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Biomedical subjects

R Y Calne

Publications and source records attributed to R Y Calne.

At least 145 records · Page 8Linked to original sources

Serum F protein estimation in liver allograft recipients with graft dysfunction.

Serum levels of F protein, a 44 kD cytoplasmic protein mainly found in hepatocytes, became elevated during episodes of graft dysfunction following orthotopic liver transplantation. In a study of 27 liver transplant recipients, the rise in F protein did not precede rises in the other conventional biochemical indices of hepatic dysfunction. Serum F protein concentration significantly correlated with serum levels of aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and bilirubin (all P less than 0.001) and also with the prothrombin time (P = 0.048). Despite its high concentration in liver cells, this marker does not provide any additional benefit in the diagnosis of graft dysfunction or in monitoring liver allograft function following transplantation.

Adolescent↗

Mortality during intensive care after orthotopic liver transplantation.

The postoperative course of 335 adult patients who underwent orthotopic liver transplantation from 1968-1987 was reviewed retrospectively to identify patients who died in the intensive care unit and the causes of death. Forty-four percent of all deaths occurred in the intensive care unit. The mortality rate in the intensive care unit peaked in 1984 (48%), but decreased to 11% in 1987. The main causes for death in the intensive care unit were infection (55%) and haemorrhage (19%). The patients who died spent more time in the intensive care unit, had a longer period of tracheal intubation and received a larger intra-operative blood transfusion than patients who died in other locations.

Adult↗

Studies of the entero-insular axis following pancreas transplantation in man: neural or hormonal control?

To study the role of hormonal and neural factors in the control of the entero-insular axis the insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) responses to oral and intravenous glucose were investigated in 5 patients who had received a combined kidney and paratopic pancreas transplant, with physiological portal venous drainage. The incremental areas under the insulin and C-peptide responses to oral glucose were significantly greater than the responses to intravenous glucose (insulin: patients 7983 +/- 1937 (+/- SE) vs 3513 +/- 2188 mU l-1 min, p less than 0.002, control subjects 5505 +/- 1035 vs 1066 +/- 484 mU l-1 min, p less than 0.004; C peptide: patients 440 +/- 80 vs 144 +/- 61 nmol l-1 min, p less than 0.01, control subjects 200 +/- 38 vs 63 +/- 16 nmol l-1 min, P less than 0.01). The incretin effects for insulin (patients 4.4 +/- 1.4, control subjects 7.7 +/- 1.8) and C-peptide (patients 4.4 +/- 0.9, control subjects 3.7 +/- 0.9) and the GIP responses to oral and intravenous glucose were not significantly different between transplant patients and control subjects. As the incretin effect was preserved, despite a denervated pancreas, hormonal rather than neural factors may be more important in mediating increased insulin secretion after oral carbohydrate. The normal GIP response is compatible with its proposed role as an insulinotropic hormone.

Adult↗

Renovascular hypertension in neurofibromatosis.

We present two patients with renovascular hypertension in association with neurofibromatosis. In both cases the diagnosis was established by angiography. The first patient suffered occlusion of the right renal artery combined with intrarenal arterial lesions. Treatment was by autotransplantation. The second patient suffered bilateral intrarenal arterial lesions alone and was treated medically. In both patients, control of the hypertension was established. We discuss the aetiology of renovascular hypertension in neurofibromatosis and consider its treatment.

Adolescent↗

Long-term survival of kidney allografts in dogs after withdrawal of immunosuppression with ciclosporin and azathioprine.

We have examined the immunosuppressive effects of combined azathioprine (Aza) and ciclosporin (CS) in two groups of mongrel dogs receiving kidney allografts. In group 1, Aza and CS were given together daily after transplantation and in group 2 twice the dose of each drug was given separately on alternate days. Doses were halved in each group at successive 84-day intervals and all immunosuppression was stopped on day 336. Thus the same total amounts of Aza and CS were given to all recipients in both groups. Up to day-60 the incidence of rejection in each group was similar, thereafter recipients in group 1 were more susceptible to fatal infection and marrow hypoplasia. This accounted for the difference in long-term survival between the two groups (1/14 in group 1, 5/12 in group 2 at day 420). Subsequently, two long-term survivors in group 2 died, 1 on day 452 from chronic rejection and the other on day 529 from gastroenteritis with a histologically normal allograft kidney. An in vitro analysis of the alloreactive repertoire of two healthy recipients in group 2, bearing each other's kidneys for more than 2.5 years and more than 500 days without immunosuppression, showed a profound donor-specific defect which could account for their operationally tolerant state.

Animals↗

Results with combined kidney and paratopic segmental-pancreas transplantation.

