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Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

At least 289 records · Page 16Linked to original sources
PubMed1988

The treatment of advanced cardiac allograft rejection.

Severe cardiac allograft rejection remains a serious problem despite the advances of cyclosporine-based immunosuppression. This study analyzes our experience with 202 recipients of cardiac allografts who were treated primarily with cyclosporine and prednisone. Failure of such therapy in 86 patients (43%) resulted in 105 episodes of advanced cardiac allograft rejection as diagnosed by endomyocardial biopsy. Of 101 rejection episodes that were initially treated with intravenous pulse therapy, 48 (48%) were successfully resolved, yet 60% of these successes were associated with major infections. Patients in whom steroid therapy failed or was contra-indicated received intravenous antithymocyte globulin (ATG) or intravenous monoclonal antibody (OKT3). ATG and OKT3 successfully reversed severe rejection in 26 (81%) of 32 and in 13 (93%) of 14 episodes, respectively. Infectious complication rates were 54% and 21%, respectively. Because the majority (87%) of these rejection episodes occurred within the first 30 days after treatment, many of them may have resulted from inadequate immunosuppressive induction therapy. Based on our results, we believe that advanced cardiac allograft rejection may be managed best by individualizing immunosuppressive therapy, thus enhancing prevention, and by adding OKT3 to the regimen when rejection occurs.

Adolescent↗
PubMed1988

The impact of HLA A, B, and DR blood transfusions and immune responder status on cardiac allograft recipients treated with cyclosporine.

From July 1982 to August 1986, 137 patients received heart allografts at our transplant (Tx) center. Recipients were treated postoperatively with cyclosporine (CsA) and prednisone (Pred), with a minority of patients receiving CsA, Pred, and azathioprine (Aza) as immunosuppression. The impact of pre-Tx immune factors on survival was evaluated, including HLA A, B, and DR mismatches (MM), blood transfusions (BT), immune responder status, crossmatch results, and donor and recipient AIDS-virus (human immunodeficiency virus, HIV-1) status. The overall patient survivals were 75%, 68%, and 62% at one, two, and three years respectively. Pre-Tx, 15/137 (11%) recipient sera and 5/137 (3.6%) donor sera were HIV-1 reactive in both enzyme immunoassay (EIA) and Western blot antibody assays. Two of the 5 recipients of HIV-1 (+) donor allografts are alive 11 and 29 months post-Tx, whereas the other 3 recipients died at 1, 31, and 36 months post-Tx from diseases unrelated to AIDS. All 5 were pre-Tx HIV-1 nonreactive. The survivals for the 15 recipients who tested pre-Tx HIV-1 (+) were 87%, 87%, and 69% at 1, 2, and 3 years, respectively, comparable to the overall group survivals. Pre-Tx strong and weak immune responders had comparable 12-month survivals of 73% and 80%, respectively. Six patients displayed a positive pre-Tx donor crossmatch, two were attributed to autoantibody, and 4 were attributed to donor T cell reactivity. Five of the six patients presently survive 14, 16, 30, 36, and 44 months post-Tx. Recipients treated pre-Tx with 1-4 BTs displayed significantly better 12-month survival (81% vs. 69%, P less than 0.05) and fewer rejections (1.3 +/- 0.9 vs. 1.9 +/- 1.0, P less than 0.05) than untransfused recipients. Recipients of a 0-1 vs. 2 DR donor antigen-mismatch experienced fewer rejections (1.3 +/- 1.0 vs. 1.8 +/- 1.1, P less than 0.05). Evaluation of the combined influence of HLA DR as well as pre-Tx BTs suggested a significantly improved survival (80% vs. 61%, P less than 0.05) and fewer rejection episodes (1.4 +/- 0.9 vs. 2.0 +/- 1.1, P less than 0.05) for 29 well-matched, transfused (0-1 DR MM and 1-4 BT) compared with 43 poorly matched, untransfused (2 DR MM and 0-BT) heart allograft recipients. Moreover, the benefit of DR matching was only observed in untransfused, but not transfused, cardiac recipients.

