Activation antigen expression on the helper-inducer and cytotoxic-suppressor T cell subpopulations after allogeneic human marrow transplantation.
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Biomedical subjects
Publications and source records attributed to K Britton.
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Cyclosporin A (CyA) was used to minimize graft-versus-host disease (GVHD) in 28 recipients of allogeneic marrow transplants. When given orally, the absorption of CyA was markedly dependent on normal gut function. Patients without gut dysfunction showed normal serum concentration-time curves while those with diarrhoea from any cause (chemo-radiation enteritis, acute GVHD of the gut, infectious enteritis) showed minimal absorption of the drug. These data indicate the desirability of the intravenous administration of CyA during periods of gut dysfunction in marrow transplant recipients.
In patients receiving cyclosporin to minimise graft versus host disease after allogeneic bone marrow transplantation, whole blood cyclosporin concentration was roughly twice the serum concentration when blood was separated at 37 degrees C. In turn, blood separation at 37 degrees C resulted in a doubling of serum cyclosporin concentration compared with separation at room temperature. In vitro studies showed that the latter phenomenon was due to a temperature dependent partitioning of cyclosporin between plasma and red cells, such that increased cyclosporin was taken up from the serum into red cells at room temperature. Increasing delay in separation of patient blood (at either temperature) resulted in a gradually increasing cyclosporin serum concentration. Further in vitro studies showed that a distribution equilibrium between blood components was reached within 30 min incubation. Red cell uptake of cyclosporin was saturable at an incubation concentration of greater than 4 microgram/ml, while plasma and mononuclear cells showed a linear uptake to 7 micrograms/ml. The cellular cyclosporin content of a mononuclear cell was roughly 1000 times greater than that of an erythrocyte. For clinical monitoring we recommend the measurement of cyclosporin concentration either in whole blood or in serum separated at 37 degrees C without delay after venepuncture.
Groups of mice were given cyclosporin A (CyA) subcutaneously for 6 wk at a dose of 12.5, 50 or 200 mg/kg/d. After 7, 21 and 42 days of CyA administration the CyA content of serum, thymus, mesenteric lymph nodes, spleen, kidney, liver, lung, small and large intestine and brain was measured, each organ was examined histologically, and the total viable nucleated cell content of thymus, mesenteric lymph nodes, spleen and femoral marrow was analysed. CyA was detected in every organ assayed at each concentration of CyA administered. The mean concentration of CyA per organ was consistently highest in organs of mice given CyA 200 mg/kg/d and lowest in those given 12.5 mg/kg/d at each time point, but there was pronounced variability in the concentration of CyA between individual mice. Repeated administration of CyA after the first week did not further elevate CyA tissue concentrations. At doses of 50 or 200 mg/kg/d CyA caused weight loss, diarrhea, intussusception and fatal neurotoxicity. In addition, the spleen, thymus and mesenteric lymph nodes of mice given CyA 50 or 200 mg/kg/d were hypocellular and disorganized, and all lymphoid organs contained numerous pyknotic lymphocytes. The liver showed fatty change and the kidney degeneration of proximal tubules. Femoral marrow showed enlarged and congested sinuses. No abnormalities were noted in mice given CyA 12.5 mg/kg/d.
The monoclonal antibody HMFG-2 which is directed to an oligosaccharide determinant on a large molecular weight mucin-like molecule found in the human milk fat globule reacts positively with breast and ovarian carcinomas. The purified antibody, labelled with 123I has been used successfully to locate ovarian tumours and their metastases in 20 out of 22 patients tested. Here we discuss those features of a) the antibody, b) the antigenic site it reacts with, c) the radioactive label and d) the scanning technique, which have contributed to the successful application of HMFG-2 to the effective imaging of ovarian tumours.
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The thyroids of forty patients were imaged using 2 mCi(74 MBq) 99mTc pertechnetate (99mTcO4) followed within one week by 2 mCi (74 MBq) 123I Iodide. The images obtained were evaluated by eight observers for 6 morphological criteria and assigned to 6 diagnostic categories with a confidence grading on a seven level scale (grade 1 being that for maximum confidence). Images were obtained with 123I for the same counts and the same times as those with 99mTcO4 and compared using an index in which the number of diagnostic categories and the mean confidence grading within each category were taken into account. The mean index obtained for 99mTcO4 images (9.2) was significantly greater (P less than 0.05, thus representing a lower observer confidence and less interobserver diagnostic agreement) than the mean indices for 123I equal count images (5.6) and 123I equal time images (6.8). The diagnoses made on the basis of 123I images were more frequently concordant with the final diagnosis after six months follow up (75% for equal counts and 77% for equal time) than those with 99mTcO4(63%). The radioisotope of iodine most suited to modern nuclear medicine instrumentation and with the most favourable radiation dosimetry is 123I which is recommended for those areas of thyroid imaging where iodine is superior.
A specific application of single photon emission tomography to the relative quantitation of the pituitary region is described together with the results obtained in 19 patients with pituitary adenoma proven by air encephalography. These are compared with those obtained by X-ray computer tomography and conventional brain imaging and a superiority of single photon emission tomography is demonstrated in this small series.
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