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Biomedical subjects

A D Mayer

Publications and source records attributed to A D Mayer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Changing referral pattern of biliary injuries sustained during laparoscopic cholecystectomy.

SUMMARY: More patients with less severe type biliary injury are being referred earlier to a specialist hepatobiliary unit. Most patients still have ineffective corrective surgery before transfer. Presented in part to the European Congress of the International Hepato-Pancreatico-Biliary Association in Budapest, Hungary, May 1999 and published in abstract form as Digestive Surgery 1999; 16(Suppl 1): 32.

Bile Ducts↗
PubMed2000

Factors predicting perioperative cytokine response in patients undergoing liver transplantation.

OBJECTIVES: An exaggerated production of proinflammatory cytokines during liver transplantation stimulates the inflammatory process within the graft, and eventually promotes liver failure. This study was conducted to evaluate factors predicting perioperative response of proinflammatory cytokines during liver transplantation. DESIGN: Prospective, consecutive entry study of liver transplant candidates. SETTING: University hospital. PATIENTS: Thirty liver transplant recipients. INTERVENTIONS: Arterial blood samples were obtained perioperatively. MEASUREMENTS: Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha were measured by ELISA. Endotoxin was determined by a chromogenic endotoxin-specific method. MAIN RESULTS: The peak concentrations of IL-1beta and IL-6 in the patients with complications were significantly higher than those in the patients without complications. The peak concentration of IL-1beta was significantly correlated with the level of bilirubin at admission and the intraoperative blood product requirement. The peak concentration of IL-6 was significantly correlated with the admission bilirubin and the intraoperative blood product requirement. A multivariate regression model revealed that the serum bilirubin and the intraoperative blood product requirement were the independent factors that influenced the peak concentration of IL-1beta or IL-6. The severely jaundiced patients had a significantly higher plasma concentration of endotoxin at the end of the anhepatic phase. In addition, there was a tendency for these patients to have a higher postoperative peak concentration of endotoxin. CONCLUSIONS: Serum level of bilirubin may be a potent preoperative factor influencing perioperative cytokine response in patients undergoing liver transplantation. An enhanced perioperative response of endotoxin seen in severely jaundiced patients suggests the clinical implication of endotoxin removal during the anhepatic phase in liver transplant surgery.

Adolescent↗
PubMed1999

Outcome of liver retransplantation in children.

Irreversible liver graft failure is a life-threatening complication. We reviewed the first 200 pediatric liver transplantations in Birmingham. Forty-one children developed primary graft failure, 9 of whom developed secondary graft failure. The main indications for graft failure were primary nonfunction (PRNF; 8 patients), vascular complications (VASC; 23 patients), and chronic rejection (CHRE; 19 patients). Thirty-two children underwent retransplantation (ReTx) (21 children received reduced grafts; 11 children, whole hepatic grafts). Patient survival was significantly worse for retransplant recipients compared with children receiving a single graft (63% v 76. 5% actuarial patient survival at 1 year; P <.05). Primary graft 1-year actuarial survival was 74% in first grafts compared with 47% for regrafts (P <.05), but improved with time. The graft 1-year survival rate was 55% for whole grafts and 45% for reduced and/or split grafts in the first 100 grafts compared with 83% and 66% in the second 100 grafts, respectively (P <.01). Emergency ReTx within a month of transplantation was associated with more complications and a worse outcome (1-year survival rate, 37%) compared with patients who underwent ReTx later (1-year survival rate, 72%; P <. 01). The incidence of primary graft failure decreased from 33% in the first 100 grafts to 16% in the second 100 grafts (P <.01), as did the incidence of PRNF, which decreased from 8% to 0% (P <.05). Although the rates of graft failure from VASC decreased from 15% to 8% (P =.2) and CHRE decreased from 11% to 8% (P =.6), neither reached statistical significance. The improved results overall are because of advances in surgical techniques, intensive care management, and graft preservation and refinements in immunosuppression. We conclude that ReTx for a child with primary graft failure is justified.