Rehabilitation and quality of life after combined pancreas and kidney transplantation was assessed in 15 previously diabetic patients in renal failure and compared with 11 diabetic patients in renal failure transplanted with a kidney only. The paratopic segmental-pancreas-grafting technique, which allows physiologic insulin delivery into the portal venous system, was used in 13 patients; 2 patients received a heterotopic segmental-pancreas graft, resulting in systemic insulin delivery. A kidney was transplanted heterotopically in all cases. Mean age, duration of diabetes, retinopathy, neuropathy, mortality, infection rate, and immunosuppressive treatment did not differ significantly between the groups. Diabetic patients with only kidney transplants had difficulties adjusting to their diabetes, which may be partly due to the immunosuppressive treatment. The quality of life only marginally improved. In contrast, patients with a combined pancreas-kidney graft achieved full rehabilitation within a short time.

Adult↗

Protein C deficiency and portal thrombosis in liver transplantation in children.

Changes in plasma protein C and antithrombin concentrations after liver transplantation were monitored in fourteen children and a control group of fourteen adults. In the children, there was a persistent deficiency in the plasma concentration of protein C and a less pronounced deficiency in antithrombin during the early postoperative period, causing a hypercoaguable state. A concomitant rise in plasminogen activator inhibitor further increased the risk of thrombosis by inhibiting fibrinolysis. These changes coincided with the peak incidence of portal vessel thrombosis (4-10 days). Replacement of plasma antithrombin, together with heparin, did not prevent portal thrombosis in two of the children. It is concluded that successful prevention will require protein C replacement together with antithrombin supplements up to, but not exceeding, normal plasma activity.

Adult↗

Cytomegalovirus infection and donor/recipient HLA antigens: interdependent co-factors in pathogenesis of vanishing bile-duct syndrome after liver transplantation.

The contribution of cytomegalovirus (CMV) infection and its interrelation with HLA antigens in the development of chronic rejection (vanishing bile-duct syndrome--VBDS) was investigated in 101 patients surviving for at least 3 months after liver transplantation. A 1-2 antigen match for HLA DR antigens (30.9% vs 4.5% for zero DR match; p less than 0.002), a zero match for HLA A/B antigens (27.5% vs 10.9% for 1 or more A/B match; p less than 0.05), and active CMV infection (26.3% vs 4.4% for no CMV infection; p less than 0.005) were independently associated with an increased risk of VBDS. The coexistence of a 1-2 HLA DR match and CMV infection carried the highest relative risk (10.1) of VBDS; these two variables were probably interdependent since either alone was associated with a low relative risk (0.45 and 0.5). The association between VBDS and active CMV infection was not a consequence of alterations in immunosuppressive therapy. The findings would be consistent with precipitation of chronic rejection by CMV-induced HLA antigen expression in patients rendered susceptible by the donor/recipient HLA antigen match.

Adolescent↗

The physiological effects of vasopressin when used to control intra-abdominal bleeding.

Vasopressin was used in ten critically ill patients with massive intra-abdominal bleeding unresponsive to conventional therapy. Vasopressin controlled bleeding in four patients, three of whom had continued to bleed following laparotomy for haemostasis; in two other patients, bleeding was reduced. All the patients were intensively monitored throughout the period of the vasopressin treatment; this enabled other physiological effects of vasopressin to be documented and reported. Mean arterial pressure and central venous pressure increased following the administration of vasopressin and there was a decrease in heart rate. Core body temperature rose significantly. Although all the patients had impaired renal function before receiving vasopressin, five had a prompt diuresis following its administration. Eight patients died but only three of intra-abdominal bleeding; two patients survived to leave hospital. Four patients had post-mortem evidence of ischaemia in the heart, liver and gastrointestinal tract; vasopressin may have contributed to the development of this. Vasopressin may have a place in the management of patients with life-threatening intra-abdominal haemorrhage but its use should be confined to those patients in whom conventional therapy has failed.

Abdomen↗

Effect of cyclosporin A on hepatocyte proliferation after partial hepatectomy in rats: comparison with standard immunosuppressive agents.

The effects of cyclosporin A on the regenerating liver were studied in rats after partial hepatectomy and were compared with those of conventional immunosuppressants such as methylprednisolone and azathioprine. In Group I, a standard hepatectomy removing two thirds of the organ was performed. In Group II, an oral dose of 10 mg/kg of cyclosporin A was given 1 day before and immediately, 24 hours, and 48 hours after the same hepatectomy. In Groups III and IV, azathioprine and methylprednisolone were administered in 8 mg/kg doses by way of the tail vein by the same protocol as in Group II. The mortality rate, liver weight restoration, and histologic and mitotic characteristics of the liver remnants, as well as serum levels of animotransferase, total bilirubin, and creatinine were examined from 24 hours to 10 days after the operation. Azathioprine and methylprednisolone substantially suppressed hepatocyte mitosis when compared with the control group; however, cyclosporin A treatment did not inhibit, but may, in fact, have stimulated liver cell proliferation. Changes in other parameters coincided with this phenomenon. The noninhibitory effect of cyclosporin A on liver regeneration has also been discussed.

Animals↗