The role of several factors that have been suggested as being of etiologic importance in renovascular fibromuscular dysplasia was examined in a case-control study of 33 patients with angiographically demonstrated fibromuscular dysplasia and 61 renal transplant donor control subjects with normal renal arteries. The factors studied included use of oral contraceptive agents or markers of sex hormone dysfunction, mechanical stress to the renal artery wall, human lymphocytic antigen (HLA) type, cigarette smoking, history of hypertension for more than 5 years, and family history of cardiovascular disease. The risk of fibromuscular dysplasia was significantly (/»=0.003) increased (odds ratio=4.1, 95% confidence interval=1.5-10.9) among cigarette smokers. A significant (/xO.001) dose-response relation was noted between cigarette use and the risk of fibromuscular dysplasia developing (odds ratio=8.6 for those who had smoked more than 10 pack-years). Personal history of hypertension more than 5 years was also associated (odds ratio=5.0,95% confidence interval^ 1.1-22.8) with a significantly (p=0.036) increased risk for the development of fibromuscular dysplasia. HLA-DRw6 antigen was more common in the 33 fibromuscular dysplasia patients than in the 61 renal transplant donor control subjects (odds ratio=3.00, /?=0.067) or a second group of 934 ambulatory control subjects (odds ratio=2.51, p=0.03l). Adjustment for cigarette smoking increased the odds ratio to 5.0 (95% confidence interval=1.3-19.6). There was a positive though not statistically significant (odds ratio=1. Received November 15, 1988; accepted in revised form June 30, 1989. has yet to be determined. The most commonly mentioned putative etiologic factors include exposure to exogenous estrogens, mechanical stress to the renal arteries, and genetic predisposition. However, these suggestions have primarily been derived from patterns noted in single case reports and case series. A better understanding of the factors responsible for the etiology of FMD would provide a rational basis for planning strategies to prevent FMD. With this in mind, we conducted a casecontrol study of etiologic factors in FMD. Our study was primarily designed to examine the etiologic roles of: 1) oral contraceptive administration and markers of sex hormone function, 2) mechanical stress to the renal arterial wall resulting from excessive mobility of the kidneys, 3) genetic predisposition, 4) cigarette smoking, and 5) history of cardiovascular disease in patients or their families.

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A robust approach for analysis of variance components models is presented which does not rely on the assumption of multivariate normality for its validity. This approach uses the multivariated normal distribution as a 'working model' but obtains standard errors for the final estimators which do not depend on this underlying distribution. By using the observed variance in the first derivatives of the multivariate normal 'working model' to modify the conventional score test, hypotheses regarding specific components can also be tested without relying directly on the assumption of multivariate normality. A special case is presented where both the modified score test and the likelihood ratio test are equally robust, and simulated data are used to illustrate this situation. Measurements of triglyceride levels in 391 individuals in 60 families randomly selected from the membership of a health maintenance organization are used to illustrate this robust approach to variance components.

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BACKGROUND AND OBJECTIVE: Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea’s effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1–S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses. METHODS: T-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG). RESULTS: Compared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use. CONCLUSIONS: Hydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced.