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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 235 records · Page 13Linked to original sources
PubMed1989

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children.

Size limitations and technical barriers prohibit the use of many conventional mechanical circulatory support systems for postcardiotomy ventricular dysfunction in pediatric populations. Extracorporeal membrane oxygenation (ECMO), frequently used to treat neonatal respiratory failure, can provide cardiac support and is effective treatment of postoperative myocardial failure in children. From 1981 to 1987, 10 patients aged 2 days to 5 years were maintained on ECMO for 15 to 144 hours (mean duration, 92 +/- 16 hours) after cardiotomy. Operative procedures included repair of tetralogy of Fallot (2 patients), closure of a ventricular septal defect (2), the Senning procedure for transposition of the great arteries (1 patient), repair of interrupted aortic arch with closure of a ventricular septal defect (1), repair of a partial atrioventricular septal defect (2), closure of a ventricular septal defect with excision of an anomalous muscle bundle (1), and the Fontan procedure (1). Venoarterial ECMO was established in all 10 children. Six patients underwent transthoracic right atrium-ascending aorta cannulation, 3 had right internal jugular vein-right common carotid artery cannulation through a cervical incision, and 1 had right internal jugular vein-left axillary artery cannulation. Eight of the 10 patients were successfully weaned from ECMO, and 7 are long-term survivors. There were 3 deaths; 1 was caused by cardiac and acute renal failure complicated by sepsis two days after decannulation, another occurred 19 days after atrioventricular septal defect repair, and 1 was caused by massive pulmonary hemorrhage. Major hemorrhage developed in 3 patients while on ECMO; 2 required premature decannulation for mediastinal bleeding from operative sites and ultimately survived, and 1 died of respiratory failure as a result of endobronchial bleeding. We conclude that the use of ECMO in pediatric populations for transient postoperative ventricular dysfunction improves survival with limited overall morbidity.

Child, Preschool↗
PubMed1989

Implantable electrical left ventricular assist system: bridge to transplantation and the future.

An implantable left ventricular assist system (LVAS) utilizing an electromechanically driven dual pusher-plate blood pump has been employed in a multiinstitutional trial as a bridge to cardiac transplantation. Under development for permanent circulatory support in patients with end-stage heart disease, the LVAS, in this application, derives power and control from an external console via a percutaneous lead. The LVAS was implanted in 20 patients (16 men, 4 women) who were hemodynamically unstable or in refractory cardiogenic shock. The mean age was 44.9 years (range, 25 to 63 years). Preoperative diagnosis was evenly divided between end-stage ischemic disease, cardiomyopathy, and acute myocardial infarction. Implanted in the left upper quadrant within the anterior abdominal wall, the blood pump was connected between the left ventricular apex and ascending aorta. Total support of the systemic circulation and substantial left ventricular unloading were achieved with synchronous counterpulsation for periods up to 90 days (mean, 22.7 days). All patients were stabilized hemodynamically. The mean preoperative cardiac index of 1.5 L/min/m2 increased by a factor of 2. Pulmonary arterial pressures decreased substantially. Serious complications occurred in 16 patients, precluding cardiac transplantation in 10. Most complications (greater than 70%) were in patients who did not receive transplants; the most common complication was bleeding. Twelve of 13 patients with LVAS implants for more than seven days were mobilized, and 4 were fully ambulatory and completely rehabilitated. Orthotopic cardiac transplantation was performed in 10 patients after implants ranging from two to 90 days (mean, 30.3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Interim use of the Jarvik-7 artificial heart: lessons learned at Presbyterian-University Hospital of Pittsburgh.

Between October 1985 and March 1988, 16 patients received the Jarvik-7 total artificial heart as an interim device before transplantation. Ten patients were afflicted with cardiomyopathy, and 6 had end-stage ischemic disease. All but 1 were men; the mean age was 47 years (range, 27 to 59 years). Thirteen patients developed cardiogenic shock despite the use of intravenous inotropic agents (mean, 23 days; range, two to 83 days) and the intraaortic balloon pump (mean, 13 days; range, two to 65 days). Three other patients became candidates because of failed transplantation. The 100-mL Jarvik-7 device was used in the first 3 patients; all subsequent recipients were treated with the 70-mL Jarvik-7. Postoperative anticoagulation was designed to keep the partial thromboplastin time between 2 and 2.5 times control. The control values were obtained during administration of heparin and dipyridamole. In all cases the function of the total artificial heart was adequate to support the needs of the recipient, and there were no mechanical difficulties with the device or the drive system. The average time of implantation was 9 days (range, one to 35 days). Two patients died before transplantation, 1 with sepsis from fungus and the other with hemorrhage from a torn pulmonary arterial anastomosis. Fourteen patients received cardiac allografts, and 7 continue to survive without restrictions. Infection within the mediastinum caused the death of 4 patients after transplantation; in 3 of these mediastinitis was not recognized before transplantation but occurred within the first 2 weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The value of protective isolation procedures in cardiac allograft recipients.

The impact of protective isolation on the incidence of infection in 60 cardiac transplant recipients (mean age, 49.2 years) was studied in a prospective randomized trial. Thirty patients were randomized to protective isolation, which consisted of private room, hat, mask, sterile gown, and handwashing. Thirty patients were randomized to no isolation, which meant they recovered in a crowded, open intensive care unit and were adjacent to recipients of liver transplants or patients who were on the trauma, neurosurgical, and general surgical services, many of whom had an infection of the incision or a pulmonary infection. There was no difference between groups in the proportion of patients in whom infection developed (chi 2[1] = 0.27; p = 0.6), the number of infection-related deaths (2 in each group), the types of infection (bacterial, viral, fungal, or protozoal), or the overall outcome. Because protective isolation offered no benefit over standard care in protecting these patients from infections or the associated complications, we have discontinued its routine use after cardiac transplantation.

Adolescent↗
PubMed1989

Organ procurement for pulmonary transplantation.

Selection of suitable donors is critical to the success of clinical pulmonary transplantation. Requirements for lung donors, management before explantation, and methods of preservation were reviewed for the 70 heart-lung, eight double-lung, and two single-lung transplantations performed at the University of Pittsburgh since 1982. Careful observation of trends of hyperoxygenation studies, chest roentgenograms, and Gram stain and culture results of tracheal secretions, as well as findings on bronchoscopy, can help identify which lungs not only have adequate function but are acceptable for transplantation. In spite of the rigid criteria used, 76% of tracheal cultures from donors deemed acceptable grew organisms. The presence of oropharyngeal flora has been shown to correlate with the development of early intrathoracic infections in the recipient. Prophylactic broad-spectrum antibiotic treatment of the donor is desirable to treat microbial contamination that could cause focal injury to the donor lung and predispose to infection in the recipient. Acceptance of less than ideal donors is ill-advised even though rejection of such donors conflicts with the current shortage of organs.

Graft Survival↗
PubMed1989

Lessons learned in pediatric heart transplantation.

Between February 1, 1982, and June 30, 1988, 32 children underwent cardiac transplantation for treatment of congenital heart disease (10) and other cardiomyopathies (22). The 6-year actuarial survival was a disappointing 36% because of a high perioperative mortality (12 of 32, 37.5%) and because of five late deaths due to uncontrolable rejection. The perioperative mortality was a staggering 60% (6 of 10) for the patients with congenital heart disease. Four of the 6 recipients with congenital heart disease died because of acute failure of the donor right ventricle. This included 2 patients who required reconstruction of the pulmonary arteries for stenosis secondary to previous systemic-to-pulmonary shunts and 2 others in whom the pulmonary vascular resistances were underestimated because of undetected recent pulmonary emboli (1) and complicated pulmonary vascular anatomy (1). Five of the six late deaths were due to rejection-related events, and all were patients with acquired cardiomyopathy.

Actuarial Analysis↗
PubMed1989

Posttransplant lymphoproliferative disorders in heart-lung transplant recipients: primary presentation in the allograft.

Heart-lung transplant recipients are predisposed to acute rejection episodes, bronchiolitis obliterans, and opportunistic infections. In 9.4% of recipients at the University of Pittsburgh, a posttransplant lymphoproliferative disorder (PTLD) developed, and in 60% of cases, it presented in the allografted lungs and was associated with primary infection by Epstein-Barr virus (EBV). The PTLD is histologically indistinguishable from a primary pulmonary lymphoma and consists of a mixed population of large lymphoid cells, immunoblasts, and plasma cells. Two cases of PTLD were monoclonal with immunohistochemical and Southern blot analysis. Despite this, there was clinical recovery with reduced immunosuppression and acyclovir. We discuss the role of EBV in the development of PTLD and the pathogenesis of primary presentation in the allograft.

Adolescent↗
PubMed1989

Cytomegalovirus infection in immunocompromised guinea pigs: a model for testing antiviral agents in vivo.

An experimental model for testing antiviral agents against severe cytomegalovirus (CMV) infection in immunocompromised hosts was developed. The model consisted of cyclophosphamide (Cy) treatment of CMV-infected guinea pigs to simulate CMV infection in immunodeficient individuals. Of the 3 Cy regimens tested, a single 300 mg/kg dose administered one day after virus inoculation resulted in the most severe CMV infection considering mortality rates, mean day of death and loss of body weight. Evaluation of responses to both T and B cell mitogens suggested that the severe and lethal CMV infection resulted from the combined immunosuppressive effect of Cy and CMV. The nucleoside analog [9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) was used to assess the usefulness of the CMV-infected immunocompromised host model. DHPG (100 mg/kg/day for 8 days) prevented death but did not reduce virus infectivity titers in blood of Cy-treated, CMV-infected guinea pigs. This model of CMV infection in immunocompromised guinea pig is a relevant and convenient experimental tool for the assessment of candidate anti-CMV agents under well-defined experimental conditions, such as appropriate CMV inoculum and Cy regimen.

Acute Disease↗
PubMed1989

Gout in the heart transplant recipient: physiologic puzzle and therapeutic challenge.

PURPOSE: Hyperuricemia and gouty arthritis have been associated with cyclosporine use in renal transplant recipients. Patients requiring heart or heart-lung transplantation may have additional risk factors for the development of gout, yet it has not previously been described in this population. We share herein our clinical experience with gouty arthritis in six heart transplant recipients. PATIENTS AND METHODS: During a one-year period, six hospitalized male heart transplant patients were seen in consultation for gouty arthritis. Five were subsequently followed for gout as outpatients; the sixth died within six months. Management included trials of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, allopurinol, and intra-articular steroid injections, as well as attempts to minimize cyclosporine nephrotoxicity. RESULTS: Three patients had gout in remission at time of transplant surgery, and three others developed gout for the first time two to 45 months after transplantation. Following transplant surgery, both pre-existing and new-onset gout appeared to exhibit an accelerated course, with unusually rapid development of chronic polyarticular disease and tophi in four of the five patients followed for more than six months. Peak serum uric acid levels ranged from 11.0 mg/dL to 16.5 mg/dL. NSAIDs produced reversible renal insufficiency in four patients. Gout-related infections occurred in three patients, one of whom died. CONCLUSION: Acute gouty arthritis may occur in the heart transplant recipient despite concomitant use of immunosuppressive drugs. Cyclosporine, with its attendant hypertension and nephrotoxicity, appears to be the major risk factor for hyperuricemia in this setting, leading to the accelerated development of tophi and chronic polyarthritis. Management is complicated by the patients' renal insufficiency and propensity to infection, as well as by interaction with transplant-related medications. Prevention of hyperuricemia by minimizing cyclosporine nephrotoxicity appears to be the best management strategy, with judicious use of allopurinol for those patients in whom this preventive approach fails.

Adult↗
PubMed1989

The clinical spectrum, pathology, and clonal analysis of Epstein-Barr virus-associated lymphoproliferative disorders in heart-lung transplant recipients.

This study presents the clinical and laboratory observations on posttransplant lymphoproliferative disorders (PTLDs) occurring in 5 of 53 heart-lung transplantation recipients. Cervical lymph nodes, tonsils, lungs, and gastrointestinal tract were the common sites of involvement by PTLDs. The histopathologic findings showed a spectrum of lymphoid and immunoblastic proliferation ranging from diffuse hyperplasia to malignant lymphoma, immunoblastic or large cell type. All cases were associated with a primary Epstein-Barr virus infection, and viral DNA was demonstrated within the lesional tissue in three cases. Immunohistochemical and immunoglobulin gene rearrangement studies revealed a B-cell proliferation that was monoclonal in three cases and polyclonal in two cases. Compared with PTLDs arising in other organ transplant recipients, this series is remarkable for a high incidence of PTLDs (9.4%), a short interval to tumor diagnosis (2.2 months, mean), involvement of the primary allograft in three cases (60%), and the frequent development of bronchiolitis obliterans. Possible reasons for this distinct clinicopathologic profile are discussed.

Adolescent↗
PubMed1989

Low rate of Rhesus immunization from Rh-incompatible blood transfusions during liver and heart transplant surgery.

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh- persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh- liver, heart, and heart-lung transplant recipients received 3-153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D greater than 2 months later. Three patients developed anti-D at 11-15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, greater than 11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

Adult↗
PubMed1989

Proteins of the respiratory tract after heart-lung transplantation.

Heart-lung transplant recipients represent a unique population who experience episodic lung injury caused by infection or rejection. We hypothesized that the proteins in the respiratory lining fluids of these patients might reflect and provide insights into the in vivo immunologic and inflammatory events that occur in the transplanted lung. Structural, inflammatory, and immune proteins were quantitated in 57 samples of BAL fluid recovered from 17 heart-lung recipients when infections, rejection, or neither was present. Protein levels were compared with those of normal subjects and between the clinical transplant groups. When neither infection nor rejection was present, levels of albumin, fibronectin, and immunoglobulins G, M, and A were all higher in the transplanted lungs as compared with the normal lungs. These findings suggest that a new steady state of these proteins is established in the transplanted lungs. When infection or rejection was present, there was a further significant increase in albumin, fibronectin, IgG, and especially C5a in the transplanted lungs. These findings suggest that at least some elements of host defense remain intact in the posttransplantation period despite the use of immunosuppressive drugs and a HLA-incompatible microenvironment. The profiles of recovered alveolar proteins did not, however, help to differentiate infection from rejection. This is disappointing because distinguishing between infection and rejection without examination of lung tissue remains an unresolved and important clinical problem. Nevertheless these data provide new insights into organ tolerance and defense of the newly transplanted lung from infection or rejection.

Adolescent↗
PubMed1989

Selective inhibition of human immunodeficiency virus type 1 replication by the (-) but not the (+) enantiomer of gossypol.

The (-) enantiomer of gossypol but not the (+) enantiomer had good antiviral activity in peripheral blood mononuclear cells against human immunodeficiency virus type 1 at a concentration more than 20-fold lower than that required for cytotoxicity; however, in H9 cells the (-) enantiomer, although more potent as an antiviral agent, was more cytotoxic.

Cells, Cultured↗
PubMed1989

Coronary artery fistula in the heart transplant patient. A potential complication of endomyocardial biopsy.

All follow-up annual cardiac catheterizations performed on recipients of orthotopic heart transplant were reviewed, and 14 patients with coronary artery fistula were identified. The prevalence (8.0%, 14 of 176 patients) was strikingly higher than that for patients without transplant (0.2%) who underwent routine cardiac catheterization. These 14 patients had 21 coronary artery fistulas: single in nine and multiple in five patients. Fifty-two percent arose from the right, 43% from the left anterior descending, and 5% from the circumflex coronary artery. All drained into the right ventricle. Four patients underwent oximetric evaluation, and left-to-right shunting was not detectable. No patient had symptoms attributable to the fistula. Hemodynamic measurements were similar to those of a control group of 28 age- and sex-matched recipients of heart transplant without coronary artery fistula; however, the cardiac index (p = 0.02) and pulmonary artery oxygen saturation (p = 0.03) were significantly higher, and the arteriovenous oxygen difference (p = 0.01) was significantly lower in the group with coronary artery fistula. The histologic features of rejection, large arterioles, or epicardial fat on any biopsy specimen predating coronary artery fistula diagnosis were not associated with the development of the fistula when the two groups were compared. Nine patients (11 coronary artery fistulas) had follow-up studies performed, and three fistulas were larger, three were unchanged, two were smaller, and three had resolved. No complications of coronary artery fistula developed during a mean follow-up of 28 months (range, 12-42 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Ventilation and breathing pattern during progressive hypercapnia and hypoxia after human heart-lung transplantation.

The effects of human pulmonary denervation on the ventilatory responses to progressive hyperoxic hypercapnia and isocapnic hypoxia as well as the effect on resting breathing pattern were evaluated in nine female heart-lung transplant (H-LT) recipients. The results were compared to those obtained from 10 normal women of comparable age and stature. Testing was performed 2 to 37 months after H-LT (median, 7.5 months). Cardiac function was normal in all H-LT recipients. None of the patients had spirometric evidence of airway obstruction, while six had a restrictive pattern with forced vital capacities less than 80% of predicted values. Resting minute ventilation (VE), tidal volume (VT), and ventilatory drive (VT/TI) in the H-LT recipients were not significantly different from those of the normal subjects. Inspiratory time (TI), however, was significantly shorter in the H-LT patients (1.64 +/- 0.2 versus 2.09 +/- 0.13 s, p = 0.035), and resting breathing frequency (F) tended to be greater in the H-LT recipients (16.27 +/- 2.04 versus 12.82 +/- 0.53 breaths/min, p = 0.052). The overall ventilatory response to hypercapnia was reduced after H-LT (0.91 +/- 0.17 versus 1.5 +/- 0.27 L/min/mm Hg CO2, p less than 0.043), as was the F response (0.2 +/- 0.09 versus 0.65 +/- 0.13 breaths/min/mm Hg CO2, p less than 0.01). The VT and VT/TI responses to hypercapnia did not differ between the H-LT recipients and normal subjects. There were no significant differences between the two groups with respect to the responses to progressive hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Breathing during wakefulness and sleep after human heart-lung transplantation.

To study the effects of pulmonary denervation on breathing during sleep, sleep studies were conducted on seven heart-lung transplant recipients (H-LT) and a comparable number of sex-matched normal subjects of similar age. Four of the H-LT patients had a restrictive pattern on spirometry. The time since transplantation ranged from 45 to 1,102 days. There were no significant differences between the groups with respect to total sleep time or distribution of sleep stages. There were no significant differences between the H-LT recipients and normal subjects with respect to baseline awake oxyhemoglobin saturation (SaO2) or the nadirs of SaO2 during REM and non-REM sleep, the absolute number and frequency (number per hour of sleep) of apneas, hypopneas, desaturation events, both over the whole night of study or separately during non-REM and REM sleep. Across wakefulness and all sleep stages, the H-LT patients tended to have shorter total respiratory cycle times (Ttot) (p = 0.052) and more rapid breathing frequency (F) than the normal subjects. This was associated with significantly shorter inspiratory times (Tl) (p less than 0.001) and smaller duty cycles (Tl/Ttot) (p less than 0.005) in the H-LT recipients. During non-REM and REM sleep, F tended to be higher in the H-LT recipients with pulmonary restriction than in the nonrestricted patients. There were no significant differences between the H-LT recipients and the normal subjects with regard to the periodicity of breathing, either in terms of timing parameters or breath amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