectively. Results: We demonstrated that repeated intraperitoneal administration of pioglitazone remarkably reduced the infarct volume, improved neurological deficits and suppressed the Rac1 activity with significant reduction of excessive ROS in rat model of middle cerebral artery occlusion (MCAO. Moreover, pioglitazone alleviated the up-regulation of pyroptosis-related biomarkers and the increased cytoplasmic translocation of HMGB-1 and RAGE expression in cerebral penumbra cortex. Similarly, the protective effects of pioglitazone on cultured astrocytes were characterized by reduced Rac1 activity, pyroptosis related protein expressions and lactate dehydrogenase (LDH release. However, these protective effects of pioglitazone were neutralized with the use of GW9662, a PPAR-γ inhibitor. Interestingly, Rac1 knockdown in lentivirus with the Rac1 small hair RNA (shRNA could inhibit the OGD-induced pyroptosis of primary cultured astrocytes. Furthermore, the combination of Rac1-shRNA and pioglitazone can further strengthen the inhibitory effects on pyroptosis induced by OGD. Conclusion: The neuroprotection of pioglitazone was attributable to the alleviated ischemia/hypoxia-induced pyroptosis and was also associated with the PPARγ-mediated suppression of HGMB-1/RAGE signaling

  4. Pioglitazone Confers Neuroprotection Against Ischemia-Induced Pyroptosis due to its Inhibitory Effects on HMGB-1/RAGE and Rac1/ROS Pathway by Activating PPAR-ɤ.

    Science.gov (United States)

    Xia, Pingping; Pan, Yundan; Zhang, Fan; Wang, Na; Wang, E; Guo, Qulian; Ye, Zhi

    2018-01-01

    Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD). ELISA and Western Blot analysis were employed to the levels of PPAR-γ, pyroptosis-related biomarkers and cytoplasmic translocation of HMGB-1 and RAGE expression as well as Rac1 activity, respectively. We demonstrated that repeated intraperitoneal administration of pioglitazone remarkably reduced the infarct volume, improved neurological deficits and suppressed the Rac1 activity with significant reduction of excessive ROS in rat model of middle cerebral artery occlusion (MCAO). Moreover, pioglitazone alleviated the up-regulation of pyroptosis-related biomarkers and the increased cytoplasmic translocation of HMGB-1 and RAGE expression in cerebral penumbra cortex. Similarly, the protective effects of pioglitazone on cultured astrocytes were characterized by reduced Rac1 activity, pyroptosis related protein expressions and lactate dehydrogenase (LDH) release. However, these protective effects of pioglitazone were neutralized with the use of GW9662, a PPAR-γ inhibitor. Interestingly, Rac1 knockdown in lentivirus with the Rac1 small hair RNA (shRNA) could inhibit the OGD-induced pyroptosis of primary cultured astrocytes. Furthermore, the combination of Rac1-shRNA and pioglitazone can further strengthen the inhibitory effects on pyroptosis induced by OGD. The neuroprotection of pioglitazone was attributable to the alleviated ischemia/hypoxia-induced pyroptosis and was also associated with the PPARγ-mediated suppression of HGMB-1/RAGE signaling pathway. Moreover, the inhibition of Rac1 promoted this function

  5. A Preliminary Investigation of the Long-Term Outcome of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders

    Science.gov (United States)

    Bullis, Jacqueline R.; Fortune, Meghan R.; Farchione, Todd J.; Barlow, David H.

    2014-01-01

    Objective To conduct a preliminary examination of long-term outcomes on a broad range of affective disorder symptoms treated with a newly developed intervention: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP). Method Maintenance of treatment gains at long-term follow-up (LTFU) were explored in patients (n = 15, mean age = 32.27; 60% female) who completed a clinical trial of the UP. Results Treatment gains observed at 6-month follow-up (6MFU) on measures of clinical severity, general symptoms of depression and anxiety, and a measure of symptom interference in daily functioning were largely maintained 12 months later (at an average of 18 months posttreatment), and any significant changes from 6MFU to LTFU reflected small increases in symptoms that remained, on average, in the subclinical range. Conclusions These findings provide the first initial support for the durability of broad treatment gains following transdiagnostic treatment. PMID:25113056

  6. Evaluation of the pharmacoeconomics of drugs used for the treatment of long-term complications of sulfur mustard

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2016-08-01

    Full Text Available Sulfur Mustard (SM, a cytotoxic vesicant chemical warfare agent, has powerful irritant and blistering effects on the skin, eyes and respiratory tract. Since during the Iraq-Iran war, many Iranian soldiers and civilians were exposed to SM, there are several victims still suffering from long-term cutaneous, ocular and pulmonary complications. Currently, there is no definite treatment for long-term complications of SM, and only supportive medical care is being taken to minimize the symptoms. In this study, we compared the cost-effectiveness of common drugs that are used against long-term SM-induced complications in Iranian patients. In this review article, electronic databases were checked using the following key words: sulfur mustard, lung, skin, eye, cost-effectiveness, pharmacoeconomics and treatment. Abstracts of non-English papers and proceedings of congresses on SM were also assessed. Among the studied drugs, high-dose oral N-acetyl cysteine and long-acting inhaled corticosteroids against respiratory complications, topical corticosteroids and oral antihistamines against cutaneous complications and non-steroidal anti-inflammatory drugs and corticosteroids ophthalmic drops against ocular complications were found to be cost-effective. Usage of different drugs in the treatment of SM injuries in Iran, have imposed a significant economic burden to patients and their families because many drugs that are effective against chemical injuries are not covered by insurance. In addition, the development of more effective drugs in this field is considered as an urgent demand that should be noticed by the pharmaceutical industry.

  7. Long-term use of adalimumab in the treatment of rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Charalampos Papagoras

    2009-05-01

    Full Text Available Charalampos Papagoras, Paraskevi V Voulgari, Alexandros A DrososRheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, GreeceAbstract: Adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-alpha (TNFα, has been evaluated in various randomized placebo-controlled trials in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. In the short time frame of these trials adalimumab has been shown to be effective in reducing disease activity, slowing radiographic disease progression and improving patients’ quality of life, while at the same time demonstrating an acceptable safety profile. Furthermore, release of adalimumab on the market, prospective observational studies, as well as open-label extensions of the original double-blind trials have provided experience and data about the long-term efficacy and safety of the drug. Initial effectiveness, in terms of reducing disease activity, is sustained, while in most cases patients treated with adalimumab experienced a slower radiographic progression and consequently less disability and improved health-related quality-of-life outcomes. Moreover, long-standing treatment of thousands of patients with adalimumab outside the controlled context of clinical trials was not related to new safety signals, with the most common adverse events being respiratory infections. The most common serious adverse events seem to be tuberculosis reactivation, while a putative association with malignant lymphoma development is not yet proven. Besides, both of these adverse reactions pertain to the whole TNFα blocker group. In conclusion, adalimumab is a safe and effective option for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. Keywords: adalimumab, tumor necrosis factor-alpha, rheumatoid arthritis, ankylosing spondylitis

  8. Primary hydatid disease of the femur: unsuspected and incidental MRI findings with long-term curative results on medical treatment alone

    International Nuclear Information System (INIS)

    Poyanli, A.; Sencer, S.; Akan, K.; Poyanli, O.; Sayrak, H.

    2001-01-01

    This report describes the early magnetic resonance imaging (MRI) findings and long-term follow-up results of albendazole treatment in a 16-year-old girl with primary hydatid disease of the femur diagnosed incidentally during the course of a post-traumatic knee infection. As far as we know, this is the first report of the early MRI findings and long-term outcome of medical treatment in primary hydatid disease of the femur in this age group. (orig.)

  9. Primary hydatid disease of the femur: unsuspected and incidental MRI findings with long-term curative results on medical treatment alone

    Energy Technology Data Exchange (ETDEWEB)

    Poyanli, A.; Sencer, S. [Dept. of Radiology, Istanbul Faculty of Medicine (Turkey); Akan, K.; Poyanli, O. [Dept. of Orthopaedics and Traumatology, Goeztepe SSK Educational Hospital, Istanbul (Turkey); Sayrak, H. [Dept. of Pathology, Goeztepe SSK Educational Hospital, Istanbul (Turkey)

    2001-11-01

    This report describes the early magnetic resonance imaging (MRI) findings and long-term follow-up results of albendazole treatment in a 16-year-old girl with primary hydatid disease of the femur diagnosed incidentally during the course of a post-traumatic knee infection. As far as we know, this is the first report of the early MRI findings and long-term outcome of medical treatment in primary hydatid disease of the femur in this age group. (orig.)

  10. Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

    Science.gov (United States)

    Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

    2011-01-01

    Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

  11. The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study

    DEFF Research Database (Denmark)

    Connolly, S. J.; Wallentin, L.; Ezekowitz, M. D.

    2013-01-01

    . There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY...

  12. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Højlund, Kurt; Glintborg, Dorte; Andersen, Nicoline R

    2008-01-01

    , and we examined the effect of 16 weeks of treatment with pioglitazone in PCOS patients. RESULTS: Impaired insulin-mediated total (R(d)) oxidative and nonoxidative glucose disposal (NOGD) was paralleled by reduced insulin-stimulated Akt phosphorylation at Ser473 and Thr308 and AS160 phosphorylation......OBJECTIVE: Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo...... are less well characterized. RESEARCH DESIGN AND METHODS: We determined molecular mediators of insulin signaling to glucose transport in skeletal muscle biopsies of 24 PCOS patients and 14 matched control subjects metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry...

  13. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology.

    Directory of Open Access Journals (Sweden)

    Panayiota Papadopoulos

    Full Text Available Animal models of Alzheimer's disease (AD are invaluable in dissecting the pathogenic mechanisms and assessing the efficacy of potential new therapies. Here, we used the peroxisome proliferator-activated receptor gamma agonist pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12 months and aged (>18 months bitransgenic A/T mice that overexpress a mutated human amyloid precursor protein (APPSwe,Ind and a constitutively active form of transforming growth factor-β1 (TGF-β1. A/T mice recapitulate the AD-related cognitive deficits, amyloid beta (Aβ and cerebrovascular pathologies, as well as the altered metabolic and vascular coupling responses to increased neuronal activity. Pioglitazone normalized neurometabolic and neurovascular coupling responses to sensory stimulation, and reduced cortical astroglial and hippocampal microglial activation in both age groups. Spatial learning and memory deficits in the Morris water maze were not rescued by pioglitazone, but reversal learning was improved in the adult cohort notwithstanding a progressing Aβ pathology. While pioglitazone preserved the constitutive nitric oxide synthesis in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity in A/T mice and even exacerbated the dilatory deficits. These data demonstrate pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of comorbid amyloidosis and cerebrovascular pathology. They further suggest a potential benefit of pioglitazone in managing neuroinflammation, cerebral perfusion and glucose metabolism in AD patients devoid of cerebrovascular pathology.

  14. The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

    Science.gov (United States)

    Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

    2011-01-01

    Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

  15. Long term radioactive waste management

    International Nuclear Information System (INIS)

    Lavie, J.M.

    1984-01-01

    In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

  16. A comparison of pioglitazone with metformin in management of type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Razzaq, K.; Ahmed, W.; Anwar, R.; Khan, A.M.; Taj, M.A.; Iqbal, M.; Yousaf, M.A.

    2011-01-01

    Objectives: To compare hypo glycemic effect of Pioglitazone and Metformin in type 2 Diabetes Mellitus. Study Design: Quasi experimental study. Place and Duration of study: Department of Medicine, Military Hospital Rawalpindi Cantt. from 11-01-2007 to 12-08-2007. Material and Methods: Sixty patients of type 2 diabetes mellitus from outdoor department were selected. On arrival at OPD each patient was examined thoroughly. Therapeutic option was allocated to the patients simply by using a table of random numbers and dividing them in two equal groups. Informed written consent was obtained. Each patient was followed on monthly subsequent visits (six in total) and his HbA1c, fasting and random blood glucose were recorded carefully. All the data thus obtained was processed and analyzed using SPSS version 10.0. Mean and SD were calculated for age, BMI, fasting blood glucose, random blood glucose and HbA1c levels. Results: Mean drop of all three parameters were compared among two groups. At the end of six months, it was revealed that fasting and random (2 hours postprandial) blood glucose dropped more in Pioglitazone group; P=0.000 and 0.02 respectively. While almost comparable effect was observed in HbA1c (P=0.2). Conclusion: Pioglitazone has significantly better hypo glycemic effect than Metformin in type 2 diabetes mellitus at the end of six months therapy. (author)

  17. The long-term patient in the era of community treatment.

    Science.gov (United States)

    Lamb, H R; Goertzel, V

    1977-06-01

    Post hospital follow-up studies do not encompass the total population of long-term, psychiatrically disabled patients in the community, because a large proportion (in this study, 64%) have not had a recent hospitalization, either state or local. The authors identified a population of long-term, psychiatrically disabled patients in the community, all of whom carried functional psychotic diagnoses. Long-term disabled patients generally lead inactive lives, but in California seldom return to state hospitals. One third have been hospitalized locally within the past two years-younger patients much more than older patients. Almost half use private (Medicaid) outpatient services, but one fourth receive no mental health services at all. Less than a third live in board and care homes or cheap hotels; most live in nonsegregated, noninsitutional settings. The role of Supplemental Security Income (SSI) in enhancing adaptation of the chronically disabled was impressive to the research team.

  18. Long term effect of radioactive iodine treatment in nontoxic multinodular goitre

    International Nuclear Information System (INIS)

    Nygaard, B.; Hegedues, L.; Gervil, M.; Hjalgrim Jensen, H.; Soee-Jensen, P.; Moelholm hansen, J.E.

    1994-01-01

    The aim of this study was to investigate the long term effect of 131 I treatment on thyroid function and size in patients with non-toxic multinodular goitre. The subjects were 69 consecutive patients with multinodular non-toxic goitre selected for 131 I treatment and followed for a minimum of 12 months. Outcome measures were standard thyroid function variable and ultrasonically determined thyroid volume before and after treatment. Fifty-nine patients were treated with a single dose of 131 I, 12 with tow doses, and one with four doses. In 45 patients treated with one dose who remained euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (interquartile range 23-48) ml at 24 months. The median reuction was 40 (22-48) ml, half of which occurred within three months. Patients treated with two doses as well as those developing hypo- or hyper-thyroidism also had a significant reduction in thyroid volume. Eleven patients develeoped hypothyroidism (cumulative five year risk 22%). Side effects were few. In conclusion we find that 131 I treatment of multinodular non-toxic goitre is an attractive alternative to surgery. (au) (19 refs.)

  19. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    International Nuclear Information System (INIS)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

    2012-01-01

    Purpose: To review the impact of high–dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases–free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988–2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases–free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p 0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by

  20. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-09-01

    Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

  1. Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case–control study

    Science.gov (United States)

    Boxall, Naomi; Bennett, Dimitri; Hunger, Matthias; Dolin, Paul; Thompson, Paula L

    2016-01-01

    Objectives Investigate potential association between pioglitazone exposure and risk of prostate cancer. Research design and methods Nested, matched case–control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. Results From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (pworld, nested matched case–control study, exposure to pioglitazone was not associated with increased risk of prostate cancer. PMID:28074141

  2. Semi-passive, Chemical Oxidation Schemes for the Long-term Treatment of Contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Frank W. Schwartz

    2005-12-13

    agent from controlled release systems of varied forms and applications. We manufactured prototype single- and double-layered matrix-type controlled release systems and tested their release patterns using numerical simulations and column experiments. In a series of simulations, we demonstrated that an encapsulated, dispersed-agent polymeric matrix-type controlled release system could deliver active agent at a predetermined constant rate for long time periods of years and decades. Such long-term, constant release system is useful in the construction of fertilizers, herbicides, or implantable drug delivery devices as well as in subsurface treatment. Construction of more advanced forms of controlled release systems is currently under way.

  3. Fondaparinux in the initial and long-term treatment of venous thromboembolism.

    Science.gov (United States)

    Pesavento, Raffaele; Amitrano, Maria; Trujillo-Santos, Javier; Di Micco, Pierpaolo; Mangiacapra, Sara; López-Jiménez, Luciano; Falgá, Conxita; García-Bragado, Fernando; Piovella, Chiara; Prandoni, Paolo; Monreal, Manuel

    2015-02-01

    Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Long-term ecophysiological responses to climate change

    DEFF Research Database (Denmark)

    Boesgaard, Kristine Stove; Ro-Poulsen, Helge

    Plant physiology is affected by climate change. Acclimations of photosynthetic processes are induced by short-term changes in climatic conditions. Further acclimation can be caused by longterm adjustments to climate change due to ecosystem-feedbacks. The aim of this PhD was to investigate plant...... term responses of plant physiology to the climate change factors were investigated. In the CLIMAITE-experiment it has been shown that 2 years of treatment altered physiological responses in Deschampsiaand Calluna. In the work of this PhD similar responses were observed after 6 years of treatment...... physiological responses to climate change in a seasonal and long-term perspective. The effects of elevated CO2, passive night time warming and periodic summer drought as single factor and in combination, on plant physiology were investigated in the long-term multifactorial field experiment CLIMAITE in a Danish...

  5. Thyroid cancer treatment : Long-term effects and new developments

    NARCIS (Netherlands)

    Klein Hesselink, Esther

    2016-01-01

    Thyroid cancer is increasingly common. This is especially the case for differentiated thyroid cancer (DTC), which has a favorable prognosis. Treatment consists of surgical removal of the thyroid gland, radioiodine treatment, and life-long administration of relatively high doses of thyroid hormone.

  6. Treatment and long-term follow-up of distichiasis, with special reference to the Friesian horse: a case series

    NARCIS (Netherlands)

    Hermans, Hanneke; Ensink, Jos

    Reasons for performing study: Distichiasis is very uncommon in horses and treatment options and outcome remain unknown. Objectives: To describe treatment and long-term follow-up of distichiasis in the horse. Study design: Retrospective clinical study. Methods: Case records of horses admitted for

  7. Surgical Treatment of Nonlesional Neocortical Epilepsy: Long-term Longitudinal Study.

    Science.gov (United States)

    Kim, Dong Wook; Lee, Sang Kun; Moon, Hye-Jin; Jung, Ki-Young; Chu, Kon; Chung, Chun-Ki

    2017-03-01

    .16-0.85]) were favorable surgical outcome predictors. Our study showed that nearly 60% of patients with nonlesional neocortical epilepsy achieved freedom from long-term seizure, and that changes in postoperative seizure status were rarely observed. Several predictors of favorable surgical outcomes were identified, which can help select optimal candidates for surgical treatment among patients with nonlesional neocortical epilepsy.

  8. Long-term Results of Percutaneous Ethanol Injection for the Treatment of Hepatocellular Carcinoma in Korea

    International Nuclear Information System (INIS)

    Sung, Yon Mi; Choi, Don Gil; Lim, Hyo K.

    2006-01-01

    To evaluate the long-term follow-up results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in Korea. Sixty-eight nodular HCCs initially detected in 64 patients, were subjected to US-guided PEI as a first-line treatment. Long-term survival rates, local tumor progression rates, and complications were evaluated, as were the influences of tumor size and Child-Pugh class on these variables. No major complications occurred. The overall survival rates of the 64 patients at three and five years were 71% and 39%, and their cancer-free survival rates were 22% and 15%, respectively. The overall survival rate of patients with a small HCC (≤ 2 cm) was significantly higher (p = 0.014) than that of patients with a medium-sized HCC (≤ 2 cm). The overall survival rate of patients with Child- Pugh class A was significantly higher (p = 0.049) than that of patients with Child- Pugh class B. Of 59 cases with no residual tumor, local tumor progression was observed in ablation zones in 18, and this was not found to be significantly influenced by tumor size or Child-Pugh class. The results of our investigation of the long-term survival rates of PEI in HCC patients in Korea (a hepatitis B virus-endemic area) were consistent with those reported previously in hepatitis C endemic areas. Patients with a smaller tumor or a better liver function exhibited superior survival rates

  9. Long-term Nasal and Peri-oral Tightening by a Single Fractional Noninsulated Microneedle Radiofrequency Treatment.

    Science.gov (United States)

    Tanaka, Yohei

    2017-02-01

    Background: The skin tightening effects induced by non-insulated microneedle radiofrequency have proved long-lasting. Our previous three-dimensional volumetric assessment showed significant facial tightening for up to six months. However, nasal and peri-oral tightening effects lasted longer. The objective of this study was to investigate the distribution of the long-term volumetric reduction in facial area induced by a single fractional non-insulated microneedle radiofrequency treatment. Methods: Fifteen Asian patients underwent full facial skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with a novel fractionated pulse mode. Three-dimensional volumetric assessments were performed at six and 12 months post-treatment. Patients rated their satisfaction using a 5-point scale at each follow up. Results: Objective assessments with superimposed three-dimensional color images showed significant volumetric reduction in the nasal and peri-oral areas at 12 months post-treatment in all patients. Median volumetric reductions at six and 12 months post-treatment were 13.1 and 12.3ml, respectively. All of the patients were satisfied with their results 12 months post-treatment. Side effects were not observed. Conclusions: This single fractional NIMNRF treatment provided long-lasting nasal and peri-oral tightening as shown via 3D volumetric assessment. Moreover, NIMNRF produced minimal complications, downtime, and few side effects. This approach provides safe and effective treatment of skin tightening.

  10. 22(R)-hydroxycholesterol and pioglitazone synergistically decrease cholesterol ester via the PPARγ–LXRα–ABCA1 pathway in cholesterosis of the gallbladder

    International Nuclear Information System (INIS)

    Wang, Jing-Min; Wang, Dong; Tan, Yu-Yan; Zhao, Gang; Ji, Zhen-Ling

    2014-01-01

    Highlights: • Cholesterosis is a metabolic disease characterized by excessive lipid droplets. • Lipid droplet efflux is mediated by the ABCA1 transporter. • 22(R)-hydroxycholesterol can activate LXRα and up-regulate ABCA1. • Pioglitazone up-regulates ABCA1 in a PPARγ–LXRα–ABCA1-dependent manner. • 22(R)-hydroxycholesterol and pioglitazone synergistically decrease lipid droplets. - Abstract: Cholesterosis is a disease of cholesterol metabolism characterized by the presence of excessive lipid droplets in the cytoplasm. These lipid droplets are mainly composed of cholesterol esters derived from free cholesterol. The removal of excess cholesterol from gallbladder epithelial cells (GBECs) is very important for the maintenance of intracellular cholesterol homeostasis and the preservation of gallbladder function. Several lines of evidence have indicated that the activation of either peroxisome proliferator-activated receptor gamma (PPARγ) or liver X receptor α (LXRα) relates to cholesterol efflux. While pioglitazone can regulate the activation of PPARγ, 22(R)-hydroxycholesterol can activate LXRα and is a metabolic intermediate in the biosynthesis of steroid hormones. However, the effect of 22(R)-hydroxycholesterol in combination with pioglitazone on cholesterosis of the gallbladder is unclear. GBECs were treated with pioglitazone, 22(R)-hydroxycholesterol or PPARγ siRNA followed by Western blot analysis for ATP-binding cassette transporter A1 (ABCA1), PPARγ and LXRα. Cholesterol efflux to apoA-I was determined, and Oil Red O staining was performed to monitor variations in lipid levels in treated GBECs. Our data showed that 22(R)-hydroxycholesterol can modestly up-regulate LXRα while simultaneously increasing ABCA1 by 56%. The combination of 22(R)-hydroxycholesterol and pioglitazone resulted in a 3.64-fold increase in ABCA1 expression and a high rate of cholesterol efflux. Oil Red O staining showed an obvious reduction in the lipid droplets

  11. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Science.gov (United States)

    2012-02-29

    ... Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental... review of the uncovered finished water reservoir requirement in the Long Term 2 Enhanced Surface Water... uncovered finished water reservoir requirement and the agency's Six Year Review process. EPA also plans to...

  12. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vikram, Ajit [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India); Jena, Gopabandhu, E-mail: gbjena@gmail.com [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India)

    2010-07-23

    Research highlights: {yields}Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. {yields}Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. {yields}Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. {yields}Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ({approx}18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPAR{gamma}) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 {+-} 16.32 vs. 126.37 {+-} 27.07 mg/dl) and glucose intolerance ({approx}78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  13. Impact of Long-Term Treatment with Ivermectin on the Prevalence and Intensity of Soil-Transmitted Helminth Infections

    Science.gov (United States)

    Moncayo, Ana Lucia; Vaca, Maritza; Amorim, Leila; Rodriguez, Alejandro; Erazo, Silvia; Oviedo, Gisela; Quinzo, Isabel; Padilla, Margarita; Chico, Martha; Lovato, Raquel; Gomez, Eduardo; Barreto, Mauricio L.; Cooper, Philip J.

    2008-01-01

    Background Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children. Methods and Findings A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6–16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0–5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR =  0.06, 95% CI 0.03–0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11–0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments. Conclusion Annual and twice

  14. Long-term treatment outcomes of acromegaly patients presenting biochemically-uncontrolled at a tertiary pituitary center.

    Science.gov (United States)

    Carmichael, John D; Broder, Michael S; Cherepanov, Dasha; Chang, Eunice; Mamelak, Adam; Said, Qayyim; Neary, Maureen P; Bonert, Vivien

    2017-08-04

    Acromegaly is a rare, slowly progressive disorder resulting from excessive growth hormone (GH) production by a pituitary somatotroph tumor. The objective of this study was to examine acromegaly treatment outcomes during long-term care at a specialized pituitary center in patients presenting with lack of biochemical control. Data came from an acromegaly registry at the Cedars-Sinai Medical Center Pituitary Center (center). Acromegaly patients included in this study were those who presented biochemically-uncontrolled for care at the center. Biochemical control status, based on serum insulin-like growth factor-1 values, was determined at presentation and at study end. Patient characteristics and acromegaly treatments were reported before and after presentation by presenting treatment status and final biochemical control status. Data on long-term follow-up were recorded from 1985 through June 2013. Seventy-four patients presented uncontrolled: 40 untreated (54.1%) and 34 (45.9%) previously-treated. Mean (SD) age at diagnosis was 43.2 (14.7); 32 (43.2%) were female patients. Of 65 patients with tumor size information, 59 (90.8%) had macroadenomas. Prior treatments among the 34 previously-treated patients were pituitary surgery alone (47.1%), surgery and medication (41.2%), and medication alone (11.8%). Of the 40 patients without prior treatment, 82.5% achieved control by study end. Of the 34 with prior treatment, 50% achieved control by study end. This observational study shows that treatment outcomes of biochemically-uncontrolled acromegaly patients improve with directed care, particularly for those that initially present untreated. Patients often require multiple modalities of treatment, many of which are offered with the highest quality at specialized pituitary centers. Despite specialized care, some patients were not able to achieve biochemical control with methods of treatment that were available at the time of their treatment, showing the need for additional

  15. Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy.

    Directory of Open Access Journals (Sweden)

    Maria Vinaixa

    Full Text Available Polycystic ovary syndrome (PCOS is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients.

  16. Long-Term Patency of Lymphovenous Anastomoses: A Systematic Review.

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2016-08-01

    With advancements in technology and microsurgical techniques, lymphovenous anastomosis has become a popular reconstructive procedure in the treatment of chronic lymphedema. However, the long-term patency of these anastomoses is not clear in the literature. A systematic review of the MEDLINE and EMBASE databases was performed to assess the reported long-term patency of lymphovenous anastomoses. A total of eight studies satisfied the inclusion criteria. Pooled data from four similar experiments in normal dogs showed an average long-term (≥5 months) patency of 52 percent. The only experiment in dogs with chronic lymphedema failed to show any long-term patency. The creation of peripheral lymphovenous anastomoses with a moderate long-term patency rate has become technically possible. However, the long-term results in chronic lymphedema are limited.

  17. Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome.

    Science.gov (United States)

    Stabile, Gaspare; Borrielli, Irene; Artenisio, Alfredo Carducci; Bruno, Lucia Maria; Benvenga, Salvatore; Giunta, Loretta; La Marca, Antonio; Volpe, Annibale; Pizzo, Alfonsa

    2014-06-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17β-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  18. PPARγ agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation.

    Science.gov (United States)

    Legchenko, Ekaterina; Chouvarine, Philippe; Borchert, Paul; Fernandez-Gonzalez, Angeles; Snay, Erin; Meier, Martin; Maegel, Lavinia; Mitsialis, S Alex; Rog-Zielinska, Eva A; Kourembanas, Stella; Jonigk, Danny; Hansmann, Georg

    2018-04-25

    Right ventricular (RV) heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Peroxisome proliferator-activated receptor γ (PPARγ) acts as a vasoprotective metabolic regulator in smooth muscle and endothelial cells; however, its role in the heart is unclear. We report that deletion of PPARγ in cardiomyocytes leads to biventricular systolic dysfunction and intramyocellular lipid accumulation in mice. In the SU5416/hypoxia (SuHx) rat model, oral treatment with the PPARγ agonist pioglitazone completely reverses severe PAH and vascular remodeling and prevents RV failure. Failing RV cardiomyocytes exhibited mitochondrial disarray and increased intramyocellular lipids (lipotoxicity) in the SuHx heart, which was prevented by pioglitazone. Unbiased ventricular microRNA (miRNA) arrays, mRNA sequencing, and lipid metabolism studies revealed dysregulation of cardiac hypertrophy, fibrosis, myocardial contractility, fatty acid transport/oxidation (FAO), and transforming growth factor-β signaling in the failing RV. These epigenetic, transcriptional, and metabolic alterations were modulated by pioglitazone through miRNA/mRNA networks previously not associated with PAH/RV dysfunction. Consistently, pre-miR-197 and pre-miR-146b repressed genes that drive FAO ( Cpt1b and Fabp4 ) in primary cardiomyocytes. We recapitulated our major pathogenic findings in human end-stage PAH: (i) in the pressure-overloaded failing RV (miR-197 and miR-146b up-regulated), (ii) in peripheral pulmonary arteries (miR-146b up-regulated, miR-133b down-regulated), and (iii) in plexiform vasculopathy (miR-133b up-regulated, miR-146b down-regulated). Together, PPARγ activation can normalize epigenetic and transcriptional regulation primarily related to disturbed lipid metabolism and mitochondrial morphology/function in the failing RV and the hypertensive pulmonary vasculature, representing a therapeutic approach for PAH and other cardiovascular/pulmonary diseases. Copyright

  19. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    Science.gov (United States)

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-01-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

  20. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    Directory of Open Access Journals (Sweden)

    Antonio Costantini

    2016-01-01

    Full Text Available Myotonic dystrophy type 1, also known as Steinert′s disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1 is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC, the Muscular Impairment Rating Scale (MIRS, and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients′ activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively. The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

  1. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    Science.gov (United States)

    Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

    2016-09-01

    Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

  2. A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Hagen, Claus

    2009-01-01

    by allotetrahydrocortisol (alloTHF)/THF and androsterone/etiocholanolone (A/E) ratios. Delta values denoted changes during the treatment period (16 weeks--basal). Pyridostigmine growth hormone (GH) stimulation tests were performed, and testosterone (T), dihydrotestosterone (DHT), DHEA, DHEAS, adiponectin, and insulin...... levels. Delta A/E ratio inversely correlated with Delta IGF-I and Delta peak GH during GH stimulation tests. No significant changes were measured in T, DHT, DHEA, DHEAS, 24 h mean cortisol, or urinary excretion of steroid metabolites. CONCLUSION(S): Pioglitazone decreased relative 5alpha...

  3. Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

    Directory of Open Access Journals (Sweden)

    Nathan Elie Frenk

    Full Text Available OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

  4. Sustained favorable long-term outcome in the treatment of schizophrenia: a 3-year prospective observational study

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum Haya

    2011-08-01

    having received help with shopping and leisure activities. Conclusions Only a small percentage of patients achieved sustained favorable long-term outcome in this study, suggesting there continues to be a great need for improvement in the treatment of schizophrenia. Findings suggest that clinicians could make early projections of health states and identify those patients more likely to achieve favorable long-term outcomes enabling early therapeutic interventions to enhance benefits for patients.

  5. Long-term periodontal response to orthodontic treatment of palatally impacted maxillary canines.

    Science.gov (United States)

    Caprioglio, Alberto; Vanni, Arianna; Bolamperti, Laura

    2013-06-01

    One of the most important aspects to take into consideration when evaluating the outcome of treatment of impacted maxillary canines is the final periodontal status. The aim of the present study was to evaluate the long-term periodontal response of palatally impacted maxillary canines aligned using a codified procedure and the 'Easy Cuspid' compared with contralateral spontaneously erupted teeth. The periodontal conditions of the adjacent teeth were also considered. From an initial sample of 124 patients, 33 patients (24 females and 9 males) were selected. All patients who had undergone surgical orthodontic treatment conducted in accordance with a standardized protocol were recalled for follow-up at an average of 4.6 years after the end of treatment. The average treatment time was 29 months and the mean eruption time of the previously impacted tooth was 3.1 months. The average probing depth values showed no significant clinical differences. Probing depths recorded at the vestibular surface of the lateral incisor (P alignment of palatally impacted canines without damage to the periodontium.

