Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 19 recordsLinked to original sources

PubMed1992

Psychosocial outcome six months after heart transplant surgery: a preliminary report.

With improvement in survival of patients treated with heart transplant, evaluation of recovery with respect to psychosocial function has become an important issue. In this study, psychosocial functioning of 44 heart transplant recipients pretransplant was compared to their functioning 6 months posttransplant. Before transplantation, patients experienced considerable psychosocial distress attributable to illness. At 6 months after transplantation, the majority of patients showed significant improvement in emotional, domestic, sexual, social, and vocational functioning. However, 25% of patients showed deterioration in psychosocial adjustment and 11% showed an increase in mood disturbance. Further effort is indicated to improve psychosocial outcome of heart transplantation.

Adaptation, Psychological↗

PubMed1992

Hyperuricemia and gout among heart transplant recipients receiving cyclosporine.

PURPOSE: To determine the frequency and characteristics of hyperuricemia and gouty arthritis among cyclosporine-treated heart transplant recipients. PATIENTS AND METHODS: One hundred ninety-six surviving adult heart or heart/lung transplant recipients were evaluated. Medical records were reviewed to determine peak serum uric acid levels after transplantation, and to evaluate potential risk factors for hyperuricemia. Patients were surveyed by postal questionnaire for a history of gouty arthritis, with positive responses evaluated by telephone interview and/or examination of the patient. RESULTS: Hyperuricemia occurred in 72% of male and 81% of female patients and was not correlated with cyclosporine level, presence of hypertension, or degree of renal insufficiency. Eleven (6%) patients had gout prior to transplantation; 14 (8%) had onset of definite gout and seven (4%) had probable gout a mean of 17 months after transplantation. Polyarticular arthritis and/or tophi developed in six (43%) of the posttransplant-onset definite gout group within a mean of 31 months. CONCLUSION: Both hyperuricemia and gouty arthritis occur with increased frequency among cyclosporine-treated heart or heart/lung transplant recipients. The clinical course of gout in these patients is often accelerated, with management complicated by the patients' renal insufficiency and interaction with transplant-related medications.

Arthritis, Gouty↗

PubMed1992

Acute rejection of lung allografts with various immunosuppressive protocols.

Between February 1990 and December 1991, 69 patients who survived for a minimum of 5 days after single-lung (27), double-lung (32), or heart-lung transplantation (10) were studied to learn the incidence and severity of acute rejection and the possible effects of various immunosuppressive protocols on this rejection. Acute rejection was less common (2.1 versus 3.1 episodes/patient) after transplantation in those 30 candidates who received rabbit antithymocyte globulin for the first 5 postoperative days versus the 28 who were maintained on cyclosporine, azathioprine, and prednisone alone (p < 0.05), but no patient escaped at least one episode. Patients given cyclosporine received more 3-day courses of methylprednisolone (p < 0.02) than those given rabbit antithymocyte globulin (2.5 versus 1.7 courses). Although no disadvantage in terms of infectious morbidity was noted in the rabbit antithymocyte globulin group, no obvious intermediate advantage was noted in survival (85% at 12 months) or grade of rejection or airway flows. The most common histopathologic grades were mild (A2) and moderate (A3); the average grade was A2.3. FK 506 was tested in 11 patients, and early results are promising relative to low early and likely fewer late episodes of rejection. No differences were noted in the likelihood of rejection for any procedures.

Acute Disease↗

PubMed1992

University of Wisconsin solution for pulmonary preservation in a rat transplant model.

University of Wisconsin and modified Euro-Collins solutions for pulmonary preservation were compared in a rat orthotopic left lung isotransplant model. Heart-lung blocks of donor rats were flushed with and preserved in one of the preservation solutions at 0 degrees C. After 6 or 12 hours of cold ischemia, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as thiobarbiturate acid-reactive substances. The ratios of wet to dry weight of grafts after ischemia and after reperfusion were calculated. Histologic changes of ischemia-reperfusion injury of the lung tissue were evaluated using a graded scale. Oxygen tension after 6 hours of preservation followed by reperfusion was significantly higher with University of Wisconsin solution (308.8 +/- 81.1 mm Hg) than with Euro-Collins solution (50.8 +/- 17.8 mm Hg; p less than 0.001). Carbon dioxide tension in the University of Wisconsin solution group was also significantly lower than in the Euro-Collins solution group (28.2 +/- 2.3 versus 46.0 +/- 4.5 mm Hg; p less than 0.05). Lipid peroxide concentration after 6 hours' preservation in University of Wisconsin solution was significantly lower (0.88 +/- 0.07 mumol/g) than that in Euro-Collins solution (1.26 +/- 0.12 mumol/g; p less than 0.05). After 12 hours of preservation only lipid peroxide concentration with University of Wisconsin solution was significantly lower (1.30 +/- 0.09 mumol/g) than with Euro-Collins solution (1.71 +/- 0.15 mumol/g; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Clinical trial of FK 506 immunosuppression in adult cardiac transplantation.

The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient.

Adult↗

PubMed1992

Comparison of enzyme-linked immunosorbent and indirect immunofluorescence assays for the detection of human T-cell lymphotropic virus type-I antibodies in sera from rural Haiti.

Serum samples were obtained from 340 healthy individuals without evidence of neurologic disease living in rural Haiti. Sera were screened for antibodies to human T-cell lymphotropic virus type I (HTLV-I) using two commercially available enzyme immunoassays (EIA) and by an indirect immunofluorescence assay (IFA) using a mixture of uninfected H9 cells and HTLV-I-infected MT-2 cells. Repeatedly positive samples were confirmed by Western blot (WB). Results with the two EIA systems were concordant and detected 13 positive samples, each of which was confirmed by WB. Only 9 (69%) of 13 WB-positive sera were detected by IFA, and four additional samples, positive by IFA, could not be confirmed by WB. The prevalence of HTLV-I seropositivity in this selected rural Haitian population was 3.8% (13 of 340).

Adolescent↗

PubMed1992

Interstitial and airspace granulation tissue reactions in lung transplant recipients.

Twenty-three transbronchial and open-lung biopsies from patients who had received a lung allograft displayed fibromyxoid plugs of granulation tissue within airways, airspaces, and the interstitium in a patchy distribution. This granulation tissue-like reaction was identified in three clinicopathologic settings. First, 11 cases occurred with acute lung rejection, of which four cases had been partially treated with steroids for a previous rejection episode. Second, in seven cases the fibromyxoid tissue represented the healing phase of previously diagnosed diffuse alveolar damage resulting from preservation (harvest) injury to the allograft. Third, five cases were related to infection: herpes, Pseudomonas, Serratia, Staphylococcus, and Pneumocystis pneumonias. Although organizing pneumonia-like responses usually suggest an infectious episode, this reaction may be seen as a manifestation of acute lung rejection or ischemic lung injury.

Biopsy↗

PubMed1992

Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation.

Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0-3. Groups 4-7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/m3 with a mean particle size of 0.7 mu and estimated pulmonary depositions of CsA of 0.98-3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P less than 0.0002 and less than 0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.

Aerosols↗

PubMed1992

Mitogen responses of lymphocytes from lung transplant recipients--correlation with rejection and infection.

Proliferative responses to nonspecific mitogens were analyzed for 119 bronchoalveolar lavages and 108 concurrent peripheral blood samples from 35 lung transplant patients. The patients were classified at each time as normal, rejecting, or infected on the basis of trans-bronchial biopsy, culture results, clinical signs, and pulmonary function. During rejection episodes the bronchoalveolar lavage responses to concanavalin A and phytohemagglutinin were significantly increased (P less than 0.004 and P less than 0.006, respectively). The differences were less pronounced when rejection occurred within 30 days after bolus immunosuppressive therapy, either as immunoprophylaxis or as treatment for a previous rejection episode, and were not significantly different from normal. Differences in response during rejection were limited to the graft; analysis of circulating T cells was not helpful (P = NS). In contrast, markedly depressed responses to Con A and PHA were seen during infection. Significant differences were observed both in the graft (P less than 0.007) and in circulating lymphocytes (P less than 0.02), suggesting that global depression of mitogen response is associated with immunocompromise. Sequential analysis of 6 patients showed that individual changes in mitogen response paralleled those seen in the population (P less than 0.046, normal vs. rejection and P less than 0.043 normal). These findings suggest that mitogen assays of bronchoalveolar lavage lymphocytes and, to a lesser extent, PBL, are clinically useful in assessing intragraft immunocompetence and in distinguishing rejection from infection in lung transplant patients.

