The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Hepatitis B virus,alpha-fetoprotein synthesis,and hepatocellular carcinoma in Zaire

ABSTRACT— We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966–1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%o) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 ± 17.5 years) and females (37.40 ± 15.16 years) was significantly different (p<0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96%) vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumorous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (>20 ng/ml) in 90%) of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19 322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102 565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95%) CI: [182.8, 19952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.     

Salivary gland tumours in Congo (Zaire).

From the files of the Department of Pathology of Kinshasa University Hospital, a retrospective study on salivary gland tumours in Congo (Zaire) had been carried out in order to determine their histological and epidemiological profile. Salivary gland tumours are rare in Congo, with a relative frequency of 1.8%. Pleomorphic adenoma (55.1%) and adenoid cystic carcinoma (15.9%) are the most common tumours. Parotid gland (36.6%) is the most frequent location of salivary gland tumours in this country. People aged between 30 and 39 years (19.9%) (Mean: 37.4 +/- 16.2 years) and females (M/F = 0.8/1) are most affected. No case of adenolymphoma is recorded in this series.     

Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent

AIM: To determine the minimum effective dose and safety of micafungin in the treatment of HIV-related oesophageal candidiasis. METHOD: A total of 120 patients were enrolled in this open label study of the effects of daily 1 h infusions of micafungin on endoscopically proven fungal oesophagitis. Patients were randomly assigned to receive 12.5, 25, 50, 75 and 100 mg of micafungin daily. Response was evaluated clinically and endoscopically. RESULTS: The protocol defined minimum effective dose of micafungin was 12.5 mg. The percentage of patients experiencing clearing of physical signs and symptoms showed a dose-response relationship and reached 94.7% in the 100 mg dose group. All patients in the 50, 75 and 100 mg dose groups achieved an endoscopically verified improvement in oesophagitis. Adverse effects of micafungin were generally mild and not dose-related. No serious renal, hepatic or drug-related infusion reactions were encountered. CONCLUSION: Micafungin was found to be effective, well-tolerated and safe. The minimum effective dose was found to be 12.5 mg and a significant linear trend in the successful treatment of oesophageal candidiasis was observed across the doses used with 75 and 100 mg dose levels achieving high rates of clinical and endoscopic cure.     

Mental health first aid training for the Chinese community in Melbourne,Australia: effects on knowledge about and attitudes toward people with mental illness

Background  

The aim of this study was to investigate in members of the Chinese community in Melbourne the impact of Mental Health First Aid (MHFA) training on knowledge about mental disorders and on attitudes to people with mental illness. The hypotheses were that at the end of the training participants would have increased knowledge of mental disorders and related treatments, and decreased negative attitudes towards people with mental disorders.     

Determination of the solute removal index for urea by using a partial spent dialysate collection method

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.