  6. Heat treatment effect on structure and long-term rupture strength of γ/γ'-MeC nickel eutectic. Length memory effect

    International Nuclear Information System (INIS)

    Kishkin, S.T.; Svetlov, I.L.; Sorokina, L.P.; Morozova, S.G.; Golubovskij, E.R.; Yushakova, F.V.

    1983-01-01

    Heat treatment effect on structure, phase composition and long-term rupture strength of the directional eutectics on the nickel base with γ/γ'-MeC structure is studied at 900-1100 deg C. It is shown that quenching from the temperature of complete dissolving of γ'-phase and ageing (900 deg - 30 hr) provide an optimum size and morphology of the γ-phase and an increase of the long-term rupture strength at 900 and 1000 deg C. Repeated thermal treatment of cimens tested during definite time restores their structure, mechanical properties and dimensions

  7. LONG-TERM OUTCOMES OF RETINAL DEGENERATIVE DISORDER TREATMENT WITH PEPTIDE BIOREGULATORS

    Directory of Open Access Journals (Sweden)

    M. I. Razumovskiy

    2015-01-01

    Full Text Available Aim. To analyze long-term outcomes and efficacy of retinal degeneration treatment with Retinalamin.Patients and methods. Group I included 20 patients (40 eyes with pigmentary retinal dystrophy (15 patients, 30 eyes and retinal abiotrophy (5 patients, 10 eyes who received treatment with Retinalamin for 5‑7 years. Group II included 11 patients (22 eyes with pigmentary retinal dystrophy (9 patients, 18 eyes and retinal abiotrophy (2 patients, 4 eyes who received treatment with Retinalamin for 23‑25 years. Group III (controls included 15 patients (30 eyes with pigmentary retinal dystrophy (11 patients, 22 eyes and retinal abiotrophy (4 patients, 8 eyes who received traditional treatment (vasodilators, angioprotectors, antisclerotic agents, vitamins for 25 years. Standard ophthalmological examination, i.e., visual acuity measurement, visual field test, refractometry, biomicroscopy, ophthalmoscopy, was performed.Results. First course of treatment with Retinalamin improved vision in 58.1 % of retinal degeneration patients. Visual fields improved in 64.5 % of cases. Repeated treatment courses (1‑2 times a year for 23‑25 years preserved residual vision in 55.6 % of patients and object vision in 11.1 % of cases. In retinal abiotrophy patients, residual vision preserved in 100 % of cases.Conclusions. In retinal degenerations, Retinalamin improves vision and visual fields and decreases total area of absolute scotomas even after the first treatment course as well as preserves vision in prolonged use. 

  8. A Substance Called Food: Long-Term Psychodynamic Group Treatment for Compulsive Overeating.

    Science.gov (United States)

    Schwartz, Deborah C; Nickow, Marcia S; Arseneau, Ric; Gisslow, Mary T

    2015-07-01

    Obesity has proven difficult to treat. Many approaches neglect to address the deep-rooted underlying psychological issues. This paper describes a psychodynamically oriented approach to treating compulsive overeating as an addiction. Common to all addictions is a compulsion to consume a substance or engage in a behavior, a preoccupation with using behavior and rituals, and a lifestyle marked by an inability to manage the behavior and its harmful consequences. The approach represents a shift away from primarily medical models of intervention to integrated models focusing on the psychological underpinnings of obesity. Long-term psychodynamic group psychotherapy is recommended as a primary treatment.

  9. Symptoms and personality problems before, during and after long-term psychoanalytic treatment: A multiple-cohort study

    NARCIS (Netherlands)

    Berghout, C.C.; Zevalkink, D.J.; de Jong, J.T.V.M.

    2010-01-01

    Using a multiple cohort design, we compared symptoms and personality functioning (SCL-90, BDI-II, STAI, IIP-64, MMPI-2) of patients (N= 231) in different phases of long-term psychoanalytic treatment (before, during, end, follow-up). Our results confirmed findings from earlier meta-analyses that

  10. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for the long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are related to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product

  11. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are ralated to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product. (author)

  12. Safety of long-term PPI therapy

    DEFF Research Database (Denmark)

    Reimer, Christina

    2013-01-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

  13. [Intraabdominal fat redistribution in long-term continuous positive airway pressure treatment in obstructive sleep apnea patients].

    Science.gov (United States)

    Català, Raquel; Ferré, Raimón; Sangenís, Sandra; Cabré, Anna; Hernández-Flix, Salvador; Masana, Lluís

    2016-06-03

    Obesity is the main risk factor for obstructive sleep apnoea (OSA). The aim was to evaluate the long-term effect of continuous positive airway pressure (CPAP) on intraabdominal fat distribution in OSA patients. Fifty OSA patients with and 35 without CPAP treatment criteria were followed-up for 2 years. Visceral and subcutaneous adipose tissue (VAT and SAT) and preaortic intraabdominal fat (PIF) were assessed by sonography. In the non CPAP treated group, SAT and VAT mean values didn't change, while a significantly PIF growth was observed (55.19 [23.44] vs. 63.45 [23.94] mm, P=.021). In the CPAP treated group, VAT and PIF mean were not changed, while SAT decreased significantly (11.29 [5.69] vs. 10.47 [5.71] mm, P=.012). Long-term CPAP treatment produces intraabdominal fat redistribution and is associated with an anthropometric profile of lower cardiovascular risk in OSA patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

    Directory of Open Access Journals (Sweden)

    Kissin I

    2013-07-01

    Full Text Available Igor Kissin Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Background: For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1 there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2 the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods: Scientometric analysis of the articles representing clinical research in this area was performed to assess (1 the quality of presented evidence (type of study; and (2 the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1 editorials; (2 articles in the top specialty journals; and (3 articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles. Results: Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16 were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion: There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the

  15. A retrospective study of long-term treatment outcomes for reduced vocal intensity in hypokinetic dysarthria

    Directory of Open Access Journals (Sweden)

    Christopher R. Watts

    2016-02-01

    Full Text Available Abstract Background Reduced vocal intensity is a core impairment of hypokinetic dysarthria in Parkinson’s disease (PD. Speech treatments have been developed to rehabilitate the vocal subsystems underlying this impairment. Intensive treatment programs requiring high-intensity voice and speech exercises with clinician-guided prompting and feedback have been established as effective for improving vocal function. Less is known, however, regarding long-term outcomes of clinical benefit in speakers with PD who receive these treatments. Methods A retrospective cohort design was utilized. Data from 78 patient files across a three year period were analyzed. All patients received a structured, intensive program of voice therapy focusing on speaking intent and loudness. The dependent variable for all analyses was vocal intensity in decibels (dBSPL. Vocal intensity during sustained vowel production, reading, and novel conversational speech was compared at pre-treatment, post-treatment, six month follow-up, and twelve month follow-up periods. Results Statistically significant increases in vocal intensity were found at post-treatment, 6 months, and 12 month follow-up periods with intensity gains ranging from 5 to 17 dB depending on speaking condition and measurement period. Significant treatment effects were found in all three speaking conditions. Effect sizes for all outcome measures were large, suggesting a strong degree of practical significance. Conclusions Significant increases in vocal intensity measured at 6 and 12 moth follow-up periods suggested that the sample of patients maintained treatment benefit for up to a year. These findings are supported by outcome studies reporting treatment outcomes within a few months post-treatment, in addition to prior studies that have reported long-term outcome results. The positive treatment outcomes experienced by the PD cohort in this study are consistent with treatment responses subsequent to other treatment

  16. Long-term functional outcome of kidneys in children with urolithiasis after ESWL treatment.

    Science.gov (United States)

    Vlajković, M; Slavković, A; Radovanović, M; Sirić, Z; Stefanović, V; Perović, S

    2002-04-01

    The aim of this study was to determine the long-term functional outcome of kidneys in children with urolithiasis treated by means of extracorporeal shock wave lithotripsy (ESWL). The effectiveness and safety of this method in the management of pediatric urinary stone disease was also studied. This prospective study enrolled 84 children, 33 boys (age: 9.1 +/- 3.8 yrs) and 51 girls (age: 9.6 +/- 3.9 yrs), with urolithiasis who were treated using a second-generation "Siemens" Lithostar lithotriptor, in the period between 1988 and 1998. Dynamic kidney scintigraphy using (99 m)Tc-DTPA was done prior to, immediately following ESWL treatment, three months later, and again after an observation period of 12 - 67 months (38 +/- 13 months). Immediate fragmentation rate was 90 %, while the calculus clearance rate was 61 %. Glomerular filtration rate (GFR), measured by clearance of (99 m)Tc-DTPA, immediately after an ESWL treatment of 107 +/- 6 ml/min was significantly lower compared to the pretreatment value of 118 +/- 7 ml/min, but returned three months later to 121 +/- 6 ml/min, and to 131 +/- 10 ml/min at the end of the observation period. A separate analysis was performed on three groups of patients treated by ESWL: with acute calculous disease, chronic calculous disease, and chronic calculous with partial stasis. ESWL treatment in children with acute obstruction was associated with an immediate increase in GFR; however, in chronic calculous disease a decrease in GFR was found. A return of GFR to the pretreatment level was observed at the three-month control in these patients. In patients with acute stone obstruction, at 3 and 12 - 67 months after ESWL treatment, GFR of the treated kidney was found to be significantly increased compared to the pretreatment level. In contrast, in children with chronic calculous disease this increase was modest. This study has demonstrated ESWL to be an effective treatment option for urinary calculi management, which can be safely performed

  17. Long-term results of accelerated radiation treatment for advanced head and neck cancer

    International Nuclear Information System (INIS)

    Lamb, D.S.; Morum, P.E.; Denham, J.W.; Gray, A.J.

    1998-01-01

    Background and purpose: This report presents long-term follow-up data from a prospective but unrandomized trial of a continuous 3.5-week course of accelerated radiation treatment (ART) used as primary treatment for patients with loco-regionally advanced head and neck cancer. Materials and methods: Ninety-three patients in three centres in New Zealand and Australia were treated with ART (59.40 Gy in 33 fractions over 24-25 days). Their disease originated from three anatomical regions (oral cavity, 35 patients; pharynx, 31 patients; larynx, 27 patients). Seventy-nine of these patients had stage III or IV cancers. Results: Follow-up ranged from 68 to 203 months (median 139 months). Loco-regional (LR) failure occurred in 52 patients leading to a 10-year actuarial expectation of LR control of 38%. The actuarial expectation of LR control at 10 years was highly dependent on stage and for stage III, IVA and IVB patients it was 57±8.1%, 32±1.7% and 7±0.5%, respectively. Multivariate analysis could not confirm an independent impact of primary site or histological differentiation on LR failure. Two patients died of acute toxicity of treatment and six patients developed grade 3/4 late complications affecting soft tissues only, yielding an actuarial expectation of complications of this severity at 5 years of 9%. No cases of osteoradionecrosis or myelitis were observed. Conclusion: This ART, which has proved easy to use at a number of large and small centres, has produced encouraging long-term LR control at a cost of limited soft tissue morbidity. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. Long-term quality of life after conservative treatment versus surgery for different stages of acute sigmoid diverticulitis.

    Science.gov (United States)

    Brandlhuber, Martina; Genzinger, Christian; Brandlhuber, Bernhard; Sommer, Wieland H; Müller, Mario H; Kreis, Martin E

    2018-03-01

    It is controversial whether patients fare better with conservative or surgical treatment in certain stages of acute diverticulitis (AD), in particular when phlegmonous inflammation or covered micro- or macro-perforation are present. The aim of this study was to determine long-term quality of life (QoL) for AD patients who received either surgery or conservative treatment in different stages. We included patients treated for AD at the University Hospital Grosshadern, Munich, Germany, between January 1, 2000, and December 31, 2010. Patients were classified by the Hansen and Stock (HS) classification, the modified Hinchey classification, and the German classification of diverticular disease (CDD). Pre-therapeutic staging was based on multidetector computed tomography. Long-term QoL was assessed by the Cleveland Global Quality of Life (CGQL) questionnaire, the Short Form 36 (SF-36), and the Gastrointestinal Quality of Life Index (GIQLI). Data are mean ± SEM. Patients with phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) had a better long-term QoL on the GIQLI when they were operated (78.5 ± 2.5 vs. 70.7 ± 2.1; p life, patients fare better after elective sigmoid colectomy when abscess size exceeds 1 cm.

  19. Treatment options for nonalcoholic steatohepatitis - a safety evaluation.

    Science.gov (United States)

    Issa, Danny; Wattacheril, Julia; Sanyal, Arun J

    2017-08-01

    There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered: This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis. Expert opinion: Current therapies continue to remain suboptimal. Weight loss is effective but hard to achieve. Traditional and endoscopic bariatric procedures are promising although more randomized trials are needed and the long-term safety remains to be established. Clinical trials have demonstrated the efficacy of several drugs for the treatment of NASH. Of these, there remains some uncertainty about the long-term safety of vitamin E. Pioglitazone is associated with osteopenia, fluid retention and weight gain. Obeticholic acid causes pruritus in a substantial proportion of subjects and elafibranor has been associated with transient rises in creatinine. Several exciting therapies are under development and results of clinical and post-marketing trials will help elucidate their safety.

  20. [Psychosocial issues of long-term cancer survivors].

    Science.gov (United States)

    Weis, J; Faller, H

    2012-04-01

    Although cancer incidence rates are increasing, recent statistical studies suggest that cancer patients are showing higher cure rates as well as improved overall survival rates for most cancer locations. These advances are explained by improved strategies in early diagnoses as well as improved cancer therapies. Therefore, the number of long-term cancer survivors has also increased, but only few studies, especially within the last years, have focused on psychosocial issues of this subgroup. Some studies show that overall quality of life of long-term cancer survivors is quite high and comparable to that of the normal population. Nevertheless, a substantial percentage of former patients shows reduced quality of life and suffers from various sequelae of cancer and its treatment. This review focuses on the most common psychosocial issue of long-term survivors such as reduced psychological wellbeing, neuropsychological deficits and cancer-related fatigue syndrome. Finally, recommendations for problem-oriented interventions as well as improvement of psychosocial care of long-term survivors are given.

  1. Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic constipation in children with and without encopresis.

    Science.gov (United States)

    Pashankar, Dinesh S; Bishop, Warren P; Loening-Baucke, Vera

    2003-01-01

    Seventy-four children (43 with chronic constipation, 31 with constipation and encopresis) treated with polyethylene glycol 3350 (PEG) for longer than 3 months were studied to assess long-term efficacy. The mean duration of PEG therapy was 8.4 months (range, 3-30). Weekly stool frequency, stool consistency, and symptoms associated with constipation improved significantly with PEG therapy in all 74 patients. In 31 children with encopresis, soiling ceased completely in 16 patients and frequency of soiling decreased significantly in all others. The average effective long-term dose of PEG was 0.7 g/kg/day. Long-term PEG therapy is effective for the treatment of chronic constipation with and without encopresis in children.

  2. Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus?

    Science.gov (United States)

    Consoli, A; Formoso, G

    2013-11-01

    Thiazolidinediones have been introduced in the treatment of type 2 diabetes mellitus (T2DM) since the late 1990s. Although troglitazone was withdrawn from the market a few years later due to liver toxicity, both rosiglitazone and pioglitazone gained widespread use for T2DM treatment. In 2010, however, due to increased risk of cardiovascular events associated with its use, the European Medicines Agency recommended suspension of rosiglitazone use and the Food and Drug Administration severely restricted its use. Thus pioglitazone is the only thiazolidinedione still significantly employed for treating T2DM and it is the only molecule of this class still listed in the American Diabetes Association-European Association for the Study of Diabetes 2012 Position Statement. However, as for the other thiazolidinediones, use of pioglitazone is itself limited by several side effects, some of them potentially dangerous. This, together with the development of novel therapeutic strategies approved in the last couple of years, has made it questionable whether or not thiazolidinediones (namely pioglitazone) should still be used in the treatment of T2DM. This article will attempt to formulate an answer to this question by critically reviewing the available data on the numerous advantages and the potentially worrying shortcomings of pioglitazone treatment in T2DM. © 2013 John Wiley & Sons Ltd.

  3. CESSATION OF LONG-TERM TREATMENT WITH INHALED CORTICOSTEROID (BUDESONIDE) IN CHILDREN WITH ASTHMA RESULTS IN DETERIORATION

    NARCIS (Netherlands)

    WAALKENS, HJ; VANESSENZANDVLIET, EE; HUGHES, MD; GERRITSEN, J; DUIVERMAN, EJ; KNOL, K; KERREBIJN, KF; QUANJER, PH; SLUITER, HJ; POUW, EM; SCHOONBROOD, DFME; ROOS, CM; JANSEN, HM; BRAND, PLP; KERSTJENS, HAM; DEGOOIJER, A; POSTMA, DS; VANDERMARK, TW; KOETER, GH; DEJONG, PM; STERK, PJ; WEVER, AMJ; DEKHUIJZEN, PNR; FOLGERING, H; VANHERWAARDEN, CLA; OVERBEEK, SE; BOGAARD, JM; HILVERING, C; GANS, SJ; MENGELERS, HJJ; VANDERBRUGGEN, B; KREUKNIET, J; VANESENZANDVLIET, EEM; KOUWENBERG, JM; PRINSEN, JE; DEMONCHY, JGR; KAPTEIN, AA; DEKKER, FW; MERKUS, PJFM; POCOCK, SJ; ROBINSON, NJ; HUGHES, MD; BLEECKER, ER; MEYERS, DA

    1993-01-01

    Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age,

  4. Long-term efficacy of omalizumab in seven patients with treatment-resistant chronic spontaneous urticaria.

    Science.gov (United States)

    Silva, P M; Costa, A C; Mendes, A; Barbosa, M P

    2015-01-01

    Monoclonal anti-IgE antibody omalizumab is a promising therapeutic option in patients with chronic urticaria (CU) resistant to non-sedating H1-antihistamines (nsAH). However, data about its long-term efficacy and safety are still scant. We retrospectively analysed the clinical course of patients with severe recalcitrant CU that were treated in our department with omalizumab for a period greater than 24 months. Seven patients (six females, median 43 years) treated for a median of 35 months have been evaluated. Before treatment, all suffered from persistent symptoms despite receiving high doses of nsAH [4×/day], leukotriene antagonists and prednisolone (10-30 mg/day for a median duration of 48 months). Response to treatment was assessed using urticaria activity score (UAS) and a combined symptom/medication score. There was a complete remission of disease in four patients after the first dose of omalizumab. Before the 5th administration, all patients had a UAS of 0. We found a significant improvement in UAS between pre-treatment and first dose (p=0.017) and a gradual decrease in the symptom/medication score over the course of the first five administrations. Tapering of prednisolone was possible in all patients. Administration intervals were gradually increased, although all experienced resurgence of symptoms in cycles greater than six weeks. There were no reported adverse reactions attributable to the drug. Omalizumab was a safe and effective corticosteroid alternative for maintaining long-term remission of symptoms in these patients. Treatment intervals required individual patient-by-patient determination. The drug did not seem to alter the natural history of the disease. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  5. Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

    Science.gov (United States)

    Prager, N A; Cox, J L; Lindsay, B D; Ferguson, T B; Osborn, J L; Cain, M E

    1993-07-01

    The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

  6. Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder.

    Science.gov (United States)

    Wang, Gene-Jack; Volkow, Nora D; Wigal, Timothy; Kollins, Scott H; Newcorn, Jeffrey H; Telang, Frank; Logan, Jean; Jayne, Millard; Wong, Christopher T; Han, Hao; Fowler, Joanna S; Zhu, Wei; Swanson, James M

    2013-01-01

    Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated. We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands. Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005). Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.

  7. Craniopharyngioma in Children: Long-term Outcomes

    Science.gov (United States)

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  8. 15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and verapamil in indomethacin induced peptic ulcer rats.

    Science.gov (United States)

    Moustafa, Y M; El-Azab, M F; Fouda, A

    2013-01-01

    15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the enzyme responsible for prostaglandins (PGs) metabolism. PGs have an important role in the protection of stomach mucosa against destructive stimuli. The aim of the present study is to investigate the inhibitory effect of carbenoxolone, pioglitazone and verapamil on 15-PGDH enzyme. The experiments were carried out in the Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt from May 2011 to August 2011. Adult male albino rats were fasted for 18 hours before administration of high dose of indomethacin (30 mg/kg, p.o.), except for the negative control group which received saline only, followed by pyloric ligation to induce acute gastric ulcers. The rats were pretreated orally with saline, pioglitazone (20 mg/kg), verapamil (25 mg/kg), carbenoxolone (30 mg/kg) or their combinations 30 minutes before indomethacin. The rats were sacrificed after four hours of pyloric ligation. The effects of the previous treatments on the ulcer index (Ui), the microscopic appearance of gastric mucosa, the gastric acid output, the gastric barrier mucus content, and 15-PGDH enzyme activity were determined. Indomethacin resulted in severe ulceration and increased gastric acid output (p ulcer index, gastric acid output and 15-PGDH activity (p ulcer index, gastric acid output and 15-PGDH activity (p stomach mucosa.

  9. Long-term follow-up of behavioural treatment for primary encopresis in people with intellectual disability in the community.

    Science.gov (United States)

    Huntley, E; Smith, L

    1999-12-01

    Encopresis is a major problem in high-dependency fields such as intellectual disability. Little information is available with respect to either the prevalence or aetiology of encopresis, probably because it is widely regarded as part and parcel of the handicapping condition. Consequently, treatment reports are rare and confined to a small number of case studies. There is a dearth of long-term follow-up on the behavioural treatment of encopresis in the general population, and no long-term follow-up studies are available for the treatment of encopresis in intellectual disability. The present report provides follow-up data for nine out of 10 people with mainly severe intellectual disability who had received behavioural treatment for primary retentive or non-retentive encopresis between 5 and 17 years previously. Six out of the nine subjects for whom data were available were accident-free and a further two clients were very substantially improved. Interestingly, those whose former encopresis was retentive in nature maintained more successfully, despite the severity of their original impaction. The limitations of the present study are discussed.

  10. Is subfertility or fertility treatment associated with long-term growth in the offspring?

    DEFF Research Database (Denmark)

    Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

    2014-01-01

    . CONCLUSION(S): There were no differences in child anthropometrics at 5 years between children conceived after fertility treatment or by subfertile parents compared with that of children born to fertile parents. However, children born after fertility treatment may show catch-up growth during childhood.......(S): A total of 3,478 mother-child pairs were sampled from the Danish National Birth Cohort, and 1,773 completed the outcome measurements. A total of 69 children were born after fertility treatment, whereas 132 were born to subfertile parents conceiving spontaneously but after a time to pregnancy of more than......OBJECTIVE: To study whether fertility treatment or subfertility is associated with long-term growth in the offspring. DESIGN: A prospective follow-up study including 1,773 singletons participating in the Lifestyle During Pregnancy Study at the age of 5. SETTING: Research centers. PATIENT...

  11. Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Zerahn, Bo; Møller, Susanne

    2012-01-01

    Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.......Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

  12. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    International Nuclear Information System (INIS)

    Vikram, Ajit; Jena, Gopabandhu

    2010-01-01

    Research highlights: →Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. →Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. →Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. →Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia (∼18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPARγ) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 ± 16.32 vs. 126.37 ± 27.07 mg/dl) and glucose intolerance (∼78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  13. Long-term outcomes of fertility-sparing treatment of atypical polypoid adenomyoma with medroxyprogesterone acetate.

    Science.gov (United States)

    Nomura, Hidetaka; Sugiyama, Yuko; Tanigawa, Terumi; Matoda, Maki; Kanao, Hiroyuki; Kondo, Eiji; Takeshima, Nobuhiro

    2016-01-01

    Our objective was to analyze the long-term oncologic outcomes of fertility-preserving hormonal treatment with medroxyprogesterone acetate (MPA) in patients with APA. In a retrospective chart review, we identified patients with APA who were treated with MPA for fertility preservation at our hospital between 2001 and 2011. Eighteen patients with histologically diagnosed APA were identified. Clinical data including treatment, obstetrical, and oncologic outcomes were recorded. The mean observation period was 77.6 months (median 73.5, range 22-142), and the mean age was 33.6 years. Four patients also developed well-differentiated endometrial carcinoma. After the treatment, 14 patients (77.8 %) achieved either a complete response or partial response. Eight patients experienced recurrence, while four experienced persistent disease. Ten patients (55.6 %) eventually underwent hysterectomy. The median time to hysterectomy was 40.3 months (range 24-68). Nine patients progressed to endometrial cancer, and one experienced persistent APA. Among younger patients (years of age), four out of five patients who were married could have children. Seven patients (38.9 %) showed no evidence of the disease during the observation period (median 60 months, range 22-117 months). No one died because of the disease during the observation period. MPA yields a high response rate in APA, and if only younger patients are considered, a favorable pregnancy rate can be obtained. However, because recurrence rate is high, long-term follow-up under supervision of a trained gynecologic oncologist is required. To confirm MPA's utility, multi-center collaboration would be warranted.

  14. Lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment: A case report.

    Science.gov (United States)

    Naruse, Tomofumi; Tokuhisa, Mitsuko; Yanamoto, Souichi; Sakamoto, Yuki; Okuyama, Kohei; Tsuchihashi, Hiroki; Umeda, Masahiro

    2018-05-01

    Long-term cetuximab treatment can lead to acquired resistance, and tumor progression and/or new lesions often occur. The present report describes a case of lower gingival squamous cell carcinoma with brain metastasis during long-term cetuximab treatment in a 60-year-old man, including findings of an immunohistochemical study. The resected primary tumors, biopsy of the lung metastasis before administration of cetuximab, and brain metastasis specimens mediated by cetuximab were immunohistochemically examined. Histologically, the metastatic brain lesion showed hyperkeratinizing tumor cells with deeply stained irregular nuclei with necrotizing tumor cells, and a decrease in cell density was exhibited in part of the tumor nest. Moreover, the brain lesion was less malignant compared with the primary tumor and metastatic lung lesions. Immunohistochemically, the metastatic brain lesions showed low expression of epidermal growth factor receptor (EGFR) and high expression of N-cadherin compared with the primary tumor and metastatic lung lesions. These results suggest that acquired resistance to cetuximab may be associated with low EGFR expression and increased epithelial-to-mesenchymal transition potential.

  15. Long-term results after CT-guided percutaneous ethanol ablation for the treatment of hyper functioning adrenal disorders

    International Nuclear Information System (INIS)

    Frenk, Nathan Elie; Sebastianes, Fernando; Lerario, Antonio Marcondes; Fragoso, Maria Candida Barisson Villares; Mendonca, Berenice Bilharinho

    2016-01-01

    Objectives: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyper functioning adrenal disorders. Method: We retrospectively evaluated the long-term results of nine patients treated with computed tomography guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macro nodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. Results: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macro nodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. Conclusion: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyper functioning adrenal disorders and is not without risks. (author)

  16. Long-term results after CT-guided percutaneous ethanol ablation for the treatment of hyper functioning adrenal disorders

    Energy Technology Data Exchange (ETDEWEB)

    Frenk, Nathan Elie; Sebastianes, Fernando; Lerario, Antonio Marcondes; Fragoso, Maria Candida Barisson Villares; Mendonca, Berenice Bilharinho [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina; Menezes, Marcos Roberto de, E-mail: menezesmr@gmail.com [Instituto do Cancer do Estado de Sao Paulo, SP (Brazil)

    2016-10-15

    Objectives: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyper functioning adrenal disorders. Method: We retrospectively evaluated the long-term results of nine patients treated with computed tomography guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macro nodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. Results: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macro nodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. Conclusion: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyper functioning adrenal disorders and is not without risks. (author)

  17. Long-Term Results of Percutaneous Bilioenteric Anastomotic Stricture Treatment in Liver-Transplanted Children

    International Nuclear Information System (INIS)

    Moreira, Airton Mota; Carnevale, Francisco Cesar; Tannuri, Uenis; Suzuki, Lisa; Gibelli, Nelson; Maksoud, Joao Gilberto; Cerri, Giovanni Guido

    2010-01-01

    The purpose of this study was to evaluate the mid- and long-term results of percutaneous transhepatic cholangiography (PTC) and biliary drainage in children with isolated bilioenteric anastomotic stenosis (BAS) after pediatric liver transplantation. Sixty-four children underwent PTC from March 1993 to May 2008. Nineteen cholangiograms were normal; 10 showed intrahepatic biliary stenosis and BAS, and 35 showed isolated BAS. Cadaveric grafts were used in 19 and living donor grafts in 16 patients. Four patients received a whole liver, and 31 patients received a left lobe or left lateral segment. Roux-en-Y hepaticojejunostomy was performed in all patients. Indication for PTC was based on clinical, laboratory, and histopathologic findings. In patients with isolated BAS, dilation and biliary catheter placement, with changes every 2 months, were performed. Patients were separated into 4 groups according to number of treatment sessions required. The drainage catheter was removed if cholangiogram showed no significant residual stenosis and normal biliary emptying time after a minimum of 6 months. The relationship between risk factors (recipient's weight 20 months, 4 patients (4 of 35; 11.4%) required 1 additional treatment session (group III), and 1 patient (1 of 35; 2.9%) had a catheter placed at the end of the study period (group IV). Drainage time in group I was significantly shorter than those in groups II, III, and IV (p 0.05). The majority of complications, such as catheter displacement and leakage, were classified as minor; however, 2 patients (5.7%) with hemobilia were noted. Complications increased according to the need for reintervention. In conclusion, balloon dilation and percutaneous drainage placement is safe and effective, and it has long-term patency for children with BAS after liver transplantation. Because of prolonged treatment time, reintervention may be necessary, thereby increasing the complication rate. Balloon dilation and percutaneous drainage

  18. Long-term follow-up of psilocybin-facilitated smoking cessation.

    Science.gov (United States)

    Johnson, Matthew W; Garcia-Romeu, Albert; Griffiths, Roland R

    2017-01-01

    A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

  19. [Comparison of long-term dental treatment effects of children treated under general anesthesia and passive restraint].

    Science.gov (United States)

    Zhou, F; Xia, B; Zhang, S; Ma, W L; Xiao, Y M; Ge, L H

    2017-02-09

    Objective: To compare the long-term dental treatment effects, oral health habits and oral-health-related qualities of life of children treated under general anesthesia (GA) and passive restraint (PR), respectively. Methods: Twenty seven 2 to 4-year-old children treated under GA and thirty four children treated under PR were recruited in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology. Up to 2 years after the treatment, a follow up assessment was conducted. The data of general information, dental plaque level and the unplanned treatments were recorded and analyzed. The questionnaire of oral health habits and early childhood oral health impact scale (ECOHIS) for each child was also completed and analyzed. The survival rate and median survival time of the deciduous teeth were calculated. Multivariate analysis was performed by using Cox proportional hazard model. Results: Twenty-five children under GA and 32 under PR were finally included, with a total of 1 098 deciduous teeth. The postoperative dental plaque indicesin both GA and PR groups had significantly improved than that of before the treatments ( P= 0.019, P< 0.001). The oral health habits had also improved, and the improvement in PR group was more obvious than that in GA group. Totally 128 teeth (27.0%) appeared unplanned treatments in GA group and 232 teeth (37.2%) in PR group during the follow-ups. The new caries and recurrent caries in PR group were significantly more than that in GA group ( P< 0.001, P= 0.012). No significant differences were found between the two groups in restoration failure, secondary caries and endodontic diseases ( P= 0.129, P= 0.822, P= 0.642). However, the time of occurrence of endodontic disease and secondary caries in GA group were significantly longer than that in PR group ( P< 0.01, P< 0.001). The median survival time of teeth in GA group was 1 018 days comparing to 944 days in PR group. The difference was statistically significant ( P

  20. Long-term surgical-orthodontic management of hemimandibular hyperplasia.

    Science.gov (United States)

    Bennett, Samuel C; Goonewardene, Mithran S

    2016-05-01

    Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical unilateral elongation of the mandible becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and the dental compensatory mechanism is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is effectively managed by combined surgical-orthodontic care to address the facial, skeletal and dental problems that confront clinicians. Orthodontists are advised to assess patients with HH during the post-treatment retention stage for continuing mandibular growth and assess the stability of treatment outcomes with long-term follow-up and records as required. To present a case of hemimandibular hyperplasia treated successfully by combined surgical-orthodontic care and evaluated for stability over a seven-year follow-up period. Surgical-orthodontic management was accomplished in four stages: 1) pre-surgical orthodontic; 21 surgical; 3) post-surgical orthodontic; and 4) post-treatment orthodontic retention. Complete orthodontic records, including extra- and intra-oral photographs, study models, and cephalograms plus panoramic radiographs were taken at the pretreatment, post-treatment, and seven-year orthodontic retention time-points. Facial, skeletal and dental goals were achieved in the three planes of space and the long-term stability of the treatment results was shown during a post-treatment orthodontic retention period of seven years. Hemimandibular hyperplasia is a true growth anomaly which may be managed effectively. Clinicians may expect successful long-term correction and stability by utilising a comprehensive surgical-orthodontic treatment approach.