Bronchoalveolar Lavage Fluid↗

PubMed1992

Tumor necrosis factor-alpha production by alveolar macrophages in heart-lung transplant recipients.

Tumor necrosis factor-alpha (TNF alpha) is a cytokine produced by mononuclear cells that amplifies inflammation and modulates expression of Class I and Class II histocompatibility antigens. Because of these properties, this cytokine may exert a central role in both the defense and the rejection of the transplanted lung. Utilizing an ELISA technique, we measured TNF alpha in vivo and in vitro in several compartments of lung transplant recipients and in normal subjects that included serum, bronchoalveolar lavage fluid (BAL), and media conditioned by alveolar macrophages (AM) and by autologous peripheral blood monocytes (PBM). Overall, stimulated production of TNF alpha by AM from lung recipients in vitro was less than that of cells from normal subjects in response to lipopolysaccharide (LPS) challenge, and stimulated production of TNF alpha by AM harvested during conditions of infection or acute and chronic rejection was less than that by cells from healthy lung recipients. AM from normal subjects and allograft recipients produced substantially more TNF alpha than autologous PBM, but release in vitro by PBM from recipients was the same as that from cells of normal subjects who were not immunosuppressed. Thus, systemic immunosuppression does not seem to affect the production of TNF alpha by PBM in vitro, but it may reduce production by AM, indicating different effects of immunosuppression on different compartments of mononuclear cells. This mediator was not detected at elevated levels in serum, and it was undetectable in BAL fluid. We conclude that AM from lung recipients are capable of producing TNF alpha, which would influence the defense and immunogenicity of the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Ganciclovir prophylaxis for cytomegalovirus infections in pulmonary allograft recipients.

Cytomegalovirus (CMV) is a substantial cause of morbidity in pulmonary allograft recipients. In an attempt to decrease the prevalence of this infection, we treated 13 recipients at risk for cytomegalovirus with 3 wk of intravenous ganciclovir (5 mg/kg twice a day for 14 days, starting 5 days after the procedure, followed by 1 wk of the drug at a dose of 5 mg/kg/day). Following the ganciclovir course, patients received oral acyclovir, 800 mg three times a day for at least 2 months more. CMV infections developed in 5 recipients (38%), and none of these episodes occurred during the ganciclovir therapy. Neither of the 2 deaths in this group could be attributed to CMV. In comparison, the prevalence of CMV in the preceding cohort of 11 transplant recipients who were administered acyclovir alone was 91% (p << 0.01 by log-rank test), and there were 3 deaths due to viral infections (p = 0.08 by Fisher's exact test). Groups were similar in terms of immunosuppression and renal function during treatment, and none of the recipients developed leukopenia. We conclude that ganciclovir prophylaxis is well tolerated and appears to have considerable efficacy for prevention of CMV infections in pulmonary transplant recipients.

Administration, Oral↗

PubMed1992

Sequelae of cytomegalovirus pulmonary infections in lung allograft recipients.

Indirect effects of cytomegalovirus (CMV) infections in lung transplant recipients (LTX) have not previously been described in detail. We compared spirometric results, development of chronic rejection, rates of respiratory superinfections, and mortality as long as 2 yr after transplantation, between 62 LTX who never developed CMV (CMV-) and 56 LTX with a history of CMV pulmonary infections (CMV+). Initial spirometric parameters were near identical for both groups, but determinations > or = 6 months after transplantation showed that expiratory flows of the CMV+ were significantly reduced. Actuarial prevalences of chronic allograft rejection (CR) at 2 yr were highest among CMV+ with biopsy-proved pneumonitis (74%) compared with 22% among CMV- (p < 0.038). Bacterial or fungal pneumonias developed in 58.9% of the CMV+, whereas the rate among CMV- was 38.7% (p < 0.05). Only 36% of LTX with CMV pneumonitis lived 2 yr compared with 70% survival for CMV- (p < 0.016). Ganciclovir treatment of CMV infections decreased rates of respiratory superinfections and improved survival of patients, but it did not appear to affect subsequent development of CR. We conclude that CMV pulmonary infections among LTX result in serious late sequelae and that current treatment is ineffectual for prevention of viral-associated CR in these patients.

