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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 217 records · Page 12Linked to original sources
PubMed1990

Coronary arteriosclerosis in pediatric heart transplant survivors: limitation of long-term survival.

Because coronary atherosclerosis after heart transplantation has been a limiting problem in long-term survival of adults, we reviewed the coronary angiograms, and autopsy data when available, from 21 of 30 children who underwent orthotopic heart transplantation and survived the perioperative period. Six patients had coronary atherosclerosis, and five of these patients died 6 months to 3 years after heart transplantation. The late deaths were sudden and unexpected. Coronary angiography demonstrated several types of lesions, including concentric narrowing, tubular segmental lesions, and abrupt obliteration of major coronary vessels. Risk factors assessed included hypertension, hyperlipidemia, cytomegalovirus infection, type of immunosuppressive regimen, number of rejection episodes, and major histocompatibility antigen mismatches. Only the frequency and duration of rejection episodes seemed to be more prevalent in the patients in whom coronary atherosclerosis developed. Despite the benefits of heart transplantation in treating children with end-stage heart disease, coronary atherosclerosis may limit long-term survival. We suggest that these children should undergo serial coronary angiography to identify those at risk for subsequent events related to coronary artery disease.

Adolescent↗
PubMed1990

Proliferative responses of bronchoalveolar lavage lymphocytes from heart-lung transplant patients.

Donor-specific alloreactivity of bronchoalveolar lavage (BAL) lymphocytes was evaluated in the immunologic monitoring of lung transplant patients. The study dealt with 161 BAL performed on 28 transplant recipients. Unseparated BAL cells, separated BAL lymphocytes, and PBL were tested for donor-specific proliferative responses in 3-day primed lymphocyte testing (PLT), and for nonspecific proliferative responsiveness to exogenous IL-2. The proliferation data were analyzed for correlation with the status of the lung allograft assessed clinically, histologically, and by pulmonary function testing. Positive PLT responses of BAL lymphocytes were observed in 20 of 22 acute rejection episodes (91%) and in 24 of 35 cases (69%) when chronic rejection was diagnosed. During clinical quiescence donor-specific proliferative activity was demonstrated in only 4 of 35 cases (11%). Thus, acute rejection and chronic rejection correlated significantly (P less than 0.001) with donor-specific PLT reactivity of BAL lymphocytes. Though significant association with rejection was observed for the alloreactivity of unseparated BAL cells and PBL, the sensitivity of the PLT test with these cells was significantly lower than that with BAL lymphocytes. Similarly, the IL-2 proliferative activity of BAL lymphocytes was significantly increased during acute and chronic rejection. However, this test had lower sensitivity and specificity than did the donor-specific PLT. These findings suggest the usefulness of the donor-specific PLT of BAL lymphocytes as a reliable method for monitoring pulmonary rejection.

Adolescent↗
PubMed1990

Heart transplantation in diabetic recipients.

Preexisting diabetes mellitus (DM) has been regarded as a contraindication to heart transplantation (HT). This prejudice has been based upon concern over increased infection rates and worsening DM with the initiation of prednisone immunosuppression. To better evaluate these suppositions, we reviewed our experience with diabetic patients who underwent HT. Between 6/80 and 1/88, 367 nondiabetics (NDs) and 19 diabetics underwent HT at our institution. Of the 19 diabetic recipients (DRs), two were black and four were female. Six DRs were on insulin (average daily dose: 46 U) prior to HT, and the remainder required oral hypoglycemic agents. Following HT, five DRs had insulin substituted for oral hypoglycemics. The 11 insulin-dependent DRs now require an average daily dose of 48 U. The average duration of follow-up for the 19 DRs was 17 months (range 1-67 months). During this time, 5 hospitalizations were required for complications of diabetes. The rejection rate was not higher for the DRs than the NDs (0.37 events/100 pt. days vs. 0.51 events/100 pt. days). The DRs who have undergone coronary angiography up to 4 years following HT have had no evidence of coronary atherosclerosis. Three-year survival for DRs and NDs is similar. DRs have a slightly higher incidence of lethal infections than NDs, which is not statistically significant (16% at 17 months vs. 10% (p greater than 0.4). We conclude that carefully selected diabetics can undergo HT with minimal consequent worsening of their DM. Diabetic HT recipients do not suffer a higher incidence of graft atherosclerosis, rejection, or lethal infection.

