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J V Conte

Publications and source records attributed to J V Conte.

30 records · Page 2Linked to original sources

Pediatric heart-lung transplantation: intermediate-term results.

BACKGROUND: Adult heart-lung transplantation was initiated at Stanford in 1981 and the first pediatric heart-lung transplantation was done in 1986. Intermediate-term results of pediatric heart-lung transplantation at Stanford University are presented. METHODS: A retrospective review of the records of all pediatric heart-lung transplantations done since 1986 was conducted. RESULTS: Nineteen heart-lung transplantations were done in 17 patients. Ages ranged from 2 months to 18 years with a median age of 10 years. At the time of transplantation 5 patients were infants, 7 children, and 7 adolescents. The mean follow-up was 29 +/- 6.2 months (range 1 to 77, median 16) and follow-up was 100% complete. Diagnoses were congenital heart disease in 13, primary pulmonary hypertension in 2, and cystic fibrosis, cystic lymphangiectasia, viral pneumonia, and obliterative bronchiolitis in 1 each. Median wait on the heart-lung transplantation list was 91 days (range 2 to 707). All patients had New York Heart Association class III to IV symptoms, two were receiving ventilator support, and six were receiving oxygen. Fifteen of 19 transplant recipients were discharged from the hospital. The 30-day operative mortality rate was 5.2% (1 of 19). The actuarial survival at 1, 3, and 5 years for all patients was 67%, 51%, and 41%, respectively, and for hospital survivors was 82%, 62%, and 51%. The cause of death was obliterative bronchiolitis in 4, multisystem organ failure in 3, and graft coronary artery disease and chronic airway disease in 1 each. Three patients required retransplantation, 2 because of obliterative bronchiolitis and 1 because of viral pneumonia. Two patients underwent repeat heart-lung transplantation and 1 patient underwent single lung transplantation. Rejection was diagnosed in 73% of recipients, and obliterative bronchiolitis has developed in 32% of recipients. CONCLUSIONS: Survival in pediatric heart-lung transplantation approximates that in the adult procedure at 1, 3, and 5 years. Long-term survival has been achieved but the primary factors limiting further improved survival remain infection and obliterative bronchiolitis.

Adolescent↗

Risk factors for the development of obliterative bronchiolitis after lung transplantation.

BACKGROUND: Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables. METHODS: Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome. RESULTS: Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation. CONCLUSIONS: Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.

Adolescent↗

Obliterative bronchiolitis after lung and heart-lung transplantation.

Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.

Bronchiolitis Obliterans↗

Early inhibition of myointimal proliferation by angiopeptin after balloon catheter injury in the rabbit.

PURPOSE: Coronary artery restenosis after percutaneous transluminal angioplasty occurs in more than 40% of patients. Angiopeptin, a stable synthetic octapeptide analogue of somatostatin, attenuates accelerated coronary artery myointimal thickening in rabbit cardiac allografts and myointimal thickening after arterial injury. In this study the temporal relationship between the angiopeptin treatment schedule and efficacy was explored. The relationship between inhibition of myointimal thickening by angiopeptin and inhibition of vascular cell proliferation was also examined. METHODS: The aorta and the common and external iliac arteries of the rabbit underwent balloon injury. Angiopeptin (2 to 200 micrograms/kg/day) was administered for 1 day before injury and for 1, 5, and 21 days after injury. Morphometric studies were performed to determine measurement of intimal thickening. Inhibition of vascular cell proliferation by angiopeptin was evaluated by tritiated thymidine incorporation into the balloon-injured rabbit aorta. Thymidine was either administered intraperitoneally or added ex vivo to aorta segments of rabbits treated with angiopeptin (2, 20, or 200 micrograms/kg/day) from 1 day before injury until sacrifice 72 hours later. RESULTS: Administration of angiopeptin (2 to 200 micrograms/kg/day) significantly reduced intimal thickening by approximately 50% in all three vessels when evaluated 3 weeks after injury. This inhibitory effect was unrelated to duration of treatment and dose. Treatment initiated at the time of injury was found to be effective, but delaying treatment for 8, 18, or 27 hours abrogated the inhibitory effect of angiopeptin on myointimal thickening. Angiopeptin treatment significantly decreased thymidine-labeled nuclei of smooth muscle cells in vitro. Angiopeptin treatment similarly inhibited thymidine uptake in vitro by balloon-injured aorta segments. CONCLUSION: Angiopeptin significantly inhibits myointimal thickening by inhibiting vascular cell proliferation. Administration of angiopeptin for 2 days is as efficacious as 3 weeks treatment in inhibiting myointimal thickening. Delaying treatment for as little as 8 hours after injury abrogates the inhibitory effects of angiopeptin. This speaks to the importance of early events immediately after vascular tissue injury, suggesting that angiopeptin inhibits the expression of early genes causally related to the vascular injury response and thereby triggering vascular cell proliferation.

Animals↗

Thoracic esophageal perforations at a Virginia hospital 1979-1990.

A study was made of all patients who underwent management for distal esophageal perforation at the Fairfax Hospital from September 1979 to September 1990. The study group consisted of 13 patients. Nine were male, four female. Mean age was 60.8 yrs, ranging from 36 to 83 yrs. In the group of nine patients diagnosed early (less than 24 hrs), hospital mortality was 22.2% versus 75% in the group of four diagnosed late (greater than 24 hrs). Of the six patients treated conservatively, either medically or surgically, only one survived, but all seven patients diagnosed early and aggressively operated upon survived. Thus the authors agree with others in espousing aggressive, definitive surgery for patients diagnosed early.

Adult↗

Long-term lung preservation with the PAF antagonist BN 52021.

