Candida albicans mannan- and protein-induced humoral, cellular and cytokine responses in atopic dermatitis patients

BACKGROUND: The cytokine observed most often in atopic dermatitis (AD) is IL-4, but a role for IL-5 and IFN-gamma in the late and delayed phase reactions has been suggested. In AD with head, neck and shoulder distribution, hypersensitivity to saprophytic yeasts is an important pathogenetic factor. The yeast allergens include both the mannan polysaccharides and the proteins. Mannans are major cross-reacting allergens likely to be involved in the pathogenesis of AD. OBJECTIVE: To characterize the humoral, lymphoproliferative and cytokine (IL-2, 4, 5 and IFN-gamma) responses of peripheral blood mononuclear cells (PBMCs) induced by Candida albicans mannan and protein antigens in AD. METHODS: Fifteen AD patients and seven healthy controls were included. Ficoll-isolated PBMCs were stimulated by PHA and laboratory-generated mannan and protein extracts of C. albicans. Lymphocyte proliferation was measured and cytokine production was studied by ELISA. The antigen-specific IgG and IgE antibodies were analysed by ELISA and nitrocellulose RAST. RESULTS: In AD mannan (P < 0.005) and protein (P < 0.002), specific IgE levels were higher than in healthy controls. Both mannan and protein-specific lymphoproliferations (both: P < 0.02) were higher in AD than in healthy controls. Mannan, but not protein, induced long lasting IL-2 and IL-4 productions from 24 h lasting up to 66-96 h and IL-5 and IFN-gamma productions with elevated levels at 66 and 96 h. The mannan-induced IL-2 (P = 0.015) and IFN-gamma (P < 0.005) were increased in AD as compared with healthy controls. Significant correlations were seen between the protein-induced proliferation responses and both serum total IgE (r = 0.59, P < 0.01) and protein-specific IgE (r = 0.65, P < 0.005). The mannan-induced IL-2 responses correlated with the specific IgE (r = 0.62, P < 0.01) and proliferation (r = 0.51, P < 0.02) and S-IgE level (r = 0.71, P < 0. 002). Mannan-induced IL-4 and IFN-gamma productions also correlated (r = 0.43, P < 0.05). CONCLUSIONS: C. albicans mannan induced elevated IL-2 and IFN-gamma responses in AD patients. The correlations of the cytokine responses with mannan-induced IgE and proliferation responses suggest that C. albicans mannan induced TH1 type cytokine responses are involved in AD.     

Efficacy of amiodarone for the termination of persistent atrial fibrillation

The efficacy and safety of amiodarone in the conversion of persistent atrial fibrillation (AF) were investigated in a prospective, randomized, controlled study. Of 67 consecutive patients (32 men, mean age 64+/-9 years) with AF lasting >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical characteristics were similar in the 2 groups. Patients randomized to amiodarone received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They were also given 600 mg/day orally, divided into 3 doses, for 1 week and thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an identical amount of saline IV over 24 hours and then oral placebo for 1 month. Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who received amiodarone and in none of the 34 patients in the placebo group (p <0.001). None of the patients converted to sinus rhythm within the first 3 days. Those who converted had smaller atria than those who did not (diameter 41.9+/-7.2 vs 50.4+/-5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular ejection fraction, and the duration of AF did not differ significantly between patients who converted and those who did not. No side effects requiring discontinuation of treatment were observed in either group. Amiodarone, administered both intravenously and orally, appears to be safe and effective in the termination of persistent AF. Left atrial diameter is the sole independent predictor of conversion.     

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: An open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728]

Background

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification [8] has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine.

Methods/design

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

     

父母的母语与儿童预防性医疗行为的差异有关

目的:研究父母的母语为非英语的婴儿比父母的母语为英语的婴儿是否更不易接受推荐的预防性医疗行为。研究设计:笔者对1999年1月1日至2000年9月30日期间在华盛顿州出生的所有38793例参加医疗救助的1岁婴儿进行回顾性组群研究。主要因素为自己报告的父母的母语。笔者使用多参数回     

Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21

Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non- disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.      

Increased chondroitin sulphate proteoglycan expression (B5 immunoreactivity) in metastases of uveal melanoma

Background: Metastatic uveal melanoma has a poor prognosis andlimited therapeutic options. Proteoglycans are involved in tumorcell invasion and metastatic behavior. The mAbB5 stains a chondroitinsulphate proteoglycan (CSPG) on cutaneous melanoma cells. Here,we compare the B5-staining of CSPG in primaries and metastasesof uveal melanoma. Material and methods: Immunohistopathological staining was performedin 15 cutaneous and 39 uveal melanoma samples. A score for intracellularand surface staining was established. B5 staining was comparedin primaries and metastases of uveal melanoma using Student'st-test. Results: Eight of 11 (73%) uveal melanoma metastases were positivefor B5-staining whereas only 5 of 28 (18%) primary uveal melanomasamples were B5-positive (P < 0.001). Nine of 15 cutaneousmelanoma samples (60%) were B5-positive without significantdifference between primary and metastatic lesions. Surface stainingwas found both on uveal melanoma metastases and cutaneous melanomas. Conclusions: CSPG was expressed significantly more often inmetastases than in primaries of uveal melanoma. It potentiallymay be one factor associated with metastatic spread. Furtherstudies are needed to determine its use as prognostic factor.The mAbB5 may also be a promising tool for immunotherapy dueto its strong staining of CSPG on the surface of cutaneous andmetastatic uveal melanoma cells. Key words: uveal melanoma, ocular melanoma, chondroitin sulphate proteoglycan, immunotherapy, immunohistochemistry     

TESTS OF GEOGRAPHICAL CORRELATION WITH ADJUSTMENT FOR EXPLANATORY VARIABLES: AN APPLICATION TO DYSPNOEA IN THE ELDERLY

We propose a test of correlation of the residuals in generalized linear models which is a generalization of the spatial autocorrelation test based on Moran's I. It allows adjustment for sizes of geographical areas and for explanatory variables. A formula is given to compute the weights according to the alternative hypothesis. We compare inference using the distribution in the model and using the permutation distribution. A simulation study showed that the model-based test may be very conservative and this leads to a loss of power compared to the permutation test or to the model-based test with correction for estimated parameters. As this latter is intractable for very large samples when the model includes explanatory variables, we recommend the use of the permutation test. The permutation test is used to study geographical correlation of dyspnoea in the elderly. © 1997 by John Wiley & Sons, Ltd.