Adult↗

PubMed1992

Efficacy of antihypertensive medication in orthotopic heart transplant recipients and its effect on renal function.

The authors looked at 77 patients following orthotopic heart transplant who received a triple immunosuppressive regimen including cyclosporine to see the effect of various antihypertensive medications on mean arterial blood pressure and renal function. There were 62 men and 15 women retrospectively classified into three groups according to the antihypertensive medications they received. Group 1 included 26 patients followed up for 10.7 +/- 2.7 months who received hydralazine therapy. Group 2 included 32 patients followed up for 9.0 +/- 3.4 months who received angiotensin-converting enzyme inhibition therapy. Group 3 included 19 patients followed up for 10.1 +/- 3.3 months who received beta-adrenergic blocking agents. Mean arterial pressure (MAP), serum blood urea nitrogen (BUN), and serum creatinine (CR) were determined for each group at the start and end of the follow-up period. The MAP at the start of the study was 107 +/- 14 in group 1, 110 +/- 13 in group 2, and 100 +/- 11 in group 3. It was not statistically significantly different in any of the groups. At the end of the follow-up period, MAP was 112 +/- 10, 111 +/- 10, and 106 +/- 12 for the three groups respectively, and it was not significantly different in any group. The serum BUN in group 3 was 25 +/- 8 mg/dL at the start of the study, and it was not significantly lower than that in group 1, 28 +/- 6, but it was significantly different from that in group 2, 34 +/- 9, P less than 0.05. At the end of the follow-up period, the difference was still maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Lung transplantation at the University of Pittsburgh.

Lung transplantation appears to be a therapeutic alternative for selected patients with end-stage pulmonary vascular and/or parenchymal disease. The greatest impediment to transplantation remains the availability of donor organs. This has become more significant as additional transplant centers become operational. The primary cause of death has been infection, and this most frequently occurs in the early post-transplant period. Significant progress has been made in curbing the morbidity and mortality from bacterial pneumonia and CMV infection, and this is the primary reason for improved survival rates. If the recipient survives the initial hospital stay, the likelihood of survival at 5 years is approximately 80%. The primary long-term complication is obliterative bronchiolitis which is poorly understood and difficult to treat. Nevertheless, the improvement in survival provides impetus to refine and improve the procedure so that survival can reach that attained by recipients of other major organ allografts.

Academic Medical Centers↗

PubMed1992

Right ventricular/arterial coupling in the patient with left ventricular assistance.

BACKGROUND: Improvements are known to occur in right ventricular (RV) ejection fraction after the use of a left ventricular assist device (LVAD); less is known, however, about the mechanism of this improvement. The concept of ventricular/arterial coupling was applied to investigate whether systolic pump function or afterload reduction was the major contributing factor leading to the improvement in RV ejection fraction. METHODS AND RESULTS: Eight consecutive patients who underwent Novacor LVAD implantation as a bridge to transplantation were studied intraoperatively with transesophageal echocardiogram and a catheter-tip manometer to examine the RV end-systolic pressure-area relation (ESPAR) before and after LVAD implantation. Fractional area change (FAC) obtained by echocardiogram was used as an approximation of ejection fraction. End-systolic elastance (Ees), area axis intercept of ESPAR (A0), maximal area (Amax), and pulmonary effective arterial elastance (Ea) were obtained. RV FAC improved from 0.20 +/- 0.09 to 0.29 +/- 0.13 (p < 0.05). There was a decrease in Ea from 12.06 +/- 5.79 to 4.92 +/- 2.51 mm Hg/cm2 (p < 0.01), which indicated a reduction in RV afterload. A0 increased from -0.14 +/- 7.81 to 6.83 +/- 9.42 cm2 (p < 0.05), which implied impaired systolic pump function. There was no difference in Ees and Amax. CONCLUSIONS: The concept of ventricular/arterial coupling predicts that an increase of A0 (reduced RV systolic mechanics) decreases FAC, whereas a reduction in Ea improves FAC. The improvement in RV FAC (improved RV pump performance) may result from the effect of reduced Ea (afterload reduction) overwhelming the effect of increased A0. Afterload reduction is the most likely mechanism by which RV ejection fraction improves after LVAD implantation.

