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Biomedical subjects

K A Porter

Publications and source records attributed to K A Porter.

At least 73 records · Page 4Linked to original sources

Liver allograft. Its use in chronic active hepatitis with macronodular cirrhosis, hepatitis B surface antigen.

A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HBsAg), was treated with an orthotopic liver allograft. The HBs antigenemia, as measured with several precipitation tests and by complement fixation, became negative after transplantation and remained so for about 2 1/2 months. During the interval, very low titers of the antigen were detectable by radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HBsAg became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1 1/2 years of her life. She died of disseminated nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic immunosuppression on the features of chronic active hepatitis.

Adult↗

Should the ruptured renal allograft be removed?

During a 16-month period when 93 renal transplants were performed, eight kidney graft ruptures were detected within 18 days of transplantation, without evidence of venous obstruction. Six grafts were removed at the time of an exploratory operation for rupture and only one showed signs of probable irreversible rejection when examined by microscopy. Two graft ruptures were repaired and one of these grafts has had good long-term function 22 months later. These observations suggest that if bleeding at the site of grafts has had good long-term function 22 months later. These observations suggest that if bleeding at the site of graft rupture can be securely controlled and if the conditions of the patient and of the graft are favorable except for the rupture, it may be possible to save more than one of eight grafts.

Adolescent↗

Liver transplantation--1978.

The development of liver transplantation has been made difficult because of the enormous technical difficulties of the procedure and because the postoperative management in early cases was defective in many instances. With surgical and medical improvements, the prospects for success have markedly increased recently. The wider use of thoracic duct fistula as an adjuvant measure during the first 1 or 2 postoperative months is being explored.

Age Factors↗

Fifteen years of clinical liver transplantation.

Liver transplantation in humans was first attempted more than 15 yr ago. The 1-yr survival has slowly improved until it has now reached about 50%. In our experience, 46 patients have lived for at least 1 yr, with the longest survival being 9 yr. The high acute mortality in early trials was due in many cases to technical and management errors and to the use of damaged organs. With elimination of such factors, survival increased. Further improvements will depend upon better immunosuppression. Orthotopic liver transplantation (liver replacement) is the preferred operation in most cases, but placement of an extra liver (auxiliary transplantation) may have a role under special circumstances.

Adolescent↗

Liver replacement for pediatric patients.

Between March 1963 and January 1978, 74 patients 18 years of age or younger have had liver replacements at the University of Colorado Medical Center, Denver. The most common cause of native liver failure was biliary atresis (48/74, 65%); the second most common cause was chronic aggressive hepatitis (12/74, 16%). Twenty-nine patients (39%) lived for at least one year, and 16 are still alive one to nine years after transplantation. Technical surgical problems, rejection, and infection were the main causes of death. Improved immunosuppression is needed; nevertheless, the quality of life in the long-term survivors has encouraged continuation of this difficult work.

Adolescent↗

The quality of life after liver transplantation.

The quality of life after liver transplantation ranges from poor to superior. The social and vocational outcome is dependent on the quality of homograft function and on the steroid doses necessary to maintain function. A good long-term prognosis is usually evident by 1 year postoperatively. The complete rehabilitation of so many patients has encouraged us to continue our efforts in this difficult field.

Adolescent↗

Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus.

Nine of 48 adult patients who underwent orthotopic liver transplantation developed significant clinical neurological abnormalities recognized shortly after operation. Decrease in consciousness occurred with resultant coma, focal and generalized seizures and the occasional appearance of a state of akinetic mutism. Neuropathological abnormalities consisted of multifocal areas of infarction in cerebral cortex and basal ganglia in five patients, central pontine myelinolysis in five (often more extensive than usually reported), Wernicke's encephalopathy in three, glial nodules in two, and fungal abscesses in one. Alzheimer II astrocytosis was found in all brains available for retrospective study. There was direct evidence in two of the patients that air embolization from the homografts had occurred. Correlation of this with the brain infarcts in these and other cases seems reasonable. The ease with which air passed to the systemic circulation is explicable by the right to left venous--arterial shunts that are common in chronic liver disease. With the delination of this cause for the neurologic complications, measures to prevent it in future cases have been described.

