Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo

Objective. T cells treated with DNA methylation inhibitors overexpress lymphocyte function-associated antigen 1 (LFA-1), which results in autoreactivity, and the autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by which some agents may cause drug-induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA-1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity. Methods. Cloned murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo. Results. Pca and Hyd were more potent than their analogs or HU in all 3 assays. Conclusion. The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.     

Decentralization of forensic services

Decentralization of mental health services to persons in contact with the criminal justice system is essential in the application of community mental health concepts. This is feasible considering the levels of "dangerousness" of such persons, costs of the typical isolated central facility, and implications of the Supreme Court decision Jackson v. Indiana (406 U.S. 715, 1972). In Tennessee, reform began with legal review of unit records, pretrial screening in mental health centers, revision of state law, liaison with the Tennessee Board of Pardons and Paroles, and use of consultant staff. The results are positive wherever decentralization of services has been maintained.     

Malignant melanoma incidence in Connecticut (United States): time trends and age-period-cohort modeling by anatomic site

This study examined time trends and age-period-cohort patterns in the incidence of cutaneous malignant melanoma (CMM) by gender and anatomic site in Connecticut (United States) between 1950 and 1989, using data from the population-based Connecticut Tumor Registry. A total of 8,249 invasive CMM incident cases were included. Cases were grouped into melanomas of the head and neck, upper limb, lower limb, and trunk. Between 1950 and 1989, rates increased substantially for all sites. The largest relative increases occurred in melanoma of the upper limb for both males and females; the largest absolute increase occurred for melanoma of the trunk in males; and the smallest increase occurred in head and neck melanoma in females. Recent trends for time periods 1970–89 among birth cohorts 1930–69 indicated that the rate of increase of CMM is slowing substantially among males, but not among females. Nevertheless, continued overall increases in CMM incidence are likely in Connecticut in the 1990s in both genders, with a decrease in the male-female ratio. The age-period-cohort patterns were significantly different between the genders and among anatomic sites, suggesting different trends in carcinogenic exposures (mainly ultraviolet radiation from the sun) or etiologic distinctions between males and females and among the sites.This study was supported by the National Institute of Health grant # CA-62986, and #CA-30931. Dr Dubrow received support from a National Cancer Institute Preventive Oncology Academic Award (K07-CA01463).     

Tobacco use and prostate cancer in Blacks and Whites in the United States

Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR]=1.1, 95 percent confidence interval [CI]=0.7–1.5) and in Whites (OR=1.2, CI=0.9–1.6), or for current cigarette smokers, in Blacks (OR=1.0, CI=0.7–1.4) and in Whites (OR=1.2, CI=0.8–1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR=1.4, CI=1.0–1.5) and current (OR=1.5, CI=1.0–2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR=1.5, CI=1.0–2.3) and former (OR=1.7, CI=1.1–2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking. Risks also were not elevated for former or current users of pipes, cigars, or chewing tobacco, but the risk associated with current snuff use was OR=5.5 (CI=1.2–26.2). This subgroup finding may have been due to chance. The results of the present study may be consistent with a small excess risk for prostate cancer associated with tobacco use, but the lack of consistent findings in population subgroups and the lack of a clear dose-response relationship argue more strongly that no causal association exists. The data do not indicate that the Black-White difference in prostate cancer risk is related to tobacco use.This research was performed under contracts: NO1-CP-51090, NO1-CN-0522, NO1-CP-51089, NO1-CN-31022, NO1-CP-51092, and NO1-CN-5227.     

Maxillary and sphenoid sinusitis complicated by acute inflammatory optic neuritis in a 12-year-old patient]

Acute inflammatory optic neuritis (retrobulbar optic neuritis) is an uncommon but described complication of acute sinusitis. It is due to a close anatomic relationship between the sinus and the optic nerve. Inflammatory mechanism is dominant with a possible bilateral neuritis, especially among children. In the reported case, as usual in childhood, visual acuity loss has been particularly severe, and recovery slow (it takes usually 6 weeks) but almost complete. Primary treatment is medical, with antibiotics and corticosteroids that must be prescribed for a prolonged time.