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Biomedical subjects

D Spence

Publications and source records attributed to D Spence.

70 records · Page 4Linked to original sources

Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation.

Cyclosporin A has been used in conjunction with allogeneic bone-marrow transplantation in the treatment of 23 patients--21 with acute leukaemia, 1 with chronic granulocytic leukaemia, and 1 with aplastic anaemia. The drug was given twice daily from the day before transplant. At the start of the study cyclosporin prophylaxis was stopped in 3 patients within 44 days of transplantation because of non-specific rashes and/or deteriorating renal function. All 3 patients had acute graft-versus-host disease (GVHD) and died. Thereafter the drug was not stopped because of possible toxic manifestations, and 20 patients have been studied (median follow-up 7 months; maximum 13 months). 2 patients have acquired GVHD; 1 patient died of acute GVHD and 1 has chronic mild disease. 3 other patients have died, 2 of recurrent leukaemia and a third of staphylococcal pneumonia with renal failure. Of the remaining patients, 1 has recurrent leukaemia and 1 has moderately severe renal failure. Several toxic effects of cyclosporin A have been observed but they are mostly reversible and no second malignant neoplasm has developed.

Adolescent↗

Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-dose melphalan.

In a Phase I study, melphalan 140 mg/m2 was administered to 8 patients with disseminated malignant melanoma. Marrow was removed from the patients immediately before melphalan administration and returned i.v. 8 h later. Studies on marrow culture and melphalan pharmacokinetics predicted that this was a safe time to administer non-cryopreserved marrow. Four patients received lower doses of i.v. melphalan without autologous marrow. In the group receiving autologous marrow the time for recovery of peripheral-blood granulocytes to 800/mm2 or greater was significantly less (P = 0.01) than in those not receiving marrow. In 7 patients the tumour showed evidence of response to the drug and there was 1 complete remission. This treatment deserves investigation in patients with tumours more sensitive to drugs than melanoma.

Adult↗

Determination of radium-226 in environmental and personal monitoring samples.

Radium-226 is a member of the Uranium-238 natural decay series and is the most hazardous radionuclide released to the environment from uranium mining and milling. Due to its long half-life (1600 years) and radiological effects it is one of the most important isotopes to be determined among the naturally occurring nuclides in environmental samples. It is also among the most toxic long-lived alpha-emitters present in environmental samples, as well as one of the most widespread. The requirement for the determination of radium has become a matter of interest in public health due to its hazardous nature with respect to internal exposure. It is concentrated in bones, thus increasing the internal radiation dose of individuals. The methodology developed involves dissolving solid samples by microwave digestion. The radium is then separated from matrix interferents by cation exchange chromatography and subsequently electrodeposited onto a stainless steel disc. Alpha-Spectrometry is employed to determine the activity in the sample. A limit of detection of 20 mBq l(-1) for ground water samples (100 ml) and 20 mBq g(-1) for solid samples (0.1 g) is achievable. The method has been validated via an intercomparison exercise and analysis of a marine sediment reference material. Samples analysed include run off waters from uranium mines, coal and fly ash and also trapping media such as silica gel, charcoal and activated carbon.

Environmental Exposure↗

Bone marrow transplantation in patients with Fanconi anemia: experience with cyclophosphamide and total body irradiation conditioning regimen.

Eleven patients with Fanconi anemia (FA) underwent bone marrow transplantation (BMT) between March 1985 and May 1990 in a single institution. Ten patients received bone marrow from healthy full human leukocyte antigen (HLA) matched siblings and one patient from her father (one antigen mismatch). Ten patients were conditioned with cyclophosphamide (Cy) at a dose of 5 mg/kg per day for 4 days followed by total body irradiation (TBI) for a total of 600 cGy over 3 days. Six of the 11 patients are alive and have normal reconstitution of their bone marrow. Median follow-up was 72 months (range 42-84). Three of the 10 patients who received Cy and TBI (two HLA compatible, one antigen mismatch) had graft failure. Five patients developed at least grade III acute graft-versus-host disease (GVHD). The rates of graft failure and GVHD are, however, still significantly high. Modification of the conditioning regimen and GVHD prophylaxis is needed to improve the outcome.

Adolescent↗

Engraftment failure following bone marrow transplantation in children with thalassemia major using busulfan and cyclophosphamide conditioning.

Thirteen children older than 3 years of age with beta-thalassemia major underwent allogeneic bone marrow transplantation (BMT) from a full human leukocyte antigen (HLA) matched sibling donor in a single institution. These patients received busulfan (Bu). 16 mg/kg followed by cyclophosphamide (Cy) 200 mg/kg for conditioning. Eight of the 13 patients (Group 1) engrafted and have a median age of 13 years (range 5-15 years). The five patients (Group 2) who failed to engraft have a median age of 6 years (range 3-8 years). The association with the following factors was found to be statistically significant: age (older in Group 1), duration of nadir of white blood count (WBC) of < or = .1 x 10(9)/L (longer in Group 1), and the dose of Bu administered to each patient calculated on the basis of body surface area (higher dose in Group 1). The high rate of engraftment failure (5 out of 13) may be related to the suboptimal systemic exposure of Bu in younger children leading to inadequate bone marrow ablation when the standard dose of 16 mg/kg is used.

Bone Marrow Transplantation↗

Fluorophotometric studies on postmortem changes in porcine corneal endothelial barrier functions.

Using an in vitro fluorophotometric technique, we studied the effect of postmortem storage duration on the endothelial barrier function of porcine corneas. A marked decay in endothelial barrier function was demonstrated that correlated with duration of storage. This decay appears to be nearly complete after 2 weeks of storage. This loss of barrier function correlated grossly with ultrastructural changes demonstrated on scanning electron microscopy.

Animals↗