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R Duane Davis

Publications and source records attributed to R Duane Davis.

52 records · Page 3Linked to original sources
PubMed2003

Clinical outcome after coronary artery revascularization and lung transplantation.

BACKGROUND: Presence of coronary artery disease (CAD) in otherwise eligible lung transplant candidates is considered a contraindication to lung transplantation. We reviewed the clinical outcome of our experience in lung transplant recipients with operable coronary artery disease and normal left ventricular function. METHODS: Medical records of all transplant recipients with coronary artery disease were reviewed. Data analyzed include demographics, coronary angiograms, coronary artery revascularization procedure, and clinical outcome after lung transplantation. RESULTS: Between April 1992 and August 2001, 354 lung transplant procedures were performed. Eighteen patients (5%) had significant CAD (greater than 50% stenoses). Six male patients (mean age 59 years) underwent percutaneous transluminal coronary angioplasty/stent and after lung transplantation all were discharged after a median hospital stay of 8.5 days. All recipients are alive at a median follow-up time of 14.5 months after their transplant. Twelve male patients (mean age 58 years) had combined coronary artery bypass grafting and lung transplantation. All recipients were discharged after a median hospital stay of 16 days. Nine recipients are alive at a median follow-up time of 7.5 months after transplant. One-year survival by the Kaplan-Meier method is 88% for the 18 patients with coronary artery disease who underwent revascularization and lung transplantation. CONCLUSIONS: Despite the traditional criteria of excluding all eligible transplant candidates due to coronary artery disease, coronary revascularization in select candidates with favorable anatomy and normal left ventricular function can allow patients to undergo lung transplantation with acceptable outcomes.

Adult↗
PubMed2003

Gastroesophageal reflux disease in lung transplant recipients.

BACKGROUND: Chronic allograft dysfunction after lung transplantation contributes to poor long-term survival. A link between gastric aspiration and post-transplant lung dysfunction has been suggested, but little is known about the significance of gastroesophageal reflux disease (GERD) after lung transplantation. METHODS: A retrospective study was performed to determine the prevalence of GERD in lung transplant recipients. Patients who underwent lung transplantation at Duke University, survived at least 6 months and had post-transplant 24-h pH studies were included in the analysis. Antireflux medications were discontinued prior to the pH study. Demographic data, pH study date and results, FEV1 at the time of the pH study, confirmed acute rejection episodes, and current medications were collected. The FEV1 ratio was calculated at the time of pH study (current FEV1/best post-transplant FEV1). RESULTS: Forty-three patients met entry criteria. Studies were performed at a median of 558 d post-transplant. Thirty of forty-three (69.8%) patients tested had abnormal total acid contact times (normal: <5%). The mean acid contact times for all patients were 10% total, 11.8% upright and 7.9% supine. A negative correlation was found between total or upright acid reflux and FEV1 ratio at the time of studies (-0.341 and -0.419; p = 0.025 and p = 0.005, respectively). The effect of acid reflux on FEV1 ratio remained significant after multivariable analysis. CONCLUSIONS: There is a high prevalence of GERD among selected lung transplant recipients who had pH studies performed and its presence is associated with worse pulmonary function. Future studies are needed to assess whether GERD contributes to the pathogenesis of bronchiolitis obliterans syndrome (BOS).

Environmental Monitoring↗
PubMed2003

The role of antibodies and von Willebrand factor in discordant pulmonary xenotransplantation.

Pulmonary xenotransplantation is one potential solution to the paucity of donors but is currently limited by rapid failure of the graft. Unlike cardiac and renal xenotransplants, pulmonary xenografts release large quantities of swine von Willebrand factor (vWF). Swine vWF binds xenoreactive antibodies and is capable of activating primate platelets. The contribution of swine vWF to lung xenograft dysfunction is not entirely clear. To probe the role vWF plays in xenograft dysfunction, we traced the fate of xenoantibodies in vWF+ and von Willebrand factor-deficient (vWFD) swine lungs. These studies showed that the vast majority of xenoantibodies bind the vWF released from the vWF+ swine lung, and thus do not remain bound on lung endothelium. The vWF complexed to xenoantibody remained capable of aggregating primate platelets. With this information, we performed swine-to-baboon lung transplants using vWF+ and vWFD donors. Without vWF present to complex xenoantibodies, a picture of hyperacute rejection more typical of heart and kidney xenografts, with antibody deposition along the graft endothelium, interstitial hemorrhage, and edema occurred. These findings suggest that porcine vWF plays a major role in the pathogenesis of pulmonary xenograft dysfunction, and suggests promising strategies to treat lung xenograft dysfunction.

