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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

At least 73 records · Page 4Linked to original sources
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

Cyclosporine nephrotoxicity in cardiac allograft patients--a seven-year follow-up.

Renal function was observed retrospectively in a population of 228 adults who underwent a cardiac allograft at the University of Pittsburgh from June 1980 through June 1987, survived a minimum of one year, and received cyclosporine. Renal function was determined by serial measurement of serum creatinine concentration. Serum creatinine rose from 1.2 +/- 0.0 mg/dl at time of hospital discharge to 2.0 +/- 0.0 mg/dl at two and four years and 3.3 +/- 0.1 mg/dl at seven years. The fall in renal function was biphasic, with a rapid decline (reciprocal creatinine slope -0.018 dl/mg-mo) through 24 months and a slower decline thereafter -0.0036 dl/mg/month). This occurred despite a progressive decrease in cyclosporine levels from 668 +/- 23 ng/ml (whole blood RIA) to 380 +/- 12 ng/ml at seven years. Three of 222 patients (1.6%) developed end-stage renal disease within 18 months of initiation of cyclosporine therapy. Only one additional patient of 26 followed through 54 months (3.8%) developed end-stage disease thereafter. The decline in renal function seen with cyclosporine is rapid in the first 18 months, with a slower but continuing decline seen with later follow up. At least in heart transplantation, the risk of end-stage renal disease is significant, but not prohibitive.

Adult↗
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

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↗
PubMed1989

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children.

Size limitations and technical barriers prohibit the use of many conventional mechanical circulatory support systems for postcardiotomy ventricular dysfunction in pediatric populations. Extracorporeal membrane oxygenation (ECMO), frequently used to treat neonatal respiratory failure, can provide cardiac support and is effective treatment of postoperative myocardial failure in children. From 1981 to 1987, 10 patients aged 2 days to 5 years were maintained on ECMO for 15 to 144 hours (mean duration, 92 +/- 16 hours) after cardiotomy. Operative procedures included repair of tetralogy of Fallot (2 patients), closure of a ventricular septal defect (2), the Senning procedure for transposition of the great arteries (1 patient), repair of interrupted aortic arch with closure of a ventricular septal defect (1), repair of a partial atrioventricular septal defect (2), closure of a ventricular septal defect with excision of an anomalous muscle bundle (1), and the Fontan procedure (1). Venoarterial ECMO was established in all 10 children. Six patients underwent transthoracic right atrium-ascending aorta cannulation, 3 had right internal jugular vein-right common carotid artery cannulation through a cervical incision, and 1 had right internal jugular vein-left axillary artery cannulation. Eight of the 10 patients were successfully weaned from ECMO, and 7 are long-term survivors. There were 3 deaths; 1 was caused by cardiac and acute renal failure complicated by sepsis two days after decannulation, another occurred 19 days after atrioventricular septal defect repair, and 1 was caused by massive pulmonary hemorrhage. Major hemorrhage developed in 3 patients while on ECMO; 2 required premature decannulation for mediastinal bleeding from operative sites and ultimately survived, and 1 died of respiratory failure as a result of endobronchial bleeding. We conclude that the use of ECMO in pediatric populations for transient postoperative ventricular dysfunction improves survival with limited overall morbidity.

Child, Preschool↗
PubMed1989

The value of protective isolation procedures in cardiac allograft recipients.

The impact of protective isolation on the incidence of infection in 60 cardiac transplant recipients (mean age, 49.2 years) was studied in a prospective randomized trial. Thirty patients were randomized to protective isolation, which consisted of private room, hat, mask, sterile gown, and handwashing. Thirty patients were randomized to no isolation, which meant they recovered in a crowded, open intensive care unit and were adjacent to recipients of liver transplants or patients who were on the trauma, neurosurgical, and general surgical services, many of whom had an infection of the incision or a pulmonary infection. There was no difference between groups in the proportion of patients in whom infection developed (chi 2[1] = 0.27; p = 0.6), the number of infection-related deaths (2 in each group), the types of infection (bacterial, viral, fungal, or protozoal), or the overall outcome. Because protective isolation offered no benefit over standard care in protecting these patients from infections or the associated complications, we have discontinued its routine use after cardiac transplantation.

Adolescent↗
PubMed1989

Organ procurement for pulmonary transplantation.

