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Biomedical subjects

V A Starnes

Publications and source records attributed to V A Starnes.

At least 91 records · Page 5Linked to original sources
PubMed1993

Cytokine gene expression in human lung transplant recipients.

The polymerase chain reaction was used to evaluate cytokine gene expression in bronchoalveolar lavage (BAL) cells and peripheral blood leukocytes in 31 human lung transplant recipients. All patients were maintained on a triple immunosuppression regimen consisting of CsA, AZA, and prednisone. Posttransplant survival ranged from 0.5 to 100.5 months (mean = 16.3 months). Cytokines IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, TNF-beta, and IFN-gamma were studied. In BAL, transcripts for IL-1 alpha, IL-7, IL-8, and TNF-beta were found in over 60% of samples and those for IL-5, IL-6, and IFN-gamma in 40-50%, while IL-2 and IL-4 mRNA were rarely found (< 20%). Considerable variation in the frequency of cytokine gene expression between BAL and peripheral blood was observed. When analyzed for the presence of acute pulmonary allograft rejection (without infection), transcripts for IL-4 and IL-6 in BAL demonstrated the greatest increase in frequency compared with nil rejection (P = 0.07 and P = 0.17, respectively). Pulmonary infection (without rejection) was associated with a modest increase in the expression of genes for IL-1 alpha and IFN-gamma (> 10%). Transcripts for IL-4 were not found in association with pulmonary infection, suggesting that this cytokine may be useful as a discriminatory rejection marker.

Adolescent↗
PubMed1993

Pediatric lung transplantation.

As the first decade of successful clinical lung transplantation draws to a close, the number of patients who are able to benefit from it continues to increase. Pulmonary transplantation in the pediatric age group is possible for an expanding range of diagnoses currently known to cause end-stage lung disease. However, more experience will be required before the answers to a number of clinical problems are found. The following issues are particularly pertinent to the pediatric age group: (1) Controversy still exists as to the most appropriate operation for certain clinical situations (eg, single- or double-lung transplants for primary pulmonary hypertension, or secondary pulmonary hypertension after cardiac repair). These decisions are made based on physiological considerations as well as donor availability and the need to use the donor pool as efficiently as possible. (2) Technical controversies in pediatric lung transplantation include the optimal technique for performing the bronchial anastomosis in a manner that will permit healing without stenosis of the airway. Cardiopulmonary bypass is required for most lung transplants in children. (3) OB continues to plague the long-term results of lung transplantation and may be more common in the pediatric age group. OB may respond to increased immunosuppression. (4) Lobar transplantation in children may be an effective method of increasing the availability of donors. More experience will be necessary to further refine this technique.

Adolescent↗
PubMed1993

Neoplastic disorders after pediatric heart transplantation.

BACKGROUND: Because of their life-long requirement for immunosuppressive therapy, neoplastic disorders could represent a significant threat to long-term survival in infants and children after heart transplantation. This study determined the incidence and clinical spectrum of neoplastic disorders in 80 pediatric patients who underwent heart transplantation between 1974 and 1992. METHODS AND RESULTS: Follow-up ranged from 6 to 189 months (mean, 50.0 months). Tumors occurred in 10 patients (12.5%). Time to detection ranged from 3.3 to 139.2 months (mean, 52.7 months). Tumor incidence was greatest in 9 patients transplanted before the cyclosporine era (44%) compared with the subsequent 71 patients (8.5%, P < .05). There was no increase in risk related to sex, age, underlying disease, or blood type; however, patients with tumors received higher initial doses of cyclosporine and prednisone and had more rejection episodes in the first 3 months (P < .05). There was an increased risk associated with anti-thymocyte globulin (33%, P < .05) but not with OKT3 (6%, P = NS). There were eight lymphoproliferative disorders (four B-cell, one T-cell, three not determined) and one hepatocellular and one squamous cell carcinomas. Six cases of lymphoproliferative disorder had in situ evidence of Epstein-Barr virus. Patients were treated by reducing immunosuppression (7), radiotherapy (2), and chemotherapy (1). There were five deaths: two tumor related and the others due to rejection, renal failure, and infection. Of 5 survivors, 1 had tumor recurrence 4 years after diagnosis, and 4 are disease free. CONCLUSIONS: Tumors represent a small but serious long-term risk to pediatric heart transplant recipients. The incidence in children transplanted in the cyclosporine era is similar to that in adults, and the majority of tumors are lymphoproliferative disorders that often regress by reducing immunosuppression.

Actuarial Analysis↗
PubMed1992

Cardiac function after domino-donor heart transplantation.