Animals↗
PubMed2003

Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation.

OBJECTIVES: Bronchiolitis obliterans is the greatest limitation to the long-term applicability of lung transplantation. Although alloimmune events are important, nonimmune events, such as gastroesophageal reflux, might contribute to lung injury and the development of bronchiolitis obliterans syndrome. METHODS: We retrospectively studied the 396 patients who underwent lung transplantation at the Duke Lung Transplant Program from April 1992 to April 2002. Reflux was assessed for using an ambulatory 24-hour esophageal pH probe. RESULTS: Reflux assessment with an esophageal pH probe was obtained in 128 patients after lung transplantation. Abnormal pH study results were present in 93 (73%) patients. Forty-three patients underwent a surgical fundoplication. There was no in-hospital or 30-day mortality in the patients undergoing fundoplication. At the time of fundoplication, 26 patients met the criteria for bronchiolitis obliterans syndrome. After fundoplication, 16 patients had improved bronchiolitis obliterans syndrome scores, with 13 of these patients no longer meeting the criteria for bronchiolitis obliterans syndrome. In patients at least 6 months after lung transplantation and 6 months after fundoplication, the forced expiratory volume in 1 second improved by an average of 24% (mean forced expiratory volume in 1 second before fundoplication, 1.87 L; mean forced expiratory volume in 1 second after fundoplication, 2.19 L/sec; P <.0002). Overall actuarial survival was significantly better in patients who had either normal pH studies or who had fundoplication. CONCLUSIONS: Gastroesophageal reflux disease is very common after lung transplantation and appears to contribute to mortality and development of bronchiolitis obliterans syndrome. Fundoplication in lung transplant recipients with gastroesophageal reflux disease is associated with significant improvements in lung function, particularly if performed before the late stages of bronchiolitis obliterans syndrome.

Actuarial Analysis↗
PubMed2003

Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients.

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) is a relatively infrequent but devastating complication that occurs after solid-organ transplantation. Although the optimal treatment for this condition is unknown, rituximab, a murine/human chimeric monoclonal antibody, has shown promise in the treatment of PTLD. In this report, we define the incidence, clinical features at presentation, and response to treatment of all cases of PTLD observed at our institution over a 10-year period, including four patients who received treatment with rituximab. METHODS: A review of all patients who underwent lung or heart-lung transplant at Duke University from 1992 to 2002 was performed (n = 400), and demographic and clinical outcome data were extracted. RESULTS: PTLD was observed in 10 of 400 patients (2.5%). Patients who acquired PTLD were predominantly > 55 years old (8 of 10 patients) and with a native disease of COPD (7 of 10 patients). Diagnosis of PTLD was made a median of 343 days after transplant. The type of transplant and Epstein-Barr virus (EBV) status prior to transplant did not appear to influence the risk for PTLD. Patients presented with thoracic organ involvement (7 of 10 patients), extrapulmonary disease (2 of 10 patients), or both (1 of 10 patients). Histologic subtypes included polymorphic B cell (n = 4), monomorphic B cell (n = 3), B cell without further classification (n = 2), and anaplastic T cell (n = 1). Only one patient responded to reduced immunosuppression alone. Patients treated with surgery or radiation (n = 2) or rituximab (n = 4) had favorable responses to therapy. Both patients treated with chemotherapy died related to complications of treatment and PTLD. CONCLUSIONS: Presentation and histologic appearance of PTLD varies considerably among lung transplant recipients. PTLD was more frequent among older patients with COPD, regardless of pretransplant EBV serology. Rituximab appears effective as a first-line therapy for PTLD, but additional studies are needed in order to define its efficacy and side effect profile in this population of patients.

