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Selected AbstractsGENETIC STUDY: Association between dopamine transporter genotypes and smoking cessation: a meta-analysisADDICTION BIOLOGY, Issue 2 2007John A. Stapleton ABSTRACT This review assessed the evidence of an association between genotypes of the dopamine transporter (DAT1, SLC6A3) 3, untranslated region (3,UTR) variable number of tandem repeats (VNTR) and smoking cessation. Five studies (seven cohorts) comprising 2155 subjects were included in the meta-analysis. All gave data on the number of smokers who had stopped smoking and the number still smoking for those with one or more variant 9-repeat alleles and other genotypes. Three studies (comprising five cohorts) were cross-sectional population surveys and two were smoking cessation treatment programs with follow-up. Four of the five studies (six of the seven cohorts) showed a trend in favor of cessation when the variant 9-repeat allele was present, although only one study showed a statistically significant effect. The pooled odds ratio in favor of a greater likelihood of cessation for the variant 9-repeat allele was 1.15 [95% confidence interval (CI) = 0.97,1.37]. In a more refined analysis where cohorts within studies were treated as separate samples and adjusted odds ratios were used, the overall pooled odds ratio in favor of cessation with the 9-repeat alleles was 1.20 (95% CI = 1.01,1.43). These results support the hypothesis that the DAT1 3,UTR VNTR polymorphism is associated with smoking cessation. One or more variant 9-repeat alleles relative to the more common 10-repeat allele confers a greater likelihood of cessation, indicative of lower dependence on tobacco. The effect was a 20% increase in the odds of cessation for those with a variant allele. [source] Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a reviewHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2003*Article first published online: 11 DEC 200, Michel Bourin Abstract Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive, compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. There is wide interindividual variation in the pharmacokinetics of paroxetine in adults as well as in the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment, however, serious adverse events are extremely rare even in overdose. A Pub Med search was used to collect information on the efficacy and tolerability in elderly patients. There are few studies of depression in the elderly and only one study in the old,old. In anxiety disorders including general anxiety disorder, panic disorder, obsessive,compulsive disorder and social anxiety, there are no studies at all in the elderly. However, the safety of the drug allows its prescription in the elderly. In summary, paroxetine is well tolerated in the treatment of depression in those between the ages of 65 and 75, although few studies have examined its use in those of 75 and older. Copyright © 2002 John Wiley & Sons, Ltd. [source] A systematic review of intervention studies about anxiety in caregivers of people with dementiaINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2007Claudia Cooper Abstract Background There is considerable literature on managing depression, burden and psychological morbidity in caregivers of people with dementia (CG). Anxiety has been a relatively neglected outcome measure but may require specific interventions. Objective To synthesise evidence regarding interventions that reduce anxiety in CGs. Methods Twenty-four studies met our inclusion criteria. We rated the methodology of studies, and awarded grades of recommendation (GR) for each type of intervention according to Centre for Evidence Based Medicine guidelines, from A (highest level of evidence) to D. Results Anxiety level was the primary outcome measure in only one study and no studies were predicated on a power calculation for anxiety level. There was little evidence of efficacy for any intervention. The only RCT to report significantly reduced anxiety involved a CBT and relaxation-based intervention specifically devised to treat anxiety, and there was preliminary evidence (no randomised controlled trials) that caregiver groups involving yoga and relaxation without CBT were effective. There was grade B evidence that behavioural management, exercise therapies and respite were ineffective. Limitations Many interventions were heterogeneous, so there is some overlap between groups. Lack of evidence of efficacy is not evidence of lack of efficacy. Conclusions CBT and other therapies developed primarily to target depression did not effectively treat anxiety. Good RCTs are needed to specifically target anxiety which might include relaxation techniques. Some of the interventions focussed on reducing contact with the care recipients but caregivers may want to cope with caring and preliminary evidence suggests strategies to help CGs manage caring demands may be more effective. Copyright © 2006 John Wiley & Sons, Ltd. [source] The Role of Benzodiazepines in the Treatment of InsomniaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2001Meta-Analysis of Benzodiazepine Use in the Treatment of Insomnia PURPOSE: To obtain a precise