Coronary Disease↗
PubMed1990

Optimal perioperative immunosuppression in cardiac transplantation using rabbit antithymocyte globulin.

A randomized trial of RATG (polyclonal) vs. OKT3 (monoclonal) antibody prophylaxis was carried out in 82 cardiac transplant recipients who, in addition, received baseline immunosuppression with cyclosporine, azathioprine and prednisone. One-year actuarial survival was comparable between groups (95% and 98%). The incidence of moderate or severe rejection within the first 30 days of transplant was over 7 times greater in patients receiving OKT3 vs. those receiving RATG. 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 RATG patients (67 days). At 120 days, 52% of RATG patients were free of rejection while only 37% of the OKT3 patients were rejection-free. There was no difference in the incidence of major or minor bacterial or viral infection between groups. Patients receiving OKT3 showed a less-prolonged depression of the CD3 and CD4 T cell subsets than did those receiving RATG. Significant hemodynamic side-effects were seen after the first dose of OKT3 and there was a 5% incidence of aseptic meningitis associated with its use.

Antibodies, Monoclonal↗
PubMed1990

Hemodynamic parameters influencing clinical performance of Novacor left ventricular assist system.

The interrelationships between hemodynamic variables including right ventricular (RV) performance with filling/ejection dynamics of the Novacor left ventricular assist system (LVAS) were determined in 10 of 11 patients who received LVAS as a bridge to heart transplant. Nine were successfully transplanted. Data were obtained intraoperatively, at periodic intervals up to 48 h postimplant and at explant. The hypotheses investigated included (a) RV performance influences LVAS filling characteristics and (b) LVAS pump output is influenced by systemic vascular resistance (SVR). During the period of LVAS support (2-126 days), pumping characteristics included a mean filling volume of 51 ml (range, 24-70), residual volume of 4.9 ml (range, 1-18), pump rate of 113/min (range, 63-175), and pump output of 5.81/min (range, 2.8-8.2). Multiple regression analysis identified pulmonary vascular resistance (PVR), RV stroke work index (RVSWI), and pulmonary capillary wedge pressure, but not RV ejection fraction, pulmonary artery pressure, or central venous pressure (CVP) as the most important correlates with LVAS filling volume (p less than 0.001, R2 = 0.6). In addition, LVAS pump output was influenced mainly by RVSWI, PVR, and SVR (p less than 0.001, R2 = 0.7). It was concluded that LVAS performance is highly dependent on RV function and systemic/pulmonary vascular resistances.

Equipment Design↗
PubMed1990

Role of primary and secondary maternal viremia in transplacental guinea pig cytomegalovirus transfer.

The modulation of the outcome of intrauterine guinea pig cytomegalovirus (GPCMV) infection by maternal viremia was investigated in the guinea pig model. Virus assay and in situ hybridization were used to study GPCMV infection of maternal blood, placentas, and fetuses following inoculation of pregnant guinea pigs by the subcutaneous, intracardiac, or intranasal route. Animals were inoculated in early gestation and were evaluated every 7 to 10 days throughout pregnancy. Although placental and fetal infections occurred in all groups examined, transfer of GPCMV to placentas and fetuses was most efficient in mothers inoculated subcutaneously. Primary viremia was followed by virus clearance from blood and by an episode of secondary viremia in the three groups of mothers examined. Placental and fetal infections in animals infected subcutaneously or intracardially were first detected at the time of primary viremia, persisted throughout gestation, and increased during secondary viremia. In contrast, placental and fetal infections in animals inoculated intranasally were demonstrated primarily during secondary viremia. Fetal infection was detected in all mothers with detectable primary and secondary viremia but in only 33% of mothers that experienced only primary viremia. These results suggest that secondary maternal viremia is associated with increased placental and fetal GPCMV infections.

Abortion, Spontaneous↗
PubMed1990

Biomedical engineering management of Novacor left ventricular assist system (LVAS) patients.

As the number of cardiac transplant centres increases, there is an associated decrease in the availability of donor organs per centre. Subsequently, hospitals are utilizing cardiac assist systems (total artificial heart and ventricular assist devices) as a bridge to cardiac transplantation. Because of the engineering complexities related to the clinical implantation and follow up of these devices, a successful centre should have a well co-ordinated biomedical engineering programme. These engineers are responsible for the calibration, monitoring, and continued operation of these units. This paper is intended to serve as a guide to any centre interested in utilizing total artificial heart and ventricular assist systems, in particular the Novacor left ventricular assist system, and focuses on the management and function of the biomedical engineering component of our cardiac assist programme.