Adolescent↗

The effect upon the liver of evisceration with or without hormone replacement.

All, or nearly all, of the nonhepatic splanchnic viscera were removed in dogs. In most untreated dogs, the liver cells underwent changes similar to those caused by portacaval shunt, including structural deterioration of organelles and fatty metamorphosis. The rate of division of the hepatocytes, as measured by the mitotic index and by autoradiography, was depressed as were deoxyribonucleic acid synthesis and adenylate cyclase activity. These changes were restored to, or toward, normal with the intraportal administration of commercial or purified insulin but not with glucagon or epidermal growth factor. The results of both the pathologic and biochemical studies were consistent, except for an incongruity in some of the dogs in which the colon was retained.

Abdomen↗

The effect of splanchnic viscera removal upon canine liver regeneration.

The influence of portal blood factors on canine liver regeneration was studied with graded nonhepatic splanchnic evisceration, coupled with 44 and 72 per cent hepatectomies. In one type of experiment, the pancreas was retained while the rest of the intra-abdominal gastrointestinal tract was removed. In a second variety, total pancreatectomy was performed with preservation of the intra-abdominal organs. In a third kind of experiment, total nonhepatic splanchnic evisceration was performed. Liver regeneration after hepatectomy was decreased by all three kinds of viscera removed as judged by deoxyribonucleic acid synthesis, autoradiography and mitotic index. Pancreatectomy and nonpancreatic splanchnic evisceration caused almost equal decreases in the regenerative response. Total nonhepatic splanchnic evisceration essentially halted regeneration during the first three postoperative days and intraportal infusions of insulin or glucagon, or both together, did not reverse this effect. The decrease in liver membrane bound adenyl cyclase activity and biphasic change in liver cyclic 3', 5' -adenosine monophosphate concentrations normally seen after partial hepatectomy were disrupted after the various eviscerations. Adenyl cyclase activity and cyclic 3', 5' -adenosine monophosphate concentrations tended to be higher than normal in the eviscerated dogs. These observations provide more support for our previously proposed hypothesis that control of liver regeneration is by multiple factors. Pancreatic hormones are important modifiers of this response but, by no means, exercise exclusive control. Other substances of gastrointestinal origin, presumably including hormones and nutrient supply apparently play important specific roles. The volume of portal flow is a secondary and nonspecific, but possibly significant, factor.

Adenylyl Cyclases↗

Portacaval shunt for glycogen storage disease and hyperlipidaemia.

Complete portacaval shunt was used to treat 10 patients with glycogen storage disease. A favourable effect was noted on body growth and a number of metabolic abnormalities. More recently, continous night feedings with an intermittently placed gastric tube or through a gastrostomy has been shown to be helpful either before or after portacaval shunts. Such alimentation techniques may eliminate the need for shunts in some patients and be of adjuvant benefit in others. Portacaval shunt was also used for three children who had homozygous Type II hyperlipidaemia. Substantial reductions in serum cholesterol concentration were observed, as well as resorption of xanthomas. Reversal of some cardiovascular lesions has been documented. The benefits of portacaval shunt in these disorders is probably due to the change in the hormone climate of the liver and the whole organism brought about by diversion of the hormone-rich splanchnic venous blood around the liver.

Adolescent↗

A hundred years of the hepatotrophic controversy.

Venous blood returning from the splanchnic viscera has liver-supporting (hepatotrophic) qualities not found to the same degree in other kinds of arterial or venous blood. The effects of portal blood have been noted in animals with two livers (or a differential portal blood supply to different regions of one liver) to include hypertrophy, glycogen storage, hyperplasia, capacity for regeneration, increase of several synthetic functions, and maintenance of normal structure. The main splanchnic venous hepatotrophic factors are endogenous hormones of which the single most important is insulin. Thus, the foregoing portal hepatotrophic effects are largely eliminated with the diabetes produced by alloxan or total pancreatectomy. The injury of portacaval shunt is caused by the diversion of the hormones around the liver. Accordingly, the atrophy, injury to the organelles, and loss of the capacity for cell renewal is minimized if insulin is infused into the portally deprived liver. In these and other experiments, exogenous glucagon alone or the addition of glucagon to insulin has had no effect, but this may be because of the masking presence of gut glucagon and other hormonal or non-hormonal substances in our models. At present, the effects on the liver of exogenous insulin, glucagon, epidermal growth factor, and numerous other hormones are being determined by their intraportal infusion into eviscerated dogs in which other endogenous splanchnic factors have been eliminated.

