Islet Xenotransplantation: Are We Really Ready for Clinical Trials?

Four clinical trials of porcine islet transplantation have been reported, and there are verbal reports that clinical trials on much larger scales are continuing in centers in China and Russia. The four reported trials are briefly reviewed and, in the light of the present status of experimental islet xenotransplantation, consideration is given to whether such trials are currently justified. The Ethics Committee of the International Xenotransplantation Association has (1) emphasized the need for encouraging studies in non-human primates before clinical trials should be undertaken, (2) mandatory monitoring for the transfer of porcine microorganisms, and (3) careful regulation and oversight by recognized bodies. Other aspects of the topic, such as the need for informed consent, are briefly discussed. We conclude that, at the present time, more data documenting convincing efficacy, focused on clinically applicable immunosuppressive regimens, are needed to justify the initiation of closely monitored clinical trials. A clinical trial may then be justified even though the potential risk to the patients, and possibly for society, will not be zero.     

Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

Notification of rheumatic fever in South Africa -- evidence for underreporting by health care professionals and administrators.

OBJECTIVE: To determine whether under-reporting of rheumatic fever occurs at hospital, municipal, provincial and national levels of the South African health system. BACKGROUND: Information on the incidence of rheumatic fever (RF) and the prevalence of rheumatic heart disease (RHD) is required for the prevention of valvular heart disease in developing countries. In South Africa, RF was made a notifiable condition in 1989. It has recently been suggested that the reporting of RF cases may be incomplete, possibly because of underreporting by health care professionals and deficient administration of the disease notification system in South Africa. METHOD AND RESULTS: We assessed whether underreporting of RF cases occurs by comparing the numbers of RF cases reported per year at hospital, municipal, provincial and national levels from 1990 to 2004. There was a fall in the number of RF cases reported per year at national and provincial level over the 15 years of observation. A detailed analysis of the number of RF cases reported at hospital, municipal and provincial level for a 5-year period showed that more cases were diagnosed in one hospital (serving a smaller population) than were captured at municipal and provincial level (serving a larger population), suggesting underreporting by health care professionals. There were discrepancies in the number of cases reported at municipal, provincial and national level, suggesting poor administration of the notification system. CONCLUSION: There appears to be underreporting of RF cases by health care professionals, and poor administration of the RF notification system. Health care professionals need to be educated about the statutory requirement to notify all RF cases in South Africa. An effective national disease notification system is required.     

UVB靶向光疗治疗斑块型银屑病

目的:确定UVB靶向光疗治疗局限性银屑病是否安全有效及是否存在量效关系。设计:随机、对评估者设盲对照研究。机构:泰国曼谷大学医院皮肤病门诊。患者:14例稳定性局限性斑块型银屑病患者。干预:依据预定的最小红斑量(M EDs),随机给予患者不同通量的UVB靶向光线治疗,3次/周。在4     

Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy.

INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I). MATERIALS AND METHODS: After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7). RESULTS: In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed. CONCLUSION: These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage.