The prevalence of and factors associated with diabetic retinopathy in the Australian population

OBJECTIVE: To determine the prevalence and factors associated with diabetic retinopathy in the Australian population and to estimate the time difference between disease onset and clinical diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: The Australian Diabetes, Obesity and Lifestyle study (AusDiab) included 11,247 adults aged > or =25 years in 42 randomly selected areas of Australia. Retinopathy was assessed in participants identified as having diabetes (based on self-report and oral glucose tolerance test), impaired fasting glucose, and impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,177 participants. RESULTS: Overall, 15.3% of those with diabetes had retinopathy. The prevalence of retinopathy was 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of proliferative diabetic retinopathy (PDR) was 2.1% in those with KDM. No cases of PDR were found in those with NDM. Untreated vision threatening retinopathy (presence of PDR or macular edema) was present in 1.2% (n = 4). Factors associated with retinopathy were duration of diabetes, HbA(1c), and systolic blood pressure. Using linear extrapolation of the prevalence of retinopathy with diabetes duration, the onset of diabetes in this population was approximately the time of diagnosis. CONCLUSIONS: This is one of the first national studies of diabetic retinopathy in a developed country. The prevalence of retinopathy was similar to that in other population-based studies. Vision threatening retinopathy was relatively rare; however, four untreated cases were identified. Regular screening for diabetic retinopathy and more aggressive management of modifiable risk factors could reduce the numbers of people who develop vision-threatening retinopathy.     

Pharmacokinetic analysis of a case of isopropanol intoxication

A comatose 46-year-old woman, admitted to the emergency room, had isopropanol and acetone concentrations of 2000 and 120 mg/L, respectively, in her serum. She had no known history of acute isopropanol intoxication and was otherwise physically healthy. Pharmacokinetic analysis showed that the elimination of both isopropanol and its major metabolite acetone obeyed apparent first-order kinetics with half-lives of 6.4 and 22.4 h, respectively. These data contrast with the commonly held view that isopropanol is slowly metabolized. Concentrations of these analytes in cerebrospinal fluid 6 h after admission were similar to those in serum. This is the first report of the pharmacokinetics of both agents in a nonalcoholic person, and it gives the first data on concentrations of these substances in cerebrospinal fluid.     

Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular diagnosis resulting in end-stage renal disease. Defects in several podocyte proteins have been implicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP), and TRPC6. Despite our growing understanding of genes involved in the pathogenesis of focal segmental sclerosis, the vast majority of patients with this disease, even those with a familial linkage, lack a clear genetic diagnosis. Here, we tested whether combinations of genetic heterozygosity (bigenic heterozygosity) that alone do not result in clinical kidney disease could function together to enhance susceptibility to glomerular damage and FSGS. Combinations of Cd2ap heterozygosity and heterozygosity of either synaptopodin (Synpo) or Fyn proto-oncogene (Fyn) but not kin of IRRE like 1 (Neph1) resulted in spontaneous proteinuria and in FSGS-like glomerular damage. These genetic interactions were also reflected at a functional level, as we found that CD2AP associates with Fyn and Synpo but not with Neph1. This demonstrates that bigenic heterozygosity can lead to FSGS and suggests that combined mutations in 2 or multiple podocyte genes may be a common etiology for glomerular disease.     

自体骨髓间充质干细胞移植后心肌缝隙连接蛋白43表达与室性心动过速发生的关系

目的:缝隙连接蛋白43对维持心肌细胞的连接通讯功能、电信号传导和正常的节律性收缩起重要作用,其表达和分布的异常是多种室性心律失常的解剖学基础,建立小型猪急性心肌梗死模型.观察自体骨髓间充质干细胞移植后室性心动过速的发生及心肌缝隙连接蛋白43的表达方法:实验于2006-01/2007-01在河北省人民医院导管室完成。①材料:选取8～12月龄小型猪22头,由河北医科大学实验动物中心提供,体质量20～30 kg,随机数字表法分为细胞移植组12头、模型对照组10头.实验过程中对动物的处置符合动物伦理学际准②实验方法:无菌条件下抽取猪双侧股骨骨髓20 mL,percoll法 贴壁法分离培养骨髓间充质干细胞,待细胞生长达75%融合时用胰酶消化传代。将传至第2代细胞加入终浓度为10μmol/L的5-氮胞苷进行诱导,用胶体金标记12 h后继续培养20 d用于移植:两组小型猪均采用球囊堵闭法建立急性心肌梗死模型.心电图监测示相关至少2个导联ST段抬高大于0.2 mV、术后血肌钙蛋白和肌酸磷酸激酶同工酶升高超过正常的两倍为建模成功标准:细胞移植组于造模成功后经OTW球囊于第一对角支远端1 cm处再次阻断血流,注入经胶体金标记的10×10~7个骨髓间充质干细胞。③实验评估:于细胞移植后2 h及4周行电生理程序刺激.观察室性心动过速的发生情况。末次电生理检查后、采用免疫组化染色法检测心肌缝隙连接蛋白43的表达.计算其积分吸光度值。结果:①模型建立指标检测:与术前比较.造模后所有小型猪血肌钙蛋白含量和肌酸磷酸激酶同工酶活性均增高,峰值浓度分别为(21.3±3.6)μg/L和(178.3×41.4)IU/L,术中心电图ST段平均抬高(10.67±1.43)mm.证明急性心肌梗死模型成功建立。②骨髓间充质干细胞移植后室性心动过速的发生情况:与模型对照组诱发出室性心动过速的动物数量比较,术后2 h细胞移植组无明显变化(X~2=0.201,P=0.650),术后4周细胞移植组明显降低(X~2=4.455.P=0.035)。②骨髓间充质干细胞移植后梗死心肌缝隙连接蛋白43的表达:术后4周移植到梗死心肌的骨髓间充质干细胞与宿主心肌生长为一体,移植部位颜色变黑,苏木精-伊红染色示移植细胞的胞浆呈紫红色。细胞移植组心肌梗死区缝隙连接蛋白43积分吸光度值明显高于模型对照组(t=16,82.P=0.00),细胞移植组中未发生室性心动过速小型猪的梗死心肌缝隙连接蛋白43的表达明显高于发生室性心动过速小型猪(t=5.06,P=0.00)。结论:自体骨髓间充质干细胞移植可促进急性心肌梗死猪心肌缝隙连接蛋白43的表达,其表达程度可能与急性心肌梗死室性心动过速的发生有关。     

Chloramphenicol Resistance in Streptococcus pneumoniae: Enzymatic Acetylation and Possible Plasmid Linkage

Clinical isolates of Streptococcus pneumoniae resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of S. pneumoniae in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be O-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a "cured" clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in S. pneumoniae.     

Malignant PEComa of the lumbar vertebra: a rare bone tumour

We describe the case of a 26-year-old patient with a perivascular epithelioid cell tumour (PEComa) involving the 5th lumbar vertebra. Radiological findings, pathological features and treatment are presented. We conclude that PEComas should be considered in the differential diagnosis of vertebral lesions.