Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Abstract   We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15–2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

A simple method for screening assessment of acute toxicity of chemicals

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD₅₀ values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD₅₀ values reported in the literature. Our toxicological data also showed that LD₅₀ values were about 2–2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD₅₀ of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD₅₀ values of chemicals and for screening for necessity for classical full LD₅₀ test using many animals.This work was supported by a grant from Ministry of Health and Welfare in Japan (No. 467 and 511)     

浙江省某乡村慢性肾脏病的流行病学研究

目的 研究我国南方某农村人群中慢性肾脏病（CKD）的患病率及相关因素。方法 对浙江省东阳市某乡村18岁以上的常住居民慢性肾脏病情况及相关因素进行调查和检测。结果 获得完整资料的居民占该村18岁以上自然人口的76．2％。将该村自然人口按年龄性别构成校正后，白蛋白尿发生率为10．4％；肾小球滤过率〈60ml·min^-1·（1．73m^2）^-1的发生率为3．0％；血尿发生率为1．4％。本研究中40岁以上调查对象与北京市某社区及NHANESⅢ中40岁以上调查对象相比，高血压及糖尿病的患病率较低，白蛋白尿和肾功能下降的发生率介于2者之间。多因素Logistic回归提示，年龄增加10岁、糖代谢异常及收缩压水平与白蛋白尿的发生独立相关；女性、年龄增加10岁、高尿酸血症与肾功能下降独立相关；年龄增加10岁及吸烟与血尿独立相关。结论 在该经济快速发展的南方乡村，CKD的疾病谱和相关因素已经与我国大城市和发达国家类似。此外，该人群可能另有导致CKD高发的特殊原因，需进一步研究。     

A screening programme for microalbuminuria at a diabetes clinic in Apulia,southern Italy

Microalbuminuria is a predictor of renal and cardiovascular disease in both type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes. We report on a screening programme for microalbuminuria at a diabetes clinic in Italy. All diabetic patients without Albustix-positive proteinuria attending the clinic between April and September 1991 were screened. Microalbuminuria was defined as a urinary albumin/creatinine ratio, on an early morning sterile urine sample, >3 in at least two consecutive urine collections. Three hundred and fifty patients, 45 (20 female, 25 female) type 1 and 305 (145 male, 160 female) type 2 diabetics, were examined. The age range was 18–42 years and 36–73 years and duration of diabetes 1–24 and 1–35 years for type 1 and type 2 diabetic patients respectively. Blood pressure, lipids, glycosylated haemoglobin, body mass index and insulin dose, where appropriate, were measured in all patients. Microalbuminuria was found in 8 (22%) of the type 1 diabetics. These patients had a longer duration of diabetes (17.5 vs 7.4 years,P<0.001), higher diastolic blood pressure (86±2.1 vs 76±2.6 mmHg,P<0.05) and an increased total serum cholesterol level (203±23 vs 180±25 mg/dl,P<0.05) compared with diabetic patients with microalbuminuria. Of the type 2 diabetic patients 95 (33%) were found to have microalbuminuria and 210 (69%) nor-moalbumiuria. The prevalence of hypertension (defined blood pressure >140/90 mmHg or antihypertensive treatment) and of dyslipidaemia (defined as total cholesterol >200 and triglycerides >170 or hypolipidaemic treatment) were significantly higher (P<0.001 and 0.01 respectively) in patients with microalbuminuria. This study shows a prevalence of microalbuminuria in type 1 and type 2 diabetic patients similar to that reported in surveys of diabetes clinic outpatients in northern Europe. The association between microalbuminuria and recognized risk factors for cardiovascular and renal disease justifies screening programmes for microalbuminuria for early detection of at-risk diabetic patients and for the implementation of preventive therapeutic measures.     

应用荧光斑点法和比值法检测G6PD

目的建立适合于G6PD缺乏的新生儿筛查及确诊方法。方法应用荧光斑点法(FST)对新生儿筛查滤纸干血片进行检测，对可疑阳性者召回，抽静脉血以D6PD／6PGD比值法进行确诊，同时结合新生儿父母亲的G6PD结果，根据遗传关系综合分析。结果FST筛查25000例新生儿，G6PD缺乏阳性率为4．56％，确诊检出率为4．09％。与比值法的符合率为90．4％，G6PD重度缺乏者的符合率为100％，G6PD中间缺乏者的符合率为78．5％，室间质量控制结果与反馈结果符合率为100％。结论FST汀具有高的敏感性、特异性和准确性，方法简便、快捷、费用低廉，可对滤纸干血片标本进行大规模的筛查检测，同时利用比值法进行确诊，可减少假阳性及假阴性，有利于早期诊断和防治G6PD缺乏所致的新生儿黄疸和急性溶血。     

Cytological detection of epithelial dysplasia in the oral mucosa using Feulgen-DNA-image cytometry

Cytological scrape material of the oral mucosa from 114 patients with epithelial dysplasia and with oral cancer was stained with the Feulgen-reaction and investigated with an image analyzer. The size and the integrated optical density of cell nuclei, and four chromatin texture features were measured. All tumor slides contained cell nuclei with DNA greater than 5c, 16% of the slides had cell nuclei with DNA greater than 8c. A total of 14.5% of the tumor patients showed significantly increased DNA values in nuclei distant from the tumor. Two smears with severe epithelial dysplasia showed nuclei with DNA greater than 5c both in the tumor material and far from the tumor. Texture analysis allowed discrimination between benign, dysplastic and malignant smears. No correlation was found between DNA content and tumor staging. Image cytometry was a reliable method for detecting tumor cells. Epithelial dysplasia in areas distant from the tumor is probably due to "field canceration" of the epithelium.