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Biomedical subjects

R A Sells

Publications and source records attributed to R A Sells.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ethical issues in transplantation.

The transplantation of gastrointestinal organs has relied on cadaver donors for its successful development. The fact that success has been achieved is largely due to the certainty with which brain death can be diagnosed, and the acceptance of these criteria as signifying actual death by doctors, in particular, intensivists. If continuing goodwill leads to further co-operative effort, cadaveric liver, pancreas and eventually, small bowel transplants, should become more frequent. At present the numbers of recipients requiring these operations are considerably less than those in need of kidneys. There are grounds for believing therefore that the pressure to subvert good ethical standards in acquiring these organs (that pressure imposed by long waiting lists and a high death rate on those waiting lists) should be avoidable. The solution to the problem of deficits in cadaveric liver and pancreatic grafts will be achieved only by better education of nurses and doctors, professionalization and expansion of co-ordinator organizations, legal reform, and cultural change. Only by such progress, achieved at medical, governmental, and societal levels can we avoid the insidious tendency to commercialism which we have witnessed with disquiet in renal transplantation.

Altruism↗
PubMed1993

Uromodulin levels are decreased in urine during acute tubular necrosis but not during immune rejection after renal transplantation.

1. Uromodulin, an immunosuppressive glycoprotein found in urine, is a high-affinity binding ligand for certain cytokines, including tumour necrosis factor. 2. Its occurrence in urine was monitored after renal transplantation to investigate whether this simple urine test might differentiate common early causes of graft failure: acute immune rejection and acute tubular necrosis. 3. Diluted urine was assayed for uromodulin using a sandwich enzyme-linked immunosorbent assay. When graft function failed due to acute tubular necrosis, urinary uromodulin levels were significantly depressed compared with levels in urine produced during biopsy-proven acute immune rejection episodes (P < 0.01) or during periods of stable graft function (P < 0.02). This suggests that urinary levels of uromodulin may reflect tubular damage rather than other causes of graft functional failure. 4. The cytokine tumour necrosis factor, which binds with high affinity to uromodulin, was found in 30% of urine samples in association with immune rejection episodes, but not during acute tubular necrosis. However, the presence of urinary tumour necrosis factor was not related to levels of uromodulin in the same sample.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

TNF staining of graft biopsy in renal transplantation.

Tumour Necrosis Factor (TNF) is a cytokine which may be found in patients' plasma and urine in association with acute rejection in renal transplantation. TNF is produced mainly by macrophage/monocytes and activated lymphocytes and its release in acute rejection may damage the nephron leading to renal dysfunction. However localization of TNF in renal grafts has not yet been demonstrated. We investigated TNF localization in renal graft tissue and the association with acute rejection compared with non-immunological events (cyclosporine toxicity and acute tubular necrosis) in graft biopsy.

Biopsy↗
PubMed1992

T-cell receptor Vbeta gene usage by lymphocytes infiltrating human renal allografts.

T cell lines have been derived from human kidney allograft biopsies using mitogenic stimulation. Southern blotting using a T-cell receptor (TCR) Cbeta probe revealed an oligoclonal pattern of rearranged bands in all 12 samples analysed. In some cases, differences in band patterns were noted between independent cultures from the same biopsy. Most T-cell clones derived from 2 biopsies showed different patterns of rearranged bands. The polymerase chain reaction (PCR) was used to study TCR Vbeta gene usage in allograft-derived T-cell cultures. This was more sensitive and more informative than Southern blotting and revealed that most TCR Vbeta genes were expressed in T cells from biopsies showing cellular rejection. The potential usefulness of this technique to quantify TCR V gene usage in allospecific T-cell populations is discussed.

DNA↗
PubMed1992

Endolymphatic delivery of IL2 in patients with melanoma and lymphoma.

UNLABELLED: During this phase I/II study, enodolymphatic cannulae were placed in the iliac lymphatics under general anaesthesia. IL2 was then infused via this route at escalating doses until the highest tolerated dose was achieved; then, continuous infusion was maintained for 2 to 3 weeks. Seven patients with advanced cancer (3 lymphoma, 4 melanoma), resistant to all other modalities of treatment received such therapy. Most patients tolerated 4 to 5 x 10(6) u/day of IL2 for 2 to 3 weeks with less toxicity as compared to the equivalent dosage given intravenously. No severe perioperative morbidity was experienced. One melanoma patient had a minor clinical response. Changes in circulating lymphocyte numbers and cytotoxicity demonstrated a systemic effect of endolymphatic IL2 therapy. CONCLUSIONS: The endolymphatic administration of IL2 is associated with less toxicity than the intravenous route but still achieves a systemic effect; a lower tumour burden may prove more responsive to this therapy.

Adult↗
PubMed1992

A phase I clinical evaluation of liposome-entrapped doxorubicin (Lip-Dox) in patients with primary and metastatic hepatic malignancy.

Liposome-entrapped doxorubicin (Lip-Dox) was evaluated in two phase I clinical trials in patients with hepatic malignancy. Patients with metastases from primary gastric or colonic tumours and patients with hepatoma were eligible. Lip-Dox was extremely well tolerated and acute toxicities such as nausea and vomiting were totally eliminated; no antiemetics were used even at doses of 80 mg/m2. Toxicities such as alopecia and myelosuppression were also ameliorated. There were tumor regressions and reductions in hepatomegaly in patients treated on both the weekly and 21-day studies. The maximum tolerated dose (MTD) in the weekly study was 22.5 mg/m2/week and in the 21-day trial the MTD was 70 mg/m2.

Adult↗