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Vaughn A Starnes

Publications and source records attributed to Vaughn A Starnes.

At least 19 recordsLinked to original sources
PubMed2006

Current surgical therapy for Ebstein anomaly in neonates.

OBJECTIVE: Neonates with profound heart failure resulting from Ebstein anomaly have historically had poor outcomes. We report our institutional experience with the surgical management of Ebstein anomaly in severely symptomatic neonates. METHODS: A retrospective review of all patients (n = 16) undergoing neonatal intervention for Ebstein anomaly between 1992 and 2005 has been carried out. The indications for operation were overt heart failure, cyanosis, and acidosis associated with tricuspid regurgitation, depressed right ventricular function, and severe cardiomegaly. The magnitude of cardiac enlargement was assessed by cardiothoracic ratio and Great Ormond Street ratio (area of right atrium + atrialized right ventricle/area of functional left atrium + left ventricle). The operative strategy was first to assess for the possibility of tricuspid valve repair with or without right ventricular outflow tract reconstruction. If this was not feasible, then right ventricular exclusion was performed by oversewing the tricuspid valve with a pericardial patch. A reduction atrioplasty was done and, depending on the extent of the atrialized portion of the right ventricle, plication was performed. A modified Blalock-Taussig shunt provided pulmonary blood flow. This univentricular approach (Starnes procedure) evolved to include a fenestration in the tricuspid valve patch to allow for right ventricular decompression. Analysis included overall and group-specific survival as well as the testing of perioperative clinical, morphologic, and surgical variables for correlation with mortality and morbidity. RESULTS: Mean age and weight at operation were 8 +/-10 days and 3.1 +/- 0.4 kg. Tricuspid valve repair was undertaken in 3 patients with 1 requiring conversion to right ventricular exclusion 3 months after the initial operation. In those with right ventricular exclusion, the tricuspid valve patch was fenestrated in 10 and nonfenestrated in 3. One patient had heart transplant as the initial procedure. There were 5 hospital deaths (31%) and no late deaths among the survivors. Survival in the cohort with a fenestrated tricuspid valve patch was 80% (8/10) versus 33% (1/3) for the nonfenestrated group. This difference did not reach statistical significance, although the trend seems clinically important. There was no difference in the cardiothoracic ratio (0.82 fenestrated vs 0.84 nonfenestrated: P = .802) or the Great Ormond Street ratio (1.2 fenestrated vs 1.02 nonfenestrated: P = .477) between the two groups. Among the 9 survivors of right ventricular exclusion, 3 have had completion of their Fontan, and all 9 have undergone a bidirectional Glenn procedure. All operations including homograft placement in the right ventricular outflow tract, whether during repair or during right ventricular exclusion, ended in death. CONCLUSION: Right ventricular exclusion with a fenestrated tricuspid valve patch combined with right atrioplasty and right ventriculoplasty and a Blalock-Taussig shunt (Starnes procedure) has provided effective palliation for neonates presenting with critical Ebstein anomaly and a tricuspid valve that cannot be repaired.

Cardiac Surgical Procedures↗
PubMed2006

Perioperative cyclooxygenase 2 inhibition to reduce tumor cell adhesion and metastatic potential of circulating tumor cells in non-small cell lung cancer.

OBJECTIVE: Surgical manipulation of lung cancers may increase circulating tumor cells and contribute to metastatic recurrence after resection. Cyclooxygenase 2 is overexpressed in most non-small cell lung cancer and upregulates the cell adhesion receptor CD44. Our goal was to examine the effects of perioperative cyclooxygenase blockade on the metastatic potential of circulating tumor cells, CD44 expression, and adhesion of cancer cells to extracellular matrix. METHODS: Human non-small cell lung cancer cells (A549) were injected through the lateral tail vein in an in vivo murine model of tumor metastasis with three random treatment groups: no treatment, perioperative selective cyclooxygenase 2 inhibition (celecoxib) only, and continuous celecoxib. Lung metastases were assessed at 6 weeks by a blinded observer. For in vitro experiments, cells were treated with celecoxib, and expression of CD44 was determined by Western blotting. Extracellular matrix adhesion was assessed by Matrigel (BD Labware, Bedford, Mass) assay. RESULTS: In vivo lung metastases were significantly decreased relative to control by both perioperative and continuous celecoxib (P = .0135). There was no significant difference in number of metastases between continuous and perioperative treatment groups. In vitro adhesion to the extracellular matrix was significantly inhibited by celecoxib in a dose-dependent manner (P < .01). A549 cells expressed high levels of CD44, upregulated by interleukin 1beta and downregulated by celecoxib. CONCLUSION: Celecoxib significantly reduced establishment of metastases by circulating tumor cells in a murine model. It also inhibited CD44 expression and extracellular matrix adhesion in vitro. Perioperative modulation of cyclooxygenase 2 may be a novel strategy to minimize metastases from circulating tumor cells during this high-risk period.

