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Biomedical subjects

Vaughn A Starnes

Publications and source records attributed to Vaughn A Starnes.

At least 37 records · Page 2Linked to original sources
PubMed2004

Previous thoracic surgery does not increase peri-operative mortality in pediatric heart-lung transplant recipients.

BACKGROUND: Heart-lung transplant (HLT) is indicated in select children with end-stage cardiopulmonary disease. We sought to determine whether previous thoracic surgery increases peri-operative morbidity and mortality. METHODS: Retrospective data were analyzed using unpaired Student's t-test and Fisher's exact test. Results are reported as mean +/- SD. Peri-operative mortality was defined as death at </=30 days post-transplant. RESULTS: From August 1993 through April 2001, 13 patients (mean age 7.9 +/- 5.3 years; 9 girls, 4 boys) underwent HLT at our center. Eight of 13 (62%) had previous thoracic surgery and 5 of 13 (38%) did not. Interval of last surgery to transplant date was 45.5 +/- 26.4 months (range 6 to 79 months). We compared HLT patients who had previous thoracic surgery to HLT recipients who did not. There was no significant difference in weight (18.6 +/- 14.3 vs 36.5 +/- 20.7 kg, p = 0.09), age (6.5 +/- 4.5 vs 10.2 +/- 6.1 years, p = 0.23) or duration of intubation (14.1 +/- 12.9 vs 17.0 +/- 30.3 days, p = 0.83). There were no caval or tracheal anastomotic stenoses in either group. There was no significant difference in blood products transfused </=48 hours after HLT: packed red blood cells (p = 0.16); fresh frozen plasma (p = 0.13); platelets (p = 0.59), and cryoprecipitate (p = 0.27). There was no difference in cardiopulmonary bypass time (129.3 +/- 48.2 vs 160.6 +/- 73.9 minutes, p 0.39); post-operative diaphragm dysfunction (4 of 8 vs 0 of 5, p = 0.1); re-exploration for bleeding (2 of 8 vs 1 of 5, p = 1.0); or peri-operative mortality (2 of 8 vs 0 of 5, p = 0.48). CONCLUSIONS: We conclude that previous thoracic surgery in HLT recipients does not significantly increase blood product transfusion, cardiopulmonary bypass time or peri-operative mortality.

Adolescent↗
PubMed2004

Potential role for antiangiogenic proteins in the myocardial infarction repair process.

OBJECTIVE: Although angiogenic proteins have been identified as positive modulators of myocardial revascularization following acute myocardial infarction, little if anything is known regarding the role that antiangiogenic proteins have in myocardial revascularization. We explored the temporospatial distribution of endothelial-monocyte activating polypeptide (EMAP) II to determine whether antiangiogenic proteins have a role in the repair of myocardial tissue following infarction. METHODS: A rat model of myocardial infarction was utilized to examine EMAP II distribution (in situ hybridization) and protein expression (Western analysis) over a 6-week period. RESULTS: At baseline, EMAP II protein and mRNA are minimally expressed with transcription products localizing predominately to the perivascular stroma region in the normal rat myocardium. Six hours following myocardial infarction, EMAP II changes its distribution from the perivascular stroma to an invading inflammatory cell population. This is associated with a 2-fold (P < 0.0009) increase in EMAP II protein and its transcription primarily localized to the infarct region. EMAP II protein expression remains elevated throughout the weeks following the infarction with transcription limited to the infarct region and a notable decrease in EMAP II transcription products noted in the viable vasculature surrounding the infarct zone. Six weeks following myocardial infarction, EMAP II protein is elevated above control, changes its location of transcription from the inflammatory cell population to that of the fibroblasts located in the relative avascular scar tissue, and has resumed its perivascular stromal distribution in the viable periinfarct tissue. CONCLUSIONS: Thus, the temporospatial distribution of this antiangiogenic protein suggests that negative vascular modulators may have a function in the revascularization process following acute myocardial infarction.

Angiogenesis Inhibitors↗
PubMed2004

A decade of living lobar lung transplantation: recipient outcomes.

OBJECTIVE: Living lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation. METHODS: One hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 +/- 7.7 years), and 39 were pediatric patients (age, 13.9 +/- 2.9 years). RESULTS: The primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients (P =.65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P =.03; Kaplan-Meier P =.002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50). CONCLUSION: These results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations.

Adolescent↗
PubMed2004

Neochordal repair of the posterior mitral leaflet.

BACKGROUND: Myxomatous mitral valve insufficiency is traditionally repaired by posterior leaflet quadrangular resection and reconstruction. A simplified repair technique without leaflet resection is described, and our initial experience is reviewed. METHODS: Thirty-nine consecutive patients with significant mitral regurgitation underwent repair since January 2000 by placement of expanded polytetrafluoroethylene sutures between the leading (coapting) edge of the posterior leaflet and the corresponding papillary muscle. An annuloplasty ring was placed, and no leaflet tissue was resected. Patient medical records were obtained and retrospectively reviewed. RESULTS: Twenty-five men and 14 women (median age, 61 years; range, 40-88 years) had their mitral valve repaired by a variety of surgical approaches, including robotic (18 patients), right thoracotomy (6 patients), and sternal (15 patients). Three patients have required valve replacement: 1 at the initial operation, 1 because of dehiscence of the annuloplasty ring, and 1 after subsequent rupture of a previously normal native chorda. At follow-up (median, 12 months), 92% (33/36) of the remaining patients had an intact mitral repair with no to mild regurgitation, 8.3% (3/36) of patients had moderate regurgitation, and 92% of all patients (36/39) were in New York Heart Association class I. There were no deaths. CONCLUSIONS: Myxomatous mitral regurgitation due to posterior leaflet insufficiency can be repaired without leaflet resection by placement of neochordae. This repair technique is effective and is readily accomplished by traditional and minimally invasive surgical approaches.

Adult↗
PubMed2004

Identification, functional analysis and expression in a heterotopic heart transplant model of CXCL9 in the rat.

CXCR3 chemokines are of particular interest because of their potential involvement in a variety of inflammatory diseases, including the rejection of organ transplants. Although the rat is one of the most appropriate animals for using to study transplantation biology, the structural and functional characteristics of CXCL9 [monokine induced by interferon-gamma (Mig)] in this experimental model have not been described. Therefore, we recently conducted a series of experiments to identify and characterize the rat CXCL9 gene. Accordingly, we isolated rat CXCL9 cDNA and genomic DNA. The rat CXCL9 gene encodes a protein of 125 amino acids and spans a 3.5 kbp DNA segment containing four exons in the protein-coding region. We then analysed mRNA expression in various tissues. Transcripts for the gene were found to be expressed at high levels in the lymph nodes and spleen. Then, to confirm the function of the identified gene, rat CXCL9 was transiently expressed in COS-1 cells. Rat recombinant Mig displayed chemotactic properties and induced CXCR3 internalization in CD4+ T cells. Lastly, we analysed the expression of rat CXCL9 in a heterotopic heart allograft model. Both mRNA and protein levels of intragraft CXCL9 were significantly increased following transplantation of ACI to LEW hearts when compared with syngeneic controls. These findings indicate that rat CXCL9 has an in vivo role in the infiltration of CD4+ T cells in the transplanted graft.

Amino Acid Sequence↗
PubMed2004

A decade of living lobar lung transplantation: perioperative complications after 253 donor lobectomies.

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long-term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for >/=14 d for persistent air leaks and/or drainage. Right-sided donors were more likely to have a perioperative complication than left-sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

Adult↗
PubMed2003

Evidence for recipient derived fibroblast recruitment and activation during the development of chronic cardiac allograft rejection.

BACKGROUND: Allograft fibrosis is a prominent feature of chronic rejection. Although intragraft fibroblasts contribute to this process, their origin and exact role remain poorly understood. METHODS: Using a rat model of chronic rejection, LEW to F344, cardiac fibroblasts were isolated at the point of rejection and examined in a collagen gel contraction assay to measure fibroblast activation. The allograft microenvironment was examined using immunohistochemistry for fibrogenic markers (transforming growth factor [TGF]-beta, platelet-derived growth factor [PDGF], tissue plasminogen activator [TPA], plasminogen activator inhibitor [PAI]-1, matrix metalloproteinase [MMP]-2, and tissue inhibitor of matrix metalloproteinase [TIMP]-2). The origin of intragraft fibroblasts was studied using female to male allografts followed by polymerase chain reaction [PCR] and in situ hybridization for the male sry gene. RESULTS: The cardiac fibroblasts isolated from allografts with chronic rejection exhibited higher gel contractibility (50.9% +/- 6.1% and 68.2% +/- 3.8% at 4 and 24 hr) compared with naive cardiac fibroblasts (30.7% +/- 3.5% and 55.3% +/- 6.6% at 4 and 24 hr; P<0.05 and <0.05, respectively). Immunostaining for TGF-beta, PDGF, TPA, PAI-1, MMP-2 and TIMP-2 was observed in all allografts at the time of rejection. In situ hybridization demonstrated the presence of sry positive cells in female allografts rejected by male recipients. Sixty-five percent of fibroblast colonies (55 of 85) isolated from female heart allografts expressed the male sry gene. CONCLUSION: Cardiac fibroblasts are activated and exist in a profibrogenic microenvironment in allografts undergoing chronic rejection. A substantial proportion of intragraft fibroblasts are recruited from allograft recipients in this experimental model of chronic cardiac allograft rejection.

