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Biomedical subjects

V A Starnes

Publications and source records attributed to V A Starnes.

At least 73 records · Page 4Linked to original sources
PubMed1995

Analysis of bronchoalveolar lavage from human lung transplant recipients by flow cytometry.

Bronchoalveolar lavage (BAL) cells and peripheral blood leucocytes (PBL) from 24 lung transplant recipients were analysed for leucocyte subsets and expression of cell surface antigens. Total and differential white cell counts were performed on BAL, and lymphocyte subsets were evaluated in both BAL and peripheral blood. Measurement of immunofluorescence by flow cytometry was used to assess the percentage of: T cells (CD3+); T-helper cells (CD4+); T-cytotoxic/suppressor cells (CD8+); and activated lymphocytes (HLA-DR+). Lymphocyte subsets in BAL demonstrated marked differences to those in blood. A lower percentage of CD3+ and CD4+ lymphocytes were found in BAL, whereas CD8+ cells were more prevalent in BAL than in PBL. The mean CD4:CD8 ratio was significantly lower in BAL (1:1) than in blood (2.1:1). In the absence of pulmonary infection, there was a trend for a lower CD4:CD8 ratio in BAL associated with acute rejection (1.1:1) and obliterative bronchiolitis (1:1), when compared to the group with no evidence of rejection (1.4:1). In the absence of pulmonary rejection, pulmonary infection was associated with a marginally lower CD4:CD8 ratio in BAL (0.7:1), than when infection was absent (1.4:1). This difference was more evident in cases of cytomegalovirus (CMV) infection with a mean CD4:CD8 ratio of 0.3:1, compared to 1.5:1 in the absence of CMV disease (P < 0.05).

Adolescent↗
PubMed1995

Successful use of transesophageal echocardiography during extracorporeal membrane oxygenation in infants after cardiac operations.

We report the use of transesophageal echocardiography in infants after cardiac operations while supported on extracorporeal membrane oxygenation. In all patients transesophageal echocardiography provided valuable information when standard transthoracic echocardiographic evaluation was limited by poor acoustic windows. This report describes the application of transesophageal echocardiography during extracorporeal membrane oxygenation after cardiac operations.

Cardiac Surgical Procedures↗
PubMed1994

Recovery of the right ventricle after single-lung transplantation in pulmonary hypertension.

Single-lung transplantation has been successfully performed in patients with pulmonary fibrosis and emphysema. In contrast, patients with end-stage pulmonary hypertension (either primary or secondary to Eisenmenger's syndrome) have conventionally been offered heart-lung transplantation. The rationale underlying this approach is that chronic pulmonary hypertension results in irreversible right ventricular dilatation and failure. Recovery of the right ventricle has previously been reported after thromboendarterectomy for chronic large-vessel pulmonary embolism, correction of atrial septal defect or mitral valve replacement. The evolution of right ventricular morphology and function after lung transplantation has not been previously described. This study examines the reversibility of right ventricle dysfunction following normalization of pulmonary artery pressure after single-lung transplantation in 4 patients with pulmonary hypertension. Cardiac function was assessed using electrocardiography, echocardiography and radionuclide angiography. Pulmonary hemodynamic measurements, including pulmonary artery pressure and pulmonary vascular resistance, decreased in all patients after single-lung transplantation. Electrocardiographic changes observed were leftward shift in the QRS axis, and a decrease in P-wave amplitude and in right ventricular force. Echocardiographic examination revealed decreased right atrial, right ventricular and tricuspid valve annular dimensions, normalization of septal motion, and decreased tricuspid regurgitation. Thus, improved pulmonary hemodynamics after single-lung transplantation for pulmonary vascular disease results in reversal of right heart dilatation and dysfunction, and improved myocardial performance. The extent of right ventricular dysfunction beyond which recovery is unlikely to occur has yet to be determined.

Adult↗
PubMed1994

Living-related donor lobectomy for bilateral lobar transplantation in patients with cystic fibrosis.