A major limitation in cardiac transplantation is donor availability. A possible way to increase the supply of donor hearts is to use explanted hearts from patients undergoing heart-lung transplantation for primary lung disease. One potential advantage of this approach, termed domino-donor transplantation, is the existence of a donor right ventricle already adapted to pulmonary hypertension, which would therefore theoretically decrease the likelihood of acute donor right heart failure in recipients with preexisting elevation of pulmonary vascular resistance. Potential disadvantages include graft failure secondary to chronic effects of pulmonary hypertension on the right ventricle, arrhythmia and infections. Seven domino-donor transplants were performed at Stanford University Hospital; graft and patient survival to date are 100% at a mean follow-up of 20 months (range 1 to 26). Infection and rejection rates have been comparable to those of the current Stanford experience for conventional orthotopic transplantation. Right ventricular function and size have either improved or remained unchanged in all patients after transplantation. Transient early postoperative donor right ventricular dilation, a characteristic adaptive response seen in nondomino transplants, occurred in 4 patients with pulmonary hypertension before surgery. These data indicate that, with adequate assessment before surgery, domino-donor cardiac transplantation is an appropriate means of augmenting the donor pool.

Actuarial Analysis↗
PubMed1992

Heart, heart-lung, and lung transplantation in the first year of life.

Seventeen infants less than 1 year of age have undergone heart (12), heart-lung (3), and lung (2) transplantation for end-stage cardiopulmonary disease. The infants undergoing heart transplantation had a mean age of 4.5 months (range, 19 days to 12 months) with the diagnosis of cardiomyopathy in 4 and congenital heart disease in 8. Four of the 8 patients (50%) had hypoplastic left heart syndrome. Actuarial survival at 1 and 2 years was 74% and compared favorably with the survival of older children at 1 and 2 years of 82% and 69%. The linearized rejection rate was less in infants as compared with children more than 1 year of age (0.61 versus 1.48 episodes per 100 patient days). In intermediate follow-up, no graft atherosclerosis has been noted. Immunosuppression has included a three-drug protocol of cyclosporine, azathioprine, and prednisone. A steroid taper to alternate day steroids or off completely by 6 months has been the goal and has been accomplished in 6 of 12 infants. Heart-lung and lung transplantation has been performed in 5 infants. One infant in each group died: 1 infant secondary to airway complications and sepsis and another due to pulmonary sepsis. A pulmonary lobe from a larger and older donor was transplanted into a 4-week-old infant as a single-lung transplant with good outcome. The 3 surviving infants are well 24, 18, and 2 months after transplantation. Obliterative bronchiolitis has not been clinically apparent in this group. These data support the clinical efficacy of heart, heart-lung, and lung transplantation in the first year of life.

Actuarial Analysis↗
PubMed1992

Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii infections in heart-lung and lung transplantation--how effective and for how long?

Pneumocystis carinii pneumonia (PCP) is a common clinical problem in the setting of organ transplantation, particularly in heart-lung and lung allograft recipients. Without prophylactic measurements, the incidence of P carinii pneumonia can reach up to 88% of heart-lung transplant recipients. We conducted a retrospective analysis of the Stanford heart-lung and lung transplant experience in order to assess the efficacy of the prophylactic therapy and to try to define the duration of therapy necessary for prevention. During a 9-year period 82 heart-lung and 13 single-lung transplants were performed. Of the patients not on prophylaxis therapy 27% (13 patients) developed P carinii infection as compared with 0% of patients on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. The incidence of PCP infection peaked between 3 and 6 months posttransplantation. No case of infection was observed before the 7th week posttransplant. PCP was more common following induction immunosuppression with OKT3 as compared with RATG (P less than 0.05). All cases of infections later than one year posttransplant were associated with recent increase in the immunosuppression regimen with high-dose corticosteroids for treatment of acute or chronic (obliterative bronchiolitis) rejection. Although our study is retrospective and based on various immunosuppressive and diagnostic technique periods, it seems that TMP-SMX is highly effective in preventing PCP infections in heart-lung and lung transplant recipients. Twelve months of therapy is probably a sufficient length of therapy if immunosuppressive therapy is stable. However, whenever augmentation in the immunosuppression regimen is indicated, prophylactic therapy should promptly be restarted.

Adrenal Cortex Hormones↗
PubMed1992

Cytokine gene expression in rejecting cardiac allografts.

Heart transplantation is now a viable therapeutic option for patients with certain end-stage cardiac diseases. However, episodes of rejection, opportunistic infection, and life-threatening side effects of generalized immunosuppression remain very real problems for these patients. A better understanding of the molecular mechanisms underlying rejection may provide the basis for the development of more specific, less toxic immunosuppressive therapies. While cytokines have long been implicated in the pathogenesis of rejection, the precise role of each cytokine in this process has yet to be defined. We report here the application of the polymerase chain reaction (PCR) to the detection of cytokine mRNA in biopsies obtained from heterotopic abdominal cardiac allografts in cynomolgus monkeys. With the exception of IL-6 and IL-8, cytokine transcripts were undetectable in samples obtained from the donor heart pretransplant. In contrast, IFN-gamma transcripts were detected in all transplants two days after surgery before evidence of rejection was demonstrable by histopathologic analysis. IL-1 beta, IL-2, and IL-6 transcripts were detected when minimal rejection was noted. At later times, IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF-beta, and IFN-gamma transcripts were detectable. Further characterization of the spectrum of cytokines expressed at various stages of rejection may lead to insights into the biology of transplant rejection and to the development of more specific and potent reagents to diagnose and/or treat rejection.

Animals↗
PubMed1992

Communication between the two pleural cavities after major cardiothoracic surgery: relevance to percutaneous intervention.

The authors describe evidence of communication between the two pleural cavities after major cardiothoracic surgery (combined heart and lung transplantation, heart transplantation, and correction of complex congenital heart disease) performed in three patients. In two patients, unilateral lung biopsy caused a symptomatic bilateral pneumothorax. This was successfully treated with insertion of a single chest tube in one patient and two chest tubes in the other patient. In the third patient, simultaneous evacuation of large bilateral pleural effusions was performed by means of unilateral thoracentesis because of the presence of a common pleural cavity.

Biopsy, Needle↗
PubMed1992

Current approach to hypoplastic left heart syndrome. Palliation, transplantation, or both?

Over the past 3 years, 35 newborn infants have been referred for surgical management of hypoplastic left heart syndrome. Surgical palliation (first-stage Norwood) or cardiac transplantation was offered. Twenty-four families (68%) chose palliation and 11 families (32%) chose cardiac transplantation. Of the 11 infants listed for cardiac transplantation, five underwent transplantation. Because of a lack of donors after an average wait of 25 days (19 to 31), the remaining six infants underwent palliation, with no perioperative deaths. Of the 30 infants undergoing palliation, including crossovers, 20 (67%) survived the first operative stage. Among the last 19 infants undergoing palliation in 1990, the early survival was 84%. Risk factors determined for poor outcome were year of operation (p less than 0.001) and circulatory arrest time greater than 50 minutes (p less than 0.001). Among the 13 infants undergoing palliation with a circulatory arrest time of less than 50 minutes, there were 12 survivors (92%); among 12 having a circulatory arrest time of more than 50 minutes, there were four survivors (33%). At intermediate follow-up, six infants have undergone second-stage procedures (Glenn), with five survivors. There were eight late deaths, four caused by respiratory infections and four caused by cardiac problems, including a thrombosed shunt in one infant. Three of five infants are alive and doing well after cardiac transplantation. Size of aorta, tricuspid regurgitation, and ventricular wall thickness did not prove to be risk factors. Given the existing data, we believe these infants should be managed selectively on the basis of donor availability and family wishes.

Actuarial Analysis↗
PubMed1992

Current trends in lung transplantation. Lobar transplantation and expanded use of single lungs.

Heart-lung transplantation remains the only therapeutic option for patients with combined end-stage cardiopulmonary disease. Because of the scarcity of heart-lung donors, we have been investigating other surgical alternatives for patients with end-stage vascular and parenchymal lung disease. From June 1989 through June 1991, 48 patients underwent pulmonary transplantation. Seventeen of the 48 patients underwent single lung transplantation. Of the 17 patients in the single lung group, eight patients had pulmonary hypertension and nine had parenchymal lung disease. Four of the 17 patients underwent repair of a cardiac defect with single lung transplantation. One-year actuarial survival was 68%. Pulmonary function has been excellent. The forced expiratory volume in 1 second was 79.6 +/- 13.6 (percent predicted), forced expiratory flow 25%-75% was 72.6 +/- 14.5 (percent predicted), and arterial oxygen tension was 82.8 +/- 10.06 mm Hg when measured at annual follow-up in a group of eight patients without obliterative bronchiolitis. Pulmonary artery pressures of systemic level or greater in the group with pulmonary vascular disease were normal at annual catheterization. Most patients had at least one episode of allograft rejection. Actuarial freedom from rejection at the end of 3 months was 30%. Three of the 17 single lung patients receiving lung lobes were children. Two children received living-related lobe transplants and one neonate received a lobe from a 2-year-old cadaver donor. Single lung transplantation is an effective therapeutic option for selected patients with vascular or parenchymal lung disease. Expanding indications will permit more individuals to receive transplants from the existing donor pool. Living-related and cadaver lobe transplantation will also increase the options available to children in need of lung transplantation.

Adolescent↗
PubMed1992

Cystic fibrosis. Target population for lung transplantation in North America in the 1990s.