  1. Long-term outcome of using posterior-thigh fasciocutaneous flaps for the treatment of ischial pressure sores.

    Science.gov (United States)

    Lin, Haodong; Hou, Chunlin; Chen, Aimin; Xu, Zhen

    2010-08-01

    Among the many difficult problems presented by patients with spinal cord injuries, management of ischial pressure ulcers remains challenging for reconstructive surgeons. This study describes the long-term outcome of using posterior-thigh fasciocutaneous flaps for the treatment of ischial pressure sores. Between January 1999 and June 2003, 12 patients with ischial sores were enrolled in this study. All the patients underwent early aggressive surgical debridement followed by surgical reconstruction with a laterally based posterior-thigh fasciocutaneous flap. The follow-up period ranged from 24 months to 97 months (mean, 62 months). All the flaps survived, and there were no partial flap losses. Primary-wound healing occurred in all the cases. In two patients, Grade II ischial pressure sores recurred 24 months and 27 months after the operation. There was no recurrence in the other 10 patients. The posterior-thigh fasciocutaneous pedicled flap was a good method for treating ischial bed sores. This flap could be used to treat recurrences observed after primary bed-sore treatment with other methods. The flap was easy to raise, and it did not cause any donor-site morbidity. The long-term outcome of using posterior-thigh fasciocutaneous flaps for the treatment of ischial pressure sores was generally good. (c) Thieme Medical Publishers.

  2. Audit of long-term and short-term liabilities

    Directory of Open Access Journals (Sweden)

    Korinko M.D.

    2017-03-01

    Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

  3. Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study.

    Science.gov (United States)

    Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; Provost, Scott E; Fitzmaurice, Garrett M; McDermott, Katherine A; Srisarajivakul, Emily N; Dodd, Dorian R; Dreifuss, Jessica A; McHugh, R Kathryn; Carroll, Kathleen M

    2015-05-01

    Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, popioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

    Science.gov (United States)

    Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

    2016-06-01

    To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. 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/

  5. Sulfur flow in a soil-plant system-effects of long-term treatment history and soil properties

    DEFF Research Database (Denmark)

    Boye, Kristin; Eriksen, Jørgen; Nilsson, Ingvar

    2010-01-01

    deficiency, reduced biomass production and lower total S uptake by the rye grass. The isotopic measurements revealed that more than two thirds of the plant S was derived from non-labeled soil organic S, even in the + S treatment, and that all organic S pools (physically unprotected/protected and residual...... organic S) in the soil were involved in the S transformations. The long-term FYM treatment had resulted in higher S cycling rates and a slightly higher resistance to S deficiency than the CR treatment. The influence of soil type on S flow patterns was important, but probably only partly related...

  6. Proteome Modification in Tomato Plants upon Long-Term Aluminum Treatment.

    Science.gov (United States)

    Zhou, Suping; Okekeogbu, Ikenna; Sangireddy, Sasikiran; Ye, Zhujia; Li, Hui; Bhatti, Sarabjit; Hui, Dafeng; McDonald, Daniel W; Yang, Yong; Giri, Shree; Howe, Kevin J; Fish, Tara; Thannhauser, Theodore W

    2016-05-06

    This study aimed to identify the aluminum (Al)-induced proteomes in tomato (Solanum lycopersicum, "Micro-Tom") after long-term exposure to the stress factor. Plants were treated in Magnavaca's solution (pH 4.5) supplemented with 7.5 μM Al(3+) ion activity over a 4 month period beginning at the emergence of flower buds and ending when the lower mature leaves started to turn yellow. Proteomes were identified using a 8-plex isobaric tags for relative and absolute quantification (iTRAQ) labeling strategy followed by a two-dimensional (high- and low-pH) chromatographic separation and final generation of tandem mass spectrometry (MS/MS) spectra of tryptic peptides on an LTQ-Orbitrap Elite mass spectrometer. Principal component analysis revealed that the Al-treatment had induced systemic alterations in the proteomes from roots and leaves but not seed tissues. The significantly changed root proteins were shown to have putative functions in Al(3+) ion uptake and transportation, root development, and a multitude of other cellular processes. Changes in the leaf proteome indicate that the light reaction centers of photosynthetic machinery are the primary targets of Al-induced stress. Embryo and seed-coat tissues derived from Al-treated plants were enriched with stress proteins. The biological processes involving these Al-induced proteins concur with the physiological and morphological changes, such as the disturbance of mineral homeostasis (higher contents of Al, P, and Fe and reduced contents of S, Zn, and Mn in Al-treated compared to nontreated plants) in roots and smaller sizes of roots and the whole plants. More importantly, the identified significant proteins might represent a molecular mechanism for plants to develop toward establishing the Al tolerance and adaptation mechanism over a long period of stress treatment.

  7. Long-term duration of function of ovarian tissue transplants

    DEFF Research Database (Denmark)

    Andersen, Claus; Silber, Sherman J; Berghold, Stinne Holm

    2012-01-01

    These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian...... or to alleviate its symptoms. These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had...

  8. Physician personal characteristics influencing long-term treatment of patients with cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Strokova E.V.

    2013-06-01

    Full Text Available The main purpose of the article is to identify the peculiarities of a doctor personality, affecting long-term therapy in patients with cardiovascular diseases. Materials and methods: To determine the type of temperament, the presence and intensity of the syndrome of emotional burnout and capacity for empathy therapists and cardiologists were asked to fill in a number of questionnaires. Each doctor had a group of patients contacting by telephone for a year after the discharge from the hospital. During the telephone contact, the patients were asked about the continuation of their therapy recommended in the hospital, the regularity of therapy, the frequency of absence, and the assessment of a physician by the patients. Results: 35 questionnaires were suitable for interpretation. Through one year after the discharge from the hospital it was able to contact with 147 patients, 18.4% (27 of patients completely stopped the treatment by recommended drugs. Positive assessment of physicians was associated with the continuation of the therapy by recommended drugs and regularity of drug taking (p=0,03. Patients assessed physicians positively more often in cases of low level of emotional state, high level of depersonalization (cynicism and the reduction of personal accomplishment (feeling of professional inefficiency in a doctor. Conclusion: Assessment of physicians by patients is reliably and significantly influenced by continuation of long-term therapy and regularity of drug taking.

  9. Etanercept provides an effective, safe and flexible short- and long-term treatment regimen for moderate-to-severe psoriasis: a systematic review of current evidence.

    Science.gov (United States)

    Strohal, Robert; Chimenti, Sergio; Vena, Gino Antonio; Girolomoni, Giampiero

    2013-06-01

    The treatment of psoriasis requires long-lasting intervention. Conventional treatments for psoriasis comprise topical, phototherapeutic and systemic modalities, such as methotrexate or cyclosporine. Biological therapies are advocated by treatment guidelines for the use in moderate-to-severe psoriasis, when conventional treatments have failed, are contraindicated or are associated with severe adverse events. Etanercept is an anti-TNF recombinant fusion protein that has emerged as a standard biologic treatment option for moderate-to-severe psoriasis. The present review summarizes data from pivotal and post-marketing randomized controlled etanercept trials to treat moderate-to-severe psoriasis for 24 weeks and longer. During the first 12 weeks, etanercept can be administered in different dosing regimens: 50 mg twice weekly (BIW) and 50 mg once weekly. Although both regimens are effective, it has been shown that the 50 mg BIW dosage leads to higher response rates at week 24. In addition, after 24 weeks' treatment etanercept provides the unique possibility of continuous or intermittent long-term treatment programmes. The medium- to long-term efficacy of etanercept was consistent, regardless of whether etanercept therapy was interrupted or continuous. Taking the chronic nature of psoriasis into account, this flexibility in dosing regimen bestows a key advantage in facilitating individualisation of long-term treatment according to patient needs.

  10. Managing treatment fatigue in patients with multiple sclerosis on long-term therapy: the role of multiple sclerosis nurses

    Directory of Open Access Journals (Sweden)

    Crawford A

    2014-08-01

    Full Text Available Ann Crawford, Sally Jewell,* Holly Mara, Laura McCatty, Regina Pelfrey The Lash Group; Frisco, TX, USA *Sally Jewell is now retired Abstract: This article discusses the many ways that nurses can address the factors that lead to treatment fatigue in patients with multiple sclerosis (MS on long-term disease-modifying therapy, ultimately helping to preserve the patient’s health and quality of life. Patients with MS on long-term therapy may suffer from treatment fatigue and poor adherence due to a variety of different factors, including difficulties with injections, anxiety/depression, financial problems, and inaccurate beliefs about the MS disease process. Because MS nurses have regular interactions with patients, they are ideally situated to help patients cope with these and other factors that may limit adherence. Keywords: multiple sclerosis, disease-modifying therapy, injection, nurse

  11. Treatment Decision Regret Among Long-Term Survivors of Localized Prostate Cancer: Results From the Prostate Cancer Outcomes Study.

    Science.gov (United States)

    Hoffman, Richard M; Lo, Mary; Clark, Jack A; Albertsen, Peter C; Barry, Michael J; Goodman, Michael; Penson, David F; Stanford, Janet L; Stroup, Antoinette M; Hamilton, Ann S

    2017-07-10

    Purpose To determine the demographic, clinical, decision-making, and quality-of-life factors that are associated with treatment decision regret among long-term survivors of localized prostate cancer. Patients and Methods We evaluated men who were age ≤ 75 years when diagnosed with localized prostate cancer between October 1994 and October 1995 in one of six SEER tumor registries and who completed a 15-year follow-up survey. The survey obtained demographic, socioeconomic, and clinical data and measured treatment decision regret, informed decision making, general- and disease-specific quality of life, health worry, prostate-specific antigen (PSA) concern, and outlook on life. We used multivariable logistic regression analyses to identify factors associated with regret. Results We surveyed 934 participants, 69.3% of known survivors. Among the cohort, 59.1% had low-risk tumor characteristics (PSA decision regret: 8.2% of those whose disease was managed conservatively, 15.0% of those who received surgery, and 16.6% of those who underwent radiotherapy. Factors associated with regret on multivariable analysis included reporting moderate or big sexual function bother (reported by 39.0%; OR, 2.77; 95% CI, 1.51 to 5.0), moderate or big bowel function bother (reported by 7.7%; OR, 2.32; 95% CI, 1.04 to 5.15), and PSA concern (mean score 52.8; OR, 1.01 per point change; 95% CI, 1.00 to 1.02). Increasing age at diagnosis and report of having made an informed treatment decision were inversely associated with regret. Conclusion Regret was a relatively infrequently reported outcome among long-term survivors of localized prostate cancer; however, our results suggest that better informing men about treatment options, in particular, conservative treatment, might help mitigate long-term regret. These findings are timely for men with low-risk cancers who are being encouraged to consider active surveillance.

  12. Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis

    OpenAIRE

    Kotaniemi, Kaisu; S?il?, Hanna; Kautiainen, Hannu

    2011-01-01

    Kaisu Kotaniemi1,2, Hanna Säilä2, Hannu Kautiainen31Helsinki University Hospital, Helsinki, Finland; 2Orton Orthopaedic Hospital and Rehabilitation Unit, Helsinki, Finland; 3Unit of Primary Health Care, Kuopio University Hospital, Kuopio, FinlandBackground: The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis.Methods: Adalimumab was...

  13. Long term treatment with metformin in patients with type 2 diabetes and vitamin B 12

    Directory of Open Access Journals (Sweden)

    Yu V Pankratova

    2012-12-01

    Full Text Available Реферат по статье: De Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181.

  14. Liquid chromatographic determination of pioglitazone in pharmaceuticals, serum and urine samples

    International Nuclear Information System (INIS)

    Abro, K.; Memon, N.; Bhanger, M.I.; Mahesar, S.A.; Parveen, S.

    2011-01-01

    A rapid and reliable analytical method based on high-performance liquid chromatography (HPLC) with UV detection (221 nm) has been developed for the determination of the anti-hyper glycemic agent Pioglitazone in pharmaceutical formulations and biological fluids (serum and urine) after clean-up with solid-phase extraction. Chromatographic separation was achieved with a Chromolith Performance RP-18e (10 4.6mm) column using mobile phase composition of acetonitrile: mixed phosphate buffer (pH 2.5; 10mM) (30:70, v/v) with a flow rate of 2.0mL/min. The total run time was 2 min. under optimized conditions. The calibration curve was found to be linear in the range of 1-10 mu g mL/sup -1/ with regression coefficient of 0.9996, and the lower limit of detection 72 ng/20 mu L injection. The method has been validated for the system suitability, linearity, precision and accuracy, limits of detection, specificity, stability and robustness. The %recovery of Pioglitazone in pharmaceutical formulations was found to be 104.7%. The assay has been applied successfully to the pharmaceutical Tablet samples and biological fluids (serum and urine) of healthy volunteers. (author)

  15. REMISSION OF CHILDHOOD ASTHMA AFTER LONG-TERM TREATMENT WITH AN INHALED CORTICOSTEROID (BUDESONIDE) - CAN IT BE ACHIEVED

    NARCIS (Netherlands)

    VANESSENZANDVLIET, EE; HUGHES, MD; WAALKENS, HJ; DUIVERMAN, EJ; KERREBIJN, KF

    This study was undertaken in order to determine whether long-term treatment with inhaled corticosteroid can induce a remission in childhood asthma, and to decide when stabilization of airway responsiveness occurred. We therefore carried out, an extended follow-up of 28-36 months in one of two groups

  16. A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis

    NARCIS (Netherlands)

    A. Tran-Duy (An); A. Boonen (Annelies); M.A.F.J. van de Laar (Mart); A. Franke (Andre); J.L. Severens (Hans)

    2011-01-01

    textabstractObjective: To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Methods: Discrete event simulation paradigm was selected for model

  17. A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis

    NARCIS (Netherlands)

    Tran-Duy, A.; Boonen, A.; Laar, M.A.F.J.; Franke, A.C.; Severens, J.L.

    2011-01-01

    Objective To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Methods Discrete event simulation paradigm was selected for model development. Drug

  18. Haloperidol for long-term aggression in psychosis.

    Science.gov (United States)

    Khushu, Abha; Powney, Melanie J

    2016-11-27

    Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study

  19. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B

    DEFF Research Database (Denmark)

    Krogsgaard, K

    1998-01-01

    , irrespective of previous treatment category. Overall response rate was not significantly affected by gender, sexual inclination or ethnic origin. Durability of response did not depend upon ethnic origin or presence of cirrhosis. At the end of the original trial periods, 253 patients were histologically...... published multicentre, randomized, controlled trials were analysed. Information about survival and response during long-term follow-up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA......) was unrelated to original treatment category and response to treatment. Hence, 90% of responding patients will, irrespective of treatment category, have a sustained response. At least 30% of responding patients will eventually lose HBsAg. For a number of reasons, the present patient population and observation...

  20. The long-term power purchase: Recovery of capacity costs

    International Nuclear Information System (INIS)

    Cross, P.S.

    1990-01-01

    As electric utilities increase their reliance on the long-term power purchase as an alternative to utility-owned generation, the appropriate rate treatment of the costs established in the purchase agreement assumes growing importance. In the November 9, 1989, issue, the authors examined the recent trend among state regulators to treat the long-term purchase in a manner similar to the addition by a utility of a new plant, including a full-scale prudence review. This installment will review recent rulings on the related issue of rate recovery of long-term capacity costs through the fuel cost adjustment clause

  1. Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery

    International Nuclear Information System (INIS)

    Haasbeek, Cornelis J.A.; Uitterhoeve, Apollonia L.J.; Velden, Jacobus van der; Gonzalez, Dionisio Gonzalez; Stalpers, Lukas J.A.

    2008-01-01

    Abstarct: Background and purpose: Tumor recurrence after surgery for cervical carcinoma is associated with high fatality and morbidity, forming a major therapeutic challenge. This paper presents our experience with treatment of this patient group by salvage radiotherapy with curative intent. Materials and methods: Thirty-five patients with a pelvic recurrence after hysterectomy received high-dose radiotherapy. A retrospective analysis of long-term outcome and prognostic factors was performed. Results: After a median follow-up period of 12.1 years, actuarial 2-,5- and 10-year overall survival rates were 66%, 43% and 33%; disease-free survival rates were 62%, 45% and 41%, respectively. Pelvic control rates at 2-,5- and 10-years were 77%, 69% and 62%. Unfavorable prognostic factors on univariate analysis for survival were: recurrence extending to the pelvic wall versus central recurrence, early recurrence after surgery, external boost versus brachytherapy boost, low total dose and high age. Only a brachytherapy boost and a long interval between surgery and recurrence were significant on multivariate analysis. Severe complications (≥grade 3) were seen in 6 patients (17%; actuarial after 5 years, 21%). Conclusions: Salvage radiotherapy for recurrent cervical carcinoma following surgery may result in 40-50% long-term disease-free survival and an acceptable risk of severe treatment complications, even in patient with recurrences extending to the pelvic wall

  2. Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study

    Directory of Open Access Journals (Sweden)

    Aman Goyal

    2017-01-01

    Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

  3. Gender differences in success at quitting smoking: Short- and long-term outcomes.

    Science.gov (United States)

    Marqueta, Adriana; Nerín, Isabel; Gargallo, Pilar; Beamonte, Asunción

    2016-06-14

    Smoking cessation treatments are effective in men and women. However, possible sex-related differences in the outcome of these treatments remain a controversial topic. This study evaluated whether there were differences between men and women in the success of smoking cessation treatment, including gender-tailored components, in the short and long term (> 1 year). A telephone survey was carried out between September 2008 and June 2009 in smokers attended in a Smoking Cessation Clinic. All patients who have successfully completed treatment (3 months) were surveyed by telephone to determine their long-term abstinence. Those who remained abstinent were requested to attend the Smoking Cessation Clinic for biochemical validation (expired CO ≤10 ppm). The probability of remaining abstinent in the long-term was calculated using a Kaplan-Meier survival analysis. The treatment success rate at 3-months was 41.3% (538/1302) with no differences by sex 89% (479/538) among those located in the telephonic follow-up study and 47.6% (256/479) were abstinent without differences by sex (p = .519); abstinence was validated with CO less than 10 ppm in 191 of the 256 (53.9% men and 46.1% women). In the survival analysis, the probability of men and women remaining abstinent in the long-term was not significant. There are no differences by sex in the outcome of smoking cessation treatment that included gender-tailored components in the short and long term (> 1 year).

  4. Altered regulation of Akt signaling with murine cerebral malaria, effects on long-term neuro-cognitive function, restoration with lithium treatment.

    Directory of Open Access Journals (Sweden)

    Minxian Dai

    Full Text Available Neurological and cognitive impairment persist in more than 20% of cerebral malaria (CM patients long after successful anti-parasitic treatment. We recently reported that long term memory and motor coordination deficits are also present in our experimental cerebral malaria model (ECM. We also documented, in a murine model, a lack of obvious pathology or inflammation after parasite elimination, suggesting that the long-term negative neurological outcomes result from potentially reversible biochemical and physiological changes in brains of ECM mice, subsequent to acute ischemic and inflammatory processes. Here, we demonstrate for the first time that acute ECM results in significantly reduced activation of protein kinase B (PKB or Akt leading to decreased Akt phosphorylation and inhibition of the glycogen kinase synthase (GSK3β in the brains of mice infected with Plasmodium berghei ANKA (PbA compared to uninfected controls and to mice infected with the non-neurotrophic P. berghei NK65 (PbN. Though Akt activation improved to control levels after chloroquine treatment in PbA-infected mice, the addition of lithium chloride, a compound which inhibits GSK3β activity and stimulates Akt activation, induced a modest, but significant activation of Akt in the brains of infected mice when compared to uninfected controls treated with chloroquine with and without lithium. In addition, lithium significantly reversed the long-term spatial and visual memory impairment as well as the motor coordination deficits which persisted after successful anti-parasitic treatment. GSK3β inhibition was significantly increased after chloroquine treatment, both in lithium and non-lithium treated PbA-infected mice. These data indicate that acute ECM is associated with abnormalities in cell survival pathways that result in neuronal damage. Regulation of Akt/GSK3β with lithium reduces neuronal degeneration and may have neuroprotective effects in ECM. Aberrant regulation of Akt

  5. Combination Therapy with Losartan and Pioglitazone Additively Reduces Renal Oxidative and Nitrative Stress Induced by Chronic High Fat, Sucrose, and Sodium Intake

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2012-01-01

    Full Text Available We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47phox, and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.

  6. Long-term management of GERD in the elderly with pantoprazole

    Directory of Open Access Journals (Sweden)

    Carlo Calabrese

    2007-04-01

    Full Text Available Carlo Calabrese, Anna Fabbri, Giulio Di FeboDepartment of Internal Medicine and Gastroenterology, University of Bologna, ItalyAbstract: The prevalence of gastroesophageal reflux disease (GERD increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD.Keywords: GERD, long-term management, pantoprazole, safety, efficacy, tolerability

  7. Interventional devascularization for the treatment of upper gastrointestinal hemorrhage in patients with portal hypertension: mid-term to long-term results

    International Nuclear Information System (INIS)

    Liu Wei; Chen Hongbo; Chen Gensheng; Zhang Weiping; Zheng Qun

    2009-01-01

    Objective: To assess the mid-term to long-term results of interventional devascularization in the treatment of upper gastrointestinal hemorrhage in patients with portal hypertension. Methods: Interventional devascularization was performed in 49 patients with upper gastrointestinal hemorrhage due to portal hypertension caused by cirrhosis. The patients were followed up for 6-36 months after the procedure. The recurrence of bleeding, postoperative complications and outcome. were observed and analyzed. Results: The technical success rate was 98.0% (48 / 49) and the mortality was 2%. The re-bleeding occurrence rate at 1, 6, 12, 24 and 36 months was 0%, 2.1%, 12.5%, 24.5% and 27.9%, respectively. The causes of re-bleeding included re-rupture of varicose vein (25%), portal hypertensive gastropathy (58.3%) and peptic ulcer (16.7%). Conclusion: The interventional devascularization is a simple, safe and effective method for the treatment of upper gastrointestinal hemorrhage due to portal hypertension. (authors)

  8. Change in healthcare utilization and costs following initiation of benzodiazepine therapy for long-term treatment of generalized anxiety disorder: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Berger Ariel

    2012-10-01

    Full Text Available Abstract Background Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepine anxiolytics are used in the US to treat generalized anxiety disorder (GAD. While benzodiazepines typically provide rapid symptomatic relief, long-term use is not recommended due to risks of dependency, sedation, falls, and accidents. Methods Using a US health insurance database, we identified all persons with GAD (ICD-9-CM diagnosis code 300.02 who began a long-term course of treatment (≥90 days with a benzodiazepine anxiolytic between 1/1/2003 and 12/31/2007, We compared healthcare utilization and costs over the six-month periods preceding and following the date of treatment initiation (“pretreatment” and “post-treatment”, respectively, and focused attention on accident-related encounters (e.g., for treatment of fractures and care received for other reasons possibly related benzodiazepine use (e.g., sedation, dizziness. Results A total of 866 patients met all study entry criteria; 25% of patients began treatment on an add-on basis (i.e., adjunctive to escitalopram, paroxetine, sertraline, or venlafaxine, while 75% of patients did not receive concomitant therapy. Mean total healthcare costs increased by $2334 between the pretreatment and post-treatment periods (from $4637 [SD=$9840] to $6971 [$17,002]; p Conclusions Healthcare costs increase in patients with GAD beginning long-term (≥90 days treatment with a benzodiazepine anxiolytic; a substantial proportion of this increase is attributable to care associated with accidents and other known sequelae of long-term benzodiazepine use.

  9. Hydrocephalus treatment in children: long-term outcome in 975 consecutive patients.

    Science.gov (United States)

    Beuriat, Pierre-Aurelien; Puget, Stephanie; Cinalli, Giuseppe; Blauwblomme, Thomas; Beccaria, Kevin; Zerah, Michel; Sainte-Rose, Christian

    2017-07-01

    OBJECTIVE Hydrocephalus remains one of the more common pathologies managed in pediatric neurosurgical units. Endoscopic third ventriculostomy (ETV) has an advantage over ventriculoperitoneal shunting as it enables patients to remain device free. Multiple shunt devices with various valve designs exist, with no one valve proven to be superior to another. The aim of this study was to describe the management of hydrocephalus and its long-term outcome. METHODS The authors retrospectively reviewed the medical records of all patients who had been treated for hydrocephalus at the Hôpital Necker-Enfants Malades in the period from 1985 to 1995. RESULTS Nine hundred seventy-five children had been treated for hydrocephalus. The mean follow-up was 11 ± 7.4 years (mean ± standard deviation). The most common cause of hydrocephalus was tumor related (32.3%), followed by malformative (24.5%) and inflammatory (20.9%) causes. Two hundred eighty patients underwent ETV as the first-line treatment. The procedure was effective in controlling hydrocephalus due to posterior fossa tumors and aqueductal stenosis. Six hundred ninety-five children had initial shunt insertion, with the majority receiving an Orbis-Sigma valve (OSV). The overall OSV shunt survival was 70% at 1 year, 58% at 10 years, and 49% at 20 years. The most common cause for mechanical shunt failure was obstruction (50.7%). Overall shunt survival was statistically different between the OSV and the differential-pressure valve (p = 0.009). CONCLUSIONS Endoscopic third ventriculostomy is effective in the management of childhood hydrocephalus. Its success is directly related to the underlying pathology. In the long term, the OSV has significantly higher event-free shunt survival than the classic differential-pressure valve systems.

  10. Long-term safety and efficacy of autologous platelet lysate drops for treatment of ocular GvHD.

    Science.gov (United States)

    Pezzotta, S; Del Fante, C; Scudeller, L; Rossi, G C; Perotti, C; Bianchi, P E; Antoniazzi, E

    2017-01-01

    Current ocular GvHD (oGvHD) treatments are suboptimal. We investigated the safety and efficacy of long-term continuous treatment with autologous platelet lysate (PL) drops in patients with oGvHD Dry Eye Syndrome (DES) score 2-3 refractory to topical conventional therapy. Ophthalmic evaluation was performed at 6 month intervals. Symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were defined 'responders' when showing a reduction at least one grade on National Institutes of Health Eye Score from baseline at the 6 month visit. Thirty-one patients were included, and 16 (51%) completed 36 months of follow-up (range 6.5-72.7). At 6 months all patients were classified as responders: median GSS symptom score decreased from 70 to 41 (33 at 36 months), median GSS function score reduced from 68 to 46 (33 at 36 months) (all P<0.001). Median Tear Break Up Time improved from 3 to 6 s after 6 months and was maintained over time. All signs improved at 6 and 36 months (clinical and statistical significance). No severe adverse events occurred. Long-term treatment with PL drops is secure and effective for oGvHD and can be an efficient therapy option from initial stages of oGvHD to prevent permanent ocular impairment and improving quality of life.

  11. Functional interpretation of metabolomics data as a new method for predicting long-term side effects: treatment of atopic dermatitis in infants.

    Science.gov (United States)

    Lee, Seul Ji; Woo, Sung-il; Ahn, Soo Hyun; Lim, Dong Kyu; Hong, Ji Yeon; Park, Jeong Hill; Lim, Johan; Kim, Mi-kyeong; Kwon, Sung Won

    2014-12-10

    Topical steroids are used for the treatment of primary atopic dermatitis (AD); however, their associated risk of serious complications is great due to the presence of vulnerable lesions in young children with AD. Topical calcineurin inhibitors (TCIs) are steroid-free, anti-inflammatory agents used for topical AD therapy. However, their use is prohibited in infants side effects. The 1% pimecrolimus cream displayed similar efficacy and exceptional safety compared with the 0.05% desonide cream. Metabolomics-based long-term toxicity tests effectively predicted long-term side effects using short-term clinical models. This applicable method for the functional interpretation of metabolomics data sets the foundation for future studies involving the prediction of the toxicity and systemic reactions caused by long-term medication administration.

  12. Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men

    NARCIS (Netherlands)

    Bravenboer, N; Holzmann, PJ; ter Maaten, JC; Stuurman, LM; Roos, JC; Lips, P

    2005-01-01

    Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. Introduction: Adults with growth hormone (GH) deficiency have

  13. Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.

    Directory of Open Access Journals (Sweden)

    Francisco J Rubio

    2013-05-01

    Full Text Available Antidepressant drugs are usually administered for long time for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor fluoxetine to naϊve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of treatment with 0.7 mg/kg of fluoxetine on long-term potentiation (LTP and long-term depression (LTD in the Schaffer collateral-CA1 synapses and the perforant path-CA1 synapses. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum together with increased GluA2-containing, Ca2+-impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.

  14. Long term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Tate, David J.; Hunt, Sharon A.; Strober, Samuel; Hoppe, Richard T.

    1996-01-01

    Purpose: To evaluate the short and long term effects of total lymphoid irradiation (TLI) in the treatment of allograft rejection in cardiac transplant patients. Materials and Methods: From 1986 to 1995, 48 courses of TLI were delivered to 47 patients who had received cardiac transplants at Stanford University. In 38 cases, TLI was administered for chronic, intractable allograft rejection despite conventional anti-rejection therapy, including corticosteroids, azathioprine, cyclosporine, OKT3, DHPG, RATG, and methotrexate. Ten patients received TLI prophylactically, beginning radiation between 5 and 16 days after heart transplantation. The prescribed radiation dose was 800 cGy given in 80 cGy fractions twice weekly to all major lymph node regions using mantle and inverted Y fields. Patients continued to receive all medications except azathioprine which was held during TLI to prevent severe marrow suppression. All patients were closely monitored for episodes of rejection, infection, prednisone requirements, blood counts, and complications of treatment. Post-irradiation follow up ranged from 6 months to 9.1 years with a mean of 3.1 years. Results: The actual mean dose of radiation was 730 cGy delivered over a mean of 39 calendar days. Fifty six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, the frequency of rejection dropped from 0.46 episodes/patient/month before radiation to 0.14 episodes/patient/month during TLI (p 3 during TLI (p = 0.01) and remained low at 167.6 cells/mm 3 2-4 months after treatment (p = 0.05). CD8+ lymphocytes also decreased during treatment from 233.2 to 65.8 cells/mm 3 (p = 0.003) but rose significantly above normal to 381.3 cells/mm 3 2-4 months after TLI (p 0.05). Thus, the ratio of helper/suppresser T-cells was chronically decreased. Infection rates were not significantly different before, during or after

  15. Thin-plate spline analysis of mandibular morphological changes induced by early class III treatment: a long-term evaluation.

    Science.gov (United States)

    Franchi, Lorenzo; Pavoni, Chiara; Cerroni, Silvia; Cozza, Paola

    2014-08-01

    To evaluate the long-term mandibular morphological changes induced by early treatment of class III malocclusion with rapid maxillary expansion (RME) and facial mask (FM). Twenty-five subjects [10 boys, 15 girls; mean age at T1 (start of treatment) 9.3±1.6 years] with class III disharmony were treated with RME and FM therapy followed by fixed appliances. The patients were re-evaluated at the end of growth (T2), about 8.5 years after the end of the treatment (mean age, 18.6±2.0 years). Sixteen subjects with untreated class III malocclusion comprised the control group. Mandibular shape changes were analysed on the lateral cephalograms of the subjects of both groups by means of thin-plate spline (TPS) analysis. Procrustes average mandibular configurations were subjected to TPS analysis by means of both cross-sectional between-group comparisons at T1 and at T2 and longitudinal within-group comparisons. Statistical analysis of shape differences was performed using a generalized Goodall F test. In the long term, the treated group exhibited a significant upward and forward direction of condylar growth. On the contrary, untreated class III subjects showed an upward and backward direction of condylar growth associated with a downward and forward deformation of the mandibular symphysis. Limitations are related to the small sample size of both treated and control groups and to the retrospective nature of the study. Early treatment of class III malocclusion with RME and FM is able to produce significant and favourable long-term mandibular shape changes characterized by an anterior morphogenetic rotation. © The Author 2013. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Percutaneous imaging-guided treatment of hydatid liver cysts: Do long-term results make it a first choice?

