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Biomedical subjects

P McMaster

Publications and source records attributed to P McMaster.

At least 91 records · Page 5Linked to original sources
PubMed1996

Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis.

BACKGROUND: Orthotopic liver transplantation in patients positive for hepatitis B virus (HBV) DNA is associated with a high reinfection rate, even with hepatitis B immunoglobulin (HBIG) prophylaxis. Nucleoside analogues that inhibit hepatitis B replication in patients with chronic hepatitis B could prevent reinfection after transplantation. The aim of this study was to analyse the efficacy and safety of prophylaxis both before and after transplantation with the nucleoside analogue lamivudine, without HBIG, in patients undergoing liver transplantation. METHODS: 17 HBsAg-positive patients with decompensated cirrhosis and previous evidence of viral replication were enrolled. 12 were HBV-DNA-positive by a signal amplification assay. Patients were treated with oral lamivudine (100 mg daily) for at least 4 weeks before transplantation and followed up for 18-90 weeks after transplantation. FINDINGS: HBV DNA became undetectable in serum before transplantation in all HBV-DNA-positive patients. Four died before transplantation from complications of cirrhosis; one patient was withdrawn from the study because of a cerebrovascular accident. The remaining 12 patients underwent transplantation. Two patients died after transplantation (one at 3 days and one [suicide] at 20 weeks). HBV DNA reappeared in one patient with histological evidence of recurrent hepatitis (72 weeks). By week 24 the nine remaining patients had lost HBsAg and remained negative for HBV DNA. INTERPRETATION: Lamivudine treatment may prove useful in preventing recurrence of hepatitis B after liver transplantation. The effect on survival of patients after transplantation remains to be assessed.

DNA, Viral↗
PubMed1996

Transplantation for end stage liver disease related to alpha 1 antitrypsin.

Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.

Adult↗
PubMed1996

Two-year data from the European multicentre tacrolimus (FK506) liver study.

To provide a more definitive assessment of the efficacy and safety of tacrolimus therapy in comparison with cyclosporin, the extended follow-up of the European multicentre study is reported. Two-year Kaplan-Meier estimates indicated significant reductions in acute (tacrolimus 45.4%, cyclosporin 55.8%; P = 0.006), refractory (1.2% versus 6.4%; P = 0.003) and chronic rejection (2.0% versus 6.9%; P = 0.015) despite significantly lower steroid usage in patients receiving tacrolimus therapy. Patient and graft survival rates (80.6% versus 74.8% and 74.5% versus 70.0%, respectively) were also superior, although these failed to reach statistical significance. Safety profiles were comparable for most major categories (including renal, neurological and glucose metabolic disorders) and in certain aspects were more favourable for tacrolimus. Hypertension (28.0% versus 39.6%, P < 0.01) and cytomegalovirus infection (14.8% versus 22.3%, P < 0.01), two events with important long-term clinical consequences, were reported significantly less frequently. Hirsutism (0.0% versus 8.7%, P < 0.01) and gum hyperplasia (0.0% versus 2.3%, P < 0.05) were absent in patients receiving tacrolimus. Tacrolimus appears to provide effective and safe long-term immunosuppression.

Adolescent↗
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

Effect of RS61443 in combination with leflunomide or FK506 on rat heart allograft survival.

Mycophenolate Mofetil (RS61443) is a potent inhibitor of de novo purine synthesis and lymphocyte proliferation. It is known to prevent ongoing rejection and even reverse established rejection, alone and in combination with, cyclosporin. We investigated whether RS61443 in combination with leflunomide (Lef) or FK506 (FK) could prolong allograft survival in a rat heart model, since combination therapy might help to overcome drug toxicity. Abdominal heart grafting was performed from DA to LEW rats (250 g) and RS61443, 10 mg/kg or 30 mg/kg monotherapy or combination treatment (RS 10 mg/kg with Lef 5 mg/kg or FK 0.5 mg/kg) was begun orally at transplantation and continued daily until the ninth posttransplant (post-Tx) day. Ventricular motion was graded daily and rejection was defined as lack of contractions, confirmed by histology. Results were analysed using non-parametric tests. A two-tail P value < 0.05 was considered significant. RS at 10 mg/kg was ineffective and all grafts were rejected under immunosuppression between 5 and 6 post-Tx day, whereas RS at 30 mg/kg was immunosuppressive for as long as it was given. The combinations of RS at 10 mg/kg with either Lef at 5 mg/kg or FK at 0.5 mg/kg were immunosuppressive in the majority of cases, for as long as they were given. However, the combination of RS at 10 mg/kg with FK at 0.5 mg/kg was attendant with graft vein anastomosis rupture (3/5). The combination of RS with Lef was clinically therapeutic for as long as it was given; grafts were rejected 3-4 days after withdrawing immunosuppression. The combination of RS with FK resulted in over-immunosuppression, leading to graft vein anastomosis non-healing and rupture within 5 days of grafting; histology demonstrated evidence of bacterial infection with complete destruction of the vein wall. These data suggest that the combination of RS with Lef or FK in subtherapeutic doses might be a potentially promising strategy for combination therapy in solid organ transplantation.

