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Biomedical subjects

V Warty

Publications and source records attributed to V Warty.

At least 37 records · Page 2Linked to original sources
PubMed1993

Baboon-to-human liver transplantation.

Our ability to control both the cellular and humoral components of xenograft rejection in laboratory experiments, together with an organ shortage that has placed limits on clinical transplantation services, prompted us to undertake a liver transplantation from a baboon to a 35-year-old man with B virus-associated chronic active hepatitis and human immunodeficiency virus infection. Liver replacement was performed according to conventional surgical techniques. Immunosuppression was with the FK 506-prednisone-prostaglandin regimen used routinely for hepatic allotransplantation, to which a daily non-myelotoxic dose of cyclophosphamide was added. During 70 days of survival, there was little evidence of hepatic rejection by biochemical monitoring or histopathological examination. Products of hepatic synthesis, including clotting factors, became those of the baboon liver with no obvious adverse effects. Death followed a cerebral and subarachnoid haemorrhage that was caused by an angioinvasive aspergillus infection. However, the underlying cause of death was widespread biliary sludge that formed in the biliary tree despite a seemingly satisfactory choledochojejunostomy. During life and in necropsy samples, there was evidence of the chimerism that we believe is integral to the acceptance of both xenografts and allografts. Our experience has shown the feasibility of controlling the rejection of the baboon liver xenograft in a human recipient. The biliary stasis that was the beginning of lethal infectious complications may be correctable by modifications of surgical technique. In further trials, the error of over-immunosuppression should be avoidable.

AIDS-Related Opportunistic Infections↗
PubMed1993

Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion.

The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half-life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate post-operative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.

Adult↗
PubMed1993

FK506 measurement: comparison of different analytical methods.

In this study, we used solid-phase extraction with Sep-Pak and a liquid-liquid extraction with methylene chloride as two primary methods of extracting FK506 from plasma. The extracts were either analyzed directly by enzyme-linked immunosorbent assay (ELISA) or subjected to high-performance liquid chromatography (HPLC) separation and different fractions were analyzed by ELISA. Serial blood samples were obtained from four kidney transplant patients and four patients who underwent liver transplantation, from day 1 until day 30-35 posttransplantation. There was no significant difference in the FK506 plasma concentration as measured by all four methods in normal transplant patients. However, in liver transplant patients, the solid-phase extraction method gave higher FK506 concentrations than the methylene chloride extraction during the early postoperative period. The concentrations measured after methylene chloride extraction were higher than that after HPLC-ELISA. This higher FK506 concentration measured by direct ELISA could be attributed to possible cross-reacting metabolites that were present in the plasma of patients with abnormal liver functions. Once liver function returns to normal, all four methods give identical plasma concentrations for FK506.

Chemistry Techniques, Analytical↗
PubMed1993

The effect of FK506 on canine bile flow.

While the primary immunosuppressive agents utilized in solid-organ transplantation are steroids and cyclosporine, the more recently introduced agent FK506 is assuming a progressively more important role as an immunosuppressant, particularly in liver transplantation. While the effect of cyclosporine on rat and canine bile flow has been well evaluated, no information is available regarding the effect of FK506 on bile flow. Dogs with chronic biliary fistulas were utilized, enabling unanesthetized animals to be studied. FK506 was administered intravenously in varying doses, and bile volume, bile salts, and bile electrolytes were measured. FK506 produced dose-related increases in bile volume and bile chloride concentration and output, with 8 micrograms/kg-1hr-1 being the maximal dose. To ascertain that the response was not osmotic in association with FK506 secretion in bile, 500 micrograms/kg-1hr-1 FK506 was administered, which did not produce a choleresis significantly greater than 8 micrograms/kg-1hr-1. FK506 was subsequently administered orally in daily dose of 0.15 mg/kg-1 for two weeks. Oral FK506 did not consistently increase bile flow, as evaluated by a bile salt dose-response curve (9, 18, 36 mumol/min sodium taurocholate) but did significantly increase bile chloride secretion. Two weeks of oral administration of FK506 in therapeutic doses did not significantly alter serum bile salt concentrations. The results of this study indicate that intravenous FK506 produces a chloride-rich choleresis in dogs.

Animals↗
PubMed1993

The relationship of physical fitness to lipid and lipoprotein(a) levels in adolescents with IDDM.