    International Nuclear Information System (INIS)

    Kabaalioglu, Adnan; Ceken, Kagan; Alimoglu, Emel; Apaydin, Ali

    2006-01-01

    Aim: To evaluate the long-term results of percutaneous imaging-guided treatment of hydatid liver cysts. Materials and methods: Sixty patients with 77 hydatid liver cysts underwent percutaneous treatment with ultrasonography (US) or computed tomography (CT) guidance. Absolute alcohol and hypertonic saline were used for sclerosing the cysts after aspiration. Prophylactic albendazole treatment was given before and after the procedures. Follow-up US and CT were obtained periodically, and changes in cyst morphology were recorded. Minimum follow-up period for the patients included in this study was 12 months. Serological correlation was also available for a group of patients. The outcome of the procedures were categorized into five groups based on morphological changes observed by imaging. Results: Procedures were regarded as successful in 80% and unsuccessful in 20% of patients. Failures most often occurred with type III cysts; less than half (39%) of the total type III cysts had a successful outcome. On the other hand, all type I cysts ended up with cure. Anaphylaxis, pneumotorax and severe pain interrupting the procedures were also among the reasons of failure. Conclusion: Percutaneous aspiration, injection and reaspiration (PAIR) of types I and II hydatid liver cysts is effective and safe in the long-term. Surgery should no longer be regarded as the first choice treatment in all hydatid liver cysts but should be reserved for type III and certain active type IV cysts

  17. Percutaneous imaging-guided treatment of hydatid liver cysts: Do long-term results make it a first choice?

    Energy Technology Data Exchange (ETDEWEB)

    Kabaalioglu, Adnan [Department of Radiology, Akdeniz University Hospital, Antalya (Turkey)]. E-mail: adnank@akdeniz.edu.tr; Ceken, Kagan [Department of Radiology, Akdeniz University Hospital, Antalya (Turkey); Alimoglu, Emel [Department of Radiology, Akdeniz University Hospital, Antalya (Turkey); Apaydin, Ali [Department of Radiology, Akdeniz University Hospital, Antalya (Turkey)

    2006-07-15

    Aim: To evaluate the long-term results of percutaneous imaging-guided treatment of hydatid liver cysts. Materials and methods: Sixty patients with 77 hydatid liver cysts underwent percutaneous treatment with ultrasonography (US) or computed tomography (CT) guidance. Absolute alcohol and hypertonic saline were used for sclerosing the cysts after aspiration. Prophylactic albendazole treatment was given before and after the procedures. Follow-up US and CT were obtained periodically, and changes in cyst morphology were recorded. Minimum follow-up period for the patients included in this study was 12 months. Serological correlation was also available for a group of patients. The outcome of the procedures were categorized into five groups based on morphological changes observed by imaging. Results: Procedures were regarded as successful in 80% and unsuccessful in 20% of patients. Failures most often occurred with type III cysts; less than half (39%) of the total type III cysts had a successful outcome. On the other hand, all type I cysts ended up with cure. Anaphylaxis, pneumotorax and severe pain interrupting the procedures were also among the reasons of failure. Conclusion: Percutaneous aspiration, injection and reaspiration (PAIR) of types I and II hydatid liver cysts is effective and safe in the long-term. Surgery should no longer be regarded as the first choice treatment in all hydatid liver cysts but should be reserved for type III and certain active type IV cysts.

  18. A Controlled Single-Case Treatment of Severe Long-Term Selective Mutism in a Child with Mental Retardation

    Science.gov (United States)

    Facon, Bruno; Sahiri, Safia; Riviere, Vinca

    2008-01-01

    The aim of the present study was to demonstrate the efficacy of combining two operant learning procedures--shaping and fading--for treating selective mutism. The participant was a 12-year-old boy with mental retardation presenting a severe long-term selective mutism. The treatment was aimed at increasing the loudness of his vocalizations in an…

  19. LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.

    Science.gov (United States)

    Espinosa-de-Los-Monteros, Ana Laura; Sosa-Eroza, Ernesto; Espinosa, Etual; Mendoza, Victoria; Arreola, Rocio; Mercado, Moises

    2017-07-01

    Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD. We evaluated the hospital charts of 84 patients (77 female, median age 34 years, median follow up 6.3 years) with CD diagnosed, treated, and followed at our multidisciplinary clinic according to a pre-established protocol. Of the 81 patients who were initially treated with transsphenoidal surgery (TSS), 61.7% had a long-lasting remission, 16% had persistent disease, and 22% achieved remission but relapsed during follow-up. The most frequently used secondary treatment was pituitary re-intervention, followed by ketoconazole, RT, and BA. Early remissions were observed in 66.6% of the re-operated and in 58.3% of the radiated patients; long-lasting remission was achieved in 33.3% and 41.6% of these patients, respectively. Nelson syndrome developed in 41.6% of the patients who underwent BA. Upon last follow-up, 88% of all the patients are in remission, and 9.5% are biochemically controlled with ketoconazole. The efficacy of treatment alternatives for recurrent or persistent CD varies considerably among patients and multiple interventions are often required to achieve long-lasting remission. ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CBG = cabergoline; CD = Cushing disease; CV = coefficient of variation; DXM = dexamethasone; IQR = interquartile range; RT = radiation therapy; SRS = stereotactic radiosurgery; TSS = transsphenoidal surgery; UFC = urinary free cortisol; ULN = upper limit of normal.

  20. The effect of long-term dexfenfluramine treatment on 24-hour energy expenditure in man. A double-blind placebo controlled study

    DEFF Research Database (Denmark)

    Breum, L; Astrup, A; Andersen, T

    1990-01-01

    In order to investigate the effect of long-term treatment with dexfenfluramine (dF) on 24-hour energy expenditure (EE), 10 obese females were studied in a double-blind design. Shortly before and 4 weeks after cessation of a 13 months treatment period with either dF (30 mg/day) or placebo (PL...... differences. The conclusion is therefore that dF possesses no significant thermogenic effect during long-term administration in human obese subjects.......) the 24-hour EE was measured. The measurements were performed using a 24 m3 direct heat sink calorimeter with continuous real time measurements of evaporative and sensible heat losses. The patients performed a standardized program of exercise, rest and meals. The measurements were performed at 24 degrees...

  1. Long-term effects of pediatric extracorporeal shockwave lithotripsy on renal function

    Science.gov (United States)

    Akin, Yigit; Yucel, Selcuk

    2014-01-01

    Introduction Extracorporeal shock wave lithotripsy (ESWL) is a well-known and successful treatment modality. In addition, it can be used in premature infants. ESWL is used to treat kidney and ureter stones in children. However, although it is a preferred noninvasive treatment in that setting, there is debate about its long-term effects on growing kidneys in children. Objectives To investigate the long-term effects of pediatric ESWL on renal function in light of updated literature. Methods PubMed and Medline were searched for studies on ESWL in a pediatric population with keywords including efficacy, child, kidney calculi, ureter calculi, lithotripsy, injury, vascular trauma, and shock waves. The research was limited to the English literature during a period from 1980 to 2014. In total, 3,000 articles were evaluated, but only 151 papers were considered. Only the manuscripts directly related to the reviewed subjects were included in the current study. Results However, the acute effects of ESWL in kidney are well-described. Although there are limited studies on the long-term effects of ESWL in children, there is a widespread opinion that ESWL is not affecting renal functions in the long-term. Conclusion ESWL is a safe, effective, and noninvasive treatment option in children. Although ESWL can cause some acute effects in the kidney, there is no long-term effect on the growing kidneys of children. PMID:24892029

  2. Long-term treatment with probiotics in primary care patients with irritable bowel syndrome--a randomised, double-blind, placebo controlled trial

    DEFF Research Database (Denmark)

    Begtrup, Luise Mølenberg; de Muckadell, Ove B Schaffalitzky; Kjeldsen, Jens

    2013-01-01

    OBJECTIVE. Meta-analyses have indicated effect of probiotics on irritable bowel syndrome (IBS). However, few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting. We aimed to investigate the effect of probiotics compared...... with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up. MATERIAL AND METHODS. We randomized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp....../67) in the probiotic group versus 41% (26/64) in the placebo group, p = 0.18. Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment. Patients improved in HrQOL, but with no statistically significant difference between the groups. CONCLUSION. During a 6-month treatment...

  3. [Long-term psychiatric hospitalizations].

    Science.gov (United States)

    Plancke, L; Amariei, A

    2017-02-01

    Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

  4. Eating habits, weight reduction strategies and long-term treatment results in obese men : The "Gustaf" study

    OpenAIRE

    Andersson, Ingalena

    1997-01-01

    Eating habits, weight reduction strategies and long-term treatment resultsin obese men. The "Gustaf" study. Ingalena Andersson Obesity Unit and Health Behaviour Research, Department of Medicine, HuddingeHospital, Karolinska Institute, Stockholm, Sweden. Abdominal male obesity is associated with hypertension, abnormal blood lipidsand diabetes type 11. For development of a weight loss program for such males, 86obese men (BMI 37.7 [4.4] kg/m2) (mean [SD] ) from the wa...

  5. A gradual change between methanogenesis and sulfidogenesis during a long-term UASB treatment of sulfate-rich chemical wastewater.

    Science.gov (United States)

    Wu, Jiang; Niu, Qigui; Li, Lu; Hu, Yong; Mribet, Chaimaa; Hojo, Toshimasa; Li, Yu-You

    2018-04-25

    The competition between methane-producing archaea and sulfate-reducing bacteria is an important topic in anaerobic wastewater treatment. In this study, an Up-flow Anaerobic Sludge Blanket Reactor (UASB) was operated for 330 days to evaluate the treatment performance of sulfate-rich wastewater. The effects of competition change between methane production and sulfate reduction on the organic removal efficiency, methane production, and electrons allocation were investigated. Synthetic wastewater was composed of ethanol and acetate with a chemical oxygen demand (COD)/SO 4 2- of 1.0. As a result, the COD removal efficiency achieved in long-term treatment was higher than 90%. During the initial stage, methane production was the dominant reaction. Sulfate-reducing bacteria (SRB) could only partially oxidize ethanol to acetate, and methane-producing archaea (MPA) utilized acetate for methane production. Methane production declined gradually over the long-term operation, whereas the sulfate-reducing efficiency increased. However, UASB performed well throughout the experiment because there was no significant inhibition. After the complete reduction of the sulfate, MPA converted the remaining COD into methane. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study.

    Science.gov (United States)

    Stumbo, Scott P; Ford, James H; Green, Carla A

    2017-11-01

    A greater understanding of the factors that influence long-term sustainment of quality improvement (QI) initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007-2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1) finding alignment between business- and client-centered practices; (2) staff engagement early in QI process added legitimacy which facilitated sustainment; (3) commitment to integrating data into monitoring practices and the identification of a data champion; and (4) adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1) lack of evidence of impact on business practices led to discontinuation; (2) disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3) no data integration into overall business practices and no identified data champion; and (4) high staff turnover. In addition, we found that many agencies' current use of NIATx methods and tools suggested a legacy effect that might improve quality elsewhere, even absent overall sustainment of

  7. AD-venture program: therapeutic biking for the treatment of depression in long-term care residents with dementia.

    Science.gov (United States)

    Buettner, Linda L; Fitzsimmons, Suzanne

    2002-01-01

    This project tested an innovative intervention in a controlled clinical investigation of a nonpharmacological treatment of depression in long-term care residents with dementia. This treatment utilized a wheelchair bicycle in a recreation therapy protocol, which combined small group activity therapy and one-to-one bike rides with a staff member. Depression levels were significantly reduced in the two-week portion of the study with levels maintained in the 10-week maintenance period. Improvements were also found in sleep and levels of activity engagement.

  8. Role of water balance in the long-term stability of hazardous waste site cover treatments

    International Nuclear Information System (INIS)

    Barnes, F.J.; Rodgers, J.C.; Trujillo, G.

    1986-01-01

    After the 30-year post-closure maintenance period at hazardous waste landfills, long-term stability must be assured without continued intervention. Understanding water balance in the established vegetative cover system is central to predicting such stability. A Los Alamos National Laboratory research project has established a series of experimental cover treatment plots on a closed waste disposal site which will permit the determination of the effects of such critical parameters as soil cover design, leaf area index, and rooting characteristics on water balance under varied conditions. Data from these experiments are being analyzed by water balance modeling and other means. The results show consistent differences in soil moisture storage between soil profiles and between vegetation cover treatments

  9. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer

    International Nuclear Information System (INIS)

    Byrne, J.; Mulvihill, J.J.; Myers, M.H.

    1987-01-01

    In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease

  10. Combined motor disturbances following severe traumatic brain injury: an integrative long-term treatment approach.

    Science.gov (United States)

    Keren, O; Reznik, J; Groswasser, Z

    2001-07-01

    Patients surviving severe traumatic brain injury (TBI) often suffer from residual impairments in motor control, communication skills, cognition and social behaviour. These distinctly hamper their capability to return to their 'pre-trauma' activity. Comprehensive and integrated rehabilitation programmes initiate, during the acute phase, a prolonged treatment process which starts at the most sophisticated medical systems. There is no clear end point for the treatment of these patients, since the recovery process and the rehabilitation activity may continue for years, even after patients return home to live with their families. The inherent inability to make a firm early prediction regarding outcome of patients and the late appearance of additional symptoms stress the need for a comprehensive close long-term follow-up. The following presentation concerns the description of the treatment strategy and long-term improvement of a 22-year-old male who suffered from very severe TBI. On admission to the emergency room, he was in the decerebrated position and his Glasgow Coma Scale (GCS) was at the lowest (3). The focus of this presentation is on the recovery of motor function. The initial motor disabilities included weakness in all four limbs, in particular left hemiplegia, and right hemiparesis with severe bilateral ataxic elements and a marked tremor of the right arm. Range of motion was limited in hips, and he suffered from stiff trunk and neck. Goals of physiotherapy were directed towards improving range of motion (ROM) and active movement. Casting, use of orthoses, biofeedback, hydrotherapy, hippotherapy, medication and nerve blocks for reducing spasticity were timely applied during the process. The motor improvement in this very severe TBI patient who is now over 3 years post-injury still continues and has a functional meaning. He has succeeded in being able to stand up by himself from a chair and is able to walk unaided and without orthoses for very short distances

  11. Long-term follow-up and treatment of congenital alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Muensterer Oliver J

    2011-08-01

    Full Text Available Abstract Background Clinical presentation, diagnosis, management and outcome of molecularly defined congenital pulmonary alveolar proteinosis (PAP due to mutations in the GM-CSF receptor are not well known. Case presentation A 2 1/2 years old girl was diagnosed as having alveolar proteinosis. Whole lung lavages were performed with a new catheter balloon technique, feasible in small sized airways. Because of some interstitial inflammation in the lung biopsy and to further improve the condition, empirical therapy with systemic steroids and azathioprin, and inhaled and subcutaneous GMCSF, were used. Based on clinical measures, total protein and lipid recovered by whole lung lavages, all these treatments were without benefit. Conversely, severe respiratory viral infections and an invasive aspergillosis with aspergilloma formation occurred. Recently the novel homozygous stop mutation p.Ser25X of the GMCSF receptor alpha chain was identified in the patient. This mutation leads to a lack of functional GMCSF receptor and a reduced response to GMCSF stimulation of CD11b expression of mononuclear cells of the patient. Subsequently a very intense treatment with monthly lavages was initiated, resulting for the first time in complete resolution of partial respiratory insufficiency and a significant improvement of the overall somato-psychosocial condition of the child. Conclusions The long term management from early childhood into young adolescence of severe alveolar proteinosis due to GMCSF receptor deficiency requires a dedicated specialized team to perform technically demanding whole lung lavages and cope with complications.

  12. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  13. Long-term effects of an intracavitary treatment with californium-252 on normal tissue

    International Nuclear Information System (INIS)

    Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

    1976-01-01

    About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with 252 Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from 252 Cf and 7000 rad from 226 Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for 252 Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from 252 Cf and 5000 rad from 226 Ra

  14. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye.

    Science.gov (United States)

    Koh, Shizuka; Ikeda, Chikako; Takai, Yoshihiro; Watanabe, Hitoshi; Maeda, Naoyuki; Nishida, Kohji

    2013-09-01

    To evaluate the preliminary long-term efficacy of diquafosol ophthalmic solution for aqueous-deficient dry eye. Fifteen patients with mild-to-moderate aqueous-deficient dry eye were enrolled. After a washout period, the patients were treated with 3 % diquafosol ophthalmic solution for 6 months. We assessed 12 subjective dry eye symptoms, corneal and conjunctival staining with fluorescein, tear film break-up time (BUT), lower tear meniscus height measured with anterior-segment optical coherence tomography, Schirmer's testing, and adverse reactions at baseline and 1, 3, and 6 months after the start of treatment. Treatment with diquafosol ophthalmic solution significantly improved dry eye symptoms, corneal staining, BUT, and tear meniscus height at 1 month and maintained the effectiveness for 6 months. Conjunctival staining significantly improved 3 and 6 months after treatment. No significant adverse reactions developed. Prolonged use of diquafosol ophthalmic solution for 6 months produced significant improvement both subjectively (dry eye symptom score) and objectively (ocular staining score and tear function tests) for aqueous-deficient dry eye.

  15. Clinical research and long-term follow-up of early hypothyroidism after 131I treatment for hyperthyroidism

    International Nuclear Information System (INIS)

    Liu Jianfeng; Zhang Youren; Xing Jialiu; Ye Genyao

    2004-01-01

    Objective: To evaluate the clinical research and long-term follow-up results of early hypothyroidism after 131 I treatment for hyperthyroidism. Methods: One hundred and forty-five patients with hyperthyroidism who developed hypothyroidism within 12 months after 131 I therapy were evaluated by clinical symptoms and plasma T 3 , T 4 , thyroid-stimulating hormone (TSH). One year after treatment, 121 of 145 patients were divided into two groups according to the occurrence of hypothyroidism. Results: 1) Group 1: transient hypothyroidism (n=33), 64%(21/33) of the patients developed euthyroidism and 36%(12/33) patients had recurrent hyperthyroidism within 1 year after being diagnosed with hypothyroidism after 131 I treatment. The long-term follow-up showed 2 patients were with euthyroidism and 2 patients who were previously with hyperthyroidism developed permanent hypothyroidism after 3 months ∼6 years. Three patients who were previously with hyperthyroidism developed euthyroidism after 3 months ∼5 years. Group 2: permanent hypothyroidism (n=88), 82.95% (73/88) patients of group 2 were treated with low-dose 131 I, 86.36% (76/88) cases of this group were found with clinical hypothyroidism. Conclusions: 72.73% (88/121) patients of early hypothyroidism after 131 I therapy developed permanent hypothyroidism. The incidence of permanent hypothyroidism in the patients treated with low-dose 131 I was higher. Recovery of transient hypothyroidism after 131 I therapy did not predict future thyroid function. (authors)

  16. Testicular function in young men in long-term remission after treatment for the early stages of Hodgkin's disease

    DEFF Research Database (Denmark)

    Specht, L; Geisler, C; Hansen, M M

    1984-01-01

    16 young men in long-term remission after standard treatment for the early stages of Hodgkin's disease were examined for testicular function 48 to 125 months after termination of therapy. The patients had received mantle field irradiation, plus either irradiation of infradiaphragmatic lymph nodes...... to chemotherapy, especially including alkylating agents....

  17. Short and long term effectiveness of a subject's specific novel brain and vestibular rehabilitation treatment modality in combat veterans suffering from PTSD

    Directory of Open Access Journals (Sweden)

    Frederick Robert Carrick

    2015-06-01

    Full Text Available AbstractIntroduction: Treatment for post-traumatic stress disorder (PTSD in combat veterans that have a long-term positive clinical effect has the potential to modify the treatment of PTSD. This outcome may result in changed and saved lives of our service personnel and their families. In a previous before-after-intervention study we demonstrated high statistical and substantively significant short-term changes in the Clinician Administered DSM-IV PTSD Scale (CAPS scores after a two week trial of a subject's particular novel brain and vestibular rehabilitation (VR program. The long-term maintenance of PTSD severity reduction was the subject of this study.Material and Methods:We studied the short and long term effectiveness of a subject's particular novel brain and VR treatment of PTSD in subjects who had suffered combat-related traumatic brain injuries in terms of PTSD symptom reduction. The trial was registered as ClinicalTrials.gov Identifier: NCT02003352. We analyzed the difference in the CAPS scores pre and post treatment (one week and three months using our subjects as their matched controls. Results:The generalized least squares (GLS technique demonstrated that with our 26 subjects in the 3 timed groups the R2 within groups was 0.000, R2 between groups was 0.000 and overall the R2 was 0.000. The GLS regression was strongly statistically significant z = 21.29, p < 0.001, 95% CI [58.7, 70.63]. The linear predictive margins over time demonstrated strong statistical and substantive significance of decreasing PTSD severity scores for all timed CAPS tests.Discussion:Our investigation has the promise of the development of superior outcomes of treatments in this area that will benefit a global society. The length of the treatment intervention involved (two weeks is less that other currently available treatments and has profound implications for cost, duration of disability and outcomes in the treatment of PTSD in combat veterans.

  18. Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.

    Science.gov (United States)

    Anderson, George M; Scahill, Lawrence; McCracken, James T; McDougle, Christopher J; Aman, Michael G; Tierney, Elaine; Arnold, L Eugene; Martin, Andrés; Katsovich, Liliya; Posey, David J; Shah, Bhavik; Vitiello, Benedetto

    2007-02-15

    The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.

  19. Long-Term Clinical Practice Experience with Cinacalcet for Treatment of Hypercalcemic Hyperparathyroidism after Kidney Transplantation

    Science.gov (United States)

    Gessl, Alois; Borchhardt, Kyra

    2015-01-01

    Within this prospective, open-label, self-controlled study, we evaluated the long-term effects of the calcimimetic cinacalcet on calcium and phosphate homeostasis in 44 kidney transplant recipients (KTRs) with hypercalcemic hyperparathyroidism by comparing biochemical parameters of mineral metabolism between pre- and posttreatment periods. Results are described as mean differences (95% CIs) between pre- and posttreatment medians that summarize all repeated measurements of a parameter of interest between the date of initial hypercalcemia and cinacalcet initiation (median of 1.6 (IQR: 0.6–3.8) years) and up to four years after treatment start, respectively. Cinacalcet was initiated after 1.8 (0.8–4.7) years posttransplant and maintained for 6.2 (3.9–7.6) years. It significantly decreased total serum calcium (−0.30 (−0.34 to −0.26) mmol/L, P hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs. PMID:25861621

  20. Long-term progress of six cases of malignant peripheral nerve sheath tumors of the mediastinum that underwent surgical treatment: Case report series

    Directory of Open Access Journals (Sweden)

    Yuki Nakajima

    2016-01-01

    Discussion and conclusions: Nerve sheath tumors localized within the membrane offer good long-term prognosis even if malignant. Furthermore, long-term survival is possible even if the tumor has invaded neighboring organs, provided it can be completely excised. In cases where complete excision is difficult, a multidisciplinary approach including radiotherapy and anti-cancer drug treatment may contribute to improved prognosis but this is a subject that requires further study.

  1. Disrupted Bone Metabolism in Long-Term Bedridden Patients.

    Science.gov (United States)

    Eimori, Keiko; Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

    2016-01-01

    Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

  2. Speech-language pathology care and short- and long-term outcomes of oropharyngeal cancer treatment in the elderly.

    Science.gov (United States)

    Webster, Kimberly T; Tippett, Donna; Simpson, Marissa; Abrams, Rina; Pietsch, Kristine; Herbert, Robert J; Eisele, David W; Gourin, Christine G

    2018-06-01

    To examine associations between speech-language pathology (SLP) care and pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients treated for oropharyngeal squamous cell cancer (SCCA). Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. SLP care was documented in 25% of patients. High-volume hospital care (odds ratio (OR) = 3.2 [1.0-10.0]) and dysphagia during treatment (OR = 13.0 [3.6-47.1]) were the only significant predictors of SLP care during the initial treatment period. SLP care was significantly more likely during the first year (OR = 5.3 [3.1-9.1]) and second year (OR = 4.5 [2.4-8.2]) following initial treatment. Subsequent dysphagia (OR = 32.5 [16.9-62.4]), stricture (OR = 2.2 [1.2-4.0]), gastrostomy (OR = 1.7 [1.1-2.7]), and tracheostomy tube use (OR = 2.4 [1.2-4.8]) were significantly associated with long-term SLP care. After controlling for patient, tumor, and treatment-related variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (93%), stricture (35%), weight loss (8%), and airway obstruction (34%). Survival analysis, controlling for all other variables, demonstrated improved survival for patients under SLP care (hazard ratio = 0.73 [0.57-0.95]). SLP care is underutilized in elderly oropharyngeal SCCA patients and largely utilized after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care in this population during the initial treatment period and beyond. 2c. Laryngoscope, 128:1403-1411, 2018. © 2017 The American Laryngological, Rhinological and Otological Society

  3. Lanthanum-modified drinking water treatment residue for initial rapid and long-term equilibrium phosphorus immobilization to control eutrophication.

    Science.gov (United States)

    Wang, Changhui; Wu, Yu; Wang, Youquan; Bai, Leilei; Jiang, Helong; Yu, Juhua

    2018-06-15

    This study presents an approach for developing inactivating materials to achieve an initial rapid and a long-term equilibrium P immobilization to control eutrophication based on drinking water treatment residue (DWTR), which is a byproduct of potable water production. By taking advantage of the long-term equilibrium P adsorption by DWTR, the La chemical properties, and the previous success of using La-modified bentonite clay (Phoslock ® ), we used DWTR as a La carrier with different ratios to develop the specific materials. The La loading mechanisms, the potentially toxic effect of La-modified DWTR on snail Bellamya aeruginosa (within 120 d), and the short- and long-term (within 80 d) P immobilization characteristics of the modified DWTR were investigated to understand the performance of the developed materials. The results showed that La loading into DWTR was based on ligand exchanges and the formation of new particles; DWTR loaded with <5% La had no toxicity against the snail. Most importantly, the loading of 5% La to DWTR substantially enhanced the rapid immobilization capacity of DWTR, achieving an initial rapid and a long-term equilibrium P adsorption in aqueous solutions. This study promotes the beneficial recycling of DWTR and results in a win-win situation for lake restoration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Effects of long-term alendronate treatment on bone mineralisation, resorption parameters and biomechanics of single human vertebral trabeculae

    Directory of Open Access Journals (Sweden)

    M Krause

    2014-09-01

    Full Text Available Due to their well-established fracture risk reduction, bisphosphonates are the most frequently used therapeutic agent to treat osteoporosis. Bisphosphonates reduce fracture risk by suppressing bone resorption, but the lower bone turnover could have a negative impact on bone quality at the tissue level. Here, we directly assess the structural and mechanical characteristics of cancellous bone from the lumbar vertebrae (L5 in non-treated osteoporotic controls (n = 21, mid-term alendronate-treated osteoporotic patients (n = 6, and long-term alendronate-treated osteoporotic patients (n = 7. The strength and toughness of single trabeculae were evaluated, while the structure was characterised through measurements of microdamage accumulation, mineralisation distribution, and histological indices. The alendronate-treated cases had a reduced eroded surface (ES/BS, p < 0.001 and a higher bone mineralisation in comparison to non-treated controls (p = 0.037, which is indicative of low turnover associated with treatment. However, the amount of microdamage and the mechanical properties were similar among the control and treatment groups. As the tissue mineral density (TMD increased significantly with alendronate treatment compared to non-treated osteoporotic controls, the reduction in resorption cavities could counterbalance the higher TMD allowing the alendronate-treated bone to maintain its mechanical properties and resist microdamage accumulation. A multivariate analysis of the possible predictors supports the theory that multiple factors (e.g., body mass index, TMD, and ES/BS can impact the mechanical properties. Our results suggest that long-term alendronate treatment shows no adverse impact on mechanical cancellous bone characteristics.

  5. [Challenge and treatment strategy for ocular surface damage in patients with long term use of antiglaucoma drugs].

    Science.gov (United States)

    He, Xiang-Ge

    2011-02-01

    Long term use of topical anti-glaucoma drugs has been shown to induce chronic conjunctivitis, superficial punctate keratitis (SPK) and dry eye symptom. Under these conditions, a loss of goblet cells in conjunctiva, epithelial squamous metaplasia and apoptosis were morphologically revealed. Benzalkonium Chloride (BKC), a most frequently used preservative in eye drops, has been found to be an important factor causing ocular surface damage. Furthermore, a big challenge for ophthalmologists is that toxic damage of medication to ocular surface tissues is mild, poor specificity, and delayed manifestation in patients, especially when coexisting with other ocular surface diseases. Impairment of ocular surface tissues greatly impacts the life quality of patients and subsequently influences compliance with glaucoma therapy. This paper emphasizes to take measures to prevent ocular surface tissue damage resulted from chronic use of topical anti-glaucoma drugs and further discusses the treatment strategy. Effective and long-lasting action drugs should always be selected for glaucomatous patients in order to decrease the frequency of topical instillation or at a more expensive medication, a fixed combination formula can be considered for glaucoma therapy. An early surgery or laser treatment is also proposed for the patients who require an IOP reduction with an existing ocular surface impairment. Future investigation and development of new medications with long-term efficacy and appropriate BKC are suggested and preservative-free or drugs with new preservative materials recommended.

  6. Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment Resting State fMRI and Random Forest Machine Learning.

    Science.gov (United States)

    Kesler, Shelli R; Rao, Arvind; Blayney, Douglas W; Oakley-Girvan, Ingrid A; Karuturi, Meghan; Palesh, Oxana

    2017-01-01

    We aimed to determine if resting state functional magnetic resonance imaging (fMRI) acquired at pre-treatment baseline could accurately predict breast cancer-related cognitive impairment at long-term follow-up. We evaluated 31 patients with breast cancer (age 34-65) prior to any treatment, post-chemotherapy and 1 year later. Cognitive testing scores were normalized based on data obtained from 43 healthy female controls and then used to categorize patients as impaired or not based on longitudinal changes. We measured clustering coefficient, a measure of local connectivity, by applying graph theory to baseline resting state fMRI and entered these metrics along with relevant patient-related and medical variables into random forest classification. Incidence of cognitive impairment at 1 year follow-up was 55% and was predicted by classification algorithms with up to 100% accuracy ( p breast cancer. This information could inform treatment decision making by identifying patients at highest risk for long-term cognitive impairment.

  7. The needs of the caregiver in the long-term treatment of Alzheimer disease.

    Science.gov (United States)

    Bullock, Roger

    2004-01-01

    The long-term well-being of caregivers should be included as part of the treatment of patients with Alzheimer disease (AD). Throughout the process of caring for patients with AD, caregivers frequently experience social, emotional, physical, and financial losses, which become more significant as the disease progresses. Minimizing these losses is a goal in the overall management of AD. Successful treatment of the patient has been shown to positively impact quality of life for the caregiver. Randomized, controlled studies of acetylcholinesterase inhibitors (AChEIs) have demonstrated the effectiveness of these agents in stabilizing cognitive function and delaying behavioral symptoms. Moreover, a decrease in the incidence of nursing home placement has been associated with this therapy. The growing burden of AD on families and society as a whole warrants the investigation of ways to minimize the impact of AD. AChEIs play an important role in this effort. Further studies are needed to more closely examine the impact of specific AChEIs on caregiver burden.

  8. Long-term self-reported treatment effects and experience of radiofrequency-induced thermotherapy of the inferior turbinates performed under local anesthesia: a retrospective analysis.

    Science.gov (United States)

    Safiruddin, F; Vroegop, A V M T; Ravesloot, M J L; de Vries, N

    2013-05-01

    Nasal obstruction due to inferior turbinate hypertrophy is a common complaint. Radiofrequency-induced thermotherapy of the inferior turbinates (RFITT) under local anesthesia is now a widely used treatment, however reports of assessment of the long-term self-reported benefits and patient satisfaction of the treatment are scarce. This study focuses on the self-reported long-term effects of treatment and experience of RFITT. A questionnaire was sent to 441 patients who underwent RFITT in our clinic to treat symptoms of impaired nasal passage due to enlarged inferior turbinates. All patients had enlarged inferior turbinates on nasal examination. Patients were included if RFITT was done under local anaesthesia, was performed more than a year before the questionnaire was forwarded and on the indication-significant nasal obstruction because of enlarged inferior turbinates. Improvement of nasal breathing (by means of a Visual Analog Scale, VAS), changes in use of nasal spray (VAS), usage of pain medication, patient friendliness of the treatment, complaints reported after treatment, permanent effect of treatment during day and night time and willingness to recommend treatment to others were analyzed. No significant post-operative complications were observed. There was a significant reduction in use of nasal spray and the majority of patients interviewed reported long-term positive effects of RFITT during the daytime. This study shows that RFITT performed under local anesthesia is a valuable, minimally invasive, patient-friendly and well-tolerated treatment in patients with impaired nasal passage due to inferior turbinate hypertrophy.

  9. Additive effects of glucagon-like peptide 1 and pioglitazone in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, Mette; Christiansen, Allan; Madsbad, Sten

    2004-01-01

    .01). Glucagon levels were reduced in GLP-1 and combination therapy compared with saline and monotherapy with pioglitazone (P breakfast (area under the curve, 0-3 h) were reduced in combination therapy compared with saline (P = 0.03). Sensation of appetite was reduced during monotherapy...

