Juvenile dermatomyositis: the association of the TNF alpha-308A allele and disease chronicity

Little is known concerning factors associated with the outcome of juvenile dermatomyositis (JDM), which can be variable and lethal. Previous work has documented that the association of DQA1*0501 with JDM is higher than in control groups and that the first symptoms (rash and weakness) of JDM appear to follow evidence of an infectious process--most frequently upper respiratory in nature. Preliminary data show that a long period of symptoms being left untreated before starting therapy and the TNF alpha-308A allele are associated with prolonged JDM symptoms requiring > or = 36 months of immunosuppressive therapy. A short duration of untreated disease is associated with a relative increase in CD8(+) T cells and CD56(+) natural killer (NK) cells in the untreated JDM muscle biopsy compared with a longer duration of untreated disease. The TNF alpha-308A allele is overrepresented in white children with JDM. In addition, it is associated with pathologic calcifications, increased production of TNF alpha by peripheral blood mononuclear cells in vitro and JDM muscle fibers in vivo, and occlusion of capillaries, which may be mediated in part by elevated circulating levels of thrombospondin-1, a potent anti-angiogenic factor. We speculate that DQA1*0501 is associated with JDM susceptibility to an infectious process, eliciting and activating NK cells early in the disease course. We conclude that the TNF alpha-308A allele indicates directly (or is a surrogate marker of) children with JDM who produce higher concentrations of TNF alpha in response to this undefined inflammatory stimulus, as well as increased concentrations of TSP-1 with resultant small vessel occlusion, contributing to subsequent disease chronicity.     

杀虫剂诱导人外周血淋巴细胞DNA损伤

目的:用人外周血淋巴细胞彗星试验检测乐果、甲基对硫磷、氯氰菊酯、扑灭司林等杀虫剂的遗传毒性。方法:分别用10,50,100,200μg/ml浓度的乐果、甲基对硫磷、氯氰菊酯、扑灭司林在37℃下染毒人外周血淋巴细胞0.5 h,同时用100μg/ml的过氧化氢(H2O2)作阳性对照,用磷酸盐缓冲液(PBS)作阴性对照。用彗星试验检测以上4种农药对人外周血淋巴细胞DNA损伤作用。结果:与阴性对照相比,乐果和对硫磷在100μg/ml浓度,扑灭司林和氯氰菊酯在200μg/ml浓度对人外周血淋巴细胞DNA损伤作用明显增强(P<0.01)。结论:受试的4种农药可引起DNA损伤。     

Malaysian Dialysis and Transplant Registry Report

SUMMARY: This report summarizes data for dialysis and transplant patients up to the end of 1995. We estimate coverage to be about 30% of dialysis patients and near complete ascertainment of transplant patients. On the 31 December 1995, there were 2224 patients on renal replacement therapy (RRT), comprising 50% on haemodialysis (HD), 12% on continuous ambulatory peritoneal dialysis (CAPD) and 38% with functioning transplants. the prevalence rate for dialysis was 68 per million population (p.m.p.) and that of transplant 42 p.m.p. the new dialysis acceptance rate was 15 p.m.p. and transplant 5 p.m.p. Forty-seven per cent of new patients had unknown primary renal disease and 30% was due to non-insulin dependent diabetes mellitus. Mean age of prevalent HD patients was 42 years, CAPD 46 years and 34 years for transplant. Patient survival on CAPD was 85% at 1 year and for HD was 88%. One year transplant patient survival was 94% and graft survival 91%.     

IMPROVED TOLERABILITY OF FELODIPINE COMPARED WITH AMLODIPINE IN ELDERLY HYPERTENSIVES: A RANDOMISED,DOUBLE-BLIND STUDY IN 535 PATIENTS,FOCUSING ON VASODILATORY ADVERSE EVENTS

SUMMARY The primary aim of this double-blind, parallel group trial was to compare incidence of newly occurring vasodilatory adverse events in elderly patients treated with recommended once-daily doses of felodipine extended release (ER) or amlodipine. A total of 535 patients over 65 years old with a sitting diastolic blood pressure of 90-115 mmHg and/or systolic blood pressure 160-220 mmHg, were recruited at 46 centres worldwide. Patients were randomised to felodipine ER 2.5 mg or amlodipine 5 mg. If blood pressure was >160/90 mmHg after three or six weeks, felodipine ER was increased to 5 and 10 mg and amlodipine to 10 mg. After nine weeks, average doses of felodipine ER and amlodipine were 5.5 mg and 7.3 mg, respectively. Newly occurring vasodilatory adverse events were reported by 32% of felodipine ER patients and 43% of amlodipine patients (p=0.007). Both treatments effectively reduced blood pressure 24 hours post-dose. Using a low starting dose and individual titration, felodipine ER achieves good control of blood pressure with few vasodilatory side-effects.     

An analysis of factors affecting the incidence of inhibitor formation in patients with congenital haemophilia in Japan

Summary. Studies conducted in European and North American countries have demonstrated that various factors including races affect the frequency of inhibitor formation in haemophilia patients. The present study was undertaken to analyse factors affecting the incidence of inhibitor formation in Japanese haemophilia A and B patients. Analytical data were retrospectively collected from haemophilia A and B patients born after 1988, the year when monoclonal antibody‐purified factor VIII products were first marketed in Japan. Various data were collected from 184 patients (153 cases of haemophilia A; 31 cases of haemophilia B). The sample size of haemophilia B cases was too small to reveal any significant differences between the inhibitor formation group and the inhibitor‐free group in any of background variables. For patients with haemophilia A, on the other hand, univariate analysis identified the severity of haemophilia and a positive family history of inhibitor development as risk factors for the formation of inhibitors. In analyses of the clotting factor products used, the incidence of inhibitor formation did not differ significantly between the group treated with plasma‐derived products (29.7%) and the group treated with recombinant products (25.0%). When background variables were compared, age was higher in the group treated with plasma‐derived products but none of the other background variables differed between the two groups. These results suggest that in Japanese haemophilia patients, the type of clotting factor preparations used for therapy has not influenced the incidence of inhibitor formation.     

Microbial Burden of Some Herbal Antimalarials Marketed at Elele, Rivers State

Herbal antimalarials still remain an alternative to our traditional communities who can not afford orthodox antimalarials. This study was aimed at investigating the microbial quality of six herbal antimalarials using standard microbiological methods. Of the six preparations analyzed, “schnapps”, palm wine and water were the media of preparation; the water base preparations recorded higher microbial load. The mean microbial load was 159.5×10⁵ cfu/ml and 217.4×10²cfu/ml in water and alcohol base preparations respectively. The microbial profile of the preparations showed that the schnapps base preparations were predominantly contaminated with Bacillus sp (Aerobic spore bearers) and Mucor spp. The palm wine preparation harboured Bacillus sp, yeasts and Mucor spp while the water base preparations had several isolates such as Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli 0157H7, Proteus mirabilis, Enterococcus feacalis, Serratia marcensces, Staph. aureus, Bacillus spp and Mucor spp. Conclusively, this study underlines the public health importance of these preparations given the high burden of such human pathogen as Ecoli O157H7, Ps aeruginosa, Stahp aureus, etc. in the preparations.