Platelet activating factor (PAF, 1-alkyl-2(R)-acetyl-glycero-3- phosphorylcholine) is a phospholipid that is released by a variety of cells. The similarity between the pathophysiological effects of PAF and posttransplant pulmonary dysfunction led to an evaluation of a PAF antagonist as an adjunct to lung preservation. The ginkgolide B, BN 52021, was selected as the PAF antagonist to be studied because of the large data base available on this compound. BN 52021 was given to the donor and recipient (10 mg/kg i.v.) prior to harvest and transplantation and was included in 1 L of preservation solution (10 mg/kg) used for flushing the pulmonary artery and for storage. Left single-lung transplantation was performed following a 22-hr preservation period at 10 degrees C. Arterial oxygen tension (pO2), pulmonary vascular resistance (PVR), alveolar arterial oxygen difference (A-aDO2), and dynamic lung compliance (DLC) were recorded for 6 hours following ligation of the native pulmonary artery. At the end of 6 hr pO2 was 243.5 +/- 61.5 vs. 71.7 +/- 10.2 mmHg (P less than 0.02) for the controls. A-aDO2 was less in the BN 52021 groups: 431.8 +/- 58.3 vs. 606.0 +/- 9.8 mmHg in the control groups (P less than 0.001), and PVR was significantly less in the BN 52021 group: 346 +/- 70.8 vs. 663 +/- 64.3 dynes/sec/cm-5 (P less than 0.035). We conclude that PAF antagonists like BN 52021 may be useful adjuncts for lung preservation. The effects of BN 52021 are easily explained by PAF antagonist activity in ischemic and reperfusion-induced pulmonary dysfunction. However this study does not exclude that BN 52021 may have direct effects.

Animals↗

Peptide inhibition of neointimal hyperplasia in vein grafts.

Angiopeptin, a novel synthetic octapeptide, was evaluated as a new approach toward the inhibition of neointimal hyperplasia in vein grafts. Male New Zealand white rabbits (n = 22) underwent carotid artery interposition bypass grafting with autologous reversed jugular vein. Nine rabbits were in the treatment group, and 13 were in the control group. The treatment group received angiopeptin 20 micrograms/kg/day by subcutaneous injection beginning 1 day before operation and continuing for 3 weeks until they were killed. At death the vein grafts were fixed in situ with 10% buffered formalyn at 80 mm Hg perfusion pressure. Histologic sections through each vein graft were analyzed by computerized morphometric analysis for area of neointimal hyperplasia (mm2). Neointimal hyperplasia in the control animals was 0.080 + 0.017 mm2 (mean + SEM), whereas neointimal hyperplasia in the group treated with angiopeptin was 0.022 + 0.006 mm2 (mean + SEM) (p = 0.02). This is the first time that peptide inhibition of neointimal hyperplasia has been demonstrated in vein grafts and may have significant implications for future use in vascular surgery.

Animals↗

Iron chelation therapy and lung transplantation. Effects of deferoxamine on lung preservation in canine single lung transplantation.

Reperfusion injury is a limiting factor in lung transplantation. Deferoxamine is an iron chelator that inhibits the formation of oxygen-derived free radicals. We investigated the effects of deferoxamine on posttransplantation lung function in a canine model of single lung transplantation. Twelve dogs underwent left lung transplantation after 20- to 24-hour hypothermic storage in a modified Euro-Collins solution. In six experiments donor and recipient received a 10 mg/kg dose of deferoxamine before harvest and transplantation, and 10 mg/kg was added to the preservation solution. Arterial oxygen tension, alveolar-arterial oxygen difference, pulmonary vascular resistance, and dynamic lung compliance were measured. Data were recorded for 6 hours after ligation of the native pulmonary artery. At the end of the study the mean arterial oxygen tension was 175.1 mm Hg for the deferoxamine treated group versus 71.1 mm Hg for the control group (p less than 0.001), and the alveolar-arterial oxygen difference was less in the deferoxamine-treated group: 502.3 versus 606.0 mm Hg (p less than 0.001). The mean pulmonary vascular resistance was lower throughout the study, and after 6 hours it was 455.1 dynes/sec/cm(-5) in the deferoxamine-treated group versus 663.7 dynes/sec/cm(-5) in the control group (p less than 0.035). Compliance was similar in both groups. We conclude that deferoxamine improves lung preservation and early posttransplantation function in canine single lung transplantation.

Animals↗

Treatment of bleeding stomal varices. Report of a case and review of the literature.

Variceal bleeding from ileostomy, colostomy, or ileal conduit stomas is unusual. There is no consensus on which of the various treatment options is best. A case of bleeding ileostomy varices is presented. The English-language medical literature since 1962 is reviewed and an additional 71 cases of stomal variceal bleeding are identified. Treatment options evaluated include stomal manipulation, variceal ligation, sclerotherapy, beta blockade, and surgical shunting. The incidence of rebleeding, requirement for additional procedures, and survival with the various options are compared. Although stomal manipulation was the most commonly performed procedure, portosystemic shunting had the lowest incidence of both rebleeding and need for additional procedures (4 percent each) and provided the longest mean postoperative survival (50 months). The authors conclude that portosystemic shunting is the treatment of choice in patients with bleeding from stomal varices who are good surgical candidates.

Adult↗

Overview and future practice patterns in cardiac and pulmonary preservation.

Heart and lung transplantation have become standard therapy for many patients with end-stage heart and lung disease. Successful transplantation requires preservation of allografts until they can be implanted and reperfused. In the decades since the transplantation of thoracic organs became a clinical reality, many advances have been made in preoperative donor management, procurement, and preservation techniques. This article summarizes the state of the art in heart and lung preservation and review some of the areas of current research that may lead to improvements in preservation techniques in the future.

Forecasting↗