estimate of the efficacy and common adverse effects of benzodiazepines for the treatment of insomnia compared with those of placebo and other treatments. BACKGROUND: Insomnia, also referred to as disorder of initiating or maintaining sleep, is a common problem and its prevalence among older people is estimated to be 23% to 34%.1 The total direct cost in the United States for insomnia in 1995 was estimated to be $13.9 billion.2 The complaint of insomnia in older people is associated with chronic medical conditions; psychiatric problems, mainly depression, chronic pain, and poor perceived general condition;1,3,4 and use of sleep medications.5 Thus in most cases, insomnia is due to some other underlying problem and is not just a consequence of aging.6 Accordingly, the management of insomnia should focus on addressing the primary problem and not just short-term treatment of the insomnia. Benzodiazepines belong to the drug class of choice for the symptomatic treatment of primary insomnia.7 This abstract will appraise a meta-analysis that compared the effect of benzodiazepines for short-term treatment of primary insomnia with placebo or other treatment. DATA SOURCES: Data sources included articles listed in Medline from 1966 to December 1998 and the Cochrane Controlled Trials Registry. The medical subject heading (MeSH) search terms used were "benzodiazepine" (exploded) or "benzodiazepine tranquillizers" (exploded) or "clonazepam,""drug therapy,""randomized controlled trial" or "random allocation" or "all random,""human," and "English language." In addition, bibliographies of retrieved articles were scanned for additional articles and manufacturers of brand-name benzodiazepines were asked for reports of early trials not published in the literature. STUDY SELECTION CRITERIA: Reports of randomized controlled trials of benzodiazepine therapy for primary insomnia were considered for the meta-analysis if they compared a benzodiazepine with a placebo or an alternative active drug. DATA EXTRACTION: Data were abstracted from 45 randomized controlled trials representing 2,672 patients, 47% of whom were women. Fifteen studies included patients age 65 and older and four studies involved exclusively older patients. Twenty-five studies were based in the community and nine involved inpatients. The duration of the studies ranged from 1 day to 6 weeks, with a mean of 12.2 days and median of 7.5 days. The primary outcome measures analyzed were sleep latency and total sleep duration after a sleep study, subjects' estimates of sleep latency and sleep duration, and subjects' report of adverse effects. Interrater reliability was checked through duplicate, independent abstraction of the first 21 articles. Overall agreement was between 95% and 98% (kappa value of 0.90 and 0.95 accordingly) for classification of the studies and validity of therapy, and 76% (kappa value of 0.51) for study of harmful effects. A scale of 0 to 5 was used to rate the individual reports, taking into account the quality of randomization, blinding, follow-up, and control for baseline differences between groups. Tests for homogeneity were applied across the individual studies and, when studies were found to be heterogeneous, subgroup analysis according to a predefined group was performed. MAIN RESULTS: The drugs used in the meta-analysis included triazolam in 16 studies; flurazepam in 14 studies; temazepam in 13 studies; midazolam in five studies; nitrazepam in four studies; and estazolam, lorazepam, and diazepam in two studies each. Alternative drug therapies included zopiclone in 13 studies and diphenhydramine, glutethimide, and promethazine in one study each. Only one article reported on a nonpharmacological treatment (behavioral therapy). The mean age of patients was reported in 33 of the 45 studies and ranged between 29 and 82. SLEEP LATENCY: In four studies involving 159 subjects, there was sleep-record latency (time to fall asleep) data for analysis. The pooled difference indicated that the latency to sleep for patients receiving a benzodiazepine was 4.2 minutes (95% CI = (,0.7) (,9.2)) shorter than for those receiving placebo. Patient's estimates of sleep latency examined in eight studies showed a difference of 14.3 minutes (95% CI = 10.6,18.0) in favor of benzodiazepines over placebo. TOTAL SLEEP DURATION: Analysis of two studies involving 35 patients in which total sleep duration using sleep-record results was compared indicated that patients in the benzodiazepine groups slept for an average of 61.8 minutes (95% CI = 37.4,86.2) longer than those in the placebo groups. Patient's estimates of sleep duration from eight studies (566 points) showed total sleep duration to be 48.4 minutes (95% CI = 39.6,57.1) longer for patients taking benzodiazepines than for those on placebo. ADVERSE EFFECTS: Analysis of eight studies (889 subjects) showed that those in the benzodiazepine groups were more likely than those in the placebo groups to complain of daytime drowsiness (odds ratio (OR) 2.4, 95% confidence interval (CI) = 1.8,3.4). Analysis of four studies (326 subjects) also showed that subjects in the benzodiazepine groups were more likely to complain of dizziness or lightheadedness than