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Biomedical subjects

J G Turcotte

Publications and source records attributed to J G Turcotte.

At least 19 recordsLinked to original sources
PubMed1992

Isolation of experimental anti-AIDS glycerophospholipids by micro-preparative reversed-phase high-performance liquid chromatography.

The experimental anti-AIDS glycerophosphatidic acid: nucleoside (sn-1/sn-2 diacylglycerol:dideoxynucleotide) drugs 3'-azido-3'-deoxythymidine monophosphate diglyceride (AZT-MP-DG) and 2',3'-dideoxycytidine monophosphate diglyceride (ddC-MP-DG) were isolated and purified by reversed-phase high-performance liquid chromatography (HPLC). The chromatographic separation was based on the glycerophospholipid moiety of the drugs and detection of the nucleoside component. The separations were optimized on method development columns packed with the stationary phase to be used in the micro-preparative column and monitored by a UV detector. Fractions were collected and analyzed for purity by analytical-scale HPLC and by thin-layer chromatography (TLC). The purity of the recovered drugs based on UV and light-scattering detection and on TLC was greater than 99%. The purified compounds were isolated for studies on structure confirmation, physical, biophysical and formulation properties and anti-HIV efficacy in culture.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Resource utilization and outcome of liver transplantation for alcoholic cirrhosis. A case-control study.

Liver transplantation for alcoholic cirrhosis remains controversial at some transplantation centers. We compared resource utilization and outcome in alcoholic and nonalcoholic cirrhotic patients undergoing liver transplantation. Data were collected from 56 patients who underwent transplantation for alcohol-related cirrhosis from August 1985 to February 1991 and compared with data from a control group matched for age, sex, Child-Pugh class, and date of transplantation. No significant differences were noted in the resource utilization variables examined or in outcome (as assessed by indicators of early graft function, frequency of sepsis, incidence of rejection, renal function, and retransplantation rate). One-year survival was not significantly different (75% for the alcoholic cirrhotic group vs 76% for the nonalcoholic cirrhotic group). We conclude that liver transplantation for end-stage alcohol-related cirrhosis provides excellent results and that resource utilization appears to be equivalent to that for patients undergoing transplantation for non-alcohol-related cirrhosis.

Actuarial Analysis↗
PubMed1992

Biochemical and histopathological correlation in liver transplant: the first 180 days.

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Selection for and outcome of liver transplantation in alcoholic liver disease.

It has been proposed that evaluation of alcoholic patients for liver transplantation should comprise a multidisciplinary program including medical, surgical, and psychiatric assessment. This article presents the outcome in 99 alcoholic persons evaluated from 1985 through 1989. Alcoholism was defined as alcohol dependence or abuse according to the DSM-III-R. Forty-five patients (43%) were considered suitable candidates and underwent transplantation. Actuarial survival in this group was 78% and 73% at 12 and 24 months, respectively, and did not differ from that observed in nonalcoholic recipients. Return to alcohol use after transplantation has been documented in 5 persons, 2 of whom have had episodes of uncontrolled drinking. Of 54 patients not selected for transplantation, 17 were considered too well and suitable for alternative therapy. Actuarial survival was 93% at 12 and 18 months but declined to 59% at 24 months. Nineteen patients were medically unsuitable and had very poor survival; survival was 35% at 3 months and 0% at 12 months. Seventeen patients were not selected on psychiatric grounds. Actuarial survival in this group (65% at 12 months, 43% at 18 months) was significantly less than that in alcoholics with transplants (P less than 0.05). There were no differences in age, sex ratio, degree of hepatic dysfunction, or duration of abstinence between alcoholics with transplants and those considered psychiatrically unsuitable. It was concluded that liver transplantation is successful in selected patients with alcoholic cirrhosis, that patients who are not selected because they are "too well" need continuing surveillance as a significant decline in survival can occur 18-24 months after initial evaluation and, finally, that patients not selected on psychiatric grounds have a significantly worse survival rate than those with transplants.

Adolescent↗
PubMed1992

Preoperative risk factor assessment in liver transplantation.

BACKGROUND: Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS: We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS: The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS: These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.

Adult↗
PubMed1991

Chemical synthesis and surface activity of lung surfactant phospholipid analogs. II. Racemic N-substituted diether phosphonolipids.

