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Biomedical subjects

K A Porter

Publications and source records attributed to K A Porter.

At least 37 records · Page 2Linked to original sources

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↗

Pain insensitivity in schizophrenia. Case report and review of the literature.

We describe a schizophrenic man whose lack of pain and related objective signs of a perforated small bowel led to a delay in diagnosis and surgical intervention. A review of the literature suggests that both psychodynamic and specific biologic factors can produce atypical presentations in psychotic patients with illnesses in which pain is characteristically a prominent presenting symptom. While research into the cause of altered pain perception in psychotic patients is continuing, clinicians should maintain a high index of suspicion of serious medical illness when evaluating such patients.

Abdomen, Acute↗

The hepatotropic influence of cyclosporine.

The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.6, and 4.0 mg/kg/day. Control animals received the intravenous vehicle of cyclosporine at the same rate as the treated animals; a second control group received insulin, 0.42 units/kg/day. Hepatocyte 3H-thymidine-labeled mitoses (index of hyperplasia) and hepatocyte volume (index of hypertrophy) were studied in the left (infused) and right (control) lobes in each animal. Cyclosporine vehicle had no measurable effect on hepatocytes that suffered typical atrophy and moderate increase in mitotic index after the Eck fistula. Cyclosporine infusion stimulated cell renewal significantly and restored hepatocyte size in the infused lobes with a dose-response relation. Similar positive effects were observed in the right (nonperfused) lobes, although they were less than those in the left (infused) lobes. This was because of an unmistakable spillover of cyclosporine from the infused lobes, especially in the large-dose group. No sign of hepatotoxicity was detected at any cyclosporine infusion rate. Cyclosporine has a remarkable hepatotropic effect that may be helpful in the context of liver transplantation.

Animals↗

Disseminated, nonmeningeal gastrointestinal cryptococcal infection in an HIV-negative patient.

Gastrointestinal cryptococcosis is extremely rare, especially in patients with no involvement of the central nervous system. We describe a 63-yr-old man undergoing prednisone therapy for chronic hepatitis and cirrhosis who presented with peritonitis, colitis, and skin lesions. Pathological studies revealed necrosis and numerous cryptococcal organisms in the colon, omentum, and skin, and cultures yielded Cryptococcus neoformans. The patient died of multisystem organ failure following emergency exploratory surgery performed when he had onset of symptoms of a bowel perforation after an endoscopic biopsy. Clinicians should be aware that gastrointestinal cryptococcosis can occur in the absence of infection of the central nervous system or lungs, and that it may affect relatively healthy patients who are immunocompromised because of splenectomy, chronic liver disease, or steroid therapy.

Colitis↗

Transplantation of multiple abdominal viscera.

Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus-associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival.

Animals↗

Serum fatty acid profiles after intravenous medium chain triglyceride administration.

The serum fatty acid profiles of patients receiving either intravenous medium or long chain triglycerides were studied. Seventeen hospitalized patients, dependent on total parenteral nutrition, were randomly enrolled into a prospective study. The total parenteral nutrition (TPN) delivered amino acids and glucose and either a 75% medium chain triglyceride and 25% long chain triglyceride (MCT group) physical mixture or all long chain triglyceride (LCT group), as the respective fat sources. The amino acids and glucose were given continuously, and the lipid was given for 10 hours each day over five days. Fatty acid profiles on serum triglycerides and free fatty acids were done in the morning before any lipid was given and also later in the afternoon, near the end of the lipid administration, on days 1, 3 and 5. Medium chain fatty acids rose quickly in the triglyceride fraction in patients given MCT. Rapid MCT hydrolysis occurred as evidenced by the appearance of medium chain fatty acids in the free fatty acid fraction in the afternoon sampling. Clearance of the hydrolyzed medium chain free fatty acids (MCFFA) occurred so that little, if any, were present in the morning sampling one day later. Long chain fatty acids, as either triglycerides or free fatty acids, showed expected increases during the daily infusion, but not of such relative magnitude as the medium chain fatty acids. Medium chain fatty acid incorporation into the phospholipid or cholesterol ester fractions by the end of the five-day feeding period was present but minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Safety of iron dextran in total parenteral nutrition: a case report.

Parenteral iron, in the form of intramuscular injection or intravenous infusion of iron dextran, is commonly used to treat iron deficiency. Constitutional symptoms, anaphylaxis, and rarely death are risks associated with the use of iron dextran for this purpose. However, iron supplementation of TPN solutions to meet daily requirements can be accomplished safely. We propose that iron dextran added to TPN is well tolerated by patients because the amounts employed are small and the infusion times are long. To illustrate, we present a case where rapid administration of parenteral iron was associated with allergic type symptoms. Inclusion of daily requirements of iron in the TPN solution prior to and subsequent to this reaction did not elicit symptoms.

