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Biomedical subjects

A D Mayer

Publications and source records attributed to A D Mayer.

At least 55 records · Page 3Linked to original sources
PubMed1997

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Adolescent↗
PubMed1997

Influence of intraoperative blood loss on plasma levels of cytokines and endotoxin and subsequent graft liver function.

BACKGROUND: Excessive blood transfusion during orthotopic liver transplantation (OLT) is correlated with a lower graft survival rate. Experimentally, excessive hemorrhage is associated with endotoxemia and release of proinflammatory cytokines. OBJECTIVES: To measure the concentrations of plasma endotoxin and proinflammatory cytokines during OLT and to investigate their relation to intraoperative blood loss and graft viability. DESIGN AND SETTING: A prospective case series in a liver transplantation center. PATIENTS: Thirty patients who underwent OLT. Group 1 comprised 6 patients whose operative blood transfusion requirement was 10 U or more; group 2 comprised 24 patients whose operative blood transfusion requirement was less than 10 U. INTERVENTIONS: The following factors were measured in the plasma before and after OLT: interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha, hepatocyte growth factor, endotoxin, hyaluronic acid, and lactate. MAIN OUTCOME MEASURE: Graft viability. RESULTS: Two patients in group 1 died. All 24 patients in group 2 survived after they underwent OLT. The responses of IL-6 and IL-1 beta in group 1 were striking compared with those in group 2, and they were accompanied by an elevation of the endotoxin concentration and a subsequent elevation of the concentrations of hepatocyte growth factor, hyaluronic acid, lactate, and other factors that reflected graft viability. CONCLUSIONS: The changes in IL-6 seemed to respond to the excessive intraoperative hemorrhage, to provoke the elevation of the endotoxin concentration, and to be associated with the graft viability. The prevention of excessive intraoperative bleeding and the subsequent response of proinflammatory cytokines may be contributing factors to the success of liver transplant surgery.

Adolescent↗
PubMed1997

Neoral in de novo liver transplantation: adequate immunosuppression without intravenous cyclosporine.

Absorption of cyclosporine from the traditional oral formulation Sandimmune (Novartis Pharma, Basel, Switzerland) is particularly unpredictable in the early stages after liver transplantation. The absorption of cyclosporine is influenced by liver function, postoperative paralytic ileus, and graft dysfunction. Oral absorption of cyclosporine from Sandimmune is also bile dependent; cholestasis and external biliary drainage are associated with low cyclosporine absorption. Postoperative administration of intravenous Sandimmune is therefore often necessary to obtain adequate immunosuppression, despite the increased risk of renal and neurological toxicity. A microemulsion formulation of cyclosporine, Neoral (Novartis), has been developed to overcome the problems of poor and variable absorption of cyclosporine from Sandimmune. Uptake of cyclosporine from Neoral is rapid and less dependent on bile secretion so that higher peak concentrations are reached and absorption is less variable than with Sandimmune. A review of several open studies in which Neoral was administered to liver transplant patients immediately after transplantation is presented. The results suggest that the use of Neoral as a primary immunosuppressive therapy provides adequate cyclosporine trough levels, minimizing or obviating the need for intravenous cyclosporine administration. In addition, Neoral appears to reduce the risk of acute rejection episodes compared with immunosuppressive regimens involving intravenous cyclosporine.

Absorption↗
PubMed1997

Clinical features and prognosis of children assessed for isolated small bowel or combined small bowel and liver transplantation.

The hepatic histology and clinical status of 37 children on long-term parenteral nutrition (PN) referred for consideration of small bowel transplantation were determined. Seventy five percent of the children had splenomegaly and plasma bilirubin level of greater than 100 mumol/L. All of 21 children who underwent liver biopsy, had increased fibrosis, but only half had established cirrhosis. Thirty-one children were considered to be in need of transplantation (combined liver and bowel transplant, 29; isolated bowel transplant, 2), but only 13 were stable enough to be placed on the transplant list. Seven out of the thirteen children waiting have died because of lack of size-matched organs, and the overall mortality rate of the 37 children was 70%. The main risk factors for death within 6 months were bilirubin level of greater than 100 mumol/L, splenomegaly, and cirrhosis (P = .01). The natural history of PN-associated liver disease is that of progressive liver failure and death 6 to 12 months after onset of cholestasis, defined as bilirubin level of greater than 100 mumol/L. The development of cirrhosis occurs after the onset of jaundice, so early referral may also permit some children to be offered isolated bowel transplantation, which has better outcome than combined liver and bowel transplantation.

Adolescent↗
PubMed1997

Outcome of surgery for chronic pancreatitis.

