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Biomedical subjects

C Kaufman

Publications and source records attributed to C Kaufman.

At least 19 recordsLinked to original sources

A double-blind placebo-controlled crossover trial of intravenous magnesium sulfate for foscarnet-induced ionized hypocalcemia and hypomagnesemia in patients with AIDS and cytomegalovirus infection.

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO(4) at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO(4) reduced or eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnet-induced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO(4) was safe in this chronically ill population. Since parenteral MgSO(4) did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet.

AIDS-Related Opportunistic Infections↗

Health information resources: tradition and innovation in a medical school curriculum.

Changes in LCME accreditation for medical colleges fostered the development of Health Information Resources, a required, for-credit course created by the Saint Louis University Health Sciences Center Library Reference Department for the first-year medical school curriculum. Six content areas were developed for inclusion in the syllabus: "Electronic Resources Survival Kit"; "Introduction to Problem Based Resources"; "Introduction to Literature Searching"; "MEDLINE Searching Hands-On/Publishing Pearls & Pitfalls"; "The World Wide Web and Patient Information"; and "Introduction to Electronic Mail." A combination of lectures, hands-on instruction, and active learning techniques were employed in the teaching of this class. Submission of a Health Information Resource Guide and a two-part final exam were required.

Academic Medical Centers↗

Donor-specific tolerance induction in composite tissue allografts.

BACKGROUND: Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting would be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a strongly antigenic MHC mismatch without the need for long-term immunosuppression. METHODS: Chimeras were prepared using rat strains with strong MHC incompatibility [WF (RT1Au) + ACI (RT1Aa) --> WF, n = 13]. Syngeneic (WF) and allogeneic (ACI) bone marrow (BM) was harvested and T-cell depleted. Following confirmation of T-cell depletion by flow cytometry, a mixture of T-cell depleted syngeneic and allogeneic BM was injected into the recipient animals (all recipients pretreated with low-dose irradiation, 500 to 700 cGy). In addition, the recipient animals received a single dose of ALS (10 mg) 5 days prior to bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day prior to BMT to 10 days postoperatively. Rat chimeras were characterized by flow cytometry at 3 and 12 months after BM reconstitution and following hindlimb transplantation. RESULTS: Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 10 of 13 animals. Multilineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60%, there was no sign of limb rejection for the duration of the study. All animals with chimerism <20% developed moderate signs of rejection clinically and histologically. Gross motor and sensory reinnervation (weight bearing, toe spread) occurred at >60 days in 6 of 9 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n = 7). CONCLUSIONS: Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. This represents the first reliable model demonstrating rejection-free CTA survival in an adult animal without the long-term use of immunosuppressive agents across a strongly antigenic MHC mismatch.

Animals↗

Hydrocarbon exposure and chronic renal disease.

The study objective was to investigate further the potential role of long-term exposure to hydrocarbons (HCs) in the development of idiopathic chronic glomerulopathy (ICG) using a more refined measurement of HC exposure. A total of 321 pairs of cases and controls, matched by age, gender, and geographical area, were assembled. A detailed questionnaire was blindly administered to cases and controls to collect information on occupational and medical history and sociodemographic data. By integrating quantified measurements of HC exposure from a variety of sources with each subject's occupational history, a lifetime HC exposure score could be estimated and expressed in parts per million (ppm). Cases had an hydrocarbon exposure mean score of 165 ppm (median 48 ppm) as compared to 162 ppm (median 43 ppm) for controls (P = 0.757). When using hydrocarbon exposure as a dichotomous variable with a cutoff point at 100 ppm, cases had a higher proportion of exposed than controls, but the difference was not statistically significant at the 0.05 level, even after controlling for possible confounders through logistic regression. Subgroup analyses showed mixed results. In most subgroups differences between cases and controls tended to become significant when hydrocarbon was used as a dichotomous variable. Results from this study do not sufficiently support the hypothesized association of HC exposure and ICG in general. Subgroup analyses need further investigations. Efforts to generate accurate estimates of lifetime HC exposure should be emphasized for future investigations.

Case-Control Studies↗

A longitudinal psychopathological schedule.

A schedule is described for rating the symptoms of mental illness over a period of time which includes several episodes. The reliability was measured in a study involving six raters. The sources of information required were studied, in 20 patients, by comparing an interview with the patient, a similar interview with an informant and an analysis of the case records. A synopsis of interview and record data are necessary to obtain adequate information about longitudinal psychopathology and 'lifetime' diagnosis.

Adolescent↗

Schizophrenia, bipolar disorder and depression. A discriminant analysis, using 'lifetime' psychopathology ratings.

Discriminant and canonical variate analyses were performed using 302 patients, on whom ratings of lifetime psychopathology and course of illness has been made. DSM-III diagnoses were used to form the criterion groups. Bipolar disorder emerged as a distinct grouping, but there are reasons for dissatisfaction with its definition. The remaining patients formed a 'schizodepressive continuum', but this also had a tendency to bimodality. It is possible that the distinction between schizophrenia and depression was obscured by inadequacies in the data and the inclusion of excessive numbers of patients with schizoaffective depression in this study.

Adolescent↗

Propagation of alloreactive lymphocytes from histologically negative endomyocardial biopsies from heart transplant patients. Association with subsequent histological evidence of allograft rejection.

Endomyocardial biopsies from heart transplant patients were cultured in vitro in the presence of Interleukin-2 and irradiated feeder cells to propagate graft-infiltrating lymphocytes. A correlation was seen between the frequency of lymphocyte growth and the degree of cellular infiltration of the biopsies. In this study, 43 of 113 (38%) histologically negative biopsies obtained from 55 patients during the first month post-transplant yielded lymphocyte cultures. The cumulative incidence of subsequent histological rejection was considerably higher in patients with such "grower" biopsies than in patients with "nongrower" biopsies. In the grower group, we were able to obtain data on alloreactivity of 32 lymphocyte cultures assayed by primed lymphocyte testing (PLT). The presence of donor-specific PLT reactivity in the cultured lymphocytes was associated with an additional risk for subsequent histological rejection. These findings suggest that the in vitro culturing of histologically negative endomyocardial biopsies will identify patients at increased risk for developing heart transplant rejection.

Biopsy↗

In vitro studies of endomyocardial biopsies from heart transplant recipients on RATG and OKT3 immunoprophylaxis protocols.

Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.

Adult↗

Assessment of c-myc expression in individual leukemic cells.

The expression of the proto-oncogene c-myc was studied at the protein level in cells obtained from patients with AML and CML. In florid AML and during the blastic phase of CML the majority of cells contain c-myc protein with the amount of protein differing widely among the cells of individual patients. In contrast, during complete remission in AML and during the chronic phase of CML cells containing c-myc protein are rare. Several studies demonstrated a discordance in the amount of c-myc transcript and the amount of c-myc protein present in cell populations thereby suggesting the presence of translational or post-translational regulation of c-myc expression. Further, the data suggest that high levels of c-myc protein in the leukemic cells of AML patients are associated with a poor response to therapy and that high levels in AML patients in CR or in the peripheral blood of chronic phase CML patients may be indicative of impending acute leukemia.

Gene Expression Regulation↗