Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 397 records · Page 22Linked to original sources

PubMedDate not supplied

Interleukin-6, a marker of preservation injury in clinical lung transplantation.

Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284 +/- 78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (> 7 days), (2) the arterial/alveolar oxygen tension ratio (PaO2/PAO2 ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n = 6) and group II (n = 10), depending on whether the 4-hour IL-6 level was more than 1000 pg/ml or less than 500 pg/ml, respectively. Group I patients required longer intubation (p < 0.01) and had a lower PaO2/PAO2 ratio (p < 0.001), more diffuse alveolar damage (p < 0.01), and a lower graft survival rate (p < 0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Graft cytokine mRNA activity in rat single lung transplants by reverse transcription-polymerase chain reaction: effect of cyclosporine.

Intragraft levels of cytokine mRNA were studied in an orthotopic rat left lung transplant model. Three groups of rats were compared at 7 days after transplantation. Isogeneic (Lewis to Lewis), allogeneic (Brown-Norway to Lewis) untreated, and cyclosporine-treated (25 mg/kg/day, intramuscularly) allogeneic animals underwent analysis of cytokine mRNA isolated from total RNA in freshly excised grafts. Reverse transcription-polymerase chain reaction amplification of interleukin (IL)-2, IL-4, and actin (control) mRNA was performed with custom-synthesized oligonucleotide amplimers targeted to known sequences of rat IL-2 and IL-4 cDNA. Semiquantitative analysis was performed by radioanalytic scanning of gel preparations. Sample specimens from the retrieved grafts were also graded histologically for rejection on a five-point scale. Rejection was most severe in the untreated allografts (p < 0.003). IL-2 mRNA was significantly greater in the untreated allografts when compared with isografts (p < 0.05) and cyclosporine-treated allografts (p < 0.05). No significant differences in IL-4 mRNA between groups were observed. We conclude that semiquantitative analysis of cytokine mRNA by reverse transcription-polymerase chain reaction is a useful and sensitive method for the study of acute rejection in lung grafts and that this technique may become an important tool in future studies of cytokine-mediated responses in cyclosporine-treated allografts.

Actins↗

PubMedDate not supplied

Utility of prostaglandin E1 in the pretransplantation evaluation of heart failure patients with significant pulmonary hypertension.

Patients with chronic heart failure frequently have pulmonary hypertension. Because severe preoperative pulmonary hypertension predicts a poor outcome after orthotopic transplantation, pulmonary vasoreactivity is evaluated frequently in the pretransplantation screening of heart failure patients. We prospectively evaluated the utility of the direct pulmonary vasodilator, prostaglandin E1, and compared it to the nonspecific vasodilators, nitroglycerin and sodium nitroprusside, in the evaluation of pulmonary hypertension in 39 heart transplantation candidates. Prostaglandin E1 significantly lowered pulmonary artery pressure, transpulmonary pressure gradient, and pulmonary vascular resistance. An adequate pulmonary vasodilator response (defined as a decline in transpulmonary pressure gradient to less than 15 mm Hg) occurred in 31 patients (79%). In a subgroup of nine patients also tested with nitroglycerin, greater reductions (p less than 0.01) in both transpulmonary pressure gradient and pulmonary vascular resistance occurred with prostaglandin E1, compared to nitroglycerin. Five of six patients who did not respond to nitroglycerin responded to prostaglandin E1. In another subgroup of 12 patients who were also evaluated with sodium nitroprusside, prostaglandin E1 produced a larger decline (p less than 0.05) in transpulmonary pressure gradient and pulmonary vascular resistance than did sodium nitroprusside. Six of eight patients who did not respond to sodium nitroprusside responded to prostaglandin E1. Based on pulmonary vasodilator response to prostaglandin E1, 27 patients were accepted on the transplantation waiting list, and eight patients underwent orthotopic transplantation. Postoperatively, acute right ventricular failure of the donor heart developed in none of these patients. Significant hemodynamic improvement occurred by 24 hours and persisted through 4 weeks of postoperative follow-up in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

PubMedDate not supplied

Donor cerebral emboli as a cause of acute graft dysfunction in lung transplantation.

