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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 343 records · Page 19Linked to original sources

Principles of multiple organ procurement from cadaver donors.

The need for cadaveric organs other than kidneys for transplantation is increasing. Principles and techniques that allow their procurement without jeopardizing renal recovery are outlined. These include utilization of brain dead donors, careful donor selection, and surgery which minimizes warm ischema while avoiding iatrogenic injury. Utilizing this approach, a variety of combinations of organs have been removed and transplanted resulting in satisfactory functional results.

Cadaver↗

Cardiac transplantation with cyclosporin A and prednisone.

Influenced by continuing improvement in results from Stanford, cardiac transplantation was resumed at the University Health Center of Pittsburgh in June 1980. Cyclosporin A (CyA) became available to the authors early in 1981. This report describes the preliminary experience with 21 patients who were treated between March 1981 and April 10, 1982 with cyclosporin A and low-dose steroids. Age ranged from eight to 53 years, median 46 years. Median age of ten patients disabled because of idiopathic myocardiopathy was 33 years; it was 45 years in the 11 suffering from ischemic heart disease. Sixteen of the 21 patients survived. Eleven have survived for three months, if which six have survived for six months, giving a cumulative survival of 74 and 66%, respectively. Four died perioperatively; one died at six weeks and one at four months. Hyperacute rejection resulted in one death at 12 hours even though the warm and cold lymphocytotoxic crossmatch for T and B cells was negative as evaluated by trypan blue. The two late deaths were related to infection. No late death has occurred because of rejection, and a unique feature is that three recipients with a lymphocytotoxic mismatch did not develop hyperacute rejection. The number of infectious episodes and nonviral infections appears to be less than that associated with the use of azathiaprine and larger doses of steroids. Cyclosporin A (5-10 mg/kg/d) and low-dose prednisone (rapidly tapered in seven days from 200 mg to 15-20 mg/d) is effective in preventing early morbid rejection of the transplanted heart.

Adolescent↗

Neutrophil response and function during acute cytomegalovirus infection in guinea pigs.

The mobilization and functional characteristics of polymorphonuclear leukocytes (PMNs) at the site of an inflammatory stimulus were studied during acute cytomegalovirus infection in guinea pigs. Weanling Hartley strain guinea pigs were inoculated subcutaneously with approximately 10(6) 50% tissue culture infective doses of virulent salivary gland-passaged guinea pig cytomegalovirus. The virus was uniformly present in bone marrow, buffy coat, and casein-elicited peritoneal exudate cells 5 to 7 days after the inoculation. The mean numbers of circulating PMNs in the animals were 2,862/microliters in uninfected controls and 880/microliters in infected animals. The total peritoneal PMNs recovered 14 h after casein injection were 491 X 10(6) and 237 X 10(6) in control and infected animals, respectively. The number of 50% tissue culture infective doses of guinea pig cytomegalovirus per 10(6) purified peritoneal PMNs was 10(2.17). Neutrophil O2 consumption was similar in infected and control animals in response to either stimulation by a neutrophil activator, phorbol myristate acetate, or phagocytosis of Staphylococcus aureus. However, the maximal rate of H2O2 release and the percent killing of S. aureus by peritoneal exudate cells from infected animals were significantly reduced compared with uninfected controls during acute infection. Granulocytopenia, a decreased mobilization of PMNs to the site of the inflammatory stimulus, a diminished cellular release of H2O2 in response to a bacterial stimulus, and a modest reduction in bacterial killing were demonstrated during experimental acute cytomegalovirus infection. Such reductions in granulocyte number and function at inflammatory sites during this type of infection could alter antimicrobial defenses.

Animals↗

Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs.