Adolescent↗
PubMed1988

Cardiac transplantation in a Jehovah's witness.

Between July 1982 and October 1987, surgeons at our institution performed 215 cardiac transplantation procedures, 1 of which was in a 46-year-old Jehovah's Witness with congestive cardiomyopathy, who required preoperative intra-aortic balloon pump support. At surgery, the cardiopulmonary bypass system was primed with 1600 ml of Ringer's lactate solution and dextrose. In the 57 minutes during which the patient was on cardiopulmonary bypass, the intra-aortic balloon was removed and successful orthotopic heart transplantation was performed. No supplemental blood or blood product was used, either during or after the procedure. The estimated intraoperative blood loss was 300 ml, and the postoperative chest tube drainage amounted to 1495 ml. Postoperative hematologic abnormalities (mild hypoprothrombinemia, mild thrombocytopenia, mild platelet dysfunction, and moderate hypochromic microcytic anemia) were corrected with Imferon, vitamin K, and desmopressin acetate administered intravenously, and with ferrous sulfate administered orally. This case, which to our knowledge is only the 2nd cardiac transplant in a Jehovah's Witness, further establishes that these patients can undergo even the most major of open-heart procedures without supplemental blood.

Journal Article↗
PubMed1988

Complications in cardiac transplant patients requiring general surgery.

With the advent of cyclosporine A, heart transplantation has become a widely accepted treatment for patients with end-stage cardiac disease that is not amenable to medical or surgical treatment. Between July 1982 and December 1985, 86 heart transplantations were performed at the Texas Heart Institute with cyclosporine A and prednisone used for immunosuppression. Thirty patients had complications requiring general surgical consultation. The pancreas and biliary tracts were most commonly affected. Pancreatitis developed in sixteen patients; five patients required operative intervention, resulting in a 40% mortality rate. Five of nine patients with cholecystitis required cholecystectomy. All patients survived the procedures. Other gastrointestinal complications included colonic ileus, bowel perforation, gastrointestinal bleeding, gastric outlet obstruction, and perirectal abscess. Patients who have undergone cardiac transplantation are susceptible to life-threatening infections and are at risk of serious complications requiring general surgical intervention. Better results can be obtained in these complex clinical situations when complications are identified early and managed aggressively through the adjustment of immunosuppression, adequate selection of antimicrobial agents, and proper timing of surgical intervention.

Cholecystitis↗
PubMed1988

Cyclosporine A pharmacokinetics in a cardiac allograft recipient with a jejuno-ileal bypass.

A 41-year-old man with a 13-year history of JI bypass for morbid obesity developed idiopathic cardiomyopathy. A pretransplant CsA pharmacokinetic profile demonstrated inadequate PO absorption with no appreciable enterohepatic recirculation. Inadequate levels occurred after three hours and became undetectable after 18 hours. The patient's status did not permit JI bypass reversal before transplantation. IV CsA was administered before cardiac transplantation, and a continuous IV CsA infusion was maintained for 72 days through episodes of CMV reactivation infection and complications common to the immunosuppressed patient. JI bypass reversal was subsequently performed and IV CsA converted to oral form as intestinal function improved. A repeat PO CsA pharmacokinetic profile demonstrated a threefold rise in peak concentration, delayed smaller peak concentrations representing enterohepatic recirculation, and a steady-state blood level that persisted for 23 hours. We have found that pretransplant CsA pharmacokinetic analysis predicts CsA bioavailability and serves as a guide for achieving optimal CsA serum concentrations; adequate PO absorption and enterohepatic recirculation of CsA depends on the anatomical and functional integrity of the jejunum and ileum; continuous IV CsA infusion can be precisely adjusted for optimal therapeutic efficiency; and long-term CsA infusion can benefit critically ill transplant patients without increased morbidity.

Adult↗
PubMed1987

Occlusive coronary arteritis: a cause of early death in a cardiac transplant patient.

