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Biomedical subjects

H E Wahlstrom

Publications and source records attributed to H E Wahlstrom.

18 recordsLinked to original sources

Conventional care of fulminant hepatic failure: medical and surgical aspects.

Fulminant hepatic failure (FHF) is a clinical syndrome with a poor outcome. Survival rates are between 10% and 40% depending on the etiology of hepatic necrosis. Multiple supportive modalities have been tried to improve patient outcome. However, orthotopic liver transplantation has been shown to be the most effective therapy at improving survival. Management of these patients requires invasive monitoring, mechanical ventilation, and infection prophylaxis, all of which are conducted most efficiently in specialized units. The goal is to allow the native liver to regenerate and to prevent the development of complications while maintaining the patient in a condition suitable for orthotopic liver transplantation. Therapeutic plasma exchange improves survival in patients with sufficient residual capacity for regeneration. It is effective in restoring hemostasis, improving neurological function, and prolonging biochemical stability of patients awaiting liver transplantation. Hepatoprotective and hepatotrophic substances are still in the experimental stage. Auxiliary liver grafting and artificial liver support devices have proved to be an adjunct or a bridge to transplantation; however, they are not yet widely available.

Combined Modality Therapy↗

Nutritional support for liver transplantation: identifying caloric and protein requirements.

OBJECTIVE: To characterize the caloric and protein requirements of patients with end-stage liver disease before and for 28 days after liver transplantation. DESIGN: We prospectively assessed 16 adult patients who were scheduled to undergo liver transplantation between December 1989 and September 1990. MATERIAL AND METHODS: Nitrogen balance, 24-hour urinary creatinine, 3-methylhistidine, and resting energy expenditure were determined before transplantation and on days 1, 3, 5, 14, and 28 after transplantation. The investigators were unaware of the results of these measurements, and patients were fed in accordance with a previously established clinical protocol. RESULTS: Resting energy expenditure did not increase from preoperative values; however, urinary nitrogen and 3-methylhistidine increased significantly after liver transplantation, an indication of protein catabolism from a myofibrillar source. A negative nitrogen balance persisted for 28 days post-operatively. CONCLUSION: We recommend that caloric intake be determined by using the formulation provided by the Harris-Benedict equation at ideal body weight plus 20%. We also recommend that intake of protein be adjusted on the basis of preoperative nutritional assessment, perioperative hepatic and renal function, and results of tests used to measure the adequacy of administered protein. Parenterally or enterally administered protein of more than 1.2 g/kg daily should be well tolerated in most patients who have undergone liver transplantation.

Adult↗

Ischemic-type biliary complications after orthotopic liver transplantation.

Nonanastomotic biliary strictures that involve only the biliary tree of the graft occur after orthotopic liver transplantation in patients with hepatic artery thrombosis, chronic ductopenic rejection and ABO blood group incompatibility. This complication may also occur in the absence of these known risk factors. The major focus of our study was to evaluate the risk factors for nonanastomotic biliary stricturing of unknown cause after orthotopic liver transplantation. Results demonstrate that the development of biliary strictures is strongly associated with the duration of cold ischemic storage of allografts in both Euro-Collins solution and University of Wisconsin solution. Results also demonstrate that strictures are not associated with the type of biliary reconstruction, the primary liver disease, cytomegalovirus infection, allograft rejection or the presence of a positive lymphocytotoxic crossmatch. More recently, we have markedly reduced the occurrence of nonanastomotic biliary stricturing by decreasing the ischemia time of our allografts. Thus nonanastomotic biliary strictures appear to be the result of the ischemia/reperfusion-induced tissue injury associated with the harvest and implantation of allografts.

Adenosine↗

Papillary bile duct dysplasia in primary sclerosing cholangitis.

A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9-year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC.

Bile Ducts↗

Systemic and local toxicity in the rat of methyl tert-butyl ether: a gallstone dissolution agent.

