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Good Responders (good + responder)
Selected AbstractsThe hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosisHEPATOLOGY, Issue 5 2000Carlo Merkel In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was ,12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow-up was significantly higher in poor responders (41%) than in good responders (7%; P = .0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow-up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (, = 1.91; SE(,) = 0.80; P = .01). During follow-up 11 patients died of hepatic causes. Survival was related to Child-Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta-blockers or beta-blockers plus nitrates. [source] Genetic imbalances revealed by comparative genomic hybridization in osteosarcomasINTERNATIONAL JOURNAL OF CANCER, Issue 4 2002Toshifumi Ozaki Abstract Osteosarcomas are the most frequent bone sarcomas. The molecular chromosomal aberrations in osteosarcomas were analyzed by comparative genomic hybridization (CGH). We studied 47 frozen tumors (41 primary samples, 6 relapses) in osteosarcoma patients registered in the Cooperative Osteosarcoma Study (COSS) protocol. Genomic imbalances were detected in 40 of 41 primary tumors and 6 of 6 relapsed tumors. Gains were more frequent than losses (ratio of 1.3:1). The median number of changes was 16 and 12 in primary and relapsed osteosarcomas, respectively. The median number of aberrations in primary high-grade osteosarcomas (17.0) was significantly higher than in low- or intermediate-grade osteosarcoma subtypes (3.0) (p = 0.038). The most frequent gains included 8q, 1p21-p31 and 1q21-q24, and the most frequent losses were 10q, 5q and 13q. High-level gains were observed on 8q23-q24, 17p13 and 1q21-q24. A gain of 19p (p < 0.001) or loss of 9p (p = 0.027) was more frequent in poor responders than in good responders. Univariate analysis revealed that patients with primary metastases (p = 0.002), poor histologic responses (p = 0.005), high-level gains of 19p (p = 0.012) or losses of 13q14 (p = 0.042) had significantly lower event-free survival (EFS), whereas patients with a loss of 5q (p = 0.007) or a loss of 10q21-22 (p = 0.017) had significantly higher EFS than patients without these aberrations. Multivariate analysis demonstrated that primary metastasis, loss of 13q14 and loss of 5q were independent prognostic factors. The findings of our study seem to be useful for evaluating the prognosis of patients and may finally lead to treatment strategies based on genetic background of osteosarcoma. © 2002 Wiley-Liss, Inc. [source] Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 7 2005Peter J. Connelly Abstract Background Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. Methods A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). Results 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4,,139),=,5.60, p,<,0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p,<,0.05 in each case). This effect could not be explained by age or by smoking status. Conclusion Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome. Copyright © 2005 John Wiley & Sons, Ltd. [source] Dark therapy for mania: a pilot studyBIPOLAR DISORDERS, Issue 1 2005Barbara Barbini Background:, Recent findings suggest that extended bed rest and darkness could stabilize mood swings in rapid cycling bipolar patients. Method:, We exposed 16 bipolar inpatients affected by a manic episode to a regimen of 14 h of enforced darkness from 6 p.m. to 8 a.m. each night for three consecutive days [dark therapy (DT)]. Pattern of mood changes were recorded with the Young Mania Rating Scale (YMRS) and compared with a control group of 16 inpatients matched for age, sex, age at onset, number of previous illness episodes and duration of current episode, and were treated with therapy as usual (TAU). Results:, Adding DT to TAU resulted in a significantly faster decrease of YMRS scores when patients were treated within 2 weeks from the onset of the current manic episode. When duration of current episode was longer, DT had no effect. Follow-up confirmed that good responders needed a lower dose of antimanic drugs and were discharged earlier from the hospital. Conclusions:, Chronobiological interventions and control of environmental stimuli can be a useful add-on for the treatment of acute mania in a hospital setting. [source] Acute treatment of bipolar depression with adjunctive zonisamide: a retrospective chart reviewBIPOLAR DISORDERS, Issue 5 2004Claudia F Baldassano Background:, This retrospective chart review evaluated the use of zonisamide as adjunctive treatment in patients with bipolar depression. Method:, The charts of outpatients with bipolar I or II disorder treated with adjunctive zonisamide were reviewed. The efficacy of zonisamide was assessed via comparison of physician-rated Global Assessment of Functioning (GAF) and Clinical Global Impression of Severity (CGI-S) Scale scores at baseline and after 6 weeks of therapy using paired t -tests. Patients who scored ,2 on the CGI-S after 6 weeks of zonisamide therapy were considered good responders to zonisamide. Results:, Charts for 12 patients (four men and eight women) with a mean (±SD) age of 39.6 (±7.6) years were evaluated. Patients received a mean (±SD) zonisamide dosage of 236 (±68) mg/day. Mean GAF scores significantly improved from 44.0 at baseline to 59.3 at week 6 (P = 0.05). Mean CGI-S scores improved from 4.54 at baseline to 3.42 at week 6, but the change was not statistically significant. Six patients (50.0%) were considered responders to zonisamide. Four patients discontinued zonisamide therapy, two for an adverse