Biomedical Engineering↗
PubMed1990

Bronchial cartilage alterations in lung transplantation.

Changes in the hyaline cartilage of the proximal bronchial tree were investigated in a group of combined heart-lung and double-lung recipients with and without OB. Ossification, calcification and fibrovascular ingrowth into the normally avascular hyaline bronchial cartilage were observed in almost all patients and were independent of small or large airway inflammation. Alterations in the integrity of hyaline cartilage have been produced by others in animals by ligation of the blood supply. Finding similar changes in airway cartilage of all transplanted lungs argues that there is relatively poor perfusion to the proximal air-conducting passage. Such a mechanism may contribute to the development of OB, bronchiectasis and a predilection for infections following pulmonary transplantation.

Bronchi↗
PubMed1990

The pulmonary donor.

This article discusses the Pittsburgh experience with the pulmonary donor and provides guidelines for the maintenance and selection of appropriate donor lungs. Criteria for the selection of the pulmonary donor include absence of radiographic abnormality, minimal ventilation-perfusion mismatch, and an absence of identifiable infection. Because early thoracic infections result in a high mortality, donors are excluded if white cells, fungi, or bacteria are noted in samples obtained from tracheal aspirates or bronchoscopic examination. A number of techniques for the procurement of donor lungs are currently satisfactory and include core cooling with the use of cardiopulmonary bypass and different hypothermic pulmonary artery flush solutions. Other clinical preservation techniques are discussed, including autoperfusion and the use of blood-based pulmoplegia and University of Wisconsin storage solution. Because so much of the outcome following pulmonary allografting is based on the quality of the donor lungs, much of the future direction in pulmonary transplantation must be directed toward a continuing investigation of better methods for selection and maintenance of the donor and ex vivo preservation.

Adult↗
PubMed1990

Bradyarrhythmia after heart transplantation. Incidence, time course, and outcome.

From June 1980 to April 1989, 72 of 401 (18%) adult recipients of orthotopic heart transplantation developed prolonged (greater than 24 hours) bradyarrhythmias (less than 60 beats/min) within 5 days after transplantation. Junctional bradycardia occurred in 50 (69%) recipients, sinus bradycardia in 18 (25%), and slow ventricular response during atrial fibrillation in four (6%). Fifty-five of 72 (76%) patients had bradyarrhythmias of less than 20 days' duration (less than 7 days, 50 patients; 7-20 days, five patients). Fifty patients returned to sinus rhythm (greater than 60 beats/min) by the time of discharge. Five patients expired within 20 days. Seventeen of 72 (24%) patients had bradyarrhythmia for more than 20 days, which was symptomatic in 11. All 17 patients (junctional bradycardia, 13 patients; sinus bradycardia, four patients) received a permanent pacemaker within 40 days after transplantation. Between 1 and 12 months (mean, 4 +/- 3 months) after pacemaker implantation, 12 patients recovered sinus rhythm (greater than 70 beats/min). The other five patients had intrinsic rates of 32-57 beats/min (mean, 48 +/- 10 beats/min) during 1-9 months (mean, 4 +/- 3 months) of follow-up. The donor ischemic time in bradyarrhythmia patients was 202 +/- 34 minutes, which was significantly longer (p less than 0.01) than the 173 +/- 43 minutes for those patients without bradyarrhythmia. Conclusively, the incidence of posttransplantation bradyarrhythmia is relatively high. It is usually temporary, however, even in patients with a prolonged duration of bradyarrhythmia. A relation appears to exist between donor ischemic time and the incidence of bradyarrhythmia.

Adult↗
PubMed1990

Aerosolized cyclosporine as single-agent immunotherapy in canine lung allografts.

