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Biomedical subjects

O Bronsther

Publications and source records attributed to O Bronsther.

At least 37 records · Page 2Linked to original sources
PubMed1994

Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression.

OBJECTIVE: The efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined. SUMMARY BACKGROUND DATA: After 3 years of preclinical research, a clinical trial of FK 506 for orthotopic liver transplantation was begun in February 1989, first as a rescue therapy for patients with intractable rejection with conventional immunosuppression, then as a primary drug. METHODS: Between August 1989 and December 1993, 1391 recipients (1188 adult and 203 pediatric) of primary liver allografts were treated with FK 506 from the outset. Results from these patients were analyzed and compared with those of 1212 historical control patients (971 adult and 241 pediatric) given cyclosporine-based immunosuppression. RESULTS: Actuarial survival at 4 years was 86.2% with FK 506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and 71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was reduced significantly for FK 506 patients. Four-year graft survival was 77.0% with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p < 0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult recipients (p < 0.0000). Regression analysis revealed that reduction in mortality or graft loss from uncontrollable rejection, sepsis, technical failure, and recurrent original liver disease were responsible for the improved results with FK 506 therapy. CONCLUSIONS: FK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation.

Actuarial Analysis↗
PubMed1993

Recent advances in hepatic transplantation at the University of Pittsburgh.

FK506 undoubtedly improved the survival advantage of hepatic allotransplantation. Hepatic-intestinal and multivisceral transplantation has also become a feasible therapy for patients with combined intestinal and liver failure. With better understanding of the immunologic and metabolic aspects of allo- and xenotransplantation, further clinical attempts to transplant animal organs to humans may be considered with the hope for a better outcome in the very near future.

Academic Medical Centers↗
PubMed1992

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies.

Twenty-six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch-positive state on early graft function and on the immunopathological and histopathological findings was compared with that of 52 crossmatch-negative control recipients. The presensitized (crossmatch-positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p less than 0.05) and within 10 days of transplantation (p less than 0.01). They also had a higher incidence of graft failure in the first 180 days (p less than 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatch-positive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection.

Adult↗
PubMed1992

Total hepatectomy and liver transplant for hepatocellular adenomatosis and focal nodular hyperplasia.

Extensive hepatocellular adenomatosis (HA) and focal nodular hyperplasia (FNH) represent a proliferation of hepatic cells that occurs most frequently in women. These lesions are uncommon in the pediatric age group, accounting for 2% of pediatric hepatic tumors, and are extremely rare in males. The etiology of HA and FNH has been correlated with the use of oral contraceptives. We report to the best of our knowledge the first series of patients treated with OLTx for HA and FNH (five cases). All these patients had lesions involving at least 90% of the hepatic parenchyma and all underwent major hepatic surgery before OLTx because of life threatening complications. One patient died in the immediate postoperative period following retransplantation for primary non-function of the first OLTx. Four out of five patients are currently alive from 4.1 to 9.6 years after OLTx. Our results justify the use of OLTx for symptomatic patients with HA and FNH who cannot be treated with conventional hepatic resections.

Adenoma, Liver Cell↗
PubMed1992

The adverse impact on liver transplantation of using positive cytotoxic crossmatch donors.

Because of the liver graft's ability to resist cytotoxic antibody-mediated rejection, it has become dogma that the conventional transplant crossmatch used to avoid hyperacute rejection of other organs is irrelevant to the liver. We examined this hypothesis in a consecutive series of adult primary liver recipients treated with FK506 and low-dose steroids. Twenty-five of 231 (10.8%) patients received a liver from a cytotoxic-positive crossmatch donor (more than 50% of donor T lymphocytes were killed by dithiothreitol-pretreated recipient serum). The outcome was compared with that of 50 negative crossmatch patients who had their transplantations just before and after the crossmatch positive cases. The one-year graft and patient survivals were 56% and 68%, for positive and 82% and 86% for negative crossmatch patients (P = 0.004, P = 0.03, respectively). The difference between patient and first graft survival was accounted for by retransplantation, which was 4 times more frequent in the positive-crossmatch cases. Histologically, failed allografts obtained at the time of retransplantation revealed a spectrum of pathologic findings related to vascular injury. This study showed a higher difficulty of intraoperative blood product management, a degraded prognosis, and a poorer average quality of ultimate graft function when liver transplantation was performed against positive cytotoxic crossmatches. In such patients for whom crossmatch-negative donors may never be found because of the broad extent and intensity of sensitization, special therapeutic strategies perioperatively must be evolved if results are to improve.