Adolescent↗
PubMed2003

Psychiatric disorder and quality of life in patients awaiting lung transplantation.

STUDY OBJECTIVE: To examine the relationship between psychiatric comorbidity and quality of life in patients awaiting lung transplantation. SETTING: Duke University Medical Center/Lung Transplantation Program. PARTICIPANTS: One hundred patients with end-stage pulmonary disease listed for lung transplantation. MEASUREMENTS AND RESULTS: Twenty-five percent (n = 25) of the sample met diagnostic criteria for at least one current mood or anxiety disorder. Controlling for age, gender, ethnicity, percentage of predicted FEV, and lung disease diagnosis, patients with a current psychiatric diagnosis reported poorer general quality of life (p < 0.0001), poorer disease-specific quality of life (p < 0.0001), greater shortness of breath (p = 0.01), more symptoms of psychological distress (p < 0.0001), lower levels of social support (p < 0.0001), and fewer positive health habits (p < 0.04) than their counterparts without a psychiatric diagnosis. CONCLUSIONS: Psychiatric comorbidity affects a significant portion of patients awaiting lung transplantation and is associated with decreased health-related quality of life.

Anxiety Disorders↗
PubMed2003

Lung transplantation exacerbates gastroesophageal reflux disease.

INTRODUCTION: A high prevalence of gastroesophageal reflux (GER) has been reported in lung transplant recipients and is possibly linked to the development of bronchiolitis obliterans syndrome. The etiology of posttransplant GER remains unknown but may occur due to the transplant operation or posttransplant medications, or represent preexisting GER disease. We evaluated these possibilities by studying the nature and severity of GER in a cohort of patients before and after lung transplantation. METHODS: Total, upright, and supine acid contact times were recorded in lung transplant recipients who underwent 24-h pH studies before and after transplantation. Patients also underwent esophageal manometry and gastric-emptying studies. Medications for acid suppression and gastric motility were discontinued before testing. Paired comparison between pretransplant and posttransplant results was performed using a paired t test. RESULTS: Twenty-three patients were included in the analysis. The mean age was 51.5 years, and native diseases included emphysema (n = 11), cystic fibrosis (n = 4), pulmonary fibrosis (n = 3), and others (n = 5). Posttransplant studies occurred a median of 100 days after transplantation. After lung transplantation, the total acid contact time increased a mean of 3.7% (p = 0.03) and the supine acid contact time increased a mean of 6.4% (p = 0.019). Thirty-five percent (8 of 23 patients) had abnormal acid contact times before transplant, and 65% (15 of 23 patients) had abnormal acid contact after transplant. Changes in acid contact times were not explained by changes in esophageal or gastric motility. Only 20% (3 of 15 patients) with abnormal posttransplant pH studies were symptomatic. CONCLUSIONS: There is a significant increase in GER after lung transplantation, as measured objectively by 24-h pH studies, despite a lack of symptoms in most patients. Further research is needed to determine the physiologic mechanisms of posttransplant GER and its impact on long-term allograft function.

Esophagus↗
PubMed2002

The role of the porcine von Willebrand factor: baboon platelet interactions in pulmonary xenotransplantation.

BACKGROUND: Porcine von Willebrand factor (pvWF) has been shown to bind to human glycoprotein Ib (GPIb) and cause activation of human (or primate) platelets in the absence of shear stress. Pulmonary xenografts develop disseminated intravascular coagulation (DIC) and microvascular thrombosis within hours of reperfusion, and the aberrant interaction between pvWF and human platelets may be a possible cause of xenograft-associated DIC. METHODS: Experimental baboons (n=3) received mouse anti-human GPIb monoclonal antibody before undergoing orthotopic pulmonary xenotransplantation with porcine lungs expressing human membrane cofactor protein (CD46). RESULTS: Blocking the pvWF-GPIb interaction with a monoclonal antibody to GPIb prevented the agglutination of human and baboon platelets by pvWF in vitro. In vivo, the anti-GPIb antibody prevented platelet deposition and prevented the increases in D-Dimers (P=0.011) seen in control xenograft recipients (n=5). However, there was no difference in elevations of prothrombin times (PT) or improvement in the vasoconstriction associated with the loss of xenograft function. CONCLUSIONS: This study indicates that the DIC associated with the hyperacute dysfunction of pulmonary xenografts is a complex phenomenon that is affected by, but not solely dependent on, activation of platelets. Aberrant interactions between pvWF and GPIb play a significant role in DIC associated with pulmonary xenotransplantation.