  10. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus

    NARCIS (Netherlands)

    van der Meer, Rutger W.; Rijzewijk, Luuk J.; de Jong, Hugo W. A. M.; Lamb, Hildo J.; Lubberink, Mark; Romijn, Johannes A.; Bax, Jeroen J.; de Roos, Albert; Kamp, Otto; Paulus, Walter J.; Heine, Robert J.; Lammertsma, Adriaan A.; Smit, Johannes W. A.; Diamant, Michaela

    2009-01-01

    Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy

  11. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  12. Pediatric polytrauma : Short-term and long-term outcomes

    NARCIS (Netherlands)

    vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

    Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

  13. Regional cerebral blood flow in Alzheimer's disease. Comparison between short and long-term donepezil therapy

    International Nuclear Information System (INIS)

    Ushijima, Yo; Okuyama, Chio; Kubota, Takao; Nakai, Takako; Nishimura, Tsunehiko; Mori, Satoru

    2006-01-01

    Treatment with donepezil improves cognitive function of patients with Alzheimer's disease (AD) when compared to a placebo-controlled group. The purpose of this study was to investigate changes in regional cerebral blood flow (rCBF) of AD patients in short-term and long-term treatment with donepezil. rCBF was measured by N-isopropyl-p- 123 I-iodoamphetamine (IMP) autoradiography method. CBF measurements were performed in 17 AD patients before treatment and after 3 months (short-term therapy) and 1 year (long-term therapy). Regions of interest were set at cerebral cortex and cerebellar hemisphere. We used absolute CBF and relative CBF expressed as ratio to cerebellar CBF. Significant increases in relative rCBF were noted in the frontal, parietal and temporal lobes at the end of short-term therapy. rCBF was decreased after the long-term therapy, whereas rCBF was still increased to a slight extent, as compared with the pre-treatment levels. Absolute rCBF showed minimal change and a tendency to decline. Relative rCBF significantly increased in the short-term donepezil therapy, while following the long-term therapy, rCBF decreased to the pre-treatment level. (author)

  14. Long-term outcomes of unilateral transtibial amputations.

    Science.gov (United States)

    Ebrahimzadeh, Mohamad H; Hariri, Sanaz

    2009-06-01

    the long-term outcomes of wartime transtibial amputations have not been well documented. The purpose of this case series is to present the long-term functional, social, and psychological outcomes of modern-day military unilateral transtibial amputees. the Iranian Veterans Administration of the Khorasan province invited their Iranian military amputees from the Iran-Iraq War (1980-1988) to its medical center for evaluation. The patients filled out a detailed questionnaire and were interviewed and examined by each team member. two hundred (77%) of the 260 invited amputees were willing and able to come back for follow-up. Ninety-six of these patients (48%) were unilateral transtibial amputation. The average follow-up was 17.4 years (range 15-22 years). Land mines were the leading cause of war injury necessitating a transtibial amputation (68%). The most common symptoms about their amputated limbs were phantom sensations (54%), phantom pain (17%), and stump pain (42%). Lower back pain, contralateral (nonamputated limb) knee pain, and ipsilateral (amputated limb) knee pain were reported by 44%, 38%, and 13% of subjects, respectively. Sixty-five percent of patients were employed or had been employed for multiple years after their war injury. All patients were married, and 97% had children. Fifty-four percent of amputees reported psychological problems; 26% were currently utilizing psychological support services. at long-term follow-up, most military transtibial amputees experienced phantom sensation or some type of stump pain. More than half had persistent psychiatric problems, but only about half of these patients were receiving psychological treatment. Although this case series reports the status of these amputees, the next step would be to prospectively follow modern wartime amputees using standardized, validated outcome measures. With the goal of optimizing long-term amputee outcomes, researchers should correlate outcomes with demographics, injury characteristics, and

  15. Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

    Science.gov (United States)

    Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

    2017-09-01

    Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

  16. Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality: A randomized controlled trial

    NARCIS (Netherlands)

    Zuidersma, M.; Conradi, H.J.; van Melle, J.P.; Ormel, J.; de Jonge, P.

    2013-01-01

    Objective: Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infarction (MI)-patients on long-term cardiovascular outcomes and all-cause mortality. Methods: MI-patients were evaluated for the presence of a diagnosis of post-MI depression at 3, 6, 9

  17. Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality : A randomized controlled trial

    NARCIS (Netherlands)

    Zuidersma, Marij; Conradi, Henk Jan; van Melle, Joost P.; Ormel, Johan; de Jonge, Peter

    Objective: Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infarction (MI)-patients on long-term cardiovascular outcomes and all-cause mortality. Methods: MI-patients were evaluated for the presence of a diagnosis of post-MI depression at 3, 6, 9

  18. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma

    DEFF Research Database (Denmark)

    Jacobsen, L; Niggemann, B; Dreborg, S

    2007-01-01

    BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. OBJECTIVE: We......: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination....

  19. Short- and long-term subjective medical treatment outcome of trauma surgery patients: the importance of physician empathy

    Directory of Open Access Journals (Sweden)

    Steinhausen S

    2014-09-01

    Full Text Available Simone Steinhausen,1 Oliver Ommen,2 Sunya-Lee Antoine,1 Thorsten Koehler,3 Holger Pfaff,4 Edmund Neugebauer11Institute for Research in Operative Medicine (IFOM, Witten/Herdecke University, Campus Cologne-Merheim, Germany; 2Federal Centre for Health Education (BZgA, Cologne, Germany; 3Institute for Applied Social Sciences (infas, Bonn, Germany; 4Institute for Medical Sociology, Health Services Research and Rehabilitation Science (IMVR, Faculty of Human Science and Faculty of Medicine, University of Cologne, Germany Purpose: To investigate accident casualties’ long-term subjective evaluation of treatment outcome 6 weeks and 12 months after discharge and its relation to the experienced surgeon’s empathy during hospital treatment after trauma in consideration of patient-, injury-, and health-related factors. The long-term results are compared to the 6-week follow-up outcomes.Patients and methods: Two hundred and seventeen surgery patients were surveyed at 6 weeks, and 206 patients at 12 months after discharge from the trauma surgical general ward. The subjective evaluation of medical treatment outcome was measured 6 weeks and 12 months after discharge with the respective scale from the Cologne Patient Questionnaire. Physician Empathy was assessed with the Consultation and Relational Empathy Measure. The correlation between physician empathy and control variables with the subjective evaluation of medical treatment outcome 12 months after discharge was identified by means of logistic regression analysis under control of sociodemographic and injury-related factors.Results: One hundred and thirty-six patients were included within the logistic regression analysis at the 12-month follow-up. Compared to the 6-week follow-up, the level of subjective evaluation of medical treatment outcome was slightly lower and the association with physician empathy was weaker. Compared to patients who rated the empathy of their surgeon lower than 31 points, patients

  20. Long-term effect of urethral dilatation and internal urethrotomy for urethral strictures.

    Science.gov (United States)

    Veeratterapillay, Rajan; Pickard, Rob S

    2012-11-01

    Urethral dilatation and direct visual internal urethrotomy (DVIU) are widely used minimally invasive options to manage men with urethral strictures. Advances in open urethroplasty with better long-term cure rates have fuelled the continuing debate as to which treatment is best for primary and recurrent urethral strictures. We reviewed recent literature to identify contemporary practice of urethral dilatation and DVIU and the long-term outcome of these procedures. Systematic literature search for the period January 2010 to December 2011 showed that urethral dilatation and DVIU remain frequently used treatment options as confirmed by surveys of urologists in the USA and the Netherlands. Multiple reports of laser DVIU confirm the safety of this approach but long-term data were lacking. Stricture free rates from urethra dilatation and DVIU vary from 10 to 90% at 12 months, although adjunctive intermittent self-dilatation can reduce time to recurrence. Although quality-of-life benefit appears good in the short term, repeated procedures may harm sexual function in the long-term. Urethral dilatation and DVIU remain widely used in urethral stricture management but high-level comparative evidence of benefit and harms against urethroplasty in the short and long-term is still lacking.

  1. Long-term preservation of anammox bacteria.

    Science.gov (United States)

    Rothrock, Michael J; Vanotti, Matias B; Szögi, Ariel A; Gonzalez, Maria Cruz Garcia; Fujii, Takao

    2011-10-01

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass was frozen or lyophilized at two different freezing temperatures (-60°C and in liquid nitrogen (-200°C)) in skim milk media (with and without glycerol), and the reactivation of anammox activity was monitored after a 4-month storage period. Of the different preservation treatments tested, only anammox biomass preserved via freezing in liquid nitrogen followed by lyophilization in skim milk media without glycerol achieved stoichiometric ratios for the anammox reaction similar to the biomass in both the parent bioreactor and in the freshly harvested control treatment. A freezing temperature of -60°C alone, or in conjunction with lyophilization, resulted in the partial recovery of the anammox bacteria, with an equal mixture of anammox and nitrifying bacteria in the reactivated biomass. To our knowledge, this is the first report of the successful reactivation of anammox biomass preserved via sub-zero freezing and/or lyophilization. The simple preservation protocol developed from this study could be beneficial to accelerate the integration of anammox-based processes into current treatment systems through a highly efficient starting anammox biomass.

  2. LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA.

    Science.gov (United States)

    Schumer, Maya C; Panza, Kaitlyn E; Mulqueen, Jilian M; Jakubovski, Ewgeni; Bloch, Michael H

    2015-10-01

    To examine long-term outcome in children with trichotillomania. We conducted follow-up clinical assessments an average of 2.8 ± 0.8 years after baseline evaluation in 30 of 39 children who previously participated in a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) for pediatric trichotillomania. Our primary outcome was change in hairpulling severity on the Massachusetts General Hospital Hairpulling Hospital Hairpulling Scale (MGH-HPS) between the end of the acute phase and follow-up evaluation. We also obtained secondary measures examining styles of hairpulling, comorbid anxiety and depressive symptoms, as well as continued treatment utilization. We examined both correlates and predictors of outcome (change in MGH-HPS score) using linear regression. None of the participants continued to take NAC at the time of follow-up assessment. No significant changes in hairpulling severity were reported over the follow-up period. Subjects reported significantly increased anxiety and depressive symptoms but improvement in automatic pulling symptoms. Increased hairpulling symptoms during the follow-up period were associated with increased depression and anxiety symptoms and increased focused pulling. Older age and greater focused pulling at baseline assessment were associated with poor long-term prognosis. Our findings suggest that few children with trichotillomania experience a significant improvement in trichotillomania symptoms if behavioral treatments are inaccessible or have failed to produce adequate symptom relief. Our findings also confirm results of previous cross-sectional studies that suggest an increased risk of depression and anxiety symptoms with age in pediatric trichotillomania. Increased focused pulling and older age among children with trichotillomania symptoms may be associated with poorer long-term prognosis. © 2015 Wiley Periodicals, Inc.

  3. Analysis and Long-Term Follow-Up of the Surgical Treatment of Children With Craniopharyngioma.

    Science.gov (United States)

    Cheng, Jing; Shao, Qiang; Pan, Zhiyong; You, Jin

    2016-11-01

    To investigate the relationship between the operative approach, clinical pathological factors, and curative effect of the surgical treatment in the patients with craniopharyngioma; to provide a theoretical basis for determining the prognosis and reducing the recurrence rate during the long-term postoperative follow-up in children. This was a retrospective analysis of the clinical data of 92 children who underwent surgical treatment in our department from May 2011 to January 2005. Long-term follow-up was performed from 12 months to 8 years. The pterional approach was used in 49 patients, the interhemispheric approach in 20 patients, the corpus callosum approach in 16 patients, and the butterfly approach in 7 patients. Pathological classification was performed by hematoxylin and eosin stain staining of the pathological tissues and evaluated according to the different surgical approaches, MRI calcification status, calcification type, pathological type, whether radiotherapy was performed, postoperative recurrence, and death. For the pterion approach resection, there was near total resection in 46 patients (93.9%) with the lowest recurrence rate. The operative approach and postoperative recurrence rates were compared; the difference was statistically significant (P 0.05). There was not a significant difference between the MRI classification and postoperative recurrence rate (P >0.05). Comparing the degree of tumor calcification with the recurrence rate after operation and the mortality rate, the difference was statistically significant (P craniopharyngioma and squamous papillary craniopharyngioma in 2 groups following operation were compared, and the differences were statistically significant (P craniopharyngioma relapse rate is higher, which could be because invasion of craniopharyngioma only occurs with adamantimous craniopharyngioma. Postoperative radiotherapy can significantly prolong the recurrence time and reduce the mortality rate of patients with

  4. Influence of long-term fertilization on soil physicochemical properties in a brown soil

    Science.gov (United States)

    Li, Dongdong; Luo, Peiyu; Han, Xiaori; Yang, Jinfeng

    2018-01-01

    This study aims to explore the influence on soil physicochemical properties under a 38-y long-term fertilization in a brown soil. Soil samples (0-20 cm)were taken from the six treatments of the long-term fertilization trial in October 2016:no fertilizer (CK), N1(mineral nitrogen fertilizer), N1P (mineral nitrogen and phosphate fertilizer), N1PK (mineral nitrogen, phosphate and potassic fertilizer), pig manure (M2), M2N1P (pig manure, mineral nitrogen and phosphate fertilizer).The results showed thatthe long-term application of chemical fertilizers reduced soil pH value, while the application of organic fertilizers increased pH value. Fertilization significantly increased the content of AHN, TN and SOM. Compared with the CK treatment and chemical fertilizer treatments, organic fertilizer treatments significantly increased the content of AP and TP. The content of AK and TK were no significant difference in different treatment.

  5. Characteristics of asthma attack with long-term management for bronchial asthma.

    Science.gov (United States)

    Kawahara, Noriko; Hasegawa, Shunji; Hashimoto, Kunio; Matsubara, Tomoyo; Ichiyama, Takashi; Furukawa, Susumu

    2009-10-01

    There have been no reports on the evaluation of the usefulness of long-term asthma management based on the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2005 (JPGL 2005). The purpose of the present study was to retrospectively investigate the records of 350 patients admitted to Yamaguchi University Hospital who had asthma attacks from January 2006 to June 2008. There were 149 patients who were treated for more than 3 months in accordance with the guideline (long-term management group) and 201 who were not (non-long-term management group). The patients were divided into three age groups: 100 infants, 159 toddlers, and 91 schoolchildren. The onset age of asthma in the long-term management group was earlier than that in the non-long-term management group in toddlers and schoolchildren. The white blood cell counts and C-reactive protein levels were higher in the non-long-term management group in schoolchildren, suggesting the complication of some infections. The severity of asthma in the long-term management group was greater than that in the non-long-term management group among all three age groups. There were no significant differences, however, in the severity of asthma attack at admission between the long-term and non-long-term management groups in the three age groups. Patients who had severe asthma tended to be treated with long-term management, which suggests that long-term asthma management according to JPGL 2005 may reduce the severity of asthma attack at that admission, because the severity of asthma in patients undergoing long-term management correlates with the severity of asthma attack.

  6. Frozen shoulder : long-term outcome following arthrographic distension.

    Science.gov (United States)

    Clement, Rhys G E; Ray, Andrew G; Davidson, Colin; Robinson, C Mike; Perks, Fergus J

    2013-08-01

    Arthrographic distension of the glenohumeral joint was adopted as a mainstream treatment for frozen shoulder before any randomised controlled trials were performed. Interpretation of the effectiveness of this procedure rests mostly on data from cohort studies of which there are few of high quality. Papers reporting long-term results have either excluded diabetic patients or failed to report patient orientated outcomes. The authors present a long-term prospective cohort study of 51 patients (12 diabetics and 39 non-diabetics), with 53 frozen shoulders, who had an arthrographic distension performed by a single radiologist as a primary intervention. Oxford shoulder score (OSS), visual analogue pain score (VAS), and range of movement (ROM) were recorded pre-distension, at 2 days and 1 month post-distension. OSS and VAS were recorded again at a mean of 14 months post distension (range : 8-26 months). OSS improved from a pre-distension mean of 22.3 by 16.9 points at final follow-up (p diabetic patients was the same as in non-diabetic patients. Arthrographic distension is a safe and effective treatment for frozen shoulder; it is also effective in diabetic patients. It gives long-term improvement. The authors believe that the low number of patients requiring a secondary procedure makes arthrographic distension preferable to manipulation under anaesthesia.

  7. Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades

    Directory of Open Access Journals (Sweden)

    MÔNICA R.M. VIANNA

    2000-09-01

    Full Text Available Since William James (1890 first distinguished primary from secondary memory, equivalent to short- and long-term memory, respectively, it has been assumed that short-term memory processes are in charge of cognition while long-term memory is being consolidated. From those days a major question has been whether short-term memory is merely a initial phase of long-term memory, or a separate phenomena. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus and related brain areas after one-trial avoidance learning can effectively cancel short-term memory without affecting long-term memory formation. This shows that short-term memory and long-term memory involve separate mechanisms and are independently processed. Other treatments, however, influence both memory types similarly, suggesting links between both at the receptor and at the post-receptor level, which should not be surprising as they both deal with nearly the same sensorimotor representations. This review examines recent advances in short- and long-term memory mechanisms based on the effect of intra-hippocampal infusion of drugs acting upon neurotransmitter and signal transduction systems on both memory types.

  8. Long-term associations between serum lipids and panretinal photocoagulation in type 1 diabetes

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Skovlund; Mejnert Jørgensen, Trine; Green, Anders

    2013-01-01

    To examine the predictive value of serum lipids on the need for panretinal photocoagulation (PRP) treatment in a long-term follow-up of a cohort of Danish type 1 diabetic patients.......To examine the predictive value of serum lipids on the need for panretinal photocoagulation (PRP) treatment in a long-term follow-up of a cohort of Danish type 1 diabetic patients....

  9. Near-Term Actions to Address Long-Term Climate Risk

    Science.gov (United States)

    Lempert, R. J.

    2014-12-01

    Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

  10. Body proportions during long-term growth hormone treatment in girls with Turner syndrome participating in a randomized dose-response trial

    NARCIS (Netherlands)

    T.C.J. Sas (Theo); W.J. Gerver; R. de Bruin (Rob); Th. Stijnen (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); T.J. Cole (Trevor); A. van Teunenbroek (Arne); S.L.S. Drop (Stenvert)

    1999-01-01

    textabstractTo assess body proportions in girls with Turner syndrome (TS) during long term GH treatment, height, sitting height (SH), hand (Hand) and foot (Foot) lengths, and biacromial (Biac) and biiliacal (Biil) diameters were measured in 68 girls with TS

  11. Proteome modification in tomato plants upon long-term aluminum treatment

    Science.gov (United States)

    This study aimed to identify the aluminum (Al)-induced proteomes in tomato (Solanum lycopersicum, “Micro-Tom”) after long-term exposure to the stress factor. Plants were treated in Magnavaca’s solution (pH 4.5) supplemented with 7.5 uM Al3+ ion activity over a 4 month period beginning at the emergen...

  12. Long Term Follow-Up of Sulfur Mustard Related Bronchiolitis Obliterans Treatment

    Directory of Open Access Journals (Sweden)

    Hamidreza Abtahi

    2016-10-01

    Full Text Available Bronchiolitis obliterans (BO is the most remarkable pulmonary sequels of war-related sulfur mustard inhalation. There is little if any data about long-term efficacy of associated BO treatment. Five years spirometric records of three groups of patients with obstructive pulmonary diseases (asthma, COPD, BO and documented sulfur mustard inhalation were evaluated. The BO patients were treated with inhaled Seretide 125-250/25 (2 puffs BID, azithromycin (250 mg, three times/week and N-acetylcysteine (1200-1800/day. Asthma and COPD patients were treated according to existing guidelines. Seventy-three (38 asthma, 16 COPD and 19 BO patients completed the 5 years follow-up. Basal and final FEV1 in BO patients (2.69±0.81 and 2.39±0.65 respectively were not significantly different from COPD patients (2.46±0.56 and 1.96±0.76 respectively. There was also no significant difference between the yearly FEV1 decline in BO patients compared to COPD patients (60±84 cc vs. 99±79 cc respectively, P=0.163. The non-significant difference of FEV1 decline in BO compared to COPD patients suggests the effectiveness of azithromycin, inhaled steroid and N-acetyl cysteine in BO patients. Considering safety and possible effectiveness, this treatment is recommended until more data is available from controlled clinical studies.

  13. PSA modeling of long-term accident sequences

    International Nuclear Information System (INIS)

    Georgescu, Gabriel; Corenwinder, Francois; Lanore, Jeanne-Marie

    2014-01-01

    In the context of the extension of PSA scope to include external hazards, in France, both operator (EDF) and IRSN work for the improvement of methods to better take into account in the PSA the accident sequences induced by initiators which affect a whole site containing several nuclear units (reactors, fuel pools,...). These methodological improvements represent an essential prerequisite for the development of external hazards PSA. However, it has to be noted that in French PSA, even before Fukushima, long term accident sequences were taken into account: many insight were therefore used, as complementary information, to enhance the safety level of the plants. IRSN proposed an external events PSA development program. One of the first steps of the program is the development of methods to model in the PSA the long term accident sequences, based on the experience gained. At short term IRSN intends to enhance the modeling of the 'long term' accident sequences induced by the loss of the heat sink or/and the loss of external power supply. The experience gained by IRSN and EDF from the development of several probabilistic studies treating long term accident sequences shows that the simple extension of the mission time of the mitigation systems from 24 hours to longer times is not sufficient to realistically quantify the risk and to obtain a correct ranking of the risk contributions and that treatment of recoveries is also necessary. IRSN intends to develop a generic study which can be used as a general methodology for the assessment of the long term accident sequences, mainly generated by external hazards and their combinations. This first attempt to develop this generic study allowed identifying some aspects, which may be hazard (or combinations of hazards) or related to initial boundary conditions, which should be taken into account for further developments. (authors)

  14. [Autologous serum tears: Long-term treatment in dry eye syndrome].

    Science.gov (United States)

    Beylerian, M; Lazaro, M; Magalon, J; Veran, J; Darque, A; Grimaud, F; Stolowy, N; Beylerian, H; Sabatier, F; Hoffart, L

    2018-03-01

    Dry eye disease is a multifactorial pathology of the ocular surface. The high incidence of this pathology, as well as its significant impact on quality of life and vision and its financial cost, makes it a real public health problem. While the treatment of mild cases is generally simple and effective, treatment of severe forms is often disappointing. The use of autologous serum tears (AST) represents a therapeutic alternative for the most severe cases. The purpose of our study is to evaluate the efficacy of long-term AST treatment in patients with severe dry eye disease refractory to conventional treatment or secondary to systemic diseases such as Sjögren's syndrome or Graft versus Host disease (GVH), or ocular pathologies such as neurotrophic keratitis, chemical burns and ocular cicatricial pemphigoid. This is a monocentric retrospective observational study conducted on 47 patients, with 83 eyes treated with autologous serum eye drops for isolated or secondary dry eye disease at the Marseille Public Hospitals between April 2014 and April 2017. The patients' subjective symptoms (ocular surface disease index [OSDI] score), their degree of satisfaction and the side effects were collected using questionnaires. Tear Break Up Time (BUT) and Schirmer scores were noted. A clinical evaluation based on fluorescein staining (Oxford score) was carried out prior to treatment with AST at P0 followed by 5 periods: P1 (between 1 and 3 months), P2 (3 to 9 months), P3 (9 to 15 months), P4 (15 months to 24 months), and P5 (>24 months). Out of the 83 eyes treated, the mean age was 54.39±21.56. There were 20 males (42.55 %) and 27 females (57.44 %); treatment indications consisted mainly of 25.53 % GVH, 21.27 % severe dry eye disease and 19.14 % Sjögren syndrome. The mean duration of follow-up was 9.82 months±15.50. The OSDI score decreased by 19.32 points±29.37 (Pdry eye symptoms over time with AST, significantly at P1 (Peyes treated with ASD, clinical

  15. Factors influencing the long-term sustainment of quality improvements made in addiction treatment facilities: a qualitative study

    Directory of Open Access Journals (Sweden)

    Scott P. Stumbo

    2017-11-01

    Full Text Available Abstract Background A greater understanding of the factors that influence long-term sustainment of quality improvement (QI initiatives is needed to promote organizational ability to sustain QI practices over time, help improve future interventions, and increase the value of QI investments. Methods We approached 83 of 201 executive sponsors or change leaders at addiction treatment organizations that participated in the 2007–2009 NIATx200 QI intervention. We completed semi-structured interviews with 33 individuals between November 2015 and April 2016. NIATx200 goals were to decrease wait time, increase admissions and improve retention in treatment. Interviews sought to understand factors that either facilitated or impeded long-term sustainment of organizational QI practices made during the intervention. We used thematic analysis to organize the data and group patterns of responses. We assessed available quantitative outcome data and intervention engagement data to corroborate qualitative results. Results We used narrative analysis to group four important themes related to long-term sustainment of QI practices: (1 finding alignment between business- and client-centered practices; (2 staff engagement early in QI process added legitimacy which facilitated sustainment; (3 commitment to integrating data into monitoring practices and the identification of a data champion; and (4 adequate organizational human resources devoted to sustainment. We found four corollary factors among agencies which did not sustain practices: (1 lack of evidence of impact on business practices led to discontinuation; (2 disengaged staff and lack of organizational capacity during implementation period led to lack of sustainment; (3 no data integration into overall business practices and no identified data champion; and (4 high staff turnover. In addition, we found that many agencies’ current use of NIATx methods and tools suggested a legacy effect that might improve

  16. Long Term Effectiveness of Cognitive Behavioral Group Therapy for Treatment of Major Depressive Disorder: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ceren Gokdag

    2016-03-01

    Full Text Available The aim of the study was to conduct systematic review the articles on long term effectiveness of cognitive-behavioral group therapy for treatment of major depressive disorder. Articles in English and Turkish published between the years of 2000 and 2015 (January were searched in national and international databases. The articles that did not include follow-up studies were excluded. Although the main aim of this study is to evaluate permanent effect of the cognitive behavioral group therapy, 21 articles that met the criteria were examined also in terms of some other variables such as research method, therapy characteristics and post test results. The findings of the articles revealed that cognitive-behavioral group therapy is effective for major depressive disorder and post therapy gains are maintained for a long time. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(Supplement 1: 23-38

  17. Long-term use of adalimumab in the treatment of moderate to severe plaque psoriasis: a review of the literature

    Directory of Open Access Journals (Sweden)

    Angela Y Moore

    2010-04-01

    Full Text Available Angela Y Moore, Blakely S RichardsonArlington Center for Dermatology, Arlington, Texas, USAAbstract: Psoriasis is a chronic T-cell-mediated inflammatory disease that primarily affects the skin and joints. Patients with moderate to severe psoriasis constitute about 30% of the psoriasis population. Treatment of this group is challenging due to the long-term side effects, toxicities and inconvenience of conventional treatments such as phototherapy, methotrexate and cyclosporine. However, recent advances in our understanding of the pathogenesis of psoriasis have led to the popular use of biologics, which offer a safer, more convenient and effective targeted therapy. Adalimumab was originally approved for treating rheumatoid arthritis. Currently, adalimumab is also approved for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy or when other systemic therapies are medically less appropriate. Since the onset of the use of biologics, there have been concerns over safety and efficacy when used as long-term therapy. This paper reviews all publications, posters and abstracts reporting original data on the efficacy and/or safety of adalimumab in patients treated for chronic plaque psoriasis for more than 1 year.Keywords: psoriasis, adalimumab, biologics

  18. Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment

    DEFF Research Database (Denmark)

    Østergaard, Lauge; Oestergaard, Louise Bruun; Lauridsen, Trine Kiilerich

    2018-01-01

    OBJECTIVES: It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. METHODS: Using Danish administrative registries, we identified patients...... admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We...... examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group...

  19. Long Term Financing of Infrastructure

    OpenAIRE

    Sinha, Sidharth

    2014-01-01

    Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

  20. Long-term follow up after uterine artery embolization for symptomatic uterine leiomyomas

    DEFF Research Database (Denmark)

    Poulsen, Bente; Munk, Torben; Ravn, Pernille

    2011-01-01

    Uterine artery embolization is one of the established treatment options for symptomatic uterine leiomyomas, with a proven effect on the size of leiomyomas and providing short-term relief of symptoms. Only few studies have addressed long-term satisfaction with the treatment. We conducted...

  1. Self-reported immature defense style as a predictor of outcome in short-term and long-term psychotherapy.

    Science.gov (United States)

    Laaksonen, Maarit A; Sirkiä, Carlos; Knekt, Paul; Lindfors, Olavi

    2014-07-01

    Identification of pretreatment patient characteristics predictive of psychotherapy outcome could help to guide treatment choices. This study evaluates patients' initial level of immature defense style as a predictor of the outcome of short-term versus long-term psychotherapy. In the Helsinki Psychotherapy Study, 326 adult outpatients with mood or anxiety disorder were randomized to individual short-term (psychodynamic or solution-focused) or long-term (psychodynamic) psychotherapy. Their defense style was assessed at baseline using the 88-item Defense Style Questionnaire and classified as low or high around the median value of the respective score. Both specific (Beck Depression Inventory [BDI], Hamilton Depression Rating Scale [HDRS], Symptom Check List Anxiety Scale [SCL-90-Anx], Hamilton Anxiety Rating Scale [HARS]) and global (Symptom Check List Global Severity Index [SCL-90-GSI], Global Assessment of Functioning Scale [GAF]) psychiatric symptoms were measured at baseline and 3-7 times during a 3-year follow-up. Patients with high use of immature defense style experienced greater symptom reduction in long-term than in short-term psychotherapy by the end of the 3-year follow-up (50% vs. 34%). Patients with low use of immature defense style experienced faster symptom reduction in short-term than in long-term psychotherapy during the first year of follow-up (34% vs. 19%). Knowledge of patients' initial level of immature defense style may potentially be utilized in tailoring treatments. Further research on defense styles as outcome predictors in psychotherapies of different types is needed.

  2. Long-Term Outcomes of Youth Treated for an Anxiety Disorder: A Critical Review.

    Science.gov (United States)

    Gibby, Brittany A; Casline, Elizabeth P; Ginsburg, Golda S

    2017-06-01

    Pediatric anxiety disorders are common, disabling, and chronic conditions. Efforts over the past two decades have focused on developing and testing effective treatments. Short-term efficacy of both Cognitive Behavioral Therapy (CBT) and selective serotonin reuptake inhibitors has been established. Data are emerging on the long-term (i.e., 2 years or longer) effectiveness of these treatments, but this literature has yet to be adequately synthesized. This study presents a systematic and critical qualitative review of published long-term follow-up (LTFU) studies of youth treated for an anxiety disorder. A comprehensive search of several databases identified 21 published reports (representing 15 LTFU cohorts of treated youth) meeting specified inclusion criteria. LTFU assessments occurred a mean of 5.85 years after initial treatment (range 2-19 years). Diagnostic rates at LTFU and predictors (e.g., demographic, baseline child clinical variables, treatment type) of outcomes at LTFU were also examined. A discussion of the limitations of this literature is provided to qualify interpretations of findings and to inform future studies. Findings can aid clinicians and families in making treatment decisions and setting reasonable expectations for the long-term prognosis after treatment for anxiety.

  3. Long-term Risedronate Treatment Normalizes Mineralization and Continues to Preserve Trabecular Architecture: Sequential Triple Biopsy Studies with Micro-Computed Tomography

    International Nuclear Information System (INIS)

    Borah, B.; Dufresne, T.; Ritman, E.; Jorgensen, S.; Liu, S.; Chmielewski, P.; Phipps, R.; Zhou, X.; Sibonga, J.; Turner, R.