The virologic and histologic characteristics of congenital cytomegalovirus infection (CMV) were defined in 65 neonatal guinea pigs born from 27 mothers infected pregnancy. Infectious virus or tissue lesions were present in 54% of the neonates tested. Guinea pig CMV was detected most often in the salivary glands (72%) and spleen (33%) of infected guinea pigs. Less frequently, virus was also detected in the brain, lung, pancreas and liver. Tissue lesions were most frequently observed in the brain and kidney, but also occurred in the salivary glands, liver, pancreas, thymus and spleen. The histopathology was identical to that observed in infants with congenital CMV infection. Infectious virus and histopathology were present in newborn guinea pigs born from mothers infected at any time during gestation. Newborns from mothers infected during early stages of gestation and virus present most frequently in the salivary glands, whereas offspring of mothers infected in late pregnancy had virus present in several tissues. Acute maternal guinea pig CMV infection produced generalized CMV infection of the offspring which was followed by persistent infection in neonatal salivary glands. Lesions remained present in several neonatal tissues including the brain. The long term consequences of such lesions in affected guinea pigs remain to be determined. The results of the study emphasize the similarities between human congenital CMV infection and congenital guinea pig CMV infection, thereby underlining the utility of this animal model as a means of understanding human congenital CMV infection.

Animals↗

Pulmonary valvulotomy alone for pulmonary stenosis: results in children with and without muscular infundibular hypertrophy.

Pulmonary valvulotomy for valvular pulmonic stenosis has been performed in 78 children at the Children's Hospital of Pittsburgh. Although 27 patients had muscular hypertrophy of the infundibulum, a muscle resection was employed in only one child. Examinations 2 to 18 years after operation have not demonstrated electrocardiographic (ECG) or clinical evidence of persistent right ventricular hypertension, indicating resolution of the muscular outflow tract narrowing. Systolic right ventricular pressure averaged 30 mm Hg in 10 patients at postoperative catheterization: Six of these patients had peak right ventricular pressures greater than 100 mm Hg immediately after valvulotomy. The diameter of the infundibulum in systole was compared to valve ring diameter and expressed as a ratio (I/V). This correlated with the preoperative and intraoperative right ventricular pressures, but did not identify patients who might fail to resolve secondary muscular hypertrophy. A murmur of pulmonary regurgitation was present in 70% of the patients after operation, but was without clinical significance. In the absence of fixed infundibular obstruction or excessive right ventricular hypertension above 200 mm Hg, resection of infundibular hypertrophy is not recommended.

Adolescent↗

Cytomegalovirus-induced mononucleosis in guinea pigs.

The effects of cytomegalovirus (CMV) infection on hematopoietic and lymphoid tissues were studied in guinea pigs. Blood parameters, histopathology, and virus distribution in the bone marrow, spleen, lymph nodes, and thymus were assessed during primary nonlethal acute and chronic guinea pig CMV infection. Transient hematological changes comparable to those seen in human CMV mononucleosis were observed during acute infection. These included anemia and leukocytosis with atypical lymphocytes. Splenomegaly and stimulation of spleen and lymph node T- and B-cell areas were also noted. These changes occurred at the peak of virus recovery from all tissues tested, as well as from macrophages and B- and T- cell-enriched spleen subpopulations. Virus was cleared rapidly from blood and bone marrow; blood counts, spleen size, and histology returned to normal within 1 month after virus inoculation. However, guinea pigs failed to eliminate the virus completely from lymphoid tissues, since virus persisted in splenic macrophage and B-lymphocyte-enriched populations during chronic infection. The data suggest that CMV-infected mononuclear cells play a role in the establishment of generalized acute infection and virus persistence.

Animals↗

Lead systems for internal ventricular fibrillation.

We examined the feasibility of using a standby automatic implantable defibrillator and established thresholds for internal defibrillation. The implantable defibrillator senses ventricular fibrillation and delivers an electrical impulse for defibrillation. Two lead systems for the device have been investigated. System I consists of two 12-cm2 silicone-covered titanium mesh patches attached to the atrial and diaphragmatic pericardial surfaces. System II has an identical diaphragmatic patch and a titanium spring catheter, with a 12-cm2 surface area of conductivity, placed transvenously in the right atrium. Both systems were implanted by thoracotomy in 12 dogs (mean weight 20 kg) and by a subxiphoid approach in 10 pigs (mean weight 20 kg). The defibrillation threshold (lowest energy required for 80% success) was determined periodically for 54 weeks in the dogs (615 trials) and at 6 weeks for the pigs (100 trials). In dogs, the mean defibrillation threshold with system I leads at 4 weeks was 10.5 J and did not change significantly over a 54-week period (p greater than 0.05). Similar results were obtained in the pig at 4 weeks. The defibrillation thresholds for both lead systems in dogs and pigs using a transpleural thoracotomy or a subxiphoid approach are satisfactory for an implantable defibrillator that produces 20-35 J.

