Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Acute renal failure as a result of bilateral ureteral obstruction by Candida albicans fungus balls

A 73-year-old male with a history of diabetes mellitus was admitted to our hospital for acute renal failure. An ultrasonogram revealed bilateral hydronephrosis, which worsened despite insertion of a bladder catheter. Nephrostomy catheters were positioned bilaterally, and Candida albicans was found in the urine culture. The patient was successfully treated with intermittent direct irrigation and i.v. antifungal agent therapy. Since 1977, approximately 50 cases of fungus balls or fungal bezoars in the urinary tract have been reported, but the majority of these cases have been characterized by unilateral ureteral or bladder involvement. Herein, we report a case of acute renal failure as a result of bilateral ureteral obstruction by Candida albicans fungus balls.     

Comparing histological data from different brains: Sources of error and strategies for minimizing them

The recent development of brain atlases with computer graphics templates, and of huge databases of neurohistochemical data on the internet, has forced a systematic re-examination of errors associated with comparing histological features between adjacent sections of the same brain, between brains treated in the same way, and between brains from groups treated in different ways. The long-term goal is to compare as accurately as possible a broad array of data from experimental brains within the framework of reference atlases. Main sources of error, each of which ideally should be measured and minimized, include intrinsic biological variation, linear and nonlinear distortion of histological sections, plane of section differences between each brain, section alignment problems, and sampling errors. These variables are discussed, along with approaches to error estimation and minimization in terms of a specific example—the distribution of neuroendocrine neurons in the rat paraventricular nucleus. Based on the strategy developed here, the main conclusion is that the best long-term solution is a high-resolution 3D computer graphics model of the brain that can be sliced in any plane and used as the framework for quantitative neuroanatomy, databases, knowledge management systems, and structure–function modeling. However, any approach to the automatic annotation of neuroanatomical data—relating its spatial distribution to a reference atlas—should deal systematically with these sources of error, which reduce localization reliability.     

肥胖类型与脑卒中亚型的相关性研究

目的探讨肥胖类型与脑卒中亚型的相关性。方法将573例急性脑卒中患者分为脑出血组126例,脑梗死组447例,脑梗死组再分为脑血栓形成组(215例)和腔隙性脑梗死组(232例),另外选择277例无脑卒中者为对照组。测量腰围、臀围和体重,计算体重指数和腰臀比(WHR),分析肥胖参数与脑卒中各亚组的关系。结果脑卒中各亚组与对照组肥胖发生率差异无显著性意义(P>0.05);各组WHR明显大于对照组(P<0.05)。WHR增大明显增加脑卒中各亚组的危险性(P<0.05);女性腹围增大患腔隙性脑梗死危险性升高(P<0.05);男性体重增加患脑出血的危险性升高(P<0.01)。结论腹型肥胖是脑出血、脑血栓形成和腔隙性脑梗死的危险因素之一。     

重症胆管炎23例临床治疗分析

目的：探讨急性重症胆管炎患者的手术时机和死亡原因。方法：回顾性分析23例急性重症胆管炎患者的治疗及预后情况。结果：死亡2例（手术死亡及传统治疗死亡各1例）。早期大剂量短期应用糖皮质激素患者休克得到纠正率85％，明显高于未用糖皮质激素患者休克纠正率50％。结论：急性重症胆管炎患者应在出现休克和（或）精神症状之前手术，对已出现休克的患者，应先给予充分的保守治疗，待病情稳定后再手术。贻误手术时机，严重合并症如多器官功能衰竭及高龄是死亡的主要原因。