Adenocarcinoma↗
PubMed2006

Gastrointestinal morbidity after Norwood palliation for hypoplastic left heart syndrome.

BACKGROUND: Neonates with hypoplastic left heart syndrome are at high risk for developing gastrointestinal complications after first stage palliation. These complications likely play a major role in their morbidity and mortality. The goal of this review was to examine the incidence and clinical impact of gastrointestinal morbidities in these newborns. METHODS: The charts of all neonates with hypoplastic left heart syndrome who underwent stage-one palliation between January 1997 and December 2001 were reviewed to determine the incidence of gastrointestinal complications. Demographic, perioperative, and procedural variables were collected and correlated with major gastrointestinal problems. RESULTS: There were 117 patients in our study population, and survival to discharge was 87% (102 of 117). Gastrointestinal complications occurred in 48 (41%), including 18% with necrotizing enterocolitis, 18% who required home feeding tubes, and 8% who required prolonged hospital length of stay for nutritional support. These infants had a longer length of stay (52 days versus 22 days; p < 0.0001). Multivariate logistic regression analysis revealed that weight less than 2.5 kg and development of necrotizing enterocolitis were each independently related to death. Neonates with a birth weight less than 2.5 kg had an odds ratio for death of 5.7 (95% confidence interval: 1.14 to 28.86), and the odds ratio for death with necrotizing enterocolitis was 5.6 (95% confidence interval: 1.55 to 20.67). CONCLUSIONS: Gastrointestinal complications in infants with hypoplastic left heart syndrome are common, and necrotizing enterocolitis increases the risk of death. Measures directed at reducing the incidence of gastrointestinal complications may improve outcomes and reduce costs in this population.

Aorta, Thoracic↗
PubMed2006

Mesenteric blood flow velocities in the newborn with single-ventricle physiology: modified Blalock-Taussig shunt versus right ventricle-pulmonary artery conduit.

BACKGROUND: Neonates with ductal-dependent single-ventricle congenital heart disease palliated with a modified Blalock-Taussig shunt (mBTS) commonly have retrograde diastolic flow in the aorta, which may place them at increased risk of mesenteric ischemia. Recently, palliation with a right ventricle-to-pulmonary artery conduit, known as the Sano procedure, has been shown to eliminate retrograde diastolic flow, theoretically leading to better systemic perfusion. OBJECTIVE: To compare the changes in superior mesenteric artery (SMA) and celiac artery velocities and flow after a bolus enteral feed in patients with single-ventricle congenital heart disease palliated with an mBTS vs. those palliated with the right ventricle-to-pulmonary artery conduit. DESIGN: Prospective clinical study. SETTING: Cardiothoracic intensive care unit and pediatric ward of a tertiary care children's hospital. PATIENTS: A total of 27 patients with single-ventricle congenital heart disease (15 with mBTS, 12 with Sano) after stage-1 palliation. INTERVENTION: Doppler ultrasound of the SMA and celiac artery was performed 30 mins before and after a bolus enteral feed. MEASUREMENTS AND MAIN RESULTS: SMA and celiac artery peak systolic flow velocity, mean flow velocity, and time-velocity integral were measured. After a bolus enteral feed, 8 of 15 infants palliated with an mBTS had retrograde diastolic flow through the SMA yet demonstrated significant increases in all variables of both the SMA and celiac artery flow velocities (SMA peak systolic flow velocity: 0.96 +/- 0.33 vs. 1.2 +/- 0.4 m/sec, p = .01). Those palliated with the Sano procedure did not demonstrate SMA retrograde diastolic flow but also did not have any significant changes in their mesenteric flow variables (SMA peak systolic flow velocity: 0.79 +/- 0.16 vs. 0.89 +/- 0.26 m/sec, p = .2). CONCLUSION: Postprandial retrograde diastolic flow was observed in the majority of patients palliated with an mBTS vs. none of the patients in the Sano group. However, contrary to expectations, postprandial mesenteric blood flow velocities in those palliated with an mBTS are significantly higher than in Sano patients, although the increase is not as high as that historically seen in normal neonates. This may place this population at risk for mesenteric ischemia and feeding intolerance in the postoperative period, and the risk may be even greater for those neonates palliated with a right ventricle-to-pulmonary artery conduit.

