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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 289 records · Page 16Linked to original sources
PubMed1987

Cardiac transplantation: improved quality of survival with a modified immunosuppressive protocol.

The effects on renal function on two different immunosuppressive protocols were evaluated retrospectively in two subsequent groups of heart transplant recipients. In group I, cyclosporine was given before the procedure at a loading dose of 17.5 mg/kg and then continued after the procedure to keep a whole blood level about 1000 ng/ml. In group II, cyclosporine was started only after the procedure at a lower dosage and was complemented by azathioprine, which was used for the first postoperative week. Group II showed a better perioperative renal function as determined by serum blood urea nitrogen and serum creatinine levels. Group II also showed a significant decrease of chronic nephrotoxicity secondary to long-term therapy with cyclosporine. Despite this improvement in late renal function, group II still shows a slow rise in serum creatinine. We think that even these lower dosages of cyclosporine can cause chronic nephrotoxicity and that further modification of the immunosuppressive regimen is required to completely abolish this toxic side effect.

Actuarial Analysis↗
PubMed1987

Autoperfusion of the heart and lungs for preservation during distant procurement.

A modified autoperfusing Starling preparation was used to provide pulmonary and coronary blood flow to extend the period of preservation for heart-lung transplantation. Twenty successful donations were achieved, 14 performed, and both the heart and lungs were well preserved in 14 of them. In four recipients it was not possible to assess the adequacy of preservation. In one recipient the preservation was not satisfactory, and in another the selection of the donor was responsible for poor cardiac function. Ten patients are alive who would not be were it not for this technique.

Adolescent↗
PubMed1987

Experience with heart transplantation in children.

Between March 1981 and March 1986, 200 orthotopic heart transplantations were performed at the University of Pittsburgh. Fourteen of those procedures were carried out in children 2 to 16 years of age. Two children received combined liver and heart transplants; one because of familial hypercholesterolemia with associated ischemic heart disease, and the other because of dilated cardiomyopathy associated with intrahepatic biliary atresia. Eight patients had dilated cardiomyopathy, and two had myocarditis. Two had heart transplantations for congenital heart disease: one had multiple muscular ventricular septal defects repaired in infancy and had an associated cardiomyopathy, and the other developed a cardiomyopathic ventricle from a congenital right coronary artery to right atrial fistula. Chronic immune suppression consisted 0.2 to 0.5 mg/kg/d of prednisone and 5 to 50 mg/kg/d cyclosporine, with the addition of antithymocyte globulin for unresolved moderate or severe acute rejection. There were three early postoperative deaths: one from intracranial bleeding, one from Pseudomonas mediastinitis, and one from ischemic injury to transplanted organs. Early postoperative complications included reversible renal failure, hypertension, and seizures. Late problems were related to allograft rejection and side effects of cyclosporine and corticosteroids. Significant rejection episodes occurred in all patients surviving longer than 2 weeks, with seven requiring antithymocyte globulin. Two patients died 8 months following transplantation of severe acute and chronic rejection; another patient required retransplantation for ischemic cardiomyopathy resulting from chronic rejection but subsequently died of recurring rejection 3 months after the second transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

The contrasting effects of cyclosporin-A and azathioprine on arterial blood pressure and renal function following cardiac transplantation.

