First report of a de novo germline mutation in the MLH1 gene

Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associated with colorectal and endometrial cancer and a range of other tumor types. Germline mutations in the DNA mismatch repair (MMR) genes, particularly MLH1, MSH2, and MSH6, underlie this disorder. The vast majority of these HNPCC-associated mutations have been proven, or assumed, given the family history of cancer, to be transmitted through several generations. To the best of our knowledge, only a single case of a de novo germline MMR gene mutation (in MSH2) has been reported till now. Here, we report a patient with a de novo mutation in MLH1. We identified a MLH1 Q701X truncating mutation in the blood lymphocytes of a male who had been diagnosed with rectal cancer at the age of 35. His family history of cancer was negative for the first- and second-degree relatives. The mutation could not be detected in the patient' parents and sibling and paternity was confirmed with a set of highly polymorphic markers. Non-penetrance and small family size is the common explanation of verified negative family histories of cancer in patients with a germline MMR gene mutation. However, in addition to some cases explained by non-paternity, de novo germline mutations should be considered as a possible explanation as well. As guidelines that stress not to restrict MMR gene mutation testing to patients with a positive family history are more widely introduced, more cases of de novo MMR gene germline mutations may be revealed.     

Undetected chronic obstructive pulmonary disease and asthma in people over 50 years with persistent cough

Background

Chronic obstructive pulmonary disease (COPD) and asthma are underdiagnosed in primary care.

Aim

To determine how often COPD or asthma are present in middle-aged and older patients who consult their GP for persistent cough.

Design of study

A cross-sectional study in 353 patients older than 50 years, visiting their GP for persistent cough and not known to have COPD or asthma.

Setting

General practice in the Netherlands.

Method

All participants underwent extensive diagnostic work-up, including symptoms, signs, spirometry, and body plethysmography. All results were studied by an expert panel to diagnose or exclude COPD and/or asthma. The reproducibility of the panel diagnosis was assessed by calculation of Cohen''s κ statistic in a sample of 41 participants.

Results

Of the 353 participants, 102 (29%, 95% confidence interval [CI] = 24 to 34%) were diagnosed with COPD. In 14 of these 102 participants, both COPD and asthma were diagnosed (4%, 95% CI = 2 to 7%). Asthma (without COPD) was diagnosed in 23 (7%, 95% CI = 4 to 10%) participants. Mean duration of cough was 93 days (median 40 days). The reproducibility of the expert panel was good (Cohen''s κ = 0.90).

Conclusion

In patients aged over 50 years who consult their GP for persistent cough, undetected COPD or asthma is frequently present.     

Pre-dialysis education and patient choice

The discussion was initiated by a paper on the influence of a pre-dialysis education programme on the mode of renal replacement therapy by Goovaerts et al (NDT 2005). Barriers to the uptake of self-care treatment modalities, including late referral, limited availability of treatment options, reimbursement, support from staff and families, the requirement for a helper and the length of the training programmes for home haemodialysis (HD) were discussed by 21 participants from 12 countries. The 'take-home' messages from the discussion were that to optimise the uptake of self-care modalities, renal units should try to ensure the all patients who are able to choose are fully informed before starting dialysis, even if they are referred to the unit very late. Offering a wide range of treatment options to new patients, and allowing (or encouraging) home HD without a helper, may also increase the number of patients who start and stay on a self-care modality. It should be possible to provide an acceptable level of training, without compromising on safety, within 3 weeks if the patient is confident with needling.     

European practice in haemodialysis: results of the EPD

The European Practice Database (EPD) project, developed by the EDTNA/ERCA Research Board, collects data on renal practice at centre level in different European countries. Results presented in this paper focus on the European Practice in Haemodialysis centres from 8 European countries or regions following data collection from 2002 to 2004. These results will enable international comparison in practice and will stimulate further research and the development of new practice recommendations.     

心梗后患者12周康复锻炼后一次递增负荷运动中VO2、HR、%HRmax、RPP、ST、RPE变化及其相互关系

目的:探讨12周运动心脏康复锻炼对心梗后患者(PMI患者)心脏机能的影响。方法:112名男性PMI患者(均进行了12周运动心脏康复锻炼)进行一次递增负荷运动实验(Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ级负荷跑速分别为1.7、1.7、1.7、2.5、3.5mph;坡度分别为0.5 %、10 %、12 %、14 %,每一级负荷运动3分钟) ,其间记录每级负荷时的VO2、HR、血压和自我用力感觉(RPE) ,计算心率血压乘积(RPP) ,并持续监测12导联心电图(ECG) ,然后对上述指标进行相关分析并建立了用HR和RPE推测VO2和RPP的回归方程。结果:(1)相邻两级负荷间的VO2、HR、RPP、RPE具有显著差异(P<0.01) ;(2)VO2、HR、最大心率百分数( %HRmax)、RPP、ST段水平(ST)和RPE的峰值分别为26.4±7.1ml·kg-1·min-1、126.8±20.3beats·min-1、80.4±12.9 %、209.0±46.3beats·mmHg·100-1、-1.0±0.7mm和14.9±2.1;(3)运动中VO2、HR、%HRmax、RPP、RPE呈高度正相关,它们与ST呈高度负相关(P<0.01或P<0.05) ,建立了用HR和RPE推测VO2和RPP的回归方程。结论:(1)康复锻炼后利用改良Bruce跑台方案进行机能测试有效;(2)12周康复锻炼后,PMI患者进行运动时其强度不宜超过80 %HRmax或RPE不超过15 ;(3)利用本研究建立的预测方程,可在PMI患者康复活动中,根据其心率或RPE变化间接得知其呼吸循环机能的反应和心肌的耗氧状况。