BACKGROUND: In patients with chronic pancreatitis, surgery is indicated for the management of intractable pain or for the treatment of complications. METHODS: Sixty-three consecutive patients (49 men and 14 women of median age 40 (range 20-72) years) who had undergone surgery over an 8-year interval for chronic pancreatitis were studied. The mortality and morbidity rates associated with surgery were assessed and quality of life was reviewed based on relief of symptoms, analgesic use, employment and long-term sequelae. RESULTS: Forty-four patients (70 per cent) had alcoholic chronic pancreatitis. In 60 patients the principal indication for surgery was intractable pain. Eighteen patients had a duodenum-preserving resection of the pancreatic head (Beger operation); the other surgical procedures were Whipple resection (15), left-sided resection (13), total pancreatectomy (seven), pseudocystjejunostomy (five), pancreaticojejunostomy (one) and bypass procedures (four). The median inpatient stay was 12 days; 23 patients had postoperative complications including one death (2 per cent). There was improved pain control (P < 0.001), a reduction in opiate analgesia use, increase in percentage weight gain (P < 0.01 at 2 years) and return to employment following surgery. Although there was an increase in diabetes mellitus and need for enzyme supplementation these were easily controlled. CONCLUSION: Surgery is an effective treatment in carefully selected patients with chronic pancreatitis but must be tailored to the pattern of disease in each individual.

Adult↗
PubMed1997

Bile duct injury following laparoscopic cholecystectomy: referral pattern and management.

BACKGROUND: Laparoscopic cholecystectomy is associated with a higher incidence of bile duct injury than open cholecystectomy. This study reviews the management of bile duct injury in a tertiary hepatobiliary unit. METHODS: From 1991 to 1995, 27 patients (18 women) of median age 49 (range 25-67) years were referred to this unit with bile duct injury following elective laparoscopic cholecystectomy. Laparoscopic cholecystectomy was described as 'uneventful' in 14 and 'difficult' in 13 patients; six injuries were recognized at operation. RESULTS: Patients were transferred a median of 26 (range 0-990) days after laparoscopic cholecystectomy, although initial symptoms were recorded a median of 3 (range 0-700) days after cholecystectomy. Fifteen patients underwent additional surgery before referral. Management before referral included surgical exploration (15 patients), endoscopic cholangiography (ERC) and stent insertion (three), external drainage of bile collections (five), and conservative management (five). Management after referral included surgical reconstruction (19 patients), laparotomy with drainage (one), percutaneous drainage (two), ERC and stent insertion (two), percutaneous cholangiography with dilatation and stent placement (three), and conservative management (two). One patient died and the median inpatient stay following referral was 14 (range 7-78) days. Ten of 15 patients who had surgery before referral required a further biliary reconstruction. After median follow-up of 30 (range 3-60) months, four of nine patients with complex high injuries continue to have episodes of cholangitis and one patient has developed secondary biliary cirrhosis. CONCLUSION: Bile duct injury following laparoscopic cholecystectomy is a complex management problem and results in significant postoperative morbidity. Most patients referred after attempted repair require further reconstructive surgery, and patients with complex high injuries have a risk of long-term morbidity.

Adult↗
PubMed1996

Bile duct splintage in liver transplantation: is it necessary?

The choledochochole-dochal (duct-duct, D-D) anastomosis in orthotopic liver transplantation (OLT) is usually splinted by a T-tube to facilitate easy cholangiography, monitor bile quality and allow biliary decompression. T-tubes, however, are a focus for sepsis and sludge deposition, and their removal may result in bile leakage. From January 1993 to December 1994, 199 consecutive adult OLTs in 183 patients (median age 50 years, range 16-69 years, 118 females) with a D-D anastomosis were studied prospectively with a median follow-up of 16 (3-27) months. Of the 199 OLTs, 110 had an 8 Fr T-tube (group 1) and 89 had no T-tube (group 2). The two groups were similar for indication, preservation solution, median cold and warm ischaemia times and early graft function parameters. Biliary complications developed in 26/110 patients, including 10 with bile leaks on T-tube removal in group 1 compared to 10/89 biliary complications in group 2 (P = 0.024). The use of T-tubes is associated with increased morbidity and their routine use should be discontinued.

Adolescent↗
PubMed1996

Effect of pre-reperfusion portal venous blood flush on early liver transplant function.

Portal venous blood for rinsing out the University of Wisconsin solution (UWs) has the advantages of being a physiological fluid, removing acidotic mesenteric venous blood and perhaps resulting in more stable haemodynamic parameters during reperfusion. A group of 209 consecutive adult OLTs carried out between July 1993 and February 1995 were studied prospectively. The UWs was flushed out with 500 ml portal blood in 95 OLTs (group 1) and with 1.0 L 0.5% dextrose at 37 degrees C in 114 OLTs (group 2). The median day 1 and peak day 1-5 AST levels were significantly elevated in the 5% dextrose group: median 755 (118-11090) vs. 546 (121-6150) IU/I (P = 0.007, Wilcoxon); and median 1095 (159-11090) vs. 744 (157-7870) IU/l (p = 0.008, Wilcoxon), respectively. A median of 5 (0-27) units of blood were transfused in group 1 compared to 4 (0-54) units in group 2 (n.s.). There was no difference in peak bilirubin, lowest day 1-5 PT levels, primary nonfunction, median ITU stay, total inpatient stay and 1-month graft survival between the two groups (89% vs. 88%). Pre-reperfusion blood flush may be associated with less hepatocellular damage, without significant additional blood usage.