the placebo groups. (OR 2.6, 95% CI = 0.7,10.3). Despite the increased reported side effects in the benzodiazepine groups, drop-out rates were similar in the benzodiazepine and placebo groups. For patient reported outcome, there was no strong correlation found for sleep latency data, (r = 0.4, 95% CI = (,0.3) (,0.9)) or for sleep duration (r = 0.2, 95% CI = ,0.8,0.4) between benzodiazepine dose and outcome. COMPARISON WITH OTHER DRUGS AND TREATMENTS: In three trials with 96 subjects, meta-analysis of the results comparing benzodiazepines with zopiclone, did not show significant difference in sleep latency in the benzodiazepine and placebo groups, but the benzodiazepine groups had increased total sleep duration (23.1 min. 95% CI = 5.6,40.6). In four trials with 252 subjects, the side effect profile did not show a statistically significant difference (OR 1.5, CI 0.8,2.9). There was only one study comparing the effect of behavioral therapy with triazolam. The result showed that triazolam was more effective than behavioral therapy in decreasing sleep latency, but its efficacy declined by the second week of treatment. Behavioral therapy remained effective throughout the 9-week follow-up period. There were four small trials that involved older patients exclusively, with three of the studies having less than 2 weeks of follow-up. The results were mixed regarding benefits and adverse effects were poorly reported. CONCLUSION: The result of the meta-analysis shows that the use of benzodiazepines results in a decrease in sleep latency and a significant increase in total sleep time as compared with placebo. There was also a report of significantly increased side effects, but this did not result in increased discontinuation rate. There was no dose-response relationship for beneficial effect seen with the use of benzodiazepines, although the data are scant. Zopiclone was the only alternative pharmacological therapy that could be studied with any precision. There was no significant difference in the outcome when benzodiazepines were compared with zopiclone. There was only one study that compared the effect of benzodiazepines with nonpharmacological therapy; thus available data are insufficient to comment. [source] An integrative literature review of lifestyle interventions for the prevention of type II diabetes mellitusJOURNAL OF CLINICAL NURSING, Issue 17 2008Suzanne G Madden Aims and objectives., An integrative literature review was undertaken to determine what type II diabetes prevention programmes have been evaluated, what type of programme is the most effective and how adherent to lifestyle changes adults are after participating in a prevention programme. Background., Type II diabetes is important because the disease is affecting millions of people worldwide. Obesity and sedentary lifestyles are preventable risk factors for type II diabetes, leading many researchers from around the world to examine different programmes that are focussed on prevention of the disease. Design., Integrative literature review. Method., Search of electronic databases. Results., Diet, exercise, counselling and diet plus exercise were the types of prevention programmes, with the diet plus exercise being the most efficacious. Although many studies demonstrated excellent results initially, maintaining the effects of the lifestyle behaviour change proved to be difficult for participants, with only one study demonstrating the persistence of results after six years. Conclusion., Future research should focus on long-term maintenance programmes, rather than just short-term prevention programmes to determine the need for booster interventions or other means to ultimately decrease the incidence of type II diabetes. Relevance to clinical practice., As front-line healthcare providers working across a broad array of settings, nurses are particularly well-suited to play an integral part in future applications of diabetes prevention programmes. Lifestyle interventions are being delivered in a variety of settings and venues such as the workplace, the Internet and places of worship. In addition, at-risk populations also can be targeted, particularly overweight and obese persons, with at least one parent having type II diabetes or persons with gestational diabetes. [source] Use of exogenous erythropoietin in critically ill patientsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2004R. MacLaren PharmD Summary Objective:, Review the literature regarding the use of recombinant human erythropoietin (rHuEPO) to prevent red blood cell (RBC) transfusion in critically ill patients. Data sources:, A computerized search of MEDLINE and EMBASE from 1966 through June 2003 was conducted using the terms erythropoietin, anemia, hemoglobin, critical care, intensive care, surgery, trauma, burn, and transfusion. References of selected articles were reviewed. A manual search of critical care, surgery, trauma, burn, hematology, and pharmacy journals was conducted to identify relevant abstracts. Results:, Six randomized studies have evaluated exogenous administration of erythropoietin to prevent RBC transfusions in critically ill patients. Studies vary with respect to rHuEPO dosage regimens, dose of