Animals↗

Extracorporeal membrane oxygenation. Successful treatment of persistent fetal circulation following repair of congenital diaphragmatic hernia.

Four neonates (three having undergone repair of a congenital diaphragmatic hernia and developing a persistent fetal circulatory pattern and one having severe infant respiratory distress syndrome) have been supported with prolonged extracorporeal membrane oxygenation (ECMO) at Children's Hospital of Pittsburgh between December of 1979 and April of 1980. Three have survived. This encouraging experience indicates that the pattern of persistent fetal circulation in the newborn infant who has undergone repair of a diaphragmatic hernia can be successfully managed with ECMO even when efforts to lower pulmonary hypertension and improve oxygenation with vasodilators (tolazoline, phenothiazine, acetylcholine, or prostaglandin E1) and have been ineffective. The effectiveness and safety of ECMO is convincing enough to warrant its consideration as therapy for congenital diaphragmatic hernia and persistent fetal circulation prior to the use of vasodilators.

Blood Flow Velocity↗

Clinical experience with pediatric microporous oxygenator for profound hypothermia.

The Travenol TMO Total Bypass Membrane Oxygenator-Pediatric satisfactorily transfers oxygen and carbon dioxide under standardized conditions of operation during total high-flow bypass at normothermia or moderate hypothermia. This oxygenator has not been used at rates of flow less than 1 L/min or at temperatures below 23 degrees C. The current technique requires a venous and arterial pump with 5% recirculation to assure that pressure in the blood phase does not exceed the pressure above which blood may seep through the adhesive seals into the gas envelope. Conventional methods of perfusion were modified for use at profound hypothermia (18 degrees C) with low-flow bypass or circulatory arrest. Clinical experience with 22 children, preceded by six laboratory experiments, indicates that satisfactory control of arterial gases can be achieved and maintained.

Cardiopulmonary Bypass↗

Cardiopulmonary dynamics during arteriovenous perfusion: cardiac output, pulmonary arterial resistance, and right venticular stroke work.

The effects of arteriovenous perfusion on myocardial performance, pulmonary circulatory dynamics, and organ preservation were studied in dogs in order to evaluate the applicability of arteriovenous extracorporeal membrane oxygenation for partial respiratory support. Studies were made on normally oxygenated dogs, on dogs made hypoxic by oxygen deprivation and ventilatory depression, and on dogs with pulmonary injury and moderate pulmonary hypertension induced by injection of oleic acid into the right ventricle. The latter two groups were included to assess the changes that occur in cardiopulmonary dynamics in the presence of hypoxia and pulmonary hypertension. A microchannel membrane oxygenator was employed to provide partial respiratory support to the group of animals with pulmonary injury. The results indicate that no deleterious hemodynamic changes occurred in any of the groups of animals with arteriovenous flow for periods of up to 5 hours at rates corresponding to 20 to 35% of the total cardiac output. Adequate systemic oxygenation was provided by the microchannel oxygenator at these rates of arteriovenous perfusion.

Animals↗

Cytomegalovirus infection in guinea pigs. IV. Maternal infection at different stages of gestation.

The effects of maternal infections with guinea pig cytomegalovirus (CMV) at different stages of gestation were evaluated in mothers, fetuses, and newborn animals. Increased cervical excretion of guinea pig CMV was detected in pregnant animals one to 30 days after inoculation. Fetal infection occurred in utero regardless of the time of maternal infection. The frequencies of stillbirths and viral infection in newborn offspring were higher in mothers infected in late gestation than in mothers infected during the first trimester of pregnancy. The major factor affecting isolation of guinea pig CMV from offspring was the duration of maternal infection. Virus was detected most often in fetuses and newborn animals within two weeks after inoculation of the mothers. Thereafter, guinea pig CMV disappeared progressively in the progeny, although histological lesions were observed and virus was found in the salivary glands of some offspring for as long as 14 weeks after delivery.

Animals↗

Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus.

