The Impact of Total Gastrectomy on Pharmacokinetics in Kidney Transplant Immunosuppressive Drug Regimes: A Case Study.

BACKGROUND: Ensuring reliable gastrointestinal drug absorption of orally administered immunosuppressive medications posttransplant is critical to ensuring graft survival. METHODS: A 66-year-old man of East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy. The Gastrointestinal Quality of Life Index and Gastrointestinal Rating Scale questionnaires were administered to gauge immunosuppressive medication-related side effects in the absence of a stomach. RESULTS: The patient's ability to absorb cyclosporin, tacrolimus (Tac), enteric-coated mycophenolate sodium (EC-MPS) and sirolimus (SRL) in oral dosage forms was well-preserved. Compared to nongastrectomy reference populations, the rate and extent of absorption of SRL and mycophenolic acid from EC-MPS were similar. The absorption of Tac and cyclosporin was greater than expected. Mycophenolate mofetil did not provide mycophenolic acid absorption as well as EC-MPS. The patient had worsened gastrointestinal symptoms with mycophenolate mofetil or EC-MPS in combination with Tac and cyclosporin, but this was not seen with isolated SRL. CONCLUSIONS: This case demonstrates that commonly used postkidney transplantation immunosuppressive regimes may be prescribed after total gastrectomy as long as their limitations are noted.

Brain cancer in a residential area bordering on an oil refinery.

Both in response to community concerns about brain cancer related to an oil refinery and in order to more fully understand the etiology of primary site brain cancer (glioma), a highly focused cancer cluster investigation was conducted. The components included: (1) a literature review of occupational exposures in the petroleum refining and petrochemical industries, (2) comparisons between observed and expected cases, (3) comparisons between mean age at diagnosis and median survival time and (4) interviews concerning exposures of cases. Evidence from the literature review revealed little, if any, effect of petroleum refinery or petrochemical exposure on the risk for brain cancer. There was no statistically significant increase in the number of brain cancer cases in the community (observed = 12, expected = 9.46, standardized mortality ratio = 1.27). There was no statistically significant decrease in mean age at diagnosis or median survival time among those most exposed. Reports of exposure from the case interviews were highest for eating processed meats (98.5%), dental X-rays (96.6%), dog ownership (91.2%) and swimming (80.3%). There were no major occupational exposures identified. It seems unlikely that petrochemicals are involved in any significant way in the etiology of most brain cancers (gliomas). A follow-up case-control study should focus primarily on those risk factors mentioned frequently by the cases.

Influenza: prospect for prevention and control.

Influenza is an emerging and re-emerging disease. Since the late 1930s influenza viruses have been isolated yearly from different parts of the world during epidemics and pandemics. The "epidemiologic success" of influenza is due largely to rapid and unpredictable antigenic changes (antigenic drift) among human influenza viruses, and the emergence of new subtypes (antigenic shift), mostly from reassortment between human and avian influenza viruses. Antigenic shifts were attributed to the global pandemic viruses of 1957 (H2N2 Asian flu) and 1968 (H3N2 Hong Kong flu). Concern over possible new pandemics has been heightened by recent reports of human infection in Asia in 1997 with avian viruses (H5N1) and in 1999 (H9N2) and isolation of human-avian reassorted viruses from pigs and humans in Europe. Influenza has a high rate of inapparent infection, short incubation and high infectivity; epidemics usually start abruptly and spread rapidly to neighboring communities and countries. Isolation and quarantine are often unsuccessful in preventing the spread of the infection. Although not perfect, immunization and chemoprophylaxis are highly effective at minimizing the spread of influenza and reducing morbidity and mortality, social disruption and economic loss. Plans for future influenza epidemics and pandemics require national and international programs to be in place for the monitoring of influenza activity, the dissemination and exchange of information and the provision and delivery of sufficient quantities of vaccines and antiviral agents. This paper reviews and discusses the antigenic variations of the influenza virus, potential influenza pandemics, protective efficacy of inactivated vaccines and antiviral agents and preparation for control of future epidemics and pandemics.

Serologic responses of children after primary vaccination and revaccination against smallpox

Three serologic test methods were used to study immunologic responses of 36 children vaccinated against smallpox. Following successful primary vaccination, 97 percent of the children converted for neutralizing and HI antibodies and 18 percent for CF antibodies, 3 of 33 children had a 4-fold or greater decrease for neutralizing antibodies, but 29 of 33 children had a decrease for HI antibodies. All children became negative for CF antibodies. After the second vaccination 15 months later in which only one child failed to respond clinically, 78 percent of the children had a 4-fold or greater neutralizing antibody rise; in contrast only 18 per cent showed a significant HI antibody titer increase; 44 per cent converted for CF antibodies. (AU)