The effects of cyclosporin-A and azathioprine on the postoperative development of systemic hypertension and renal dysfunction in patients undergoing cardiac transplantation were compared retrospectively in 18 patients receiving cyclosporin-A and in 12 patients receiving azathioprine. Twelve months postoperatively, the average mean blood pressure was 116 +/- 13 mm Hg and 98 +/- 7.5 mm Hg; the average preoperative serum creatinine was 1.2 +/- 0.3 mg% and 1.5 +/- 0.3 mg%; and the postoperative serum creatinine was 2.2 +/- 0.8 mg% and 1.1 +/- 0.2 mg% (P less than 0.0001) in the cyclosporin-A-and azathioprine-treated groups respectively. Hemodynamic studies were done to characterize the de novo postoperative hypertension developing in the cyclosporin-A group. The pre- and postoperative cardiac output was 3.7 and 4.91/min, respectively (P less than 0.01). The pre- and postoperative systemic vascular resistance was 1707 and 1941 dynes sec X cm-5, respectively (P greater than 0.2). Peripheral renin activity and 24-hour urinary catecholamine excretion were not elevated. The mechanism of the hypertension developing in cyclosporin-A-treated patients is unknown, but is associated with normalization of cardiac output, an abnormally elevated systemic vascular resistance, and modest impairment of renal function. These findings are in marked contrast to azathioprine-treated patients, in whom postoperative hypertension and renal dysfunction do not occur. These observations implicate cyclosporin-A as the major contributing factor in the development of hypertension and renal dysfunction.

Adult↗
PubMed1986

Extracorporeal membrane oxygenation experience at the University of Pittsburgh.

Between January, 1981, and May, 1985, 33 infants suffering from acute cardiorespiratory failure were treated with extracorporeal membrane oxygenation (ECMO) when all other forms of conventional management had failed. Only the patients with respiratory failure that was thought to be reversible were treated. Prolonged conventional respiratory management (more than five days) was considered a contraindication to ECMO support because of irreversible damage to the lungs caused by the barotrauma associated with conventional ventilation. Eighteen of the 33 patients (54%) survived and were discharged from the hospital. Patients with congenital diaphragmatic hernia had a high incidence of fatal bleeding complications (8 of 14). Good results were obtained in the newborns with persistent fetal circulation and meconium aspiration syndrome. We conclude that ECMO markedly improves the survival of newborns with severe respiratory failure who would have a mortality close to 100% with conventional respiratory management.

Acute Disease↗
PubMed1986

Mortally ill patients and excellent survival following cardiac transplantation.

Cardiac transplantation was resumed in 1980 at the University Health Center of Pittsburgh. Generally accepted criteria for selection of patients were used, one being the expectation that survival would not reach 6 months. All of the initial recipients were in New York Heart Association Functional Class IV, but many were ambulant. We soon saw patients who were more clearly terminally ill. They were characterized by a systolic arterial pressure of less than 80 mm Hg, a cardiac index of less than 2 L/min/m2, evidence of reduced blood flow as indicated by urine output of less than 20 ml per hour, impaired mental function, and signs of decreased peripheral perfusion. The initial success of cardiac transplantation in these patients prompted us to reconsider selection criteria to include them among less strikingly ill candidates and to develop a therapeutic protocol designed to maintain peripheral perfusion and adequate renal and hepatic function until transplantation could be accomplished. Actuarial survival at 30 months for the group of terminally ill patients was 75% compared with 67% for the less critically ill group. Actuarial survival at 30 months for the combined group of 77 patients was 67%. Twenty-nine of the 33 mortally ill patients were alive and active at the time of writing, January, 1985.

Adult↗
PubMed1986

Development and organization of a multiple organ transplantation program.

Multiple organ transplantation has come of age. Indications are that it will continue to grow, if not flourish. The complexity of modern surgical care, its multiperson dependency, and the need for the surgeon to retain knowledge and involvement with his patient's care and problems are nowhere more evident than in multiple organ transplantation. Each organ presents its own associated challenges, the prime solution of which lies with a skillful and dedicated surgeon; but with all organs there are challenges of expectantly waiting patients, housing during the wait and for postoperative observation, procurement, erratic scheduling of the operating room, nursing, social service, immunosuppression, immunopathology, interest of hospital public relations and of the news media, and perennial care. This report concerns the growth and development of the multiple organ transplant program at the University Health Center of Pittsburgh and describes some answers to the challenges presented.

Academic Medical Centers↗
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

Inbred guinea pig model of intrauterine infection with cytomegalovirus.

Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.

Animals↗