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Biomedical subjects

G Alexander Patterson

Publications and source records attributed to G Alexander Patterson.

At least 73 records · Page 4Linked to original sources
PubMed2003

Bronchial fenestration improves expiratory flow in emphysematous human lungs.

BACKGROUND: The crippling effects of emphysema are due in part to dynamic hyperinflation, resulting in altered respiratory mechanics, an increased work of breathing, and a pervasive sense of dyspnea. Because of the extensive collateral ventilation present in emphysematous lungs, we hypothesize that placement of stents between pulmonary parenchyma and large airways could effectively improve expiratory flow, thus reducing dynamic hyperinflation. METHODS: Twelve human emphysematous lungs, removed at the time of lung transplantation, were placed in an airtight ventilation chamber with the bronchus attached to a tube traversing the chamber wall, and attached to a pneumotachometer. The chamber was evacuated to -10 cm H2O pressure for lung inflation. A forced expiratory maneuver was simulated by rapidly pressurizing the chamber to 20 cm H2O, while the expiratory volume was continuously recorded. A flexible bronchoscope was then inserted into the airway and a radiofrequency catheter (Broncus Technologies) was used to create a passage through the wall of three separate segmental bronchi into the adjacent lung parenchyma. An expandable stent, 1.5 cm in length and 3 mm in diameter, was then inserted through each passage. Expiratory volumes were then remeasured as above. In six experiments, two additional stents were then inserted and forced expiratory volumes again determined. RESULTS: The forced expiratory volume in 1 second (FEV1) increased from 245 +/- 107 mL at baseline to 447 +/- 199 mL after placement of three bronchopulmonary stents (p < 0.001). With two additional stents, the FEV1 increased to 666 +/- 284 mL (p < 0.001). CONCLUSIONS: Creation of extra-anatomic bronchopulmonary passages is a potential therapeutic option for emphysematous patients with marked hyperinflation and severe homogeneous pulmonary destruction.

Feasibility Studies↗
PubMed2003

Effect of a cardiac-specific didactic course on thoracic surgery in-training examination performance.

BACKGROUND: The purpose of this study was to determine which factors influenced performance on the Thoracic Surgery In-Training Examination (TSITE) and whether the addition of a cardiac-specific didactic study course improved scores. METHODS: Between 1989 and 2002, 59 TSITE scores (overall, cardiac [C-TSITE], and thoracic [T-TSITE]) were collected from 33 residents (23 cardiac track, 10 thoracic). Factors assessed with univariate and multivariate analysis included calendar year, year of training (31 year I, 28 year II), standardized test-taking history (average National Board and American Board of Surgery in-training scores), subjective faculty assessment of cardiothoracic knowledge, months on cardiac versus thoracic service, clinical performance, and participation in a cardiac-specific didactic series with faculty lectures and board question reviews (12 residents). RESULTS: Cardiac-track residents had higher C-TSITE percentile scores (53% +/- 27% versus 38% +/- 27%, p < 0.05), whereas thoracic-track residents had higher T-TSITE scores (70% +/- 24% versus 51% +/- 25%, p < 0.01). Multivariate analysis identified 3 factors associated with higher overall TSITE scores: standardized test-taking history (p < 0.001), subjective faculty assessment of knowledge (p < 0.001), and year of training (p < 0.007). Inclusion in the cardiac-specific didactic series did not affect C-TSITE scores (50% +/- 30% versus 48% +/- 27%, p > 0.82) or overall TSITE scores (p > 0.23). CONCLUSIONS: Standardized test-taking history and subjective faculty assessment of knowledge were associated with higher TSITE scores, but implementation of a cardiac-specific didactic series had no influence. These findings suggest that independent study and reading may be the best way to improve TSITE scores.

Educational Measurement↗
PubMed2003

Comparison of open subxiphoid pericardial drainage with percutaneous catheter drainage for symptomatic pericardial effusion.

BACKGROUND: The optimal therapy for symptomatic pericardial effusions remains controversial. This paper compares outcomes after the two most commonly used techniques, percutaneous catheter drainage and operative subxiphoid pericardial drainage. METHODS: We performed a 5-year retrospective, single-institution study to analyze outcomes after either percutaneous catheter drainage or subxiphoid open pericardial drainage for symptomatic pericardial effusions. RESULTS: Symptomatic pericardial effusions in 246 patients were treated by open pericardiotomy and tube drainage (n = 150) or percutaneous catheter drainage (n = 96). Drainage duration, total drainage volume, and duration of follow-up (2.6 years) were similar in both groups. Effusions were classified malignant in 79 (32%) patients and benign in 167 (68%) patients. No direct procedural mortality occurred, but the hospital mortality was 16 patients (10.7%) in the open group and 22 (22.9%) in the percutaneous group (p = 0.01) The 5-year survival rate was 51% in the open group versus 45% in the percutaneous group, despite a greater percentage of the open group having a preoperative malignant diagnosis (35% versus 28%). Symptomatic effusions recurred in 16.5% of the percutaneous group compared with 4.6% in the open group (p = 0.002), and sclerosis did not appear to reduce recurrence rates (10.7% with sclerosis versus 15.6% without; p > 0.05). The diagnosis of malignancy was confirmed in 16 of 27 (59%) percutaneous procedures performed on patients with known malignancy. In the open group, cytologic and pathologic evaluation of the pericardial specimen revealed malignancy in 32 of 52 (62%) patients with known malignancy. CONCLUSIONS: Subxiphoid and percutaneous pericardial drainage of symptomatic pericardial effusions can be performed safely; however, death occurs from underlying disease. Open subxiphoid pericardial drainage with pericardial biopsy appears to decrease recurrence but does not improve diagnostic accuracy of malignancy over cytology alone.

Catheterization↗
PubMed2003

Feasibility and safety of the airway bypass procedure for patients with emphysema.

OBJECTIVE: We have proposed that direct passages created between pulmonary parenchyma and large airways (airway bypass) could take advantage of the extensive collateral ventilation present in emphysematous lungs to provide improvement in expiratory flow and respiratory mechanics. A critical step in the safe performance of these procedures is to create passages through the airway wall into lung parenchyma while avoiding injury to adjacent blood vessels. METHODS: The procedure consists of selection of a target site bronchoscopically, use of a Doppler catheter to detect and avoid peribronchial blood vessels, and creation of a passage through the airway wall with a cautery probe. To evaluate the safety of airway bypass, 10 patients were treated during prescheduled lobectomies for neoplasm. The procedure was done after thoracotomy and immediately before resection and was confined to airways in the lung identified for removal. Airway bypass was subsequently performed in 5 patients undergoing lung transplantation for emphysema just before lung excision to evaluate the procedure in emphysematous patients. RESULTS: Twenty-nine passages (1-5 per subject) were created in the patients undergoing lobectomy. Eighteen passages were created (3-4 per subject) in the patients undergoing transplantation. There were 2 instances of mild bleeding in the patients undergoing lobectomy and no bleeding in the patients undergoing transplantation. Both instances were treated with suction and topical application of epinephrine and resolved without incident. CONCLUSION: The results of this study confirm that passages can be made safely through the airways of human subjects. These clinical results support further investigation of the efficacy of the airway bypass procedure in patients with emphysema.

Adult↗
PubMed2003

Tumor necrosis factor inhibitor gene transfer ameliorates lung graft ischemia-reperfusion injury.

