Biomedical subjects
Publications and source records attributed to L J Koep.
We present two cases of patients with coincidental pancreatic disease and abdominal aortic aneurysm. Initial pancreaticoduodenectomy was followed by staged abdominal aortic aneurysm repair via a retroperitoneal approach in both cases. We recommend the retroperitoneal approach over the transperitoneal approach as an easier and safer method of aortic aneurysmorrhaphy after the Whipple procedure.
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The ability to cryopreserve human liver slices would greatly enhance the opportunities to test potentially hepatotoxic drugs and environmental contaminants as well as the metabolism of these compounds. This study focused on trying to cryopreserve pig and human liver slices. Since the acquisition of human liver tissue is unpredictable and scarce, an animal model was sought to predict problems associated with cryopreservation of human tissue. The pig liver was chosen because of its anatomical and physiological resemblance to human liver. The human liver tissues that did become available were obtained through the Arizona Organ Bank and the National Disease Research Interchange and from surgical liver resections. An in vitro culture system that employed precision-cut liver slices was used in this study. Different types and concentrations of cryoprotectants, cooling rates, and culture media were all tried in an attempt to cryopreserve pig and human liver slices. The viabilities of fresh and cryopreserved liver slices were evaluated using slice K+ retention and protein synthesis. Pig liver slices following cryopreservation retained between 80 and 85% of intracellular K+ content and protein synthesis as compared to controls using 1.4 M Me2SO, a 12 degrees C/min cooling rate, and a rapid rewarming rate of direct submersion of the slice into 37 degrees C fetal calf serum. Human liver slices following cryopreservation retained between 54 and 89% of intracellular K+ content and protein synthesis as compared to controls using the same protocol as for pigs, except that lower cooling rates were giving better results. The large variation seen in cryopreserved human liver slices was due to the length of warm and cold ischemia to which the tissue was exposed before arriving at the laboratory. This study indicated that pig and human liver slices can be cryopreserved and used for future toxicological and metabolic studies.
Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K+ retention and Ca2+ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse much greater than induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat greater than pig = human.
Perineurial cell basement membrane (PCBM) thickening is a consistent feature in diabetes mellitus (DM) and may have relevance to the cause of DM neuropathy. In this ultrastructural morphometric study of identical twins discordant for DM, we found that the PCBM was significantly thicker in the dermal nerves of the diabetic twin. Following pancreas transplantation (PT) and a 2-year period of euglycemia, the PCBM in both dermal and sural nerves was significantly thinner. At the end of the 2nd year post-PT, the PCBM thickness in the dermal nerves of the diabetic was not significantly different from the non-DM twin. The correction of diabetic dysmetabolism may have played a role in the regression of PCBM. These data suggest that PCBM thickening may not be a permanent legacy of DM.
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Embryonal rhabdomyosarcoma of the bile ducts is associated with a poor prognosis because complete resection rarely is considered possible. We reviewed the literature and report our experience with the management of 3 consecutive patients. The patients were 1, 4, and 9 yr old at presentation, and had jaundice, cachexia, and an abdominal mass. The tumor arose in the common hepatic duct in 2 patients, and in the left hepatic duct in the other. All had tumor extension into both lobes of the liver and residual disease was noted after resection. Two patients were given tumor bed irradiation and all received multiple-drug chemotherapy. Two patients are alive, jaundice free, and with no evidence of disease at 9 mo and 14 yr follow-up. The other patient was a long-term survivor, but developed local recurrent tumor after cessation of chemotherapy and expired 33 mo after diagnosis. The traditional anatomic criteria of hepatic tumor resectability may not apply to botryoid sarcoma of the bile ducts. Aggressive surgery combined with the new adjuvant therapies appears to provide the best chance for a longer survival.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Fifteen patients had hepatic hemangiomas removed with liver resections that ranged in extent from local excision to right trisegmentectomy. There was no mortality and little morbidity. The propriety and feasibility of extirpative treatment of such liver tumors has been emphasized by this experience.