Adult↗

An assessment of Nva2-cyclosporine in primate cardiac transplantation.

The immunosuppressive potency, hepatotoxicity, and nephrotoxicity of Norvaline2-cyclosporine (Nva2-CsA), an analog of cyclosporine (CsA), were tested in a primate cardiac transplant model. After orthotopic cardiac transplantation in cynomolgus monkeys, immunosuppression was maintained with 16 mg/kg/day of either CsA or Nva2-CsA given intramuscularly in two divided daily doses. Immunosuppression was augmented with i.m. methyl-prednisolone, 1.0 mg/kg/day, which was tapered weekly by .1 mg/kg/day to a maintenance dose of .1 mg/kg/day. A group of 6 untransplanted monkeys were treated for a year with this dose of either CsA or Nva2-CsA and steroids. Renal biopsies were performed at one year. Among the transplanted monkeys, mean survival was 77.3 +/- 73 days for the CsA group and 16 +/- 8 days for the Nva2-CsA group. All 11 animals in the Nva2-CsA group died of cardiac rejection, but only 7 of 10 treated with CsA died of rejection. There was mild hepatic and renal dysfunction in both treatment groups, but no significant difference between groups as judged by blood urea nitrogen, creatinine, total bilirubin, serum glutamic oxaloacetic transaminate, and alkaline phosphatase. Cyclosporine levels were significantly higher in the CsA group. There were important morphological changes in both groups on histological examination of the kidneys, with proximal tubular vacuolation and enlargement of the juxtaglomerular apparatus predominating. It is concluded that Nva2-CsA is a less effective immunosuppressant than CsA when given parenterally in equal doses.

Animals↗

Use of OKT3 with cyclosporin and steroids for reversal of acute kidney and liver allograft rejection.

OKT3 monoclonal antibody therapy was added to preexisting baseline immunosuppressive treatment with ciclosporin and steroids to treat rejection in 52 recipients of cadaveric livers and 10 recipients of cadaveric kidneys. Rejection was controlled in 75% of patients treated, often after high-dose steroid therapy had failed. Rejection recurred during the 17-month follow-up period, after completion of OKT3, in only 25% of the patients who had responded. The safety and effectiveness of this monoclonal therapy, added to ciclosporin and steroids, has been established in this study.

Adolescent↗

Concentration and molecular forms of active and inactive renin in human fetal kidney, amniotic fluid and adrenal gland: evidence for renin-angiotensin system hyperactivity in 2nd trimester of pregnancy.

In a study of 38 fetuses total kidney renin was significantly correlated with gestational age (r = 0.63). Although whole fetal kidney renin specific activity was found to decrease with gestational age (r = -0.65), the mean value of the specific activity was about 20 times greater than in normal adult cortex and double that in tissue from patients with renal artery stenosis, suggesting renin-angiotensin system hyperactivity. In approximately 40% of fetal kidneys examined, evidence for an inactive (trypsin-activatable) renin precursor was found. The molecular weight of this form was indistinguishable from active renin (45 000 daltons) by Sephadex chromatography. Amniotic fluid from nine cases (100%) contained angiotensin (ANG) 1, angiotensin converting enzyme (ACE), renin substrate, active and inactive renin (both 45 000 daltons). Five of the 38 (13%) fetal adrenal glands contained renin, but no evidence for trypsin-activatable forms. Aldosterone was present in low concentration in the earliest adrenals examined, and a positive correlation existed between total tissue aldosterone and gestational age (r = 0.73). These findings suggest that the fetal renin-angiotensin system has an important role to play in the maintenance of extracellular fluid volume and blood pressure in the developing fetus.

Adrenal Glands↗

Canine liver transplantation under Nva2-cyclosporine versus cyclosporine.

The immunosuppressive qualities and other features of a new cyclosporine (CsA) analogue, Nva2-cyclosporine (Nva2-CsA) were examined using canine orthotopic liver allografts. The mean survival time was 11.8 +/- 9.6 (SD) days in dogs without treatment, 60.8 +/- 4.4 days with Nva2-CsA and 65.1 +/- 33.0 days with CsA. Functional abnormalities indicating toxic side effects were not noted either with Nva2-CsA or with CsA. Using the same oral dose, the rate of blood level rise and the amount of the rise were greater with Nva2-CsA. Histopathologically, Nva2-CsA treatment was associated with the same degree of hydropic vocuolation in the pars recta of the proximal tubules as CsA treatment. Thus, in the dog, Nva2-CsA had identical immunosuppressive properties as CsA, with no functionally detectable toxicity affecting the liver and kidney.

Animals↗