OBJECTIVE: Tumor necrosis factor is an important mediator of lung transplant ischemia-reperfusion injury, and soluble type I tumor necrosis factor receptor binds to tumor necrosis factor and works as a tumor necrosis factor inhibitor. The objectives of this study were to demonstrate that gene transfer of type I tumor necrosis factor receptor-IgG fusion protein reduces lung isograft ischemia-reperfusion injury and to compare donor endobronchial versus recipient intramuscular transfection strategies. METHODS: Three donor groups of Fischer rats (n = 6/group) underwent endobronchial transfection with either saline, 2 x 10(7) plaque-forming units of control adenovirus encoding beta-galactosidase, or 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein. Left lungs were harvested 24 hours later. Two recipient groups (n = 6/group) underwent intramuscular transfection with 2 x 10(7) plaque-forming units or 1 x 10(10) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein 24 hours before transplantation. All donor lung grafts were stored for 18 hours before orthotopic lung transplantation. Graft function was assessed 24 hours after reperfusion. Transgene expression was evaluated by means of enzyme-linked immunosorbent assay and immunohistochemistry of type I tumor necrosis factor receptor. RESULTS: Endobronchial transfection of donor lung grafts with 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein significantly improved arterial oxygenation compared with the saline and beta-galactosidase donor groups (366.6 +/- 137.9 vs 138.8 +/- 159.9 and 140.6 +/- 131.4 mm Hg, P =.009 and.010, respectively). Recipient intramuscular transfection with 1 x 10(10) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein improved lung graft oxygenation compared with that seen in the low-dose intramuscular group (2 x 10(7); 320.3 +/- 188.6 vs 143.6 +/- 20.2 mm Hg, P =.038). Type I tumor necrosis factor receptor-IgG fusion protein was expressed in endobronchial transfected grafts. In addition, intramuscular type I tumor necrosis factor receptor-IgG fusion protein expression was dose dependent. CONCLUSIONS: Donor endobronchial and recipient intramuscular adenovirus-mediated gene transfer of type I tumor necrosis factor receptor-IgG fusion protein improved experimental lung graft oxygenation after prolonged ischemia. However, donor endobronchial transfection required 500-fold less vector. Furthermore, at low vector doses, it does not create significant graft inflammation.

Adenoviridae↗
PubMed2003

Adenovirus encoding soluble tumor necrosis factor alpha receptor immunoglobulin prolongs gene expression of a cotransfected reporter gene in rat lung.

OBJECTIVE: Because almost all pulmonary diseases are not caused by one gene, multiple gene transfection is required for current gene therapy. Adenovirus is an important gene therapy vector, but a short duration and the inability of repeated administration remain limitations. The aims of this study were to evaluate whether adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolongs gene expression and facilitates repeated vector administration to investigate the feasibility of a cotransfection strategy. METHODS: F344 rats received intratracheal administration of 1 x 10(9) plaque-forming units of adenoviral vector encoding beta-galactosidase or both adenoviral vector encoding beta-galactosidase and adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin. In the expression study beta-galactosidase gene expression in the lung was examined by means of enzyme-linked immunosorbent assay on days 2, 7, 14, 28, and 56 (n = 4/day). In the repeated transfection study, soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase were readministered once (7 days after the first adenovirus administration) or twice (on days 7 and 14; n = 4/day). A 2-way factorial analysis of variance was used for statistical analysis. RESULTS: Soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolonged the duration of beta-galactosidase expression. However, antiadenovirus antibody production was significantly increased in the cotransfection group. In addition, there was no increase in beta-galactosidase expression after readministration of soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase. CONCLUSION: Adenoviral vector encoding soluble tumor necrosis factor alpha receptor immunoglobulin and beta-galactosidase cotransfection prolongs beta-galactosidase expression but does not increase beta-galactosidase expression after repeated administration. These results suggest that tumor necrosis factor alpha is one of the most important factors in regulating the duration of gene expression. The cotransfection approach is feasible, but the increase of antiadenovirus antibodies might make repeated cotransfection unfeasible.

Adenoviridae↗
PubMed2003

Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: a possible mechanism for bronchiolitis obliterans syndrome.

