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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 253 records · Page 14Linked to original sources
PubMed1989

Pulmonary capillary hemangiomatosis. A report of three cases and a review of the literature.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. At present, only eleven cases have been reported. This report describes the clinical and pathologic findings in three additional cases who presented to the University of Pittsburgh for heart-lung transplantation and integrates the clinical features of all fourteen cases. Clinically, this disorder should be suspected in a patient who presents with pulmonary hypertension, hemoptysis, a reticulonodular infiltrate on chest radiograph, a lung scan showing inhomogeneously enhanced perfusion (particularly in the lower lobes), and pulmonary angiography showing increased peripheral vascularity corresponding to both the radiographic infiltrate and the areas of enhanced perfusion on lung scan. Histologic features consist of nodular proliferation of capillary-sized vessels that infiltrate the pulmonary interstitium, vascular walls, and lumens as well as the alveolar septa. The vascular invasion results in a secondary veno-occlusive phenomenon that explains the clinical confusion with pulmonary veno-occlusive disease.

Adult↗
PubMed1989

Infections in mortally ill cardiac transplant recipients.

A total of 351 cardiac transplantations performed between June 1, 1980, and Sept. 30, 1987, were reviewed to determine if infectious complications were more frequent in those patients requiring preoperative intravenous inotropic support, placement of an intraaortic balloon pump, or mechanical support with a left ventricular assist device or total artificial heart. One hundred forty-nine transplants (45%) were performed in these mortally ill patients. There was no statistically significant difference between patients with and without infection within each support group for the following: the number of in-patient days awaiting a donor heart, the number of days receiving support, the percent of patients with preoperative tracheal intubation, the length of the operation, and the percent of patients requiring reoperation for bleeding. The need for invasive methods of support (intraaortic balloon pump, left ventricular assist device, or total artificial heart) in patients awaiting heart transplantation increases the prevalence of perioperative nonviral infection. Preoperative mechanical support with a left ventricular assist device or total artificial heart significantly increases the risk of infection-related mortality.

Adult↗
PubMed1989

Host defense response to cytomegalovirus in the central nervous system. Predominance of the monocyte.

Cytomegalovirus (CMV) infection of the brain is common in AIDS; however, little is known of the host defense response to CMV in the central nervous system (CNS). A guinea pig model was developed to study this problem. In the present studies the percentages of T cells and monocytes invading the leptomeninges during the course of acute CMV infection were compared. In addition, qualitative observations on parenchymal infiltrates were made. Such studies have not been performed previously in CMV infection of the CNS. Monocytes, defined cytochemically, predominated in the leptomeninges and in parenchymal foci. In contrast, T cells, defined immunohistologically, were found in a low percentage in the leptomeningeal reaction and only rarely in the parenchyma. These novel results differ significantly from other viral infections in which the T cell predominates in the leptomeningeal response and plays a major role in the parenchyma.

Animals↗
PubMed1989

Viremia and glial nodule encephalitis after experimental systemic cytomegalovirus infection.

Despite the importance of cytomegalovirus (CMV) infection of the central nervous system in acquired immune deficiency syndrome, a well characterized laboratory model of glial nodule encephalitis after systemic CMV infection is not available. We now report that after intraperitoneal infection of young guinea pigs with CMV, infection of the brain was routinely found in the 2nd week. Recovery of virus from the brain was achieved at the time of viremia. Histopathologic changes in the brain followed the recovery of virus and continued beyond the point that virus was cleared from the brain. Microglial nodules, which were sometimes observed in association with intranuclear inclusion bearing cells, were the predominant feature. Other histopathology included perivascular infiltrates, vascular endothelial swelling, subependymal infiltrates, and sporadic focal leptomeningitis. In comparison to our previous studies after intracerebral inoculation, parenchymal changes dominated and leptomeningitis was found infrequently. The present studies suggest that focal central nervous system infection by CMV may be relatively common, though clinically silent, in the course of systemic infection. Relevant to acquired immune deficiency syndrome, the model should facilitate studies of the mechanism of brain infection, local central nervous system host defense, and mechanisms of injury to the brain.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Infections in pediatric orthotopic heart transplant recipients.