A patient died 5 months after undergoing cardiac transplantation. Endomyocardial biopsies performed prior to death showed no evidence of severe rejection. At autopsy, nonnecrotizing occlusive coronary arteritis was present. The intima of the coronary arteries contained numerous lymphocytes and plasma cells. Chronic rejection appeared to be responsible for the arteritis. The onset of coronary occlusive disease is insidious, and recognition depends on the performance of coronary arteriography, which is usually not done until the one-year follow-up. Early coronary arteriography is suggested to rule out occlusive coronary arteritis when cardiac allograft function is not satisfactory, even when the endomyocardial biopsy shows no evidence of rejection.

Arteritis↗
PubMed1987

Hypothermic regional perfusion for protection of the spinal cord during periods of ischemia.

Ischemic spinal cord injury with resulting postoperative paraplegia is an inherent risk for operations on the thoracic aorta. The mechanism of injury is not clearly understood, and numerous adjuncts to avoid this complication have been suggested, with conflicting clinical results. A new technique of hypothermic regional perfusion of the spinal cord is described. Fifteen female pigs weighing 21 to 39 kg were used for the experiment. The control group consisted of 5 animals in which the thoracic aorta was clamped at the distal arch for 30 minutes. All of these animals sustained postoperative neurological damage. Eighty percent sustained postoperative paraplegia, and 20% had severe spasticity of the hind legs that precluded normal ambulation. The experimental group consisted of 10 animals in which hypothermic regional perfusion was performed for 30 minutes after cross-clamping of the distal arch. Perfusion cooling was followed by 30 minutes of ischemia in 5 animals and 45 minutes of ischemia in the remaining 5. All animals that underwent hypothermic regional perfusion were able to walk postoperatively, and no evidence of ischemic injury was found at postmortem examination of the spinal cords. This technique proved to be simple and effective in protecting the spinal cord for up to 45 minutes of ischemia in the experimental group. The clinical implications of this concept are promising for patients undergoing operations on the thoracic aorta.

Animals↗
PubMed1987

Exacerbation of cyclosporine toxicity by concomitant administration of erythromycin.

Cyclosporine (CsA), an immunosuppressive drug widely used in clinical organ transplantation, causes a variety of side effects, including parenchymal complications of nephrotoxicity and hepatotoxicity. Erythromycin ethinylsuccinate (EES), a macrolide antibiotic frequently administered to transplant patients afflicted with pneumonias caused by Mycoplasma pneumoniae and Legionella pneumophila, markedly potentiated parenchymal drug toxicity in nine (three renal and six cardiac) CsA-treated allograft recipients. The mean and median blood urea nitrogen (BUN), creatinine, and total bilirubin increased upon initiation of EES treatment: in the renal recipients from 27, 1.7, and 0.5 mg/dl, respectively, before, to a mean and median of 81/101, 8.3/3.9, and 2.1/1.2 mg/dl during, and to 72/22, 1.9/1.7, and 0.6/0.5 mg/dl after cessation of EES treatment. The median serum radioimmunoassay (RIA)-determined CsA trough value of 147 ng/ml prior, rose to a zenith of 1125 ng/ml during, EES therapy. In the six cardiac recipients, the mean and median BUN, creatinine, and total bilirubin of 51/45, 1.5/1.3, 1.2/1.3 mg/dl, respectively, before, rose to 100/91, 3.7/3.6, and 2.3/2.1 mg/dl during, and fell to 49/44, 1.8/2.1, and 1.0/0.8 mg/dl after, cessation of EES. The mean serum CsA trough value of 185 ng/ml rose to 815 ng/ml during EES administration. Since EES and CsA are both metabolized by the hepatic cytochrome P450 mixed-function oxidase system, simultaneous use of these two drugs may decrease CsA metabolism, with consequent elevation of blood levels and induction of CsA toxicity. Therefore, blood level monitoring and careful regulation of CsA dose are necessary, in order to achieve the safe use of EES in transplant recipients.

Bilirubin↗