Four renal isografts have been performed and all have had satisfactory function for 7 1/2 to 17 2/3 years without prophylactic or therapeutic immunosuppression. Three of these patients originally had glomerulonephritis, and in one there was histologic evidence of recurrent disease, 7 1/2 years after transplantation, without proteinura and without change in renal function. Although this experience is small, it suggests that prophylactic immunosuppression is not appropriate for recipients of renal isografts.
Imaging of diffuse liver disease is traditionally done with Tc-99m-sulfur colloid. The advent of Tc-99m-labeled hepatobiliary agents led the authors to reevaluate the role of Tc-99m-sulfur colloid. A total of 95 paired Tc-99m-diethyl-IDA and Tc-99m-sulfur colloid studies were performed in 61 patients (60 paired studies in liver transplant patients and 35 paired studies patients who had not received liver transplants). The following parameters were visually graded on a five-point scale: Tc-99m-diethyl-IDA clearance and time of appearance of appearance of intestinal activity; and Tc-99m-sulfur colloid liver size, bone marrow activity, splenic size, splenic activity, lung activity. Total serum bilirubin levels were used as the standard measure of liver function. The Tc-99m-diethyl-IDA parameters correlated more highly with total serum bilirubin than did the Tc-99m-sulfur colloid parameters in both the transplant and nontransplant groups. In conclusion, Tc-99m-diethyl-IDA appears to be the preferred radiopharmaceutical for evaluation of hepatocellular function, although both agents may be needed in certain clinical situations.
Tc-99m-diethyl-IDA imaging demonstrated intrahepatic bile leaks in two patients. The first patient had an intrahepatic abscess associated with a common bile duct stone; he was successfully treated with common duct lithotomy and antibiotics, but without surgical drainage of the intrahepatic abscess. The second patient had bile leakage into an intrahepatic cavitary hematoma after abdominal trauma.
Fifteen patients with a wide range of hepatobiliary function were studied with both 99mTc-diethyl-IDA and 99mTc-PIPIDA. In images obtained 5 to 60 minutes after injection, 99mTc-diethyl-IDA was clearly superior with respect to liver/background, hepatic ducts/liver, and small bowel/background ratios. The 99mTc-diethyl-IDA transit time from blood to small intestine averaged 12.2 minutes less than that of 99mTc-PIPIDA. Quantification of relative hepatocyte extraction efficiency indicated that it was 2.15 times higher for 99mTc-diethyl-IDA. Cumulative 3-hour urine collections following injection demonstrated increasing renal excretion of 99mTc-PIPIDA with rising total serum bilirubin levels in a manner quantitatively similar to that determined previously for 99mTc-diethyl-IDA. The authors conclude that 99mTc-diethyl-IDA is superior to 99mTc-PIPIDA for studies of the hepatobiliary system.
Eighteen patients were treated with primary cadaveric renal transplantation using cyclosporin A therapy, and four more patients undersent cadaveric retransplantation. Eleven of the 22 recipients were conditioned with lymphoid depletion before transplantation, using thoracic duct drainage or lymphapheresis for two to eight and one-half weeks. Cyclosporin A was begun a few hours before grafting. The other 11 patients were pretreated with cyclosporin A for from one day to 18 days. After transplantation, the majority of patients in both subgroups of 11 had rejection develop, but in most, the immunologic process was readily controlled with relatively small dosages of prednisone. After follow-up periods of two to four and one-half months, one patient has died of the complications of a coronary artery reconstruction that was not related to the transplantation. Another graft was lost from rejection, and a third organ was removed because of ureteral necrosis. Nineteen of the original 22 cadaveric kidneys are functioning, including 17 of the 18 kidneys given to patients who were undergoing transplantation for the first time. The only loss in the latter group of 18 patients was in the patient who died after an open heart operation. Results of these studies have shown that cyclosporin A is a superior and safe immunosuppressive drug but that, for optimal use in cadaveric transplantation, it usually should not be given alone. Steroid therapy greatly amplified the value of cyclosporin A. Unless major delayed morbidity develops which is not obvious so far, this drug combination should permit revolutionary advances in the transplantation of all organs. Other adjuncts to the cyclosporin A-steroid combination, including lymphoid depletion techniques, will require further investigation.
Prolonged thoracic duct drainage as an immunosuppressive adjunct was accomplished in 96 per cent of organ recipients upon whom it was attempted.