PubMed HealthSearch

Biomedical subjects

K A Porter

Publications and source records attributed to K A Porter.

At least 19 recordsLinked to original sources

Prognostic factors in sterile pancreatic necrosis.

Although the overall mortality in sterile pancreatic necrosis is low, patients who experience systemic complications may have a higher mortality. To study the impact of systemic complications and other factors on survival, possible prognostic factors were evaluated among 26 patients who experienced at least one systemic complication. Mortality was 38%. Factors that correlated with a fatal outcome were high Ranson's scores during the first 48 hours (P = 0.01), high APACHE-II scores at admission (P = 0.04) and at 48 hours (P = 0.03), shock (P < 0.001), renal insufficiency (P < 0.05), multiple systemic complications (P < 0.001), and high body mass index (P = 0.01). Most systemic complications occurred during the first 2 weeks of illness. Logistic regression analysis showed that shock was the best predictor of a fatal outcome. Patients with favorable prognostic factors survived whether treated medically or surgically, whereas those with unfavorable factors had a fatal outcome whether treated medically or surgically. It is concluded that patients with severe sterile necrosis have a high mortality rate and that shock and other prognostic factors identify which patients are most likely to have a fatal outcome.

Adult

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506.

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell-deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506-treated nude rats increased hepatocyte proliferation when added to third-party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways.

Animals

Hepatotrophic effects of FK506 in dogs.

Portacaval shunt (Eck fistula) in dogs causes hepatocyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this procedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of hepatocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506's efficacy for the treatment of chronic liver rejection. Also, the observations support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cytosolic binding sites of FK506, repatomycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.

Amino Acid Isomerases

Selected topics on FK 506, with special references to rescue of extrahepatic whole organ grafts, transplantation of "forbidden organs," side effects, mechanisms, and practical pharmacokinetics.

FK 506 is a superior immunosuppressive agent that should improve the grafting of organs that already are part of our every day transplant practices, as well as those which are presently impractical. Immune intervention for serious autoimmune diseases also should be a more attractive option with this drug. Lessons are still being learned about dosage and what determines safe dose schedules. At a basic level, the study of FK 506 and its comparison to CyA may have shed light on mechanisms and characteristics of the whole class of so-called macrolide immunosuppresants and their cytosolic binding sites.

Amino Acid Isomerases

Growth-stimulating factor in regenerating canine liver.

Extracts from dog livers which had been regenerating for 24, 48, and 72 h after hepatectomy were infused for 6 h into the left portal vein of animals which had fresh portacaval shunts (Eck fistula) and which were killed 2 and 3 days later. The brief exposure to the 48-h and especially the 72-h regenerating liver extracts induced a delayed proliferative response predominantly in the left liver lobes, with a slight spillover effect to the right liver lobes but none to the kidney. The response reached its peak 3 days later. In the left but not the right liver lobes, both the 48-h and the 72-h regenerating liver extract reversed the atrophy ordinarily caused by Eck fistula in 3 days and partly prevented the ultrastructural hepatocyte deterioration characteristic of Eck fistula. The active liver extracts apparently contained a growth-control factor or factors which is (are) not insulin or glucagon.

Animals

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