Donor lobectomy has been performed in 14 patients enabling 7 recipients with cystic fibrosis to undergo bilateral living-related lobar pulmonary transplantation. Donors included 11 patients, 2 brothers, and 1 uncle. Donor mean age was 43 years (range 24 to 55 years). Their mean height and weight was 170 cm (range, 169 to 180 cm) and 72.4 kg (range, 55 to 90 kg), respectively, compared with 161 cm (range, 140 to 175 cm) and 42.4 kg (range, 27 to 55 kg), respectively, in the recipient group. Donor pulmonary evaluation consisted of a history and physical examination, chest roentgenogram and computed tomographic scan, spirometry with arterial blood gas measurement, echocardiography, and perfusion scanning. From each pair of donors, one was selected for right lower lobectomy and the other for left lower lobectomy. Standard lobectomy techniques were modified to facilitate implantation and optimize preservation of the donor lobes. On the right side, the middle lobe was removed and discarded in the first three donors to provide an adequate cuff of pulmonary artery and bronchus for implantation. With increased experience, this has proved not to be necessary. There have been no deaths and no long-term complications in the donor group. Prolonged postoperative air leaks occurred in the 3 patients who underwent right lower and middle lobectomies. All donors have been able to resume their previous lifestyles. Living-related donor lobectomy provides an alternative to cadaveric organs in select patients in need of pulmonary transplantation.

Adolescent↗
PubMed1994

Current surgical management of tetralogy of Fallot.

The surgical management of tetralogy of Fallot has undergone important changes in recent years. Earlier repair of tetralogy of Fallot is now favored by many institutions. At Stanford University Medical Center, we have performed definitive repair of tetralogy of Fallot at the time of presentation, regardless of the child's age, with few exceptions. In this report, we describe our results with early repair, and we believe these support the contention that infants who undergo early repair (< 1 year of age) have postoperative results similar to those of children who undergo repair at an older age. Complications related to shunts are prevented by the infant repairs, and, in the future, reduced ventricular ectopy may be demonstrated to be a benefit of such repairs.

Age Factors↗
PubMed1994

Transesophageal echocardiography in the postoperative child with an open sternum.

We report the use of transesophageal echocardiography in 3 children whose sternums remained open for several days postoperatively. In these patients transesophageal echocardiography provided critical information when transthoracic echocardiography was ineffective due to limited acoustic windows. This report points out the application of transesophageal echocardiography in children with chest wall distortion.

Cardiac Tamponade↗
PubMed1994

Aspergillosis of the posterior mediastinum.

Invasive pulmonary Aspergillus, although rare in the general population, represents an important cause of morbidity and mortality among immunosuppressed patients. However, mediastinal invasion by Aspergillus is very uncommon, with few cases documented in the literature. Among 13 immunosuppressed pediatric patients recently diagnosed with invasive pulmonary aspergillosis, 3 have had posterior mediastinal invasion with severe complications. Rupture of a mycotic aortic aneurysm occurred in 2 patients, one of whom was operated on successfully. The infection involved the spinal cord with severe neurologic sequelae in 2 patients. We report our experience to make our colleagues aware of this problematic disease, which may be more prevalent in the current population of highly immunosuppressed pediatric patients.

Adolescent↗
PubMed1994

Lobar lung transplantation as a treatment for congenital diaphragmatic hernia.

