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Biomedical subjects

R A Sells

Publications and source records attributed to R A Sells.

At least 73 records · Page 4Linked to original sources

The chyloesophageal fistula. A new approach to thoracic duct drainage.

The main reason for the virtual abandonment of external thoracic duct drainage as an immunosuppressive measure is not its lack of efficacy, but the time-consuming technical problems of maintaining cannula patency and replacing the large obligatory losses of fluid and protein. In an effort to overcome these problems we have devised a method of diverting thoracic duct lymph internally into the esophagus of the sheep, our hypothesis being that fluid and protein should be resorbed, but lymphocytes and antibodies destroyed. By isolating that part of the venous system into which the thoracic duct drains and anastomosing this conduit to the cervical esophagus a chyloesophageal fistula was created. A mean patency of 19 days was demonstrated radiologically and there was a reproducible peripheral blood lymphopenia of over 50% of preoperative values at 4 weeks. Although plasma albumin levels fell from 37 g/L to 29 g/L at 1 week, they remained stable thereafter. No parenteral fluid or protein was administered, yet the animals remained well with no significant weight loss or overt signs of dehydration or hypoproteinemia. Skin allograft mean survival time was prolonged from 9 to 11.8 days (P less than 0.01).

Animals↗

Cyclosporin A has differential effects on the responses of murine B cells to TI antigens and B-cell mitogens.

The effect of cyclosporin A (CyA) on the response of murine splenocytes to B-cell mitogens, TI-1 and TI-2 antigens was investigated. The proliferative response to LPS was found to be four- to five-fold less sensitive to inhibition than that to dextran sulphate. Antibody responses to a TI-2 antigen in vivo were suppressed by CyA treatment, whereas responses to the TI-1 antigen DNP-LPS were markedly enhanced. Enhanced antibody responses to DNP-LPS were also demonstrable in vitro in the presence of CyA, and the enhancement was not removed by T-cell depletion. LPS-induced antibody production in vitro was enhanced at the same CyA concentrations that inhibited proliferation by 40-50%. The implications of these findings for the mechanism of action of CyA and for our understanding of B-cell differentiation are discussed.

Animals↗

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation.

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.

Adolescent↗

Ocular complications of systemic steroid after renal transplantation and their association with HLA.

The eyes of 62 patients who had received allogenic renal transplants were examined for eye disease. Thirty-six patients were found to have steroid induced cataract. Six patients had ocular hypertension. Twelve patients showed arteriosclerotic changes in their fundi relating to their previous hypertensin. There was no significant difference in HLA type in patients who developed cataract and those who did not. 83.3% of the 6 patients with ocular hypertension had HLA B12 in common. None of the patients had cytomegalic retinitis.

Adult↗

Contaminated renal allografts.

Bacterial contamination of a renal allograft may cause infection of the transplant with eventual loss of the graft and possibly death of the patient. We report two cases that illustrate these complications and that support the suggestion that culture of the transport medium is a valuable investigation prior to transplantation.

Bacteroides Infections↗

Serum gastrin in patients with chronic renal failure.

The realisation that circulating gastrin is heterogeneous necessitates a reappraisal of gastrin's role in the increased incidence of duodenal ulcer disease that occurs in chronic renal failure. Radioimmunoassays employing region-specific antisera have been used to examine renal and extrarenal factors controlling serum gastrin concentration in patients with chronic renal failure. The present study has shown that basal serum gastrin concentrations measured with a carboxyl-terminal specific antibody were significantly higher in eight patients with chronic renal failure treated by dietary restriction (388+/-196 pM) than in 14 patients with chronic renal failure treated by haemodialysis (28.7+/-4.6 pM). However, basal gastrin concentrations in both groups of patients were significantly higher than in 25 normal subjects (12.3+/-1.8 pM) and showed significant negative correlations with maximal gastric acid secretion (p < 0.01). Markedly raised basal gastrin concentrations were observed only in chronic renal failure patients who were also achlorhydric. Although the peak postprandial increment in big gastrin concentration in 11 chronic renal failure patients (34.0+/-7.5 pM) was significantly greater (p < 0.05) than in 25 normal subjects (19.5+/-4.6 pM), the little gastrin responses were not significantly different. In addition, clearance of exogenous little gastrin was similar in four chronic failure patients (clearance half time: 8.1+/-0.7 min) and four normal subjects (clearance half time: 6.5+/-1.2 min). These studies suggest that the human kidney is unimportant in the metabolism of little gastrin. As circulating little gastrin is six times more potent than big gastrin in stimulating acid secretion, these studies suggest that the raised gastrin concentrations observed in patients with chronic renal failure have little significance in terms of their increased incidence of duodenal ulcer disease.

Food↗

Adenosine triphosphate regeneration and function in the rat kidney following warm ischaemia.

Tissue levels of adonosine triphosphate (ATP) have been measured in rat kidneys following periods of warm ischaemia: (1) immediately after the ischaemic period and (2) after the kidney had been reperfused with blood for 10 min. ATP levels at the end of the period of ischaemia are similar for ischaemic periods of 10 to 60 min and give no indication of the kidneys subsequent functional ability. The amount of ATP regenerated in 10 min of reperfusion correlates both with the duration of the period of ischaemia and with the subsequent functional ability of the kidney.

Adenosine Triphosphate↗

Oral lesions in renal transplant patients.

Plaque-like lesions of the oral mucosa have been observed in seven immunosuppressed renal transplant patients. Whilst bearing a superficial resemblance to acute pseudomembranous candidiasis (thrush), these lesions have been shown to be associated with bacterial overgrowth and not with fungi. Treatment has depended on the use of appropriate antibiotics and antiseptics together with the adoption of measures to cause disintegration of the mucoid matrix of the lesions.

Adult↗