We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.
Varicocele is a bilateral vascular disease which occurs when the one-way valves in the internal spermatic veins, the testicular venous drainage system, malfunction. Based on new findings and fluid-mechanics analysis we showed that this process results in vertical blood columns, which cause pathological hydrostatic pressure in the testicular venous microcirculatory system. Ultimately, these pressures exceed the pressure in the arteriolar system. This unique phenomenon of reversal of pressures gradient between the arteriolar and venular systems leads to persistent hypoxia in the testosterone production site, namely, the Leydig cells. The result of bilateral varicocele is decreased testosterone production. Adequate treatment of bilateral varicocele significantly elevates the testosterone production. We found that the prevalence of varicocele increases with age with a rise of about 10% for each decade of life with the incidence reaching 75% in the eight decade of life. Based on our findings the following statements can be made: (1) varicocele prevalence is increased over time. (2) The rise of the incidence is about 10% for each decade of life. (3) 75% of men in the eight decade of their life have varicocele. As varicocele decreases testosterone production and it is reversible by appropriate treatment, it raises two interesting and important issues to be studied: (i) it is possible that varicocele accelerates the process of the ageing male. (ii) It is possible to retard, at least partially, the process of ageing in men by adequate treatment of bilateral varicocele.
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