The mortality rate for infants severely affected with congenital diaphragmatic hernia (CDH) remains high despite significant advances in surgical and neonatal intensive care including delayed repair and extracorporeal membrane oxygenation (ECMO). Because of the increasingly successful experience with single-lung transplantation in adults; this approach has been suggested as a potential treatment for CDH infants with unsalvageable pulmonary hypoplasia. The authors report on a newborn female infant who was the product of a pregnancy complicated by polyhydramnios. At birth, she was found to have a right-sided CDH and initially was treated with preoperative ECMO, followed by delayed surgical repair. Despite the CDH repair and apparent resolution of pulmonary hypertension, the infant's condition deteriorated gradually after decannulation, and escalating ventilator settings were required as well as neuromuscular paralysis and pressor support because of progressive hypoxemia and hypercarbia. A lung transplant was performed 8 days after decannulation, using the right lung obtained from a 6-week-old donor. The right middle lobe was excised because of the size discrepancy between the donor and recipient. After transplantation, the patient was found to have duodenal stenosis and gastroesophageal reflux, which required duodenoduodenostomy and fundoplication. The patient was discharged from the hospital 90 days posttransplantation, at 3 1/2 months of age. Currently she is 24 months old and doing well except for poor growth. This case shows the feasibility of single-lung transplantation for infants with CDH, and the potential use of ECMO as a temporary bridge to transplantation. Lobar lung transplantation allowed for less stringent size constraints for the donor lung.

Extracorporeal Membrane Oxygenation↗
PubMed1994

Cytokine gene expression in human cardiac allograft recipients.

The long-term success of heart transplantation for end-stage heart disease has been hindered by the problems associated with acute and chronic graft rejection, opportunistic infections and potentially fatal complications of intensive immunosuppression. A more complete understanding of the biology of transplant rejection should provide the basis for the development of improved methods for controlling and monitoring rejection. Cytokines, the soluble factors which regulate the immune response, are central to the rejection process. The objective of this study was to analyse cytokine mRNA transcripts in 99 biopsy samples and 89 blood samples from 65 and 35 Stanford Medical Center cardiac transplant recipients, respectively, gathered between January 1990 and January 1992. Following RNA extraction and conversion to cDNA, samples were amplified with cytokine-specific primers for interleukins (IL) 1 to 8, TNF-beta (tumour necrosis factor-beta) and IFN-gamma (interferon-gamma) and were analysed by gel electrophoresis and Southern blot hybridization. Our results demonstrate that despite chronic immunosuppressive therapy, the peripheral blood of transplant recipients expressed a higher combined percentage of different cytokine transcripts than did peripheral blood obtained from normal volunteers. In transplant patients, detection of cytokine transcripts for IL-1 alpha, IL-1 beta and IL-2 increased with time after transplantation. Intragraft IL-7 gene expression was significantly increased in biopsies diagnosed with mild (grade 1) rejection when compared to those with no evidence of rejection or with moderate to severe rejection. Implications of these results in light of possible mechanisms of rejection and of new approaches to immunotherapy are discussed.

Blotting, Southern↗
PubMed1994

[Intrathoracic half-working heart and lung transplantation in the rat].

A new technique of intrathoracic half-working heart-lung transplantation in the rat was established. Donor heart-left lung graft was transplanted into left hemithorax of the recipient with aorta-aorta, bronchus-bronchus and superior vena cava (SVC)-SVC anastomoses, and the recipient's descending aorta proximal to the anastomosis was ligated. Five isografts (Lewis-Lewis) showed excellent cardiopulmonary function 4 weeks after transplantation. In 11 allografts (DA-Lewis), 5 rats without immunosuppression survived in 4-6 postoperative days and 6 rats with cyclosporine 10 mg/kg/day were alive during 8-14 days after operation. Nine of 11 allografts demonstrated moderate to severe (ISHLT grade 3-4) acute rejection and the grade of lung rejection was higher than that of heart rejection in 4 of 9 allografts.

Acute Disease↗
PubMed1994

Pediatric cardiac transplantation. The Stanford experience.

