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Week Treatment (week + treatment)
Terms modified by Week Treatment Selected AbstractsRobust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy databaseDIABETES OBESITY & METABOLISM, Issue 10 2008R. E. Pratley Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [source] Improvement of insulin sensitivity and ,-cell function by nateglinide and repaglinide in type 2 diabetic patients , a randomized controlled double-blind and double-dummy multicentre clinical trialDIABETES OBESITY & METABOLISM, Issue 4 2007J. Li Aim:, To evaluate the efficacy of nateglinide vs. repaglinide in blood glucose (BG) control and the effect on insulin resistance and ,-Cell function in patients with type 2 diabetes. Methods:, A randomized controlled double-blind and double-dummy multicentre clinical trial was conducted. A total of 230 Chinese patients with type 2 diabetes were enrolled in five clinical centres. The patients were divided randomly into group A [repaglinide 1.0 mg three times daily (t.i.d.), n = 115] or group B (nateglinide 90 mg t.i.d., n = 115). At baseline and end of the 12-week clinical trial, standard mixed meal tolerance tests were performed. Results:, A total of 223 patients (96.9%) completed the trial. There was no significant difference between repaglinide and nateglinide groups in the effects of reducing fasting blood glucose (FBG), 30-, 60- and 120-min BG during 12 weeks (p > 0.05). At week 12, no significant difference was shown between the two groups in BG or haemoglobin A1c (HbA1c) (p > 0.05). However, the effect on HbA1c in repaglinide group was stronger than that in nateglinide group (p < 0.05). After 12-week treatment, area under the curve (AUC) of BG decreased (p < 0.05), and AUC of insulin and C-peptide (CP) increased in both groups (p < 0.05). The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide (p > 0.05). There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 (p > 0.05). Furthermore, homeostasis model assessment of insulin resistance (HOMA-IR) and ,-cell function indexes measured by HOMA-,, ,I30/,G30 and (,I30/,G30)/HOMA-IR were improved significantly in both groups during 12 weeks (p < 0.05). The effects of improving HOMA-IR and ,-cell function indexes in nateglinide group were comparable with that of repaglinide group (p > 0.05). Conclusions:, The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the effect of repaglinide 1.0 mg t.i.d. on HbA1c is stronger than that of nateglinide 90 mg t.i.d.. This trial had shown that nateglinide and repaglinide could comparably improve insulin sensitivity and ,-cell function. [source] Cost-effectiveness of extended buprenorphine,naloxone treatment for opioid-dependent youth: data from a randomized trialADDICTION, Issue 9 2010Daniel Polsky ABSTRACT Aims The objective is to estimate cost, net social cost and cost-effectiveness in a clinical trial of extended buprenorphine,naloxone (BUP) treatment versus brief detoxification treatment in opioid-dependent youth. Design Economic evaluation of a clinical trial conducted at six community out-patient treatment programs from July 2003 to December 2006, who were randomized to 12 weeks of BUP or a 14-day taper (DETOX). BUP patients were prescribed up to 24 mg per day for 9 weeks and then tapered to zero at the end of week 12. DETOX patients were prescribed up to 14 mg per day and then tapered to zero on day 14. All were offered twice-weekly drug counseling. Participants 152 patients aged 15,21 years. Measurements Data were collected prospectively during the 12-week treatment and at follow-up interviews at months 6, 9 and 12. Findings The 12-week out-patient study treatment cost was $1514 (P < 0.001) higher for BUP relative to DETOX. One-year total direct medical cost was only $83 higher for BUP (P = 0.97). The cost-effectiveness ratio of BUP relative to DETOX was $1376 in terms of 1-year direct medical cost per quality-adjusted life year (QALY) and $25 049 in terms of out-patient treatment program cost per QALY. The acceptability curve suggests that the cost-effectiveness ratio of BUP relative to DETOX has an 86% chance of being accepted as cost-effective for a threshold of $100 000 per QALY. Conclusions Extended BUP treatment relative to brief detoxification is cost effective in the US health-care system for the outpatient treatment of opioid-dependent youth. [source] Extended treatment of older cigarette smokersADDICTION, Issue 6 2009Sharon M. Hall ABSTRACT Aims Tobacco dependence treatments achieve abstinence rates of 25,30% at 1 year. Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder. The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers , 50 years of age, and to determine if gender differences in efficacy existed. Design Open randomized clinical trial. Setting A free-standing, smoking treatment research clinic. Participants A total of 402 smokers of , 10 cigarettes per day, all 50 years of age or older. Intervention Participants completed a 12-week treatment that included group counseling, nicotine replacement therapy (NRT) and bupropion. Participants, independent of smoking status, were then assigned randomly to follow-up conditions: (i) standard treatment (ST; no further treatment); (ii) extended NRT (E-NRT; 40 weeks of nicotine gum availability); (iii) extended cognitive behavioral therapy (E-CBT; 11 cognitive behavioral sessions over a 40-week period); or (iv) E-CBT plus E-NRT (E-combined; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability). Measurements Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24, 52, 64 and 104. Findings The most clinically important findings were significant main effects for treatment condition, time and the treatment × time interaction. The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [(week 24 (58%), 52 (55%), 64 (55%) and 104 (55%)], and was significantly more effective than E-NRT and ST across that period. No other treatment condition was significantly different to ST. No effects for gender were found. Conclusions Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women. NRT does not add to the efficacy of extended CBT, and may hamper its efficacy. Research is needed to determine if these results can be replicated in a sample with a greater range of ages, and improved upon with the addition of medications other than NRT. [source] Eslicarbazepine Acetate: A Double-blind, Add-on, Placebo-controlled Exploratory Trial in Adult Patients with Partial-onset SeizuresEPILEPSIA, Issue 3 2007Christian Elger Summary:,Objective: To explore the efficacy and safety of eslicarbazepine acetate (BIA 2-093), a new antiepileptic drug, as adjunctive therapy in adult patients with partial epilepsy. Methods: A multicenter, double-blind, randomized, placebo-controlled study was conducted in 143 refractory patients aged 18,65 years with ,4 partial-onset seizures/month. The study consisted of a 12-week treatment period followed by a 1-week tapering off. Patients were randomly assigned to one of three groups: treatment with eslicarbazepine acetate once daily (QD, n = 50), twice daily (BID, n = 46), or placebo (PL, n = 47). The daily dose was titrated from 400 mg to 800 mg and to 1,200 mg at 4-week intervals. The proportion of responders (patients with a ,50% seizure reduction) was the primary end point. Results: The percentage of responders versus baseline showed a statistically significant difference between QD and PL groups (54% vs. 28%; 90% CI =,,, ,14; p = 0.008). The difference between the BID (41%) and PL did not reach statistical significance (90% CI =,,, ,1; p = 0.12). A significantly higher proportion of responders in weeks 5,8 was found in the QD group than in the BID group (58% vs. 33%, respectively, p = 0.022). At the end of the 12-week treatment, the number of seizure-free patients in the QD and BID groups was 24%, which was significantly different from the PL group. The incidence of adverse events was similar between the treatment groups and no drug-related serious adverse events occurred. Conclusion: Eslicarbazepine acetate was efficacious and well tolerated as an adjunctive therapy of refractory epileptic patients. [source] Clenbuterol antagonizes glucocorticoid-induced atrophy and fibre type transformation in miceEXPERIMENTAL PHYSIOLOGY, Issue 1 2004Maria Antonietta Pellegrino Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg,1 day,1 in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg,1 day,1s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids. [source] Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C,,HEPATOLOGY, Issue 2 2008Stefan Zeuzem The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFN,)-2a 180 ,g one time per week (qwk), or alb-IFN 900 or 1,200 ,g once every two weeks (q2wk), or 1,200 ,g once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intention-to-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 ,g q2wk, 55.5% (61/110) with 1,200 ,g q2wk, and 50.9% (59/116) with 1,200 ,g q4wk, and 57.9% (66/114) with PEG-IFN,-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 ,g q2wk, 18.2% with 1,200 ,g q2wk and 12.1% with 1,200 ,g q4wk, and 6.1% with PEG-IFN,-2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment-associated missed workdays were significantly lower with alb-IFN 900 ,g q2wk versus PEG-IFN,-2a (1.1 versus 4.3 days; P = 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFN,-2a. (HEPATOLOGY 2008;48:407,417.) [source] Influence of dietary ß-glucan on growth performance, lymphocyte proliferation, specific immune response and haptoglobin plasma concentrations in pigsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2003S. Hiss Summary Immunomodulatory feed additives might offer alternatives to anti-microbial growth promoters in swine production. The present study was conducted to assess the effects of ,-1,3/1,6 glucans, i.e. of specific yeast cell wall components, on immune function and growth performance in pigs. After weaning at 4 weeks of age, 75 piglets were allocated to 3 different groups for 4 weeks, the diet was supplemented with 0, 0.015 or 0.03% of ,-glucan, respectively. All animals were vaccinated against porcine reproductive and respiratory syndrome (PRRS). After 4 weeks, average daily gains (ADG) of ,-glucan treated pigs were not different from the controls. Feed intake was tendentiously (p < 0.1) increased at 0.03%,-glucan, without alteration of feed efficiency. Serum haptoglobin concentrations at the end of the 4 week treatment were increased in all groups when compared to the initial levels (p < 0.001), without differences between the groups (p > 0.05). Haptoglobin levels were inversely related to ADG. Lymphocyte proliferation indices were not different in control and treatment groups. Specific vaccination responses, as quantified by the PRRS antibody titres occurred in all animals, but no relation with ,-glucan feeding was observed. Our results indicate marginal benefits of ,-glucan supplements for growth performance and