Early graft dysfunction in lung transplantation has many causes, most commonly preservation injury. This report details a more unusual cause of graft failure and respiratory decompensation in the early postoperative period donor cerebral emboli occluding segments of the pulmonary arterial tree in the implanted lung allografts of two patients who had received single lung implants from a common donor in whom massive cerebral trauma had been incurred in a motor vehicle accident. The incidence, complications, and clinical manifestations of cerebral emboli are discussed.

Adolescent↗

PubMedDate not supplied

Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography.

Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Cytomegalovirus infection and survival in lung transplant recipients.

Fifty-nine patients who survived more than 30 days after lung transplantation (52 heart-lung, seven double lung, and two single lung) were studied for mortality and morbidity related to cytomegalovirus (CMV) infection. CMV infection developed in 32 patients (54%) and was more common in the preoperatively CMV seropositive group (95%) as compared with the seronegative group (38%). Symptomatic infections, pneumonitis, and CMV-related mortality, however, were higher in the seronegative (primary infection) group and actuarial survival was worse in these patients (40% and 23% at 1 and 5 years, respectively). Transplantation of CMV-seropositive donor organs was associated with a significantly higher incidence of primary infection and use of seronegative blood products led to a decrease in the primary CMV infection rate. The mortality of primary CMV infection was 54% and this was associated with a significantly higher rate of pulmonary superinfections in the first year after transplantation. The incidence of late pulmonary infections was associated with the development of chronic rejection rather than CMV status. We conclude that primary CMV infection has a major impact on the outcome after lung transplantation. The high mortality of primary infections justifies an aggressive approach to prevention and treatment in the at-risk seronegative group.

Actuarial Analysis↗

PubMedDate not supplied

Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression.

Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989. The overall incidence of posttransplant lymphoproliferative disease in patients who survived more than 30 days is 4%. The incidence after heart transplantation is 3.4% and after lung transplantation is 7.9% (p = 0.08). The peak occurrence of posttransplant lymphoproliferative disease is 3 to 4 months after transplantation. However, posttransplant lymphoproliferative disease occurring early versus late (defined as before or after 1 year after transplantation) appears to have different clinical outcomes. The mortality of early onset of posttransplant lymphoproliferative disease as a result of lymphoma is 36%; response to reduction in immunotherapy occurs in 89% and presentation with disseminated disease occurs in 23%. The mortality of late onset of posttransplant lymphoproliferative disease as a result of lymphoma is 70%; no patient responded to reduction in immunotherapy and presentation with disseminated disease occurs in 86% of patients. Epstein-Barr virus primary infection was present in 14 and secondary Epstein-Barr virus infection was present in three of the 20 patients with posttransplant lymphoproliferative disease. The other three patients were positive for Epstein-Barr virus also but had no pretransplant sera for comparison. There is no correlation with immunoprophylaxis or maintenance immunosuppression and the development of posttransplant lymphoproliferative disease in our series.

Cyclosporine↗

PubMedDate not supplied

Thrombin generation in cardiac device recipients.

Thrombin generation measured after LVAS (4 patients) and TAH (1 patient) implantation was found to be elevated (3 times normal) in the first postoperative week and declined to normal levels when anticoagulation was begun. Thrombin generation was not elevated at the times of thromboembolic events (TIAs; N = 4 episodes).

Heart, Artificial↗

PubMedDate not supplied

Univentricular support results in reduction of pulmonary resistance and improved right ventricular function.

A retrospective analysis was performed to assess the effects of univentricular support on the transpulmonary gradient (TPG), pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and right ventricular ejection fraction (RVEF) in 16 patients who spent from 2 to 144 days (mean, 61) on the Novacor left ventricular assist system ([LVAS] Novacor Corp., Baxter Healthcare, Oakland, CA) as a bridge to cardiac transplantation. Results revealed a significant reduction in the TPR, and improvement in RVEF while patients were on the LVAS. After orthotopic heart transplantation (OHTx), TPG and PVR were significantly lower than when calculated before support. It was concluded, therefore, that the reduction in the TPR and the improvement in the RVEF, seen in patients who were provided univentricular support with the Novacor LVAS, are associated with a significant reduction in the TPG and the PVR, which are persistent after OHTx. Four patients who otherwise would have been considered at higher risk for OHTx because of elevated pulmonary resistance before veniventricular support underwent successful OHTx after LVAS support.

Adolescent↗

PubMedDate not supplied

Effects of long-term Novacor artificial heart support on blood rheology.