Adolescent↗

PubMed1992

Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model.

Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid-reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 +/- 0.07 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 +/- 70 vs 27 +/- 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 +/- 2.7 vs 47.7 +/- 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 +/- 0.07 vs 1.30 +/- 0.09 mumol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model.

Adenosine↗

PubMed1992

Donor-transmitted pneumonia in experimental lung allografts. Successful prevention with donor antibiotic therapy.

Bacterial pneumonia is the most common cause of early morbidity and mortality (less than 2 weeks) after heart-lung transplantation. The majority (76%) of cultures taken from human donor tracheas at the time of explant grew bacteria. The abnormal immune response of the lung allograft and the common finding of bacterial contamination of lung donors led us to hypothesize that clinically silent bacterial contamination of the donor lung progresses to pneumonia in the recipient and that antibiotic treatment of donors will prevent the development of pneumonia in the recipient. Inocula of Streptococcus pneumoniae were instilled into the left middle lobe of normal and donor dogs to identify the number of bacteria that would result in pneumonia in a normal animal and the amount that, when given to a donor, would result in pneumonia in the recipient. Initial studies established that inocula of 10(4) colony-forming units of S. pneumoniae did not result in pneumonia in normal or immunosuppressed animals. When 10(4) colony-forming units or as few as 10(2) were instilled into the left middle lobe of donors 24 hours before explantation and use of the lung for transplantation, severe acute bronchopneumonia developed in all 18 recipients. Treatment of donors with aerosol and intravenous antibiotics, but not with either alone, prevented pneumonia in the recipients. We conclude that bacterial contamination of the donor lung leads to pneumonia in recipients. Intravenous and aerosol antibiotic treatment of donors with bacterial contamination prevents pneumonia in canine lung recipients. Treatment of human donors with this antibiotic regimen may decrease the prevalence of early bacterial pneumonia.

Administration, Inhalation↗

PubMed1991

Immunosuppression with aerosolized cyclosporine for prevention of lung rejection in a rat model.

The efficacy of local delivery of aerosol cyclosporine (CsA) for prevention of lung rejection was compared with the intramuscular route (IM) in a fully allogeneic rat model (BN/LEW) of lung transplantation (LTx). Control rats (group 1, n = 6) received no CsA after LTx. Rats in group 2 (n = 10) received 4 doses of CsA in olive oil (25 mg/kg) intramuscularly starting on postoperative day (POD) 0. Group 3 (n = 9) was treated with aerosolized CsA for 3 h/day for 7 days starting on POD 0. All animals were sacrificed on POD 6. Transplanted lungs were graded histologically in a blind manner on a 0-4 scale. Control animals all showed grade 4 rejection. i.m. CsA therapy reduced lung rejection with a rejection grade of 1.8 +/- 0.35 (mean +/- SD) but was associated with a 50% incidence of pneumonia. Aerosol CsA provided better control of rejection with a rejection grade of 1.2 +/- 0.4 (group 3 vs. group 2: P less than 0.05 Wilcoxon) and none of these animals had penumonia. Trough blood levels of CsA were significantly lower in the group treated with aerosolized CsA when compared with the IM group (P less than 0.05). Therefore we conclude that: (1) aerosol CsA is effective in preventing lung allograft rejection following lung transplantation in rats, and (2) local delivery of aerosol CsA is superior to the i.m. route because better control of rejection is achieved with a lower systemic delivery of CsA.

Aerosols↗