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J G Turcotte

Publications and source records attributed to J G Turcotte.

At least 19 recordsLinked to original sources
PubMed1997

A diether phosphonolipid surfactant analog, DEPN-8, is resistant to phospholipase-C cleavage.

Increased activities of phospholipase A2 and C (PLC) have been observed in the bronchoalveolar lavages of patients with adult respiratory distress syndrome (ARDS). DL-alpha-Di-O-hexadecylphosphonocholine [(R)(S)-DEPN-8], a surfactant analog of superior surface activity to the major lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), is not a substrate for phospholipases A1, A2 and D, but is a substrate for PLC. (R)(S)-DEPN-8 was found in vitro to undergo significantly less PLC-catalyzed degradation as compared to DPPC. The results suggest that (R)(S)-DEPN-8 and structurally related analogs may be useful as components of exogenous replacement surfactant formulations for the treatment of ARDS-related lung injuries.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Restoration of lung compliance with calf lung surfactant extract and a surfactant analog in an in situ model of surfactant deficiency in rats.

We have developed a standardized in situ lung surfactant deficiency model in the rat by using a single bronchoalveolar lavage (BAL). The purpose of this study was to assess the usefulness of surfactants and surfactant analogs in terms of their in vivo physiological properties. Calf lung surfactant extract (CLSE) was shown to improve lung compliance in a dose-dependent manner in this surfactant deficiency model when administered intratracheally immediately after BAL. In addition, CLSE formulated with a diether (palmityl) phosphonolipid surfactant analog significantly improved the compliance post-BAL as compared to CLSE alone. We propose that this in situ bioassay may be useful for the assessment of physiological capabilities of surfactants, surfactant analogs and surfactant formulations.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Update of the Adult and Pediatric Liver Transplant Program at the University of Michigan.

Significant technical innovations and improvements in immunosuppression have been introduced into our liver transplant program since its inception in 1985. The indications for transplantation have been extended to younger and older patients, and simultaneously more patients with comorbidities have been accepted for transplant. The net impact of these changes has been a continuing trend toward improved survival. Overall, patients with hepatitis B or malignancy have had poor survival rates. The introduction of prophylactic anti-hepatitis B immunoglobulin and lamivudine, and better selection of patients with malignancy may improve results for these patients in the future. As in other programs, our most vexing problem is the continuing scarcity of donor organs which has led to an ever-expanding waiting list, more deaths while awaiting transplant, and more suffering before transplantation. The introduction of living donor hepatic transplantation will be of some help in alleviating this shortage. We are confident that the evolution of our program into a joint multidisciplinary structure will provide more efficient, convenient and cost-effective care to our patients.

Adolescent↗
PubMed1995

Corticosteroid withdrawal after liver transplantation.

BACKGROUND: Long-term side effects of corticosteroids (CSs) result in > major morbidity for recipients of orthotopic liver transplants (OLT). We instituted a program of CS withdrawal among OLT recipients to quantify the contribution of CS to adverse clinical sequelae and to determine whether long-term CS administration is necessary to avoid rejection. METHODS: Recipients who had normal allograft function on CS, cyclosporine, and azathioprine more than 1 year after OLT were offered CS withdrawal during 12 to 22 weeks. Patients underwent routine clinical monitoring and laboratory studies. Continuous variables were compared by paired t test analysis. RESULTS: CSs were discontinued in 51 recipients; 45 (88%) of 51 patients remain steroid-free after a mean follow-up of 13.8 months (range, 4 to 36). CS therapy was reinstituted in 6 patients who had abnormal transaminase levels during routine follow-up. Among the patients who remain off CS, there were no significant changes in blood pressure, transaminase, alkaline phosphatase, bilirubin, or glucose levels during the study period. Mean number of blood pressure medications decreased from 0.7 +/- 0.1 to 0.4 +/- 0.1 (p = 0.007). Cholesterol decreased from 217 +/- 8 mg/dl on CS to 204 +/- 9 mg/dl at 1 month (p = 0.0001), 183 +/- 10 mg/dl at 3 months (p = 0.0001), 198 +/- 8 mg/dl at 6 months (p = 0.04), 213 +/- 11 mg/dl at 12 months (p = 0.01), 209 mg/dl +/- 16 at 18 months (p = 0.02), and 183 +/- 19 mg/dl at 24 months (p = 0.2) off CS. Weight loss occurred in 88% of patients and averaged 9.5 pounds. CONCLUSIONS: CS therapy can be successfully withdrawn without precipitating rejection in liver transplant recipients who have stable graft function 1 year after OLT. The incidence and severity of hypertension and hypercholesterolemia are reduced in patients whose CSs have been withdrawn.

Adrenal Cortex Hormones↗
PubMed1995

Bilayer characteristics of a diether phosphonolipid analog of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine.

