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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1991

Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type 1 replication in primary macrophages.

Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 to productively infect macrophages may be influenced by endogenous cytokines that alter the activation state of these cells. In this study, the effect of tumor necrosis factor-alpha/cachectin (TNF alpha), a cytokine with macrophage-activating properties, on HIV-1 replication in primary blood monocyte-derived macrophages was examined. Treatment of macrophages with recombinant human TNF alpha (rTNF alpha), starting before or after HIV-1 infection, consistently enhanced viral production fivefold or greater above control (P less than .01). rTNF alpha was active at low concentrations (0.05-50 ng/ml) and increased the replication of both lymphocyte-tropic (human T lymphotropic virus type IIIB) and macrophage-tropic (human T lymphotropic virus type III BaL) strains of HIV-1. These findings provide additional evidence that TNF alpha may play a role in the pathogenesis of HIV-1 infection by upregulating viral expression in macrophages.

Cells, Cultured↗
PubMed1991

Evolving experience with mechanical circulatory support.

Since 1985 total mechanical circulatory support for mortally ill transplant candidates has been progressively integrated into the authors' program. During this period 379 patients underwent transplantation. Of this group of patients, 62 required some form of mechanical support other than the intra-aortic balloon pump. Because intra-aortic balloon pump assist was limited in therapeutic effect and was associated with patient immobility and line-related sepsis, the next logical step toward support was the artificial heart. Of 20 patients implanted with the Jarvik heart, 17 underwent transplantation, but only 9 of these survived to discharge. In 1988, the authors abandoned the preferential use of the total artificial heart because of excessive cumulative probability of death from wound infection. They began to use the Novacor electrical assist device with the percutaneous power cord because they believed that univentricular support would be adequate for most patients, because its heterotopic position would reduce the likelihood of infection, and because it had the potential for chronic implantation. Twenty-three patients with biventricular failure (right ventricular ejection fraction less than 20%, 18/23) received the electrical assist device for an average of 50.4 days (range 1-193 days). All 17 transplanted patients survived until discharge. Only one of the five deaths that occurred after implantation, but without transplantation, was due to infection (candidiasis). Remarkably, all patients who survived the perioperative period ultimately survived with univentricular support alone. Based on this experience, survival of mechanically supported patients is now comparable to that of those less mortally ill.

Adolescent↗
PubMed1991

Similarity of pulmonary rejection patterns among heart-lung and double-lung transplant recipients.

The transbronchial biopsy and clinical courses of 9 double-lung and 1 single-lung recipients surviving greater than 10 days were analyzed and compared to those of 15 heart-lung transplants performed during the same time period. Of these, 8 isolated lung (LT) and 11 heart-lung transplant (HLT) recipients survived greater than 50 days and were at risk of developing obliterative bronchiolitis believed to be a form of chronic rejection. Cyclosporine-based immunosuppression, in combination with azathioprine and steroids, was used for 22 of 25 patients. Two double-lung recipients and 1 heart-lung patient received FK506 as the sole immunosuppressive agent; 90% and 62% of LT, and 67% and 54% of HLT recipients developed acute and chronic rejection, respectively (P = NS). The average time to first episode of acute (30.2 days [LT] versus 21.5 days [HLT]) and chronic rejection (146 days [LT] versus 193.7 days [HLT]) was not different between groups (P = NS). Age (34.2 [LT] versus 29.1 [HLT]) and sex (M:F, 5:5 [LT] versus 5:10 [HLT]) were also not found to be discriminators. The histologic diagnosis of chronic rejection was associated with significant declines in FEV1.0 and FEF25-75 (P less than 0.02). There was only one instance of cardiac rejection among the heart-lung transplant recipients. Heart-lung and isolated lung transplant patients appear to be at similar risk for developing acute or chronic pulmonary rejection.

Adult↗
PubMed1991

Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation.