Adolescent↗
PubMed1999

Energy storage and cytokine response in patients undergoing liver transplantation.

Overproduction of pro-inflammatory cytokines during surgery has been known to exert tissue-damaging and lethal effects on the host. Hypermetabolism-associated malnutrition, a common feature of patients with end-stage liver diseases, is related to the presence of a systemic inflammatory response, as reflected by enhanced levels of proinflammatory cytokines. The present study was designed to evaluate energy status of 29 liver transplant recipients, and to assess the relation of energy storage to post-operative cytokine response. The glycogen contents of the graft, and the recipient's abdominal muscle and old liver were measured. The plasma concentrations of tumour necrosis factor alpha, interleukin 1beta, interleukin 6, lactate, pyruvate and total ketone bodies were determined during and after surgery. In undernourished patients, ketone bodies seemed to be the major fuel available to muscle. The concentration of ketone bodies decreased rapidly after the incision, and remained at a low level after reperfusion. These patients had higher plasma levels of lactate/pyruvate ratio and aromatic amino acids during the anhepatic phase, followed by an exaggerated response of cytokines. Depletion of energy storage of the recipients may be involved in the deterioration of peri-operative energy metabolism and the exaggerated post-operative cytokine response.

Adolescent↗
PubMed1999

Indications and outcome of liver transplantation in tyrosinaemia type 1.

UNLABELLED: A retrospective analysis was performed on 17 patients presenting with tyrosinaemia type 1 (TT1) between 1989-1997; 7 pre 1992 prior to the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and 10 post 1992. During this time, eight children (5 males) underwent orthotopic liver transplantation (OLT); six prior to the introduction of NTBC in 1992 and two on NTBC therapy. The primary indications for OLT pre-1992 were risk of hepatocellular carcinoma with evidence of hepatic dysplasia in all, associated with liver failure in two, and rise in alpha-fetoprotein (AFP) in four. Two of the ten treated with NTBC required OLT. The indications were non-response to NTBC in one child and development of hepatic dysplasia associated with poor quality of life in the second patient. Median age for OLT was 64 months (range 5-127 months) with a median weight of 24 kg (range 6-25 kg). The histology of hepatectomy specimens at transplantation showed: cirrhosis in 8, hepatic dysplasia in 6 and hepatocellular carcinoma in 1. Plasma tyrosine and AFP returned to normal in all cases. Urinary succinylacetone reduced but persisted in small amounts (median 7.7 micromol/mmol creatinine). Hypertrophic cardiomyopathy resolved in 3/3 patients. Hypoglycaemia, not responding to dietary therapy or NTBC treatment, resolved post-transplant in one patient. There were two deaths, one from primary non-function and one from chronic rejection. Late complications in survivors (n=6) include post-transplant lymphoproliferative disease of the iris in one child which resolved and renal dysfunction with a fall in glomerular filtration rate in three (50%). Median follow up post OLT is 6.7 years (range 1-7 years). Quality of life post-transplant in survivors is good with unrestricted diet in all. CONCLUSION: Liver transplantation is an effective treatment for TT1 with good quality of life. The current indications of OLT in TT1 are non-response to NTBC, risk of malignancy and poor quality of life related to dietary restriction and frequency of blood sampling.

Adolescent↗
PubMed1999

Orthotopic liver transplantation for unresectable hepatoblastoma: a single center's experience.

