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Biomedical subjects

J G Turcotte

Publications and source records attributed to J G Turcotte.

At least 55 records · Page 3Linked to original sources

Analytical-scale high-performance liquid chromatography of omega-3 fatty acid esters derived from fish oils.

Fish oil triglycerides were transesterified to their corresponding methyl and ethyl esters. The esters were separated by reversed-phase high-performance liquid chromatography on a 10-cm column of 5-microns octadecylsilyl silica, using a ternary mobile phase of acetonitrile-tetrahydrofuran-water (9:5:11). The separation of principal saturated and unsaturated C14-C22 fatty acid esters was accomplished in 60 min. For the polyenoic acid esters, detection limits of ca. 26 micrograms were observed, and baseline resolution of the important critical pair of esters of the omega 3 fatty acids, eicosapentaenoic acid (C20:5 omega 3) and docosahexaenoic acid (C22:6 omega 3) was achieved. However, to obtain baseline resolution of the esters from minor fatty acid esters, a urea crystallization procedure was required prior to chromatographic analysis. The influence on the reversed-phase chromatographic retention of four different ester moieties on the fatty acids were also studied. The n-alkyl esters exhibited an increase in ln k' with increasing chain length and with increasing lipophilic character of the alkyl ester moieties; however, with the aromatic benzyl derivatives there was a decrease in ln k' compared with the alkyl esters.

Chromatography, High Pressure Liquid↗

Amelioration of chronic renal allograft dysfunction in cyclosporine-treated patients by addition of azathioprine.

Management of chronic renal allograft dysfunction in cyclosporine-prednisone treated renal allograft recipients remains problematic. We therefore initiated a protocol of azathioprine addition (1.0-1.5 mg/kg/day) to ongoing CsA/Pred therapy. Three groups were treated. Group A (n = 21) had chronic progressive renal dysfunction (serum creatinine greater than or equal to 2.5 mg/dl or more than 15% above baseline) four or more months after transplantation. Group B (n = 8) had frequent or severe rejection episodes occurring despite adequate CsA levels. Group C (n = 7) had constitutional side effects of CsA with or without renal dysfunction persisting despite drug taper or financial difficulty in affording CsA. Aza was initiated 17.8 +/- 2.8 months after transplantation in group A, the mean serum creatinine having risen from 2.55 +/- 27 mg/dl to 3.04 +/- .20 mg/dl (P = .07) over the six months preceding Aza initiation, despite stable and low therapeutic range HPLC whole-blood CsA levels (118 +/- 10 ng/ml vs. 133 +/- 11 ng/ml, P = NS). Renal function declined at a rate of -0.20 +/- .06 Cr1/year in the six-month period before addition of Aza, and then improved at a rate of 0.09 +/- .04 Cr-1/year after addition of Aza (P = .002). These changes in renal function occurred without a decrease in CsA levels (118 +/- 10 six months before Aza vs. 126 +/- 26 six months after Aza, P = NS). In group B Aza was initiated at 58 +/- 8 days after transplantation when mean sCr was 3.56 +/- .29 mg/dl and mean CsA level was 222 +/- 17 ng/ml. At least follow-up 12.7 +/- 2.0 months after addition of Aza, all group B grafts were functioning, mean sCr was 2.69 +/- .31 mg/dl (P = .09 compared with baseline), and mean CsA level was 128 +/- 34 ng/ml (P = .07 compared with baseline). Group C patients had addition of Aza at 43 +/- 19 months after transplantation when mean sCr was 2.97 +/- .60 and mean CsA level was 125 +/- 30 ng/ml; addition of Aza had no influence on the rate of decline in renal function in this group. Of these 36 patients, 6 received therapy for acute rejection over the entire follow-up period of 12.3 +/- 1.4 months after addition of Aza; 4 of these retain graft function. Infectious complications consisted of 2 urinary tract infections, 1 bacterial pneumonia, and one case of otitis media.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

No improvement of pancreas transplant endocrine function by exogenous insulin infusion (islet rest) in the postoperative period.

The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n = 8) received constant insulin infusion for 7 days after transplantation; the control group (n = 5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27 +/- 0.04 ng/ml) as compared to the control group (0.66 +/- 0.08 ng/ml) (P less than 0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were -1.79 and -1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

Animals↗

The hepatic artery in liver transplantation.