Development of anti-HLA class I antibodies is associated with bronchiolitis obliterans syndrome (BOS) after lung transplantation. BOS is characterized histologically by significant fibrosis and airway epithelial cell (AEC) apoptosis. Thus, this study was designed to determine whether anti-HLA class I antibodies can activate AECs to produce growth factors and to undergo apoptosis. KCC-266 AECs were activated with the W6/32 anti-HLA class I monoclonal antibody. Proliferation and apoptosis levels were determined after 24, 48, and 72 hours. The induction of fibroblast and bronchial smooth muscle cell proliferation by anti-HLA class I activated AECs was assessed in the presence of neutralizing antibodies against various growth factors. The anti-HLA class I induced AEC proliferation after 24 hours followed by significant induction of apoptosis after 48 hours. Anti-HLA class I activated AECs produced soluble growth factors that stimulated fibroblasts but not bronchial smooth muscle cells. The stimulation of fibroblast proliferation was inhibited by antibodies against platelet-derived growth factor, heparin-binding epidermal growth factor, insulin-like growth factor 1, and basic fibroblast growth factor. The results from this study suggest that anti-HLA class I alloantibodies may play an important role in the pathogenesis of BOS by inducing proliferation, growth factor production, and apoptotic cell death in AECs.

Antibodies, Monoclonal↗
PubMed2003

Technical considerations in lung transplantation.

The technical aspects of lung transplantation have been refined over the past two decades. Anomalous donor anatomy and suboptimal harvests do not preclude transplantation, but they must be appropriately dealt with to ensure good outcomes. New techniques have been developed to increase the donor pool. Techniques for recipient pneumonectomy and graft implantation have been optimized, and ways of dealing with difficult exposures and anatomic variants have been designed. Novel methods for prevention of ischemia-reperfusion injury have been developed based on experimental studies, but more complete clinical scrutiny is needed to determine their impact.

Humans↗
PubMed2003

Concomitant allorecognition of mismatched donor HLA class I- and class II-derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome.

BACKGROUND: The authors' previous studies with 2 different adult patient populations demonstrated a correlation between indirect allorecognition of mismatched donor HLA Class I- and Class II-derived peptides and the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of this study was to determine whether a parallel allorecognition of mismatched donor HLA Class I- and Class II-derived peptides occurs after lung transplantation and to determine its correlation with the development of BOS after lung transplantation in a group of pediatric patients. METHODS: Peripheral blood mononuclear cells from 7 BOS-positive and 6 BOS-negative pediatric lung transplant recipients (age, 11.5 +/- 4.4 years) were cultured in the presence of synthetic peptides corresponding to the alpha-chain hypervariable regions of a mismatched donor HLA Class I molecule and the beta-chain hypervariable region of a mismatched donor HLA-DR molecule. The frequencies of HLA Class I and Class II alloreactive T cells were determined using limiting dilution analysis. RESULTS: A significant increase (p = 0.025) in HLA Class I-alloreactive T cells was observed in BOS-positive patients (7.1 x 10(-5) +/- 4.3 x 10(-5)) compared with BOS-negative patients (2.1 x 10(-5) +/- 1.8 x 10(-6)). In addition, a significant increase (p = 0.033) in HLA Class II-alloreactive T cells also was observed in BOS-positive patients (9.6 x 10(-5) +/- 7.9 x 10(-5)) compared with BOS-negative patients (1.3 x 10(-5) +/- 2.1 x 10(-6)). CONCLUSIONS: This study indicates that a parallel CD4+ T-cell alloreactivity to both donor HLA Class I and Class II molecules may play a role in the pathogenesis of BOS both in adult and pediatric lung transplant recipients.

Bronchiolitis Obliterans↗
PubMed2003

Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema.

