Lawrence Brettschneider

Orthotopic homotransplantation of the human liver.

Orthotopic Homotransplantation of the Human Liver Thomas Starzl;Carl Groth;Lawrence Brettschneider;Israel Penn;Vincent Fulginiti;John Moon;Herve Blanchard;Alfred Martin;Ken Porter; Annals of Surgery

Shwartzman Reaction after Human Renal Homotransplantation

Abstract In three human recipients, five renal homografts were destroyed within a few minutes to hours after their revascularization in the new host. The kidneys, removed one to 54 days later, had cortical necrosis. The major vessels were patent, but the arterioles and glomeruli were the site of fibrin deposition. There was little or no fixation of host immunoglobulins in the homografts. The findings were characteristic of a generalized Shwartzman reaction. Although the cause (or causes) of the Shwartzman reaction in our patients is not known, they may have been conditioned by the bacterial contamination and hemolysis that often attend hemodialysis, by immunosuppression and by the transplantation itself. Some of the patients have preformed lymphocytotoxic antibodies. Thus, certain patients may be predisposed. High-risk patients should be recognized and treated prophylactically with anticoagulants.

Infections in Recipients of Liver Homografts

Abstract Seventeen patients received liver homografts between 1963 and May, 1968. The eight treated before July, 1967, died within 34 days; seven had progressive infections with gram-negative bacilli, Candida albicans and cytomegalovirus. The infections were similar to but more fulminating than those after renal homotransplantation. In nine later cases, there was more discriminating donor selection, improved immunosuppression, and better organ preservation. In the first five of these nine patients, all infants, lobar hepatic gangrene apparently secondary to delayed right hepatic arterial thrombosis developed. Two died within a few days, two and three and a half months after transplantation. The three who did not die immediately subsequently had multiple bacteremias, fungemias and cytomegalovirus pulmonary infections. One of these children is alive twelve months after transplantation; the others died after four and a half and six months. In contrast, the last four patients, in whom septic liver infarctions...

Clinical Reactions and Serologic Changes After the Administration of Heterologous Antilymphocyte Globulin to Human Recipients of Renal Homografts

Clinical reactions and serologic changes after intramuscular administration of horse anti-human lymphocyte globulin (ALG) were studied in 53 human recipients of renal homografts. The ALG was used as an adjuvant immunosuppressive drug. In the usual case 47 injections were given over a 4-month period. All patients had pain, tenderness, erythema, and swelling at the injection sites. Benign systemic side effects included fever in all cases, hives in eight cases, rash in five, pruritus in five, arthralgia in three, and periorbital edema in one. Anaphylactic reactions occurred in 11 cases. These were easily treated, and there was complete recovery in every instance within 90 min. In eight of these cases the ALG administration was discontinued. Subsequent injections were given in the other three. Four of 11 patients tested had positive skin tests to ALG before therapy. Antibodies against sheep red blood cells developed during therapy in 39 of 40 patients; 10 reached titers as high as 1:128 to 1:512. Precipitin antibodies as measured with an electroimmunodiffusion technique developed in 36 of 40 patients. All three immunologic tests were of value in predicting the probability of an anaphylactic reaction, but the discrimination was imperfect Immunoelectrophoretic studies of sera from 13 patients showed antibodies to horse beta globulins in all cases, to alpha globulins in 9 cases, and to gamma globulins in only 1. This finding indicates that a safer ALG could be made by removing the trace quantities of alpha and beta globulins from the immunologically more active gamma globulins.

The clinical use of antilymphocyte globulin in renal homotransplantation

Twenty patients were treated with antilymphocyte globulin (ALG) which was prepared from the serum of immunized horses. The ALG was used as an adjuvant to azathioprine and prednisone and its use limited to 4 months. The surviving patients are now 1 to 7 months postoperative. There was 1 death, the consequence of a technical accident. The function in the remaining 19 patients is excellent, despite reduced doses of azathioprine and especially prednisone. Biopsies were obtained in the first 8 consecutive cases from 108 to 145 days after operation. There was no evidence in the specimens of either Masugi-like or serum sickness nephritis.

HOMOTRANSPLANTATION OF THE LIVER

The feasibility of hepatic homotransplantation has been clearly established in principle inasmuch as several animals are still alive almost 3 years after complete hepatectomy and liver replacement. Both orthotopic and auxiliary operations are complicated surgical techniques. Nevertheless, the results in dogs are comparable to those which can be obtained with homotransplantation of the kidney. In man the problem is more difficult. In patients who have a need for such operations, there is invariably a metabolic disorder more complex than that caused by renal failure. In addition, the new organ must function efficiently from the beginning since its complete functional failure leads to death within a few hours. There is no recourse to an artificial liver to maintain life until the reversal of an injury which is caused by either ischemia or rejection. Nevertheless, research of several kinds may soon make possible the successful use of hepatic transplantation procedures for the definitive treatment of human liver disease as exemplified by the reports in this symposium concerning new techniques of organ preservation, histocompatibility analysis, and immunosuppression.

Immunofluorescent examination of biopsies from long-term renal allografts.

Abstract Immunofluorescent examination of open renal biopsies revealed clear-cut glomerular localization of immunoglobulins not related clearly to the quality of donor-recipient histocompatibility ...

Hypermagnesemia After Renal Homotransplantation

Abstract The clinical and biochemical features of three patients who developed magnesium intoxication after renal homotransplantation are described. All patients were receiving magnesium-containing...

Renal transplantation at the university of Colorado

From March 1962 to April 1963, 118 patients were treated with renal transplantation, 3 with kidneys from identical twins, 9 with cadaveric homografts, and 106 with homografts from volunteer donors. Sixty-two of the patients are still alive after nine months to almost five years. The only completely satisfactory group was that of the identical twin recipients. The results after homotransplantation have not materially improved during this time despite the acquisition of increased experience, adjustments of timing and dosage of azathioprine and prednisone, and attempts to identify biologically suitable donors in advance of operation by tissue typing. It is suggested that an impasse has been reached, beyond which further reduction in mortality and morbidity will depend primarily upon the effective application of new immunosuppressive techniques.

Organ Transplantation, Past and Present

There can no longer be doubt that transplantation of tissues and organs will be practiced with increased frequency and success in the future. The number of patients who have been returned to a useful place in society after renal homotransplantation has risen steadily since 1962.* Clinical transplantations of the liver,11, 49, 62, 63, 72 lung,17, 40,. 88 heart,16, 32, 33 spleen41, 69 and pancreas 27 have also recently been undertaken. Progress in various areas of transplantation research has been summarized in several books, monographs and special issues of journals5, 10, 12, 38, 58, 61, 86, 87 and will not be recapitulated here. Instead, attention will be focused upon several specific questions that pertain to transplantation of the kidney and liver, but that probably also have relevance to the transplantation of other organs.