Current systemic immunosuppressive regimens are unable to prevent lung allograft rejection consistently and are associated with significant morbidity and death. Acute rejection has occurred in 40% and chronic rejection in 50% of our lung recipients. We hypothesized that regional immunotherapy with aerosolized cyclosporine would prevent or reduce lung allograft rejection while allowing for low systemic drug delivery. In a canine model of unilateral lung allotransplantation, aerosolized cyclosporine was delivered directly to the allograft. Acute rejection was prevented or reduced in all treated recipients. All control animals had severe acute rejection. Intragraft cyclosporine concentration was high and systemic drug delivery was low, as evidenced by low whole-blood cyclosporine levels and low tissue cyclosporine levels in skeletal muscle. Ninety-five percent of whole-blood trough cyclosporine levels were less than 150 ng/ml. Aerosolized cyclosporine was able to prevent or reduce acute pulmonary rejection and resulted in minimal systemic drug delivery.

Aerosols↗
PubMed1989

Resolution of severe pulmonary hypertension after heterotopic cardiac transplantation.

In patients with severe congestive heart failure, a marked elevation in pulmonary vascular resistance limits the success of orthotopic cardiac transplantation, thus providing the rationale for heterotopic transplantation. To determine the changes in pulmonary hemodynamics after heterotopic cardiac transplantation, postoperative right heart pressures were serially measured in five patients who underwent this operation for end-stage congestive heart failure accompanied by severe secondary pulmonary hypertension and elevation in calculated pulmonary vascular resistance. Hemodynamics were compared with those of a matched group of 10 orthotopic cardiac transplant recipients. Preoperatively, pulmonary artery mean and wedge pressures, pulmonary vascular resistance and transpulmonary pressure gradient (pulmonary artery mean minus wedge pressure) were significantly higher in the heterotopic group. Postoperatively, significant improvement in pulmonary hemodynamics occurred in both groups and, by 12 months, the pulmonary artery mean pressure, wedge pressure, pulmonary vascular resistance and transpulmonary pressure gradient were similar in the two groups. These findings suggest that pulmonary hypertension secondary to congestive heart failure, even when severe and associated with a high pulmonary vascular resistance, is to a great extent reversible.

Adult↗
PubMed1989

Central nervous system infections in heart and heart-lung transplant recipients.

Infections, a major cause of morbidity and mortality in immunosuppressed heart and heart-lung transplant recipients, frequently involve the central nervous system and can produce devastating neurologic sequelae. Between 1980 and 1987, a total of 363 heart transplant and 54 heart-lung transplant recipients at the University of Pittsburgh sustained 13 intracranial infections two to 143 weeks after transplantation. Computed tomography demonstrated well-defined Nocardia and Aspergillus abscesses in four patients. Cerebrospinal fluid was normal in all cases studied, including in those patients in whom culture confirmed meningitis. Computed tomography-guided stereotactic surgery was used to diagnose and aspirate two nocardial brain abscesses. The prognosis for patients with central nervous system infections was related to their overall condition at the time of diagnosis. Both patients with nocardial abscesses and one patient with Listeria leptomeningitis survived, but all ten other patients died because of extensive multisystem infectious complications.

Adolescent↗
PubMed1989

Hemodynamic abnormalities following cardiac transplantation: relationship to hypertension and survival.

The prevalence and long-term implications of hemodynamic abnormalities seen at 1 year following orthotopic heart transplantation and their relationship to post-transplant hypertension were prospectively evaluated in 82 consecutive asymptomatic recipients taking cyclosporine and prednisone who underwent annual catheterization. Abnormal left ventricular end-diastolic pressure (LVEDP), ejection fraction (EF), and left ventricular end-diastolic pressure-volume ratio (R) were the most prevalent hemodynamic abnormalities (27%, 14%, and 23%, respectively, at 1 year). Patients with abnormal LVEDP or R had higher (p less than 0.05) mean systemic arterial pressure (MAP). During follow-up, hemodynamic abnormalities disappeared in some patients while they developed in some others. Transplant patients with abnormal LVEDP, EF, or R at 1 year who normalized at 2 years had a significant (p less than 0.05) decrease in MAP. Likewise, patients with normal LVEDP, EF, or R at 1 year who subsequently developed abnormalities had a significant (p less than 0.05) increase in MAP. The presence of hemodynamic abnormalities at 1 year was not associated with a poorer survival (mean follow-up 2.6 +/- 1.1 years). In summary, hemodynamic abnormalities in asymptomatic transplant recipients taking cyclosporine and prednisone appear to be related to the level of post-transplant hypertension and do not signify an adverse prognosis over the first 3 years.

Adult↗