Anastomosis, Surgical↗
PubMed2005

Tolerance induction by lentiviral gene therapy with a nonmyeloablative regimen.

Antibodies (Abs) directed at the Gal alpha1,3Gal beta1,4GlcNAc-R (alphaGal) carbohydrate epitope initiate xenograft rejection. Previously, we have shown that bone marrow transplantation (BMT) with lentivirus-mediated gene transfer of porcine alpha1,3 galactosyltransferase (GalT) is able to induce tolerance to alphaGal-expressing heart grafts following a lethal dose of irradiation. Here we show the first demonstration of permanent survival of alphaGal+ hearts following transplantation with autologous, lentivirus-transduced BM using a nonmyeloablative regimen. Autologous BM from GalT knockout (GalT-/-) mice was transduced with a lentiviral vector expressing porcine GalT and transplanted into sublethally irradiated (3 Gy) GalT-/- mice. Chimerism in the peripheral blood cells (PBCs) remained low but was higher in the BM, especially within the stromal cell population. Mice reconstituted with GalT did not produce anti-alphaGal Abs over time. We immunized these mice with alphaGal-expressing cells and assessed humoral immune responses. Anti-alphaGal xenoantibodies were not produced in mice reconstituted with GalT, but normal Ab responses to other xenoantigens were detected. Mice reconstituted with GalT accepted alphaGal+ heart grafts over 100 days. Transduction with lentiviral vectors results in chimerism at levels sufficient to induce long-term tolerance under nonmyeloablative conditions.

Animals↗
PubMed2005

Transforming growth factor-beta/interleukin-2-induced regulatory CD4+ T cells prolong cardiac allograft survival in rats.

BACKGROUND: Treatment of naive CD4+ T cells in vitro with transforming growth factor-beta (TGF-beta) or TGF-beta/interleukin-2 (IL-2), combined with stimulation in a mixed lymphoid culture (MLC), has been shown to generate CD4+ CD25+ regulatory T cells. However, little is known about the effect of these regulatory T cells on cardiac allograft survival in vivo. METHODS: CD4+ CD25+ T cells were generated from Lewis (LEW) rat spleen through a primary MLC with TGF-beta (10 ng/ml) or TGF-beta/IL-2 (10 U/ml). The effect of adoptive transfer of the CD4+ CD25+ T cells (5.0 x 10(7)) was evaluated using an animal model of ACI rat cardiac allograft survival in LEW recipients. RESULTS: The MLC with TGF-beta or TGF-beta/IL-2 generated CD4+ CD25+ regulatory T cells, which suppressed the cytotoxic activity of LEW spleen T cells against irradiated ACI spleen cells in vitro. Adoptive transfer of the CD4+ CD25+ regulatory T cells intravenously to naive syngeneic recipients significantly prolonged the ACI cardiac allograft survival (N = 6, 13.5 +/- 3.4 days) compared with the control group (N = 6, 5.0 +/- 0.6 days). CONCLUSIONS: Intravenous administration of CD4+ CD25+ regulatory T cells, successfully generated by TGF-beta/IL-2 treatment, had a significant effect on cardiac allograft survival in this rat model. Adoptive transfer of regulatory T cells may represent a novel approach for preventing allograft rejection.

Animals↗
PubMed2005

Dimethyl celecoxib as a novel non-cyclooxygenase 2 therapy in the treatment of non-small cell lung cancer.