Adolescent↗
PubMed1996

Living related liver transplantation. Progress or regress?

The impetus for the development of living related liver programmes lies with donor shortage, which relates inversely to the success of generating cadaveric donors. A shrinking or non-existent cadaveric donor pool leads to an increased death rate among potential recipients awaiting transplantation. The living related liver programmes have by and large been successful, though it is accepted that there is potentially a significant risk to the donors. The technique of live donor liver transplantation is clearly here to stay, but the selection of suitable donors is between the family and the unit. Consequently, because of the lack of international guidelines, the programmes are open to abuse. Steps should be taken to establish either mechanisms of control or a worldwide register to combat this potential.

Adult↗
PubMed1996

Unresectable hepatic tumors in childhood and the role of liver transplantation.

Liver transplantation has been performed in five children with unresectable hepatic tumors who did not have extrahepatic metastases at the time of surgery. Two of the children had hepatoblastomas, one had an infantile hemangioendothelioma, and two had a hepatoma. The two children who had hepatoblastoma are well (37 and 25 months posttransplant) and have no evidence of recurrence. The child with infantile hemangioendothelioma had a successful operation, with good quality of life, but died of tumor recurrence 41 months after transplantation. Both children with hepatomas died, one of graft failure owing to chronic rejection and the other of tumor recurrence 5 months posttransplant. These results suggest that liver transplantation may be successful in children with unresectable hepatic tumors without extrahepatic spread and should be considered particularly for the treatment of hepatoblastoma.

Carcinoma, Hepatocellular↗
PubMed1996

Recurrence of primary biliary cirrhosis in the liver allograft: the effect of immunosuppression.

BACKGROUND: Recurrence of primary biliary cirrhosis in the liver allograft remains controversial. METHODS: We have examined the liver allograft biopsies taken at 1 and 2 years after transplantation from patients receiving either FK506 or cyclosporin as part of a multi-centre trial. RESULTS: Histological features characteristic for primary biliary cirrhosis, including bile duct damage, ductopenia, bile duct proliferation and portal granulomas, were found more commonly and earlier after transplantation in patients receiving FK506 than cyclosporin. During the 2-year period, seven of 16 patients receiving FK506 and only one of 11 on cyclosporin had a graft biopsy suggestive of recurrent primary biliary cirrhosis. CONCLUSIONS: These findings confirm earlier reports that features of primary biliary cirrhosis recur in the liver allograft in some patients and suggest that the rate of recurrence may be affected by the immunosuppression regimen used.

Adult↗
PubMed1996

Risk factors for liver rejection: evidence to suggest enhanced allograft tolerance in infancy.

After liver transplantation, a relatively low intensity immunosuppressive regimen is employed in our unit: after initial triple therapy (prednisolone, azathioprine, cyclosporin), prednisolone is discontinued at three months and azathioprine at one year. A retrospective study was therefore performed to determine the incidence of rejection, and to identify risk factors for rejection in our patient population. Over a 10 year period, 135 transplants were performed on 109 children. Thirty four (25%) were on infants less than 1 year old. Incidences of acute rejection and irreversible chronic rejection were calculated for grafts surviving more than one and four weeks respectively. Acute rejection occurred in 51 of 101 allografts (50%), and irreversible chronic rejection in 11 of 91 allografts (12%). The immunosuppression strategy was not associated with an increased incidence of rejection. Acute rejection occurred in only eight of 28 allografts (29%) in those transplanted during their first year, compared with 43 of 73 (59%) in older children. Logistic and Cox regression analysis supported age at transplantation as a significant risk factor for acute rejection. Irreversible chronic rejection did not occur in any of 24 grafts in patients transplanted before one year, compared with 11 of 67 (16%) in older recipients. This suggests possible enhanced allograft tolerance with transplantation during the first year of life. This unexpected and potentially important finding now requires confirmation in other large patient series, with blind interpretation of post-transplant liver biopsies.

Adolescent↗
PubMed1995

Inflammatory bowel disease in primary sclerosing cholangitis: an analysis of patients undergoing liver transplantation.

Fifty-five patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) were reviewed retrospectively. After OLT there were significantly more episodes of acute rejection in 31 patients with a previous history of inflammatory bowel disease (IBD) than in 24 without such a history. Patients who had severe acute rejection were significantly younger at diagnosis of IBD. Five patients with histological features suggestive of recurrent PSC after OLT were significantly younger at the time of transplantation than those who did not develop recurrence. Patients with poor control of IBD after OLT had a significantly lower age at diagnosis of bowel inflammation. The presence of IBD did not affect the outcome after OLT, but was associated with a higher rate of acute rejection. Younger patients had a greater risk of developing severe rejection, recurrent PSC and poor control of IBD after liver transplantation.

Adolescent↗