Genetic susceptibility for human familial essential hypertension in a region of homology with blood pressure linkage on rat chromosome 10

Hypertension is a significant risk factor for heart attack and stroke and represents a major public health burden because of its high prevalence (e.g. 15-20% of the European and American populations). Although blood pressure is known to have a strong genetic determination, the genes responsible for susceptibility to essential hypertension are mostly unknown. Loci involved in blood pressure regulation have been found by linkage in experimental hereditary hypertensive rat strains, but their relationship to human hypertension has not been extensively investigated. One of the principal blood pressure loci has been mapped to rat chromosome 10 and we have undertaken an investigation of the homologous region on human chromosome 17 in familial essential hypertension. Affected sib-pair analysis and parametric analysis with ascertainment correction gave significant evidence of linkage ( P <0.0001 in some analyses) near two closely linked microsatellite markers, D17S183 and D17S934, that reside 18 cM proximal to the ACE locus in the homology region. Our results indicate that chromosome 17q could contain a susceptibility locus for human hypertension and show that comparative mapping may be a useful approach for identification of such loci in humans.      

Recovery from unilateral neglect after right-hemisphere stroke

Purpose:?To show the recovery process for different forms of unilateral neglect (UN)—including personal neglect and neglect of far space—in relationship to impairment, disability, cognition and mood.

Method:?Patients were tested at 2?–?4 weeks, at 6 months and at 1 year. We used the Behaviour Inattention Test and a test for personal neglect. We also used the NIH Stroke Scale, the Functional Independence Measure (FIM), the Mini-Mental State Evaluation and the Geriatric Depression Scale.

Results:?Peripersonal neglect diminishes within 6 months, but complete recovery occurred in only 13%. The prognosis for personal neglect and neglect of far space is better, with a recovery ratio at 6 months of 52% and 46%, respective. The correlations between UN and FIM are high. A few patients deteriorate in the absence of recurrent stroke.

Conclusions:?For clinical purposes, it is practical to postpone UN evaluation until a couple of weeks after a stroke. Many of the patients who then have UN are likely to retain their UN, although many will improve. Patients with UN should receive special attention in the rehabilitation phase, as well as at discharge. One explanation of the worsening of UN seen in some patients, may be continuing cerebral atherosclerosis.     

Space headache: a new secondary headache

Headache is a common, but rarely voiced, complaint during space flights, usually attributed to space motion sickness (SMS). We used a specifically designed questionnaire based on the criteria of the International Classification of Headache Disorders, 2nd edn (ICHD-II). Of the 16 male and one female astronauts who participated in the survey, 12 (71%) reported having experienced at least one headache episode while in space, whereas they had not suffered from headache when on earth. There were in total 21 space headache episodes, of moderate to severe intensity in 71%. In two astronauts (12%) the headache and associated symptoms would match the ICHD-II criteria for migraine and in three (18%) astronauts for tension-type headache; in 12 (70%) astronauts the headache was non-specific. The vast majority of headache episodes (76%) were not associated with symptoms of SMS. We conclude that space flights may trigger headaches without other SMS symptoms in otherwise 'super-healthy' male subjects. We propose to classify space headache as a separate entity among the secondary headaches attributed to disorders of homeostasis.     

Early growth patterns and cardiometabolic function at the age of 5 in a multiethnic birth cohort: the ABCD study

Background  

The relation between fetal growth retardation and cardiovascular and metabolic diseases in later life has been demonstrated in many studies. However, debate exists around the potential independent role of postnatal growth acceleration. Furthermore, it is unknown whether a potential effect of growth acceleration on cardiovascular and metabolic function is confined to certain timeframes.     

Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3

Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a multifactorial disorder with significant genetic influence. Recently, evidence of linkage on chromosome 7q near the intestinal mucin gene MUC3 was reported by an affected sib-pair analysis. Previous reports indicate a possible mucin abnormality in UC patients, but whether genetic differences in a specific mucin gene are associated with UC is unknown. Here we analysed polymorphisms of variable number of tandem repeats (VNTRs) within this gene using DNAs obtained from 243 Japanese (75 patients with UC and 168 controls), and to confirm the result we undertook a two-stage examination using 328 Caucasian samples (72 and 85 with UC in the first and second stages, respectively, and 171 controls). When the frequency of patients carrying one or two rare VNTR alleles was compared with that of controls, a significant increase was found first in Japanese patients (odds ratio 2.72, 95% CI 1.17- 6.32, P = 0. 0308). In Caucasians, the odds ratio was 2.80 (95% CI 1.36- 5.75, P = 0.0079) in the first stage, 2.43 (95% CI 1.20-4.92, P = 0.0196) in the second stage and 2.60 (95% CI 1.41-4.80, P = 0.0024) in total. The overall odds ratio was 2.64 (95% CI 1.60-4.33, P = 0.0001). This result suggests that rare alleles of the MUC3 gene may confer genetic predisposition to UC.      