no effect on the immune parameters tested. The observed trend towards increased feed intake needs further elucidation. [source] Feasibility of individualized treatment for hepatitis C patients in the real worldJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2010Tsung-Ming Chen Abstract Background and Aim:, Individualized treatment with a combination of peg-interferon and ribavirin for patients with hepatitis C virus (HCV) infection has been validated in randomized controlled clinical trials, but its usefulness in the real world is unknown. The aim of the present study was to assess the feasibility of individualized treatment for HCV patients compared with standard therapy in a real-life clinical setting. Methods:, A total of 253 naïve patients with HCV infection who received peg-interferon and ribavirin combination treatment were analyzed and grouped into one of three clinical settings: (i) infection with genotype non-1 (HCV non-1) and treatment for standard 24 weeks (n = 105; none received an abbreviated therapy); (ii) genotype 1 (HCV-1) and standard therapy for either 24 weeks (n = 71) or 48 weeks (n = 21); and (iii) HCV-1 and individualized treatment (n = 56). The individualized therapy used was an abbreviated 24-week treatment for HCV-1 patients who achieved a rapid virological response, otherwise patients received a 48-week course of treatment. Early termination of treatment at week 16 was recommended for non-responders. Results:, A sustained virological response (SVR) was achieved in 83.8% of patients with HCV non-1 infection. Among the HCV-1-infected patients, 53.5% of patients who underwent standard 24-week treatment, 66.7% of patients who underwent standard 48-week treatment, and 64.3% of patients treated by individualized therapy achieved SVR. Patients infected with HCV-1 and treated by individualized therapy had a similar efficacy response compared with the standard 48-week therapy (adjusted odds ratio [OR] 0.765, 95% confidence interval [CI], 0.220,2.659, P = 0.673). Both individualized therapy (adjusted OR 2.855, 95% CI 1.189,6.855, P = 0.019) or standard 48-week treatment (adjusted OR 3.733, 95% CI 1.073,12.986, P = 0.038) had significantly higher odds of SVR compared with HCV-1 patients treated by standard 24-week course. Conclusion:, Individualized therapy is feasible in the real world, especially for patients with HCV-1 infection. [source] Variation in GABRA2 Predicts Drinking Behavior in Project MATCH SubjectsALCOHOLISM, Issue 11 2007Lance O. Bauer Background:, Previous studies demonstrated, and replicated, an association between single nucleotide polymorphisms (SNPs) within the GABRA2 gene and risk for alcohol dependence. The present study examines the association of a GABRA2 SNP with another definition of alcohol involvement and with the effects of psychosocial treatment. Methods:, European-American subjects (n = 812, 73.4% male) provided DNA samples for the analysis. All were participants in Project Matching Alcoholism Treatment to Client Heterogeneity (MATCH), a multi-center randomized clinical trial evaluating the efficacy of 3 types of psychosocial treatment for alcoholism: Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET), or twelve-step facilitation (TSF). The daily probabilities of drinking and heavy drinking were estimated during the 12-week treatment and 12-month post-treatment periods. Results:, Subjects homozygous for the allele associated with low risk for alcohol dependence in previous studies had lower daily probabilities of drinking and heavy drinking in the present study. This low-risk allele was also associated with a greater difference in drinking outcomes between the treatments. In addition, it enhanced the relative superiority of TSF over CBT and MET. Population stratification was excluded as a confound using ancestry informative marker analysis. Conclusions:, The assessment of genetic vulnerability may be relevant to studies of the efficacy of psychosocial treatment: GABRA2 genotype modifies the variance in drinking and can therefore moderate power for resolving differences between treatments. [source] A randomized, single-blind, placebo-controlled, split-face study with pimecrolimus cream 1% for papulopustular rosaceaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2008AA Karabulut Abstract Background, Rosacea is a common inflammatory skin disorder for which the pathogenesis is unclear. Currently, there is no cure for rosacea, and it seems that standard therapies have focused mainly on minimizing inflammation. Objectives, The aim of this study is to investigate the potential efficacy, tolerability and safety profile of 1% pimecrolimus cream for the treatment of rosacea. Methods, Twenty-five patients with papulopustular rosacea were enrolled to a randomized, single-blinded, placebo-controlled, split-face trial of pimecrolimus cream 1% consisting 4 week treatment and 2 week follow-up period. The patients were instructed to apply first the ,left side cream' labelled placebo cream (Ultrabase cream, Intendis GmbH, Berlin, Germany) to the left hemi-face then the ,right side cream' labelled 1% pimecrolimus cream (Elidel; Novartis Pharma, Nuremberg, Germany) to the right hemi-face, twice daily. They were informed to apply a standard amount of each cream with the fingertip-unit and not allowed to use any other agent concomittantly other than sunblock. Clinical evaluation and subjective severity assessment were obtained along with photographic documentation at baseline, first, second, and fourth weeks of the therapy and at the follow-up visit. Rosacea severity score for each sign of erythema, papules, pustules, oedema, and telengiectesia were graded from 0 to 3. Patients were questioned for the subjective symptoms, overall improvement on appearance and side-effects. Results, Twenty-four patients completed the study with an exceptional compliance and tolerable safety profile. One patient withdrew from the study due to severe flare-up reaction affecting both hemi-faces. The mean baseline total rosacea severity scores were 5.06 + 1.29 for both sides and reduced to 2.5 ± 1.06 vs. 3.25 ± 1.24 on pimecrolimus vs. placebo applied sides without the significance (P = 0.06). There was not any significant difference concerning each rosacea sign scores and total rosacea severity scores except for the significant improvement in erythema score and total rosacea severity score obtained on the pimecrolimus-applied hemi-face at 2nd week of therapy (P =0.01 and P = 0.03, respectively). The reduction rates of the mean subjective severity scores at 4th week were 49.77% vs. 38.89% for pimecrolimus vs. placebo, respectively, without a statistical significance (P = 0.15). Subjective symptoms responded well in 54.16% of patients concerning pimecrolimus application compared with 12.50% for the placebo application. The side-effects were mostly transient local irritations. Conclusion, Our data implicated that pimecrolimus cream is not superior to placebo except for its efficacy on erythema. We believe that pimecrolimus cream can be a treatment option for rosacea patients with high erythema score for whom an initial accelerated improvement is needed. We believe further studies with topical pimecrolimus cream on larger study groups with different subtypes and severity of rosacea will clarify the potential effect of pimecrolimus cream for the treatment of rosacea. [source] Clinical trial: extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late respondersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009M. NAGAKI Summary Background, The benefits of prolonging peginterferon and ribavirin after 48 weeks of treatment to maximize sustained virological responses (SVR) in hepatitis C virus (HCV) genotype 1-infected patients remain to be understood. Aim, To investigate whether extended treatment longer than 72 weeks may be superior to 72-week treatment. Methods, A total of 120 treatment-naïve or retreated patients with HCV genotype 1 were treated with peginterferon-alpha-2b (1.5 ,g/kg/week) plus weight-based ribavirin. We had 34 late responders, in whom HCV RNA first became undetectable at week 12,48, and randomized them into three groups receiving standard-dose peginterferon-alpha-2b plus low-dose ribavirin (200 mg/day) for extended 24 weeks (group A), receiving low-dose peginterferon-alpha-2b (0.75 ,g/kg/week) plus low-dose ribavirin for extended 48 weeks (group B) or no extended treatment (group C), and evaluated the outcome according to their virological response. Results, Multivariate analysis showed that the treatment for 96 weeks was identified as a significant, independent factor associated with SVR in HCV genotype 1-infected late responders in comparison with group A [odds ratio (OR), 10.002; P = 0.080] and group C (OR, 17.748; P = 0.025). Conclusion, Extending the treatment duration from 48 weeks to 96 weeks improves SVR rates in genotype 1-infected patients with late virological response to peginterferon-alpha-2b and ribavirin. [source] Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 9 2006Qi He Abstract: Background/Aims: The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C (CHC). The aim of this study was to explore the relationship of the toll-like receptor (TLR) expression with the outcome of antiviral therapy in hepatitis C viral infection. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC patients before a 48-week treatment with pegylated interferon (PEG IFN) ,-2a and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase chain reaction (RT-PCR) was used to compare the relative abundance of TLR2,9 transcripts. Results: mRNA levels of TLR2, 3 and 6 were significantly higher in CHC subjects compared with normal controls (n=8). When patients were classified into non-responders (n=8) and sustained virological responders (n=7) according to the virological outcome of the treatment, there was a clear difference in baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition, the mRNA expression of IFN-, and nuclear factor of activated T cells (NFAT), which is exclusively expressed in activated T cells, was inversely correlated with that of TLR4, 6 and 9 in non-responders. Conclusions: TLRs mRNA levels are differentially expressed in baseline PBMC of chronic HCV-infected subjects with or without responsiveness to antiviral therapy. [source] Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthmaALLERGY, Issue 7 2010N. Scichilone To cite this article: Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternò A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010; 65: 897,902. Abstract Background:, Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. Aim:, To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. Methods:, After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 ,g daily or fluticasone propionate/salmeterol (FP/S) 500/100 ,g daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Results:, Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV1) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV1 