A series of racemic 16:0 disaturated N-substituted diether phosphonolipid analogs of glycerophospholipids have been synthesized and purified. Isosteric methylene substitution at three of the four ester sites (carboxyl, phosphate) of conventional glycerophospholipids enhanced the hydrophobicity of analog compounds compared with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the nitrogen headgroup also contributed to hydrophobicity/hydrophilicity characteristics, as well as allowing graded variations in headgroup size among the members of the diether phosphonolipid analog series. Interfacial property studies showed that these compounds had significant differences in surface activity characteristics compared with DPPC, including increased adsorption and respreading facility, plus an enhanced ability to generate low surface tension (less than 1 to 4 mN/m) on an oscillating bubble apparatus at 37 degrees C. In addition, pressure-volume mechanical studies in surfactant-deficient excised rat lungs showed that the diether phosphonate analog of DPPC could partially restore pressure-volume characteristics toward normal, both as a pure component and in binary mixtures with palmitoyl-oleoyl phosphatidylglycerol. These findings suggest that selected analog compounds, synthesized with relatively small structural modifications from biologic glycerophospholipids, may have eventual applications as components of synthetic exogenous lung surfactants. Of more immediate importance, analog molecules with defined structural variations are convenient molecular probes for developing structure-surface activity correlates for phospholipid-like surfactants and for investigating the specificity of interactions between glycerophospholipids and other compounds such as proteins.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

High-performance liquid chromatographic analysis of 3'-azido-3'-deoxythymidine monophosphate diglyceride, an anti-HIV glycerophospholipid.

A reversed-phase chromatographic method is described for the analysis of an experimental anti-AIDS drug 3'-azido-3'-deoxythymidine monophosphate diglyceride (AZT-MP-DG) [J.M. Steim et al., Biochem. Biophys. Res. Commun. 171, 458-464 (1990)] [1], a phosphatidic acid derivative of AZT. Analytical conditions were based upon conventional separations of glycerophospholipid species. Where AZT-MP-DG was monitored by UV absorption, there were two wavelength maxima. The response was linear in the concentration range used in this study. The peak was characterized by absorbance ratios with a rapid scanning UV detector.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Liver transplant for fulminant hepatic failure.

Fulminant hepatic failure is a challenging indication for liver transplantation because of associated multiple organ failure, profound neurologic abnormalities and coagulopathy. Sixteen patients have undergone emergent orthotopic liver transplantation for this indication at the University of Michigan, Ann Arbor, Michigan. Despite the associated problems, patient survival (68.2% at 2 years), intra-operative blood product utilization and duration of surgery were comparable to patients receiving liver transplants for other indications. All patients experienced complete recovery from preoperative neurologic abnormalities. Recurrent viral hepatitis did occur but did not result in allograft loss. For selected patients, orthotopic liver transplantation is excellent therapy for patients presenting with fulminant hepatic failure.

Adolescent↗
PubMed1991

Obesity and renal transplantation.

In this study, we examined the influence of pre-existing obesity (weight more than 120 per cent of ideal body weight) on outcome after renal transplantation. Among 263 cyclosporine-treated recipients of renal allografts, 223 (85 per cent) were nonobese and 40 (15 per cent) were obese prior to transplantation. Obese and nonobese recipients were similar with regard to age, sex, renal diagnosis, history of prior transplant, donor source, pretransplant blood pressure, pretransplant antihypertensive agents, diabetic recipients with insulin requirements more than 40 units per day and pretransplant serum cholesterol. Duration of hospitalization was similar (26 +/- 25 versus 25 +/- 14 days; p = NS). There was a significantly higher incidence of wound infections in obese recipients (17.5 versus 6.3 per cent; p = 0.036); other complications occurred with similar incidence. Preoperative per cent of ideal body weight correlated with post-transplant weight gain during the first post-transplant year (p = 0.00002). After one year, obese recipients had gained 14.2 +/- 2.2 kilograms compared with 8.9 +/- 0.6 kilograms for nonobese patients (p = 0.002). Mean doses of prednisone, azathioprine and cyclosporine were similar at three, six and 12 months post-transplant. There were no differences in blood cyclosporine, serum cholesterol or blood glucose levels at any time. Blood pressure measurements were similar throughout the first post-transplant year. There was no difference in the incidence or number of rejection episodes. Actuarial patient survival rate for nonobese patients was 93 per cent at three years. For obese patients, three year actuarial patient survival rate was 90.5 per cent (p = NS). Actuarial graft survival rate among nonobese patients was 71.8 per cent at three years. For obese patients, three year actuarial graft survival rate was 64.5 per cent (p = NS). In conclusion, obese patients with end stage renal disease are good candidates for renal transplantation. Obesity does not seem to constitute a major risk factor, the most notable adverse outcomes being an increased incidence of wound infection and continued weight gain through the first post-transplant year.

Actuarial Analysis↗
PubMed1990

Isolation and purification of lecithin by preparative high-performance liquid chromatography.

Mixed-chain, multispecies, egg yolk-derived lecithin was isolated and purified on a silica column with isocratic elution. A method development column (20 x 0.46 cm I.D.) packed with YMC 15-30 microns, 120 A spherical silica and a mobile phase consisting of 5 mM ammonium acetate in acetonitrile-2-propanol-methanol-water (80:13:5:12) was used to separate the lecithin from other phospholipids. The mobile phase conditions for the method development system was adopted for two types of preparative HPLC systems: a Separations Technology SepTech NovaPrep 5000 system with a 20 x 1.93 cm I.D. column and a ST/800A system with a 20 x 5.00 cm I.D. Annular Expansion (A/E) column. The maximum load was 50 microliters of crude solution (2 mg) for the method development column, 0.90 ml (35 mg) for the 20 x 1.93 cm I.D. column and 6.0 ml (240 mg) for the 20 x 5.00 cm I.D. A/E column. The flow-rates were 2, 35 and 235 ml/min, respectively. The fractions collected from the preparative systems were analyzed for purity by analytical-scale high-performance liquid chromatography and by thin-layer chromatography with selective detection with molybdenum blue for phospholipids and detection of all organic compounds by sulfuric acid. Purity of the recovered lecithin was greater than 99%.