concurrently administered iron, patient characteristics, and transfusion thresholds. Administration of rHuEPO rapidly produces erythropoiesis to reduce the need for RBC transfusions. The largest study conducted to date used weekly rHuEPO administration and found a modest decrease in transfusion requirements although the time to first transfusion was delayed. Reduced intensive care unit (ICU) length of stay (LOS) was shown in only one study of surgical/trauma patients. Reduced LOS after ICU discharge was found in another study of severely ill patients (APACHE II score >22). Other clinical outcomes were not altered by rHuEPO use. No adverse events were associated with rHuEPO use although studies were not designed to evaluate safety. Conclusions:, rHuEPO reduces the need for transfusions. A cost-effectiveness analysis of rHuEPO for this indication is needed. Defining an optimal dosage regimen, identifying patients most likely to respond to rHuEPO, and determining risk factors for ICU associated anaemia would provide information for appropriate rHuEPO utilization. [source] Root competition: beyond resource depletionJOURNAL OF ECOLOGY, Issue 4 2006H. JOCHEN SCHENK Summary 1Root competition is defined as a reduction in the availability of a soil resource to roots that is caused by other roots. Resource availability to competitors can be affected through resource depletion (scramble competition) and by mechanisms that inhibit access of other roots to resources (contest competition, such as allelopathy). 2It has been proposed that soil heterogeneity can cause size-asymmetric root competition. Support for this hypothesis is limited and contradictory, possibly because resource uptake is affected more by the amount and spatial distribution of resource-acquiring organs, relative to the spatial distribution of resources, than by root system size per se. 3Root competition intensity between individual plants generally decreases as resource availability (but not necessarily habitat productivity) increases, but the importance of root competition relative to other factors that structure communities may increase with resource availability. 4Soil organisms play important, and often species-specific, roles in root interactions. 5The findings that some roots can detect other roots, or inert objects, before they are contacted and can distinguish between self and non-self roots create experimental challenges for those attempting to untangle the effects of self/non-self root recognition, self-inhibition and root segregation or proliferation in response to competition. Recent studies suggesting that root competition may represent a ,tragedy-of-the-commons' may have failed to account for this complexity. 6Theories about potential effects of root competition on plant diversity (and vice versa) appear to be ahead of the experimental evidence, with only one study documenting different effects of root competition on plant diversity under different levels of resource availability. 7Roots can interact with their biotic and abiotic environments using a large variety of often species-specific mechanisms, far beyond the traditional view that plants interact mainly through resource depletion. Research on root interactions between exotic invasives and native species holds great promise for a better understanding of the way in which root competition may affect community structure and plant diversity, and may create new insights into coevolution of plants, their competitors and the soil community. [source] New method for the determination of fecal consistency and its optimal value in the general populationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2002SHIGEYUKI NAKAJI Abstract Background : Although fecal consistency is an important factor, there has been only one study measuring this parameter. We developed a new method to measure fecal consistency and studied the relationship between fecal consistency and other fecal factors, including water content and weight. Methods : The new method is a modification of the method of Exton-Smith and used an even balance. Subjects in the initial trial were 26 healthy women. Subsequently, fecal consistency was measured in a representative sample of the general Japanese population, in order to evaluate the optimal value to maintain large bowel function. Results : Correlations between fecal consistency and fecal water content and weight were statistically consistent, although not highly correlated with each other. The optimal mean value was around 300 cm2: ,normal' in ,subjective defecatory state', 295.5 cm2 and 305.2 cm2; ,once/day' in ,defecation frequency', 296.1 cm2 and 310.2 cm2; ,soft and plump' in ,fecal characteristics', 293.6 cm2 and 298.3 cm2, in males and females, respectively. The coefficient of variation of this method ranged from 5.2% to 6.3%. Conclusions : This method is thought to be applicable to large-scale epidemiological surveys. The optimal value of fecal consistency in the general population was evaluated at approximately 300 g/cm2. © 2002 Blackwell Publishing Asia Pty Ltd [source] Electromyography of scoliotic patients treated with a braceJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2003Daniel