Live guinea pig cytomegalovirus (CMV) vaccine was prepared after 11 serial passages in tissue culture; noninfectious envelope antigen vaccine was prepared by n-octyl glucoside treatment of CMV-derived dense bodies and virions. Hartley strain guinea pigs immunized with either vaccine were compared with guinea pigs inoculated with virulent, salivary gland-passaged CMV (approximating natural infection), with passively immunized animals, and with nonimmune controls. All vaccinated animals had neutralizing antibodies to CMV. After challenge with virulent CMV, animals previously inoculated with either tissue culture-passaged or virulent CMV were protected against acute viremia and death; pregnant animals previously inoculated with live CMV vaccine had lower incidences of viremia and generalized maternal and fetal infection. Envelope antigen-vaccinated and passively immunized pregnant animals showed acute viremia after similar challenge with virulent virus; however, infection was less generalized than that in control animals, and CMV was not isolated from the fetuses of these vaccinated mothers.

Animals↗

Thromboresistant surface coatings for the measurement of cardiac output through continuous low flow peripheral A-V shunts.

The dilution technique for determining cardiac output using indocyanine green dye is limited in patients weighing less than 20 kg because of the obligatory volume loss. Reproducible achieved using the green dye dilution method by the establishment of a low flow peripheral arteriovenous shunt. The shunt materials were treated with thromboresistant agents--TDMAC (7%) and albumin (1 g/dl)--to facilitate the use of this technique without heparin. For A-V shunt flow rates of 8-30 cc/min reproducible values of cardiac output were obtained for up to 38 hours which were in good agreement with determinations made using the conventional technique of dye dilution.

Animals↗

Selected lobar injury after infusion of oleic acid.

A model of respiratory distress has been developed using sheep in which an isolated lobar injury is induced by infusion of oleic acid into a selected lobar artery. The directed insult permits acute and chronic phase study without the requirement of intensive pulmonary support. One hour after selective lobar injury the affected pulmonary venous oxygenation (Ppvo2) was reduced from greater than 310 to 66-90 Torr. Ppvo2 was most impaired at 48 h (40-55 Torr), but showed improvement by 96 h postinjury. Radionuclide estimates of lobar ventilation and perfusion demonstrated an initial fall in ventilation by 51% and corresponding 41% reduction in perfusion. By 24 h the depression of perfusion matched that of ventilation. Sequential light and scanning electron microscopy demonstrated the presence of a nonhomogeneous injury with areas of both complete parenchymal replacement by fibrous tissue and those with minimal architectural distortion. The selective injury model offers a useful methodology for the evaluation of the effects of various agents on the acute and chronic response of the lung to injury.

Acute Disease↗

Arteriovenous ECMO for neonatal respiratory support. A study in perigestational lambs.

A study was undertaken to investigate the applicability of the arteriovenous mode of perfusion for partial support of neonatal respiration. Perigestational lambs, delivered by cesarean section, served as the animal model of respiratory distress. Arteriovenous flow was accomplished between a single umbilical artery and vein. A microchannel membrane oxygenator was used to provide partial respiratory support to the newborn lambs. Total systemic flow, pulmonary blood flow, and pulmonary vascular resistance were assessed at various rates of arteriovenous perfusion and correlated with systemic oxygenation. A reduction in right-to-left shunting of blood and pulmonary vascular resistance occurred as arterial oxygenation rose from conditions of hypoxemia to PaO2 values higher than 50 torr. Myocardial performance was not impaired at rates of arteriovenous perfusion below 30 percent of the total systemic flow, as evidenced by normal electrocardiographic tracings, pulmonary capillary wedge pressures, and central venous pressures. Arteriovenous extracorporeal membrane oxgenation (ECMO) may be particularly suitable for use in infants with hypoxia and high pulmonary vascular resistance.

Animals↗

Dynamic computed tomography of the lung: regional ventilation measurements.

The spatial resolution provided by computed tomography (CT) yields excellent anatomic specificity, and fast scanners are capable of the serial imaging necessary to monitor rapid changes in tracer concentration over time. In this study, sequential CT imaging defined the temporal changes of xenon concentration in peripheral lung tissue of a nonhuman primate and three sheep, both during and after xenon inhalation. Ventilation rate constants (K) in lung tissue with normal and impaired function in the evaluation of regional ventilation using xenon enhanced CT are discussed.

Animals↗