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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

At least 127 records · Page 7Linked to original sources
PubMed1986

Cardiac transplantation. Emerging from an experiment to a service.

Cardiac transplantation was resumed at the University Health Center of Pittsburgh in 1980 after a hiatus of 12 years. Prior to April 15, 1986, 270 hearts had been transplanted. Participants have been forced to reorder personal, professional, and institutional commitments to adapt to new demands of pre- and post-operative care and to develop flexibility in the operative scheduling of routine cardiac surgical cases. The actuarial survival has been 78, 69, and 64% at 1, 2, and 3 years. Much has been learned about evolving immunosuppression based on cyclosporine and of the allogenic response. An increasing proportion of recipients are mortally ill (54%), and for these urgent patients the wait for a donor organ continues to lengthen. The cardiac surgeon performing transplantations will need to grow with allied developments in xenotransplantation and mechanical cardiac support devices in order to keep pace with his evolving specialty.

Cyclosporins↗
PubMed1986

Allospecificity of activated T cells grown from endomyocardial biopsies from heart transplant patients.

Studies were conducted to determine the functional characteristics of lymphocytes infiltrating human heart allografts. We have developed methodologies to generate lymphocyte cultures from endomyocardial biopsies. Thirteen biopsies from four heart transplant recipients, obtained at different days during a posttransplant period of less than two months, were cultured in interleukin-2 (IL-2)-containing medium supplemented with irradiated autologous peripheral blood lymphocytes as feeder cells. Lymphocyte cultures were obtained from all 13 biopsies and they exhibited a proliferative response to IL-2, suggesting the presence of activated T cells that express IL-2 receptors. Several cultures consisted of Leu 3 (helper/inducer) T cells, whereas others were primarily Leu 2 (cytotoxic/suppressor) T cells or a mixture of both types of cells. Cultured lymphocytes were also shown to be able to undergo secondary proliferation to donor-specific leukocytes as measured by primed lymphocyte testing (PLT). The PLT specificity of these cells was frequently toward class II HLA antigens of the donor, but certain cultures had PLT specificity associated with class I HLA antigens. These results demonstrate the feasibility of growing functionally active T cells from heart transplant biopsies. An analysis of the phenotypes and allospecificity, as well as a functional characterization of these cells, should generate useful information about the types of T cells involved in cardiac transplant rejection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Infections in heart-lung transplant recipients.

Infectious episodes were analyzed in 14 heart-lung transplant recipients who survived more than one week after transplantation. These patients had higher rates of infection than heart transplant recipients at our institution (P less than 0.01) and greater than 90% of all infections were potentially life-threatening. A total of 67% of all infections involved the lung or thoracic cavity as a primary site, and most of the rest were disseminated viral or fungal infections. Pneumocystis carinii infections occurred in six patients and were more common in this group than in patients who received heart transplants in the same period (P less than 0.005). Two patients followed more than one year developed a syndrome of chronic sputum production and bronchial colonization with Pseudomonas aeruginosa, which required recurrent treatment with i.v. antibiotics for symptomatic relief. The high rate of pulmonary infections in these patients presents a challenge to clinical management, and suggests that intensive and invasive monitoring for pulmonary infection is desirable.

Adult↗
PubMed1986

Assessment of lung injury in the adult respiratory distress syndrome using multiple indicator dilution curves.

To assess its usefulness as an index of lung injury in critically ill patients with respiratory failure, the lung microvascular permeability surface area product for urea (14C-PSu) was measured using a multiple radioisotopic indicator dilution technique in 10 patients with the adult respiratory distress syndrome (ARDS) and in a control population of 5 patients without ARDS. The mean values for 14C-PSu and for extravascular lung water (EVLW) were both significantly elevated in patients with ARDS compared with those in control patients (14C-PSu: 18.7 +/- 4.4 versus 7.6 +/- 0.7, p less than 0.05; EVLW: 676 +/- 55 versus 269 +/- 53, p less than 0.001); 14C-PSu and EVLW were significantly correlated (R = 0.52, p less than 0.001). In the patients with ARDS, 14C-PSu and oxygenation, assessed as the alveolar-arterial oxygen difference, did not appear to be correlated. Repeated measurements of 14C-PSu were variable in the 3 control patients in whom 4 or more measurements were obtained (SD = 50, 57, and 54% of the mean values, respectively); 14C-PSu did not predict clinical outcome assessed by survival of individual patients with ARDS. These data suggest that measurement of 14C-PSu in critically ill patients is a clinically applicable parameter that reflects the degree of microvascular injury in groups of patients. However, our study did not indicate a clear advantage of 14C-PSu over EVLW in assessing lung injury in this patient population. The variability in 14C-PSu control patients also suggests that directional changes in 14C-PSu, as a measure of changes in the degree of lung microvascular dysfunction, should be interpreted with caution.

