Biomedical subjects
Publications and source records attributed to K A Porter.
Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiari syndrome. She is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases.
Insulin, glucagon, and insulin/glucagon mixtures have been infused for four days into the left portal vein of dogs after portacaval shunt. In the left but not in the right liver lobes, insulin alone reduced atrophy, preserved hepatocyte ultrastructure, and trebled cell renewal. Glucagon alone had no effect. In small doses, glucagon did not potentiate the action of insulin and in large doses it may have reduced the insulin benefit. These studies explain the development of the previously mysterious Eck fistula syndrome, provide clues about in-vivo cell growth control by hormones, and suggests new lines of inquiry about the pathogenesis and/or treatment of several human disease processes.
In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant.
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Six baboons of varying weights and estimated ages had complete portal diversion. All animals became emaciated and lost hair. Five of the 6 developed hepatic encephalopathy so serious that it either killed them or required their sacrifice after an average of 109 days. One exceptional animal which lived for 208 days without encephalopathy had markedly elevated blood ammonia levels. In one brain that was examined, greatly increased numbers of Alzeheimer's Type II astrocytes were diffusely distributed in the cerebral cortex. Changes in liver function tests were similar to those reported by many authors in dogs. The 6 baboon's livers underwent striking atrophy during the 49 to 208 days of postoperative observation. With some variations in degree, the same light and electron microscopic changes were observed that have now also been seen after completely diverting portacaval shunt in rats, dogs and humans. Thru the hepatic injury of Eck fistula is common to all species so far studied although most of the metabolic consequences of the procedure seem to selectively spare rats and man.
During the 11 1/2 year period ending 13 months ago, 93 consecutive patients were treated with orthotopic liver transplantation. Fifty-six of the recipients were 18 years old or younger, and the other 37 were adults. The most common indications for operation were biliary atresia, primary hepatic malignant tumor, chronic aggressive hepatitis and alcoholic cirrhosis. There has been a gradual improvement in results throughout the period of study, although to a satisfactory level. Twenty-seven of the 93 patients survived for at least one year after liver replacement with a maximum of six years, and 16 are still alive after 13 to 71 months. The 11 late deaths after one to six years were caused by chronic rejection, biliary obstruction, recurrence of hepatoma, systemic infection or hepatitis of the homograft. Rejection of the liver as judged by classical histopathologic criteria played a surprisingly small role in the heavy over-all mortality, accounting for less than 10 per cent of the deaths. Technical or mechanical problems, especially those of biliary duct reconstruction, were a far greater cause of failure, as were systemic infections. Six of the 37 adult recipients had lethal cerebrovascular accidents during, or just after, operation. When abnormalities of liver function developed in the postoperative period, the nearly automatic diagnosis of homograft rejection, in retrospect, proved to have been wrong in most instances. Further development of liver transplantation depends upon two kinds of progress. There must be reduction of operative and early postoperative accidents and complications by more discriminating patient selection, purely technical improvement and better standardization of biliary duct reconstruction. The second area will be in sharpening the criteria for the differnetial diagnosis of postoperative hepatic malfunction, including the liberal use of transhepatic cholangiography and needle biopsy. Only then can better decisions be made about changes in medication or about the need for secondary corrective surgical procedures.
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4 days after portacaval shunt, the livers of normal dogs had pronounced atrophy and other structural abnormalities. These changes were greatly reduced in the left liver lobes, but not in the right, by a constant infusion to the left portal vein of insulin in non-hypoglycaemic doses. These experimental findings should have implications in clinical medicine.
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The results of attempts to detect circulating immune complexes in sera by two methods are described. Both rely on the binding of the first complement component (C1) to the complex for its detection. The results, using these methods, of attempts to show which patients have complexes which contain nucleic acid and hence possibly viral antigens in the complexes are discussed. The anti-complementary complexes found in some patients seem to be associated with immune-complex vascular disease.
The acute influence of portal blood hepatotrophyic factors upon the canine liver and upon hepatic regeneration was studied after surgical operations which provided qualitatively different portal venous perfusion to the right and left liver lobes. With one such procedure called splanchnic division, the nutrient rich venous return from the intestines was directed to the left lobes, whereas the hormone rich blood from the pancreas and other splanchnic organs of the upper part of the abdomen passed to the right lobes. Within three to five days, the rate of cell division on both liver sides was increased as judged by autoradiography, but the hormone influenced right lobes exhibited hypertrophy and hyperplasia relative to the nutrient enriched left lobes. In the latter, the hepatocytes underwent pronounced atrophy, deglycogenation, depletion or distortion of the rough endoplasmic reticulum, fatty vacuolization and other structural changes. When 30 or 60 per cent hepatic resection was carried out at the same time as splanchnic division, the regeneration of the hormone dominated hepatic tissue after three to five days was greater than that of the hepatic tissue receiving the intestinal venous effluent, as judged by multiple criteria, although both liver sides participated in the regeneration process. The advantage enjoyed by the right liver lobes in relation to the left liver lobes both in the resting or in the regeneration state after splanchnic division was reduced or eliminated by pre-existing alloxan-induced diabetes or after concomitant total pancreatectomy. Similar, but less complete, observations about the effect of pancreatectomy were made in dogs submitted to the procedure of partial portacaval transposition, in which all the splanchnic venous blood passed to the right lobes, whereas the left lobes were revascularized with systemic venous blood from the vena cava. These observations have added to the recent torrent of evidence that insulin is the most easily demonstrable and, therefore, probably the most important specific hepatotrophic factor in portal venous blood. At the same time, further subtle support has been added to our previously proposed hypothesis that mutliple other hormonal and possibly nonhormonal factors from the splanchnic viscera and other sources also contribute to the essence of the hepatotrophic effects. These effects were evident and quite advanced within a few days. A prominent hepatotrophic role of glucagon was not identifiable.
Cyclophosphamide significantly diminished the canine humoral antibody response to sheep red blood cells and tended to prevent arterial lesions in renal homografts. However, cyclophosphamide failed to prolong renal homograft survival when administered to dogs as the sole immunosuppressive agent, and it did not add to the effectiveness of azathioprine when given as a supplement to the azathioprine and administered simultaneously or sequentially.
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Sixty-four consecutive patients underwent renal homotransplantation 10 1/6 to 11(1/2) years ago, 46 from related and 18 from nonrelated living donors. Thirty-six of these recipients were alive when this series was presented to the American Surgical Assocation in 1965. Now, nine years later, 26 (72%) of the 36 still survive, in 22 instances with function of their original grafts. The 10 who died in the interim tended to have subnormal renal function or graft failure. However, the actual causes of death included 2 or more examples each of myocardial infarction, hepatitis, or other systemic infections. The prognosis for achieving a one decade survival was not obviously related to HL-A tissue match. The best results were with related kidneys, within which subgroup 24 (52%) of the original recipients are still alive. However, there was no particular category of consanguineous donor that had a marked superiority. Only 2 of 18 nonrelated recipients are still alive. All 36 patients who were alive in 1965 had a biopsy of their renal homograft. Kidneys that were destined to function for a decade tended to have relatively minor histopathologic abnormalities. If serious glomerular lesions were found, the outlook for long graft survival was grave. Vascular lesions had a somewhat less serious import. Mononuclear cell infiltration, tubular atrophy, and interstitial fibrosis proved prognostically to be the least significant. Long-term followup of these early cases has shown the durability of chronic renal homografts, particularly if these are from related donors, and has demonstrated the very high degree of rehabilitation that could be achieved even in the early days of renal homotransplantation.
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