Animals↗
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

Clinical significance of serum hepatocyte growth factor in orthotopic liver transplantation.

BACKGROUND: Hepatocyte growth factor (HGF) plays a key role in the regulation of liver regeneration after hepatocyte damage. Changes in HGF production reflect the status of the regeneration process. METHODS: Serum concentrations of HGF and energy substrates were measured during and after liver transplantation in 30 recipients. RESULTS: In the patients with compromised grafts (group A) HGF concentrations were persistently high after reperfusion, whereas in the patients with well-functioning grafts (group B), HGF concentrations decreased rapidly and remained low 4 hours after reperfusion. The patients in group A who died had persistently high concentrations of HGF. The surviving patients with reversible primary graft dysfunction in group A exhibited low concentrations 48 hours after reperfusion. The decrease in HGF concentration preceded the decrease in aspartate aminotransferase concentration. The metabolic parameters that reflect carbohydrate metabolism by the graft paralleled the changes in HGF. CONCLUSIONS: HGF may be more sensitive and specific in predicting early graft function than prothrombin time, ratio, aspartate aminotransferase, or arterial ketone body ratio. The determination of HGF levels after liver transplantation may yield valuable information for evaluating early graft function and making an early decision to repeat a graft procedure in an acutely ill patient.

Adolescent↗
PubMed1996

Personal child health record and advice booklet programme in Tuzla, Bosnia Herzegovina.

Personal child health records, held by the parents, have potential advantages in times of civil disorder. Via health and community workers, 939 booklets (incorporating health records and health advice) were distributed to displaced and other families near Tuzla. Subsequently mothers were invited to bring their children for examination. Five hundred and seventy-one children with their booklets returned to the clinics. The survey revealed high rates of dental caries (305 cases), anaemia (36), and scabies (20). The war had not affected the duration of breast feeding, and the children's nutrition was generally satisfactory. Immunization status was generally good, though rates were unacceptably low in children from certain areas, reflecting not only deficient provision in their place of origin but also failings in the programme for displaced persons. An informal survey indicated that parents and older children appreciated the health-information content of the booklet. In a disaster of this sort, the personal child health record and advice booklet serves the combined purpose of yielding essential epidemiological data, providing a permanent health record, and meeting a need for health education material.

Adolescent↗
PubMed1996

Sequential parenteral and oral ciprofloxacin regimen versus parenteral therapy for bacteremia: a pharmacoeconomic analysis.

OBJECTIVE: To compare, in patients with gram-negative bacteremia, a course of parenteral antibiotic therapy alone with initial parenteral therapy followed by oral ciprofloxacin in terms of the length of hospitalization, clinical effectiveness, toxicity, and cost. DESIGN: A prospective, controlled, randomized, open trial in select hospitalized patients. SETTING: Large metropolitan teaching hospital. PATIENTS: Fifty hospitalized patients with proven gram-negative bacteremia were randomized to receive either oral ciprofloxacin (group 1) following a 72-hour initial intravenous antibiotic regimen or to continue parenteral therapy alone (group 2). To compare the length of hospitalization, an additional group of 50 hospitalized patients with bacteremia (not enrolled in the study, group 3) were analyzed. INTERVENTION: Parenteral antibiotics for 72 hours followed by continuation of a parenteral regimen or oral ciprofloxacin 750 mg bid. MAIN OUTCOME MEASURES: Clinical response, toxicity, and length of hospitalization. RESULTS: Clinical resolution was comparable in the 24 group 1 patients receiving intravenous antibiotics followed by oral ciprofloxacin (83%), the 26 group 2 patients receiving parenteral therapy alone (77%), and the 50 comparison patients (76%). There was little toxicity noted in any group, and the initial parenteral antibiotic regimens were similar. The mean numbers of hospital days on antibiotics were 9.1, 11.2, and 10.6 days in groups 1,2, and 3, respectively (p < 0.05 for group 1 vs. group 2 or 3), and the lengths of hospitalization were 9.8, 15.7, and 12.1 days, respectively (p < 0.05 for group 1 vs. group 2 or 3). Shortening the length of hospitalization and days of antibiotic therapy was associated with a cost savings of up to $78 000 for group 1 patients. CONCLUSIONS: Parenteral therapy for 72 hours followed by oral ciprofloxacin significantly shortened both the number of hospital days taking antibiotics and the length of stay compared with parenteral therapy alone. Both regimens were equally effective and safe in the therapy of gram-negative bacteremia, and initial parenteral therapy followed by oral ciprofloxacin was cost-effective.

Administration, Oral↗