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Biomedical subjects

P McMaster

Publications and source records attributed to P McMaster.

At least 73 records · Page 4Linked to original sources
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

[Use of normal human hepatocytes in a hybrid organ system].

Using the bioreactor model developed by J. Gerlach, we examined the potential of normal human hepatocytes for application in bioartificial liver devices. From normal human donor livers 1.5 x 10(8) hepatocytes were isolated. Hepatocytes were perfused in a woven multi-compartment capillary system in serum-free culture medium containing ammoniachloride over a period of 2 weeks. These cells demonstrated a well differentiated ultrastructure with formation of junctional complexes and bile canaliculi between adjacent cells. During reactor run, a constant albumin synthesis with levels above 11 mg/ml and maintenance of urea production and lignocaine metabolism (MEGX-test) were detected. These initial results indicate that normal human hepatocytes express typical morphology and ultrastructure and are able to keep differentiated functions in suitable perfusion models. Combination of the distinct human liver cell populations might enable promotion of further specific functions (clotting factors) and induction of liver cell proliferation.

Cell Survival↗
PubMed1997

A positive crossmatch in liver transplantation--no effect or inappropriate analysis? A prospective study.

BACKGROUND: Controversy over the relationship of preformed lymphocytotoxic antibodies and liver graft outcome remains. Because graft loss associated with preformed lymphocytotoxic antibodies probably occurs early after transplant, analysis of long-term survival is of questionable value. We therefore prospectively analyzed the effect on short- and long-term graft survival of the presence of lymphocytotoxic alloantibody in 207 primary adult liver allograft recipients. METHODS: Pretransplant serum was tested for donor-specific lymphocytotoxic antibodies and panel-reactive antibodies (PRA) using donor splenic lymphocytes and lymphocytes obtained for routine tissue typing. RESULTS: A positive crossmatch was detected in 24 recipients (11.5%): T-cell positive in 11 recipients and B-cell positive in 13 recipients. PRA were detected in 68 of 179 recipients tested (37.4%). High T-cell PRA (>55%) was detected in 17 recipients, and high B-cell PRA was detected in 20 recipients. Low PRA (<15%) against T cells was detected in 19 recipients and against B cells in 24 recipients. Graft failures occurred in 5 of 24 (21%) crossmatch-positive recipients and in 7 of 172 (4%) crossmatch-negative recipients. Graft survival was significantly lower in crossmatch-positive recipients at 1 month after transplant (chi-square=10.3, P=0.00133) but not at 3 months or 1 year. Causes of early graft loss were associated with immunological mechanisms, whereas later losses were due to nonimmunological mechanisms. CONCLUSIONS: Early graft loss may be increased in those recipients who are crossmatch positive. However, the logistical problems and consequences associated with allocation probably outweigh the benefits of prospective crossmatching.

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

Liver transplantation for alcoholic liver disease: evaluation of a selection protocol.

We have used a formal transplant protocol to select patients with alcoholic liver disease (ALD) for transplantation. We retrospectively analyzed all the patients with ALD who were referred specifically for transplantation to our Liver Unit between 1987 and 1994. Patients were selected for liver transplantation if they had end-stage liver disease and had remained abstinent from the time they were medically advised to stop alcohol intake. Of the 180 patients referred for transplantation, 43 (none of whom were transplanted) had case records insufficiently complete for full analysis; this may bias the analysis. Of the remaining 137 patients, 39 were transplanted and 4 were awaiting transplantation at the time of analysis. Of the patients who were not accepted for transplantation, 13 died during the assessment, 7 were considered to be unlikely to survive the procedure, 29 were found to be medically unsuitable, 16 psychologically unsuitable, 7 patients refused the offer of transplantation, and an additional 19 either showed clinical improvement or were considered too well for transplantation. Special investigations, such as brain computerized tomography (CT) scan and echocardiograph, changed the clinical decision to transplant in only a small number of cases (4% and 5%, respectively). Nine of the transplanted patients died and the remaining were followed up for a median of 25 (range, 7-63) months. One year actuarial survival for the transplanted patients was 79%, for those considered too sick was 0%, for medically unsuitable patients was 44%, for psychologically unsuitable patients was 65% and for those considered too well was 94%. Only 5 of the transplanted patients (13%) reverted to drinking. The observed actuarial survival of nontransplanted patients was compared with the expected survival calculated by 'the Beclere model.' The observed actuarial survival in the nontransplanted groups was much better than anticipated from the Beclere model, which therefore, is not applicable to our patients. The proportional hazards regression analysis of our nontransplanted patients identified serum bilirubin, serum albumin, blood urea, ascites, and spontaneous bacterial peritonitis as factors significantly predictive of their probability of survival. Using a model based on these parameters, the expected survival of our transplanted patients was calculated. Although we applied the model to a different population, the observed actuarial survival in the transplanted patients was found to be better than their expected survival (P < or = .001). Our protocol was useful in selecting suitable patients with ALD for liver transplantation, which resulted in significant survival advantage with low recidivism rate.

Adult↗
PubMed1997

Tacrolimus-based immunosuppression after liver transplantation: a randomised study comparing dual versus triple low-dose oral regimens.

