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Biomedical subjects

R Y Calne

Publications and source records attributed to R Y Calne.

At least 91 records · Page 5Linked to original sources
PubMed1993

Ethnic variations in patient and graft survival after liver transplantation. Identification of a new risk factor for chronic allograft rejection.

The ethnic origin of renal graft recipients is recognized as an important determinant of graft survival. In liver transplantation, the effect of racial origin has been studied in black American recipients and has suggested a trend toward inferior graft survival in this group. In this study, we have analyzed outcome of transplantation in a large multiethnic liver transplant program. Non-Caucasoid recipients had an inferior patient survival compared with Caucasoids and, in particular, European Caucasoids at 1, 3, and 5 years after transplantation (46.7% vs. 60.2% at 3 years, P = 0.05). Non-European recipients had an inferior graft survival compared with European recipients at 1, 2, and 3 years after transplantation (e.g., north Europeans 53.5%, south Europeans 48.5%, Middle Eastern 40%, and non-Caucasoids 27% at 3 years, P < 0.01). Different frequencies of chronic allograft rejection in the ethnic groups contributed to the rates of graft survival, with the non-European recipients developing chronic rejection at over twice the rate of European recipients (12.6% vs. 5.9%, respectively, P = 0.002). The findings in this study support the evidence from renal transplant programs that the ethnic origin of recipients is an important determinant of outcome after transplantation, with increasing frequency of chronic rejection in recipients nonindigenous to the donor population contributing to the variations in patient and graft survival rates.

Adult↗
PubMed1993

Prodigiosin 25C: effect in in vitro models for T cell activation and T cell cycling and in vivo for rat heart allografts.

Prodigiosin 25C inhibited both lymphocyte activation (concanavalin-A-activated mouse spleen cells) and constitutive cell cycling of T cells and fibroblasts. This suggests that prodigiosin 25C is not selective for activation of T lymphocytes as has been previously reported. Use of prodigiosin 25C to suppress allograft rejection of rat hearts (DA to PVG) showed that 1 mg/kg/day i.p. had no effect whilst 10 mg/kg/day i.p. was toxic as manifest by weight loss and diarrhoea at 3 days. Although this toxicity was reversible upon reversion to 1 mg/kg/day, no major prolongation in allograft survival was seen. Our data suggests that prodigiosin 25C has a low therapeutic index and may not be selective for T cell activation.

Animals↗
PubMed1992

Liver transplantation in 100 children: Cambridge and King's College Hospital series.

OBJECTIVE: To review the results of the Addenbrooke's and King's College Hospital children's liver transplantation programme. DESIGN: Retrospective analysis of the first 100 children to receive liver grafts at Addenbrooke's Hospital, Cambridge, from December 1983 to March 1990. SETTING: Addenbrooke's Hospital, Cambridge, and King's College Hospital, London. SUBJECTS: 153 children assessed for liver transplantation, of whom 22 died before a donor became available and 31 were considered unsuitable. 100 children received grafts, of whom 27 had second grafts. RESULTS: One year actuarial patient survival was 71%, with 57% one year graft survival. In the last two years survival rates had improved considerably, with 86% of patients and 63% of grafts surviving for at least one year. Sixty five children were alive 12 to 86 months after transplantation; 63 were well and leading normal active lives and 56 had entirely normal liver function. Children's growth and development were essentially normal, with many showing remarkable catch up growth. CONCLUSIONS: Liver transplantation offers children with terminal liver disease a high chance of a return to full quality life and normal development. Improved surgical and medical care have progressively improved survival. The timing of transplantation is critical but has been constrained particularly by the availability of donors and resources.

Adolescent↗
PubMed1992

Donated organ as a source of cytomegalovirus in orthotopic liver transplantation.

The importance of the donated organ as a source of CMV was assessed in 120 patients following orthotopic liver transplant and the CMV infections that developed in these patients were graded by severity. Forty-four recipients were CMV antibody negative pre-transplant. Eighteen of these received organs from CMV antibody positive donors and 15 (83%) developed primary CMV infections, 13 (87%) of which were symptomatic. Twenty-six received organs from CMV antibody negative donors and only 2 (8%) became CMV positive post transplant (P less than 0.001). These data suggest that there would be a considerable advantage in matching CMV antibody negative recipients with negative donors. Forty-five percent of secondary infections were asymptomatic compared with 12% of primary infections, and only 11% became disseminated compared with 53% of primary infections. The secondary infections that followed transplantation of an organ from a CMV antibody positive donor were more likely to be symptomatic and were more severe than those in patients who received seronegative livers.

Antibodies, Viral↗
PubMed1992

Immunomodulation of dog islets using a cocktail of monoclonal antibodies.

Islet allografts are particularly vulnerable to rejection, and current immunosuppressive agents are deleterious to their function. They are, however, highly suitable for 'immunomodulation', i.e., the removal or inactivation of passenger leukocytes to reduce their immunogenicity. For this purpose we have used 3 rat anti-dog monoclonal antibodies (Mabs) which are synergistic for leukocytolysis in the presence of autologous dog serum. Spleen cells or purified islets treated with these Mabs together with autologous serum were tested in mixed leukocyte and islet co-culture assays. The stimulatory properties of the Mab-pretreated splenocytes or islets were markedly reduced; moreover, the Mab cytolytic activity was shown to be confined to the leukocyte target cells and did not affect islet secretory function upon glucose stimulation. We conclude that this method of modifying the immunogenicity of dog islets could lead to successful islet grafting in vivo, allowing the reduction of conventional immunosuppression. Successful in vivo studies in this model, which are currently in progress, could have implications for clinical islet transplantation.