    2006-01-01

    The objective of the study was to assess the time course of changes in bone mineralization and architecture using sequential triple biopsies from women with postmenopausal osteoporosis (PMO) who received long-term treatment with risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at baseline and after 3 and 5 years of treatment with 5 mg daily risedronate. Mineralization was measured using 3-dimensional (3D) micro-computed tomography (CT) with synchrotron radiation and was compared to levels in healthy premenopausal women (n = 12). Compared to the untreated PMO women at baseline, the premenopausal women had higher average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively, and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area (BMR-S) by 73.3% (P = 0.005) and 61.7% (P 0.003), respectively. Relative to baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9 ± 1.1%, P = 0.016) and Peak-MIN (6.2 ± 1.5%, P = 0.016), and significantly decreased BMR-V (-68.4 ± 7.3%, P = 0.016) and BMR-S (-50.2 ± 5.7%, P = 0.016) in the PMO women. The changes were maintained at the same level when treatment was continued up to 5 years. These results are consistent with the significant reduction of turnover observed after 3 years of treatment and which was similarly maintained through 5 years of treatment. Risedronate restored the degree of mineralization and the ratios of low- to high-mineralized bone to premenopausal levels after 3 years of treatment, suggesting that treatment reduced bone turnover in PMO women to healthy premenopausal levels. Conventional micro-CT analysis further demonstrated that bone volume (BV/TV) and trabecular architecture did not change from baseline up to 5 years of treatment, suggesting that risedronate provided long-term preservation of trabecular architecture in the PMO women. Overall, risedronate provided sustained

  4. Influence of Vegetation on Long-term Phosphorus Sequestration in Subtropical Treatment Wetlands.

    Science.gov (United States)

    Bhomia, R K; Reddy, K R

    2018-03-01

    Sustainable operation of a treatment wetland depends on its continued treatment of influent water to achieve desired outflow water quality targets. Water treatment or nutrient reduction is attained by a combination of biotic and abiotic processes. We studied one of the world's largest treatment wetlands established to revive the Florida Everglades from impacts of excessive phosphorus (P) inputs. Phosphorus retained in the treatment wetlands is sequestered within the accumulated material via biotic and abiotic pathways that are influenced by the existing wetland vegetation. Recently accreted soils (RAS) provide a major sink for stored P, and long-term P removal efficiency of treatment wetlands is governed by the stability of accreted P because more stable P pools are less susceptible to mobilization and loss. We quantified reactive P (extracted with acid and alkali) and nonreactive P (not extracted with acid and alkali) pools in wetland soils by using an operationally defined P fractionation scheme and assessed the effect of emergent vs. submerged vegetation communities on stability of sequestered P. Reactive P comprised 63 to 79% of total P in wetland soils without a clear difference between two vegetation groups. The quantities of reactive P forms (inorganic vs. organic P) were significantly different between two vegetation types. A higher proportion of reactive P was stored as organic P in flocculent detrital organic matter (floc) and RAS under emergent vegetation (46-47% total P) in comparison with submerged vegetation (21-34% total P). The dominant P removal pathway in the submerged vegetation system was associated with calcium whereas plant uptake and peat burial appeared to be the main pathway in the emergent vegetation system. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  5. Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

    Science.gov (United States)

    Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

    2016-04-01

    Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

  6. Changes in bone mineral density during long-term treatment with adalimumab in patients with rheumatoid arthritis: a cohort study

    NARCIS (Netherlands)

    Krieckaert, C.L.M.; Nurmohamed, M.T.; Wolbink, G.; Lems, W.F.

    2013-01-01

    Objective. To investigate the effect of long-term adalimumab treatment on BMD of the lumbar spine, total hip and hands in patients with RA. Methods. In 184 established RA patients treated with adalimumab for at least 1 year, BMD measurements of the total hip and lumbar spine were performed using

  7. Long-term trends in restoration and associated land treatments in the southwestern United States

    Science.gov (United States)

    Copeland, Stella M.; Munson, Seth M.; Pilliod, David S.; Welty, Justin L.; Bradford, John B.; Butterfield, Bradley J.

    2018-01-01

    Restoration treatments, such as revegetation with seeding or invasive species removal, have been applied on U.S. public lands for decades. Temporal trends in these management actions have not been extensively summarized previously, particularly in the southwestern United States where invasive plant species, drought, and fire have altered dryland ecosystems. We assessed long-term (1940–2010) trends in restoration using approximately 4,000 vegetation treatments conducted on Bureau of Land Management lands across the southwestern United States. We found that since 1940, the proportions of seeding and vegetation/soil manipulation (e.g. vegetation removal or plowing) treatments have declined, while the proportions of prescribed burn and invasive species treatments have increased. Treatments in pinyon-juniper and big sagebrush communities declined in comparison to treatments in desert scrub, creosote bush, and riparian woodland communities. Restoration-focused treatment objectives increased relative to resource extraction objectives. Species richness and proportion of native species used in seeding treatments also increased. Inflation-adjusted costs per area rose 750% for vegetation/soil manipulation, 600% for seeding, and 400% for prescribed burn treatments in the decades from 1981 to 2010. Seeding treatments were implemented in warmer and drier years when compared to the climate conditions of the entire study period and warmer and wetter years relative to several years before and after the treatment. These results suggest that treatments over a 70-year period on public lands in the southwestern United States are shifting toward restoration practices that are increasingly large, expensive, and related to fire and invasive species control.

  8. Rigiflex Balloon dilation without fluoroscopy for treatment of Achalasia: A long-term follow-up of 99 patients

    Directory of Open Access Journals (Sweden)

    "Mikaeli J

    2002-06-01

    Full Text Available Achalasia is a well- defined esophageal motor disorder. Graded pneumatic dilation using Rigiflex ballon is one of the therapeutic modalities that had not been evaluated in a large long-term study. We aimed at evaluating long-term efficacy of graded Rigiflex pneumatic dilation in the treatment of achalasia. Symptomatic patients with achalasia who had been referred to our center were consecutively enrolled. The diagnosis was established by clinical, radiographic and endoscopic criteria. Exclusion criteria included pregnancy, coagulopathy, serious medical illness or malignancy. Initially all patients were clinically scored based on the severity of five main symptoms and then underwent pneumatic dilation wit at 3 cm ballon. Symptom scores were evaluated at 1, 6, 12 .. months. Clinical recurrence was defined as an increase of symptom with 3.5 cm balloon dilation. If recurrence occurred again, third dilation was done with a 4 cm ballon. Over a five-year period, 99 patients [mean age: 35.6 (3.0-72 years.] were followed to an average length of 47.4 (18-20 months. 35 patients needed- retreatment, only 6 of them required third dilation. After third dilation two patients did not reveal improvement and underwent cardiomyotomy. Over this time period, cumulative remission rate was 65% without redilation and 94% with redilation. The mean remission period was 44.7 months (95% CI, 43.52-51.27 for single pneumatic dilation by use of Kaplan- Meier survival analysis. There was no significant predictive value for age, gender, previous treatment and severity of initial score to outcome (P>0.4 by use of Cox regression analysis. Pneumatic dilation by a Rigiflex balloon using a graded approach is effective long-term therapy for achalasia in majority of patients.

  9. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  10. Long-term effects of the Focus on Families project on substance use disorders among children of parents in methadone treatment.

    Science.gov (United States)

    Haggerty, Kevin P; Skinner, Martie; Fleming, Charles B; Gainey, Randy R; Catalano, Richard F

    2008-12-01

    This study examines the efficacy of the Focus on Families project (currently called Families Facing the Future), a preventive intervention to reduce substance use disorders among children in families with a parent in methadone treatment. One hundred and thirty families were assigned randomly to a methadone clinic treatment-as-usual control condition or treatment-as-usual plus the Focus on Families intervention between 1991 and 1993. Setting Participants were recruited from two methadone clinics in the Pacific Northwest. This study examines the development of substance use disorders among the 177 children (56.84% male) involved in the program using data from a long-term follow-up in 2005, when these participants ranged in age from 15 to 29 years. The intervention was delivered through group parent-training workshops at the methadone clinics and through individualized home-based services. The intervention taught parenting skills and skills for avoiding relapse to drug abuse. At long-term follow-up, substance use disorders were measured by the Composite International Diagnostic Interview (CIDI). Survival analyses were used to assess intervention versus control differences in the hazard of developing substance use disorders. Overall, intervention and control participants did not differ significantly in risk of developing substance use disorders. However, there was evidence of a significant difference in intervention effect by gender. There was a significant reduction in the risk of developing a substance use disorder for intervention group males compared to control group males (hazard ratio = 0.53, P = 0.03), while intervention versus control differences among females were non-significant and favored the control condition. Results from this study suggest that helping parents in recovery focus on both reducing their drug use and improving their parenting skills may have long-term effects on reducing substance use disorders among their male children. However, the overall

  11. EFFECTS OF LONG-TERM ALENDRONATE TREATMENT ON A LARGE SAMPLE OF PEDIATRIC PATIENTS WITH OSTEOGENESIS IMPERFECTA.

    Science.gov (United States)

    Lv, Fang; Liu, Yi; Xu, Xiaojie; Wang, Jianyi; Ma, Doudou; Jiang, Yan; Wang, Ou; Xia, Weibo; Xing, Xiaoping; Yu, Wei; Li, Mei

    2016-12-01

    Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI. In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured. After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (Posteogenesis imperfecta PTH = parathyroid hormone.

  12. Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation.

    Science.gov (United States)

    Musicki, Biljana; Champion, Hunter C; Becker, Robyn E; Liu, Tongyun; Kramer, Melissa F; Burnett, Arthur L

    2005-07-01

    Despite demonstrated clinical efficacy of sildenafil for the temporary treatment of erectile dysfunction, the possibility that sildenafil used long-term durably augments erectile ability remains unclear. We investigated whether continuous long-term administration of sildenafil at clinically relevant levels to aged rats "primes" the penis for improved erectile ability and involves nitric oxide (NO) or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil prolonged erection and increased the protein expressions of phosphorylated endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine-473 in penes. Only in the young rat penis, protein expressions of phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited phosphodiesterase-5 activity in penes of young and aged rats coincident with assayed free plasma levels of the drug equivalent to clinically therapeutic measurements. We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack of erectile ability enhancement in young rats by long-term phosphodiesterase-5 inhibition may relate to restrained NO signaling by phosphodiesterase-5 up-regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho-kinase signaling in the penis.

  13. Conversion of short-term to long-term memory in the novel object recognition paradigm.

    Science.gov (United States)

    Moore, Shannon J; Deshpande, Kaivalya; Stinnett, Gwen S; Seasholtz, Audrey F; Murphy, Geoffrey G

    2013-10-01

    It is well-known that stress can significantly impact learning; however, whether this effect facilitates or impairs the resultant memory depends on the characteristics of the stressor. Investigation of these dynamics can be confounded by the role of the stressor in motivating performance in a task. Positing a cohesive model of the effect of stress on learning and memory necessitates elucidating the consequences of stressful stimuli independently from task-specific functions. Therefore, the goal of this study was to examine the effect of manipulating a task-independent stressor (elevated light level) on short-term and long-term memory in the novel object recognition paradigm. Short-term memory was elicited in both low light and high light conditions, but long-term memory specifically required high light conditions during the acquisition phase (familiarization trial) and was independent of the light level during retrieval (test trial). Additionally, long-term memory appeared to be independent of stress-mediated glucocorticoid release, as both low and high light produced similar levels of plasma corticosterone, which further did not correlate with subsequent memory performance. Finally, both short-term and long-term memory showed no savings between repeated experiments suggesting that this novel object recognition paradigm may be useful for longitudinal studies, particularly when investigating treatments to stabilize or enhance weak memories in neurodegenerative diseases or during age-related cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database

    Directory of Open Access Journals (Sweden)

    Sunghwan Suh

    2015-06-01

    Full Text Available BackgroundWe assessed the association of dipeptidyl peptidase 4 inhibitors (DPP4i with hospitalization for heart failure (HF using the Korean Health Insurance claims database.MethodsWe collected data on newly prescribed sitagliptin, vildagliptin, and pioglitazone between January 1, 2009 and December 31, 2012 (mean follow-up of 336.8 days to 935,519 patients with diabetes (518,614 males and 416,905 females aged 40 to 79 years (mean age of 59.4 years.ResultsDuring the study, 998 patients were hospitalized for primary HF (115.7 per 100,000 patient-years. The incidence rate of hospitalization for HF was 117.7 per 100,000 per patient-years among patients on pioglitazone, 105.7 for sitagliptin, and 135.8 for vildagliptin. The hospitalization rate for HF was greatest in the first 30 days after starting the medication, which corresponded to a significantly higher incidence at days 0 to 30 compared with days 31 to 360 for all three drugs. The hazard ratios were 1.85 (pioglitazone, 2.00 (sitagliptin, and 1.79 (vildagliptin. The incidence of hospitalization for HF did not differ between the drugs for any time period.ConclusionThis study showed an increase in hospitalization for HF in the initial 30 days of the DPP4i and pioglitazone compared with the subsequent follow-up period. However, the differences between the drugs were not significant.

  15. THE ANALYSIS OF LONG-TERM OUTCOMES AND ADHERENT TO TREATMENT IN PATIENTS AFTER MYOCARDIAL INFARCTION: KHABAROVSK REGISTER DATA

    Directory of Open Access Journals (Sweden)

    I. M. Davidovich

    2017-01-01

    Full Text Available Objective. To evaluate the long-term outcomes and medical treatment in patients during 2.5 years after reference acute myocardial infarction (AMI, to study adherent to medical treatment and the role of various factors affecting the long-term prognosis.Materials and methods. The AMI Register included data about all patients, whom are consistently hospitalized in the regional vascular center (RVC of Khabarovsk during the period from 01.01.14 till 31.03.14. The 2.5 years outcomes and adherence to treatment were evaluated by using phone interview.Results. According to prospective part of the AMI Register of 292 patients discharged from the regional vascular center (RVC, the vital status in 2.5 years managed to be established at 274 (93.8 % from which died 45 (16.42 %, or 15.40 % from all discharged patients. In structure of a mortality the proportion of dead from cardiovascular disease (СVD patients made 86.6 %. The long-term mortality of patients with myocardial infarction with ST-segment elevation was 19.3 %, the myocardial infarction non-ST-segment elevation – 13.2 %; р = 0.632.The new predictors of death 2.5 years after the onset of AMI were cerebrovascular diseases, the absence of the antihypertensive drugs and β-blockers before reference AMI, not prescribing antiplatelet drugs in loading doses in the early hours of the disease. Frequency of real reception of statins was 65.1 %, angiotensin-renin blockers –76.0  %, β-blocker – 73.8 % of patients after AMI. Only 55.9 % patients Received double antithrombocytic therapy (DATT  during a year. By  the Moriscors–Green test adherent were only 109 (47.6 %. 79 (34.5 % know their values cholesterol, blood pressure and blood glucose.Conclusions. Indicators of the remote lethality among patients authentically didn’t differ with a myocardial infarction with ST-segment elevation in AMI and a myocardial infarction non-ST-segment elevation in AMI in the remote period. The register AMI taped

  16. Efficacy of modest dose irradiation in combination with long-term endocrinal treatment for high-risk prostate cancer. A preliminary report

    International Nuclear Information System (INIS)

    Sasaki, Tomonari; Nakamura, Katsumasa; Shioyama, Yoshiyuki

    2004-01-01

    Although radiotherapy in combination with endocrinal manipulation has been identified as an effective treatment for patients with high-risk prostate cancer, the optimal dose for locoregional control of prostate cancer in combination with hormonal therapy has not yet been determined. The efficacy of modest doses of irradiation (60-62 Gy) combined with long-term endocrinal treatment for patients with high-risk prostate cancer (defined as a pretreatment prostate-specific antigen (PSA) level greater than 20 ng/ml or a Gleason's score of 8-10 or T3-T4 disease) was analyzed in 60 Japanese patients. The patients included in this study had received radical radiotherapy with long-term endocrinal manipulation in the period between 1993 and 2000. The median age of the patients was 70 years (range, 56-83). Neoadjuvant hormonal therapy with a median duration of 3.9 months was performed prior to radiotherapy, and hormonal therapy was continued until recurrence. A median dose of 61.4 Gy (range, 44-71.4) was delivered to the prostate. Pelvic node irradiation was performed in 49 patients (81.6%). After a median follow-up period of 28.5 months, the overall survival, cause-specific survival and biochemical relapse-free survival at 3 years were 94.4%, 96% and 89.8%, respectively. Local failure was observed in one patient, distant metastases were observed in three patients and a late toxic effect greater than Grade 2 was not observed in any patients. This study, though preliminary due to a short-term follow-up period, reveals the possibility that modest doses of irradiation combined with long-term endocrinal treatment could be an effective means of achieving excellent local control of high-risk prostate cancer. (author)

  17. Successful long-term treatment of Cushing disease with mifepristone (RU486).

    Science.gov (United States)

    Basina, Marina; Liu, Hau; Hoffman, Andrew R; Feldman, David

    2012-01-01

    We describe a girl with Cushing disease for whom surgery and radiation treatments failed and the subsequent clinical course with mifepristone therapy. We present the patient's clinical, biochemical, and imaging findings. A 16-year-old girl presented with classic Cushing disease. After transsphenoidal surgery, Cyberknife radiosurgery, ketoconazole, and metyrapone did not control her disease, and she was prescribed mifepristone, which was titrated to a maximal dosage of 1200 mg daily with subsequent symptom improvement. Mifepristone (RU486) is a high-affinity, nonselective antagonist of the glucocorticoid receptor. There is limited literature on its use as an off-label medication to treat refractory Cushing disease. Over her 8-year treatment with mifepristone, her therapy was complicated by hypertension and hypokalemia requiring spironolactone and potassium chloride. She received a 2-month drug holiday every 4 to 6 months to allow for withdrawal menstrual bleeding with medroxyprogesterone acetate. Urinary cortisol, serum cortisol, and corticotropin levels remained elevated during mifepristone drug holidays. While on mifepristone, her signs and symptoms of Cushing disease resolved. Repeated magnetic resonance imaging demonstrated stable appearance of the residual pituitary mass. Bilateral adrenalectomy was performed, and mifepristone was discontinued after 95 months of medical therapy. We describe the longest duration of mifepristone therapy thus reported for the treatment of refractory Cushing disease. Mifepristone effectively controlled all signs and symptoms of hypercortisolism. Menstruating women who take the drug on a long-term basis should receive periodic drug holidays to allow for menses. The lack of reliable serum biomarkers to monitor the success of mifepristone therapy requires careful clinical judgment and may make its use difficult in Cushing disease.

  18. Clinical trials with rasagiline: evidence for short-term and long-term effects.

    Science.gov (United States)

    Siderowf, Andrew; Stern, Matthew

    2006-05-23

    Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

  19. Long-term response to recombinant human growth hormone treatment: a new predictive mathematical method.

    Science.gov (United States)

    Migliaretti, G; Ditaranto, S; Guiot, C; Vannelli, S; Matarazzo, P; Cappello, N; Stura, I; Cavallo, F

    2018-07-01

    Recombinant GH has been offered to GH-deficient (GHD) subjects for more than 30 years, in order to improve height and growth velocity in children and to enhance metabolic effects in adults. The aim of our work is to describe the long-term effect of rhGH treatment in GHD pediatric patients, suggesting a growth prediction model. A homogeneous database is defined for diagnosis and treatment modalities, based on GHD patients afferent to Hospital Regina Margherita in Turin (Italy). In this study, 232 GHD patients are selected (204 idiopathic GHD and 28 organic GHD). Each measure is shown in terms of mean with relative standard deviations (SD) and 95% confidence interval (95% CI). To estimate the final height of each patient on the basis of few measures, a mathematical growth prediction model [based on Gompertzian function and a mixed method based on the radial basis functions (RBFs) and the particle swarm optimization (PSO) models] was performed. The results seem to highlight the benefits of an early start of treatment, further confirming what is suggested by the literature. Generally, the RBF-PSO method shows a good reliability in the prediction of the final height. Indeed, RMSE is always lower than 4, i.e., in average the forecast will differ at most of 4 cm to the real value. In conclusion, the large and accurate database of Italian GHD patients allowed us to assess the rhGH treatment efficacy and compare the results with those obtained in other Countries. Moreover, we proposed and validated a new mathematical model forecasting the expected final height after therapy which was validated on our cohort.

  20. Long-term effects of pediatric extracorporeal shockwave lithotripsy on renal function

    Directory of Open Access Journals (Sweden)

    Akin Y

    2014-04-01

    Full Text Available Yigit Akin,1 Selcuk Yucel21Department of Urology, Harran University School of Medicine, Sanliurfa, Turkey; 2Department of Urology, Acibadem University School of Medicine, Istanbul, TurkeyIntroduction: Extracorporeal shock wave lithotripsy (ESWL is a well-known and successful treatment modality. In addition, it can be used in premature infants. ESWL is used to treat kidney and ureter stones in children. However, although it is a preferred noninvasive treatment in that setting, there is debate about its long-term effects on growing kidneys in children.Objectives: To investigate the long-term effects of pediatric ESWL on renal function in light of updated literature.Methods: PubMed and Medline were searched for studies on ESWL in a pediatric population with keywords including efficacy, child, kidney calculi, ureter calculi, lithotripsy, injury, vascular trauma, and shock waves. The research was limited to the English literature during a period from 1980 to 2014. In total, 3,000 articles were evaluated, but only 151 papers were considered. Only the manuscripts directly related to the reviewed subjects were included in the current study.Results: However, the acute effects of ESWL in kidney are well-described. Although there are limited studies on the long-term effects of ESWL in children, there is a widespread opinion that ESWL is not affecting renal functions in the long-term.Conclusion: ESWL is a safe, effective, and noninvasive treatment option in children. Although ESWL can cause some acute effects in the kidney, there is no long-term effect on the growing kidneys of children.Keywords: child, lithotripsy, nephrolithiasis, renal injury, vascular trauma

  1. Mid- and Long-Term Results of Endovascular Treatment in Thoracic Aorta Blunt Trauma

    Directory of Open Access Journals (Sweden)

    Luigi Irace

    2012-01-01

    Full Text Available Study Aim. Evaluation of results in blunt injury of the thoracic aorta (BAI endovascular treatment. Materials and Methods. Sixteen patients were treated for BAI. Thirteen patients had associated polytrauma, 4 of these had a serious hypotensive status and 4 had an hemothorax. In the remaining 3, two had a post-traumatic false aneurysm of the isthmus and 1 had a segmental dissection. In those 13 patients a periaortic hematoma was associated to hemothorax in 4. All patients were submitted to an endovascular treatment, in two cases the subclavian artery ostium was intentionally covered. Results. One patient died for disseminated intravascular coagulation. No paraplegia was recorded. No ischemic complications were observed. A type I endoleak was treated by an adjunctive cuff. During the followup (1–9 years 3 patients were lost. A good patency and no endoleaks were observed in all cases. One infolding and 1 migration of the endografts were corrected by an adjunctive cuff. Conclusion. The medium and long term results of the endovascular treatment of BAI are encouraging with a low incidence rate of mortality and complications. More suitable endo-suite and endografts could be a crucial point for the further improvement of these results.

  2. The long-term outcomes of epilepsy surgery

    Science.gov (United States)

    Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

    2018-01-01

    Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with

  3. Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

    DEFF Research Database (Denmark)

    Bruun, N E; Ibsen, H; Skøtt, P

    1988-01-01

    1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155...... were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks....../101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates...

  4. Long-term weight loss maintenance for obesity: a multidisciplinary approach

    Directory of Open Access Journals (Sweden)

    Montesi L

    2016-02-01

    Full Text Available Luca Montesi,1 Marwan El Ghoch,2 Lucia Brodosi,1 Simona Calugi,2 Giulio Marchesini,1 Riccardo Dalle Grave2 1Unit of Metabolic Diseases, S Orsola-Malpighi Hospital, “Alma Mater Studiorum” University, Bologna, Italy; 2Department of Eating and Weight Disorders, Villa Garda Hospital, Verona, Italy Abstract: The long-term weight management of obesity remains a very difficult task, associated with a high risk of failure and weight regain. However, many people report that they have successfully managed weight loss maintenance in the long term. Several factors have been associated with better weight loss maintenance in long-term observational and randomized studies. A few pertain to the behavioral area (eg, high levels of physical activity, eating a low-calorie, low-fat diet; frequent self-monitoring of weight, a few to the cognitive component (eg, reduced disinhibition, satisfaction with results achieved, confidence in being able to lose weight without professional help, and a few to personality traits (eg, low novelty seeking and patient–therapist interaction. Trials based on the most recent protocols of lifestyle modification, with a prolonged extended treatment after the weight loss phase, have also shown promising long-term weight loss results. These data should stimulate the adoption of a lifestyle modification-based approach for the management of obesity, featuring a nonphysician lifestyle counselor (also called “lifestyle trainer” or “healthy lifestyle practitioner” as a pivotal component of the multidisciplinary team. The obesity physicians maintain a primary role in engaging patients, in team coordination and supervision, in managing the complications associated with obesity and, in selected cases, in the decision for drug treatment or bariatric surgery, as possible more intensive, add-on interventions to lifestyle treatment. Keywords: obesity, lifestyle modification, cognitive behavior therapy, multidisciplinary treatment

  5. Seed quality preservation advantage of gamma irradiation seed pre-treatment during long term storage in soybean

    International Nuclear Information System (INIS)

    Guha, Sameer Kumar; Sumedha; Singh, Bhupinder

    2014-01-01

    The experiment was conducted to analyse the effect of gamma irradiation seed pre-treatment on insect damage and quality preservation of soybean seeds during long term storage at ambient temperature (27-42 ℃) and relative humidity (50-95%). Freshly harvested seeds of soybean (cv. Pusa-9814) were treated with control (0), 0.01, 0.05, 0.5, 1.0, 3.0, 5.0 kGy gamma radiation on a Gamma irradiator (Gamma Chamber 5000, 60 Co source, activity 12000 Ci, BRIT, Mumbai, India) at the Nuclear Research Laboratory, IARI, New Delhi and were stored over one year in cotton cloth bags under ambient conditions. Protein and oil per cent and fatty acid profile was measured in freshly harvested zero time unirradiated control, aged unirradiated control and other treatments of ionizing radiation. Seed oil was extracted through the soxhlet extraction method and oil profiling was done by gas chromatography. Change in saturated and unsaturated fatty acids like palmitic, stearic, oleic, linolic, linolenic acid and oleic to linoleic ratio was measured. Oil content of unirradiated stored seeds compared to that of the freshly harvested control was lower. However, radiation in general, helped in maintaining a higher seed oil during storage when compared with that of the aged unirradiated control and was insignificantly reduced over the fresh unirrradiated control. Further, gamma irradiation treatment did not yield any adverse affect on the seed protein even after prolonged storage. The results reveal a reduced rate of lipid degradation and improved seed hardness over untreated control with no significant change in fatty acid profile of the irradiated and the unirradiated seeds over a long term storage period. (author)

  6. Long-term remission of folliculitis decalvans after treatment with the long-pulsed Nd:YAG laser.

    Science.gov (United States)

    Meesters, Arne A; Van der Veen, J P Wietze; Wolkerstorfer, Albert

    2014-04-01

    Folliculitis decalvans (FD) is a rare inflammatory scalp disorder presenting with tufted folliculitis, follicular papules and pustules, progressing to cicatricial alopecia. Current treatments mainly consist of antibiotic and immunomodulatory therapies and are often disappointing. FD has previously shown to respond to treatment with neodymium:yttrium aluminium garnet (Nd:YAG) laser in one case. We present a case of recalcitrant FD, successfully treated with a long-pulsed Nd:YAG laser.

  7. Long-Term Outcomes of Stereotactic Radiosurgery for Treatment of Cavernous Sinus Meningiomas

    International Nuclear Information System (INIS)

    Santos, Marcos Antonio dos; Bustos Pérez de Salcedo, José; Gutiérrez Diaz, José Angel; Calvo, Felipe A.; Samblás, José; Marsiglia, Hugo; Sallabanda, Kita

    2011-01-01

    Purpose: Patients with cavernous sinus meningiomas (CSM) have an elevated risk of surgical morbidity and mortality. Recurrence is often observed after partial resection. Stereotactic radiosurgery (SRS), either alone or combined with surgery, represents an important advance in CSM management, but long-term results are lacking. Methods and Materials: A total of 88 CSM patients, treated from January 1991 to December 2005, were retrospectively reviewed. The mean follow-up was 86.8 months (range, 17.1–179.4 months). Among the patients, 22 were followed for more than 10 years. There was a female predominance (84.1%). The age varied from 16 to 90 years (mean, 51.6). In all, 47 patients (53.4%) received SRS alone, and 41 patients (46.6%) had undergone surgery before SRS. A dose of 14 Gy was prescribed to isodose curves from 50% to 90%. In 25 patients (28.4%), as a result of the proximity to organs at risk, the prescribed dose did not completely cover the target. Results: After SRS, 65 (73.8%) patients presented with tumor volume reduction; 14 (15.9%) remained stable, and 9 (10.2%) had tumor progression. The progression-free survival was 92.5% at 5 years, and 82.5% at 10 years. Age, sex, maximal diameter of the treated tumor, previous surgery, and complete target coverage did not show significant associations with prognosis. Among the 88 treated patients, 17 experienced morbidity that was related to SRS, and 6 of these patients spontaneously recovered. Conclusions: SRS is an effective and safe treatment for CSM, feasible either in the primary or the postsurgical setting. Incomplete coverage of the target did not worsen outcomes. More than 80% of the patients remained free of disease progression during long-term follow-up.

  8. Long-Term Outcomes of Stereotactic Radiosurgery for Treatment of Cavernous Sinus Meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcos Antonio dos, E-mail: marcosrxt@gmail.com [Radiotherapy Department, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Bustos Perez de Salcedo, Jose; Gutierrez Diaz, Jose Angel [Radiotherapy Department, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Neurosurgery Department, Sanatorio San Francisco de Asis, Madrid (Spain); Calvo, Felipe A. [Radiotherapy Department, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Department of Oncology, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Samblas, Jose [Radiotherapy Department, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Neurosurgery Department, Sanatorio San Francisco de Asis, Madrid (Spain); Marsiglia, Hugo [Radiotherapy Department, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Sallabanda, Kita [Radiotherapy Department, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Neurosurgery Department, Sanatorio San Francisco de Asis, Madrid (Spain)

    2011-12-01

    Purpose: Patients with cavernous sinus meningiomas (CSM) have an elevated risk of surgical morbidity and mortality. Recurrence is often observed after partial resection. Stereotactic radiosurgery (SRS), either alone or combined with surgery, represents an important advance in CSM management, but long-term results are lacking. Methods and Materials: A total of 88 CSM patients, treated from January 1991 to December 2005, were retrospectively reviewed. The mean follow-up was 86.8 months (range, 17.1-179.4 months). Among the patients, 22 were followed for more than 10 years. There was a female predominance (84.1%). The age varied from 16 to 90 years (mean, 51.6). In all, 47 patients (53.4%) received SRS alone, and 41 patients (46.6%) had undergone surgery before SRS. A dose of 14 Gy was prescribed to isodose curves from 50% to 90%. In 25 patients (28.4%), as a result of the proximity to organs at risk, the prescribed dose did not completely cover the target. Results: After SRS, 65 (73.8%) patients presented with tumor volume reduction; 14 (15.9%) remained stable, and 9 (10.2%) had tumor progression. The progression-free survival was 92.5% at 5 years, and 82.5% at 10 years. Age, sex, maximal diameter of the treated tumor, previous surgery, and complete target coverage did not show significant associations with prognosis. Among the 88 treated patients, 17 experienced morbidity that was related to SRS, and 6 of these patients spontaneously recovered. Conclusions: SRS is an effective and safe treatment for CSM, feasible either in the primary or the postsurgical setting. Incomplete coverage of the target did not worsen outcomes. More than 80% of the patients remained free of disease progression during long-term follow-up.

  9. A Portable Dynamic Laser Speckle System for Sensing Long-Term Changes Caused by Treatments in Painting Conservation.

    Science.gov (United States)

    Pérez, Alberto J; González-Peña, Rolando J; Braga, Roberto; Perles, Ángel; Pérez-Marín, Eva; García-Diego, Fernando J

    2018-01-11

    Dynamic laser speckle (DLS) is used as a reliable sensor of activity for all types of materials. Traditional applications are based on high-rate captures (usually greater than 10 frames-per-second, fps). Even for drying processes in conservation treatments, where there is a high level of activity in the first moments after the application and slower activity after some minutes or hours, the process is based on the acquisition of images at a time rate that is the same in moments of high and low activity. In this work, we present an alternative approach to track the drying process of protective layers and other painting conservation processes that take a long time to reduce their levels of activity. We illuminate, using three different wavelength lasers, a temporary protector (cyclododecane) and a varnish, and monitor them using a low fps rate during long-term drying. The results are compared to the traditional method. This work also presents a monitoring method that uses portable equipment. The results present the feasibility of using the portable device and show the improved sensitivity of the dynamic laser speckle when sensing the long-term process for drying cyclododecane and varnish in conservation.

  10. A Portable Dynamic Laser Speckle System for Sensing Long-Term Changes Caused by Treatments in Painting Conservation

    Science.gov (United States)

    Pérez, Alberto J.; Braga, Roberto; Perles, Ángel; Pérez–Marín, Eva; García-Diego, Fernando J.

    2018-01-01

    Dynamic laser speckle (DLS) is used as a reliable sensor of activity for all types of materials. Traditional applications are based on high-rate captures (usually greater than 10 frames-per-second, fps). Even for drying processes in conservation treatments, where there is a high level of activity in the first moments after the application and slower activity after some minutes or hours, the process is based on the acquisition of images at a time rate that is the same in moments of high and low activity. In this work, we present an alternative approach to track the drying process of protective layers and other painting conservation processes that take a long time to reduce their levels of activity. We illuminate, using three different wavelength lasers, a temporary protector (cyclododecane) and a varnish, and monitor them using a low fps rate during long-term drying. The results are compared to the traditional method. This work also presents a monitoring method that uses portable equipment. The results present the feasibility of using the portable device and show the improved sensitivity of the dynamic laser speckle when sensing the long-term process for drying cyclododecane and varnish in conservation. PMID:29324692

  11. Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy.

