We report the results of a randomized, double-blind, placebo-controlled exploratory trial of the chimeric monoclonal anti-CD4 antibody cM-T412 in 71 patients suffering from active relapsing-remitting and secondary progressive multiple sclerosis. Infusion of the antibody produced frequent but usually minor side effects and resulted in a long-lasting reduction of circulating CD4-positive T cells. There was no significant effect on the primary measure of efficacy, the number of active lesions on monthly gadolinium-enhanced MRI over 9 months. Further statistical evaluation provided evidence that the degree of depletion of CD4-positive cells was important with regard to treatment efficacy; using CD4 counts as a covariate there was a statistically significant effect on the number of active lesions over 18 months (p = 0.04). There was a statistically significant reduction of 41% in the number of clinical relapses (a secondary efficacy parameter) after 9 months (p = 0.02), which was still present after 18 months, but this finding may be partly due to physician unblinding. Other secondary efficacy parameters (Expanded Disability Status Scale progression, number of courses of methylprednisolone) were not influenced by anti-CD4 treatment. We conclude that intravenous treatment with the monoclonal antibody cM-T412 in the dosage we used results in a substantial and sustained reduction of the number of circulating CD4-positive cells, but is not able to reduce MS activity as measured by monthly gadolinium-enhanced MRI, and is therefore unlikely to have a beneficial effect on the clinical disease course. We found preliminary evidence suggesting that more aggressive depletion of CD4-positive cells might lead to a more substantial reduction in MRI activity.

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A simple staging system allows easy assessment of the progress of cerebral gyration and sulcation in preterm and term infants.

Objectives-Serial brain MRI is widely used in pilot studies of new agents to monitor treatment eYcacy in relapsingremitting (RR) and secondary progressive (SP) multiple sclerosis (MS). For pilot trials, sample size calculations for the RR subgroup are based on the data from small numbers of patients and separate calculations for the SP subgroup have not been performed. The present study considers these issues. Methods-The sample size calculations were based on data from six months of monthly T2 weighted and gadolinium enhanced MRI in 31 RR and 28 SP untreated patients undergoing natural history studies or in the placebo arm of a therapeutic trial. The calculations were for a placebo controlled, parallel groups design lasting six months. The sample sizes were based on bootstrap analysis with an 80% likelihood of showing a given treatment eVect. Results-With a single pretreatment scan, demonstration of a 70% reduction in newly active lesions required 2×30 RR and 2×50 SP patients. With an extra run-in scan one month before treatment, the sample sizes were 2×20 for RR and 2×30 for SP patients. Conclusions-The sample sizes required for RR patients were comparable with previous smaller studies. Larger sample sizes were needed for the SP group, but the extra run in scan resulted in a reduction in both groups. The larger sample sizes in the SPMS group were probably due to the combination of a higher proportion of patients with low MRI activity (<2 active MRI lesions in 50% of SP and 32% RR patients), as well as a few patients who displayed extremely high activity, thus increasing interpatient variability. These data should be considered in planning pilot MRI outcome trials. (J Neurol Neurosurg Psychiatry 1998;64:50-55)

Background: Chronic venous insufficiency (CVI) in the occupational population is often poorly recognized. The dimensions of this problem have never been thoroughly investigated in the Netherlands. Objective: To study the epidemiology and risk factors of CVI in males with a standing position at work. To develop a simple diagnostic instrument for screening an (occupational) population for CVI. Methods: 387 male workers with a standing profession were examined by means of a questionnaire, physical examination, Doppler ultrasound investigation, light reflection rheography and optical leg volume measurements. Results: CVI was present in 29% of the subjects and correlated with age, weight and duration of standing work. Complaints of the legs were reported by 81% of the individuals with CVI but also by 63% of the persons without CVI. The questionnaire had a predictive value of 80% in detecting CVI. Conclusion: CVI was a major problem because of the quantity (29%) and the accompanying complaints. Neither the questionnaire nor other investigative measures proved to be as efficient in diagnosing CVI as physical examination in combination with Doppler ultrasound investigation.