event (sedation) and two for lack of efficacy. Conclusions:, Zonisamide may be a useful adjunctive treatment for some patients with bipolar depression. Conclusions from this study are limited due to its retrospective design. Further investigation of zonisamide in the treatment of bipolar depression is warranted. [source] Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasisBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2008GGG Donders Precis, Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy than do women with other underlying causes. Objective, To explain differences in response rates to maintenance therapy with fluconazole in women suffering from RVC by evaluating associations with a polymorphism in the gene coding for mannose-binding lectin (MBL). Design, Follow-up study, neted case-control group. Setting, Women attending vulvoginitis clinic for RVC. Population, Women participating in a multicentric study in Belgium with a degressive dose of fluconazole for RVC (the ReCiDiF trial) were divided into good responders, intermediate responders and nonresponders according to the number of relapses they experienced during therapy. From 109 of these women with adequate follow-up data, vaginal lavage with 2 ml of saline were performed at the moment of a proven acute attack at inclusion in the study, before maintenance treatment was started. A buccal swab was obtained from 55 age-matched women without a history of Candida infections, serving as a control group. Methods, Extracted DNA from buccal or vaginal cells was tested for codon 54 MBL2 gene polymorphism by polymerase chain reaction and endonuclease digestion. Main outcome measures, Frequency of MBL2 condon 54 allele B in women with optimal or poor response to maintenance therapy in composition with controls. Results, Women (n = 109) suffering from RVC were more likely to carry the variant MBL2 codon 54 allele B than control women (20 versus 6.6%, OR 3.4 [95% CI 1.3,8.2], P = 0.01). B alleles were present in 25% of the 36 women not suffering from any recurrence during the maintenance therapy with decreasing doses of fluconazole (OR 4.9 [95% CI 1.9,12.5], P = 0.0007 versus controls), in 20% of the 43 women with sporadic recurrences (OR 3.6 [95% CI 1.4,9.2], P = 0.007 versus controls) and in 15% of the 30 women who had to interrupt the treatment regimen due to frequent relapses (P = 0.097 versus controls). Conclusions, The MBL2 codon 54 gene polymorphism is more frequent in Belgian women suffering from RVC than in controls. The presence of the B allele is associated with a superior response to fluconazole maintenance therapy as compared with RVC patients without this polymorphism. We conclude that RVC due to deficient MBL production is more easily helped with antifungal medication than is RVC due to some other mechanism. [source] Immunotherapy for allergic rhinitis: clinical benefits and its working mechanismsCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2009Y. Nakai Summary Pollen immunotherapy exerts greater efficacy in the pollen season when the pollen count is not high than when it is high. Every pollen season, around half or more patients who have received pollen immunotherapy for >5 years are judged as good responders; those who have received immunotherapy for <5 years generally do less well. Therefore, the clinical response seems to depend on natural pollen counts and the duration of immunotherapy. In this study, peripheral blood mononuclear cells (PBMCs) were sampled before and during the pollen season to examine IL-4, IL-5, and IFN-, levels. It was revealed that pollen immunotherapy could decrease IL-4 and -5 expression by pollen antigen-stimulated PBMCs. When patients under immunotherapy were divided into good and poor response groups, clinical effectiveness was related to the depressed level of IL-5 synthesis, but not to that of IL-4 synthesis. Our study suggests that a decrease of IL-5 expression during the pollen season is a key working mechanism of immunotherapy related to clinical effectiveness. In our patients, the incidence of systemic reactions was 5.8%/patient and <0.1%/injection. A higher incidence of systemic reactions was observed in patients with the presence or a past history of asthma, the presence but not a past history of atopic dermatitis, and higher levels of total IgE (>1000 U/mL). The incidence of systemic reactions in patients with 1 risk factor such as asthma, atopic dermatitis, and high IgE was 16.9%/patient and 0.1%/injection, whereas that in those without risk factors was 1.6%/patient and <0.1/injection. [source] Cardiovascular pharmacogenetics in the SNP eraJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2003V. Mooser Summary., In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the ,good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics , the study of variability in drug responses attributed to hereditary factors in different populations , may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200 000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of patients who are predisposed to developing a hypersensitivity reaction to abacavir, an anti-HIV agent. Data collected thus far on the HLA locus on chromosome 6 indicate that this approach is feasible. Extended linkage disequilibrium can be detected readily, even across several haplotype blocks, thus potentially reducing the number of SNPs for future whole-genome scans. Finally, a modest number of cases and controls appears to be sufficient to detect genetic associations. There is little doubt that this type of approach will have an impact on the way cardiovascular drugs will be developed and prescribed in the future. [source] | ||||||||||