Animals↗

Fungus infections after liver transplantation.

The problem of fungus infections after liver transplantation was studied. In 100 consecutive recipients of orthotopic liver homografts there were 10 and 8 examples, respectively, of localized and disseminated infections caused by Candida species. Candidemia was demonstrated in 8 of these 18 patients. One patient who had a localized Candida infection also had disseminated cryptococcosis. An additional 31 patients were infested in that Candida could be cultured from sites where it is not normally found, such as the blood (8 examples), urine (8), ascitic fluid (8), and wounds (22). This exorbitant incidence of monilial infections and infestations was associated with a high frequency of complications involving the homograft as well as the hosts' gastrointestinal tract during the post-transplantation period. The yeasts found in blood, urine, ascitic fluid and elsewhere were thought to have originated from the gut. Ten of the 100 patients had aspergillosis which was localized in 7 instances and disseminated in 3. The lung was the most frequently affected organ. The fungus infections played a contributory role in the downhill course of our patients but in the event of death more fundamental and more frequent causes of failure were technical complications involving the homografts, difficulties in controlling rejection with reasonable immunosuppressive doses and bacterial sepsis. Suggestions have been made for the better control of fungal infections in liver recipients.

Ascitic Fluid↗

Renal homotransplantation with venous outflow or infusion of antigen into the portal vein of dogs or pigs. Transplantation at portal site.

Kidneys were transplanted in mongrel dogs so that renal venous drainage was into the portal system of the hosts. Thirty-one recipients were not treated, 11 were given one dose of 3 mg of azathioprine per kg, and 11 were given 2 mg of azathioprine per day. Survival was not statistically increased compared with that in three comparable series in which renal venous drainage was into the vena cava, nor were the histopathological findings favorably altered in the "portal" kidneys. The injection of semisoluble antigen into the portal vein at the same time as renal transplantation at the caval site, had an effect no different from that if the antigen were given systemically during caval site transplantation. The conclusion that drainage of grafts into the portal vein was not beneficial was reached in 20 pigs evenly divided between the portal and vena caval sites, and in 12 pairs of dog to pig or pig to dog xenografts. Thus, none of these experiments has identified an advantage of antigen delivery into the portal as opposed to the systemic venous system.

Animals↗

Biliary complications after liver transplantation: with special reference to the biliary cast syndrome and techniques of secondary duct repair.

In 93 consecutive cases of orthotopic liver transplantation, there were 24 example of biliary obstruction and eight of bile fistula formation. Six of the obstructed livers developed biliary cast formation so extensive that the smaller intrhepatic ducts became plugged to an extent that they could no longer have been treated by surgical mena. In each of the six cases, the most important causative factor was neglected obstruction of the large bile ducts with the intrahepatic lesions apparently being late and secondary. Stone and/or cast formation also occurred in other obstructed livers in the presence of bile fustulas, but these deposits were limited to the large ducts where they could have been or were removed. Although homograft bile undoubtedly has increased lithogenicity at certain posoperative times, the data from the present study have shown that biliary sludge formation essentially is always associated with defective bile duct reconstruction, and the observations have underscored the urgency with which reoperation must be considered. Techniques of secondary intervention have been described, with emphasis on conversion of cholecystojejunostomy to choledochojejunostomy. This operation has permitted salvage of homografts in eight of nine trials and the survival of seven patients.

Adolescent↗

Liver replacement for alpha1-antitrypsin deficiency.

A 16-year-old girl with advanced cirrhosis and severe alpha 1-antitrypsin deficiency of the homozygous Pi ZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal Pi MM phenotype, the alpha 1-antitrypsin concentration in the recipient's serum rose to normal; it had the Pi MM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous Pi MZ donor was followed by the identification of that phenotype in the recipient's serum. Neither liver graft developed the alpha 1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic-based inborn error of metabolism is metabolically cured by liver replacement.

Adolescent↗