Animals↗
PubMed1992

FK506 and rapamycin: differential sensitivity of human, baboon, cynomolgus monkey, dog and pig lymphocytes.

It has recently been suggested that there are species differences in the sensitivity of T lymphocytes to the immunosuppressive effect of FK506. We explore this phenomenon further and compare FK506 with rapamycin in lymphocytes from dog, pig, baboon, cynomolgus monkey and man. We found that the relative sensitivity of T cells to FK506 did not necessarily correlate with their sensitivity to rapamycin, further emphasising the different mode of action of each drug. The serum may alter results of dose-response curves, and thus autologous serum may introduce an uncontrolled variable when different species are being compared in vitro. We conclude that the differences in sensitivity of lymphocytes from various species to FK506 and rapamycin are independent of each other, and these differences are likely to reflect variation in the overall interactive pathways involved in T-cell mitogenesis.

Animals↗
PubMed1992

Computed tomography in blunt abdominal trauma: an analysis of clinical management and radiological findings.

We have retrospectively assessed the computed tomography (CT) findings in 92 patients suffering severe blunt abdominal trauma. Surgical findings and clinical follow-up were correlated with the CT findings. In nine patients CT was first used after emergency surgery and provided baseline data which was useful for further management. In two patients CT did not demonstrate small hepatic lacerations seen during previous surgery. No deaths were recorded. In 16 patients surgery followed CT within 24 h; there was good correlation between the CT and operative findings in 10 patients. However, CT failed to detect significant solid organ injury in five patients and was misleading (false positive) in another patient. There were two deaths amongst these 16 patients. Sixty-seven haemodynamically stable patients were initially managed non-operatively. Fifteen of these 67 patients had normal CT examinations; only one had subsequent laparotomy (for reasons unconnected with the trauma) where no injury was detected; there were no deaths. Of the 52 patients with an abnormal CT examination, 43 were successfully managed non-operatively. There were three deaths, including one where an injury missed at CT contributed to the demise of the patient. After an initial trial of non-operative management, the remaining six patients went to surgery where there was good concordance with the CT findings except for one missed renal injury. Active non-operative management of blunt abdominal trauma is widely accepted in haemodynamically stable patients and this report shows how CT supports this policy of surgical restraint in such cases. However, on review CT missed 13 injuries in nine patients overall; stricter attention to technique and better equipment may lead to improved results in the future.

Abdominal Injuries↗
PubMed1992

Liver transplantation in tyrosinaemia type 1: the dilemma of timing the operation.

Four children with tyrosinaemia type 1 received liver transplants. The metabolic disorder was corrected and all four had normal liver function on an unrestricted diet. Two children, transplanted at age five and seven years, proved to have occult hepatocellular carcinoma and both subsequently developed pulmonary metastases. One child was well 32 months after removal of a single pulmonary metastasis but the other child died with multiple metastases. The two younger children, transplanted at age 19 and 21 months, were well 28 and 44 months after operation, one after a second liver transplant. Our experience confirms the high risk of hepatocellular carcinoma in this disease and the potential value of early liver transplantation.

Age Factors↗
PubMed1992

Computed tomography in abdominal trauma: an audit of usage and image quality.

The use and quality of computed tomography (CT) in the evaluation of blunt abdominal trauma has been assessed by a retrospective review of 122 patients referred in the first 8 years following the installation of CT of the body. The referral patterns were analysed, and the quality of the images was assessed, with particular reference to unsatisfactory (unacceptable or poor) images. Referrals increased over the 8 years following installation. A large proportion of these examinations were performed outside normal working hours (58/122, 48%). In 64 out of 122 (52%) of examinations the images were considered of unsatisfactory quality with inadequate use of intravenous contrast medium cited as the most common cause for unsatisfactory examinations. Image quality did not improve with time. Image quality was unsatisfactory in a larger proportion of those examinations performed outside normal working hours (35/58, 60%) than those during the routine working day (29/64, 45%), although this difference did not reach statistical significance (0.1 greater than p greater than 0.05). Fewer unsatisfactory examinations were produced by a system dedicated to body CT (31/74, 42%) than by a neuroradiological system (33/48, 69%) (p less than 0.01). The proportion of unsatisfactory abdominal examinations was lower when the CT study concentrated on the abdomen (26/65, 40%) than when multiple regions (head, chest, abdomen, etc.) were examined (38/57, 67%) (p less than 0.01). This audit revealed many unsatisfactory examinations. In order to complete the audit loop we have addressed many of the contributory factors. A new CT system now provides images of high quality and is used for all abdominal work. Guidelines, which describe an optimized technique, have been issued to radiographers and radiologists. In particular, we have emphasized that there is no place for a poorly supervised "quick look" at the abdomen following a cranial or thoracic study.

Abdominal Injuries↗