BACKGROUND: Cardiac transplantation for children with endstage heart disease has become an accepted form of therapy and is being practiced with increasing frequency and improving short-term outcome. METHODS AND RESULTS: To assess the medium-term outcome of pediatric cardiac transplantation, we analyzed our experience with 72 patients under the age of 18 (range, 0.1 to 17.7 years; mean, 9 +/- 6.4 [SD]) who underwent orthotopic cardiac transplantation at Stanford University between 1977 and 1993. There were 38 male and 34 female patients. Preoperative diagnoses included congenital heart disease in 24 (33%), idiopathic cardiomyopathy in 27 (37%), viral cardiomyopathy in 12 (17%), and familial cardiomyopathy in 7 (10%) patients. Immunosuppressive management has evolved over time and has included a tapering schedule of steroids, azathioprine, rabbit antithymocyte globulin, cyclosporine in all patients after 1980, and induction with OKT3 since 1987. Operative mortality rate was 12.5 +/- 4.0% (mean +/- 70% confidence intervals). Actuarial survival estimates at 1, 5, and 10 years are 75 +/- 7.1%, 60 +/- 6.4%, and 50 +/- 8.1% (mean +/- 1 SEM), respectively. Causes of death included infection in 8 (28% of deaths), rejection in 7 (24%), graft coronary disease in 5 (17%), pulmonary hypertension in 4 (14%), and nonspecific graft failure in 2 (7%) patients. Survival rates were similar for patients over and those under age 10 years (including the infant cohort of 18 patients transplanted since 1986). Currently, there are 43 patients alive, all in New York Heart Association functional class I. Only 22 +/- 5.6% of patients were free of rejection at 1 year, but 86 +/- 5.4% were free of rejection-related death at 10 years. At 1 year, only 37 +/- 6% of patients were free from any infection, but 88 +/- 4.2% remained free of infection-related death at 5 years. Actuarial freedom from graft coronary artery disease (angiographic or autopsy proven) was 85 +/- 6.6% at 5 years and from coronary artery disease-related death was 91 +/- 4.7%. CONCLUSIONS: These data demonstrate satisfactory medium-term outcome of cardiac transplantation in selected pediatric patients with end-stage heart disease, but further progress is necessary to more effectively control rejection, infection, and graft coronary disease.

Actuarial Analysis↗
PubMed1994

Lobar transplantation. Indications, technique, and outcome.

Lobar transplantation represents a therapeutic option for children and some adults with severe end-stage pulmonary disease. Six patients including two neonates, three children, and one adult underwent lobar transplantation. Ages ranged from 17 days to 21 years. Transplant procedures were unilateral in the neonates and two of the children and bilateral in the child and adult who had cystic fibrosis. The donor lobes were from cadavers in the two neonates and living related donors in the children and the adult. Unilateral grafts involved use of the right upper lobe in the 12-year-old patient with bronchopulmonary dysplasia; right middle lobe with a ventricular septal defect repair in the 4-year-old patient with Eisenmenger's syndrome, left upper lobe in the 28-day-old patient with primary pulmonary hypertension, and the right upper and middle lobes in the 17-day-old patient with diaphragmatic hernia. Bilateral lobar transplantations were performed with the right lower and left lower lobes in the two patients with cystic fibrosis (aged 13 and 21 years). The two neonates underwent emergency transplantation with the use of extracorporeal membrane oxygenation as a bridge. Perioperative survival was 83%, with only the 4-year-old patient with ventricular septal defect/Eisenmenger's syndrome dying early. No airway complications were observed. The unilateral grafts received most of the blood flow as shown by perfusion scanning (range 74% to 99%). Living related donor complications included prolonged air leaks (> 6 days) in two patients. In urgent situations, such as an infant requiring extracorporeal membrane oxygenation, and in the existing milieu of donor shortage, lobar transplantation (living related or cadaveric) is a surgically feasible procedure and can provide a donor source in the limited time frame of these clinical situations. Bilateral lobe transplantation may be a viable option for patients with cystic fibrosis and life-threatening respiratory decompensation.

Adolescent↗
PubMed1993

Infectious complications in heart-lung transplantation. Analysis of 200 episodes.

BACKGROUND: Infection remains an important cause of morbidity and mortality in heart-lung transplant recipients. This study was designed to assess the frequency, type, and timing of infection in heart-lung transplant recipients. METHODS: A retrospective analysis of 200 episodes of serious infections occurring in 73 heart-lung recipients at Stanford (Calif) University Medical Center between 1981 and 1990. RESULTS: Bacterial infections accounted for half of all infections, with the highest incidence in the first month after transplantation. Fungal infections (14%) were also common in the first month. Cytomegalovirus was the most common viral agent (15%), occurring primarily in the second month after transplantation. Other viruses (herpes simplex, adenovirus, and respiratory syncytial virus) accounted for a further 15% of total infections. Pneumocystis carinii infections were common 4 to 6 months after transplantation, and Nocardia typically infected recipients later than 1 year after transplantation. There was no significant difference in incidence of infections between patients receiving triple (cyclosporine, prednisone, immuran) or double (cyclosporine and prednisone) immunosuppression therapy. Mortality due to infection accounted for 40% of all deaths. CONCLUSIONS: Knowledge of the incidence and timing of infection should help in the prevention, early detection, and initiation of therapy in these patients.

Cause of Death↗
PubMed1993

The use of granzyme A as a marker of heart transplant rejection in cyclosporine or anti-CD4 monoclonal antibody-treated rats.

Granzyme A is a serine protease expressed by populations of human and mouse natural killer cells and activated CD4+ and CD8+ cytotoxic lymphocytes; its expression marks a subset of inflammatory cells in allografts, autoimmune diabetes, and a number of other inflammatory lesions. In order to describe more completely the correlation between granzyme A expression and the presence of in vivo cytolytic effects, we grafted allogeneic rat hearts with vascular anastomoses in a heterotopic location, and treated the hosts with either cyclosporine, anti-CD4 monoclonal antibody (MRC OX38), or no therapy. The grafts were evaluated by palpation for cardiac functions, by immunohistochemistry for CD4/CD8 expression, by hematoxylin-and-eosin staining for inflammatory infiltration, and by in situ hybridization for granzyme A expression. The appearance of granzyme A+ cells in untreated allografts preceded both functional and standard histopathological and immunohistochemical evidence of graft rejection by two days. In donor-recipient combinations where cyclosporine and anti-CD4 treatments allowed indefinite allograft survival, the allografts showed minimal numbers of granzyme A+ cells, whether cellular infiltrates developed or not. The number of granzyme A+ cells present in the cardiac allografts in treated and untreated animals correlated with either current or impending episodes of rejection. The early time course of granzyme A expression suggests that it can be used as an early and reliable marker of graft rejection.

Animals↗
PubMed1993

Cellular mechanisms underlying differential rejection of sequential heart and lung allografts in rats.

As the simultaneous transplantation of two or more organs into a single recipient has become increasingly common, asynchronous allograft rejection has become an important clinical problem. To investigate the cellular and molecular mechanisms underlying differential organ rejection, we developed a rat model in which heart and lung allografts were transplanted sequentially. Heterotopic heart allografts transplanted into DA recipients from PVG donors survived indefinitely if the recipients were given a short course of rabbit antirat thymocyte globulin or cyclosporine at the time of transplantation. In contrast, orthotopic left lungs transplanted under the same conditions were rejected in ATG-treated recipients and accepted in most CsA-treated recipients. These animals were then given a second organ allograft from the same strain or a third party to assess whether they exhibited donor specific tolerance and whether the acceptance or rejection of the first allograft would influence the survival of the second transplant. Animals tolerized to a heart allograft with ATG rejected an orthotopic lung transplant from the same strain as the original allograft, whereas recipients treated with CsA at the time of their heart transplant accepted a subsequent lung graft. Surprisingly, animals treated with either ATG or CsA that had rejected a lung allograft accepted a subsequent heart transplant. Using limiting dilution analysis and adoptive transfer studies, we found that some recipients had developed suppressor cells while others demonstrated anergy. We conclude that major histocompatibility complex antigens as well as other antigens are involved in the differential rejection of heart and lung allografts.

Animals↗