BACKGROUND/PURPOSE: Complete surgical resection after chemotherapy is the definitive treatment for hepatoblastoma. However, orthotopic liver transplantation (OLT) is now accepted as a treatment modality for patients with unresectable tumours. The aim of this study was to review a single center's experience of OLT for unresectable hepatoblastoma. METHODS: A retrospective review of 8 patients with unresectable hepatoblastoma who were referred for liver transplantation was conducted. RESULTS: The patients assessed had an age range of 5 to 105 months at presentation; median, 24 months, (5 boys; 3 girls). Two patients have familial adenomatous polyposis, and one has right hemihypertrophy. All 8 patients had received standard chemotherapy according to SIOP (International Society of Pediatric Oncology) protocols. Extrahepatic metastases were found in 3 patients at diagnosis, but none had detectable metastases at the time of OLT. Four patients continued chemotherapy while awaiting OLT. Three patients received whole grafts, and 5 received reduced grafts. The median follow-up period was 22 months (range, 2 to 78 months). Five patients are alive and well, although 1 patient had a second OLT for biliary cirrhosis secondary to biliary stricture at 6 years. Three patients died: one 26 days post OLT of sepsis and two of disease recurrence at 22 months and 70 months posttransplant. The actuarial survival rate is 88% and 65% at 1 and 5 years, respectively, whereas the overall survival rate is 62.5%. CONCLUSION: OLT for unresectable hepatoblastoma without extra hepatic metastases is highly successful with a low recurrence rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Serum hepatocyte growth factor as an index of extensive catabolism of patients awaiting liver transplantation.

BACKGROUND: Whole body catabolism as the result of intrahepatic metabolic derangement is common in liver transplant candidates. However, individual nutritional assessment parameters lack sensitivity and specificity in determining energy status of these patients. Recently, serum hepatocyte growth factor (HGF) has been shown to reflect the recovery of hepatic energy metabolism after liver transplantation. AIMS: The relation between preoperative levels of serum HGF and metabolic variables was investigated to clarify the clinical value of measuring HGF in evaluations of the catabolism. PATIENTS/METHODS: Blood samples were obtained from 30 liver transplant recipients, and biopsy specimens were taken from each recipient's rectus muscle and the explanted liver. Preoperative serum concentration of HGF was determined. Whole body energy metabolism was assessed by measuring glycogen contents of biopsy specimens and plasma or serum levels of glucose, insulin, total ketone bodies, total carnitine, and amino acids. RESULTS: Serum HGF concentration was elevated in 22 of 30 patients and correlated with the Child-Pugh score. It showed a negative association with muscle glycogen content, and a positive correlation with serum levels of glucose, total carnitine, and total ketone bodies. Patients with elevated serum HGF concentrations had higher preoperative plasma levels of aromatic amino acids and branched chain amino acids, associated with lower branched chain to aromatic amino acid ratios. CONCLUSIONS: The elevated serum concentration of HGF in liver transplant candidates reflected inhibition of peripheral glucose storage, enhanced lipid oxidation, and increased peripheral release of branched chain amino acids, and thus extensive energy catabolism.

Adult↗
PubMed1998

Randomized trial of cyclosporine microemulsion (neoral) versus conventional cyclosporine in liver transplantation: MILTON study. Multicentre International Study in Liver Transplantation of Neoral.