in both BDP/F and FP/S groups (0.37 ± 0.13 l and 0.36 ± 0.12 l, respectively). PD20FEV1 Mch improved significantly from 90.42 (±30.08) ,g to 432.41 (±122.71) ,g in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN2 test parameters. Conclusion:, The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN2 tests. [source] The effect of Phyllanthus amarus aqueous extract on blood glucose in non-insulin dependent diabetic patientsPHYTOTHERAPY RESEARCH, Issue 7 2001Mainen J. Moshi Abstract The glycaemic response to 124.5,±,9.3 (mean,±,SD),g of pancakes was monitored in 21 non-insulin dependent diabetic (NIDDM) patients while on oral hypoglycaemics, after a 1-week washout period and after a 1-week twice daily treatment with 100,mL of an aqueous extract from 12.5,g of powdered aerial parts of Phyllanthus amarus. After the 1-week washout period, the fasting blood glucose (FBG) and postprandial blood glucose increased significantly compared with treatment on oral hypoglycaemics (,p,<,0.05). After a 1-week herbal treatment no hypoglycaemic activity was observed. Both FBG and postprandial blood glucose remained very similar to that recorded after the washout period (,p,>,0.05). Both liver and renal functions based on alanine transaminase (ALAT) and serum creatinine, respectively, were not significantly affected by the use of the extract. Although the lymphocyte and monocyte levels were significantly decreased (,p,<,0.05) and the granulocyte level was significantly increased after treatment (,p,<,0.05) the overall total white blood cell (WBC) count and haemoglobin (Hb) were not significantly affected by the 1 week herbal treatment. We conclude that 1 week treatment with the aqueous extract of Phyllanthus amarus was incapable of lowering both FBG and postprandial blood glucose in untreated NIDDM patients. Copyright © 2001 John Wiley & Sons, Ltd. [source] Safety and efficacy of tramadol in the treatment of idiopathic detrusor overactivity: a double-blind, placebo-controlled, randomized studyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2006M. R. Safarinejad Aim To evaluate the efficacy and safety of tramadol in patients with idiopathic detrusor overactivity (IDO). Methods A total of 76 patients 18 years or older with IDO were randomly assigned to receive 100 mg tramadol sustained release (group 1, n = 38) or placebo (group 2, n = 38) every 12 h for 12 weeks. Clinical evaluation was performed at baseline and every 2 weeks during treatment. All patients underwent urodynamics and ice water test at baseline and 12-week treatment. Main outcome measures were number of voids per 24 h, urine volume per void and episodes of urge incontinence per 24 h on a frequency volume chart and detailed recording of adverse effect. Results After 12 weeks of treatment mean number of voids per 24 h ± SD decreased from 9.3 ± 3.2 to 5.1 ± 2.1 (P < 0.001 vs. placebo) [95% confidence interval (CI) ,5.1-,0.4]. At that time mean urine volume per void increased from 158 ± 32 to 198 ± 76 ml (P < 0.001 vs. placebo) (95% CI 8-22), while mean number of incontinence episodes per 24 h decreased from 3.2 ± 3.3 to 1.6 ± 2.8 (P < 0.001 vs. placebo) (95% CI ,2-0.3). Tramadol induced significant improvements in urodynamic parameters. More adverse effects were associated with tramadol treatment than with placebo (P < 0.05). The main adverse event with tramadol was nausea. Conclusions In patients with non-neurogenic IDO tramadol provided beneficial clinical and urodynamic results. Further studies are required to draw final conclusions on the efficacy of this drug in IDO. [source] Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose toleranceCLINICAL ENDOCRINOLOGY, Issue 1 2005Yi-Jen Hung Summary Objective, This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, ,-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). Methods, Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) , 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. Results, After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4·25 ± 0·22 vs 4·80 ± 0·17 mmol/l, P < 0·001), high-density lipoprotein cholesterol (HDL-C) (1·25 ± 0·07 vs 1·43 ± 0·06 mmol/l, P < 0·05), and low-density lipoprotein cholesterol (LDL-C) (2·70 ± 0·15 vs 3·37 ± 0·17 mmol/l, P < 0·05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic ,-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0·38 ± 0·06 vs 0·54 ± 0·09 × 10,5 min,1/pmol, P < 0·05; 0·017 ± 0·002 vs 0·021 ± 0·001 min,1, P < 0·05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0·05). Conclusion, Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on ,-cell secretory function. [source] Effects of six antihypertensive drugs on blood pressure and hypothalamic GABA content in spontaneously hypertensive ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001Ying Guan In order to investigate the effects of antihypertensive drugs on blood pressure and ,-amino butyric acid (GABA) content in the hypothalamus and the possible relationship between blood pressure decrease and GABA content changes, blood pressure and GABA contents after chronic (20 weeks) treatments of nitrendipine, atenolol, captopril, hydrochlorothiazide, dihydralazine and prazosin were studied in spontaneously-hypertensive rats (SHR). The acute and subacute (1 week) effects of nitrendipine on GABA contents was also observed in SHR. It was found that 20 week treatments with six different antihypertensive agents produced a