Search PubMed⌕ Search

Biomedical subjects

R Y Calne

Publications and source records attributed to R Y Calne.

At least 163 records · Page 9Linked to original sources
PubMed1988

Liver transplantation for malignant disease. Results in 93 consecutive patients.

Ninety-three patients with malignant disease underwent orthotopic liver transplantation between May 1968 and April 1987 in the Cambridge/King's College Hospital program. Of 50 patients with primary hepatocellular carcinoma (HCC) (19 with cirrhosis, 31 without cirrhosis, including 7 with fibrolamellar variant), 37 (74%) survived for more than 3 months, and in this group evidence of tumor recurrence was obtained in 24 (64.9%), the longest survivor being 11.8 years post-transplant, and three survived for more than 5 years. Although there is no correlation between the frequency of tumor recurrence and underlying cirrhosis, or histologic type (except fibrolamellar variant), it was observed earlier in those with moderate/poorly differentiated tumors and also when prednisolone and azathioprine was used for immunosuppression. Tumor recurred in all but two of those with peripheral or central cholangiocarcinoma (one alive at 6.1 years) with median survival times of 34 weeks and 56 weeks for the central and peripheral types, respectively. Among the unusual primary tumors, one with epithelioid haemangioendothelioma developed tumor recurrence at 2 years, one of two patients with apudoma is tumor-free at 2.2 years, and the one patient with bile-duct papillary cystadenocarcinoma is alive at 1.7 years. For the secondary hepatic malignancy group, survival times were shorter with little palliation except for two patients with carcinoid syndrome who were free of associated symptoms at 6 and 10 months. Despite the overall high frequency of tumor recurrence in most categories of hepatic malignancy, liver transplantation gave worthwhile survival with a number of patients cured and in the others considerable palliation of symptoms.

Adenoma, Bile Duct↗
PubMed1988

An analysis of cyclosporine efficacy and toxicity after liver transplantation.

The use of cyclosporine long term after orthotopic liver transplantation has been analyzed in 73 adults with particular reference to the dose of drug used, either alone or in combination with other immunosuppressive agents, and the side effects observed. The first 22 patients were given cyclosporine 10 mg/kg/day for up to 2 years, but thereafter in these, and in all the other patients, the drug dose was regulated by whole blood trough levels. The proportion of patients maintained on cyclosporine alone increased from 11% at 3 months to 54.9% and 55.6% at 3 and 4 years, respectively. The dose of prednisolone used in combination with cyclosporine was lower than that used with azathioprine (P less than 0.05) up to 12 months after transplantation, but thereafter no significant difference was found. Acute cellular rejection was seen in 5 patients and in all instances was related to cessation of cyclosporine, while 10 patients developed chronic graft rejection manifested by the vanishing bile duct syndrome. At 12 months and onward, 54.5-73.3% of patients had normal serum bilirubin levels, and 47.6-80.0% had aspartate aminotransferase levels in the normal range. Cyclosporine was discontinued in 12 patients, in 8 cases because of impairment of renal function or hypertension. A trend toward rising serum creatinine levels was seen, and after 4 years on cyclosporine none of 12 patients had normal levels, and these exceeded 200 mumol/L in 5. The rise in creatinine levels was probably in part related to the higher doses used early in the study period. The incidence of hypertension progressively increased from 15.3% at 3 months to 63.6% at 4 years in patients maintained on cyclosporine.

Adolescent↗
PubMed1988

The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria.

A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.

Adolescent↗
PubMed1988

Outcome of orthotopic liver transplantation in the aetiological and clinical variants of acute liver failure.

Thirty-three patients with acute liver failure underwent orthotopic liver transplantation, including 16 with fulminant hepatic failure, 15 with late-onset hepatic failure and two with severe acute liver failure (coagulopathy without encephalopathy). Twenty-three (70 per cent) survived to leave hospital and 21 of these are currently alive and well. Outcome correlated with the serum bilirubin level before transplantation (p less than 0.05) but no correlation was found with the variant of acute liver failure, grade of encephalopathy, cerebral oedema, serum creatinine, white cell count, prothrombin time or platelet count at the time of transplantation. Severe coagulation factor deficiencies did not constitute a clinical problem. One patient developed a neurological deficit secondary to cerebral oedema, but otherwise the morbidity reflected that observed in the general population after transplantation. Careful monitoring of intracranial pressure and surveillance (with early aggressive therapy) for bacterial and fungal infections is very important in achieving a successful outcome after transplantation.

Acute Disease↗
PubMed1988

Kidney pathology in liver allograft recipients after long-term treatment with cyclosporin A.

Organ transplant recipients given immunosuppressive treatment with cyclosporin A are at risk of injury due to nephrotoxicity. Eight liver allografted patients whose renal function became impaired during therapy with cyclosporin A for up to 4.5 years were investigated by renal biopsy. Ischemic changes in glomeruli were found to be greater than in controls, and there was focal tubular atrophy, but an excess of lesions in small arteries could not be demonstrated. In one patient there were glomerular changes suggestive of thrombotic microangiopathy. Interstitial fibrosis and cellular infiltration were slight. The pathogenesis of the ischemia remains to be elucidated, but reasons are advanced for favoring the view that the mechanism of cyclosporin A nephrotoxicity is primarily vasomotor, causing a reduction of renal blood flow and glomerular filtration rate without permanent organic arterial narrowing; nephrons become damaged irreversibly nevertheless.

Adult↗
PubMed1988

Cyclosporin A stimulates proliferation of the liver cells after partial hepatectomy in rats.

The effects of cyclosporin A (CyA) upon regeneration of the liver were studied in rats after partial hepatectomy. In group 1, a standard two-thirds hepatectomy was performed. In group 2, CyA, a dose of 10 milligrams per kilogram, was given orally one day prior to, on the day of the operation and 24 hours after hepatectomy. The liver weight restoration, histologic findings and mitotic activities of remnant livers and serum levels of aminotransferase, albumin, total bilirubin and creatinine values were examined from 24 hours to ten days after the operation. Treatment with CyA resulted in an increase of the mitotic activities of the hepatocytes, which were twice as high as those in the control group. This phenomenon coincided well with the regenerative rate of remnant livers, histologic factors, albumin synthesis and other biochemical parameters. Our results indicate that CyA has a stimulatory effect upon liver cell proliferation after partial hepatectomy in rats. The augmentative effect of CyA on liver regeneration is discussed.

Animals↗
PubMed1987

Transplantation of liver, heart, and lungs for primary biliary cirrhosis and primary pulmonary hypertension.

Liver, heart, and lung replacement was performed in a woman with severe pulmonary hypertension, cardiorespiratory failure, and end-stage primary biliary cirrhosis. The main surgical considerations were the staging of the various parts of the operation in relation to cardiopulmonary bypass and performing the recipient procedures as expeditiously as possible to reduce the bypass time to a minimum. The patient was able to leave hospital on the 46th postoperative day on low doses of immunosuppressive agents, with excellent liver and cardiopulmonary function. This early satisfactory outcome shows the feasibility and potential of the procedure: such combined allografting may be a suitable treatment in carefully selected cases of advanced liver and lung disease from other causes.

Adolescent↗
PubMed1987

Evidence for an immune response to HLA class I antigens in the vanishing-bileduct syndrome after liver transplantation.

The relation between donor and recipient status for HLA class I and II antigens in 62 patients undergoing liver transplantation was examined with particular reference to a well-defined variant of chronic rejection, the vanishing-bileduct (VBD) syndrome. A complete mismatch for class I antigens was more common in those with the VBD syndrome than in those with normal graft function or chronic graft malfunction unrelated to the syndrome (p less than 0.025). In contrast, a complete mismatch for class II antigens was considerably less common in those with the VBD syndrome than in those without (p less than 0.02). The association of a complete mismatch for class I and a partial or complete match for class II antigens with the VBD syndrome was highly significant (p less than 0.0005). These findings support the hypothesis that in the VBD syndrome both class I antigen expression on bileduct epithelium and immunological interaction at the level of class II antigens are required for the rejection process to occur. In addition, high-titre donor-specific antibodies to class I antigen, which were present in 6 of 14 of those with the VBD syndrome but in none of those without (p less than 0.0005), may be involved in the pathogenesis of bileduct damage.

Adolescent↗
PubMed1987

Long-term survival in haemodialysis patients.

Survival rates and causes of death were analysed for 177 patients who started dialysis between 1970 and 1975. 99 patients survived 5 years of treatment, and at this stage 74 had functioning transplants; thereafter, only 4 changed between treatment by dialysis and transplantation. For patients surviving for 5 years those treated by dialysis and those treated by transplantation had a similar probability (+/- standard error) of surviving to 10 years (0.84 +/- 0.07 v 0.82 +/- 0.04), but the probability of surviving to 15 years was lower for dialysis patients than for transplant patients (0.31 +/- 0.14 v 0.63 +/- 0.08; p less than 0.05). Infection, particularly with Staphylococcus aureus, was an important cause of late mortality in dialysis patients.

Adolescent↗
PubMed1987

The prevention of renal impairment in patients undergoing orthotopic liver grafting by infusion of low dose dopamine.

Administration of low dose dopamine (2.0 micrograms/kg/minute) begun before surgery in patients undergoing liver transplantation decreases the incidence of postoperative renal impairment. Thirty-four consecutive patients in the Cambridge/King's College Hospital liver transplantation series were studied. Nineteen patients (21 transplant operations) received prophylactic low dose dopamine throughout the operative and early postoperative period, while 15 patients (15 transplant operations) received dopamine only when clinically indicated for incipient renal failure or as an inotropic agent. In the prophylactic dopamine group, only two transplant operations (9.5%) were complicated by renal impairment, whereas in the other group, 10 patients (67%) developed renal impairment (p = 0.001); of these, four developed acute renal failure (27%). Comparison of seven pairs of patients, matched for age, sex, diagnosis, operative blood loss and operative hypotension (one group receiving dopamine, the other not), revealed a significantly higher urine output in the first 24 hours and creatinine clearance 24-48 hours after surgery (p less than 0.05) in those treated prophylactically. In view of these findings, we would recommend that consideration be given to the prophylactic use of dopamine in patients undergoing orthotopic liver transplantation.

Acute Kidney Injury↗