Odermatt Abstract When a brace is used to correct spinal deviation, patients may seek to ease the discomfort from the pressure exerted by the orthosis by actively recruiting specific trunk muscles. The effect of bracing on trunk electromyography (EMG) has been reported in only one study where a limited number of electrodes were placed mainly in the thoracic region. Our hypothesis was that a multi-electrode mapping of the activity of the thoracic, lumbar, and abdominal trunk muscles would provide a more representative picture of the muscular reaction in response to bracing. With a larger number of EMG measuring sites, the presence of any brace-induced trunk muscle activity should be detected. Therefore, EMG signals of 11 adolescent idiopathic scoliosis patients who had been undergoing Boston brace treatment for 0.7-3 years were collected during four isometric tasks to evaluate the response of trunk muscles in the minutes following the application of the brace. Twenty-two pairs of bipolar electrodes were used to measure the EMG signals of the main superficial trunk muscles during four isometric tasks. EMG signals of trunk muscles were compared in braced and unbraced conditions. Brace-induced increases in EMG activity were significant in 43% of the individual measurements and in three of the four tasks for the group mean values. Increases were greater in the lumbar area, especially on the convex side of the secondary (lumbar) curve. These results thus suggest that immediately following the application of the brace, significant muscular responses can be observed in some patients. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Sensitivity to bites by the bedbug, Cimex lectulariusMEDICAL AND VETERINARY ENTOMOLOGY, Issue 2 2009K. REINHARDT Abstract Bedbugs are a public health problem and can cause significant economic losses, but little is known about the effects of bites on humans. We reviewed case reports and published papers on bedbug bites to assess the empirical basis of the commonly cited figure that only , 80% of the population are sensitive to bedbug bites. We found the sensitivity estimate to be based on only one study carried out 80 years ago. However, this study did not account for the now well-established fact that only repeated exposure to external allergens leads to skin reactions. In our sample, 18 of 19 persons showed a skin reaction after bedbug exposure, but in most cases only after repeated controlled exposure. With repeated exposure, the latency between bite and skin reactions decreased from , 10 days to a few seconds. Our results are relevant for the hospitality industry, where apparently increasing infestation rates are likely to lead to an increase in the number of tourists and hotel employees exposed to bedbugs. Medical and public health professionals may expect to see an increase in the prevalence of people with bedbug bite sensitivity. The significance of the delayed reaction time of skin to bites may also have implications in litigation cases where people seek compensation. [source] A systematic review of the effectiveness of critical appraisal skills training for cliniciansMEDICAL EDUCATION, Issue 2 2000Rod Taylor The aim of this paper is to undertake a descriptive systematic review of the effectiveness of critical appraisal skills training for clinicians. Of the 10 controlled studies which examined this issue and were found to meet the eligibility criteria of this review, all used a study population of either medical students or doctors in training. The studies used a variety of different intervention ,dosages' and reported a range of outcomes. These included participants' knowledge of epidemiology/biostatistics, their attitudes towards medical literature, their ability to appraise medical literature, and medical literature reading behaviour. An overall improvement in assessed outcomes of 68% was reported after critical appraisal skills training, particularly in knowledge relating to epidemiology and biostatistics. This review appears to provide some evidence of the benefit of teaching critical appraisal skills to clinicians, in terms of both knowledge of methodological/statistical issues in clinical research and attitudes to medical literature. However, these findings should be considered with caution as the methodological quality of studies was generally poor, with only one study employing a randomized controlled design. There is a need for educators within the field of evidence-based health to consider the implications of this review. [source] Zinc Deficiency in Pregnancy and Fetal OutcomeNUTRITION REVIEWS, Issue 1 2006Dheeraj Shah MD Maternal zinc deficiency during pregnancy has been related to adverse effects on progeny, and there are data showing that mild to moderate zinc deficiency (as assessed by available indicators) is quite common in the developing world. Observational data relating zinc deficiency to adverse fetal outcome have produced conflicting results, mainly because of the lack of a valid indicator of zinc deficiency in pregnancy. Studies of human pregnancy and zinc supplementation, including those from developing countries, have failed to document a consistent beneficial effect on fetal