Detection of linkage under heterogeneity: comparison of the two-locus vs. admixture models.

Linkage analysis under the two-locus model and the admixture model was compared on pedigree data for a common disease stimulated under a model of genetic heterogeneity. The ascertainment of families was designed so that the samples had a large proportion of families segregating for both disease loci. The two-locus linkage analysis model did not demonstrate increased power of detecting linkage or more accurate estimates of the recombination fraction, theta than did the admixture model linkage analysis. When a sample was purposely chosen so that all of the families were segregating for both loci, then the two-locus lod score analysis was better. However, the increased power depended on assuming the correct gene frequency for the linked locus. It can be concluded that under the conditions of genetic heterogeneity examined here, testing for linkage under the admixture model is the preferred method of analysis. However, this is not a general conclusion that can apply to all two-locus disease models.     

The short insulin tolerance test for determination of insulin sensitivity: a comparison with the euglycaemic clamp.

The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate KITT in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non-insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose KITT over the period 3-15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mumol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Axonal swellings in human intramuscular nerves.

The presence, morphology, distribution, and abundance of axonal swellings in intramuscular nerves were evaluated. Axonal swellings were present in intramuscular nerves in 42% of 127 muscle biopsies from patients with a variety of conditions. The incidence was highest in muscle from patients with peripheral neuropathy, but swellings were present in muscle from patients with motor neuron disease, primary muscle diseases, and some individuals without clinical or histological evidence of neuromuscular disease. The greatest number of swellings in intramuscular nerves was in muscle from patients with chronic inflammatory demyelinating neuropathy. Swellings were spherical or elliptical, 4-20 microns in diameter, 5-30 microns in length, and composed of neurofilaments. Swellings were present only in myelinated axons of intramuscular nerves, proximal to nodes of Ranvier or in internodal regions. Swellings were not associated with axonal degeneration. They were probably not transported. The formation or accumulation of swellings may reflect altered axonal dynamics common to a number of disease processes.     

Protective effect of different doses of terfenadine on the conjunctival provocation test

The protective effect of terfenadine on inOammatory processes following the early phase of conjunctival provocation tests by specific allergen was assessed in 24 patients suffering from seasonal allergic rhinoconjunctivitis, in a single-blind, randomized, placebo-controlled, parallel-group study. Patients were randomly assigned to four treatment groups, each being given terfenadine 60, 120, 180 mg daily, or placebo, respectively, for 7 days, out of the pollen season. Clinical severity (burning, itching, lacrimation and hyperemia), and number of inflammatory cells obtained by conjunctival scraping (neutrophils, eosinophils, lymphocytes, and monocytes) were evaluated before and after treatment. Pre-treatment with terfenadine resulted in a significantly higher allergen threshold dose than placebo (p<0.01), regardless of drug dose. Patients given terfenadine experienced a significant reduction (p<0.03) in conjunctival symptom severity, as compared with placebo, following conjunctival challenge. Accordingly, the number of inflammatory cells in terfenadine-treated patients was significantly lower (p<0.01) than in the placebo-treated after the conjunctival provocation test. The results of this study suggest that terfenadine has a significant protective effect on the early-phase cellular and clinical events of conjunctival reaction induced by allergen challenge in atopic patients.     

Impaired colour discrimination in Huntington's disease

Colour discrimination and visual contrast perception were investigated in 18 patients with Huntington's disease (HD) and in 18 age- and sex-matched healthy volunteers using the Farnsworth-Munsell 100 Hue test (FM) and stationary contrast targets. The mean total error score (MTES) and the partial scores for the “red-green” and the “blue-yellow” axes in the FM of the patients with HD were significantly elevated as compared to controls (MTES in HD: 113.0 ± 90.8; MTES in controls: 19.2 ± 8.8). The spatial contrast sensitivity in HD patients was normal. The colour perception dysfunction indicates that the visual system is affected in HD. The visual disorder may be related to an imbalance of certain neurotransmitters in the visual system of HD patients. Possible anatomical sites of the dysfunction responsible for colour discrimination abnormalities could be the retinal cone system and/or impaired parvocellular central visual pathways in HD.     