Chromatography, High Pressure Liquid↗
PubMed1990

Lipid conjugates of antiretroviral agents. I. Azidothymidine-monophosphate-diglyceride: anti-HIV activity, physical properties, and interaction with plasma proteins.

3'-Azido-3'-deoxythymidine-5'-phosphate diglyceride (16:0/18:1 omega 9), a phosphatic acid conjugate of AZT, is active against HIV replication in H9 cells and syncytia formation in MOLT-3 cells. The activities rank as AZT greater than pure conjugate greater than conjugate in mixed liposomes, with the pure conjugate having about one-third the activity of free AZT. The compound binds very rapidly to serum lipoproteins, but not to serum albumin, alpha and beta globulins, or red cells. Pancreatic phospholipase A2 hydrolyzes it to the lysophosphatidic acid conjugate.

Antiviral Agents↗
PubMed1990

Lipid conjugates of antiretroviral agents. II. Disodium palmityl phosphonoformate: anti-HIV activity, physical properties, and interaction with plasma proteins.

Disodium palmityl phosphonoformate, a novel lipid phosphoester of the anti HIV agent phosphonoformate (foscarnet), inhibits HIV replication in H9 cells and syncytia formation in MOLT-3 cells as effectively as foscarnet itself, as shown by dose-response data from assays for expression of p17 and p24 viral antigens and syncytia formation. Protein binding studies indicate that in serum, the derivative exists bound to albumin and the lipoproteins, and would therefore be likely to exhibit improved serum lifetime in vivo.

Antiviral Agents↗
PubMed1990

Preparative-scale high-performance liquid chromatographic separation and purification of 3'-azido-3'-deoxythymidine-5'-phosphate.

Crude 3'-azido-3'-deoxythymidine-5'-phosphate (AZT-P), obtained from direct phosphorylation of 3'-azido-3'-deoxythymidine (azidothymidine, AZT), was separated and purified by isocratic preparative high-performance liquid chromatography. The components in a 2.5-g load of crude AZT-P, obtained from work-up of the phosphorylation reaction, were separated in 50 min to give 1.8 g of 99.5% pure AZT-P. AZT-P was analyzed by high-performance liquid chromatography and by high-resolution nuclear magnetic resonance (1H, 13C, 31P) spectroscopy. The practical and rapid preparative chromatographic method is being applied to the purification of AZT-P and other antiretroviral dideoxynucleotides, used as intermediates in the synthesis of target-directed experimental drugs for the treatment of AIDS.

Chromatography, High Pressure Liquid↗
PubMed1990

A prospective controlled trial of cold-storage versus machine-perfusion preservation in cadaveric renal transplantation.

A prospective controlled study was carried out in 60 consecutive cadaver renal donors comparing cold storage to pulsatile machine-perfusion preservation. Each donor served as its own control, by allocating one of the kidneys to each of the two preservation methods. There were 51 evaluable pairs of kidneys. Recipient age, panel-reactive antibody level, history of prior renal transplant, and immunosuppressive regimen were similar in the two preservation groups. Almost all recipients were treated with cyclosporine, and over 50% received antilymphoblast globulin. Total cold ischemic time was 1262 +/- 387 min in the machine-perfused group and 1309 +/- 426 min in the cold-storage group (P = NS). Prolonged ischemia (greater than 24 hr) occurred in 31% of machine-perfused and 22% of cold-stored kidneys (P = NS). Post-operative serum creatinine levels at 1, 7, and 30 days posttransplant were similar in both groups. Dialysis requirements were also similar, with 21 recipients of machine-perfused kidneys (41%) requiring at least one dialysis treatment compared to 16 patients (31%) in the cold-stored group (P = NS); the mean number of dialysis treatments required was 3.14 +/- 1.46 and 3.06 +/- 1.29, respectively (P = NS). Long ischemic time (greater than 24 hr) was associated with a higher rate of dialysis requirement in both groups, but in neither case did this achieve statistical significance. The distribution of graft losses within the first 30 days was similar in both groups, and the incidence of preservation-related graft failure was not significantly different. These results demonstrate that, in the cyclosporine era, machine perfusion offers no significant advantages over cold storage for cadaver renal preservation. Because machine perfusion is considerably more expensive and cold storage is simpler and facilitates the logistics of organ sharing, we recommend simple hypothermic storage of renal allografts as the preservation method of choice.

Analysis of Variance↗