BACKGROUND: The new microemulsion formulation of cyclosporine (Neoral) has been developed in an effort to improve the reliability of drug absorption. The objectives of this study were to assess the efficacy, safety, and tolerability of Neoral compared to the original formulation (Sandimmun) in liver transplant recipients. METHODS: In a double-blind, parallel group study conducted in 28 centers across Europe and the United States, patients receiving primary orthotopic liver allografts were randomized within 24 hr of transplantation, 198 to Neoral and 192 to Sandimmun. Patients with and without T-tube biliary drainage were included. Postoperatively, all patients also received intravenous (i.v.) cyclosporine, together with prednisolone and azathioprine. Antibody induction was excluded. Efficacy measures were rejections, graft failure, patient survival, and the efficacy of the study medication in achieving the desired cyclosporine blood levels. Safety was assessed by reported adverse events, blood pressure, serum creatinine, and other routine laboratory measurements. RESULTS: Kaplan-Meier analyses showed that the Neoral group performed better than the Sandimmun group, with the estimates for patients free of treated rejection and histologically confirmed rejection either showing or approaching statistical significance at the 5% level. By 52 weeks, 5.8% (95% confidence limits: -4.4-15.9%) fewer patients required treatment of acute rejection in the Neoral group. The proportion of patients experiencing at least one treated rejection episode by 2 weeks was 29.8% for Neoral and 43.2% for Sandimmun. For histologically confirmed rejection, these proportions were 32.8% and 44.3%, respectively. The proportion of patients experiencing at least one steroid-resistant rejection was 2.0% for Neoral and 6.3% for Sandimmun at week 2, and 3.0% and 9.9%, respectively, at week 3. All these differences were significant at P<0.05. By 52 weeks, graft failure was 6.3% on Neoral and 11.4% on Sandimmun, with respective patient survival figures of 85.4% and 85.8%. The median duration of the initial episode of i.v. cyclosporine was 4.0 days for Neoral, compared to 6.5 days for Sandimmun (P<0.001). Within the first 2 weeks, a larger percentage of patients in the Neoral group reached the lower target level of cyclosporine (P< or =0.01). The weight-adjusted daily doses of study medication were lower in the Neoral group (median dose: 4.86 vs. 5.42 mg/kg/day, P=0.001), but the blood levels of cyclosporine showed no difference. For those with a T-tube, more of the patients on Neoral remained free of treated rejection throughout the study period (P=0.042, Wilcoxon). By week 2, 44.9% of these patients in the Sandimmun group required treatment for rejection compared to 30.2% in the Neoral group (P=0.007). There was no significant difference between the groups for serum creatinine, blood pressure, other biochemical and hematological variables, or reported adverse events. CONCLUSIONS: In liver transplantation in the normal clinical setting, the pharmacokinetic advantages of Neoral translate into clinical superiority over Sandimmun without a negative impact on safety. Recent data indicate that it is not optimal to use i.v. cyclosporine initially in this type of study, but the benefit was seen despite this. In keeping with the previous pharmacokinetic studies, patients managed by T-tube biliary drainage, and hence with no or limited bile available in the gastrointestinal tract, did particularly well with Neoral.

Adult↗
PubMed1998

Repeat orthotopic liver transplantation in the 1990s: is it justified?

Repeat orthotopic liver transplantation (ReOLT) is controversial because of limited donor organ availability and increasing health care costs. The purpose of this study is to analyse and compare the outcome of reOLT in the 1990s and the 1980s. Prospective data of 1077 adult OLT from the Liver Unit database were used for the study. The log-rank test was used for statistical analysis. Between January 1982 and December 1996, a total of 1077 adult OLTs were performed including 107 reOLTs. The proportion of retransplants decreased from 13% in the 1980s to 9% in the 1990s. There was a significant improvement in outcome; the overall 1-year graft and patient survival for reOLT was 60% and 74% in the 1990s compared to 29% (P < 0.0001) and 51% (P < 0.0001) in the 1980s. In the second half of the study between January 1990 and December 1996, 732 adult OLTs were undertaken including 70 (9%) reOLTs which consisted of 62 second, 7 third and 1 fourth grafts. The main indications for retransplantation were chronic rejection (31%), hepatic artery thrombosis (30%), primary non-function (16%), ischaemic injury (11%), recurrent disease (6%) and biliary complications (6%). During this period, the 1-year graft survival for all reOLTs was significantly lower than for primary OLTs (67% vs 78%, P < 0.001). The timing of reOLT was found to be associated with graft survival; 1-year graft survival for early reOLT (< 30 days) was 50% compared to 73% for late reOLT (P < 0.001). The worse outcome associated with early reOLT is explained by the poor preoperative medical condition of patients who were retransplanted from intensive care. Subgroup analysis of indications for reOLT revealed 1-year graft survival of 81% for late vascular complications, 75% for early vascular complications, 69% for chronic rejection and 30% for primary non-function. One-year graft survival rates for third and fourth grafts were 42% and 0%, respectively. Graft survival and resource utilisation in patients who received a late regraft for the first time is now comparable to that for primary OLT. The favourable overall results should not preclude this group of patients from consideration for reOLT.

Adult↗
PubMed1998

Early risk factors in pediatric renal transplantation at a single center.

