Arsenic: health effects, mechanisms of actions, and research issues.

A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III)] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents; b) possible bioaccumulation of As; c) interactions with other metals; d) effects of As on genetic material; e) development of animal models and cell systems to study effects of As; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research; lack of relevant animal models; difficulty with adoption of uniform methodologies; lack of accepted biomarkers; and the need for a central storage repository for stored specimens.     

Development of a rubella virus DNA vaccine

Two rubella virus DNA vaccines were constructed from a cDNA clone of the rubella virus genomic RNA, one which contained the coding sequences for all three virion proteins (C, E2 and E1) and one which contained the two envelope glycoproteins (E2 and E1). When used to immunize mice via gene gun delivery, both constructs induced an antibody response of equivalent titer to that induced by rubella virus that persisted for at least seven months. A booster injection given four weeks after the initial injection increased antibody titers by over thirty-fold. The antibody response in DNA vaccine-injected mice was directed primarily against the E1 glycoprotein, as was the case in rubella virus-injected mice, and neutralizing activity was detected. These DNA vaccines are thus prototypes for a nonreplicating rubella virus vaccine that could be used in specialized circumstances.     

Gallstone lithotripsy (GSL): results of the Technomed Sonolith 3000 multicenter trials

Gallstone lithotripsy (GSL) with the Technomed Sonolith 3000 extracorporeal lithotripter was studied in a multisite, international cooperative trial involving the United States, France, and Italy. All participating sites worked under a common protocol to investigate the safety and efficacy of GSL for symptomatic gallstone patients. These collective results are from a mix of 25 academic and community hospital sites using fixed and transportable/mobile versions of the lithotripter. As of November 1, 1990, 661 patients have been treated in this two-arm randomized study (GSL Only vs GSL + Ursodiol [Actigall]). Patients were treated with up to 2,500 shocks per session and only two treatments were allowed. All machines had standardized pressure settings (850 bar nominal) and operator adjustment of output voltage was not allowed. We saw no statistically significantly different results in initial fragmentation between patients pre-loaded with ursodiol for 2 weeks and those treated by GSL alone. Gallbladder clearance rates did vary with the stone number, size, and burden as well as the adequacy of initial fragmentation. In the GSL + Ursodiol Arm of the trial, 46.2% of patients with solitary, 5-to 20-mm calculi are stone-free at 6 months.     

A unified approach to the torn thoracic aorta

In a 3-year experience treating 12 patients with blunt torn thoracic aorta, the repair technique was "clamp and sew" with an intraluminal graft in the initial six patients and partial left heart bypass using a centrifugal pump in the more recently treated six. Patients in the two groups were similar in regard to age, sex, and injury severity score. In the intraluminal graft group, graft insertion was abandoned for sutured anastomosis in two patients. Two patients sustained spinal cord ischemia, and two developed hypertension due to "pseudo-coarctation" syndrome. Because of these side effects related to the performance of intraluminal graft, partial left heart bypass was adopted as our routine procedure and was successful in all subsequent patients. Based on our experience and on reports in the current literature, we recommend left atrial-femoral bypass with the centrifugal pump for repair of the torn thoracic aorta.     

Transitioning Adolescents with Emotional and Behavioral Disorders from Most-to-Least Possible Restrictive Environments: Views of Transition Service Providers

This study examined the transition from most-to-least possible restrictive environments for youth with emotional and behavioral disorders. Components of positive transition experiences were identified from the literature as planning for transition at intake in such a way as to promote continuity of care, family involvement, academic and employment success, and assistance in navigating the adult mental health system and services. In this phenomenological study, transition service providers were interviewed to explore the transition practices currently utilized, and results were compared to recommended practices in the literature. Transition professionals were able to identify consistency, gradual change, individualization, communication between providers, opportunities for community experiences, and youth involvement in the transition as necessary to successful transition.