OBJECTIVE: Numerous reports have confirmed the early benefits of lung volume reduction surgery for selected patients with emphysema. This report documents the long-term survival and functional results after lung volume reduction surgery. METHODS: Between January 1993 and June 2000, a total of 250 consecutive patients underwent bilateral lung volume reduction surgery through median sternotomy at our institution. All patients had disabling dyspnea, thoracic hyperinflation, and a heterogeneous pattern of emphysema with suitable target areas for resection. Preoperative pulmonary rehabilitation was required and post-rehabilitation data were used as the baseline for data analysis. Follow-up ranged from 1.8 to 9.1 years (median 4.4 years). RESULTS: Prolonged air leaks (>7 days) were the most common complication (45.2%, n = 113). Reexploration rates for air leak and bleeding were 3.2% (n = 8) and 1.2% (n = 3), respectively. Eighteen patients (7.2%) required reintubation and mechanical ventilation. The in-hospital mortality in this series was 4.8% (n = 12). The median length of hospitalization was 9 days (range 4-168 days). Kaplan-Meier survivals after lung volume reduction surgery were 93.6%, 84.4%, and 67.7% at 1, 3, and 5 years, respectively. Eighteen patients (7.2%) have subsequently undergone lung transplantation after a median interval of 4.3 years (range 2.1-6.4 years). Spirometric values, lung volumes, and gas exchange parameters improved after surgery. The forced expiratory volume in 1 second and the residual volume showed statistically significant improvements between preoperative values and each time point of follow-up. Health-related quality of life showed significant postoperative improvement and with time correlated well with the improvement in forced expiratory volume in 1 second. CONCLUSIONS: Lung volume reduction surgery produces significant functional improvement for selected patients with emphysema. For most of these patients, benefits appear to last at least 5 years.

Aged↗
PubMed2003

A prospective evaluation of lung volume reduction surgery in 200 consecutive patients.

OBJECTIVES: Though numerous studies have demonstrated the short-term efficacy of lung volume reduction surgery (LVRS) in select patients with emphysema, the longer-term follow-up studies are just being reported. The primary objectives of this study were to assess long-term health-related quality of life, satisfaction, physiologic status, and survival of patients following LVRS. DESIGN: We used a prospective cohort study design to assess the first 200 patients undergoing bilateral LVRS (from 1993 to 1998), with follow-up through the year 2000. Each patient served as his own control, initially receiving optimal medical management including exercise rehabilitation before undergoing surgery. Preoperative postrehabilitation data were used as the baseline for comparisons with postoperative data. The primary end points were the effects of LVRS on dyspnea (modified Medical Research Council dyspnea sale), general health-related quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]), patient satisfaction, and survival. The secondary end points were the effects of LVRS on pulmonary function, exercise capacity, and supplemental oxygen requirements. SETTING: A tertiary care urban university-based referral center. PATIENTS: Eligibility requirements for LVRS included disabling dyspnea due to marked airflow obstruction, thoracic hyperinflation, and heterogeneously distributed emphysema that provided target areas for resection. Patients were assessed at 6 months, 3 years, and 5 years after surgery. INTERVENTIONS: Preoperative pulmonary rehabilitation and bilateral stapling LVRS. MEASUREMENTS AND RESULTS: The 200 patients accrued 735 person-years (mean +/- SD, 3.7 +/- 1.6 years; median, 4.0 years) of follow-up. Over the three follow-up periods, an average of > 90% of evaluable patients completed testing. Six months, 3 years, and 5 years after surgery, dyspnea scores were improved in 81%, 52%, and 40% of patients, respectively. Dyspnea scores were the same or improved in 96% (6 months), 82% (3 years), and 74% (5 years) of patients. Improvements in SF-36 physical functioning were demonstrated in 93% (6 months), 78% (3 years), and 69% (5 years) of patients. Good-to-excellent satisfaction with the outcomes was reported by 96% (6 months), 89% (3 years), and 77% (5 years) of patients. The FEV(1) was improved in 92% (6 months), 72% (3 years), and 58% (5 years) of patients. Changes in dyspnea and general health-related quality-of-life scores, and patient satisfaction scores were all significantly correlated with changes in FEV(1). Following surgery, the median length of hospital stay in survivors was 9 days. The 90-day postoperative mortality was 4.5%. Annual Kaplan-Meier survival through 5 years after surgery was 93%, 88%, 83%, 74%, and 63%, respectively. During follow-up, 15 patients underwent subsequent lung transplantation. CONCLUSIONS: In stringently selected patients, LVRS resulted in substantial beneficial effects over and above those achieved with optimized medical therapy. The duration of improvement was at least 5 years in the majority of survivors.