    Science.gov (United States)

    Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

    2011-01-01

    The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate. Copyright © 2010 S. Karger AG, Basel.

  12. Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment.

    Science.gov (United States)

    Marchand, Kirsten; Oviedo-Joekes, Eugenia; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Schechter, Martin T

    2012-01-25

    Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months). A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. NCT00175357.

  13. Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment

    Directory of Open Access Journals (Sweden)

    Marchand Kirsten

    2012-01-01

    Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months. Results A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. Conclusions After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. Trial Registration NCT00175357.

  14. Adolescent idiopathic scoliosis: natural history and long term treatment effects

    Directory of Open Access Journals (Sweden)

    Asher Marc A

    2006-03-01

    risks of major surgery, a 6 to 29% chance of requiring re-operation, and the remote possibility of developing a pain management problem. Knowledge of adolescent idiopathic scoliosis natural history and long-term treatment effects is and will always remain somewhat incomplete. However, enough is know to provide patients and parents the information needed to make informed decisions about management options.

  15. Stability of rapid maxillary expansion and facemask therapy: a long-term controlled study.

    Science.gov (United States)

    Masucci, Caterina; Franchi, Lorenzo; Defraia, Efisio; Mucedero, Manuela; Cozza, Paola; Baccetti, Tiziano

    2011-10-01

    The aim of this prospective controlled study was to evaluate the long-term effects of rapid maxillary expansion and facemask therapy in Class III subjects. Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years ± 1.6) with Class III disharmony were treated consecutively with rapid maxillary expansion and facemask therapy followed by fixed appliances. The patients were reevaluated at the end of the 2-phase treatment (mean age, 14.5 years ± 1.9) and then recalled about 8.5 years after the end of rapid maxillary expansion and facemask treatment (mean age, 18.7 years ± 2.1). Two groups of controls with untreated Class III malocclusion were used for statistical comparisons of the short-term and long-term intervals. Statistical comparisons were performed with the Mann-Whitney U test. In the long term, no significant differences in maxillary changes were recorded, whereas the treatment group showed significantly smaller increases in mandibular protrusion. The sagittal maxillomandibular skeletal variables maintained significant improvements in the treatment group vs the control groups. In the long term, rapid maxillary expansion and facemask therapy led to successful outcomes in about 73% of the Class III patients. Favorable skeletal changes were mainly due to significant improvements in the sagittal position of the mandible. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  16. Metformin and pioglitazone are effective in reducing the levels of leptin and omentin

    Directory of Open Access Journals (Sweden)

    A K Lipatenkova

    2013-03-01

    Full Text Available Реферат по материалам статьи Esteghamati A, Noshad S, Rabizadeh S, Ghavami M, Zandieh A, Nakhjavani M. Comparative effects of metformin and pioglitazone on omentin and leptin concentrations in patients with newly diagnosed diabetes: A randomized clinical trial. Regul Pept. 2013 Jan 14;182C:1-6.

  17. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Dinesh M Bramhane

    2016-01-01

    Full Text Available Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE. Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD, hydroxypropyl-β-cyclodextrin (HPBCD and Sulfobutylether-7-β-cyclodextrin (SBEBCD were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC and X-Ray diffraction (XRD. Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats

  18. Long-term care policy for older Americans: building a continuum of care.

    Science.gov (United States)

    Palley, Howard A

    2003-01-01

    This paper deals primarily with social policy considerations relevant to the development of long-term care policy for the frail elderly in the United States. However, it also includes some commentary on meeting the acute care needs of the frail elderly. It defines chronic care treatment as a mix of "short-term" and "long-term" modes of care. Furthermore, it explores the need for treatment of such long-term illnesses to recognize the importance of alternative modes of caring which include strategies, both medical and nonmedical, delivered within and outside of hospitals and nursing homes. The paper includes an analysis of public and private sector priorities based in data published by the U.S. Health Care Financing Administration. It also includes some discussion of the PACE program in the United States and some other efforts to stimulate more in-home and community-based alternatives to nursing home care. Furthermore, it includes a discussion of the policy goal of "appropriateness" in developing long-term care (as well as general health priorities) and provides a critical discussion of problems with utilizing "cost/benefit analysis." The study concludes that too exclusive a focus on nursing home care for the elderly in the United States is unfortunate-both in terms of the desires of the elderly, their families and friends and in terms of focusing on "appropriateness" as a legitimate policy goal in the development of long-term care policy for the elderly in the United States.

  19. Influenza in long-term care facilities.

    Science.gov (United States)

    Lansbury, Louise E; Brown, Caroline S; Nguyen-Van-Tam, Jonathan S

    2017-09-01

    Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  20. The disposition index does not reflect β-cell function in IGT subjects treated with pioglitazone.

    Science.gov (United States)

    DeFronzo, Ralph A; Tripathy, Devjit; Abdul-Ghani, Muhammad; Musi, Nicolas; Gastaldelli, Amalia

    2014-10-01

    The insulin secretion/insulin resistance (IR) (disposition) index (ΔI/ΔG ÷ IR, where Δ is change from baseline, I is insulin, and G is glucose) is commonly used as a measure of β-cell function. This relationship is curvilinear and becomes linear when log transformed. ΔI is determined by 2 variables: insulin secretion rate (ISR) and metabolic clearance of insulin. We postulated that the characteristic curvilinear relationship would be lost if Δ plasma C-peptide (ΔCP) (instead of Δ plasma insulin) was plotted against insulin sensitivity. A total of 441 individuals with impaired glucose tolerance (IGT) from ACT NOW received an oral glucose tolerance test and were randomized to pioglitazone or placebo for 2.4 years. Pioglitazone reduced IGT conversion to diabetes by 72% (P < .0001). ΔI/ΔG vs the Matsuda index of insulin sensitivity showed the characteristic curvilinear relationship. However, when ΔCP/ΔG or ΔISR/ΔG was plotted against the Matsuda index, the curvilinear relationship was completely lost. This discordance was explained by 2 distinct physiologic effects that altered plasma insulin response in opposite directions: 1) increased ISR and 2) augmented metabolic clearance of insulin. The net result was a decline in the plasma insulin response to hyperglycemia during the oral glucose tolerance test. These findings demonstrate a physiologic control mechanism wherein the increase in ISR ensures adequate insulin delivery into the portal circulation to suppress hepatic glucose production while delivering a reduced but sufficient amount of insulin to peripheral tissues to maintain the pioglitazone-mediated improvement in insulin sensitivity without excessive hyperinsulinemia. These results demonstrate the validity of the disposition index when relating the plasma insulin response to insulin sensitivity but underscore the pitfall of this index when drawing conclusions about β-cell function, because insulin secretion declined despite an increase in the

  1. Long term sequelae of pediatric craniopharyngioma - literature review and 20 years of experience

    Directory of Open Access Journals (Sweden)

    Michal eCohen

    2011-11-01

    Full Text Available Craniopharyngioma are rare histologically benign brain tumors that develop in the pituitary- hypothalamic area. They may invade nearby anatomical structures causing significant rates of neurological, neurocognitive and endocrinological complications including remarkable hypothalamic damage. Information regarding long term implications of the tumors and treatment in the pediatric population is accumulating, and treatment goals appear to be changing accordingly. In this review we aim to present data regarding long term complications of craniopharyngioma in children and adolescents and our experience from a large tertiary center. Hypothalamic dysfunction was noted to be the most significant complication, adversely affecting quality of life in survivors. Obesity, fatigue and sleep disorders are the most notable manifestations of this dysfunction, and treatment is extremely difficult. Changes in management in recent years show a potential for improved long term outcomes; we found a trend towards less aggressive surgical management and increasing use of adjuvant treatment, accompanied by a decrease in complication rates.

  2. Antimicrobial stewardship in long term care facilities: what is effective?

    Science.gov (United States)

    Nicolle, Lindsay E

    2014-02-12

    Intense antimicrobial use in long term care facilities promotes the emergence and persistence of antimicrobial resistant organisms and leads to adverse effects such as C. difficile colitis. Guidelines recommend development of antimicrobial stewardship programs for these facilities to promote optimal antimicrobial use. However, the effectiveness of these programs or the contribution of any specific program component is not known. For this review, publications describing evaluation of antimicrobial stewardship programs for long term care facilities were identified through a systematic literature search. Interventions included education, guidelines development, feedback to practitioners, and infectious disease consultation. The studies reviewed varied in types of facilities, interventions used, implementation, and evaluation. Comprehensive programs addressing all infections were reported to have improved antimicrobial use for at least some outcomes. Targeted programs for treatment of pneumonia were minimally effective, and only for indicators of uncertain relevance for stewardship. Programs focusing on specific aspects of treatment of urinary infection - limiting treatment of asymptomatic bacteriuria or prophylaxis of urinary infection - were reported to be effective. There were no reports of cost-effectiveness, and the sustainability of most of the programs is unclear. There is a need for further evaluation to characterize effective antimicrobial stewardship for long term care facilities.

  3. Long-term follow up of revascularization using platelet-rich fibrin.

    Science.gov (United States)

    Ray, Herbert L; Marcelino, Janel; Braga, Raquel; Horwat, Richard; Lisien, Michael; Khaliq, Shahryar

    2016-02-01

    Trauma is one of the primary causes of tooth loss and pulpal injury in adolescents and children. Prior to regenerative endodontics, treatment of necrotic, immature teeth with open apices was limited to long-term calcium hydroxide (Ca(OH)2 ) apexification and subsequent root canal therapy or extraction. Through revascularization, retention of these teeth can be achieved and the elimination of patient symptoms and the radiographic appearance of continued root development were obtained. This report illustrates a revascularization protocol through a case where platelet-rich fibrin (PRF) was utilized as an autologous scaffold for traumatized, necrotic, immature teeth with incomplete root development. Through consistent follow-up reports, comprising of both clinical examination and radiographs, marked improvement in the condition of the traumatized tooth was noted. This case demonstrates the feasibility of utilizing PRF as an effective treatment protocol for traumatized teeth in lieu of traditional treatment protocols, such as long-term calcium hydroxide (Ca(OH)2 ) apexification or extraction. The choice of utilizing PRF, as opposed to other platelet concentrates, such as platelet-rich plasma (PRP) or a blood clot, lies in PRF's ability to allow for a slow, long-term release of autologous growth factors. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Long-term capital planning considering nuclear plant life-cycle management

    International Nuclear Information System (INIS)

    Negin, C.A.; Simpson, J.M.; Hostetler, D.R.

    1992-09-01

    The creation of a Life Cycle Management (LCM) group at utilities to evaluate the long term capital refurbishment needs is gaining favor. Among the functions of such groups can be the responsibility for recommending long term capital planning projects based on results of evaluations of systems, structures, and components that are not only essential to achieving the full current license term of operation, but also to extend the service life of the plant. Making such recommendations, in content and timing, requires the ability to view all recommendations in the context of an overall capital budget and long range outage impacts. This report illustrates an approach for creating a Long-Term Capital Plan with methods for deciding on, compiling, integrating, and presenting projects from the perspective of an LCM program for a nuclear power plant. It also addresses a rationale for capitalization of LCM program activities that would not be allowed under current accounting treatment

  5. Changing M3G/M6G ratios and pharmacodynamics in a cancer patient during long-term morphine treatment

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per

    2002-01-01

    A cancer patient receiving long-term oral sustained-release morphine treatment and periodically presenting with unusually high plasma M3G/M6G ratios is described. We found the patient's formation of M6G more unstable and perhaps delayed compared to the formation of M3G. There is no apparent...... explanation for this phenomenon and the high M3G/M6G ratios had no implications for the patient's pain experience or side effects from the morphine treatment....

  6. Long-term results of the corridor operation for atrial fibrillation

    NARCIS (Netherlands)

    van Hemel, N. M.; Defauw, J. J.; Kingma, J. H.; Jaarsma, W.; Vermeulen, F. E.; de Bakker, J. M.; Guiraudon, G. M.

    1994-01-01

    To investigate the long-term results of the corridor operation in the treatment of symptomatic atrial fibrillation refractory to drug treatment. The corridor operation is designed to isolate from the left and right atrium a conduit of atrial tissue connecting the sinus node area with the

  7. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  8. Brain size and neuropsychological functioning in long-term survivors of pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Mulcahy Levy, Jean M; Hunger, Stephen P

    2013-10-01

    With the increased survival of pediatric cancer patients the interest in the late effects of treatments is rapidly increasing. Long-term survival rates for children with acute lymphoblastic leukemia (ALL) now approach 90%. Treatment for ALL includes intensified central nervous system (CNS)-directed therapy, which is associated with risks for long-term neurocognitive effects. It is becoming clear that current therapies can have not only a detrimental effect on IQ, processing speed, and memory, but also on structural changes that lead to permanent alterations of the organization of the CNS. Understanding how the CNS is affected by the treatments is a critical step in evaluating current therapies and developing interventions to decrease the incidence and severity of long-term changes in brain anatomy and function.

  9. Breast Cancer Survivorship: A Comprehensive Review of Long-Term Medical Issues and Lifestyle Recommendations

    Science.gov (United States)

    Bodai, Balazs I; Tuso, Phillip

    2015-01-01

    Long-term survival rates after a diagnosis of breast cancer are steadily rising. This is good news, but clinicians must also recognize that this brings new challenges to the medical community. As breast cancer becomes a chronic condition rather than a life-threatening illness owing to advances in early diagnosis and more effective treatments, health care practitioners must recognize and manage the long-term sequelae of the constellation of therapeutic modalities. Survivors of breast cancer represent a unique and extremely complex group of patients; not only do they have the challenge of dealing with multiple long-term side effects of treatment protocols, but many are also forced to address the preexisting comorbidities of their therapies, which often include multiple other issues. Therapies have additional and/or additive side effects that may interfere with treatments directed toward the new primary diagnosis of breast cancer. Our mandate is to establish a smooth transition from patient with breast cancer to survivor of breast cancer while providing ongoing and future guidance. Certainly, the information and resources to accomplish this transition are readily available; however, they are scattered throughout the literature and therefore are not easily accessible or available to the primary care physician. It is imperative that the information available regarding survivorship issues be accessible in an organized and useful format. This article is a modest attempt to provide a comprehensive review of the long-term medical issues relevant to survivorship after the diagnosis and treatment of breast cancer. A predicted shortage of oncologists by 2020 is well-recognized. Therefore, the bulk of long-term care will become dependent on the primary care physician. This shift of care means that these physicians will need to be well educated in the long-term medical issues related to breast cancer treatment. PMID:25902343

  10. Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2014-06-01

    Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

  11. Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome).

    Science.gov (United States)

    Laron, Z; Klinger, B; Silbergeld, A

    1999-01-01

    Serum IGF-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-I. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered once daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 micrograms/kg for children and 120 micrograms/kg for adults. Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day. The serum IGF-I levels 4 hours after injection rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l. In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment. Serum IGF-I levels at 4 hours after injection rose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A progressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following serum IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated that the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administration. It is concluded that treatment with IGF-I necessitates regular monitoring of serum IGF-I levels; in patients in whom the age adjusted maximal levels are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.

  12. Pharmacological consequences of long-term morphine treatment in patients with cancer and chronic non-malignant pain

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Sjøgren, Per; Hansen, Steen Honoré

    2004-01-01

    In patients with pain of malignant origin morphine may be administered in high and often increasing doses during extended periods of time. In patients with chronic pain of non-malignant origin morphine may be an important remedy, and in these cases the goal is to keep the morphine dose stable. Th....... The pharmacokinetic as well as the pharmacodynamic consequences of long-term morphine treatment with special reference to the two most important metabolites of morphine morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) remain to be settled....

  13. Repetitive long-term hyperbaric oxygen treatment (HBOT administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function.

    Directory of Open Access Journals (Sweden)

    Klaus Kraitsy

    Full Text Available Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function.

  14. Efficacy of long-term omalizumab therapy in patients with severe asthma.

    Science.gov (United States)

    Saji, Junko; Yamamoto, Takahito; Arai, Motonaka; Mineshita, Masamichi; Miyazawa, Teruomi

    2017-03-01

    The efficacy of omalizumab, an anti-immunoglobulin E (IgE) antibody, has been studied in patients with severe bronchial asthma. We conducted a study to evaluate, on the basis of both objective and subjective measures, the efficacy of omalizumab as a long-term therapy in patients with severe and persistent asthma. Omalizumab was administered subcutaneously every two or four weeks. The results of pulmonary function tests, Asthma Control Test (ACT) and Asthma Health Questionnaire (AHQ)-33 scores, the dosage of methylprednisolone during the 12-month treatment period, and the number of emergency visits prior to the start of treatment with omalizumab were compared in patients pre- and post-treatment with omalizumab. Fourteen patients were enrolled in the study between June 2010 and February 2012. Ten patients completed the study. With omalizumab treatment, there was no improvement in lung function; however, the number of emergency visits (19.3 before treatment vs. 1.2 after treatment, p=0.020) and the dosage of methylprednisolone (871.5mg before treatment vs. 119.0mg after treatment, p=0.046) decreased significantly. ACT and AHQ-33 scores at 16 weeks after treatment were significantly better than baseline scores. Four patients continued treatment with omalizumab for four years, and a reduction in their corticosteroid usage was noted. Long-term omalizumab therapy in our patients was found to significantly reduce corticosteroid usage and the number of emergency visits. Long-term omalizumab therapy was effective and might have potential to reduce the frequency of asthma exacerbations. The trial has not been registered because it is not an intervention study. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  15. Long-term changes in neurocognition and behavior following treatment of sleep disordered breathing in school-aged children.

    Science.gov (United States)

    Biggs, Sarah N; Vlahandonis, Anna; Anderson, Vicki; Bourke, Robert; Nixon, Gillian M; Davey, Margot J; Horne, Rosemary S C

    2014-01-01

    Sleep disordered breathing (SDB) in children is associated with detrimental neurocognitive and behavioral consequences. The long term impact of treatment on these outcomes is unknown. This study examined the long-term effect of treatment of SDB on neurocognition, academic ability, and behavior in a cohort of school-aged children. Four-year longitudinal study. Children originally diagnosed with SDB and healthy non-snoring controls underwent repeat polysomnography and age-standardized neurocognitive and behavioral assessment 4y following initial testing. Melbourne Children's Sleep Centre, Melbourne, Australia. Children 12-16 years of age, originally assessed at 7-12 years, were categorized into Treated (N = 12), Untreated (N = 26), and Control (N = 18) groups. Adenotonsillectomy, Tonsillectomy, Nasal Steroids. Decision to treat was independent of this study. Changes in sleep and respiratory parameters over time were assessed. A decrease in obstructive apnea hypopnea index (OAHI) from Time 1 to Time 2 was seen in 63% and 100% of the Untreated and Treated groups, respectively. The predictive relationship between change in OAHI and standardized neurocognitive, academic, and behavioral scores over time was examined. Improvements in OAHI were predictive of improvements in Performance IQ, but not Verbal IQ or academic measures. Initial group differences in behavioral assessment on the Child Behavior Checklist did not change over time. Children with SDB at baseline continued to exhibit significantly poorer behavior than Controls at follow-up, irrespective of treatment. After four years, improvements in SDB are concomitant with improvements in some areas of neurocognition, but not academic ability or behavior in school-aged children.

  16. Long-term health benefits of appetite suppressants remain unproven

    Directory of Open Access Journals (Sweden)

    Francisco José Roma Paumgartten

    2011-12-01

    Full Text Available Because of the increasing prevalence of obesity, prevention and treatment of overweight has become a major public health concern. In addition to diet and exercise, drugs are needed for patients who failed to lose weight with behavioral treatment. The current article aimed to summarize recent concerns on the safety and efficacy of appetite suppressants. Several appetite suppressants have been banned for safety reasons. In 2010, sibutramine was withdrawn from the market because a long-term study showed it increased the risks of cardiovascular events. So far no study with a sufficiently large sample size has demonstrated that appetite suppressants can reduce morbidity and mortality associated with overweight. The withdrawal of sibutramine highlights that guidelines for the evaluation of weight control drugs must be more stringent, and studies on their long-term health benefits are needed prior to their marketing.

  17. [Chronic pain patients' readiness to change after multimodal treatment. Short- and long-term effects].

    Science.gov (United States)

    Küchler, A; Sabatowski, R; Kaiser, U

    2012-12-01

    , significant short- and long-term improvements were evident. For single outcome parameters, positive associations with the stages of readiness to change were found. The results indicate that the outpatient pain management program favorably affects patients' motivation and general quality of life. This effect also seems to be stable over a long period of time. As not all patients show an improvement in stage of readiness to change, the question arises whether the reason of the differences might lie within the patients' and whether specific interventions for motivation might be useful to enhance motivation before starting treatment.

  18. Prediction method of long-term reliability in improving residual stresses by means of surface finishing

    International Nuclear Information System (INIS)

    Sera, Takehiko; Hirano, Shinro; Chigusa, Naoki; Okano, Shigetaka; Saida, Kazuyoshi; Mochizuki, Masahito; Nishimoto, Kazutoshi

    2012-01-01

    Surface finishing methods, such as Water Jet Peening (WJP), have been applied to welds in some major components of nuclear power plants as a counter measure to Primary Water Stress Corrosion Cracking (PWSCC). In addition, the methods of surface finishing (buffing treatment) is being standardized, and thus the buffing treatment has been also recognized as the well-established method of improving stress. On the other hand, the long-term stability of peening techniques has been confirmed by accelerated test. However, the effectiveness of stress improvement by surface treatment is limited to thin layers and the effect of complicated residual stress distribution in the weld metal beneath the surface is not strictly taken into account for long-term stability. This paper, therefore, describes the accelerated tests, which confirmed that the long-term stability of the layer subjected to buffing treatment was equal to that subjected to WJP. The long-term reliability of very thin stress improved layer was also confirmed through a trial evaluation by thermal elastic-plastic creep analysis, even if the effect of complicated residual stress distribution in the weld metal was excessively taken into account. Considering the above findings, an approach is proposed for constructing the prediction method of the long-term reliability of stress improvement by surface finishing. (author)

  19. Outcome of very long-term treatment with antithyroid drugs in Graves' hyperthyroidism associated with Graves' orbitopathy.

    Science.gov (United States)

    Elbers, Laura; Mourits, Maarten; Wiersinga, Wilmar

    2011-03-01

    It is still debated which treatment modality for Graves' hyperthyroidism (GH) is most appropriate when Graves' orbitopathy (GO) is present. The preference in our center has been always to continue antithyroid drugs for GH (as the block-and-replace [B-R] regimen) until all medical and/or surgical treatments for GO are concluded and the eye disease does not require any further therapy (except prescription of lubricants). This usually takes more than 2 years. The aim of this study was to evaluate the outcome of long-term B-R regimen for GH in GO patients by assessment (after discontinuation of B-R) of (a) the recurrence rate of GH and (b) the relapse rate of GO and its association with recurrent GH and/or (131)I therapy. A retrospective follow-up study was done among all patients referred to the Academic Medical Center in Amsterdam between 1995 and 2005 for GO. The inclusion criteria for the study were a history of GH and GO and a history of treatment for GH with a B-R regimen for more than 2 years. The exclusion criteria were a history of (131)I therapy or thyroidectomy before the end of GO treatment. A questionnaire was sent to 255 patients and returned by 114. Of these patients, 73 qualified for the study. Recurrences of GH and/or GO as indicated by returned questionnaires were checked with treating physicians. Patients were treated with B-R for a median of 41 months (range: 24-132). The median follow-up after discontinuation of the B-R regimen was 57 months (range: 12-170). Recurrent GH occurred in 27 of the 73 study patients (37%) at a median of 3 months (range: 1-65) after withdrawal of antithyroid drug therapy. Nineteen of the 27 patients with recurrent hyperthyroidism were treated with (131)I therapy. A relapse of GO was not encountered in any of the 73 patients. The study suggests that long-term B-R treatment of GH in GO patients is associated with a recurrence rate of hyperthyroidism of about 37%. With the regimen employed, recurrence of hyperthyroidism and

  20. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

    Science.gov (United States)

    Zhu, G; Wang, Y; Li, J; Wang, J

    2015-04-30

    Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Does Full Wound Rupture following Median Pilonidal Closure Alter Long-Term Recurrence Rate?

    Science.gov (United States)

    Doll, Dietrich; Matevossian, Edouard; Luedi, Markus M; Schneider, Ralf; van Zypen, Dominic; Novotny, Alexander

    2015-01-01

    The purpose of this study was to examine the recurrence rate of wound rupture in primary pilonidal sinus disease (PSD) after median closure. A total of 583 patients from the German military cohort were interviewed. We compared the choice of surgical therapy, wound dehiscence (if present) and long-term recurrence-free survival for patients with primary open treatment, marsupialization and primary median treatment (closed vs. secondary open, respectively). Actuarial recurrence rate was determined using the Kaplan-Meier calculation with a follow-up of up to 20 years after primary PSD surgery. Patients with excision followed by primary open wound treatment showed a significantly lower 5- than 10-year recurrence rate (8.3 vs. 11.2%) compared to the patients with primary midline closure (17.4 vs. 20.5%, p = 0.03). The 20-year recurrence rate was 28% in primary open wound treatment versus 44% in primary midline closure without wound rupture. In contrast to these findings, long-term recurrence rates following secondary open wound treatment (12.2% at 5 years vs. 17.1% at 10 years) tended to be higher (although not significantly, p = 0.57) compared to primary open treatment (8.3% at 5 years vs. 11.2% at 10 years). There was no statistical difference in long-term recurrence rates between secondary open and primary midline closure (p = 0.7). Hence, despite only a short wound closure time experienced before wound rupture, the patient does not fully benefit from an open wound treatment in terms of recurrence rate. The postoperative pilonidal sinus wound rupture of primary midline closures did not significantly increase the 5- and 10-year long-term recurrence rates compared to uneventfully healing primary midline closures. © 2015 S. Karger AG, Basel.

  2. Heat treatment of long term serviced Cr – Mo cast steel

    Directory of Open Access Journals (Sweden)

    G. Golanski

    2010-01-01

    Full Text Available The paper presents results of research on the influence of heat treatment on the structure and properties of L20HM cast steel after long term operation at elevated temperature. Investigated cast steel was taken out from an outer frame of a steam turbine serviced for 167 424 hours at the temp. of 535 oC and pressure 12.75 MPa. In post-operating condition the investigated cast steel was characterized by mechanical properties below the required minimum and by high brittleness. Performed research on the influence of austenitizing parameters has revealed that the range of austenitizing temperatures for the examined cast steel: Ac3 + 30 ÷ 60 oC ensures obtaining of a fine austenite grain, homogeneous in size. It has been proved that tempering of bainititc – ferritic structure above 680 ÷ 690 oC causes an increase of impact energy along with a decrease of mechanical properties below the required minimum. Moreover, it has been noticed that applying of under-annealing instead of tempering, after full-annealing, guarantees the required impact energy of KV > 27J, with the mechanical properties similar to those after service.

  3. Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone

    NARCIS (Netherlands)

    T.C.J. Sas (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); Th. Stijnen (Theo); H-J. Aanstoot (Henk-Jan); S.L.S. Drop (Stenvert)

    2000-01-01

    textabstractTo assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance

  4. Long-term observations of operated and irradiated breast carcinoma

    International Nuclear Information System (INIS)

    Decker-Mroz, G.; Schroeder, R.

    1983-01-01

    498 patients with histologically established and surgically removed breast carcinomas received post-operative irradiation treatment at Moabit hospital, Berlin, between 1965 and 1975. The long-term results of this largely standardized therapy have been compiled and evaluated. (orig./MG) [de

  5. Long-term associative learning predicts verbal short-term memory performance.

    Science.gov (United States)

    Jones, Gary; Macken, Bill

    2018-02-01

    Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

  6. Brain tumors in children: long-term survival after radiation treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jenkin, Derek; Greenberg, Mark; Hoffman, Harold; Hendrick, Bruce; Humphreys, Robin; Vatter, Annette

    1995-02-01

    Purpose: To determine the cause of death in children who survive more than 5 years after radiation treatment of a brain tumor. Methods and Material: Nine hundred and twelve consecutive children with a primary brain tumor irradiated at the Princess Margaret Hospital or Toronto-Bayview Regional Cancer Center from 1958 to 1991, were evaluated for long-term outcome. Results: Overall 10- and 20-year survival rates were 44% and 37%. Subsequent survival of 377 5-year survivors was, at an additional 10 and 20 years, 78% and 67%. Most (83%) deaths that occurred more than 5 years from diagnosis were a result of relapse of the original tumor. The 10-year survival rate subsequent to relapse was 9% when the first relapse occurred less than one year from diagnosis, 17% for 1-2 years, and 31% when the time to relapse was 3 years or greater. The cumulative actuarial incidence of, and death from, second malignant tumors at 30 years from diagnosis was 18% and 13%, respectively. Conclusions: Death later than 5 years from diagnosis of a brain tumor in children is common and is usually due to progressive disease in slowly evolving low grade tumors. Death from a second malignant tumor becomes more frequent than death from the original tumor after 15 years from diagnosis.

  7. Long-term erectile function following permanent seed brachytherapy treatment for localized prostate cancer

    International Nuclear Information System (INIS)

    Ong, Wee Loon; Hindson, Benjamin R.; Beaufort, Catherine; Pharoah, Paul; Millar, Jeremy L.

    2014-01-01

    Background and purpose: Erectile function (EF) is commonly affected following prostate cancer treatment. We aim to evaluate the long-term EF following seed brachytherapy (BT) treatment. Materials and methods: The study consisted of 366 patients treated with BT at our institution, who completed the IIEF-5 questionnaire and reported no or mild erectile dysfunction (ED) pre-BT. The probability of EF preservation post-BT was estimated using the Kaplan–Meier methods. The difference in EF preservation by patient-, tumour- and treatment-related factors was assessed using the log-rank test. Multivariate Cox regression was used to estimate the effect of each factor on EF preservation. Results: Of the 366 patients, 277 (76%) reported normal EF, and 89 (24%) reported mild ED. The patients were followed-up for a median of 41 months (range: 3–124), and the 5-year actuarial rate of EF preservation was 59%. Age at BT seed implant, presence of medical comorbidities, Gleason score and the biologically effective dose (BED) are associated with EF preservation (P < 0.005). The association for these four factors remains statistically significant in multivariate analysis, with Gleason score having the strongest effect (HR = 3.7; 95% CI = 2.6–5.4). Conclusion: The 5-year actuarial rate of EF preservation post-BT in our cohort is 59%, and is influenced by multiple factors

  8. Cannabinoid hyperemesis and the cyclic vomiting syndrome in adults: recognition, diagnosis, acute and long-term treatment

    Directory of Open Access Journals (Sweden)

    Blumentrath, Christian G.

    2017-03-01

    Full Text Available The cannabinoid hyperemesis syndrome (CHS and the cyclic vomiting syndrome in adults (CVS are both characterized by recurrent episodes of heavy nausea, vomiting and frequently abdominal pain. Both syndromes are barely known among physicians. Literature is inconsistent concerning clinical features which enable differentiation between CVS and CHS. We performed a literature review using the LIVIVO search portal for life sciences to develop a pragmatic approach towards these two syndromes. Our findings indicate that complete and persistent resolution of all symptoms of the disease following cannabis cessation is the only reliable criterion applicable to distinguish CHS from CVS. Psychiatric comorbidities (e.g. panic attacks, depression, history of migraine attacks and rapid gastric emptying may serve as supportive criteria for the diagnosis of CVS. Compulsive bathing behaviour, a clinical observation previously attributed only to CHS patients is equally present in CVS patients. Long-term follow-up is essential in order to clearly separate CHS from CVS. However, long-term follow-up of CVS and CHS cases is seldom. We provide a standard operating procedure applicable to a broad spectrum of health care facilities which addresses the major issues of CVS and CHS: awareness, diagnosis, treatment, and follow-up.

  9. Long-Term Outcomes of ADHD: A Systematic Review of Self-Esteem and Social Function.

    Science.gov (United States)

    Harpin, V; Mazzone, L; Raynaud, J P; Kahle, J; Hodgkins, P

    2016-04-01

    To compare the long-term self-esteem and social function outcomes of individuals with untreated and treated ADHD across childhood, adolescence, and adulthood. A systematic search of 12 databases was performed to identify peer-reviewed, primary research articles, published January 1980 to December 2011, reporting long-term self-esteem and/or social function outcomes (≥2 years; life consequences distinct from symptoms) of individuals with untreated or treated ADHD. Overall, 127 studies reported 150 outcomes. Most outcomes were poorer in individuals with untreated ADHD versus non-ADHD controls (57% [13/23] for self-esteem; 73% [52/71] for social function). A beneficial response to treatment (pharmacological, nonpharmacological, and multimodal treatments) was reported for the majority of self-esteem (89% [8/9]) and social function (77% [17/22]) outcomes. Untreated ADHD was associated with poorer long-term self-esteem and social function outcomes compared with non-ADHD controls. Treatment for ADHD was associated with improvement in outcomes; however, further long-term outcome studies are needed. © The Author(s) 2013.