Adult↗
PubMed1986

Early function of cardiac homografts: relationship to hemodynamics in the donor and length of the ischemic period.

Twenty-four of 124 heart transplant recipients in our study group died in the perioperative period. In five patients the cause of death was unknown even after postmortem examination. The possibility that the cause of death was due either to poor donor selection or poor preservation of the donor heart was evaluated by reviewing the length of ischemic time of the cardiac homografts and the need for inotropic support in the donors before the hearts were harvested. Results of our retrospective analysis indicate that inotropic support in the form of 2 to 10 micrograms/kg/min dopamine and an ischemic time of up to 4 hr do not influence the early survival of heart transplant recipients.

Adult↗
PubMed1986

Cyclosporine pharmacokinetic profiles in liver, heart, and kidney transplant patients as determined by high-performance liquid chromatography.

Cs pharmacokinetic profiles using HPLC have aided in predicting necessary dosage alterations for specific groups of transplant patients. Additional information has been gained by HPLC profiles in nontransplant subjects who are healthy or have a stable disease state. The clinician now knows that liver disease not only impairs Cs elimination but may also have a pronounced effect upon drug absorption. While the cardiac failure patient may have reversible inhibition of Cs clearance, other factors may affect the distribution of the drug to lower dosage requirements. Impaired renal function is not an impediment to Cs elimination, but malabsorption similar to that observed in liver and bone marrow transplant patients may still occasionally complicate therapy. Pharmacokinetic information on Cs must be integrated into the complex care plan of a transplant patient to optimally utilize and monitor this pharmacologic agent.

Adult↗
PubMed1985

Changes in lung vascular permeability after heart-lung transplantation.

We have employed multiple indicator dilution techniques (MID) in six patients after heart-lung transplantation to assess changes in the lung vascular permeability-surface area product for urea (PS). Serial PS values for the patients when normalized to the predicted total lung capacity (TLC) in liters, ranged between 1.04 and 6.27 ml/sec/TLC (patient 1), 0 and 2.76 ml/sec/TLC (patient 2), 0.59 and 2.88 ml/sec/TLC (patient 3), 0.13 and 1.23 ml/sec/TLC (patient 4). The elevated values for PS in patient 1 exceed the lethal range described by K.L. Brigham et al. (J. Clin. Invest. 72:339, 1983) for severe ARDS. This strongly suggests a severely increased lung microvascular permeability in this patient possibly secondary to rejection as indicated by endomyocardial biopsy. PS values for surviving patients 2-6 fell well below the corresponding lethal value for ARDS patients. We conclude that PS urea derived from MID provides an indicator of the status of lung microvascular integrity in heart-lung transplant recipients.

Capillary Permeability↗
PubMed1985

Tracheal chondrosarcoma with an overview of other tumors of the trachea.

Chondrosarcomas of the trachea are extraordinarily rare tumors, with only four cases documented in the English literature. An additional case is reported with conventional and computed tomography correlation. Because primary tumors of the trachea are such rare neoplasms, a review of the subject is presented to put chondrosarcomas of the trachea into perspective. Malignant tumors are slightly more common than benign tumors of the trachea and occur more frequently in adults. The most common tumor involving the trachea is carcinoma, accounting for 80 to 90% of all cases. This, however, represents only 0.2% of all malignancies of the respiratory tract.

Aged↗
PubMed1985

A percutaneously adjustable device for banding of the pulmonary trunk.