Animals↗
PubMed2003

Migration of mesenchymal stem cells to heart allografts during chronic rejection.

BACKGROUND: Mesenchymal stem cells (MSC) are pluripotent progenitors for a variety of cell types, including fibroblasts and muscle cells. Their involvement in the tissue repair of allografts during the development of chronic rejection has been hypothesized, but not yet substantiated, by experimental evidence. METHODS: Rat MSC were isolated from circulation using an aortic pouch allograft as a trapping device. The plasticity of these cells was examined in differentiation cultures. One of the resulting MSC lines was immortalized and transduced to express a marker gene. The -labeled cells were then transferred to F344 rats bearing Lewis (LEW) cardiac allografts to measure their localization and contribution to graft tissue repair. RESULTS: The MSC isolated from circulation exhibited multipotential for differentiation in culture, developing into various lineages including osteoblasts, lipocytes, chondrocytes, myotubes, and fibroblasts. Intravenous engraftment of the -labeled cells into recipients of heart transplant resulted in migration of the beta-gal+ cells into the lesions of chronic rejection in the cardiac grafts and homing of the cells to the bone marrow. The majority of beta-gal+ cells present in the allografts exhibited fibroblast phenotypes, and a small number of the cells expressed desmin, indicative of myocyte differentiation. CONCLUSION: MSC vigorously migrated into the site of allograft rejection. This data suggests that they may be attracted to this site to actively participate in tissue repair during chronic rejection. In addition, given the robust migration, the inhibition of MSC differentiation toward fibroblast progeny and induction toward the myocyte lineage may serve as a new strategy for treatment of chronic rejection and allograft tissue repair.

Animals↗
PubMed2003

Cyclooxygenase-2 inhibition decreases primary and metastatic tumor burden in a murine model of orthotopic lung adenocarcinoma.

OBJECTIVE: To assess cyclooxygenase-2 inhibition on primary tumor and mediastinal metastases in a murine model of orthotopic lung adenocarcinoma. METHODS: Human lung adenocarcinoma cells (CRL5908, female nonsmoker with cyclooxygenase-2 expression by Western blot) were implanted under direct visualization through the parietal pleura in the upper lobe of the left lung (2 x 10(6) cells/animal) of SCID mice. Mice were randomly assigned to 2 groups, either untreated (n = 62) or celecoxib-treated (n = 60). Celecoxib, a selective cyclooxygenase-2 antagonist, was solubilized in the animals' drink (25 mg/kg per day). Mice were arbitrarily killed at 1, 2, 3, and 4 weeks. A blinded observer assessed primary tumor volume and metastatic disease grossly and histologically. RESULTS: Gross metastatic lymph nodes were present at 3 weeks in none of 15 (0%) treated and 12 of 15 (80.0%) untreated animals (P <.0001). Mean primary tumor volumes at 3 weeks for treated mice were 7.9 +/- 10.0 mm(3) and for untreated mice were 533.1 +/- 453.6 mm(3) (mean +/- SD, P <.0001). Gross metastatic lymph nodes were present at 4 weeks in 3 of 15 (20%) treated and 17 of 17 (100%) untreated animals (P <.0001). Mean primary tumor volumes at 4 weeks for treated mice were 37.1 +/- 46.2 mm(3) and for untreated mice were 809.6 +/- 1226.4 mm(3) (mean +/- SD, P <.0001). Mean blood levels of celecoxib in treated mice were 236.8 +/- 34.2 ng/mL (mean +/- SD). CONCLUSIONS: Cyclooxygenase-2 inhibition results in decreased primary and metastatic tumor burden in a murine model using human lung adenocarcinoma. Cyclooxygenase-2 inhibition has the potential to decrease tumor progression and metastases in patients with lung adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Living lobar transplantation.