OBJECTIVES: The cyclooxygenase 2 enzyme has become a therapeutic target in cancer treatment. Cyclooxygenase 2 blockade with selective inhibitors increases apoptosis and decreases the metastatic potential of lung cancer cells. Some of the antitumor effects of these inhibitors may occur through both cyclooxygenase 2-dependent and independent pathways. Our goal was to investigate these pathways using celecoxib (selective cyclooxygenase 2 inhibitor) and 2,5-dimethyl celecoxib, a structural analog modified to eliminate cyclooxygenase 2 inhibitory activity, while potentially maintaining antineoplastic properties. METHODS: 2,5-dimethyl celecoxib was synthesized in the Department of Chemistry at the University of Southern California. With the use of non-small cell lung cancer cells (A549), prostaglandin E2 production was quantified by enzyme-linked immunosorbent assay to assess cyclooxygenase 2 activity. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay. Cell migration was performed using transwell inserts that were matrigel coated for invasion experiments. Gelatin zymography was used to assess matrix-metalloproteinase activity. RESULTS: 2,5-dimethyl celecoxib did not inhibit interleukin-1beta-stimulated prostaglandin E2 production, whereas celecoxib did even at low doses. Both celecoxib and 2,5-dimethyl celecoxib decreased tumor cell viability and proliferation with IC50 for celecoxib and 2,5-dimethyl celecoxib of 73 and 53 micromol/L, respectively. Both drugs were also potent inducers of apoptosis, and both inhibited tumor cell migration and invasion. This was associated with down-regulation of matrix metalloproteinase activity. CONCLUSIONS: 2,5-dimethyl celecoxib is a structural analog of celecoxib that lacks cyclooxygenase 2 inhibitory activity but exhibits significant antineoplastic properties comparable to celecoxib. This suggests that the antineoplastic activities of celecoxib are, at least in part, cyclooxygenase independent and that therapeutic strategies can be developed without the side effects of global cyclooxygenase 2 blockade.

Adenocarcinoma↗
PubMed2005

Pleural space problems after living lobar transplantation.

BACKGROUND: We reviewed our experience with adult living lobar lung transplant (LL) recipients to assess whether size and shape mismatch of the donor organ to the recipient pre-disposes to the development of pleural space problems (PSP). METHODS: Eighty-seven LL were performed on 84 adult recipients from 1993 through 2003. Seventy-six patients had cystic fibrosis. Patient records were examined for PSP, defined as air leak or bronchopleural fistula for more than 7 days; pneumothorax, loculated pleural effusions, or empyema in 68 patients for which complete data were available. RESULTS: There were 24 PSP identified for an overall incidence of 35%. The most common PSP was air leak/bronchopleural fistula, accounting for 38% of PSP. The second most common PSP was loculated pleural effusion (21% of PSP). Empyema was uncommon (2 patients, 3% of total patients) in our series of patients despite the large population of cystic fibrosis patients. In 4 of these patients, computed tomography-guided drainage was used for loculated effusions after chest tube removal. Three LL patients underwent surgery for persistent air leak and required muscle flap repair. One of these required subsequent omental transfer. Two LL patients required decortication for empyema. Many patients with PSP could be managed without further surgical intervention (14/24 patients). Donor-recipient height mismatch was not significantly different between PSP and non-PSP patients (p = 0.53). CONCLUSIONS: The incidence of PSP in LL recipients is similar to that reported in the literature on cadaveric transplant recipients. The relatively small lobe in the potentially contaminated chest cavity of cystic fibrosis recipients does not significantly pre-dispose to development of empyema despite immunosuppression. Many PSP can be managed non-operatively, although early aggressive intervention for large air leaks and judicious chest tube management are essential for a good outcome.

Adult↗
PubMed2005

Proximal conduit obstruction after Sano modified Norwood procedure.

Sano and colleagues recently described a modification of first stage palliation for hypoplastic left heart syndrome utilizing a right ventricle to pulmonary artery conduit. Preliminary results are favorable, but experience with this technique is limited. We report a case of sudden death due to obstruction of the proximal conduit by fibrointimal hyperplasia. This case of lethal conduit obstruction presented 3 months after initial palliation. Early cardiac catheterization and second stage palliation may be necessary to minimize the risk of such adverse events after the Sano modification.

Death, Sudden, Cardiac↗
PubMed2005

Long-term pulmonary function after living-donor lobar lung transplantation in adults.