  10. Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection

    NARCIS (Netherlands)

    van Beurden, Yvette H.; De Groot, Pieter F.; van Nood, Els; Nieuwdorp, Max; Keller, Josbert J.; Goorhuis, Abraham

    2017-01-01

    Fecal microbiota transfer (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI), but data on procedure-related complications and long-term outcome are scarce. All patients treated with FMT for recurrent CDI at the Academic Medical Center between July 2010 and January

  11. Non-ablative fractional laser provides long-term improvement of mature burn scars

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth H; Danielsen, Patricia L; Paulsen, Ida F

    2015-01-01

    BACKGROUND AND OBJECTIVES: Non-ablative fractional laser-treatment is evolving for burn scars. The objective of this study was to evaluate clinical and histological long-term outcome of 1,540 nm fractional Erbium: Glass laser, targeting superficial, and deep components of mature burn scars....... MATERIALS & METHODS: Side-by-side scar-areas were randomized to untreated control or three monthly non-ablative fractional laser-treatments using superficial and extra-deep handpieces. Patient follow-up were at 1, 3, and 6 months. Primary outcome was improvement in overall scar-appearance on a modified...... of scar-appearance. CONCLUSIONS: Combined superficial and deep non-ablative fractional laser-treatments induce long-term clinical and histological improvement of mature burn scars....

  12. Long-term use of antiplatelet drugs by stroke patients

    DEFF Research Database (Denmark)

    Ostergaard, Kamilla; Hallas, Jesper; Bak, Søren

    2012-01-01

    PURPOSE: Treatment with antiplatelet drugs is a key element of secondary stroke prevention. We investigated long-term antiplatelet drug use in stroke patients with a focus on non-persistence. METHODS: Population-based prescription register data were used to determine antiplatelet drug use...... the dosage of a previous prescription had run out, or within 180 days after discharge. Cox regression was used to identify risk factors for non-persistence. RESULTS: The cohort comprised 503 patients with ischaemic stroke discharged in 1999-2001. During follow-up (median 2.8 years, interquartile range 0......-persistent. Stroke severity was inversely associated with the risk of non-persistence [NIHSS score on admission 0-3 (reference); 4-6: hazard risk (HR) 0.87, 95 % confidence interval (CI) 0.61-1.25; 7+: HR 0.47, 95 % CI 0.29-0.74]. CONCLUSIONS: Long-term non-persistence with antiplatelet treatment was high and more...

  13. Comparison of Efficacy of Long?term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease

    OpenAIRE

    Sent, U.; G?ssl, R.; Elliott, J.; Syme, H. M.; Zimmering, T.

    2015-01-01

    Background The efficacy and benefits of telmisartan in cats with chronic kidney disease (CKD) have not previously been reported. Hypothesis Long?term treatment of cats with CKD using telmisartan decreases urine protein?to?creatinine ratio (UP/C) similar to benazepril. Animals Two?hundred and twenty?four client?owned adult cats with CKD. Methods Prospective, multicenter, controlled, randomized, parallel group, blinded clinical trial with noninferiority design. Cats were allocated in a 1 : 1 ra...

  14. Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

    Directory of Open Access Journals (Sweden)

    L. Frimat

    2010-01-01

    Full Text Available Calcineurin inhibitor (CNI toxicity contributes to chronic allograft nephropathy (CAN. In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA reduction in combination with mycophenolate mofetil (MMF treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group. Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group. One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

  15. Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores.

    Science.gov (United States)

    Lewin, Joel W; O'Rourke, Nicholas A; Chiow, Adrian K H; Bryant, Richard; Martin, Ian; Nathanson, Leslie K; Cavallucci, David J

    2016-02-01

    This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  16. Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models

    Science.gov (United States)

    Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Joseph; Rosenfelt, Cory; Gertner, Michael J.; Campbell, Sean R.; Emerson, Danielle; Hinchey, Paul; Kollaros, Maria; Ferrick, Neal J.; Chambers, Daniel B.; Langer, Steven; Sust, Steven; Malik, Aatika; Terlizzi, Allison M.; Liebelt, David A.; Ferreiro, David; Sharma, Ali; Koenigsberg, Eric; Choi, Richard J.; Louneva, Natalia; Arnold, Steven E.; Featherstone, Robert E.; Siegel, Steven J.; Zukin, R. Suzanne; McDonald, Thomas V.; Bolduc, Francois V.; Jongens, Thomas A.; McBride, Sean M. J.

    2016-01-01

    Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model. PMID:27445731

  17. LONG-TERM SD-OCT/SLO IMAGING OF NEURORETINA AND RETINAL PIGMENT EPITHELIUM AFTER SUB-THRESHOLD INFRARED LASER TREATMENT OF DRUSEN

    Science.gov (United States)

    MOJANA, FRANCESCA; BRAR, MANPREET; CHENG, LINGYUN; BARTSCH, DIRK-UWE G.; FREEMAN, WILLIAM R.

    2012-01-01

    PURPOSE To determine the long-term effect of sub-threshold diode laser treatment for drusen in patients with non-exudative age-related macular degeneration (AMD) with spectral domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscope (SD-OCT/SLO). METHODS 8 eyes of 4 consecutive AMD patients with bilateral drusen previously treated with sub-threshold diode laser were imaged with SD-OCT/SLO. Abnormalities in the outer retina layers reflectivity as seen with SD-OCT/SLO were retrospectively analyzed and compared with color fundus pictures and autofluorescence images (AF) acquired immediately before and after the laser treatment. RESULTS A focal discrete disruptions in the reflectivity of the outer retinal layers was noted in 29% of the laser lesions. The junction in between the inner and outer segment of the photoreceptor was more frequently affected, with associated focal damage of the outer nuclear layer. Defects of the RPE were occasionally detected. These changes did not correspond to threshold burns on color fundus photography, but corresponded to focal areas of increased AF in the majority of the cases. CONCLUSIONS Sub-threshold diode laser treatment causes long-term disruption of the retinal photoreceptor layer as analyzed by SD-OCT/SLO. The concept that sub-threshold laser treatment can achieve a selected RPE effect without damage to rods and cones may be flawed. PMID:21157398

  18. Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report.

    Science.gov (United States)

    Tummolo, Albina; Melpignano, Livio; Carella, Antonella; Di Mauro, Anna Maria; Piccinno, Elvira; Vendemiale, Marcella; Ortolani, Federica; Fedele, Stefania; Masciopinto, Maristella; Papadia, Francesco

    2018-04-22

    Propionic acidemia is a rare autosomal recessive inherited metabolic disorder that can inhibit the synthesis of N-acetylglutamate, the obligatory activator in urea synthesis, leading to hyperammonemia. N-carbamylglutamate ameliorates hyperammonemia in decompensated propionic acidemia. The effects of long-term continuous N-acetylglutamate administration in such patients are unknown. We report our clinical experience with continuous administration of N-acetylglutamate for 6 years in a patient with propionic acidemia frequently presenting with hyperammonemia. A male Caucasian patient with frequently decompensated propionic acidemia and hyperammonemia was admitted 78 times for acute attacks during the first 9 years of his life. Continuous daily treatment with oral N-carbamylglutamate 100 mg/kg (50 mg/kg after 6 months) was initiated. During 6 years of treatment, he had a significant decrease in his mean plasma ammonia levels (75.7 μmol/L vs. 140.3 μmol/L before N-carbamylglutamate therapy, p N-acetylglutamate administration outside the emergency setting. If this observation is confirmed, future studies should aim to optimize the dosage and explore effects of the dosage requirements on other drugs and on protein tolerance.

  19. Long-term follow-up after cervical cancer treatment and subsequent successful surrogate pregnancy.

    Science.gov (United States)

    Agorastos, T; Zafrakas, M; Mastrominas, M

    2009-08-01

    Preservation of fertility is a major concern for premenopausal women after diagnosis of cervical cancer. Successful surrogate pregnancy after treatment for cervical cancer has very rarely been reported. In the present report, a case of successful surrogate pregnancy after radical hysterectomy, lymphadenectomy and ovarian transposition for cervical cancer, followed by radiation therapy, is presented. After stimulation of the transposed ovaries using the short gonadotrophin-releasing hormone (GnRH) analogue protocol, four oocytes were retrieved transabdominally from the genetic mother. IVF followed and two embryos were transferred to the surrogate mother, leading to an uneventful singleton pregnancy, and ultimately normal vaginal delivery of a healthy female infant at term. The unique aspect in this case is the long-lasting favourable outcome for both genetic mother and child, observed during 8.5 years of follow-up, the longest follow-up period reported to date in such cases.

  20. Long-term efficacy and safety of self-intracavernous injection of prostaglandin E1 for treatment of erectile dysfunction in China.

    Science.gov (United States)

    He, L; Wen, J; Jiang, X; Chen, H; Tang, Y

    2011-06-01

    The study evaluated the long-term efficacy and safety profiles of self-intracavernous injection of prostaglandin E1 (PGE1) for erectile dysfunction (ED). Four hundred and sixteen ED patients were treated with self-intracavernous injection of PGE1 from January 1998 to December 2007 in our outpatient service. Follow-up was made to investigate the efficacy and side effects of this treatment. It was found that 261 patients (62.7%) felt satisfied and kept using this treatment due to its advantages of satisfactory efficacy and reasonable expense. Twenty-seven of them (6.5%) got rid of PGE1 treatment after five times injections and did not need any other drugs to maintain satisfactory sexual lives. Two hundred and fourteen (51.4%) patients kept using this treatment for over 1 year, 26 (6.2%) over 5 years, 12 (2.9%) over 8 years and 7 (1.7%) over 10 years. The major complications of self-intracavernous injection of PGE1 include fibrosis of corpus cavernosum (three cases), ecchymosis associated with vascular injury due to injection (23 cases) and pain associated with injection (295 cases). There were no patients displaying priapism. It is concluded that self-intracavernous injection of PGE1 is a safe and effective treatment for ED with various aetiologies and a broad range of severity, and no serious complications were observed after long-term application. © 2011 Blackwell Verlag GmbH.

  1. Long-term outcomes of brief, intensive CBT for specific phobias: The negative impact of ADHD symptoms.

    Science.gov (United States)

    Halldorsdottir, Thorhildur; Ollendick, Thomas H

    2016-05-01

    The objectives were twofold: (a) examine long-term treatment effects in youth receiving 1-session treatment (OST) or educational support (EST) for a specific phobia (SP) and (b) examine the differential predictive and moderation effects of attention-deficit/hyperactivity disorder (ADHD) symptoms on immediate and long-term outcomes following the interventions. Eighty-three children (ages 6-15, 47% female, 89% White) with a SP were randomly assigned to receive OST or EST. Follow up assessments occurred at 1 week, 6 months, 1 year, and 4 years. Hierarchical linear growth modeling (HLGM) was used to explore the association of parent-reported ADHD symptoms, the 2 treatment conditions (i.e., OST vs. EST), and the trajectory of change in the severity of the SP from pretreatment to the 4-year follow-up. Age, conduct problems and learning problems were controlled for in all analyses. A greater immediate reduction in severity rating of the SP was observed in the OST compared to EST, whereas the trajectory of long-term outcomes was similar across conditions over time. Higher levels of ADHD symptoms predicted poor immediate and long-term treatment outcomes across treatment conditions. ADHD symptoms, however, did not moderate the relationship between treatment condition and immediate or long-term treatment outcomes. The results of the study need to be interpreted in light of several study limitations. However, if confirmed, the findings suggest that anxious youth with comorbid ADHD symptoms are less likely to benefit from brief, intensive psychotherapy and may require either longer, standard CBT treatment or adjunctive pharmacotherapy. (c) 2016 APA, all rights reserved).

  2. Long-Term Impact of Intrauterine Neuroinflammation and Treatment with Magnesium Sulphate and Betamethasone: Sex-Specific Differences in a Preterm Labor Murine Model

    Science.gov (United States)

    2017-12-20

    intrauterine neuroinflammation and treatment with magnesium sulphate and betamethasone: Sex -specific differences in a preterm labor murine model...widespread use of Mg504 in clinical practice, its effects on adult offspring are not well known nor have sex -specific differences in therapeutic...injury. Prenatal treatment with MgSOJbetamethasone confers long-term benefits beyond cerebral palsy prevention with sex -specific differences in

  3. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  4. Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus

    DEFF Research Database (Denmark)

    Vestergaard, H; Rossen, M; Urhammer, S A

    1997-01-01

    In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine......-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin......-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum...

  5. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

    DEFF Research Database (Denmark)

    Köhler, Karl Ole; Krogh, Jesper; Mors, Ole

    2016-01-01

    , nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity...

  6. Long-term bioventing performance in low-permeability soils

    International Nuclear Information System (INIS)

    Phelps, M.B.; Stanin, F.T.; Downey, D.C.

    1995-01-01

    Short-term and long-term bioventing treatability testing has shown that in situ air injection and extraction is a practical method for sustaining increased oxygen levels and enhancing aerobic biodegradation of petroleum hydrocarbons in low-permeability soils. At several test sites, initial physical parameter analysis of soils and air permeability tests indicated that impacted soils (fine sandy silts and clays) had low air permeabilities. Measurements of depleted soil-gas oxygen levels and increased soil-gas carbon dioxide levels indicated that the natural process of aerobic biodegradation of petroleum hydrocarbons was oxygen-limited. Initial treatability testing consisted of air permeability tests to measure the permeability of the soils to air and in situ respiration tests to measure the rates at which native microorganisms could biodegrade the contaminants when provided with sufficient oxygen. During the long-term treatment period, active air injection or extraction systems were operated for 1 year or longer. Soil gas was periodically monitored within the treatment zone to evaluate the success of the bioventing systems in increasing soil-gas oxygen levels in the low-permeability soils. Follow-up respiration tests and soil and soil-gas sampling were conducted to evaluate changes in respiration rates and contaminant concentrations with time

  7. Long Term Sequelae of Pediatric Craniopharyngioma – Literature Review and 20 Years of Experience

    Science.gov (United States)

    Cohen, Michal; Guger, Sharon; Hamilton, Jill

    2011-01-01

    Craniopharyngioma are rare histologically benign brain tumors that develop in the pituitary–hypothalamic area. They may invade nearby anatomical structures causing significant rates of neurological, neurocognitive, and endocrinological complications including remarkable hypothalamic damage. Information regarding long term implications of the tumors and treatment in the pediatric population is accumulating, and treatment goals appear to be changing accordingly. In this review we aim to present data regarding long term complications of craniopharyngioma in children and adolescents and our experience from a large tertiary center. Hypothalamic dysfunction was noted to be the most significant complication, adversely affecting quality of life in survivors. Obesity, fatigue, and sleep disorders are the most notable manifestations of this dysfunction, and treatment is extremely difficult. Changes in management in recent years show a potential for improved long term outcomes; we found a trend toward less aggressive surgical management and increasing use of adjuvant treatment, accompanied by a decrease in complication rates. PMID:22645511

  8. Long-term effects of Class II orthodontic treatment on oral health.

    Science.gov (United States)

    Bock, N C; Saffar, M; Hudel, H; Evälahti, M; Heikinheimo, K; Rice, D P C; Ruf, S

    2018-03-01

    To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH). All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence. Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19-44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm). Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

  9. Risk Factors for Long-Term Mortality and Amputation after Open and Endovascular Treatment of Acute Limb Ischemia.

    Science.gov (United States)

    Genovese, Elizabeth A; Chaer, Rabih A; Taha, Ashraf G; Marone, Luke K; Avgerinos, Efthymios; Makaroun, Michel S; Baril, Donald T

    2016-01-01

    Acute limb ischemia (ALI) is a highly morbid and fatal vascular emergency with little known about contemporary, long-term patient outcomes. The goal was to determine predictors of long-term mortality and amputation after open and endovascular treatment of ALI. A retrospective review of ALI patients at a single institution from 2005 to 2011 was performed to determine the impact of revascularization technique on 5-year mortality and amputation. For each main outcome 2 multivariable models were developed; the first adjusted for preoperative clinical presentation and procedure type, the second also adjusted for postoperative adverse events (AEs). A total of 445 limbs in 411 patients were treated for ALI. Interventions included surgical thrombectomy (48%), emergent bypass (18%), and endovascular revascularization (34%). Mean age was 68 ± 15 years, 54% were male, and 23% had cancer. Most patients presented with Rutherford classification IIa (54%) or IIb (39%). The etiology of ALI included embolism (27%), in situ thrombosis (28%), thrombosed bypass grafts (32%), and thrombosed stents (13%). Patients treated with open procedures had significantly more advanced ischemia and higher rates of postoperative respiratory failure, whereas patients undergoing endovascular interventions had higher rates of technical failure. Rates of postprocedural bleeding and cardiac events were similar between both treatments. Excluding Rutherford class III patients (n = 12), overall 5-year mortality was 54% (stratified by treatment, 65% for thrombectomy, 63% for bypass, and 36% for endovascular, P < 0.001); 5-year amputation was 28% (stratified by treatment, 18% for thrombectomy, 27% for bypass, and 17% for endovascular, P = 0.042). Adjusting for comorbidities, patient presentation, AEs, and treatment method, the risk of mortality increased with age (hazard ratio [HR] = 1.04, P < 0.001), female gender (HR = 1.50, P = 0.031), cancer (HR = 2.19, P < 0.001), fasciotomy (HR = 1.69, P = 0.204) in

  10. Long-Term Follow-Up of a Controlled Trial of Laser Laparoscopy for Pelvic Pain

    OpenAIRE

    Jones, Kevin D.; Haines, Patricia; Sutton, Christopher J. G.

    2001-01-01

    Background and Objectives: The purpose of this study was to assess the long-term efficacy of laparoscopic laser surgery in the treatment of painful pelvic endometriosis. Methods: We conducted a long-term follow-up of 56 patients who had participated in a randomized, double-blind controlled study at a tertiary referral center for the laparoscopic treatment of endometriosis. The patients had pelvic pain, minimal-to-moderate endometriosis, and underwent laser laparoscopy. We asked patients wheth...

  11. Long-term outcome in dogs with sinonasal aspergillosis treated with intranasal infusions of enilconazole

    OpenAIRE

    Schuller, S.; Clercx, Cécile

    2007-01-01

    Long-term outcomes (mean 38+/-17 months) were evaluated in 27 dogs with sinonasal aspergillosis after successful medical treatment using intranasal infusions of 1% or 2% enilconazole (1%, n=15; 2%, n=12). Long-term outcomes with both treatment protocols were good, with half of the dogs being asymptomatic throughout the follow-up period. The remaining dogs showed mild clinical signs compatible with chronic rhinitis/sinusitis. These clinical signs were interpreted as chronic lymphoplasmacytic r...

  12. Long-term residential substance abuse treatment for women: lessons learned from Israel

    Directory of Open Access Journals (Sweden)

    Schori M

    2012-02-01

    . Analysis of the questionnaires revealed that compared to non-completers, completers had fewer psychiatric symptoms, higher levels of introverted behavior in stressful situations, a better sense of coherence, and less ability to share emotions. No significant differences were found with regard to demographic and substance use factors. All 19 women who completed treatment and the follow-up questionnaire remained abstinent from illicit drugs for 18 months following the end of treatment.Conclusion: Results indicate that women see the women-only treatment setting as extremely significant. Also, there is a profile of psychiatric co-morbidity, extrapunitiveness, and fewer personal resources that predict a risk for attrition. Thus, women at risk for attrition may be identified early and treatment staff can utilize the results to assist clients in achieving their treatment goals. Results can inform policymakers in making decisions regarding the allocation of resources, by pointing to the importance of long-term women-only residential treatment in increasing positive treatment outcomes.Keywords: gender, drug abuse, therapeutic community, mixed methods, program evaluation

  13. The value of short-term pain relief in predicting the long-term outcome of 'indirect' cervical epidural steroid injections.

    Science.gov (United States)

    Joswig, Holger; Neff, Armin; Ruppert, Christina; Hildebrandt, Gerhard; Stienen, Martin Nikolaus

    2018-05-01

    The predictive value of short-term arm pain relief after 'indirect' cervical epidural steroid injection (ESI) for the 1-month treatment response has been previously demonstrated. It remained to be answered whether the long-term response could be estimated by the early post-interventional pain course as well. Prospective observational study, following a cohort of n = 45 patients for a period of 24 months after 'indirect' ESI for radiculopathy secondary to a single-level cervical disk herniation (CDH). Arm and neck pain on the visual analog scale (VAS), health-related quality of life with the Short Form-12 (SF-12), and functional outcome with the Neck Pain and Disability (NPAD) Scale were assessed. Any additional invasive treatment after a single injection (second injection or surgery) defined treatment outcome as 'non-response'. At 24 months, n = 30 (66.7%) patients were responders and n = 15 (33.3%) were non-responders. Non-responders exited the follow-up at 1 month (n = 10), at 3 months (n = 4), and at 6 months (n = 1). No patients were injected again or operated on between the 6- and 24-month follow-up. Patients with favorable treatment response at 24 months had significantly lower VAS arm pain (p  50% short term pain reduction was not a reliable predictor of the 24-month responder status. SF-12 and NPAD scores were better among treatment responders in the long term. Patients who require a second injection or surgery after 'indirect' cervical ESI for a symptomatic CDH do so within the first 6 months. Short-term pain relief cannot reliably predict the long-term outcome.

  14. Fractional carbon dioxide laser for the treatment of facial atrophic acne scars: prospective clinical trial with short and long-term evaluation.

    Science.gov (United States)

    Elcin, Gonca; Yalici-Armagan, Basak

    2017-12-01

    The aim of this study was to evaluate the efficacy and safety of fractional carbon dioxide laser for the treatment of acne scars. Thirty-one participants, 15 female and 16 male, whose mean age was 34.84 ± 10.94 years, were included in this prospective study. The study took place between 2012 and 2016. Participants were evaluated with the "ECCA Grading Scale" before the first session, 3 months (short-term evaluation) and 3 years after the last session (long-term evaluation). Participants received two or three treatment sessions at 4-week intervals, with a 10,600 nm fractional carbon dioxide laser with pulse energies ranging between 100 and 160 mJ, 120 spot type, 75-100 spot/cm 2 density, and 30 W power. Self-assessments by the participants were done 3 months and 3 years after the last session. The mean ECCA score was 107.90 ± 39.38 before the first session, and 82.17 ± 36.23 at the time of short-term evaluation (p = 0.000). The grade of improvement at the short-term evaluation was as follows: no improvement, mild, moderate, and significant improvement for 7 (22.6%), 11 (35.5%), 9 (29%), and 4 (12.9%) of the participants, respectively. Regarding self-assessments, 80.6 and 61.3% of the participants rated themselves as having at least mild improvement at the short-term and the long-term follow-up periods, respectively. The results of this study suggest that fractional carbon dioxide laser is an efficient treatment option for acne scars. Furthermore, self-assessment results show that more than half of the participants still experience at least mild improvement at the end of 3 years.

  15. Dopamine Modulation of Reunion Behavior in Short and Long Term Marmoset Pairs

    Directory of Open Access Journals (Sweden)

    Sarah B. Carp

    2018-05-01

    Full Text Available One major neurobiological substrate regulating social processes is dopamine (DA. DA is implicated in social behavior in species as diverse as fish and birds, and has an established role in regulating relationships between mates in socially monogamous rodents. Marmoset monkeys display traits associated with social monogamy including high rates of affiliation, biparental care, distress upon separation, and aggression toward strangers; several of these behavioral patterns change throughout the development of relationships. This temporal change may represent changing demands, as pairs are likely to jointly face new experiences (e.g., parenthood throughout pairing. We investigated the role of DA and pairing length on social behavior during reunion after separation from the mate. Marmosets were removed from their home environment and treated with agonists and antagonists for the D1 and D2 receptor subtypes. They were exposed to a novel environment containing an opposite-sex stranger and their pair mate, and then reunited with their mate in the home enclosure. Marmosets in long term pairs exhibited higher levels of food sharing during reunion than marmosets in short term pairs, with females in long term pairs sharing food more than males; no sex difference was observed in short term pairs. Subjects in short term pairs spent more time grooming their mate than receiving grooming during reunion, while marmosets in long term pairs displayed similar amounts of both initiated and received grooming. DA treatment altered pair-level behavior. When females received either a D2 agonist or antagonist, short term pairs spent less time in proximity, compared to when males received the same treatments. In long term pairs, treatment of females with either a D1 agonist or antagonist resulted in pairs spending less time in social proximity than when males were treated. These findings suggest that the function of the DA system in mate behavior may be similar between

  16. A novel method to adjust efficacy estimates for uptake of other active treatments in long-term clinical trials.

    Directory of Open Access Journals (Sweden)

    John Simes

    2010-01-01

    Full Text Available When rates of uptake of other drugs differ between treatment arms in long-term trials, the true benefit or harm of the treatment may be underestimated. Methods to allow for such contamination have often been limited by failing to preserve the randomization comparisons. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD study, patients were randomized to fenofibrate or placebo, but during the trial many started additional drugs, particularly statins, more so in the placebo group. The effects of fenofibrate estimated by intention-to-treat were likely to have been attenuated. We aimed to quantify this effect and to develop a method for use in other long-term trials.We applied efficacies of statins and other cardiovascular drugs from meta-analyses of randomized trials to adjust the effect of fenofibrate in a penalized Cox model. We assumed that future cardiovascular disease events were reduced by an average of 24% by statins, and 20% by a first other major cardiovascular drug. We applied these estimates to each patient who took these drugs for the period they were on them. We also adjusted the analysis by the rate of discontinuing fenofibrate. Among 4,900 placebo patients, average statin use was 16% over five years. Among 4,895 assigned fenofibrate, statin use was 8% and nonuse of fenofibrate was 10%. In placebo patients, use of cardiovascular drugs was 1% to 3% higher. Before adjustment, fenofibrate was associated with an 11% reduction in coronary events (coronary heart disease death or myocardial infarction (P = 0.16 and an 11% reduction in cardiovascular disease events (P = 0.04. After adjustment, the effects of fenofibrate on coronary events and cardiovascular disease events were 16% (P = 0.06 and 15% (P = 0.008, respectively.This novel application of a penalized Cox model for adjustment of a trial estimate of treatment efficacy incorporates evidence-based estimates for other therapies, preserves comparisons between the

  17. The long-term psychiatric and medical prognosis of perinatal mental illness.

    Science.gov (United States)

    Meltzer-Brody, Samantha; Stuebe, Alison

    2014-01-01

    The perinatal period provides an important window into a woman's long-term health. Perinatal mental illness is a common condition conferring potential serious long-term psychiatric and medical consequences for the mother and family. It is known that childbirth acts as a powerful trigger for depressive episodes in some women, and that women with histories of a mood disorder are particularly vulnerable. Some evidence links perinatal mental illness with obstetrical complications and reduced lactation initiation and duration. Therefore, perinatal mental illness may be a marker for long-term risk, and may contribute directly to subsequent cardiometabolic disease through both neuroendocrine mechanisms and the effects of mental illness on health behaviours. In clinical practice, these associations underscore the importance of screening and treating women with perinatal mental illness to ensure best possible long-term outcomes. Early screening and treatment may both mitigate the primary disease process and reduce the risk of comorbid medical conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Profile of mecasermin for the long-term treatment of growth failure in children and adolescents with severe primary IGF-1 deficiency

    Directory of Open Access Journals (Sweden)

    Danilo Fintini

    2009-07-01

    Full Text Available Danilo Fintini, Claudia Brufani, Marco CappaEndocrinology Unit, “Bambino Gesù” Children’s Hospital-IRCCS, Rome, ItalyAbstract: Growth hormone insensitivity syndrome (GHI or insulin-like growth factor-1 (IGF-1 deficiency (IGFD is characterized by deficit of IGF-1 production due to alteration of response of growth hormone (GH receptor to GH. This syndrome is due to mutation of GH receptor or IGF-1 gene and patients affected showed no response to GH therapy. The only treatment is recombinant IGF-1 (mecasermin, which has been available since 1986, but approved in the United States by the US Food and Drug Administration only in 2005 and in Europe by the European Medicines Agency in 2007. To date, few studies are available on long-term treatment with mecasermin in IGFD patients and some of them have a very small number of subjects. In this review we discuss briefly clinical features of severe primary IGFD, laboratory findings, and indications for treatment. Results of long-term therapy with rhIGF1 (mecasermin in patients affected by severe primary IGFD and possible side effects are explained.Keywords: mecasermin, therapy, Laron syndrome, IGF-1

  19. Successful peroral endoscopic myotomy performed in Endoscopy Department as a radical, long-term treatment for esophageal achalasia - the Greek experience.

    Science.gov (United States)

    Eleftheriadis, Nikolas; Eleftheriadou, Eleni Damianos

    2017-01-01

    Peroral endoscopic myotomy (POEM) has been considered as a minimal-invasive, innovative technique for long-term treatment of all types of esophageal achalasia and other esophageal motility disorders. We report on 20 consecutive Greek patients with manometrically proved esophageal achalasia (14 patients with type I, 4 with type II, 2 with type III, and 4 with sigmoid esophagus), with an age range of 32-92 years, mean age 59 years, 12 males, successfully treated by POEM from 2013 to 2015. The Eckardt score was 7-12 (type III). Seventeen (85%) POEM procedures were performed in the Endoscopy Department, according to a previous study. During POEM, CO 2 insufflation was mandatory, while the Triangle Tip knife was the only knife used in all procedures. Eckardt score, esophagogram and manometry before and after performing POEM were used for evaluation of our results. The follow-up period was 6 months to 3 years. Selective circular myotomy, 10-13 cm in length, was successfully completed in all patients without severe acute or late complications. Three patients (15%) showed moderate pneumomediastinum and pneumoperitoneum, which was successfully managed by abdominal needle drainage during the procedure. One patient showed mild pleural collection, and in one patient the clip-endoloop technique was used to successfully close the mucosal entry after the completion of POEM. The outcome was uneventful without any further clinical consequences. No other short- or long-term serious complications were reported. Patients were discharged after 1-3 days of hospitalization. Six months to 3 years after the POEM procedure, all patients were alive; the majority (90%) had complete clinical improvement, while two patients with sigmoid-type achalasia showed moderate-to-significant clinical improvement. Erosive esophagitis was reported in 15%. Our results are in accordance with international data, and proved the safety and efficacy of the POEM technique for radical long-term treatment of all

  20. Long-term results after fibroid embolization; Langzeitergebnisse nach Myomembolisation

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Huelsbeck, S. [Medizinischer Klinikverbund Flensburg, Akademisches Lehrkrankenhaus des Universitaetsklinikums Schleswig-Holstein, Abt. Diagnostische und interventionelle Radiologie/Neuroradiologie, Ev.-Luth. Diakonissenanstalt zu Flensburg, Flensburg (Germany)

    2008-07-15

    Fibroids (leiomyoma) are the most frequent benign tumors of the uterus during female reproductive age. In the case of clinical symptoms, uterine artery embolization (UAE) is a well established treatment option for symptomatic fibroids, resulting in promising long-term results. In order to estimate long-term success after UAE, reduction of fibroids and uterus volume is less important than complete improvement and disappearance of fibroid-related symptoms. In addition to a high technical success rate and a low perioperative complication rate, UAE results in high short-term and long-term patient satisfaction (>87%) and improvement of symptoms (>81%). Candidates for UAE should be informed about potential reinterventions in terms of repeated UAE (up to 18% of cases) or surgical treatment options. (orig.) [German] Myome sind die haeufigsten gutartigen soliden Tumoren des weiblichen Genitaltrakts im reproduktiven Alter. Bei klinischen Beschwerden stellt die Uterusarterienembolisation (UAE) zur Therapie des symptomatischen Uterus myomatosus einen fest etabliertes Verfahren dar, das mit viel versprechenden Langzeitergebnissen aufwarten kann. Im Vordergrund der Abschaetzung eines lang andauernden Therapieerfolgs nach UAE stehen weniger die Volumenreduktion eines dominanten Myoms bzw. des gesamten Uterus nach der Behandlung, sondern vielmehr die Besserung oder das voellige Verschwinden der von der Patientin initial vor der UAE angegebenen (myombedingten) Beschwerden. Neben einer hohen technischen Erfolgsrate und geringen perioperativen Komplikationsrate fuehrt die fachkundig durchgefuehrte UAE sowohl im Kurz- als auch Langzeitverlauf zu einem hohen Mass an Patientenzufriedenheit (>87%), verbunden mit einer deutlichen Symptombesserung (>81%). Ueber eine Reintervention (in bis zu ca. 18% der Faelle) im Sinne einer erneuten UAE oder einer operativen Massnahme sollten die Patientinnen allerdings im Vorfeld aufgeklaert werden. (orig.)