Although cadaveric transplantation remains the preferred option for patients who have end-stage lung disease, living lobar transplantation provides organ availability that can be life saving in severely ill pediatric and adult patients who will either die or become unsuitable recipients before a cadaveric organ becomes available. In addition, living lobar transplantation provides acceptable long-term survival when compared with recipients of cadaveric grafts; however, because this procedure presents risks to two healthy donors, appropriate recipient and donor selection and timing of transplantation are critical to minimize the morbidity to the donor and maximize the chance of a successful outcome in the recipient. The results of the authors' experience have demonstrated that the donor procedure is safe, well tolerated physiologically, and that the great majority of donors are extremely satisfied with their decision to donate. Although there have been no deaths in the donor cohort, a risk of death between 0.5% to 1% should be quoted pending further data. These encouraging results are important if this procedure is to be considered as an option at more pulmonary transplant centers in view of the institutional, regional, and intra- and international differences in the philosophical and ethical acceptance of the use of live organ donors for transplantation.

Adult↗
PubMed2003

What are the best pulmonary function test parameters for early detection of post-lung transplant bronchiolitis obliterans syndrome in children?

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV1) >or=20% of baseline (B). There have been reports in adults that FEF25-75% (>30% decline from B) is more sensitive than FEV1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF25-75%) and maximal expiratory flow rate at 80% (Vmax80%), 70% (Vmax70%) and 60% (Vmax60%) - are more sensitive indicators for early diagnosis of BOS than FEV1 in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 +/- 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV1 >or=20% of B, FEF25-75% >30% of B, and Vmax80%, Vmax70% and Vmax60% from normal occurred (635 +/- 431, 551 +/- 422 and 454 +/- 287 days, respectively; p = 0.4). However, a decline in FEV1 was the first abnormality in only 39% of the patients, while a decline in FEF25-75% and Vmax at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF25-75% rather than on FEV1.

Adolescent↗
PubMed2003

Bordetella bronchiseptica infection in pediatric lung transplant recipients.

Bordetella bronchiseptica are small, pleomorphic Gram-negative coccobacilli which are commensal organisms in the upper respiratory tract of many wild and domestic animals ('kennel cough' in dogs). While it is common for health care providers to ask about exposure to ill family/friends, most do not routinely inquire about the health or immunization status of household pets. We report two cases of B. bronchiseptica pneumonia in lung transplant recipients [cystic fibrosis (CF); ages 10 and 15 yr; one male] who contracted B. bronchiseptica from pet dogs. We compared their course and outcome to four children (two CF, one congenital heart disease and one Duchenne's muscular dystrophy; four males, age range 6 months to 14 yr) with B. bronchiseptica cultured from the respiratory tract. Two of the four patients also acquired their illnesses from pet dogs and two from unknown sources. One lung transplant recipient expired from progressive respiratory failure. We conclude that B. bronchiseptica can cause serious infections in both immunosuppressed and immunocompetent children. We speculate that a detailed history of exposure to ill pets (particularly dogs), and the immunization status of all pets should be included in the routine evaluation of all pediatric transplant recipients.

Adolescent↗
PubMed2002

Clinical findings and lung pathology in children with cystic fibrosis.

Cystic fibrosis pulmonary disease is assessed by pulmonary function tests, arterial blood gases, and chest X-rays, but the correlation with lung pathology is unknown. We reviewed the clinical findings and lung pathology of 21 cystic fibrosis patients who had lung transplant. Pulmonary function tests, Brasfield scores, arterial blood gases, and age were correlated with lung pathology. All patients had severe Brasfield scores (9.0 +/- 3.2), airways obstruction (FEV1 25.6 +/- 5.6% predicted, FEF(25-75%) 11.0 +/- 4.5% predicted), and hyperinflation (residual volume [RV] 341.8 +/- 75.8% predicted). All patients were hypoxemic (PO2 64.2 +/- 8.2 mm Hg), and 5 of 21 (24%) were hypercapneic (PCO2 > 50 mm Hg). Pulmonary function tests and Brasfield scores were within a narrow range, and did not allow correlation with lung pathology. Small airway density (airways < 2 mm/cm2) decreased with increasing age. There were no differences in small airways inflammation and fibrous narrowing between the hypercapneic and nonhypercapneic patients, but the percent of smallest airways (airways < 0.35 mm) was significantly lower in the hypercapneic group. We conclude that there is significant correlation between airway pathology and increased age and CO2 retention. We speculate that decreased small airway density in older patients and the decreased proportion of smallest airways in hypercapneic patients is caused by increased dilatation of small airways.