BACKGROUND: Living-donor lobar lung transplantation was developed as an alternative to cadaveric transplantation. However, whether two pulmonary lobes provide comparable intermediate and long-term pulmonary function to full-sized bilateral cadaveric grafts in adults is unknown. METHODS: An analysis of the pulmonary functions of 59 bilateral lobar and 43 bilateral cadaveric adult lung transplant recipients who survived more than 3 months after transplantation was performed. RESULTS: Mean follow-up was 3.8 +/- 2.8 years. In lobar recipients, mean percent predicted forced vital capacity and forced expiratory volume in 1 second improved between 1 and 6 months after transplantation (42.5% +/- 13.4% and 46.9% +/- 14.0% at 1 month versus 63.6% +/- 14.1% and 64.5% +/- 13.7% at 6 months; p < 0.001 and <0.001, respectively). In cadaveric recipients, mean percent predicted forced vital capacity improved after transplantation (54.3% +/- 14.5% at 1 month versus 74.2% +/- 21.3% at 12 months; p < 0.01). As compared with the cadaveric group, mean percent predicted forced vital capacity and forced expiratory volume in 1 second were lower 1 and 3 months after transplantation in the lobar recipients (p = 0.001 at both times); however, by 6 months after transplantation, these values were comparable and remained so throughout the follow-up period. In a subset of lobar and cadaveric recipients, maximal exercise, heart rate, peak oxygen consumption, anaerobic oxygen consumption threshold, and ability to maintain oxygen saturation were also comparable. CONCLUSIONS: In those adult recipients surviving more than 3 months after transplantation, lobar lung transplantation provides comparable intermediate and long-term pulmonary function and exercise capacity to bilateral cadaveric lung transplantation.

Actuarial Analysis↗
PubMed2005

Does the site of insertion of a systemic-pulmonary shunt influence growth of the pulmonary arteries?

BACKGROUND: The modified Blalock-Taussig shunt is a common palliative procedure for children with cyanotic congenital heart disease. The distal shunt anastomosis can be done to a branch pulmonary artery or to the main pulmonary artery. The purpose of this study was to determine if the site of shunt connection influences pulmonary artery growth. METHODS: The records of 101 patients with a modified Blalock-Taussig shunt undergoing a subsequent cardiac catheterization between January 2000 and April 2002 were retrospectively reviewed. From the cineangiograms, the diameters of the right and left pulmonary arteries at their first branching and the diameter of the descending aorta at the diaphragm were measured. RESULTS: If the distal shunt anastomosis was to the right pulmonary artery and there was no antegrade pulmonary flow then the left pulmonary artery was significantly smaller than if the distal connection was to the main pulmonary artery (p = 0.009). Absence of antegrade pulmonary blood flow resulted in significantly smaller right and left pulmonary artery size in general (p < 0.001). No significant differences in pulmonary artery growth were found with respect to gender, anatomic subtype, proximal shunt site, use of cardiopulmonary bypass or size of shunt. By multiple regression analysis absence of antegrade flow and the presence of right-sided shunts were statistically significant predictors of smaller left pulmonary artery and size discrepancy between right and left pulmonary artery. CONCLUSIONS: These data suggest that in the absence of antegrade pulmonary blood flow, a modified Blalock-Taussig shunt to the main pulmonary artery may promote more uniform branch pulmonary artery growth.

Anastomosis, Surgical↗
PubMed2005

Obstruction in modified Blalock shunts: a quantitative analysis with clinical correlation.

