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Biomedical subjects

G Stephens

Publications and source records attributed to G Stephens.

At least 19 recordsLinked to original sources

Elevated hprt mutant frequency in circulating T-lymphocytes of xeroderma pigmentosum patients.

The mutant frequency to 6-thioguanine resistance in circulating T-lymphocytes from 10 xeroderma pigmentosum patients (including complementation groups D and G and XP variants) has been determined. A highly significantly elevated frequency was observed, compared to age-matched, non-smoking control donors (x 2.1-fold higher than the mutant frequency in normal control donors, adjusted for age and cloning efficiency, p less than 0.001). The mutant frequency of 5 XP heterozygotes was in the normal range, when age, smoking habit and log cloning efficiency were taken into account. A number of possible factors which may account for the elevated mutant frequency seen in the XP donors (including an elevated spontaneous mutation rate, UV mutagenesis of the T-cells as they pass through the skin, an effect of environmental mutagens such as tobacco smoke, or as a consequence of immune deficiency) are discussed.

Adult

The induction of immunologic hyporesponsiveness by preoperative donor-specific transfusions and cyclosporine in human cadaveric transplants. A preliminary trial.

A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.

Acquired Immunodeficiency Syndrome

Comparative human cellular radiosensitivity: III. Gamma-radiation survival of cultured skin fibroblasts and resting T-lymphocytes from the peripheral blood of the same individual.

Skin and blood samples were obtained from 34 donors, for whom there was no indication of abnormal radiosensitivity. From these, in 33 cases both fibroblast and T-lymphocyte cultures were obtained and in 26 cases at least three fibroblast and at least two G0 (resting) T-lymphocyte survival assays were possible. Within this set of results, differences in radiosensitivity between donors were significant for fibroblasts but not T-lymphocytes, although the range of radiosensitivity was similar for the two cell types (D 0.90-1.68 Gy for fibroblasts; 1.26-2.15 Gy for T-lymphocytes). Furthermore, there was little evidence for a correlation in radiosensitivity between the two cell types. These results suggest limitations in the predictive value of conventional measurement of cell survival.

Cell Survival

Choledochoscopy and common bile duct exploration.

Common bile duct (CBD) exploration is often indicated when cholecystectomy is performed for gallstone disease. Choledochoscopy may help to decrease the incidence of retained common duct stones. The present study reviews 97 consecutive CBD exploration cases performed between 1980 and 1988, in order to evaluate the authors' experience with flexible choledochoscopy and CBD exploration. Fifty-nine patients had CBD exploration plus flexible choledochoscopy and 38 underwent CBD exploration alone. Retained stones were found postoperatively in ten per cent of the patients who had only CBD exploration versus four per cent in the choledochoscopy group. The retained stones in five patients were later removed by percutaneous basket retrieval (3), flush irrigation (1), and choledochoscopy (1). Flexible choledochoscopy detected additional stones after routine CBD exploration in 12 patients, clarified T-tube cholangiograms in four patients, and aided stone extraction in two patients. For these reasons, and because choledochoscopy was associated with a lower incidence of retained stones, the authors believe this procedure is a worthwhile addition in most cases of CBD exploration.

Cholecystectomy

Relationship of cataract to radiation sensitivity.

Considerable exposure to radiation always causes posterior subcapsular cataract (PSC). This investigation was conducted to ascertain whether cellular hypersensitivity to radiation may be identified as a possible cause of cataract in persons exposed to low levels of radiation. Patients were studied in whom PSC had followed probable exposure to low levels of radiation or in whom PSC had developed before the age of 60 without known exposure. The patients with cataract were compared with age and sex matched controls without cataract. Radiation sensitivity was estimated by measuring clonal growth of skin fibroblasts and peripheral blood lymphocytes after exposure to graded doses of radiation and by measuring postirradiation reconstruction of separated nuclear material from lymphocytes. The results show variations in the level of radiation sensitivity between the patients, without significant differences from the controls. It is concluded that radiation hypersensitivity, as tested by the methods used in this study, is not normally associated with the development of posterior subcapsular cataract.

Cataract

Trace metals in a family with sex-linked retinitis pigmentosa.

Lead, cadmium, copper, and zinc levels were examined in RP patients, carriers, and controls in a family with sex-linked RP. The mean plasma copper concentration was significantly higher in the RP patients and carriers than in the controls. The mean plasma zinc concentration was significantly higher in the carriers than in the RP victims or controls. The mean plasma zinc/copper ratio was significantly lower in the RP victims than in the controls or carriers. These findings may help explain the onset of RP in some sex-linked carriers and may be of diagnostic value.

Copper

On becoming a teacher of family medicine.

The emergence of family practice education in the past decade has created an unprecedented demand for faculty. Since no reservoir of trained teachers existed, it has become necessary for practicing family physicians to enter the academic world and assume the role of teacher. This paper examines the internal processes by which this transformation occurs. It begins with the fantasies common to physicians who are considering the decision to teach;, and progresses through self-assessment of qualifications to a consideration of the content of family practice teaching. It concludes with guidelines for negotiation with an academic institution and the early stages of professionalization in the new role.

Faculty, Medical

Simultaneous measurement of triiodothyronine and thyroxine in unextracted serum samples using a double-tracer radioimmunoassay method.

A method is described for the simultaneous measurement of triiodothyronine (T3) and thyroxine T4) in 0.04 ml of unextracted serum. Antibodies were prepared by immunization of rabbits with T3 and T4 conjugated with human serum albumin. Bound and free labeled hormones were separated by the double-antibody technique, and 8-anilino-1-naphthalene sulfonic acid was used to inhibit binding of the two hormones to thyroxine-binding globulin. The validity of the assay using 125I-T3 and 131I-T4 is shown by the excellent recovery of T3 and T4 added to serum and by the finding that curves obtained by assaying various dilutions of a hyperthyroid serum run parallel to the standard curves. In all clinical serum T3 and T4 values obtained using the double-tracer radioimmunoassay method were in excellent agreement with those obtained by single-tracer RIA techniques. The combined T3-T4 method appears to be accurate, sensitive, and specific, thus making the assay highly desirable as a technical time-saver.

Anilino Naphthalenesulfonates