聋儿伴发眼病的循征医学研究

背景为培养交流技巧,更好的认识自己周围的世界,聋儿需要更多的倚重于视觉功能的正常存在。因此,任何眼部疾病都会对这个过程产生负面的影响,尤其是没能在发病早期发现,影响更大。一些能够纠正和治疗的疾病,如近视和白内障,早期确认将有助于完善语言的发育和培养社会认知能力;还有一些无法纠正和治疗的疾病,如Usher综合征的视网膜色素变性,就需要多方面的适应环境,给予适当的照顾和康复治疗。目的回顾长久以来累积形成的聋儿眼病的科学知识,并评价这些文献的质量,从而更好的诊断和治疗疾病。材料和方法本研究审阅了超过1000篇的文章,其中191篇文章符合本研究的目的,因而被本文引用。总结这些研究,其中95%为描述性研究或个案报道(Ⅲ型或Ⅳ型证据),只有3%是Ⅱ型证据,2%为Ⅰ型证据。结果和结论本研究主要的结论包括以下几点:a)关于聋儿伴发眼病的研究及文献报道总体上循证医学证据的质量不高;b)聋儿眼病的发生率非常高(大约40%～60%),尽管这些疾病可能严重影响儿童交流技能的培养,但往往很多年不被发现;c)聋儿眼病筛查应得到鼓励,一旦耳聋的诊断成立,无论年龄大小,应立即展开专业的眼科检查,而且可能需要在以后的随访中经常复查;d)患儿家属应该通过与相关的专业医师讨论,被告知筛查过程的实质,并通过不同形式、不同语言给予正确的信息指导;e)进行检查的专业医师应该熟悉患眼病的聋儿的需要,并且要敏感地觉察到儿童交流的需要,尤其是进行行为测听检查需要患儿配合时;f)尽管视轴纠正师能够开展绝大多数心理物理学检测(视力和立体视觉检查,眼球运动检查等等),全面的眼科检查仍然需要开展,包括:裂隙灯显微镜检查,带状视网膜检影法,直接和间接检眼镜检查,眼内压测定等等。视网膜电流描记也经常被用来确认Usher综合征的存在;g)对于双重感觉缺陷的儿童,需要进行连续的听力检测以监测听力阈值,完善助听器的使用,对有需要的患儿进行人工耳蜗植入。     

利用常规心电图鉴别长QT综合征的基因类型

一、引言和背景　　近年来 ,先天性长 QT综合征 ( long QT syn-drome,LQTS)的临床和基础研究在国际上取得了突破性进展。截止目前 ,已从 5个致病基因上鉴定出1 77个基因突变点 ,包括 KVLQTI( LQT1) 42 % ,HERG( LQT2 ) 45% ,SCN5A( LQT3 ) 8% ,KCNE1( LQT5) 3 %和 KCNE2 ( LQT6) 2 % [1] 。LQTS在遗传学上的多样性和复杂性又给临床诊治带来困难。基于目前的技术条件 ,对于一个临床上确诊的 LQTS家系 ,找出其病变基因一般需要 1～ 3年的时间 ,而且费用昂贵 ,其阳性检出率也只有 50 %左右。为了加速实验室的基因检出率…     

The Patient Health Questionnaire-9 for detection of major depressive disorder in primary care: consequences of current thresholds in a crosssectional study

Background

The Charlson comorbidity index is widely used in ICD-9 administrative data, however, there is no translation for Read/OXMIS coded data despite increasing use of the General Practice Research Database (GPRD). Our main objective was to translate the Charlson index for use with Read/OXMIS coded data such as the GPRD and test its association with mortality. We also aimed to provide a version of the comorbidity index for other researchers using similar datasets.

Methods

Two clinicians translated the Charlson index into Read/OXMIS codes. We tested the association between comorbidity score and increased mortality in 146 441 patients from the GPRD using proportional hazards models.

Results

This Read/OXMIS translation of the Charlson index contains 3156 codes. Our validation showed a strong positive association between Charlson score and age. Cox proportional models show a positive increasing association with mortality and Charlson score. The discrimination of the logistic regression model for mortality was good (AUC = 0.853).

Conclusion

We have translated a commonly used comorbidity index into Read/OXMIS for use in UK primary care databases. The translated index showed a good discrimination in our study population. This is the first study to develop a co-morbidity index for use with the Read/OXMIS coding system and the GPRD. A copy of the co-morbidity index is provided for other researchers using similar databases.     

Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs

Background

Acute urinary tract infections (UTI) are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (10² or 10³ or 10⁵ CFU/ml). We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making.

Methods

Searches were performed through PubMed (1966 to April 2010), EMBASE (1973 to April 2010), Cochrane library (1973 to April 2010), Google scholar and reference checking. Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 10² CFU/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model.

Results

Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 10² CFU/ml; 55.4% at ≥ 10³ CFU/ml and 44.8% at ≥ 10² CFU/ml ≥ 10⁵ CFU/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 10² CFU/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41), frequency (+LR 1.10 95% CI 1.04-1.16), hematuria (+LR 1.72 95%CI 1.30-2.27), nocturia (+LR 1.30 95% CI 1.08-1.56) and urgency (+LR 1.22 95% CI 1.11-1.34) all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83) decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of UTI to 75.8% at ≥ 10² CFU/ml and 67.4% at ≥ 10³ CFU/ml. Probability of UTI increases to 93.3% and 90.1% at ≥ 10² CFU/ml and ≥ 10³ CFU/ml respectively when presence of hematuria is combined with a positive dipstick result for nitrites. Subgroup analysis shows improved diagnostic accuracy using lower reference standards ≥ 10² CFU/ml and ≥ 10³ CFU/ml.

Conclusions

Individual symptoms and signs have a modest ability to raise the pretest-risk of UTI. Diagnostic accuracy improves considerably when combined with dipstick tests particularly tests for nitrites.