An optimal result is often difficult to obtain with conventional banding of the pulmonary trunk. Furthermore, this procedure has a significant surgical morbidity and mortality. An inflatable device has therefore been developed which consists of an inflatable band and a valve. The band is made of a silicone balloon which is covered with reinforced braid. The band is applied loosely around the pulmonary trunk through a left lateral thoracotomy. The valve is implanted subcutaneously in an intercostal space. The size of the band can be adjusted postoperatively using a needle and fluid-filled syringe percutaneously to inflate or deflate the balloon. Experiments were conducted in 5 animals and follow-up evaluation by cardiac catheterization and angiocardiography was made up to 4 months after implantation of the device. The band could be effectively and reliably adjusted and no malfunction or complication occurred. This preliminary study suggests that this new technique may make banding of the pulmonary trunk a more reliable and effective procedure and may reduce surgical morbidity and mortality. It also may avoid or delay subsequent additional surgery for revision of a band which is too tight or too loose.

Animals↗
PubMed1985

Interactions between bronchoalveolar lymphocytes and macrophages in heart-lung transplant recipients.

Bronchoalveolar lavages (BAL) were obtained from heart-lung transplant patients. Following transplantation, the number of lymphocytes and macrophages are considerably increased. BAL lymphocytes frequently exhibit donor specific secondary allogeneic proliferation measured in primed lymphocyte testing (PLT) assays. We report our findings regarding a persistence of donor derived macrophages and lymphocytes in BAL during the posttransplant period. The presence of donor specific macrophages causes a proliferative response of alloreactive BAL lymphocytes from the recipient. This "Bronchoalveolar Macrophage Lymphocyte Reaction," or "BMLR," may represent a unique aspect of in vivo interactions associated with lung allograft responses. Comparative studies showed considerably lower PLT responsiveness of peripheral blood lymphocytes than that of BAL lymphocytes. These studies suggest that functional assays on BAL cells may be useful in monitoring lung transplant rejection and other immunological phenomena that affect pulmonary function of heart-lung transplant patients.

Bronchi↗
PubMed1985

Asynchronous rejection of heart and lungs following cardiopulmonary transplantation.

Eighteen patients have received 19 combined heart-lung allografts since March, 1982. During the maturation of our program of heart-lung transplantation, we have learned that isolated rejection of the lung can occur frequently and that exclusive dependence on the cardiac biopsy can be misleading. Of the 18 patients who received allografts, 10 are the basis for this report. The other patients were excluded because of death from excessive bleeding (1), inadequate lung preservation (2), an inability to differentiate rejection from infection (3), or an absence of rejection of either the heart or the lungs (2). Rejection of the lung was suggested, in the absence of clinical evidence of infection, by the radiographic appearance of a diffuse pulmonary infiltrate. It was confirmed by a prompt response to augmentation of maintenance immunosuppression with an intravenous pulse of methylprednisolone. The presence or absence of cardiac rejection was determined by the standard endomyocardial biopsy. Direct biopsy of the involved lung through a thoracotomy was performed in 4 patients so that a definitive histological diagnosis of rejection would reinforce the anticipated clinical diagnosis. The clinical course in 6 of the 10 patients plus the results of the open lung biopsy in 3 of them suggest that isolated rejection of the lung developed in the absence of cardiac findings. Patients responded within 12 to 24 hours to augmented immunosuppression with a dramatic improvement in the abnormal chest radiograph. In all 10 patients, either isolated lung or synchronous heart and lung rejection episodes were confined to the first six weeks after operation unless a severe alteration in the immunosuppression was made (2 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1985

Massive hemoptysis in patients with cystic fibrosis: three case reports and a protocol for clinical management.

The clinical management of massive hemoptysis in patients with cystic fibrosis proceeds according to the following paradigm. The site of bleeding is identified by bronchoscopy, ideally under general anesthesia. Then selective bronchial arteriography is performed. If collaterals to the spinal cord are visualized, arterial embolization is abandoned and pulmonary resection is undertaken within the limits of pulmonary function.

Adult↗
PubMed1985

Advantages of venous bypass during orthotopic transplantation of the liver.

Venous bypass restores normal hemodynamic physiology during the critical anhepatic phase of orthotopic transplantation of the liver. Its routine use in adults undergoing transplantation in Pittsburgh has resulted in lower operative blood losses, a lower frequency of postoperative renal failure, and a greater probability of survival for all but the highest risk patients. Because it allows for a longer anhepatic phase, the surgeon has the option of tailoring the native hepatectomy to the needs of the individual case, even to the point, in difficult cases, of obtaining most of the hemostasis after removal of the native liver, but before sewing in the donor organ. Selective use of bypass in children may offer similar advantages.