Thermal and lyotropic phase behavior was studied by X-ray diffraction and differential scanning calorimetry for a diether phosphonolipid analog (DEPN-8) of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine (DPPC). DEPN-8 differs in an ether, rather than an ester, bond at the acyl chain-backbone linkage and a headgroup phosphonate (isosteric methylene substitution) versus phosphate constituent. Analysis of lamellar diffraction maxima demonstrated that at high relative humidity (98%) and temperatures below the liquid crystal phase transition (approximately 45 degrees C), DEPN-8 formed interdigitated bilayers with a characteristic periodicity of 41.9-46.5 A. At low humidity the gel phase DEPN-8 bilayers were characteristic of a normal L beta phase with a periodicity equivalent to DPPC (57-59 A). Above the liquid crystal thermal phase transition, bilayer spacing for both DEPN-8 and DPPC was 51-52 A, characteristic of the L alpha phase. Complete assessments of both lamellar and in-plane X-ray scattering used to construct electron density profiles and structure-factor plots for DEPN-8 defined more fully the interdigitated bilayer state at high humidity and low temperature. Compared to DPPC, it is energetically favorable for DEPN-8 to form interdigitated bilayers under conditions of excess water and low temperature. The flexible character of the ether bonds in DEPN-8 allows increased hydrophobic interactions between acyl chains, without generating a steric penalty from the increased packing density of the molecules. Additionally, the ether bond and the phosphonate moiety may allow for more energetically favorable interactions between the choline portion of the headgroup and water. The DEPN-8 ether linkage may also contribute to the improved adsorption and film respreading found previously for this phosphonolipid compared to DPPC.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

In vivo function of surfactants containing phosphatidylcholine analogs.

Increased phospholipase A2 activity demonstrated in some forms of lung injury may contribute to surfactant dysfunction. Phospholipase A2-resistant analogs of dipalmitoylphosphatidylcholine (DPPC) with surfactant properties might therefore be useful lipid components of treatment surfactants for certain lung injuries. The in vivo function of surfactants containing DPPC or the phospholipase-resistant analogs dihexadecylphosphatidylcholine (DEPC) or dihexadecylphosphonotidylcholine (DEPnC), with or without surfactant proteins B and C (SP-B+C), was thus evaluated in preterm rabbits (27 days' gestation). Rabbits randomly received one of seven surfactants (DPPC, DEPC, DEPnC, DPPC+SP-B+C, DEPC+SP-B+C, DEPnC+SP-B+C, or lipid extract surfactant [LES]) or 0.45% NaCl (control) and were ventilated for 30 min. Lipid-only surfactants decreased ventilatory pressures (peak inspiratory pressures minus positive end-expiratory pressure) relative to control (p < 0.05). Addition of SP-B+C further decreased ventilatory pressures to levels similar to LES (p < 0.01 versus control, lipid-only surfactants). Lung dynamic compliances and postventilation pressure-volume curves improved in the following order: LES, SP-B+C lipid surfactants > lipid-only surfactants > control (p < 0.05). All surfactant preparations decreased intravascular 125I-albumin recoveries in the lungs relative to control (p < 0.01 for all surfactants versus control). These results indicate that DEPC and DEPnC were as effective as DPPC as lipid components of synthetic surfactants. And like DPPC, the analogs interacted with isolated SP-B+C and improved in vivo function to levels comparable to LES.

Animals↗
PubMed1993

Aortic revascularization of orthotopic liver allografts: indications and long-term follow-up.

BACKGROUND: Occasionally because of certain conditions that would imperil arterial supply to a hepatic graft, it is necessary to base the arterial supply on the aorta. METHODS: Twenty orthotopic liver transplants (OLTs) in 19 patients were performed with arterial revascularization based on the aorta (Ao-OLT). In two patients the donor celiac axis was anastomosed directly to the aorta and in 18 to a conduit anastomosed to either the supraceliac (n = 10) or infrarenal (n = 8) aorta. RESULTS: One thrombosis occurred 2 months after the placement of a supraceliac conduit in an adult patients, accounting for a cumulative 1-year hepatic artery patency rate of 91.7% +/- 8.0% for 16 grafts placed in 15 adults and 100% for four grafts placed in four children. In comparison, hepatic artery-based transplantation was associated with a 1-year patency rate of 92.6% +/- 1.9% for 245 adults and 94.7% +/- 5.1% for 19 children (difference not significant compared with Ao-OLT). By logistic regression analysis, the only factor independently associated with hepatic artery thrombosis was retransplantation (1-year hepatic artery patency rate 85.7% +/- 5.9% [n = 38] for retransplants vs 93.9% +/- 1.7% for primary transplantation [n = 246]; p < 0.05). For retransplantation, Ao-OLT revascularizations were superior to those based on the hepatic artery (1-year patency rate 100% [n = 11] vs 79.9% +/- 8.1% [n = 27]; p < 0.05). CONCLUSIONS: Indications for Ao-OLT include poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, friable or attenuated native hepatic arteries as may be present during retransplantation, and recipient age less than 1 year, especially those less than 15 kg or in whom the recipient artery is less than 3 mm in diameter. In these more precarious situations, Ao-OLT achieves patency rates similar to those of primary, uncomplicated OLT, is superior for retransplantation, and has technical advantages in the small pediatric liver recipient.

Adolescent↗
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↗