单纯性肥胖儿童的智力研究

本调查了１１４名不同肥胖程度的儿童智力状况。结果发现：患儿与正常体重儿童的智力水平没有显差异（Ｐ＞０．０５）。表明单纯性肥胖儿童的智力发育正常。     

冠心病患者颈动脉粥样硬化检测及意义

目的　探讨冠心病患者与颈动脉粥样硬化之间的发生关系。方法　主要应用彩色多普勒超声技术检测 10 2例冠心病患者的颈动脉 ,对其中 34例进行冠状动脉造影检查。结果　为各组冠心病患者颈动脉管壁内 -中膜厚度 ,斑块指数均显著增高 ,其中心肌梗死患者伴有明显的血流参数异常 ,34例患者冠状动脉造影与颈动脉超声检查符合率为 75 % ,而且冠状动脉病变越重 ,颈动脉硬化发生率越高。结论　颈动脉粥样硬化程度可间接反映冠状动脉病变程度。     

Food allergy and non-allergic food hypersensitivity in children and adolescents

BACKGROUND: Previous studies have shown a 10-fold discrepancy of self-reported food-induced symptoms and physician-diagnosed food hypersensitivity. Little information is available on the prevalence of food hypersensitivity in unselected paediatric populations. No data were available for German children. OBJECTIVE: To study the perception of food-induced symptoms in the paediatric population, to investigate the allergens accused, to objectify patients' reports, and to identify subgroups at risk of having food-induced allergy (FA) or non-allergic food hypersensitivity (NAFH) reactions. METHODS: This paper presents the data of the paediatric group (0-17 years) of a representative, randomly sampled, cross-sectional population-based survey studying 13 300 inhabitants of the German capital city Berlin regarding food-related symptoms. Instruments included mailed questionnaires, structured telephone interviews, physical examination, skin-prick tests, specific serum IgE and standardized, controlled and blinded oral food challenges. RESULTS: Two thousand three hundred and fifty-four individuals were contacted by mailed questionnaire, 739 (31.4%) responses could be fully evaluated. Four hundred and fifty-five (61.5%) participants reported symptoms related to food ingestion, 284 (38.4%) affirmed reproducible symptoms in the standardized telephone interview. One hundred and eighty-four (24.8%) individuals were fully examined. Reproducible symptoms to food were found in 31 (4.2%) children and adolescents: 26 (3.5%) showed symptoms of FA and five (0.7%) of NAFH. The oral allergy syndrome was most often observed. Foods most commonly identified by oral challenges were apple, hazelnut, soy, kiwi, carrot and wheat. CONCLUSION: The perception of food-related symptoms is common among children and adolescents from the general population. Self-reports could be confirmed in around one out of 10 individuals, still resulting in 4.2% of proven clinical symptoms. However, most reactions were mild and mainly because of pollen-associated FA, while NAFH reactions were less common. Severe IgE-mediated FA was observed in individuals with pre-existing atopic disease, who should be fully investigated for clinically relevant FA.     

医院感染常见细菌分布与耐药性分析

目的了解细菌分布及常见细菌的耐药性。方法回顾性分析某院2000—2004年临床标本分离的细菌及其耐药性监测结果。结果1439株细菌中，革兰阳性菌456株（31．69％），以凝固酶阴性表皮葡萄球菌为多，达206株（45．18％），其次为金黄色葡萄球菌92株（20．18％）；两种葡萄球菌的耐药率相似，对万古霉素耐药率均为0。革兰阴性菌983株，前5位依次为肠杆菌属346株（35．20％），克雷伯菌属164株（16，68％），铜绿假单胞菌155株（15．77％），埃希菌属101株（10．27％），变形杆菌属94株（9．56％）；前5位革兰阴性菌对常用抗菌药物的耐药性以半合成青霉索较明显，铜绿假单胞菌的耐药性较突出。结论应高度重视细菌变迁和耐药性监测，提高抗菌药物合理应用水平。     

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.