This study presents characteristics of hemorheology for six patients during long-term support (85-144 days) on a Novacor left ventricular assist device (LVAD) as a bridge-to-cardiac transplantation. Results indicate that a certain "baseline" rheology can be identified in patients whose support was uneventful. However, in the patients who had one or more neurologic episodes during support, these events were associated with altered hemorheology, including increases in plasma and relative blood viscosity, and red cell rigidity.

Blood Proteins↗

PubMedDate not supplied

Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation.

Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection.

Actuarial Analysis↗

PubMedDate not supplied

Increased perioperative lung preservation injury with lung procurement by Euro-Collins solution flush.

In 47 donor organ procedures for heart-lung transplantations, lungs were preserved by autoperfusion in 21 cases and by Euro-Collins solution flush in 26 cases. Criteria used to diagnose inadequate allograft function included radiographic interstitial and alveolar infiltrates and an alveolar-arterial oxygen gradient significantly greater than 100 mm Hg at 24 hours after surgery. Oxygen gradients were calculated intraoperatively, on arrival in the intensive care unit, and during the first 24 hours after surgery. With these criteria, 15 patients with perioperative preservation damage were identified. They were compared with 32 patients without evidence of preservation injury. Patients with preservation injury showed persistently elevated alveolar-arterial oxygen gradients that were significantly above noninjury values at all times (p less than 0.03). There was no difference in donor organ ex vivo time between the two groups (227.8 +/- 74.4 vs 169.5 +/- 76.9, p = NS). The incidence of perioperative preservation injury was significantly greater among patients in the Euro-Collins solution group (12/26) than in patients with autoperfusion (3/21) (p = 0.04, Fisher's exact test). Three of the 15 recipients died of primary lung graft failure. In our hands, preservation by use of a modified Euro-Collins solution flush technique has led to unpredictable results in lung transplantation.

Adolescent↗

PubMedDate not supplied

Monoclonal versus polyclonal antibody therapy for prophylaxis against rejection after heart transplantation.

Between August 1986 and December 1987, 88 patients received either RATG or OKT3 for immunoprophylaxis before heart transplantation. By the end of the first month after transplantation, 25% of the patients who received RATG had experienced a rejection episode compared with 43% of those receiving OKT3. This difference was persistent as many as 4 months after transplantation. While 50% of the OKT3 patients had a second episode of rejection, only 35% of the RATG patients did so. Randomization of these agents was complicated by severe cardiopulmonary side effects attributed to the first dose of OKT3. Five hours after the first dose of OKT3, a 25% drop in mean arterial pressure, accompanied by significant hypoxia, was seen in a majority of patients. There was no difference in the incidence of infection between the two groups.

Antibodies, Monoclonal↗

PubMedDate not supplied

Comparative trial of immunoprophylaxis with RATG versus OKT3.

A randomized trial of rabbit antithymocyte globulin (polyclonal) versus OKT3 monoclonal antibody prophylaxis was carried out in 82 heart transplant recipients, who, in addition, received baseline immunosuppression with cyclosporine, azathioprine, and prednisone. One-year actuarial survival was comparable between groups (95% to 98%), but the likelihood of histologic rejection within the first 30 days of transplant was more than seven times greater in OKT3 patients (0.58/patient vs 0.08/patient). Patients receiving OKT3 were more likely to have repeated episodes of rejection, and the mean time to rejection for patients receiving OKT3 was shorter (33 days) than for patients receiving rabbit antithymocyte globulin (67 days). At 120 days, while 52% of patients receiving rabbit antithymocyte globulin were free of rejection, versus 37% of the OKT3 patients, the difference was not significant. There was no difference in the incidence of major or minor bacterial or viral infection between groups, but significant hemodynamic side effects were seen after the first dose of OKT3, and aseptic meningitis developed in two OKT3 patients.

Animals↗

PubMedDate not supplied

Influence of the donor lung on development of early infections in lung transplant recipients.