BACKGROUND: Despite numerous reports describing the clinical course of patients undergoing a modified Blalock-Taussig shunt (MBTS), there is limited information on shunt obstruction. No studies have quantified MBTS stenosis histopathologically and correlated that with demographic and clinical risk factors. METHODS: From June 2001 to June 2003, 155 patients had MBTS takedown. The shunt operation (at median age 6 days; shunt size 3.5 mm in 56 [36%]; 4 mm in 84 [54%]; 5 mm in 15 [10%]) was performed on cardiopulmonary bypass (CPB) in 96 patients (62%). At elective takedown (at median 8.1 months), the shunt was excised and histopathologically analyzed for maximal narrowing. Demographics and clinical variables including age, weight, shunt size and duration, diagnosis, use of cardiopulmonary bypass, blood products, anastomosis sites, and concomitant antegrade flow were then tested for correlation with shunt stenosis. RESULTS: The mean value for maximal narrowing of the shunt lumen was 34% +/- 22%, and 32 patients (21%) had greater than 50% stenosis. Myofibroblastic proliferation, often associated with organized thrombus, caused the obstruction. Smaller shunt size (<4 mm) was a statistically significant risk factor for stenosis greater than 50% (odds ratio [OR] = 2.51; p = 0.028). Other variables that showed a clinically important association with obstruction but did not reach statistical significance included age less than 14 days at shunt (OR = 2.08, confidence interval [CI] 0.8 to 5.2), shunt on bypass (OR = 2.07, CI 0.9 to 4.8), and platelet use at shunt operation (OR = 1.96, CI 0.9 to 4.4). CONCLUSIONS: Most MBTS develop stenosis by the time of takedown, and 21% have greater than 50% obstruction. Shunt size less than 4 mm is a risk factor for high-grade stenosis. Younger age, CPB, and use of platelets are other clinically important factors. Better conduits and suppression of intimal proliferation could potentially improve outcomes.

Arteriovenous Shunt, Surgical↗
PubMed2005

Ascending aortic extension for enlargement of the aortopulmonary space in children with pulmonary artery stenosis.

BACKGROUND: Complex reconstruction of the aorta can be complicated by compression within the aortopulmonary space resulting in airway or pulmonary artery narrowing. Pulmonary artery compression is especially problematic in children with single ventricle physiology in which an increase in pulmonary vascular resistance may impair systemic venous flow and reduce cardiac output. METHODS: We operated on 7 patients (mean age, 2.9 years) with pulmonary artery stenosis presenting after a complex neonatal aortic reconstruction. All 7 patients underwent aortic extension with a polytetrafluoroethylene interposition graft and homograft patch angioplasty of the pulmonary artery to open the aortopulmonary space and relieve pulmonary artery narrowing. Five patients (hypoplastic left heart syndrome, n = 2; transposition of the great arteries with tricuspid atresia and aortic hypoplasia, n = 1; double outlet right ventricle with aortic hypoplasia, n = 2) had previously undergone first stage repairs for single ventricle morphology. Two of the patients had multiple interim procedures, including placement of bilateral pulmonary artery stents, prior to our repair. RESULTS: There was 1 early death secondary to fungal sepsis. Six patients were discharged from the hospital. There was 1 late, noncardiac death from aspiration pneumonia in a patient with a severe craniofacial defect. Follow-up echocardiograms in the intermediate term have demonstrated relief of pulmonary artery narrowing and unobstructed aortic flow. CONCLUSIONS: Aortic extension is an option in children with pulmonary artery compression of structures in the aortopulmonary space after complex aortic reconstruction.

Aortic Valve Stenosis↗
PubMed2005

Evaluation of cyclooxygenase-2 inhibition in an orthotopic murine model of lung cancer for dose-dependent effect.

OBJECTIVES: Cyclooxygenase-2 plays a role in growth, apoptosis, angiogenesis, and metastasis in lung cancer. Inhibition of cyclooxygenase-2 with celecoxib has been shown to inhibit tumor growth. We evaluated the effect of increasing doses of celecoxib in a murine model of human lung cancer. METHODS: Human lung adenocarcinoma cells (A549) were implanted in the left lung upper lobe of mice with severe combined immunodeficiency syndrome. Mice were randomly assigned to 4 groups at implantation (n = 10 per group): control, 125 mg/kg chow, 500 mg/kg chow, 1000 mg/kg chow. After 3 weeks, mice were killed, and a blinded observer measured total tumor volume. The dose effect of celecoxib was examined in vitro by studying cell proliferation, expression of cyclooxygenase-2 (mRNA and protein), and production of prostaglandin E 2 in unstimulated and interleukin 1beta-stimulated cells. RESULTS: All 40 mice survived for 3 weeks with no observed toxicities. Total tumor volume was inhibited in each celecoxib group ( P = .0038, Welch analysis of variance): 206.7 +/- 119.5 mm 3 (control group), 41.4 +/- 54.0 mm 3 (low-dose group), 34.5 +/- 39.3 mm 3 (medium-dose group), and 27.3 +/- 53.6 mm 3 (high-dose group). In vitro celecoxib was effective at inhibiting production of prostaglandin E 2 , even in stimulated cells, although little effect was seen on cyclooxygenase-2 protein levels. Inhibition of proliferation was evident only at doses that exceeded those used in the animal model. CONCLUSION: Inhibition of cyclooxygenase-2 with low-dose celecoxib restricted the growth of lung cancer in this model. This might be mediated by prostaglandin E 2 . Higher doses of celecoxib afforded no additional benefit. Chronic therapy with low-dose cyclooxygenase-2 inhibition has the potential to influence tumor progression in non-small cell lung cancer.