decrease in systolic blood pressure and an increase in GABA content. The blood pressure level was significantly correlated with GABA content in the hypothalamus, but not with that in the cortex. Acute treatment with a single dose of nitrendipine, did not alter GABA content. Bicuculline, a GABA receptor antagonist, did not attenuate the hypotensive effect of nitrendipine. In conclusion, chronic treatments by different antihypertensive agents produced an increase of hypothalamic GABA content and a decrease of blood pressure. The increase of GABA content induced by nitrendipine seems likely to be secondary to blood pressure decrease. [source] Effects of antipsychotic medication on muscarinic M1 receptor mRNA expression in the rat brainJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2008Mei Han Abstract Alterations in muscarinic M1 receptor protein and mRNA expression have been revealed in post-mortem brains of schizophrenia patients. Most patients had been treated with antipsychotics, so medication effects cannot be excluded as a possible explanation for these results. With in situ hybridization, this study investigated M1 receptor mRNA expression in rats treated with the typical antipsychotic haloperidol (0.3 mg/kg/day) and the atypical antipsychotics olanzapine (1.5 mg/kg/day) and aripiprazole (2.25 mg/kg/day) for 1 or 12 weeks. Compared with the control group, haloperidol significantly increased (,13,21%, P < 0.05) M1 mRNA expression in the CA1, CA2, and CA3 regions of the hippocampus after both 1 and 12 weeks of treatment, and it also increased (,17%, P < 0.01) M1 mRNA expression in the substantia nigra compacta after 1 week of treatment. Olanzapine significantly increased (14,22%, P < 0.05) M1 mRNA expression in the hippocampus (CA1, CA2, and CA3) and substantia nigra compacta after 12 weeks of treatment, but not after 1 week. Aripiprazole significantly increased (17%, P < 0.01) M1 mRNA expression in the hippocampus (CA1) after both 1 and 12 week treatments and increased (12%, P < 0.05) M1 mRNA expression in the nucleus accumbens after 1 week of treatment. Despite their different affinities for muscarinic M1 receptors, all three antipsychotic medications induced a similar trend of change in M1 mRNA expression in selected brain regions. These data suggest that the decreased M1 receptor protein and mRNA expression observed in schizophrenia patients is unlikely to be a consequence of drug treatments and implicates muscarinic M1 receptors in the pharmacotherapy of the disease. © 2007 Wiley-Liss, Inc. [source] Effects Of The New Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor Fluvastatin On Anti-Oxidant Enzyme Activities And Renal Function In Streptozotocin-Induced Diabetic RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2000Atsushi Kurusu SUMMARY 1. The effects of 11 week treatments with the new hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on renal intrinsic anti-oxidant enzyme (AOE) activities and renal function were evaluated in streptozotocin (STZ)-induced diabetic rats. 2. Renal intrinsic AOE activities, creatinine clearance and urinary albumin excretion were examined in STZ-induced diabetic rats. The levels of total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were also examined. 3. In general, renal AOE activities and function were lower in diabetic rats than in non-diabetic Sprague-Dawley rats. 4. Decreases in TC, TG and PL levels and urinary albumin excretion by the HMG-CoA reductase inhibitor fluvastatin improved renal function and produced a non-uniform alteration in renal AOE; only glutathione peroxidase (GSH-Px) activity increased significantly with fluvastatin treatment. 5. It appears that the improvement in renal function and albuminuria may be related to increases in GSH-Px activity, but there was no correlation between changes in renal function and changes in the activity of Mn-superoxide dismutase or catalase. [source] Achieving symptomatic remission in out-patients with schizophrenia , a naturalistic study with quetiapineACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009T. Wobrock Objective:, Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12-week non-interventional study (NIS) with quetiapine was conducted in Germany. Method:, For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission. Results:, Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks' treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI-S) at baseline. Predictors of non-remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse. Conclusion:, This study demonstrated that the majority of schizophrenia out-patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission. [source] Cholinesterase inhibitors in advanced Dementia with Lewy bodies: increase or stop?INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2006Sanjeet Pakrasi Abstract Introduction There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. Method We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15,mg) to resolve re-emergent neuropsychiatric symptoms. Results The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. Conclusion Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms. Copyright © 2006 John Wiley & Sons, Ltd. [source] Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearanceJOURNAL OF MEDICAL VIROLOGY, Issue 8 2007Jinlin Hou Abstract The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P,=,0.014), or genotype D alone (P,=,0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P,<,0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P,=,0.001; odds ratio 6.19, 95 confidence interval 1.94,19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055,1063, 2007. © 2007 Wiley-Liss, Inc. [source] Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma model and effects of combination treatment with cisplatin and BCNUJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2007Susan Murphy Thalidomide is currently under evaluation as an anti-angiogenic agent in cancer treatment, alone and in combination with cytotoxic agents. Thalidomide is a racemate with known pharmacologic and pharmacokinetic enantioselectivity. In a previous study with thalidomide combination chemotherapy, we found evidence of anti-tumour synergy. In this study, we examined whether the synergy involved altered pharmacokinetics of thalidomide enantiomers. Adult female F344 rats were implanted with 9L gliosarcoma tumours intracranially, subcutaneously (flank), or both. Effectiveness of oral thalidomide alone, and with intraperitoneal BCNU or cisplatin combination chemotherapy, was assessed after several weeks treatment. Presumed pseudo steady-state serum, tumour and other tissues, collected after treatment, were assayed for R - and S -thalidomide by chiral HPLC. Both serum and tissue concentrations of R -thalidomide were 40,50% greater than those of S -thalidomide. Co-administration of BCNU or cisplatin with thalidomide did not alter the concentration enantioselectivity. Poor correlation of concentration with subcutaneous anti-tumour effect was found for individual treatments, and with all treatments for intracranial tumours. The consistency of the enantiomer concentration ratios across treatments strongly suggests that the favourable anti-tumour outcomes from interactions between thalidomide and the cytotoxic agents BCNU and cisplatin did not have altered enantioselectivity of thalidomide pharmacokinetics as their basis. [source] Influence of ,2-adrenoceptor polymorphisms on the response to chronic use of albuterol in asthmatic childrenPEDIATRIC PULMONOLOGY, Issue 5 2008Verónica Giubergia MD Abstract Background Several studies have suggested that after regular use of short acting ,2-agonists the bronchodilator effect of the drug may decline and this condition would be related to polymorphisms of the ,2-adrenergic receptor (,2-AR). Objective To assess the frequency of ,2-AR polymorphisms in asthmatic children from Argentina, and to evaluate their influence on bronchodilator desensitization to albuterol over a 4-week treatment. Methods ,2-AR genotypes were determined in 117 children with asthma and 101 of them were under 4 weeks treatment with albuterol. Spirometric changes in FEV1 were recorded at the beginning (day 1) and at the end of the study (day 30) and compared to genotypes at position 16 and 27 of the receptor. The frequency of the polymorphisms was calculated in all population. Results The presence of glutamine at position 27 (Gln27) was significantly more frequent in this Argentinean study population than in other Caucasian populations. The homozygosity for Gln27 polymorphism was associated to a desensitization of the receptor with a decline in the bronchodilator response to albuterol after chronic use. Conclusion Gln27 polymorphism might be a marker for adverse clinical outcomes with chronic ,2-agonist exposure in children with asthma from Argentina. Pediatr Pulmonol. 2008; 43:421,425. © 2008 Wiley-Liss, Inc. [source] Panax ginseng reduces adriamycin-induced heart failure in ratsPHYTOTHERAPY RESEARCH, Issue 12 2005Jyh-Sheng You Abstract The purpose of this study was to investigate the protective effects of Panax ginseng on adriamycin-induced heart failure. Wistar rats were divided into four groups: control, adriamycin, ginseng and adriamycin with ginseng. Adriamycin (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks. Ginseng was administered via an oral feeding tube once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5 week post-treatment period, the hearts of the rats were used to study the synthesis rates of DNA, RNA and protein, myocardial antioxidants and lipid peroxidation. At the end of 3 weeks treatment, heart failure was characterized by ascites, congested liver and depressed cardiac function. Nucleic acid as well as protein synthesis was inhibited, lipid peroxidation was increased and myocardial glutathione peroxidase activity was decreased indicating adriamycin-induced heart failure. In contrast, the administration of ginseng, before and concurrent with adriamycin, significantly attenuated the myocardial effects, lowered the mortality as well as the amount of ascites, increased in myocardial glutathione peroxidase, macromolecular biosynthesis and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. These findings indicated that ginseng may be partially protective against adriamycin-induced heart failure. Copyright © 2005 John Wiley & Sons, Ltd. [source] Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medicationACTA OPHTHALMOLOGICA, Issue 3 2010Hannu Uusitalo Abstract. Purpose:, The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan®) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan®) treatment. Methods:, A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits. Results:, Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 ± 2.7 mmHg) as latanoprost at baseline (16.8 ± 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 ± 2.5 seconds to 7.8 ± 