The infectious complications of 31 orthotopic heart transplants in 27 patients performed between 1982 and 1987 were reviewed. Fifteen patients (56%) are alive 704 to 1829 days posttransplantation. Five of the 27 patients died within the first week posttransplantation of noninfectious causes. Infection occurred in 17 of the remaining 22 patients and was the major cause of death in 3 of the 12 fatalities. There were 10 proved and 4 probable bacterial infections. Three of the 10 proved bacterial infections were cases of sepsis with focal complications (two Pseudomonas aeruginosa, one Serratia marcescens) resulting in 2 deaths. The cases of sepsis occurred within 12 days of transplantation. There were 11 viral infections. Cytomegalovirus accounted for 7 of these including 1 fatal and 2 nonfatal episodes of disseminated disease. The mean time of onset of cytomegalovirus infection was 33 days. Two cases of fungal disease were identified at autopsy. One additional patient who received intense immunosuppression because of chronic rejection developed Pneumocystis carinii pneumonia. The most frequent site of infection was the lung with early pneumonias caused by Gram-negative bacteria and later episodes by viral (cytomegalovirus or respiratory syncytial virus) agents.

Adolescent↗
PubMed1989

Cardiac transplantation in children.

Heart transplantation is becoming an accepted treatment for children with irreversible and profoundly disabling cardiomyopathy. The risk is much higher when there is underlying congenital heart disease, and even moderately elevated pulmonary vascular resistance is a contraindication to orthotopic heart transplantation. Heterotopic or heart-lung transplantation may be considered in patients with elevated pulmonary vascular resistance. In a few centers, heart transplantation is being performed as an alternative to palliative surgical procedures in children with hypoplastic left heart syndrome. Chronic immune suppression is necessary in all patients postoperatively. Cyclosporine and prednisone are the mainstays of therapy, and azathioprine is often added to the regimen. ATG is used prophylactically in the immediate postoperative period and acute rejection episodes are treated with pulses of prednisone, ATG, or OKT3. Infection continues to be a major problem, and the chronic long-term effects of both rejection and the drugs used to treat it, especially cyclosporine, are also very important. Coronary artery disease and lymphoproliferative disease are causes of death, and hypertension and decreased renal function are present in almost all survivors. The shortage of donor hearts is becoming a progressively more important problem and may affect selection criteria in the future. On the positive side, most children can return to age-appropriate activities following transplantation and they seem to tolerate their chronic illness and its attendant repeated invasive procedures surprisingly well.

Cardiomyopathy, Dilated↗
PubMed1989

Clinical utilization of the artificial heart.

During the past 30 years the artificial heart has evolved from a bioengineering concept to clinical reality. To date four patients have had an artificial heart implanted as a permanent device, while over 150 artificial hearts have been utilized temporarily as a bridge to cardiac transplantation. Increased use of this device requires that a number of issues be critically addressed: (1) criteria for patient selection; (2) operative techniques for implantation including size of device and its position in the mediastinum; and (3) management of the patient in the intensive care unit (ICU), in particular, regimens of anticoagulation, assessment of adequacy of organ perfusion, and prevention of sepsis. This chapter is a discussion of these bioengineering and clinical concerns with respect to the Jarvik total artificial heart (TAH). Clinical data are presented which highlight the current problems with these devices and the areas of future research that need to be undertaken.

Heart Transplantation↗
PubMed1989

[New trends in combined transplantation of the heart and lungs].

Heart-lung transplantation is a surgical alternative for patients with end-stage lung disease with associated right heart failure. While the procedure is very promising, the morbidity and mortality remain high. The current understanding of the proper selection of candidates, procurement and preservation of donor organs, operative procedure and postoperative care continues to evolve. At the University of Pittsburgh, 70 heart-lung transplantations have been performed since 1982. Early infection and chronic rejection are the major factors influencing survival. Early (less than 2 weeks) intrathoracic infection occurred in 43% of heart-lung transplant recipients, with pneumonia being the most frequent infection. The incidence of pneumonia in heart-lung transplant recipients is twice that in a comparable group of heart recipients. Subclinical pneumonitis in the donor lung, abnormal muco-ciliary clearance and altered allogenic response in the transplanted lung are significant factors associated with the increased incidence of early infections. Chronic rejection, manifested as bronchiolitis obliterans, has occurred in 54% of heart-lung transplantation recipients. Infection caused by cytomegalovirus, Epstein-Barr virus and Pneumocystis carinii have been shown to increase the incidence of bronchiolitis obliterans, as have episodes of acute rejection. Recent reports of a 61% 2-year survival rate represent a substantial improvement over earlier trials. With a better understanding of the pathogenesis of infection in the transplanted lung as well as improved immunosuppressive agents, further improvements in survival can be expected.