Cystic fibrosis is the most common lethal genetic disease occurring in the white population. It is estimated that 3.5% of the 20,000 individuals with cystic fibrosis in North America will die each year of end-stage lung disease. Lung transplantation (heart-lung or double lung) is becoming more frequent as more patients are referred for this procedure. Since January 1988, we have evaluated 60 patients with cystic fibrosis for lung transplantation and have accepted 30 (50%). Nine patients (30%) died while awaiting a donor. Fifteen patients underwent transplantation (13 heart-lung and two double lung procedures). Actuarial survival at 1, 2, and 3 years is 76%. All survivors are without physical limitations. Pulmonary function, as determined by forced vital capacity, forced expiratory volume in 1 second, and arterial blood gas determinations, is within the normal range. Comparing these data with those of a group of patients without cystic fibrosis who underwent transplantation during the same period did not reveal any significant differences with respect to infection, rejection, and outcome. Preliminary data suggest that obliterative bronchiolitis is less prevalent at 1 year in patients with cystic fibrosis (19%) than in those without cystic fibrosis (41%). Patients with cystic fibrosis present a number of challenges. The problems of pleural adhesions from repeated infections, pleurodesis, and previous thoracic procedures are now readily approached through the bilateral thoracosternotomy (clam shell) incision. Insulin-dependent diabetes mellitus and low-dose corticosteroid therapy are no longer considered absolute contraindications. Both septic lungs must be removed at operation, either with heart-lung transplantation or with double lung transplantation. These data support the therapeutic efficacy of lung transplantation for patients with cystic fibrosis.

Actuarial Analysis↗
PubMed1992

Durability of porcine valves at fifteen years in a representative North American patient population.

Isolated aortic (n = 857) or mitral (n = 793) valve replacement with a porcine bioprosthesis was performed in 1650 patients between 1971 and 1980. Follow-up (total = 12,012 patient-years) extended to more than 15 years and was 96% complete. Patient age ranged from 16 to 87 years; mean age was 59 +/- 11 years (+/- 1 standard deviation) for the aortic valve replacement cohort and 56 +/- 12 years for the mitral valve replacement cohort. The operative mortality rates were 5% +/- 1% (+/- 70% confidence limits) and 8% +/- 1%, respectively, for the aortic and mitral subgroups. Estimated freedom from structural valve deterioration (+/- 1 standard error of the mean) after 10 and 15 years was significantly higher for the aortic than for the mitral valve replacement subgroup (85% +/- 0.4% and 63% +/- 3% versus 78% +/- 2% and 45% +/- 3%, respectively, p = 0.001). Reoperation-free actuarial estimates were also significantly greater for the aortic valve replacement cohort: 83% +/- 2% and 57% +/- 3% versus 78% +/- 2% and 43% +/- 3% for mitral valve replacement at 10 and 15 years, respectively. The mortality rate for reoperative aortic valve replacement was 11% +/- 1%; it was 8% +/- 1% for reoperative mitral valve replacement. Importantly, the estimates of freedom from valve-related death (including sudden, unexplained deaths) were relatively high at 10 and 15 years: 78% +/- 2% and 69% +/- 3% in the aortic cohort and 74% +/- 2% and 63% +/- 3% in the mitral cohort (p = not significant). Excluding sudden, unexplained deaths, these estimates were 81% +/- 3% (aortic) and 73% +/- 4% (mitral) at 15 years. Thromboembolism-free rates were 84% +/- 3% (aortic) and 78% +/- 6% (mitral) at 15 years, and freedom from anticoagulant-related hemorrhage was 96% +/- 1% and 89% +/- 2%, respectively. At the time of current follow-up, 13% of patients having aortic valve replacement and 50% of patients having mitral valve replacement were receiving warfarin sodium. The hazard functions for thromboembolism and prosthetic valve endocarditis were constant and remained less than 1%/pt-yr over the entire follow-up period.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1991

Heart-lung transplantation in infants, children, and adolescents.

We have performed heart-lung transplantation in 10 children for the preoperative diagnoses of primary pulmonary hypertension (4), complex congenital heart disease with pulmonary hypertension (4), pulmonary atresia (1), and cystic fibrosis (1). Ages ranged from 4 months to 18 years. There were 15 episodes of pulmonary rejection, with an occurrence rate of 1.67 episodes per patient. Pulmonary infections occurred frequently, with an occurrence rate of 3.3 episodes per patient. The actuarial survival rate at 1 and 2 years was 78% and 47%, respectively. Patient attrition between 1 and 2 years was attributable to the complications of obliterative bronchiolitis, which has effected 71% (5/7) of the long-term survivors. Four of the 5 surviving children have minimal physical limitation and are in functional class I. These data support continued investigation into heart-lung transplantation in children and set the stage for further program development into single-lung transplantation in children.

Adolescent↗