Adenocarcinoma↗
PubMed2005

The Ross procedure is an ideal aortic valve replacement operation for the teen patient.

The Ross procedure is an ideal aortic valve replacement for the teenage patient because the pulmonary autograft is durable, is nonthrombogenic, has excellent hemodynamics, and grows. Since 1992, our center has performed 194 Ross procedures, and 53 of these were in teenagers (10 to 21 years of age). In this group, there have been no perioperative deaths, hospital length of stay was 4 days, and re-operation for autograft failure was only 2% at mean follow-up of 69 months. All patients are in NYHA heart failure class I. Because of its proven efficacy, the Ross operation is our preferred aortic valve replacement for the teenage patient.

Adolescent↗
PubMed2005

Identification of the V genes encoding xenoantibodies in non-immunosuppressed rhesus monkeys.

The major immunological barrier that prevents the use of wild-type pig xenografts as an alternative source of organs for human xenotransplantation is antibody-mediated rejection. In this study, we identify the immunoglobulin variable region heavy (IgV(H)) chain genes encoding xenoantibodies to porcine heart and fetal porcine islet xenografts in non-immunosuppressed rhesus monkeys. We sought to compare the IgV(H) genes encoding xenoantibodies to porcine islets and solid organ xenografts. The immunoglobulin M (IgM) and IgG xenoantibody response was analysed by enzyme-linked immunosorbent assay and cDNA libraries from peripheral blood lymphocytes were prepared and sequenced. The relative frequency of IgV(H) gene usage was established by colony filter hybridization. Induced xenoantibodies were encoded by the IGHV3-11 germline progenitor, the same germline gene that encodes xenoantibodies in humans mounting active xenoantibody responses. The immune response to pig xenografts presented as solid organs or isolated cells is mediated by identical IgV(H) genes in rhesus monkeys. These animals represent a clinically relevant model to identify the immunological basis of pig-to-human xenograft rejection.

Amino Acid Sequence↗
PubMed2004

Use of lentiviral vectors to induce long-term tolerance to gal(+) heart grafts.

BACKGROUND: Tolerance to organ grafts has been achieved by establishing a state of stable mixed-cell chimerism after bone marrow transplantation. Gene therapy has been applied to establish chimerism for cells expressing galactose alpha 1,3 galactose in alpha 1,3 galactosyltransferase deficient (gal knockout) mice using retroviral vectors. Limitations to the success of this methodology include short-term expression of the introduced gene and rejection of gal hearts transplanted into these animals within a month. METHODS: Autologous bone marrow from gal knockout mice was transduced with a lentiviral vector expressing porcine alpha 1,3 galactosyltransferase and transplanted into lethally irradiated gal knockout mice. Chimerism was monitored by flow cytometry. Hearts from wild type mice (gal/) were transplanted into these animals and palpated daily. Xenoantibodies directed at the gal carbohydrate or porcine xenoantigens were detected by enzyme-linked immunosorbent assay. RESULTS: Hearts from wild-type gal/ donors were permanently accepted in all mice receiving autologous, transduced bone marrow before heart transplantation. Control mice rejected gal hearts within 12 to 14 days. Histologic analysis demonstrated classical signs of rejection in controls and normal myocardium with no evidence of rejection in mice chimeric for the gal carbohydrate. Anti-gal xenoantibodies were not produced in gal chimeras, but normal antibody responses to other xenoantigens were detected. Specific tolerance for the gal carbohydrate was achieved by this procedure. CONCLUSIONS: These experiments report the first demonstration of permanent survival of gal hearts after transplantation with autologous, transduced bone marrow. Transduction with lentiviral vectors results in long-term, stable chimerism at levels sufficient to induce long-term tolerance to heart grafts in mice.

Animals↗