Heart-Lung Transplantation↗
PubMed1989

Hemodynamic consequences of Foley catheter control in experiment penetrating cardiac wounds.

Insertion of the Foley catheter has been recommended to control bleeding from penetrating cardiac wounds. Potential complications from this maneuver include enlargement of the tear in the myocardium or further impediment to cardiac function by the balloon. This study was done to evaluate the hemodynamic consequences of the balloon catheter when it was used to control bleeding in cardiac stab wounds created in pigs. A significant decrease in cardiac function occurred with control of the bleeding by the balloon catheter. This effect was dependent on the size of the balloon and cardiac location.

Animals↗
PubMed1988

Evidence of an altered pattern of breathing during exercise in recipients of heart-lung transplants.

Recipients of heart-lung transplants represent an unusual opportunity to study the regulation of ventilation, because the neural pathways between the lungs and the central nervous system are disrupted in these patients. We compared the ventilation response in seven recipients of heart-lung transplants who had normal pulmonary function and seven recipients of heart transplants, all of whom performed incremental bicycle ergometry. The level of ventilation in recipients of heart-lung transplants was similar to that in heart-transplant recipients for equivalent levels of carbon dioxide production. Arterial pH and partial pressure of carbon dioxide at maximal exercise were normal and not significantly different in the two groups, also suggesting that levels of ventilation were appropriate in both groups. However, the rate of the rise in respiratory rate for increasing levels of ventilation was significantly lower in recipients of heart-lung transplants than in heart-transplant recipients, and the initial increase in tidal volume was more rapid in the former group than in the latter. Thus, recipients of heart-lung transplants have an appropriate level of ventilation during exercise as the result of a disproportionate increase in tidal volume at a reduced respiratory rate. We speculate that intrapulmonary receptors are important in regulating the pattern, but not the absolute level, of ventilation during exercise.

Acid-Base Equilibrium↗
PubMed1988

Glial nodule encephalitis in the guinea pig: serial observations following cytomegalovirus infection.

Cytomegalovirus (CMV) encephalitis, characterized by microglial nodules, is a major neurological complication in AIDS. There is a clear need for a well-characterized laboratory model of CMV encephalitis. We report here the sequential virological, histopathological, and antibody responses of young guinea pigs inoculated intracerebrally with guinea pig CMV. Virus was found to peak in the brain in the 1st week, to peak in the spleen in the 2nd week, and to be cleared from the brain with the development of serum neutralizing antibody 3 to 4 weeks post infection. Leptomeningitis peaked at the end of the 1st week, independent of the changes found in the parenchyma. Diffuse and focal infiltration of systemic cells was found in the cortex. Microglial nodules consisting of swirled and elongated cells, sometimes in association with intranuclear inclusion bearing cells, were prominent. The parenchymal changes, including scattered foci of ependymitis and ventriculitis, were most prominent in the 2nd week post infection. This model should facilitate studies of the host defense response in the brain and of the role of antiviral therapy in CMV encephalitis.

Animals↗
PubMed1988

The artificial heart: infection-related morbidity and its effect on transplantation.

Between October, 1985, and September, 1987, a total of 195 patients received cardiac allografts and 15 candidates required mechanical support with the Jarvik-7 total artificial heart. Seven of the 15 died within 60 days of total artificial heart implant. There have been no late deaths, and survivors are unrestricted. Six of 7 deaths were related to infection (mediastinitis, 5; pneumonia and sepsis, 1), and the remaining 1 was due to failure of the transplanted heart. Respiratory tract infection occurred in each of the recipients who died with infection, and the same organisms appeared to be related to subsequent mediastinitis in 3 patients (Serratia marcescens, 2; Pseudomonas, 1) and caused fatal sepsis in another (Enterobacter aerogenes, Candida albicans). One patient died with pneumonia and sepsis prior to transplantation, and another succumbed with mediastinal infection known to be present before transplantation.

Heart Transplantation↗
PubMed1988

Immunologically mediated disease of the airways after pulmonary transplantation.