Hepatic artery complications after liver transplantation are uncommon, but represent an important cause of morbidity and mortality. In addition, these complications tax an already limited supply of donor organs because of the frequent need for retransplantation in this group of patients. In this study, we examined the incidence of hepatic arterial anomalies in donors and recipients of orthotopic liver transplants, focusing on the techniques that are available for hepatic arterial reconstruction and on the occurrence of hepatic arterial complications. A total of 77 liver transplants were carried out in 68 patients. Standard recipient anatomy was present in 60 of 68 patients (88%). Anomalous vessels were identified in eight patients (12%), including six cases of replaced right hepatic artery (9%) and two cases of replaced left hepatic artery (3%). Donor liver arterial anatomy was standard in 62 cases (80%). Anomalous arterial supply was identified in 15 of 77 donor livers (20%), including replaced left hepatic artery in nine (12%) and replaced right hepatic artery in six (8%). A variety of methods were used to manage the anomalous vessels. There was one hepatic artery pseudoaneurysm, three cases of hepatic artery thrombosis (4%), and one patient developed a dissection of the native celiac axis. In primary transplants, utilization of the recipient's proper hepatic artery was associated with a significantly higher risk of hepatic artery thrombosis (P less than 0.04) when compared with the common hepatic artery or the branch patch technique. Use of a Carrel patch on the donor artery was associated with a significantly reduced incidence of hepatic artery thrombosis (P less than 0.0003). For retransplantation, it is recommended that a more proximal recipient anastomotic site be chosen. An innovative method is described that provides increased length of the donor arterial supply without the use of an arterial graft.

Hepatic Artery↗

Liver transplantation at the University of Michigan.

Liver transplantation is a highly successful therapy for liver diseases that were previously debilitating and often fatal within a few months. One-year actuarial patient survival for our first 162 patients is 74.7%. Our results have improved since the inception of the program despite the fact that the indications have been extended to higher risk patients such as those with fulminating hepatitis or thrombosed portal veins. The prognosis following transplantation for each specific indication needs to be defined, especially for hepatitis, alcoholic cirrhosis and individual cancers. We believe that a more conservative approach to immunosuppression, close attention to intravenous and enteral nutrition, and aggressive treatment of complications (including prompt reoperation when indicated) have been important improvements in our management practices.

Adolescent↗

Pancreas transplantation: an immunohistochemical analysis of pancreatic hormones and HLA-DR expression.

The immunohistochemical features of pancreatic grafts in eight patients with pancreatic transplants were analyzed and compared with pancreases from five patients with chronic pancreatitis and with three pancreatic tissues without histological abnormalities. There was a significant increase in glucagon producing cells in patients with transplanted pancreases compared with those with chronic pancreatitis (P less than 0.05). A significant decline in insulin-producing cells was seen in the transplanted pancreases with rejection in comparison with normal pancreatic tissue. Immunohistochemical staining for HLA-DR (Ia) antigens revealed expression of HLA-DR by endothelial cells, mononuclear cells, and by some ductal epithelial cells, but not by the endocrine islet cells. These results suggest that significant changes in insulin and glucagon production occur in the transplanted pancreas with rejection and that HLA-DR is not expressed by islet cells during graft rejection or with chronic inflammation.

Adult↗

Operative timing and patient survival following distal splenorenal shunt.

The importance of "operative timing" in cirrhotic patients with variceal hemorrhage is often underemphasized. To evaluate the effects of immediate versus delayed selective portasystemic decompression on hepatic function, operative mortality, and long-term patient survival, we reviewed the records of 77 patients who underwent distal splenorenal shunts (DSRS) over a 14-year period. A hepatic risk status score was calculated at the time of the index bleed (HRS1) or presentation and again just prior to operation (HRS2). Variables analyzed included age, sex, prior bleeding episodes, time from index bleed to operation, transfusion requirements, and etiology of cirrhosis. Operative mortality rates for immediate versus delayed DSRS were 46.2 per cent and 17 per cent, respectively. HRS improved significantly in elective DSRS patients from 1.46 to 1.30. Predictors of HRS2 included HRS1 and time in days from the index bleed to operation. The most important predictor of early survival for all patients after elective DSRS was the HRS2; however, for patients who underwent elective DSRS and survived, HRS1 was a better predictor of length of survival than HRS2. No other variable analyzed accurately predicted survival. We conclude that HRS can be expected to improve with supportive inhospital therapy; improved HRS at the time of operation is associated with decreased operative mortality; and the extent of liver disease as determined by HRS1 appears to be the chief determinant of long-term patient survival.

Female↗

Bile refeeding after liver transplantation and avoidance of intravenous cyclosporine.

Because absorption of cyclosporine (CyA) given orally immediately after liver transplantation is unreliable, the drug is usually given intravenously until external biliary drainage is discontinued. Intravenous CyA, however, is associated with serious side effects, making its use potentially hazardous. We report the results of a new strategy in which we used oral CyA exclusively and refed bile to enhance oral CyA absorption. Thirty-two liver transplant recipients with indwelling T tubes were studied. All were given sequential quadruple drug immunosuppression with antilymphoblast globulin, azathioprine, and steroids. Oral CyA and refeeding of bile was started when renal function was stable. By the second posttransplant week, satisfactory CyA levels were achieved, and antilymphoblast globulin therapy was stopped. There were significant associations between oral CyA dose and CyA level and between quantity of refed bile and CyA level (p less than 0.001). CyA dose and quantity of bile refed were covariates, however, and in multiple regression analysis, only the quantity of refed bile was significant (p = 0.001). CyA levels did not correlate with rejection. The incidence of rejection was 63%. At a mean follow-up of 9 months, 28/32 (88%) patients were alive, and actuarial 1-year patient survival was 84%. Current graft and renal function are excellent (serum bilirubin, 1.0 +/- 0.1 mg/dl; serum creatinine, 1.2 +/- 0.1 mg/dl). We conclude that intravenous CyA can be avoided in virtually all liver-transplant recipients by administration of oral CyA with bile in the early posttransplant period.