Animals↗
PubMed2002

Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome.

BACKGROUND: Chronic allograft rejection manifested as bronchiolitis obliterans syndrome (BOS) is the leading cause of late death after lung transplantation. Although increasing evidence suggests an association between anti-human leukocyte antigens (HLA) antibodies and chronic rejection of kidney or heart allografts, the clinical significance of anti-HLA antibodies in lung recipients is less clear, especially in previously unsensitized recipients. The use of flow cytometry based panel reactive antibody (flow-PRA) provides a highly sensitive means to identify the development of de novo anti-HLA antibodies in lung recipients. METHODS: Flow-PRA testing was used to analyze the pre- and posttransplant sera in stable BOS free lung recipients who survived at least 6 months. Patients without prior sensitization as defined by a negative pretransplant flow-PRA were analyzed posttransplant for the presence of anti-HLA antibodies by flow-PRA. A proportional hazards model was used to determine the impact of anti-HLA antibody on BOS risk. RESULTS: Sera from 90 recipients at Duke University with negative pretransplant flow-PRA were tested by flow-PRA at various time points after transplant. Sera from 11% (10/90) of recipients were found to contain anti-HLA antibodies detectable by flow-PRA. Nine patients (90%) developed anti-HLA antibodies specific for donor antigens, and one patient developed anti-HLA class II antibodies, not specific to donor antigens. Among the nine patients with donor antigen specific antibodies, flow-PRA specificity analysis demonstrated eight were specific for class II antigens and one for class I antigens. In a multivariate model that controls for other BOS risk factors, a positive posttransplant flow-PRA was significantly associated with BOS grades 1,2, or 3 (hazard ratios [HR] 3.19; 95% confidence interval [CI]: 1.41-7.12, P=0.005) and BOS grade 2 or 3 (HR 4.08; 95% CI: 1.66-10.04, P=0.002). Four patients with de novo anti-HLA antibodies died during follow-up; all four had BOS. Among BOS patients, the presence of anti-HLA antibodies was associated with a significantly worse survival (P =0.05, log-rank test). CONCLUSIONS: Although uncommon, previously unsensitized lung transplant recipients can develop anti-HLA antibodies to donor class II antigens. The development of de novo anti-HLA antibodies significantly increases the risk for BOS, independent of other posttransplant events. Furthermore, de novo anti-HLA antibodies identify BOS patients with significantly worse survival. Additional studies are needed to determine if class II-directed anti-HLA antibodies contribute mechanistically to the chronic rejection process in lung recipients.

Adult↗
PubMed2002

Disseminated intravascular coagulation in association with pig-to-primate pulmonary xenotransplantation.

BACKGROUND: Profound coagulopathy has been proposed as a barrier to xenotransplantation. Disseminated intravascular coagulation (DIC) has been observed with the rejection of renal and bone marrow xenografts but has not yet been described in pulmonary xenografts. METHODS: This study examined the coagulation parameters in five baboons that received pulmonary xenografts and one baboon that was exposed to porcine lung during an extracorporeal perfusion. Platelet counts, prothrombin times (PT), and levels of fibrinogen, D-dimers, and thrombin-antithrombin III complex (TAT) were analyzed. In addition, serum levels of plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), tissue plasminogen activator (tPA), and tissue factor (TF) were determined. RESULTS: Hyperacute pulmonary xenograft dysfunction, which occurred within 0-9 hr of graft reperfusion, was associated with clinically evident DIC. This coagulopathy was characterized by thrombocytopenia, decreased fibrinogen levels, elevations in PT, and increases in D-dimers and TAT. Furthermore, transient increases in PAI-1, increases in TM, and increases in tPA were observed in the serum of some but not all recipients. None of the baboons demonstrated measurable increases in soluble TF. CONCLUSIONS: Although DIC in renal or bone marrow xenotransplantation develops over a period of days, DIC associated with hyperacute pulmonary xenograft dysfunction develops within hours of graft reperfusion. Thus, the DIC in pulmonary xenotransplantation may represent a unique and/or accelerated version of the coagulopathy observed with renal and bone marrow xenotransplantation.