OBJECTIVE--Increased physical activity and physical fitness are recommended therapeutic modalities in addition to insulin and diet in the management of children with IDDM. The aim of this study was to assess the fitness levels of adolescents with IDDM compared with healthy control subjects and to evaluate the relationship between physical fitness and metabolic control. RESEARCH DESIGN AND METHODS--We studied 59 patients with IDDM, 28 boys and 31 girls, age 15.6 +/- 2.5 yr, duration of diabetes 7.6 +/- 3.5 yr, HbA1 10.6 +/- 2.1% (mean +/- SD), and compared them with 18 healthy, nondiabetic control subjects, 9 boys and 9 girls, matched for age, BMI, and Tanner stage. Physical fitness was measured by VO2max during progressive bicycle ergometry. HbA1 was used to determine glycemic control. Lipid profile included fasting total cholesterol, HDL, LDL, Lp(a), and TG levels. RESULTS--Patients with IDDM had lower VO2max levels than control subjects (33.7 +/- 7.0 vs. 41.0 +/- 10.4 ml.kg-1.min-1, P = 0.001). Males with IDDM had lower VO2max than male control subjects, but diabetic and control females showed no difference. In IDDM patients, VO2max correlated inversely with HbA1, insulin dose, cholesterol, LDL, TGs, and Lp(a), but did not correlate with HDL, which correlated inversely with BMI. CONCLUSIONS--We conclude that the state of physical fitness is an important correlate of lipid levels and Lp(a) in adolescents with IDDM. We speculate that higher physical fitness levels in adolescents with IDDM may decrease the risk of CVD through modulating lipid levels.

Adolescent↗
PubMed1992

Delivery of passivating proteins to sutures during passage through the vessel wall reduces subsequent platelet deposition by blocking fibrinogen adsorption.

Intraluminal vascular suture material, which attracts fewer than the expected number of platelets compared with the same biomaterial exposed to blood in vitro, differs from the untreated biomaterial in that it has been passed once through the vessel wall. The mechanism by which this apparently trivial maneuver reduces platelet deposition was investigated. Polypropylene suture (7-0 Prolene) was passed through human arteries (fetal and adult), and platelet deposition to the suture was measured in a standardized perfusion chamber. Single vessel passage of the sutures reduced platelet deposition by 68 +/- 23%, which contrasts sharply with the power of prostaglandin E1 (1 microM PGE1 is sufficient to abolish platelet shape change and aggregation), which inhibited only 11% of platelet deposition to the sutures. Aspirin treatment of the vessel (to prevent PGI2 formation) or endothelial stripping (to remove the ability to produce nitric oxide) had no effect on the degree of inhibition. Passage of the suture through a vessel analogue (expanded polytetrafluoroethylene) did not inhibit platelet deposition. 125I-fibrinogen adsorption to the suture after vessel passage was reduced to a degree similar to that of platelet deposition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins eluted from vessel-passed sutures revealed bands at 66, 47, and 16 kd. Western blotting indicated the presence of large amounts of albumin and hemoglobin, a moderate amount of haptoglobin, and only trace amounts of fibrinogen. When sutures were exposed to each of these proteins in vitro before perfusion, albumin and hemoglobin were found to reproduce the effect of vessel passage alone on platelet deposition. We conclude that albumin and hemoglobin adsorb to sutures during their passage through the vessel subendothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1990

Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary cirrhosis.

The purpose of this study was to determine the prevalence of vitamin E deficiency in adults with chronic cholestatic liver disease and to quantify the association between their psychomotor performance and vitamin E status. In 42 female patients with primary biliary cirrhosis, 43.5% met two standard criteria for vitamin E deficiency. Vitamin E-deficient patients performed less well than did healthy control subjects on six of eight neuropsychologic tests of psychomotor capacity (p less than 0.01). Vitamin E-sufficient patients did not differ significantly from normal control subjects. Serum vitamin E concentrations were significantly lower in the group classified as significantly psychomotor-impaired by two independent neuropsychologists (blind to vitamin E status) whereas liver-injury measures failed to distinguish between these two groups. Patients with low serum vitamin E exhibited clinically evident neurologic abnormalities. These data suggest that vitamin E deficiency may, in part, underlie psychomotor and neurologic disturbance found in adult patients with chronic cholestatic liver disease.

Adult↗