Dyspnea↗
PubMed2002

Interleukin-6 and interferon-gamma gene polymorphisms in the development of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: A number of genetic polymorphisms have been shown to regulate the production and secretion of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, interferon (IFN)-gamma, interleukin (IL)-6, and IL-10. Several of these genetic polymorphisms have been shown to be associated with either acute or chronic rejection of kidney, liver, and heart allografts and with development of allograft fibrosis after lung transplantation. The aim of this study was to assess the effect of these genetic polymorphisms on the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. METHODS: Genetic polymorphisms were detected by means of polymerase chain reaction in 93 lung allograft recipients for functional polymorphisms in the TNF-alpha (-308), TGF-beta1 (+869 and +915), IL-6 (-174), IFN-gamma (+874), and IL-10 (-1082, -819, and -592) genes. Then, a correlation between BOS development and the presence of these cytokine genotypes was determined using Kaplan-Meier actuarial analysis. RESULTS: A significant correlation was detected between the presence of high-expression polymorphisms of the IL-6 and IFN-gamma genes and BOS development after lung transplantation (P =0.045 and 0.039, respectively). Also, patients with high-expression polymorphisms in both genes developed BOS significantly earlier than patients with low-expression polymorphisms in one or both genes, suggesting a synergistic effect of the alleles during BOS pathogenesis (P =0.016). No correlation was detected between polymorphisms of the TNF-alpha, TGF-beta1, and IL-10 genes and development of BOS after lung transplantation. CONCLUSIONS: The presence of high-expression polymorphisms at position -174 of the IL-6 gene and position +874 of the IFN-gamma gene significantly increases the risk for BOS development after lung transplantation.

Bronchiolitis Obliterans↗
PubMed2002

Different kinetics of obliterative airway disease development in heterotopic murine tracheal allografts induced by CD4+ and CD8+ T cells.

BACKGROUND: Both T and B cells have been shown to be implicated in the pathogenesis of bronchiolitis obliterans syndrome, which is considered to represent chronic lung allograft rejection. However, the relative contributions of T cells and alloantibodies in the pathogenesis of the disease are still unknown. In this study, we used an heterotopic murine tracheal transplantation model to determine the contribution of these components of the immune system in the pathogenesis of posttransplant obliterative airway disease (OAD). METHODS: Tracheal allografts from BALB/c and HLA-A2-transgenic (HLA-A2+) mice were heterotopically transplanted into C57BL/6, CD4-knockout (KO), CD8-KO, Ig-KO, and Rag1-KO mice. In additional experiments, recipient mice were pretreated with depleting antibodies against CD4+, CD8+, and NK1.1+ cells. Development of OAD was determined by histopathology at days 10, 30, 60, 90, and 180 after transplantation. RESULTS: HLA-A2+ allografts transplanted into C57BL/6, CD8-KO, and Ig-KO mice demonstrated OAD lesions by day 30. In contrast, allografts transplanted into CD4-KO mice showed no OAD lesions at day 30, partial OAD development by days 60 and 90, and complete OAD development by day 180. No OAD development was observed in allografts transplanted into Rag1-KO mice. Treatment with anti-NK1.1 antibody did not show any effect on posttransplant OAD development. In contrast, anti-CD4+ or anti-CD8+ antibody treatments partially reduced the OAD histopathology and combined anti-CD4/CD8 antibody treatment further abrogated the histopathology of the disease. CONCLUSION: These results show that both CD4+ and CD8+ T cells have a role in the pathogenesis of OAD and that natural killer cells and alloantibodies are not necessary for the development of this disease.