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. Conclusions:, Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort. [source] CONTINUOUS FLUOXETINE ADMINISTRATION PREVENTS RECURRENCE OF PULMONARY ARTERIAL HYPERTENSION AND PROLONGS SURVIVAL IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2009Shao-Ping Zhu SUMMARY 1The serotonin transporter (SERT) is strongly implicated in the pathogenesis of pulmonary arterial hypertension (PAH) in patients and animal models. Inhibitors of SERT have been reported to attenuate or reverse experimental PAH, which makes them potential therapeutic options for the treatment of PAH in humans. However, little is known about pathophysiological features after reversal or attenuation of PAH; moreover, the long-term therapeutic effects of SERT inhibitors on PAH remain undetermined. Thus, the aim of the present study was to investigate the short- and long-term effects of fluoxetine on monocrotaline (MCT)-induced PAH and associated pathophysiological changes in PAH models. 2Rats were randomly divided into four groups as follows: (i) an M + F group, in which rats received a single injection of MCT (60 mg/kg, s.c.) and then after 3 weeks were given fluoxetine (10 mg/kg) once daily by gavage from Week 4 to Week 12; (ii) an M/F group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection, rats were given fluoxetine (10 mg/kg) by daily gavage from Week 4 to Week 6 and were then given an equivalent volume of saline once daily by gavage from Week 7 to Week 12; (iii) an MCT group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection rats were given an equivalent volume of saline by gavage from Week 4 to Week 12; and (iv) a saline group, in which rats received an equivalent volume of saline injection or gavage over the 12 week treatment period. Morphometric changes, pulmonary arterial pressure, percentage wall thickness, right ventricular hypertrophy index and SERT expression were detected at various times during the 12 week treatment period. Survival analysis was performed in each group. 3After 12 weeks treatment, it was found that even through fluoxetine treatment resulted in complete reversal of PAH, PAH recurred after fluoxetine withdrawal. In contrast, continuous administration of fluoxetine prevented the recurrence of PAH and prolonged survival. Analysis of SERT protein levels in rat lung indicated that, compared with values obtained at Week 0, SERT protein increased significantly after discontinuation of fluoxetine but continuous fluoxetine administration inhibited this increase. 4In conclusion, SERT overexpression correlates with the recurrence of PAH after withdrawal of fluoxetine in rats. Continuous fluoxetine administration prevents recurrence of PAH and prolongs survival. [source] COMPARISON OF THE EFFECTS OF TULOBUTEROL PATCH AND SALMETEROL IN MODERATE TO SEVERE ASTHMACLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2006Osamu Nishiyama SUMMARY 1Although the clinical effects of the tulobuterol patch have been reported to include an increase in morning peak expiratory flow (PEF) values and a decrease of symptoms and the frequency of the rescue use of inhaled short-acting b2 -adrenoceptor agonists, no trials comparing the efficacy of the tulobuterol patch to other standard inhaled long-acting b2 -adrenoceptor agonists have yet been conducted. The aim of the present study was to compare the clinical effects of the patch formulation of tulobuterol with those of inhaled salmeterol in moderate to severe asthma. 2Fifty-four patients with moderate to severe asthma, whose conditions were suboptimally controlled despite receiving inhaled corticosteroids, were recruited. The study was a prospective, randomized trial of cross-over design comparing the effects of 4 weeks treatment with tulobuterol patch, 2 mg once daily, and salmeterol, 50 mg twice daily. The mean prebronchodilator morning PEF during the last 14 days of each treatment period and health-related quality of life (HRQoL) were the primary outcome variables. The HRQoL was assessed using the St George's Respiratory Questionnaire. 3Forty-four patients (81.5%) completed the trial and were included in the analysis. The mean morning PEF and HRQoL score were significantly improved in both the salmeterol (P < 0.0001 and P < 0.05, respectively) and the tulobuterol patch (P < 0.01 and P < 0.05, respectively) treatment periods compared with the run-in period. Although the mean morning PEF was significantly higher in the salmeterol-treated group than in the tulobuterol-treated group (P < 0.001), the HRQoL scores were comparable. 4The tulobuterol patch may be useful as a controller medication in addition to inhaled corticosteroids in moderate to severe asthma. [source] Achieving symptomatic remission in out-patients with schizophrenia , a naturalistic study with quetiapineACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009T. Wobrock Objective:, Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12-week non-interventional study (NIS) with quetiapine was conducted in Germany. Method:, For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission. Results:, Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks' treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI-S) at baseline. Predictors of non-remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse. Conclusion:, This study demonstrated that the majority of schizophrenia out-patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission. [source] | |||||||||||||||||||||||||||||||