Selection of suitable donors is critical to the success of clinical pulmonary transplantation. Requirements for lung donors, management before explantation, and methods of preservation were reviewed for the 70 heart-lung, eight double-lung, and two single-lung transplantations performed at the University of Pittsburgh since 1982. Careful observation of trends of hyperoxygenation studies, chest roentgenograms, and Gram stain and culture results of tracheal secretions, as well as findings on bronchoscopy, can help identify which lungs not only have adequate function but are acceptable for transplantation. In spite of the rigid criteria used, 76% of tracheal cultures from donors deemed acceptable grew organisms. The presence of oropharyngeal flora has been shown to correlate with the development of early intrathoracic infections in the recipient. Prophylactic broad-spectrum antibiotic treatment of the donor is desirable to treat microbial contamination that could cause focal injury to the donor lung and predispose to infection in the recipient. Acceptance of less than ideal donors is ill-advised even though rejection of such donors conflicts with the current shortage of organs.

Graft Survival↗
PubMed1989

Lessons learned in pediatric heart transplantation.

Between February 1, 1982, and June 30, 1988, 32 children underwent cardiac transplantation for treatment of congenital heart disease (10) and other cardiomyopathies (22). The 6-year actuarial survival was a disappointing 36% because of a high perioperative mortality (12 of 32, 37.5%) and because of five late deaths due to uncontrolable rejection. The perioperative mortality was a staggering 60% (6 of 10) for the patients with congenital heart disease. Four of the 6 recipients with congenital heart disease died because of acute failure of the donor right ventricle. This included 2 patients who required reconstruction of the pulmonary arteries for stenosis secondary to previous systemic-to-pulmonary shunts and 2 others in whom the pulmonary vascular resistances were underestimated because of undetected recent pulmonary emboli (1) and complicated pulmonary vascular anatomy (1). Five of the six late deaths were due to rejection-related events, and all were patients with acquired cardiomyopathy.

Actuarial Analysis↗
PubMed1989

Low rate of Rhesus immunization from Rh-incompatible blood transfusions during liver and heart transplant surgery.

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh- persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh- liver, heart, and heart-lung transplant recipients received 3-153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D greater than 2 months later. Three patients developed anti-D at 11-15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, greater than 11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

Adult↗
PubMed1989

Proteins of the respiratory tract after heart-lung transplantation.

Heart-lung transplant recipients represent a unique population who experience episodic lung injury caused by infection or rejection. We hypothesized that the proteins in the respiratory lining fluids of these patients might reflect and provide insights into the in vivo immunologic and inflammatory events that occur in the transplanted lung. Structural, inflammatory, and immune proteins were quantitated in 57 samples of BAL fluid recovered from 17 heart-lung recipients when infections, rejection, or neither was present. Protein levels were compared with those of normal subjects and between the clinical transplant groups. When neither infection nor rejection was present, levels of albumin, fibronectin, and immunoglobulins G, M, and A were all higher in the transplanted lungs as compared with the normal lungs. These findings suggest that a new steady state of these proteins is established in the transplanted lungs. When infection or rejection was present, there was a further significant increase in albumin, fibronectin, IgG, and especially C5a in the transplanted lungs. These findings suggest that at least some elements of host defense remain intact in the posttransplantation period despite the use of immunosuppressive drugs and a HLA-incompatible microenvironment. The profiles of recovered alveolar proteins did not, however, help to differentiate infection from rejection. This is disappointing because distinguishing between infection and rejection without examination of lung tissue remains an unresolved and important clinical problem. Nevertheless these data provide new insights into organ tolerance and defense of the newly transplanted lung from infection or rejection.

Adolescent↗
PubMed1989

Coronary artery fistula in the heart transplant patient. A potential complication of endomyocardial biopsy.

All follow-up annual cardiac catheterizations performed on recipients of orthotopic heart transplant were reviewed, and 14 patients with coronary artery fistula were identified. The prevalence (8.0%, 14 of 176 patients) was strikingly higher than that for patients without transplant (0.2%) who underwent routine cardiac catheterization. These 14 patients had 21 coronary artery fistulas: single in nine and multiple in five patients. Fifty-two percent arose from the right, 43% from the left anterior descending, and 5% from the circumflex coronary artery. All drained into the right ventricle. Four patients underwent oximetric evaluation, and left-to-right shunting was not detectable. No patient had symptoms attributable to the fistula. Hemodynamic measurements were similar to those of a control group of 28 age- and sex-matched recipients of heart transplant without coronary artery fistula; however, the cardiac index (p = 0.02) and pulmonary artery oxygen saturation (p = 0.03) were significantly higher, and the arteriovenous oxygen difference (p = 0.01) was significantly lower in the group with coronary artery fistula. The histologic features of rejection, large arterioles, or epicardial fat on any biopsy specimen predating coronary artery fistula diagnosis were not associated with the development of the fistula when the two groups were compared. Nine patients (11 coronary artery fistulas) had follow-up studies performed, and three fistulas were larger, three were unchanged, two were smaller, and three had resolved. No complications of coronary artery fistula developed during a mean follow-up of 28 months (range, 12-42 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