Animals↗
PubMed2002

Mitral surgery after prior cardiac operation: port-access versus sternotomy or thoracotomy.

BACKGROUND: In reoperation for mitral valve disease, minimally invasive Port-Access (PORT) is a new alternative to standard median sternotomy (STER) or right thoracotomy (THOR); yet, the results of PORT in this setting have not been defined. The aim of this study was to evaluate the results of minimally invasive thoracotomy in reoperation for mitral valve disease. METHODS: Retrospective results are reported for three consecutive series of patients undergoing reoperation for mitral disease using either PORT (n = 60, 1996 to 2001), THOR (n = 37, 1985 to 1997), or STER (n = 155, 1985 to 1997). RESULTS: Red cell transfusion was 3 +/- 4, 14 +/- 13, and 12 +/- 12 units for PORT, THOR, and STER, respectively. Chest tube output was 352 +/- 361, 2048 +/- 3166, and 1683 +/- 3939 mL, respectively. Cardiopulmonary bypass times for these groups were 208 +/- 76 vs. 158 +/- 56 vs. 157 +/- 53 minutes. Thirty-day mortality was 0/60 (0%), 8/37 (22%), and 21/155 (14%), respectively. CONCLUSIONS: This early clinical experience suggests that PORT is an acceptable alternative to THOR or STERN in reoperation for mitral valve disease, with potential advantages of avoiding redo sternotomy and reducing the surgical incision. However, these benefits may come at the expense of longer cardiopulmonary bypass times.

Cardiac Surgical Procedures↗
PubMed2002

Binding of polyreactive antibodies to self versus foreign antigens.

Aside from their ability to bind to multiple antigens, the classic hallmark of polyreactive antibodies is their autoreactivity. Because of their ability to bind a number of common autoantigens, it has long been speculated that polyreactive antibodies are involved in the clearance of self-antigens. However, it has been demonstrated more recently that polyreactive antibodies are also capable of binding to some foreign and synthetic antigens. Although data regarding the relative reactivity of polyreactive antibodies with self versus foreign antigens is lacking, it is generally thought that both activities may play an important biological role. In this study, the relative reactivity of polyclonal human polyreactive IgM with human proteins and tissue extracts versus foreign (xenogeneic) proteins and tissue extracts was probed. The binding of affinity purified anti-ssDNA IgM from adult human serum and the binding of polyreactive IgM in human cord serum and in human adult serum were evaluated. Using competitive and direct binding assays, human polyreactive IgM were found to be generally more reactive with foreign (xenogeneic) proteins than with self or allogeneic proteins. These data shed light on the fundamental nature of polyreactive antibodies, and may provide additional insight into their putative biological roles.

Animals↗
PubMed2002

Outcome of lung transplantation in patients with mycetomas.