Twenty-seven patients received pulmonary transplants during the period since we began routine use of cytomegalovirus-seronegative blood products for CMV-seronegative recipients. Preoperative serologic status of the recipient and the occurrence of cytomegalovirus infection in the postoperative period were correlated with development of obliterative bronchiolitis (OB) as diagnosed by transbronchial biopsy (TBB). Patients included 20 heart-lung and 7 double-lung recipients. OB occurred in 18 of 27 patients. All 3 CMV seronegative recipients receiving lungs from a seropositive donor and 9 of 10 CMV recipients seropositive at the time of transplantation developed OB compared with only 6 of 14 CMV seronegative patients receiving seronegative grafts (P = 0.018). CMV infection occurred in 10/27 patients, of whom 5 were asymptomatic; 90% of these patients developed OB. Donor-specific alloreactivity, based on primed lymphocyte testing (PLT) of bronchoalveolar lavage cells was found at the time of diagnosis of OB in 23 of 27 patients. A positive PLT was significantly associated with the presence of OB (P = 0.017). We conclude that preoperative seropositive status for CMV, grafting of organs from seropositive donors, and postoperative CMV infection are significant risk factors for developing OB. That OB is, in part, an immunologically mediated form of injury and represents chronic rejection is supported by the presence of donor-specific alloreactivity in BAL lymphocytes from all recipients with OB.

Antibodies, Viral↗
PubMed1991

Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?

Clinical acute lung rejection (AR) occurs in lung allografts usually within 50 days after transplantation. While perivascular infiltrates characterize AR, with moderate-to-severe acute rejection small airway injury occurs. We investigated the significance of small airway injury in AR and its relationship to the development of bronchiolitis obliterans (OB) in 11 recipients of combined heart-lung or double-lung allografts. In general, the intensity and persistence of early acute rejection episodes associated with injury to bronchioles correlated with the development of histologic bronchiolitis obliterans. Early AR may "prime" lymphocytes for subsequent respiratory epithelial injury and airway fibrosis late in the postoperative period.

Adult↗
PubMed1991

Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation.

A histological analysis of 2564 endomyocardial biopsies was conducted in 349 cardiac transplant patients to determine potential risk factors for acute cellular rejection during the first three months following transplantation. This analysis dealt with the frequency, time of onset, and duration of cellular rejection. Patients on perioperative RATG experienced significantly less rejection than patients on OKT3 or without antilymphocyte antibody immunoprophylaxis. A trend was noted toward increased rejection in recipients diagnosed originally with chronic myocarditis compared with patients in other disease categories including ischemic heart disease and dilated cardiomyopathy. No significant differences were seen in histological rejection between male and female recipients. On the other hand, patients over 55 years of age were found at lower risk of histological rejection. The results of this analysis have demonstrated quite clearly, but not unexpectedly, that a greater degree of HLA mismatching correlates with increased cellular rejection. This effect was noted not only for the HLA-A,B and DR antigens, but also HLA-DQ and HLA-DRw52/53 antigens. In multivariate analysis, the highest level of statistical significance was obtained for the combined HLA-A,B,DR and DQ group. Sensitized patients with panel-reactive lymphocytotoxic antibodies of greater than 10% experienced more histological rejection than nonsensitized patients. On the other hand, a positive lymphocytotoxic crossmatch did not appear to influence cellular rejection of cardiac allografts. Also, no differences were seen in histological rejection between ABO-identical and compatible heart transplants. These findings further support the concept that donor HLA compatibility and pretransplant sensitization represent significant risk factors for cellular rejection in cardiac transplantation.

Adolescent↗
PubMed1991

Alveolar macrophage migration after lung transplantation.