To evaluate the efficacy and safety of oral tacrolimus-based immunosuppressive induction therapy, 130 primary orthotopic liver transplant (OLT) recipients were randomised to treatment in an open, parallel-group, European multicentre trial. Following OLT, patients were immediately administered either tacrolimus (0.10 mg/kg) and prednisolone (dual therapy group) or tacrolimus (0.06 mg/kg) in conjunction with prednisolone and azathioprine (triple therapy group) both orally. Patient survival at 1 year was 79.4% for the dual therapy group and 88.7% for the triple therapy group (P = 0.194); 1-year graft survival rates were 76.5% in the dual therapy group and 80.6% in the group receiving triple therapy (P = 0.615). The frequencies of rejection (dual therapy 42.6%, triple therapy 50.0%; P = 0.482), infection, and other complications (renal, neurological and glucose metabolic disorders) were similar in both groups. Tacrolimus whole blood trough concentrations were detectable on days 1 and 2, respectively, in the dual and triple therapy treatment groups whilst median tacrolimus blood concentrations in the triple therapy group reached levels similar to those in the dual therapy group on postoperative day 11 following a steady increase in dose. After 1 year, 54.4% of the patients randomised to dual therapy were receiving tacrolimus monotherapy and only 56.4% of the patients randomised to triple therapy continued to receive azathioprine. In conclusion, oral tacrolimus-based immunosuppression is both potent and safe when administered as induction therapy after OLT. Treatment may commence at either 0.06 or 0.10 mg/ kg per day, but doses may need to be increased to the latter value within the first 10 days to maintain effective immunosuppression.

Administration, Oral↗
PubMed1997

Donor pretreatment with leflunomide has an adverse effect on rat cardiac allograft survival.

The effect of leflunomide (Lef) donor pretreatment (DPT) on rat cardiac allograft survival was investigated. In untreated Lewis recipients of untreated DA hearts, median graft survival was 5 days. DPT (Lef 5 or 10 mg/kg per day for 30 days) reduced median graft survival to 4.0 and 4.5 days, respectively. In immunosuppressed (Lef 5 mg/kg for 10 or 30 days) Lewis recipients of untreated DA hearts, median graft survival was 21 and 33 days, respectively. DPT with Lef 5 mg/kg per day for 5 days or 30 days reduced median graft survival to 12 and 23.5 days, respectively (p < 0.05). DPT with Lef resulted in earlier graft rejection but the histological appearance at the time of rejection was the same as in untreated controls. DPT with Lef resulted in a 40% reduction in MHC class II-positive cells in the heart. Histological examination of rejecting hearts showed no obvious difference in the nature of the rejection process between DPT and untreated control hearts. The paradox between class II reduction but earlier rejection indicates that DPT is exerting a deleterious effect through some unrecognized property of the graft.

Animals↗
PubMed1997

Plasma carnitine kinetics during orthotopic liver transplantation.

BACKGROUND: Carnitine is synthesized mainly in the liver and plays an essential role in the transport of fatty acids in liver mitochondria for subsequent oxidation and energy production. METHODS: The plasma concentrations of free carnitine, acylcarnitine, total ketone bodies, lactate, pyruvate, and hepatocyte growth factor (HGF) were measured during liver transplantation. RESULTS: The plasma free carnitine and acylcarnitine concentrations and the lactate to pyruvate ratio in patients with compromised grafts (group A) were significantly higher than those in patients with well-functioning grafts (group B) after reperfusion. The acylcarnitine concentration in group B decreased after incision, but it remained at a high level in group A. Significant correlations were found between the concentrations of HGF and free and acylcarnitine after reperfusion. CONCLUSION: The accelerated flux of carnitine in the graft may be associated with deterioration of energy metabolism in the graft. An increased acylcarnitine concentration may reflect impaired liver regeneration.

Carnitine↗
PubMed1997

Glycogen content of the donor liver and its relation to postreperfusion hepatic energy metabolism.

OBJECTIVES: Many studies have suggested that glycogen in donor livers is an important fuel during cold ischemic time and at reperfusion. However, it remains unclear as to whether the depression of glycogen content in the graft results in a critical derangement of energy metabolism after reperfusion. The purpose of this study was to assess the possible implications of the glycogen concentration of donor livers for the hepatic energy metabolism after reperfusion. METHODS: The glycogen content of 28 donor livers and the plasma concentrations of metabolic substrates were measured during liver transplantation. RESULTS: Gluconeogenesis was maintained even in the glycogen-depleted graft at reperfusion. However, glycogen-depleted grafts produced more ketone bodies until 24 h after reperfusion. Free carnitine concentrations in these patients were significantly higher than those in the patients with glycogen-nondepleated grafts until 48 h after reperfusion. CONCLUSIONS: A glycogen-depleted liver graft may restore essential metabolic function by producing energy substrates through enhanced ketogenesis in the postreperfusion period. The enhanced production of carnitine by the graft provides a substrate for the production of ketone bodies and thus may be relevant to the enhanced ketogenesis.

Energy Metabolism↗
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↗
PubMed1997

[Primary angiosarcoma of the liver].

Hepatic angiosarcoma (AS) is a rare tumor with a fatal course. It represents 1-2% of all primary hepatic tumors and it is the most frequent primary mesenchymal tumor of the liver. Recently its incidence is dramatically increased because of its epidemiological association with exposure to thorotrast, vinyl chloride and other carcinogens. We present the epidemiological, clinical, diagnostic and therapeutic features of 6 patients with primary hepatic AS. No apparent predisposing factors were present. At presentation symptoms, signs and liver function tests were not specific. Four patients presented with metastatic disease: lung (2), peritoneum (1), bone and spleen (1). At time of diagnosis tumor was bilobar in 4 cases and in 2 of whom was multifocal. Median tumor size was 10.5 cm (range: 4-20 cm). Four patients with extrahepatic disease were conservatively treated with chemotherapy (VAC) and the longest survival was 8 months and 2 with tumor confined to the liver were transplanted but both had an early recurrence at 3 and 5 months post-tx respectively and the longest survival was 10 months. These disappointing results confirm the aggressive nature of hepatic AS. An early diagnosis is needed and the radical resection of the tumor is still the best form of treatment.

Adult↗