BACKGROUND: Lung transplantation has become an acceptable treatment option for many end-stage lung diseases. Pulmonary mycetomas are found in patients with end-stage lung diseases, especially sarcoidosis. The clinical course and long-term outcome of these patients after transplantation remains unknown. METHODS: We reviewed retrospectively the pathology reports of the explanted lungs from all lung and heart-lung transplantations performed at our institution between January 20, 1992, and June 26, 2000. Patients were included in our study if mycetomas were present on the specimens. Information on transplant date and type, diagnosis, information on antifungal therapy and fungal infections pretransplant and posttransplant, and clinical course after transplantation was recorded. RESULTS: Mycetomas were present in 3.0% of transplant recipients (9 of 303 patients). The underlying pulmonary diagnoses were sarcoidosis (six patients), and emphysema, idiopathic pulmonary fibrosis, and pneumoconiosis (one patient each). Seven patients received bilateral lung transplants, one patient received a heart/lung transplant, and one patient received a single lung transplant. Aspergillus was isolated from culture in five patients pretransplant and from five patients posttransplant. Six patients received treatment with itraconazole, or IV or inhaled amphotericin B prior to transplantation. All patients who survived transplantation received posttransplant antifungal therapy. Four patients died in the first month after transplantation. Two patients died at 17 months and 24 months posttransplant, respectively; one patient received a second transplant 30 months later; and two patients are alive and free from fungal infections 17 months and 18 months, respectively, after transplantation. All of the medium-term survivors received lengthy therapy with inhaled and systemic amphotericin B and itraconazole before and after transplantation. CONCLUSIONS: Lung transplant recipients with mycetomas have significantly reduced posttransplant survival. Careful selection of patients and aggressive antifungal therapies before and after transplantation have led to improved outcomes in patients with mycetomas. Additional research is needed to define the best therapeutic strategy for these patients during transplantation.

Adult↗
PubMed2002

Effects of a telephone-based psychosocial intervention for patients awaiting lung transplantation.

STUDY OBJECTIVES: To test the efficacy of a tailored telephone-based intervention consisting of supportive counseling and cognitive behavioral techniques for individuals awaiting lung transplantation on measures of quality of life and general well-being. METHOD: Patients were randomly assigned to either a telephone-based special intervention (SI; n = 36) for 8 weeks (average session length, 16.3 min) or a usual care (UC) control condition (n = 35) in which subjects received usual medical care but no special treatment or phone calls. At baseline, and immediately following the 8-week intervention, patients completed a psychometric test battery. SETTING: Duke University Medical Center, Pulmonary Transplantation Program. PATIENTS: Seventy-one patients with end-stage pulmonary disease listed for lung transplantation. PRIMARY OUTCOME MEASURES: Measures of health-related quality of life (both general and disease-specific), general psychological well-being, and social support. RESULTS: Multivariate analysis of covariance, adjusting for pretreatment baseline scores, age, gender, and time waiting on the transplant list, revealed that patients in the SI condition compared to the UC reported greater general well-being (p < 0.05), better general quality of life (p < 0.01), better disease-specific quality of life (p < 0.05), and higher levels of social support (p < 0.0001). CONCLUSION: A brief, relatively inexpensive, telephone-based psychosocial intervention is an effective method for reducing distress and increasing health-related quality of life in patients awaiting lung transplantation.

Counseling↗
PubMedDate not supplied

Gas exchange and exercise capacity affect neurocognitive performance in patients with lung disease.

OBJECTIVE: This study examined the relationship between cognitive functioning and the severity of underlying lung disease in patients awaiting lung transplantation. METHODS: Ninety-four patients with end-stage lung disease completed a test battery to assess cognitive performance in two domains: executive functioning/attention (Trails A and B, COWA, Animal Naming, Stroop Color-Word Test, Digit Symbol, and the 2 & 7 Test) and verbal memory (Digit Span-Backward and Forward, WMS-R Logical Memory and Paired Verbal Associates). RESULTS: Thirty-seven percent of the patients demonstrated moderate to severe cognitive impairment data on two or more tests. Adjusting for age and education, there were no statistically significant differences on executive functioning or verbal memory as a function of specific lung disease diagnosis. Lower PCO2 values were associated with better cognitive performance on latent measures of executive functioning and attention (p = .006) and verbal memory (p = .009), whereas higher PO2 values tended to be associated with better performance on the executive functioning/attention measure (p = .064). Distance walked in 6 minutes was positively related to verbal memory (p < .023). CONCLUSIONS: Impaired neurocognitive functioning may be relatively common in patients awaiting lung transplantation and is associated with ineffective pulmonary gas exchange and reduced exercise tolerance.

Adult↗