Pulmonary infection is a major source of morbidity and mortality in recipients of lung allografts. The alveolar macrophage plays an important role in pulmonary host defense, and to fulfill this role it must have the ability to orient and migrate in the direction of a stimulus. Thus migratory activity was measured in cells recovered from lung transplant recipients by bronchoalveolar lavage. The primary patient group consisted of recipients who had no evidence of infection or rejection at the time of bronchoalveolar lavage. These patients were further subdivided into an early postoperative group (less than 6 wk posttransplant) and a late postoperative group (greater than 6 wk posttransplant). Other categories included patients with chronic rejection and a small group of patients with Pneumocystis carinii pneumonia. Alveolar macrophages recovered by bronchoalveolar lavage were assayed for migratory response to N-formylmethlonylphenylalanine and endotoxin-activated human serum. Stimulated migration of cells from healthy recipients obtained in the late postoperative course was similar to that of normal control subjects, but stimulated migration of cells from healthy recipients in the early postoperative period and those undergoing chronic rejection was greater than expected. Spontaneous migration was similar in all groups except those with P. carinii pneumonia, in whom it was greatly increased. We conclude that alveolar macrophage migration is not impaired in lung allograft recipients without apparent signs of infection or rejection and is in fact increased during periods of possible macrophage activation (shortly after transplantation and during chronic rejection).

Bronchoalveolar Lavage Fluid↗
PubMed1991

The effect of obliterative bronchiolitis on breathing pattern during exercise in recipients of heart-lung transplants.

The more rapid and shallow ventilation pattern seen during exercise in patients with obstructive and/or restrictive lung disease has been attributed by some investigators to the effects of vagal afferents from intrapulmonary receptors. Recipients of heart-lung transplants (HLTR) offer a unique opportunity to test this hypothesis since they have denervated lungs and may develop obliterative bronchiolitis after organ rejection. We thus compared the ventilation responses to incremental bicycle ergometry of five HLTR with relatively normal pulmonary function (HLTR-N) and four with bronchiolitis obliterans (HLTR-O). We compared the slopes of the linear portion of the tidal volume versus inspired minute ventilation relationship of both groups. The rate of rise of tidal volume (VT) (slope of VT versus VI) was greater in HLTR-N (0.31 +/- 0.004) than in HLTR-O (0.023 +/- 0.007) (p less than 0.05). This corresponded to a slower increase in respiratory rate (RR) (slope of RR versus Vl/cm) in HLTR-N (0.055 +/- 0.005) than in HLTR-O (0.083 +/- 0.019) (p less than 0.01). Furthermore, values for VT, inspiratory time (TI), and duty cycle (TI/Ttot) measured during exercise at the VT break point were all significantly lower in the HLTR-O than in HLTR-N. We also evaluated the ability of HLTR with lung disease to regulate their ultimate level of ventilation during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Native right atrial tamponade with the Jarvik total artificial heart.

Following a massive myocardial infarction culminating in cardiogenic shock, a 61-year-old man underwent implantation of the Jarvik 70-ml total artificial heart. On the fifth postoperative day, hemodynamic instability coupled with subtle radiographic changes and impaired mechanical right ventricular diastolic inflow were instrumental in establishing the diagnosis of localized native right atrial tamponade. To our knowledge, this report is the first detailed discussion of this phenomenon.

Cardiac Tamponade↗
PubMed1991

Interim use of Jarvik-7 and Novacor artificial heart: blood rheology and transient ischemic attacks (TIA's).

The rheological properties of blood were studied in patients supported by both the Jarvik-7 total artificial heart (TAH) and Novacor left ventricular assist device (LVAD) as a bridge to cardiac transplantation. Both groups of patients had abnormalities in blood rheology which differed according to the type of device implanted as well as on the clinical state of the patient. The rheology of individual patients correlated well with their clinical status and outcome, with incidences of TIA's and/or stroke being accompanied by marked increases in relative blood viscosity, erythrocyte rigidity, fibrinogen concentration and platelet aggregation in varying combination. Observed abnormalities in blood rheology were also crucial to thrombus formation on artificial heart valves as well. Our results show that the therapeutic management of rheological parameters should prove to be a unique and clinically rewarding approach to these patients.

Adult↗