Methyl tert-butyl ether (MTBE) is an organic solvent that has been used to dissolve gallstones via a percutaneous transhepatic catheter into the gallbladder. To test whether MTBE might cause serious tissue injury if accidentally infused outside the gallbladder, the effect of MTBE (0.2 ml/kg) injected into the hepatic parenchyma, or administered intravenously or intraperitoneally, was examined in the rat. The toxicity of isopropyl acetate (IPA), an organic solvent with a similar chemical structure, was examined similarly. Intracaval injection of MTBE caused the highest mortality (100%). Mortality was less (59%) after intrahepatic injection and still less (17%) after peripheral vein injection. Most animals died instantaneously from cardiorespiratory arrest. Almost all animals that were injected with MTBE intrahepatically or intravenously showed localized areas of congestion, hemorrhage, and interstitial edema in the lungs. These changes were more severe in rats which survived for 24 hr than in those which died sooner. In those rats receiving intrahepatic injections, most rats which survived for 24 hr had liver necrosis at the site of injection. Intraperitoneal injection of MTBE produced 100% survival with only 1/5 rats showing a mild pulmonary injury at autopsy. IPA had toxic effects similar to those evoked by MTBE. To test whether tumor necrosis factor was involved in organ injury, serum levels were measured; they remained unchanged. These experiments indicate that two organic solvents, MTBE and IPA, are cytotoxic to local tissues and cause severe, and often fatal, lung damage when infused into a central vein. Less toxicity occurred if solvents were given into a peripheral or portal vein or intraperitoneally.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Laparoscopic cholecystectomy: early Mayo Clinic experience.

Prospective data and follow-up information were collected on the initial 200 patients who underwent laparoscopic cholecystectomy at the Mayo Clinic. The operation was completed laparoscopically in all but five patients, who required conversion to laparotomy because of dense scarring or stones in the common bile duct. The median surgical time was 85 minutes. The major postoperative complications were retained stones in the common bile duct (in seven patients), intraperitoneal hemorrhage that necessitated transfusion (in two patients), and intra-abdominal abscess and pulmonary infection (in one patient each). The median hospital stay was 1 day (range, 0 to 8 days), and the median times to full activity and normal employment were 8 days and 12 days, respectively. Laparoscopic cholecystectomy is associated with a low frequency of complications in most patients with symptomatic gallstones and allows a rapid return to normal activity. Currently, laparoscopic cholecystectomy is the treatment of choice for most patients with symptomatic cholelithiasis.

Academic Medical Centers↗

Recovery and hypersecretion of insulin and reversal of insulin resistance after withdrawal of short-term cyclosporine treatment.

We have previously demonstrated decreased insulin release and insulin resistance in dogs treated with cyclosporine (20 mg/kg/day). In this study we examine the changes caused by a lower CsA dose and evaluate the reversal of these changes. Six animals were treated for 2 weeks with oral CsA (15 mg/kg/day), after which CsA was discontinued. Glucagon stimulation tests (GST) and euglycemic clamp studies (ECS) were used to evaluate changes in insulin release and insulin resistance. GST were performed before CsA, after 2 weeks of CsA, and 3, 9, and 15 days after discontinuing CsA. ECS were performed before CsA, after 2 weeks of CsA, and 2, 4, 8, and 14 days after discontinuing CsA. The mean serum CsA level after 2 weeks of treatment was 188 +/- 28 ng/ml. GST demonstrated decreased insulin release during CsA with recovery and hypersecretion after CsA withdrawal. ECS showed peripheral insulin resistance during CsA with a rapid recovery and a temporary increase in insulin sensitivity after CsA withdrawal. Comparisons were made with our previous study group given 20 mg/kg/day of CsA. In summary, CsA induces a dose-dependent impairment of glucose homeostasis due to inhibition of insulin release and development of peripheral insulin resistance. Withdrawal of short-term CsA at commonly used therapeutic doses results in reversal of and temporary overcompensation for these changes. CsA withdrawal after long-term treatment results in a slower normalization of the insulin response as compared with after short-term treatment. The hypersecretory reaction of the beta cell may be of help in further investigations of mechanisms of CsA- and FK506-induced inhibition of insulin release.

Animals↗

Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis.

In summary, we answer the three questions we have previously posed: (a) Can liver transplantation prolong survival? Evolving data from several centers indicate that liver transplantation indeed prolongs survival in patients with PBC and PSC as compared with estimated survival using disease-specific risk scores based on the natural history of PBC and PSC. (b) Can we optimize timing of liver transplantation? Although many factors enter into the timing of liver transplantation, including when the patient is actually referred for liver transplantation and the individual desires of the patient to pursue liver transplantation, evidence is growing that having patients with chronic liver diseases like PBC and PSC undergo transplantation a little earlier in the course of the disease rather than waiting until the patients have experienced life-threatening complications or are on life-support measures can indeed improve early postliver transplant survival. In patients with PBC and PSC, the survival risk score, which reflects disease severity, can serve as an objective measurement to assess and evaluate the effect of liver disease severity on transplant outcome. Indeed, a number of studies have strongly suggested that optimal timing of liver transplantation may indeed be important to improve outcome, decrease morbidity and decrease cost. (c) Does the present allocation system in the United States allow for optimal use of our scarce donor organ resource?(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangitis, Sclerosing↗

Inhibition of insulin release by cyclosporine and production of peripheral insulin resistance in the dog.