Obliterative bronchiolitis has occurred in eleven of 30 recipients of cardiopulmonary allografts who survived at least 4 months after transplantation, has caused significant morbidity, and has been associated with four of eleven late deaths in this series. Although some improvement, or at least stability, of pulmonary function has followed augmented immune suppression, it appears that once the process is recognized clinically, much of the damage to the airways is irreversible. The histopathology, response to therapy, and, most important, the response of donor specific alloreactivity in the lymphocytes from the lung (bronchoalveolar lavage and peripheral blood) suggest immune- mediated basis for bronchiolitis obliterans. The presence of donor specific alloreactivity detected by primed lymphocyte testing predicted obliterative bronchiolitis in five of six recipients (83% sensitivity, 91% specificity) was absent in ten of eleven recipients who have not as yet developed the process (negative predicted value of 91%). Currently, the presence of a positive primed lymphocyte test in the bronchoalveolar lavage of the cardiopulmonary recipient is an indication for early treatment by augmented immune suppression.

Bronchiolitis Obliterans↗
PubMed1988

Some futuristic possibilities for resuscitation.

Future possibilities for resuscitation must take into account our still limited understanding of the reperfusion syndrome. Clinical resuscitation research must incorporate the use of prolonged life-support techniques. These may depend on the use of cardiopulmonary bypass to provide improved reperfusion of vital organs and to permit the time necessary to evaluate and treat the mediators and modifiers of the reperfusion syndrome. It is likely that some patients who require prolonged life support will need replacement organs or, should their brains fail to survive resuscitation, become organ donors. Physicians involved in resuscitation and transplantation must come to grips with the logistic problems of techniques for prolonged resuscitation.

Blood Circulation↗
PubMed1988

Efficacy of S26308 against guinea pig cytomegalovirus infection.

Prophylactic use of antiviral agents against cytomegalovirus (CMV) is particularly indicated for the immunocompromised host because morbidity and mortality due to CMV occur most frequently following immunosuppression. We have evaluated the new Riker compound S26308 for its therapeutic and prophylactic antiviral activity against CMV in guinea pigs. The efficacy of the compound was assessed in vitro in guinea pig embryo cells and in vivo in both immunocompetent and immunocompromised guinea pigs. Guinea pig CMV plaque formation was reduced only in cells treated with S26308 prior to virus infection. The antiviral activity remained even when the compound was removed after virus absorption and was due to neither virus destruction nor inhibition of cell growth. The frequency of viremia was reduced in guinea pigs for which S26308 therapy was initiated 24 h prior to virus inoculation compared with sham-treated animals. This reduction in the frequency of viremia did not prevent virus spread to target tissues but did result in a reduction of the severity of CMV-induced disease in immunocompromised guinea pigs. Low levels of interferon were detected in supernatants of S26308-treated cells, and interferon was detected in the serum of guinea pigs given S26308. These results indicate that S26308 can induce interferon and reduce CMV infectivity in vivo and in vitro when used prophylactically. This antiviral activity, although modest, was accompanied by beneficial effects on CMV-induced morbidity and mortality. Prophylactic use of S26308 in combination with other therapeutic agents may be a useful strategy against CMV infections.

Aminoquinolines↗
PubMed1988

Unexpectedly high incidence of Pneumocystis carinii infection after lung-heart transplantation. Implications for lung defense and allograft survival.

Pneumonia due to Pneumocystis carinii (PCP) is regularly encountered in organ allograft recipients who are immunosuppressed to prevent rejection. Recipients of lung/heart allografts may be particularly prone to pulmonary infection due to systemic immunosuppression and the fact that defense mechanisms in the transplanted lung may be further impaired through tissue incompatibility and the effects of surgery. In this study, we monitored 16 lung transplant recipients for infection with Pneumocystis carinii using serial bronchoalveolar lavage (BAL) and found the prevalence of Pneumocystis infection of the lung to be 88%. Six episodes were associated with the usual symptoms of pneumonia, whereas 10 episodes were associated with minimal or no symptoms. In 3 of the 6 symptomatic episodes, a concurrent bacterial infection was also found. The total number of cells recovered from the lung by BAL, the proportion of T-lymphocytes, and the number of cytotoxic/suppressor and helper/inducer cells were elevated during infection with Pneumocystis compared to before and after. Spontaneous and interleukin-2-induced proliferation of BAL cells in vitro was also higher during infection, suggesting that there was an increased number of activated T-lymphocytes in the airspaces of the infected allograft. BAL cells cultured with irradiated spleen cells from the donor proliferated at higher levels when obtained after Pneumocystis infection than when obtained before or during infection even for subclinical infections. These results indicate that in the absence of prophylaxis, the prevalence of Pneumocystis infestation is very high after lung/heart transplantation. Impaired defense of the transplanted lung does not seem to stem from the inability of activated T-lymphocytes to accumulate in the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