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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 145 records · Page 8Linked to original sources
PubMed1984

Distribution and concentration of cyclosporin in human blood.

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.

Bone Marrow Transplantation↗
PubMed1984

Tissue distribution and toxicity of cyclosporin A in the mouse.

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.

Animals↗
PubMed1983

Bone marrow transplantation in 33 patients with malignant blood diseases and severe aplastic anaemia.

Allogeneic bone marrow transplantation using HLA-identical sibling donors was performed in 29 patients with malignant blood diseases and in four patients with severe aplastic anaemia. Twenty-five patients received immunosuppressive therapy with cyclosporin A to minimize graft-versus-host disease (GVHD) and eight received methotrexate. Twenty-one of 29 patients (72%) with malignant blood diseases and three of the four patients with severe aplastic anaemia remained alive and disease-free from 0.5 to 16 (median, seven) months after transplantation. Acute GVHD, predominantly of the skin, occurred in 25 of 28 evaluable cyclosporin A recipients (of whom two died), and in all five evaluable methotrexate recipients. Mild chronic GVHD occurred in 10 of 16 evaluable patients. Interstitial pneumonitis occurred in five patients, of whom two died. HLA-identical sibling marrow transplantation is associated with a mortality similar to that of induction chemotherapy for acute leukaemia, and should be considered in adults with acute leukaemia in remission or relapse, chronic myelogenous leukaemia in metamorphosis or blastic transformation, lymphoma unresponsive to conventional therapy, and in severe aplastic anaemia.

Adolescent↗
PubMed1983

Cervical carcinoma: a drug-responsive tumor--experience with combined cisplatin, vinblastine, and bleomycin therapy.

Thirty-five patients with advanced cervical cancer were treated with a combination chemotherapy regimen comprising cisplatin, vinblastine, and bleomycin (PVB). Sixty-six percent of 33 evaluable patients showed objective tumor response and complete remissions were seen in six (18%) patients. The median duration of tumor response in patients with recurrent cervical cancer was 24 weeks (range 8 to 104 weeks). Multivariate analysis of pretreatment variables including prior radiotherapy did not identify patients with a higher response probability. Nausea and vomiting were usual side effects of chemotherapy and there was one definite treatment-related death. Cervical cancer is responsive to cisplatin based combination chemotherapy. The role of chemotherapy in conjunction with radiotherapy or surgery in the treatment of locally advanced cervical cancer remains to be defined.

Adult↗
PubMed1983

Human T lymphocyte phenotypes after bone marrow transplantation. T cells expressing Ia-like antigen.

Peripheral blood Ia-positive (Ia+) T cells were enumerated in 52 patients who had received allogeneic or syngeneic bone marrow transplantation for the treatment of acute leukemia or severe aplastic anemia. Twenty-two normal people showed 3 +/- 2% of peripheral blood T cells to be Ia+. During the first 130 days posttransplant, all patient groups showed a moderate elevation in the percentage (mean: 21-26%) of Ia+ T cells, regardless of the type of transplant performed, and regardless of the presence or absence of acute graft-versus-host disease (GVHD). Although there was marked individual variation (range 5-76%), there was a trend towards a decrease in the percentage of Ia+ T cells with increasing time after transplantation. Long-term survivors still showed a small (range 3-20%, mean 10%) but significant elevation in the relative number of Ia+ T cells 1-3.4 years after transplantation, regardless of the presence or absence of chronic GVHD. It is not currently known why Ia+ T cells are found in these patients, but accelerated lymphopoiesis, subclinical infection, and excessive immune stimulation caused by microorganisms or other foreign antigens could be contributing factors.

Acute Disease↗
PubMed1983

Cyclosporin A associated nephrotoxicity in the first 100 days after allogeneic bone marrow transplantation: three distinct syndromes.

Thirty-six patients received allogeneic (34) or syngeneic (two) bone marrow transplants as treatment for severe aplastic anaemia or acute leukaemia. Nineteen of the allogeneic recipients received methotrexate (MTX) and 15 received cyclosporin A (CyA) as the predominant immunosuppressive agent to minimize graft-versus-host disease (GVHD) post transplant. In the first 100 d post transplant renal dysfunction was much less frequent in the MTX recipients than in the CyA recipients who exhibited three distinct syndromes of nephrotoxicity: most commonly. CyA recipients developed asymptomatic azotaemia, proteinuria, urinary casts, impaired urinary concentrating ability and hypertension. Secondly, two CyA recipients developed acute reversible renal failure precipitated by systemic bacterial infection which required dialysis and in which the kidney was the sole target organ; thirdly, two recipients of HLA-genotypically non-identical grafts developed a rapidly progressive fatal syndrome with multiple organ involvement including lung, brain and kidney which clinically and histologically resembled thrombotic thrombocytopenic purpura.

Acute Kidney Injury↗
PubMed1983

Human bone marrow allograft recipients: production of, and responsiveness to, interleukin 2.

The production and utilization of interleukin 2 (IL 2) by peripheral blood mononuclear cells (PBMC) from 14 bone marrow allograft recipients was examined. PBMC from all patients were impaired in their ability to produce IL 2 when stimulated by phytohemagglutinin (PHA). On the average, the IL 2 activity produced by patients' PBMC was 8% of that from normal donors' PBMC. To examine the basis for this impaired T cell function in marrow recipients, the ability of a resting T lymphocyte population isolated from PBMC to respond to PHA and exogenously supplied IL 2 was analyzed. The proliferative response of resting T cells to PHA and IL 2, although low at early times post-transplant, reached near normal levels by 8 mo. Only two of 11 patients had normal numbers of precursor T cells that could respond. For all other patients the average number of precursor T cells was 10-fold lower than the average determined for normal donors. The impaired production of IL 2 by patients' PBMC may be due to this low precursor frequency. For some patients the rate and/or extent of clonal expansion of activated T cells appears to be greater than that of normal donors. The data suggest that the therapeutic application of IL 2 to such patients is unlikely to be successful in overcoming defects of T cell function before 8 mo post-marrow transplant.

Adult↗