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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 307 records · Page 17Linked to original sources

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↗

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↗

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↗

Transmission of maternal cytomegalovirus-specific immunity in the guinea pig.

The prenatal and perinatal transmission of maternal cytomegalovirus (CMV)-specific immunity was studied in the guinea pig by cross-fostering newborns of seropositive and seronegative mothers. Resistance to CMV was assessed by challenging the newborn and adult offspring with sublethal doses of CMV and following the course of their acute CMV disease. Newborns were found to acquire detectable CMV antibody via the placental route but not the breast milk route. When compared to neonates with no acquisition of CMV immunity, neonatal offspring born to or foster fed on seropositive mothers were protected against generalized CMV infection to various degrees. The immunity transferred by pregnant mothers that had seroconverted prior to pregnancy was short lived and was more protective in newborns with detectable CMV antibody. Mothers that experienced primary CMV infection during pregnancy conferred on their progeny the most significant and long-lasting resistance against CMV challenge. This study demonstrates that newborn guinea pigs may acquire CMV-specific immunity from seropositive mothers; the degree of protection against CMV infection depends on the route of acquisition of immunity and on the time of maternal seroconversion.

Age Factors↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The placenta as a site of cytomegalovirus infection in guinea pigs.

The development of cytomegalovirus (CMV) infection in the placenta was studied in Hartley guinea pigs inoculated at midgestation, and its role in determining the outcome of fetal CMV infection was assessed. A hematogenous spread of CMV from the mother to the placenta occurred early during the course of the infection. However, the virus remained present in placental tissues long after CMV had been cleared from maternal blood (i.e., 3 and 4 weeks postinoculation). At that time, the virus was able to replicate in placental tissues in the presence of specific maternal antibodies. Viral nucleocapsids were seen within nuclei of trophoblastic cells, and virions were present surrounding infected cells. In addition, typical CMV-induced histopathological lesions bearing CMV antigens were consistently localized at the transitional zone between the capillarized labyrinth and the noncapillarized interlobium. Whenever CMV infection of the fetus occurred, virus was isolated from the associated placenta. Among placental-fetal units with CMV-infected placentas, only 27% of the fetuses were found to be infected. In addition, there was a delay in the establishment of the infection in the fetus in relation to the placenta, although frequencies of virus isolation in placental and fetal tissues peaked at 3 weeks after CMV inoculation. These results suggest that during primary CMV infection of pregnant guinea pigs, the placenta not only serves as a reservoir for CMV but also acts to limit transmission of the virus to the fetus.

Animals↗

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↗

Anaphylactoid reactions associated with parenteral cyclosporine use: possible role of Cremophor EL.

Acute anaphylactoid reactions occurred immediately after initiation of intravenous infusions of cyclosporine in three patients post-organ transplantation. Shortness of breath, flushing, tachypnea, chest pain, pruritus, or urticaria were noted; rapid recovery followed cessation of drug infusion. Subsequently, oral cyclosporine has been used in each patient without recurrence of the observed reaction. The presence of Cremophor EL as an emulsifying agent in the parenteral dosage formulation of cyclosporine is a likely etiology for this acute adverse reaction. Slowed rates of drug infusion and antihistamine premedication may permit continued intravenous cyclosporine use in affected patients.

Adult↗

Lymphadenopathy during cytomegalovirus-induced mononucleosis in guinea pigs.

Hartley guinea pigs infected with guinea pig cytomegalovirus (GP-CMV) develop a mononucleosis syndrome during primary infection that is similar to that seen in immunocompetent humans. In the present study this animal model of human disease was used to investigate the sequential changes in the lymph nodes during the course of primary GP-CMV infection. Infectious virus could be isolated from the nodes up to eight weeks after inoculation. When compared with nodes of control animals, the nodes of GP-CMV-infected animals were found to be enlarged up to a year after infection. During the first ten days of infection, histologic changes due to virus proliferation and immune stimulation of the paracortical areas of the lymph node, in a diffuse hyperplasia pattern, were noted. Although typical cytomegalovirus inclusions were seen only rarely, many cells demonstrated intranuclear staining using an avidin-biotin immunoglucose-oxidase histochemical reaction for GP-CMV. During late acute and chronic infection, the lymph nodes showed immune stimulation of the germinal centers, in the pattern of follicular hyperplasia. Specific histologic changes related to active virus proliferation were not seen after the early acute phase.

Acute Disease↗

Vascular endothelial cell HLA-DR antigen and myocyte necrosis in human allograft rejection.

Endomyocardial biopsies were obtained from patients who had received a human heart allograft. The biopsies were stained with a monoclonal antibody to the HLA-DR framework structure and the presence of HLA-DR was determined by an immunoperoxidase staining procedure. An increase in the concentration of HLA-DR on the vascular endothelium was detected shortly after transplantation. Low concentrations of endothelial DR were rarely (1/13) associated with myocyte necrosis. Eleven of 36 biopsies having an increased concentration of vascular endothelial cell DR antigen had myocyte necrosis. This study established that rejection is associated with an increase in HLA-DR antigens on the vascular endothelial cells.

Biopsy↗