Adolescent↗
PubMed2002

The utility of preoperative routine carotid artery duplex scanning in patients undergoing aortic valve replacement.

Patients with aortic valve disease (AVD) typically have a cardiac murmur that radiates to the neck and may be indistinguishable from a cervical bruit secondary to carotid artery occlusive disease. The purpose of this report was to determine the prevalence of significant asymptomatic carotid artery occlusive disease in patients undergoing aortic valve replacement (AVR). All patients scheduled for AVR were prospectively studied. Preoperative carotid artery color-flow duplex was performed in all patients. A total of 204 patients were included in the study and significant carotid disease (>50% stenosis of the internal carotid artery) was found in 17 (8%). In patients with isolated aortic valve disease, 4/129 (3%) had significant stenosis. Of the patients with concurrent aortic valve and coronary artery disease, 13/75 (17%) had significant stenosis. The incidence of significant carotid stenosis in patients with aortic valve disease was over five fold higher in patients with concurrent coronary artery disease (3% vs. 17%, p <0.001). The yield of routine carotid duplex scanning for patients undergoing isolated AVR is low. However, in the subset of patients with concurrent coronary disease, the yield is higher. This finding supports the use of routine carotid duplex scanning in patients with coexistent aortic valve and coronary artery disease.

Adult↗
PubMed2002

Perforating Barrett's ulcer resulting in a life-threatening esophagobronchial fistula.

Perforating benign ulcer is a very rare complication of Barrett's esophagus. This report presents the management of a patient with a Barrett's ulcer that penetrated into the left mainstem bronchus resulting in a life-threatening bronchial esophageal fistula. This rare complication was successfully managed by using a staged surgical approach, which combined the principles used for treating benign esophagorespiratory fistulas and perforating Barrett's ulcers.

Aged↗
PubMed2002

Vascular endothelial cell apoptosis induced by anti-donor non-MHC antibodies: a possible injury pathway contributing to chronic allograft rejection.

BACKGROUND: Non-major histocompatibility complex (non-MHC) alloantibodies may play a pathogenic role in chronic rejection but remain poorly characterized. METHODS: The kinetics of alloantibody production and the mechanism by which non-MHC alloantibodies cause graft injury were investigated in a Lewis-to-Fischer 344 (LEW-to-F344) rat model of cardiac transplantation. RESULTS: Flow cytometry detected that all the F344 recipients of LEW allografts produced anti-donor immunoglobulin G (IgG) antibodies reactive with LEW lymphocytes and endothelial cells. A sub-group of recipients that rejected their grafts in 30 to 60 days exhibited markedly increased levels of anti-donor IgG antibodies (n = 6, mean fluorescence intensity [MFI]:23.85 +/- 2.7) than recipients with long-surviving allografts (n = 4, MFI:11.23 +/- 0.81; p = 0.00058). Passive transfer of anti-donor sera induced chronic rejection of LEW heart allografts in an immune non-responsiveness model of F344 rats induced by intrathymic inoculation of donor-specific lymphocytes. Immunoglobulin G antibodies purified from the anti-LEW sera exhibited complement-dependent cytotoxicity against LEW vascular endothelial cells in flow-cytometric cytotoxicity assay. The targeted endothelial cells displayed early (annexin V+) and late (TUNEL+) evidence for programmed cell death. Western blot analysis of poly (ADP-ribose) polymerase (PARP) demonstrated that the 25-kD PARP-cleavage fragment was present at the lysates of the vascular endothelial cells treated with anti-donor IgG antibodies, indicating apoptosis-associated caspase activity in these cells. In situ teminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining demonstrated that vascular endothelial cell apoptosis was consistently present in all LEW heart allografts with chronic rejection. CONCLUSIONS: Non-MHC alloantibodies are pathogenic and capable of causing chronic graft injury through an antibody-induced cell apoptosis mechanism. The results emphasize the importance of non-MHC antibodies as a common predisposing factor in the development of chronic rejection.

Animals↗