Adult↗
PubMed1991

The liver transplant waiting list--a single-center analysis.

At this transplant center 1340 patients were entered on the liver transplant waiting list during the first 25 months (October 1987 to November 1989) after the initiation of the UNOS allocation system for liver grafts. Of these 972 (72.5%) of the patients received a graft, 120 (9.0%) died waiting for a graft, 109 (8.1%) remained on the active list as of the study endpoint of December 15, 1989, 123 (9.2%) were withdrawn from candidacy, and 16 (1.2%) received a transplant at another center. A total of 1201 patients were candidates for a first graft. Of the 812 primary candidates who received a graft, 64.8% received their graft within one month of entry on the waiting list. Of the 109 primary candidates who died before a graft could be found, 79.0% died within a month of entry onto the waiting list. At time of transplantation, 135 (16.6%) primary recipients of a graft were UNOS class 1, 326 (40.1%) were UNOS class 2, 190 (23.4%) were UNOS class 3, and 161 (19.8%) were UNOS class 4. Actuarial survival rates (percentage) at 6 months for recipients in UNOS class 1, class 2, class 3, and class 4 were 88.7 +/- 2.9, 82.6 +/- 2.1, 78.4 +/- 3.2, and 68.4 +/- 3.9, respectively (P less than 0.001). At the time of death of recipients who failed to get a graft, 6 (5.5%) were UNOS class 1, 14 (12.8%) were UNOS class 2, 23 (21.1%) were UNOS class 3, and 66 (60.6%) were UNOS class 4. These results indicate that a high proportion of liver transplant candidates are in urgent need of a graft and that the UNOS system succeeds in giving these patients high priority. However patient mortality on the waiting list and after transplantation would lessen significantly if more patients with end-stage liver disease were referred to the transplant center in a timely manner before their condition reaches the point where the probability of survival is diminished.

ABO Blood-Group System↗
PubMed1991

Neuroendocrinology of chronic renal failure and renal transplantation.

Neuroendocrine activity in normal subjects was compared to patients with chronic renal failure on maintenance hemodialysis (CRF-HD) and to cyclosporine-treated renal transplantation (RT) recipients in an effort to further define the mechanisms underlying their associated fluid, electrolyte, and hemodynamic abnormalities. To evaluate neuroendocrine function in CRF and RT patients, plasma levels of angiotensin II (A-II), vasopressin (AVP), atrial natriuretic peptide (ANP), neuropeptide Y, neuropeptide Y (NPY), epinephrine (E), and norepinephrine (NE) were measured before and after HD and RT. Plasma concentrations of A-II, AVP, ANP, and NPY were significantly elevated in patients with CRF. HD did not produce a significant change in plasma concentrations of AVP, ANP, NPY, E, or NE. NE plasma levels, but not E levels, increased pre- and post-HD. A-II plasma levels were elevated basally in CRF patients and significantly increased following HD. Following RT, plasma levels of A-II, AVP, NPY, and creatinine decreased significantly over the first week, but AVP and NPY did not normalize. Plasma levels of ANP were elevated during the first month, then decreased to normal levels in RT patients. NE levels, but not E levels, were elevated both pre- and post-RT. Despite antihypertensive treatment, the group mean arterial pressure increased post-RT from 100 +/- 4.4 to 116 +/- 3.7 mmHg by POD 6.

Adult↗