BACKGROUND/PURPOSE: Renal transplantation is the preferred treatment for renal failure in childhood, but the incidence of graft failure is generally higher than that in adult recipients. A single center was studied to determine if there were any correctable factors that could contribute to graft failure. METHODS: Recipient, donor, and perioperative factors were analyzed using standard statistical tests in 59 pediatric renal transplants performed between 1992 and 1995 using standard cyclosporin-based immunosuppression. RESULTS: Three factors were found to be significantly different between those recipients with good graft function and those who either died or were returned to dialysis. Any history of donor hypotension was a detrimental factor (P < .05, chi(2) test). In addition, those with failed grafts were more likely to have received their grafts from younger donors (P = .025, Mann Whitney U test). A third risk factor was a low postoperative central venous pressure in those whose graft ultimately failed (P = .0012, Mann Whitney U test). CONCLUSIONS: With a pediatric recipient who is stable and has a low priority for a renal graft, small donors, particularly those who have experienced hypotension, should be considered not suitable for transplantation. The chances of a successful graft can be improved by good communication between surgeon, pediatrician, and anesthetist. The importance of maintaining a positive central venous pressure is emphasised.

Age Factors↗
PubMed1998

Postperfusion energy metabolism of steatotic graft and its relation to early graft viability following liver transplantation.

The present study was designed to assess energy metabolism of steatotic grafts and to determine its relation to early graft viability. Graft biopsies were taken, and the triglyceride content was determined in 29 grafts for the assessment of steatosis. The peak aspartate aminotransferase level and the concentrations of lactate and pyruvate were strongly correlated with the triglyceride content, suggesting that steatotic grafts are more vulnerable to preservation or reperfusion injury and that glucose oxidation is inhibited postoperatively in the steatotic grafts. Ketogenesis, an alternative pathway to produce energy substrates, was not accelerated even when the steatotic grafts produced more free carnitine to enhance the beta-oxidation of fatty acids. The deterioration of energy metabolism was associated with the increase in prothrombin time ratio, hepatocyte growth factor, and hyaluronic acid that reflected graft viability. Deterioration of postperfusion energy metabolism in the steatotic grafts may be involved in the development of irreversible graft damage.

Adult↗
PubMed1998

Encouraging results of split-liver transplantation.

BACKGROUND: Liver donor shortage presently accounts for a 10 per cent waiting list mortality rate. Split-liver transplantation (SLT) can improve utilization of this scarce resource. METHODS: Twenty-four SLTs (11 left, 13 right grafts) from 13 livers were performed in 23 patients (nine adults, 14 children), comprising 4.5 per cent of all orthotopic liver transplants (14 urgent or emergency, ten elective). The left graft comprised segments II and III, whereas the right graft comprised segments V-VIII in eight cases, IV-VIII in three, and segments I, IV-VIII, and I, V-VIII in one case each. Additional arterial extension grafts were required in six of 24 cases, and portal venous interposition graft in one. RESULTS: Twenty-one grafts showed good initial function, with one primary non-function and two initial poor function. The median peak aspartate aminotransferase level was 782 (range 94-2301) and 982 (range 382-2520) units/l for left and right grafts respectively. Five patients died (all urgent recipients), all within the first 30 days after surgery. Two SLT recipients underwent subsequent retransplantation. All ten elective recipients are alive. The 1-year actuarial patient and graft survival rates at a median follow-up of 20 months were 78 and 68 per cent respectively. CONCLUSION: These encouraging results compare favourably with those of reduced-size and whole-liver transplantation and justify wider application of this technique, thereby optimizing donor resource use.

Adult↗
PubMed1998

A method for regulating the duration of pregnancy and the time of parturition in Sprague-Dawley rats (Charles River CD strain).

A method of shifting the dark phase of the 12/12 hr photoperiod cycle on Day 7 of pregnancy is described for regulating the duration of pregnancy to 22 days and assuring that most parturitions take place between 1100 and 1500 hr. This method, in addition, has the added convenience that matings can occur during normal laboratory hours between 0700 and 1900 hr during the dark phase of the photoperiodic cycle. Litter sizes are normal (mostly 14-16 pups) and postpartum estrus behavior occurs at the normal interval of 4 to 11 1/2 hr after parturition.

Animals↗