growth, duration of gestation, and early neonatal survival. Preliminary results from unpublished studies in developing countries have also proven to be discouraging. However, recent data and some preliminary findings indicate a beneficial effect of maternal zinc supplementation on neonatal immune status and infant morbidity from infectious diseases, and there is also preliminary evidence that zinc supplementation may prevent congenital malformations (cleft lip/palate). With respect to neurobehavioral development, the evidence is conflicting, with only one study reporting a positive outcome. More research is required to assess the benefits of the large-scale introduction of zinc supplementation during pregnancy on congenital malformations, immune functions, neurobehavior, and overall neonatal survival in countries where zinc deficiency is a problem. Currently available information does not support the routine use of zinc supplementation to improve pregnancy outcome. [source] Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002J. Hanifin Summary Background One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. Objectives To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0·05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. Methods Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved ,treatment success' (Global Assessment Score ,,2, erythema, pruritus, and papulation/induration/oedema scores ,,1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring. Results A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7·7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel,Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4·6, 12·8; P < 0·001]. Paediatric subjects were 8·1 times less likely to have an AD relapse (95% CI 4·3, 15·2; P < 0·001) and adult subjects were 7·0 times less likely to have an AD relapse (95% CI 3·0, 16·7; P < 0·001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4·7 weeks. For paediatric and adult groups, this was 5·1 and 4·1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects. Conclusions In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy. [source] Alterations of the c-kit gene in testicular germ cell tumorsCANCER SCIENCE, Issue 6 2003Yuji Sakuma Expression and gain-of-function mutation of the c-kit gene, that encodes a receptor tyrosine kinase (KIT), have been reported in mast cell tumors and gastrointestinal stromal tumors (GISTs). Among human testicular germ cell tumors (GCTs), seminomas and seminoma components of mixed GCTs have also been shown to express KIT, but only one study has found the c-kit gene mutation at exon 17 in seminoma. To elucidate the frequency and location of the c-kit gene mutation of testicular GCTs, we analyzed the whole coding region of the c-kit complementary DNA along with 4 mutational hot spots (exons 9, 11, 13 and 17) of the c-kit genomic DNA by polymerase chain reaction and direct sequencing. Somatic mutations were found in 4 pure seminomas of 34 testicular GCTs (11.8%). One mutation was found in exon 11 (W557R) and the others were observed in exon 17 (D816H and D816V). These types of mutations were reported in GISTs (W557R), seminoma (D816H) and mastocytosis (D816V) and were considered to be gain-of-function mutations, although there were no differences of any clinicopathological factors or outcome between patients with and without mutations. Additionally, we also demonstrated coexpression of Gly-Asn-Asn-Lys510,513 (GNNK)+ and GNNK- isoforms of the c-kit gene with dominance of the GNNK- transcript in all testicular GCTs. The mutations and/or preferential expression of GNNK- isoform of the c-kit gene might play an important role in the development of testicular GCTs, and these tumors may also be targets for STI571, which is a promising drug for advanced and metastatic GISTs. [source] Quantifying the effect of intraocular pressure reduction on the occurrence of glaucomaACTA OPHTHALMOLOGICA, Issue 1 2010Andrea Peeters Abstract. Purpose:, To estimate the effect of reducing intraocular pressure (IOP) on: (i) the incidence of primary open-angle glaucoma (POAG) in patients with ocular hypertension (OH), and (ii) the progression of glaucoma. Methods:, A meta-analysis of relevant randomized controlled trials was conducted. A literature search was performed to identify trials with: a randomized comparison of IOP-lowering intervention versus placebo or no treatment; visual field loss or optic disc changes as outcome; and follow-up >6 months. A pooled relative risk (RR) was calculated by a random effects model. Risk reduction of glaucoma conversion per mmHg of IOP reduction was quantified in a meta-regression model. Results:, We identified nine OH and one POAG trials. A meta-analysis of OH trials gives a pooled RR of 0.61 [95% confidence interval (CI) 0.45,0.83]. A meta-regression shows a decrease of the RR of glaucoma conversion by 14% with each mmHg extra IOP reduction (P = 0.045). No meta-analysis of POAG trials was performed because only one study has been identified. Conclusion:, There is sufficient evidence that OH therapy reduces the risk of conversion to glaucoma. This risk reduction increases with greater IOP reduction. [source] | |||||||||||||