Cyclosporine has been shown to cause glucose intolerance in both humans and animals. This can result from alterations in insulin release, insulin metabolism, the sensitivity of peripheral or hepatic tissues to insulin, or a combination of these factors. The present study was designed to simultaneously evaluate the effect of CsA on these variables. A group of chronically catheterized dogs were administered oral CsA (20 mg/kg/day) for a period of 10 weeks. The glucagon stimulation test (GST) and the euglycemic glucose clamp technique, using a primed continuous infusion of 3H-3-glucose and a continuous insulin infusion (0.8 mU/kg/min), were employed to evaluate pancreatic insulin release, peripheral glucose disposal rate (Rd), hepatic glucose output (HGO), and metabolic clearance rate (MCR) of insulin. The dogs were tested before and after 2, 6, and 10 weeks of CsA administration. Serum CsA levels were 358 +/- 85, 244 +/- 48, and 355 +/- 81 ng/ml at 2, 6, and 10 weeks, respectively (P = NS). Elevated fasting glucose and an abnormal glucose response to an i.v. bolus of glucagon (0.25 U) were noted after 2, 6, and 10 weeks of CsA administration. The areas under the glucose curve (AUCG) for 0-60 min were 9605 +/- 773, 11634 +/- 1226, 12380 +/- 719, and 12626 +/- 1560 mg/min/dl at 0, 2, 6, and 10 weeks, P(F3, 15 = 5.1) = 0.012, demonstrating a CsA-induced disturbance of glucose homeostasis. The areas under the insulin curve (AUCI) for 0-20 min of the insulin response curve were 2033 +/- 203, 1089 +/- 187, 1038 +/- 179, and 972 +/- 161 uU/min/dl at 0, 2, 6, and 10 weeks, P(F3, 15 = 13.1) less than 0.001, indicating a 50% reduction during CsA treatment. CsA did not affect basal Rd, but peripheral insulin resistance was noted in the insulin-stimulated state. Rd during the third hour of the insulin infusion decreased from 6.72 +/- 0.69 to 4.42 +/- 0.44, 5.02 +/- 0.64, 4.47 +/- 0.52 mg/kg/min at 0, 2, 6, and 10 weeks, respectively, P(F3, 15 = 6.94) less than 0.004. HGO suppression by insulin and MCR of insulin were not altered by CsA. Similarly, glucagon secretion did not appear to be influenced by CsA. In conclusion, this study has simultaneously evaluated the effect of CsA on several aspects of glucose and insulin metabolism in the dog. CsA administration produces abnormal glucose homeostasis by reducing pancreatic insulin release, in addition to inducing peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A simple method of maintaining chronic vascular access in the dog.

Maintaining chronically indwelling catheters and avoiding destruction, dislodgement, or infection of the catheters is often a significant challenge for the investigator using large animals. A method is described that, in the hands of the authors, has provided long-term venous and arterial access with a low rate of malfunction and infection.

Animals↗

Aureobasidium pneumonia in a post liver transplant recipient: a case report.

This is the first report of Aureobasidium (A.) pullulans as an opportunistic pulmonary infection in a liver transplant recipient. A 46-year-old caucasian man had an orthotopic liver transplant in 1988. His liver disease was primary sclerosing cholangitis. He required 2 subsequent liver re-transplants for primary graft non-function and acute rejection. The patient had been living in the California desert for two months prior to admission and presented with ventilator-dependent acute respiratory failure and hemodialysis-dependent acute renal failure. Imaging studies revealed severe bilateral infiltrates. His initial bronchoalveolar lavage (BAL) and brushings grew A. pullulans. Pancultures, including sputum and throat cultures, were negative for bacterial or other fungal organisms. The patient responded to pulmonary support and aggressive systemic antifungal agents while being maintained on cyclosporine and prednisone for immunosuppression. He was discharged to a skilled nursing facility 37 days after hospitalisation. Delay in discharge was primarily due to severe malnutrition and renal impairment. Opportunistic fungal infections continue to be a major problem in immunosuppressed patients including liver transplant recipients. Here we report a pulmonary infection with Coccidioides (C.) immitis and superinfection with A. pullulans. Opportunistic infections such as A. pullulans can be treated successfully with systemic fluconazole when amphotericin B is not well tolerated.

Antifungal Agents↗