Infection of the lung allograft is the greatest cause of morbidity and mortality after heart-lung transplantation. To better understand the pathogenesis of these infections, we compared the results from cultures of the donor tracheas with the type and prevalence of early intrathoracic infections in the recipients. In the last 37 recipients, intrathoracic infections occurred within 2 weeks of operation in 16 (43%). Organisms isolated from the donor tracheal cultures were different from those associated with early infections, except for three of four recipients with heavy growth of Candida in donor tracheal cultures, in whom fatal invasive candidiasis developed caused by the same species of Candida isolated from the donor culture. Comparisons were made between recipients with (n = 16) and without early infection (n = 21) for age of donors and recipients, ischemic time, length of donor stay in an intensive care unit, donor arterial oxygen pressure, duration of recipient intubation, sterile donor tracheal culture or culture with presence of mouth flora, bacterial pathogens, or Candida, method of lung preservation, and antibiotic prophylaxis of donor. The only factor significantly associated with the onset of early infection was the presence of mouth flora in the donor tracheal culture (p = 0.004, Fisher's exact test, two sided). Multiple logistic regression was performed to test the additional contribution of other covariates after adjusting for the presence of mouth flora. None of the other covariates contributed to the occurrence of early infection. Recipients with early infection had a significantly lower survival compared with those without early infection (p = 0.04) by the Kaplan-Meier survival analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMedDate not supplied

Artificial heart. Hemorrheology and transient ischemic attacks.

Hemorrheology was studied in patients undergoing artificial heart support as a bridge-to-cardiac transplantation. Abnormal hemorrheology was seen in two patients, one on a Jarvik-7 total artificial heart, and the other on a Novacor left ventricular assist device. Both of these patients suffered neurologic episodes. The rheology of these two patients coincided well with their clinical status, and was accompanied by marked increases in relative blood viscosity, erythrocyte rigidity, fibrinogen concentration, and platelet aggregation. Results show that improving hemorrheology may be a beneficial avenue to pursue in preventing or treating transient ischemic attacks or other complications in patients during support with mechanical devices.

Blood Flow Velocity↗

PubMedDate not supplied

Novacor left ventricular assist filling and ejection in the presence of device complications.

In order to better understand the relationship among certain device related complications and Novacor left ventricular assist system (LVAS) pumping parameters, a Mock Circulatory Loop was utilized to simulate the following clinically realistic conditions: 1) inflow valve regurgitation, 2) inflow cannula obstruction, 3) outflow valve regurgitation, and 4) outflow cannula obstruction. Various pumping parameters (e.g., pump rate, stroke volume, pump output) were recorded at baseline (control) and during each simulation. Additionally, pump volumes were continuously recorded and differentiated for calculation of rates of pump filling (FR) and ejection (ER). The results indicate that perfusion pressures and rates of filling and ejection change significantly in the presence of device complications. The implications of these findings, as relates to assessment of pump operation in LVAS patients, are discussed.

Blood Volume↗

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Early and late tamponade with the Novacor left ventricular assist system.

Cardiac tamponade can be a major complication after implantation of the Novacor left ventricular assist system (LVAS). Between 1987 and 1989, 14 patients received an LVAS as a bridge to cardiac transplantation: 3 developed early tamponade (33 +/- 12 hr postoperatively) and 5 were diagnosed with a late tamponade (9.4 +/- 3.2 days postoperatively). One patient had both early and late tamponade. Early tamponade was more common in those with increased perioperative blood loss (5,270 +/- 1,942 ml vs. 1,420 +/- 1,160 ml in other patients, p less than 0.05). Early tamponade was suggested by reduction in mean arterial pressure (74 +/- 1 to 64 +/- 3 mmHg), LVAS output (5 +/- 0.5 to 2.7 +/- 0.7 L/min), LVAS stroke volume (55 +/- 4 to 23 +/- 5 ml), and an increase in central venous pressure (13 +/- 1 to 21 +/- 1 mmHg, p less than 0.05 for all values). Late tamponade was associated with a marked rise in central venous pressure (14 +/- 1 to 22 +/- 2 mmHg, p less than 0.05), with only a mild decrease in LVAS output (4.9 +/- 1 to 3.8 +/- 0.9 L/min) and stroke volume (49 +/- 8 to 36 +/- 3 ml), without a significant change in mean arterial pressure. Two of these five late episodes occurred in patients who were anticoagulated with heparin (PTT 52 and 100 sec), and in one other with warfarin (PT 27 sec, PTT 55 sec); two patients were not on any anticoagulants. Surgical drainage of pericardial effusions, and especially of clotted blood found frequently posterior to the left ventricle in the space created by the LVAS decompressed left ventricle, resulted in an immediate return of all hemodynamic measurements to normal in both early and late tamponade.

Adult↗