Animals↗
PubMed2002

Indirect recognition and antibody production against a single mismatched HLA-A2-transgenic molecule precede the development of obliterative airway disease in murine heterotopic tracheal allografts.

BACKGROUND: Previous studies have implicated the allogeneic immune response in the development of obliterative bronchiolitis after lung transplantation. However, the progression of specific pathogenic events leading to this form of chronic allograft dysfunction have not been well characterized. We used a murine tracheal transplantation model in which a single mismatched HLA-A2-transgenic molecule is indirectly recognized by the recipient CD4(+) T cells to show that obliterative airway disease (OAD) that developed in these allografts was preceded by indirect recognition of the HLA-A2 molecule and subsequent development of anti-HLA-A2 antibodies. METHODS: Tracheas from HLA-A2(+) C57BL/6 mice were heterotopically transplanted into C57BL/6 mice. Allograft histopathology as well as anti-HLA-A2 T-cell proliferative responses and anti-HLA-A2 antibody development were determined at days 5, 10, 20, and 28 after transplantation. RESULTS: All of the HLA-A2(+) tracheal allografts transplanted into C57BL/6 recipients demonstrated complete development of OAD by day 20. Spleen cells from the mice that underwent transplantation demonstrated significant proliferation against HLA-A2(+) cells by day 5. Indirect recognition of HLA-A2-derived peptides by spleen cells from allograft recipients was also higher on days 5 and 10 as compared with irrelevant peptides derived from HLA-A1, HLA-A3, and HLA-B44. Allograft recipients showed detectable levels of anti-HLA-A2 antibodies by day 5 and full development of anti-HLA-A2 antibodies by day 20. CONCLUSION: These results show that sensitization of CD4+ T cells against the mismatched HLA-A2 alloantigen precedes the development of anti-HLA antibodies as well as OAD, suggesting an important role for alloreactive CD4(+) T-cell activation and alloantibody development in the immunopathogenesis of OAD.

Animals↗
PubMed2002

Lung transplantation for pulmonary vascular disease.

BACKGROUND: Pulmonary hypertension (PHT) is a lethal condition resulting in markedly diminished life expectancy. Continuous prostaglandin I2 infusion has made an important contribution to symptom management, but it is not a panacea. Lung or heart-lung transplantation remains an important treatment option for end-stage PHT patients unresponsive to prostaglandin I2. This study reviews the outcomes after transplantation for PHT in our program. METHODS: A retrospective chart review was performed for 100 consecutive patients with either primary PHT (48%) or secondary PHT (52%) transplants since 1989. Living recipients were contacted to confirm health and functional status. RESULTS: Fifty-five adult and 45 pediatric patients underwent 51 bilateral lung transplants, 39 single lung transplants, and 10 heart-lung transplants. Mean age was 23.7 years (range, 1.2 months to 54.8 years) and mean pre-transplant New York Heart Association class was 3.2. Pre-transplant hemodynamics revealed a mean right atrial pressure of 9.6+/-5.4 mm Hg and mean pulmonary artery pressure of 64+/-14.4 mm Hg. Hospital mortality was 17% with early death predominantly because of graft failure and infection. With an average follow-up of 5.0 years, 1- and 5-year actuarial survival was 75% and 57%, respectively. Mean pulmonary artery pressure on follow-up catheterization was 22+/-6.0 mm Hg, and mean follow-up New York Heart Association class was 1.3 (p < 0.001 for both compared with pre-transplant). Diagnosis and type of transplant did not confer a significant difference in survival between groups. CONCLUSIONS: Whereas lung or heart-lung transplant for PHT is associated with higher early mortality than other pulmonary disease entities, it provides similar long-term outcomes with dramatic improvement in both quality of life and physiologic aspects.

Adolescent↗