Effects of low-dose prednisolone on cyclosporine pharmacokinetics in liver transplant recipients: radioimmunoassay with specific and non-specific monoclonal antibodies

The following study of cyclosporine pharmacokinetics was performed to investigate the effects of withdrawal of low-dose maintenance prednisolone (0.3-0.6 mg/kg body weight) from the routine immunosuppressive regimen given to 10 liver transplant recipients with stable liver function tests. After oral administration of cyclosporine (6.4-10.3 mg/kg) whole blood concentrations were measured by radioimmunoassay (RIA) with both a specific monoclonal antibody detecting parent drug and a non-specific antibody additionally detecting a cross-section of metabolites. Withdrawal of prednisolone produced no significant change in the mean time and concentration of maximum blood cyclosporine (3.3 h and 1160 micrograms/l, respectively), the initial and terminal elimination half-life (3.5 h and 18.4 h, respectively) and the area under the blood concentration versus time curve (AUC) measured with either the specific or non-specific monoclonal antibody. Measurements with these two antibodies indicated that the terminal elimination of cyclosporine metabolites was more rapid than for the parent drug (half-life: 14.5 vs 18.4, respectively).     

Osteoporosis in severe congenital neutropenia treated with granulocyte colony-stimulating factor

Recombinant human granulocyte colony-stimulating factor (G-CSF) has substantially improved life expectancy for children with severe congenital neutropenia (SCN). Severe osteoporosis, reported in this population, may relate to the disease process, or be a therapeutic side-effect. This report details bone loss, quantitated absorptiometrically and histomorphometrically, in a child with SCN and vertebral collapse, and the positive response to anabolic steroid and bisphosphonate therapy.     

The incidence of immunosuppression-related skin disease in long-term transplant patients

One hundred and twenty-one patients who had received a renal allograft between 4 months and 21 years previously (mean +/- SD, 71 +/- 62 months) were studied. Seventy-two patients were conventionally immunosuppressed with azathioprine and prednisolone, and 36 had been exposed to the current regime of cyclosporine, azathioprine, and prednisolone. Forty-five patients had viral warts, of whom 20 had more than 10 warts. The presence of viral warts was significantly associated with pale skin type, excess sun exposure, and with duration of allograft. Viral warts were significantly more common in those on conventional immunosuppressive therapy, but this could be solely a reflection of the difference in duration of transplant between the 2 groups. Twelve patients were found to have developed dysplastic or neoplastic skin lesions since transplantation. The incidence of dysplasia increased with increasing age and was significantly associated with pale skin type, excess sun exposure, and duration of allograft. Despite the shorter duration of treatment in those on the new treatment regime, there was no difference between the 2 groups in the proportion of patients with dysplastic skin lesions. Immunosuppression-related skin disease may be a significant problem in allograft recipients in this country, and we suspect that patients taking cyclosporine will have similar problems to those on conventional immunosuppressive drugs alone. Immunosuppressed patients should be advised to avoid sun exposure, to use sunscreens, and should be monitored carefully for the development of dysplastic lesions.     

Epidemiologists in the United States: an assessment of the current supply and the anticipated need

We provide 1985 estimates of the work force of epidemiologists in the United States, the number of graduates from training programs in epidemiology, and a projection of the future need for these health professionals. Our methods included a search of mailing lists from professional organizations, mail contact with graduate training programs, telephone interviews with experts, and a review of job announcements in professional journals. The study indicates that the current work force of epidemiologists in the United States is estimated to include 4,600 persons, more than half of whom are physicians; most epidemiologists are located in either a state with a major federal public health agency or one with a large population; and programs in epidemiology graduate an average of 475 persons with one or two years of master's level education and approximately 80 with doctoral-level education each year. After considering the factors that influence the supply of epidemiologists, we project a substantial need for more epidemiologists in the future than current sources will provide.     

Disturbances in cell recognition molecules (N-CAM and L1 antigen) in the CSF of patients with schizophrenia

Although the pathogenesis of schizophrenia is unknown, there are data which indicate that the disease may be due to neurodevelopmental disturbances. Cell recognition molecules such as N-CAM and L1 antigen are involved in cell-cell interactions during development and in plasticity of the nervous system and could therefore be altered in relation to ongoing or established pathological processes. Using the Western blot technique, we found significant increases in N-CAM immunoreactive proteins and decreases in L1 antigen in the CSF of schizophrenic patients as compared to normal controls. The decrease in L1 antigen was observed in the 140-kDa band, and N-CAM was increased only in the 120-kDa band. The 120-kDa band of N-CAM and the 140-kDa band of L1 antigen were prominent components of CSF, but in serum these bands were minor or not detectable. Neuroleptic treatment did not significantly change either N-CAM or L1 antigen concentrations in CSF. It is possible that these CSF proteins are derived from CNS cells as secreted soluble N-CAM isoforms and L1 peptides. Our results suggest the possibility of a specific pattern of abnormal cellular function in the CNS in schizophrenia.     

Sex education and the AIDS epidemic in the Former Soviet Union

This paper describes the Russian response to sexuality, sex education and AIDS. Using primarily Russian language sources, it analyses the background to the current Russian debate on sex education since the 1960s. The nature of the government response – the introduction of a health education programme designed largely to combat specific sexual diseases such as syphilis and gonorrhoea – is also explored. It is suggested that the demise of the Communist edifice has not significantly altered official attitudes towards sex and sexuality. Particular attention is devoted to the impact of the AIDS epidemic on government and popular reaction to this sex education programme. Given the adverse effects which the breakup of the FSU, economic crisis and the disintegration of the USSR Ministry of Public Health in November 1991, have had on the possibility of launching a unified, co-ordinated and systematically concerted sex education programme it is concluded that backward attitudes towards sexuality are likely to exist for many years to come and the same is true with regard to the widespread prejudices towards the victims of AIDS in the FSU.     

Asbestos bodies in lung tissue following exposure to crocidolite

A series of 206 necropsies in Western Australia (WA) have had routine counts made of asbestos bodies in samples of lung tissue using conventional light microscopy. Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log) counts of asbestos bodies in their lung tissue correlated well with estimates of their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There was no association between the number of asbestos bodies and time since exposure to asbestos ceased. In subjects without known exposure to asbestos, there was a weak but nonsignificant increase in number of asbestos bodies with increasing age, with 26% of cases having no asbestos bodies present. It is concluded that the relatively simple technique of light microscopy for counting of asbestos bodies in lung tissue provides a reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. This could be extremely useful in follow-up studies of cohorts that lack reliable measures of airborne exposure to crocidolite asbestos.     

Detection of HLA-A*24 null alleles by DNA typing methods

Abstract: A number of cases have been identified (seven unrelated individuals from the Northern Ireland bone marrow donor registry and two family groups) where an HLA-A*24 allele fails to express the normal HLA-A24 antigen. Family information has revealed common haplotypes with respect to each non-expressed allele indicating that the occurrence of these mutations has been a recent event. Two methods for the clinical typing of these alleles have been evaluated - PCR-SSOP and PCR-SSCP analysis.     

High-dose cimetidine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group study.

The Hoosier Oncology Group evaluated cimetidine in 42 patients with metastatic renal cell carcinoma. There were two complete remissions that lasted for 26 and 33+ months in 38 evaluable patients. There were no partial remissions. Toxicity was minimal. Patients with renal cell carcinoma can occasionally respond to cimetidine with long-term remission.