Evaluation Studies as Topic↗
PubMed1985

Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: the role of primary infection.

Fourteen patients who developed B cell lymphomas or lymphoproliferative lesions after kidney, liver, heart, or heart-lung transplantation in Pittsburgh during 1981-1983 had active infection with Epstein-Barr virus (EBV) of the primary (six patients), reactivated (seven patients), or chronic (one patient) type. In transplant patients without tumors, the incidence of EBV infection was 30% (39 of 128). Only three of these patients had primary infections. Thus the frequency of active infection was significantly higher in patients with tumors, and patients with primary infections were at greater risk of developing tumors. Five of 13 tumors tested contained EBV nuclear antigen (EBNA) and nine of 11 contained EBV genomes detected by DNA-DNA hybridization with BamHI K, BamHI W, or EcoRI B cloned probes. All EBNA-positive tumors, except one, were also positive by hybridization. Only one tumor was negative for both EBNA and EBV DNA. These data suggest that EBV plays an etiologic role in the development of these lesions.

Adolescent↗
PubMed1985

Morbidity of cytomegalovirus infection in recipients of heart or heart-lung transplants who received cyclosporine.

Forty-four heart and five heart-lung transplant recipients with cytomegalovirus (CMV) infection were investigated for risk factors associated with symptomatic CMV infection (17 patients) and CMV pneumonia (eight patients). Symptomatic infection was associated with primary rather than reactivated infection (P less than .005), younger age (P less than .005), heart-lung transplantation (P less than .001), and significant rises in titer of antibody to the early antigen of Epstein-Barr virus (P less than .001). Among recipients of heart transplants, patients with cardiomyopathy more often had symptomatic disease due to CMV (P less than .05). CMV pneumonia was associated with heart-lung transplantation and, in patients with primary CMV infection, earlier positive cultures for CMV after transplantation (P less than .02). CMV viremia was found in all patients with symptomatic infection, including the eight patients with CMV pneumonia, and the frequency of positive buffy coat cultures for CMV was significantly higher in patients with symptoms than in patients without symptoms (P less than .001). Neither symptomatic CMV infection nor CMV pneumonia was significantly associated with the use of antithymocyte globulin, restricted to therapy for rejection, and the use of high doses of acyclovir in 11 patients had no demonstrable impact on CMV culture positivity.

Acyclovir↗
PubMed1985

Combined transplantation of the heart and liver.

The technique of combined transplantation of the heart and liver is described and illustrated, emphasizing modifications that were used in a successful case. Two other unsuccessful attempts are reported, and the importance of relative size of donor and recipient is discussed. There may be an immunological advantage to transplanting two organs in combination from the same donor.

Adolescent↗
PubMed1985

Long-term hemodynamic follow-up of cardiac transplant patients treated with cyclosporine and prednisone.

To evaluate the long-term hemodynamic results in cardiac transplant patients treated with cyclosporine and prednisone, 19 patients were studied by cardiac catheterization and endomyocardial biopsy 13 +/- 3 months after transplantation. Immunosuppression consisted of 6 +/- 4 mg/kg/day cyclosporine and 20 +/- 8 mg/day prednisone. Eighteen patients were asymptomatic but had developed postoperative systemic hypertension (17 on antihypertensive therapy). These patients were compared with a normotensive control group of 18 patients without cardiovascular disease. Significant differences were found in heart rate; right atrial, pulmonary arterial, pulmonary arterial wedge, systemic arterial, and left ventricular end-diastolic pressures; cardiac index and stroke volume index; systemic and pulmonary vascular resistance; and end-diastolic volume index and left ventricular ejection fraction. The most frequent hemodynamic abnormalities included an elevated arterial pressure in 10 patients (56%), an elevated left ventricular end-diastolic pressure in six patients (33%), and a reduced ejection fraction in five patients (28%). Hemodynamic abnormalities tended to resolve or improve in the five patients restudied 2 years after transplantation. There was no significant relationship between fibrosis or inflammation on endomyocardial biopsy and hemodynamic abnormalities. We conclude that mild-to-moderate hemodynamic abnormalities are common in asymptomatic cardiac transplant patients receiving cyclosporine and prednisone.

Adult↗