Administration, Oral↗

Preparative-scale high-performance liquid chromatography of omega-3 polyunsaturated fatty acid esters derived from fish oil.

Marine triglyceride-derived omega-3 polyunsaturated fatty acid ethyl esters were separated by preparative high-performance liquid chromatography on a 25-microns octadecyl stationary phase using a ternary isocratic mobile phase of acetonitrile-tetrahydrofuran-water (466:233:300, v/v/v). The highest purity first-run fractions obtained were ethyl esters of the major marine polyunsaturates eicosapentaenoic acid (20:5 omega 3, 97.7%) and docosahexaenoic acid (22:6 omega 3, 93.7%), and the minor polyunsaturate octadecatetraenoic acid (18:4 omega 3, 98.1%).

Chromatography, Gas↗

Preparation of islets of Langerhans from the hamster pancreas.

We describe a method for the preparation of viable islets from the pancreas of normal 8-week-old female Syrian golden hamster, based on the injection of the pancreatic duct with collagenase and on mechanical dissociation which liberates islets that maintain their normal morphological appearance and physiologic function. In a series of 11 animals, we examined the dose response of intraductal collagenase on islet yield. The mean number of isolated islets was 423 with a range from 130 to 873 per pancreas. Islet yield was most dependent on the concentration of collagenase solution used to inject the duct. The optimal concentration was determined to be 3.5 mg/ml when a total volume of 3.0 ml was injected. Islets responded to glucose stimulus in a normal biphasic pattern. Mesh filtration, rather than Ficoll, can be performed rapidly and results in a high yield of functional islets with minimal contamination by acinar tissue.

Animals↗

Peripheral blood catalase in patients undergoing renal transplantation.

Oxygen free radicals are mediators of tissue injury and catalase is an enzyme which is involved in limiting this process. We examined peripheral blood catalase activity (PBCA) to assess its value as a marker in detecting tissue injury related to renal allograft rejection. Thirty-one consecutive recipients of kidney (n = 29) or simultaneous kidney/pancreas (n = 2) transplants and 10 normal volunteers were studied. Catalase activity, measured by the disk-flotation method, was expressed as Sigma units X 10(-3)/ml (SU/ml) of whole blood. Normal PBCA was determined to be greater than 76 SU/ml. Twenty-nine episodes of renal allograft rejection (diagnosed by clinical criteria +/- biopsy [79%]) were observed in 26 patients. PBCA (mean +/- SEM) was found to be low (64 +/- 1 SU/ml) in 28/29 episodes (chi 2 = 46.3, P less than 0.001), and the decrease (at least two consecutive daily catalase values less than 76 SU/ml) occurred 2 days prior to the clinical/biopsy diagnosis of rejection in 26/28 episodes. The sensitivity of PBCA as a discriminant of rejection was 97%, specificity was 96%, and test accuracy was 96%. PBCA less than 50 SU/ml on two or more occasions occurred in five cases and transplant nephrectomy was required in four of these because of uncontrollable rejection. Nine episodes of cyclosporine nephrotoxicity occurred in 7 patients and none of these episodes was associated with a decreased PBCA. Our data suggest that decreased PBCA is a sensitive and specific indicator of renal allograft rejection. PBCA remains normal during episodes of cyclosporine nephrotoxicity and therefore provides a rapid and inexpensive discriminant from allograft rejection.

Adolescent↗

Extravesical ureteroneocystostomy in renal transplantation.

From October 1970 to January 1986, 808 patients underwent renal transplant ureteroneocystostomy by an extravesical technique. Complications related to the anastomosis and/or ureter were reviewed. There were 23 total complications, for an over-all urological complication rate of 2.8 per cent. Of these complications 17 were related to the ureteroneocystostomy, for an anastomotic complication rate of 2.1 per cent. Complications were almost universally repaired by another operation. Two patients died and 1 lost the allograft because of urological complications.

Anastomosis, Surgical↗

Orthotopic liver transplantation totally corrects factor IX deficiency in hemophilia B.

Orthotopic liver transplantation has been performed for a growing range of liver-based inborn errors of metabolism. Previous authors have documented that liver transplantation can reverse the coagulation defect of hemophilia A. In this article we report total correction of factor IX deficiency in a patient with hemophilia B and blood product-related liver disease. Intraoperative bleeding was not excessive, and the donor liver produced normal amounts of factor IX immediately.

Adolescent↗