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Biomedical subjects

Christine L Lau

Publications and source records attributed to Christine L Lau.

11 recordsLinked to original sources

Use of an apical heart suction device for exposure in lung transplantation.

Cardiopulmonary bypass is not necessary for the performance of bilateral sequential lung transplantation in most circumstances. Inadequate exposure to the left hilum is occasionally the sole indication for institution of cardiopulmonary bypass. We report the use of a suction heart positioning device to allow lifting of the heart for improvement of left hilar exposure. This technique has decreased the need for cardiopulmonary bypass when bypass is indicated due to difficult operative exposure.

Equipment Design↗

Mycotic pulmonary artery pseudoaneurysm.

We report a rare case of a mycotic pulmonary artery pseudoaneurysm that was detected on CT examination. The pulmonary artery pseudoaneurysm appeared as a rapidly growing enhancing mass without a draining vein and with evidence of surrounding acute hemorrhage on CT.

Adult↗

Laparoscopic Nissen fundoplication for treating reflux in lung transplant recipients.

Gastroesophageal reflux disease may contribute to pulmonary injury and the development of bronchiolitis obliterans syndrome in lung transplant patients. As a result, such individuals are increasingly likely to undergo corrective gastrointestinal surgery. The present study collected outcome data for 28 lung transplant patients with documented reflux who underwent an uncomplicated laparoscopic Nissen fundoplication at our institution. The results were compared to data from 63 nontransplant reflux patients who had undergone the procedure over the same time period. All Nissen fundoplications were conducted by the same surgeon. There were no intraoperative or perioperative deaths in either patient group. Operative parameters did not differ but the postoperative hospital stay was significantly greater for the lung transplant patients (P<0.05). Seven transplant patients (25%) were readmitted within 30 days compared to two readmissions (3.2%) in the reflux group. Five transplant patients (17.9%) have died, all from pulmonary complications; on average, death occurred 15.5 months after the Nissen surgery. There have been no deaths in the reflux group. These data indicate that laparoscopic Nissen fundoplication can be performed on lung transplant recipients to treat reflux. The average hospital stay is longer and there are more frequent readmissions in this population, but this does not appear to be due to any Nissen-related morbidity.

Adult↗

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↗

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↗

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↗

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↗

Molecular staging of lung and esophageal cancer.

In both esophageal and NSCLC, the TNM stage at diagnosis remains the most important determinant of survival. Significant research to investigate the biology of NSCLC and esophageal carcinoma is ongoing, and the roles of proto-oncogenes, tumor suppressor genes, angiogenic factors, extracellular matrix proteases, and adhesion molecules are being elucidated. While evidence is accumulating that various markers are involved in NSCLC and esophageal tumor virulence, the current studies are compromised by small sample sizes, heterogeneous populations, and variations in techniques. Large prospective studies with homogenous groups designed to evaluate the role of these various markers should clarify their potential involvement in NSCLC and esophageal cancer. Identification of occult micrometastases in lymph nodes and bone marrow using immunohistochemical techniques and rt-PCR is intriguing. These techniques are promising as a method to more accurately stage patients, and therefore to predict outcomes and to determine therapies. Perhaps the most promising area of research is the development of novel drugs whose mechanism of action targets the pathways of various molecular markers. Molecular biologic substaging offers an opportunity to individualize a chemotherapeutic regimen based on the molecular profile of the tumor, thus providing the potential for improved outcomes with less morbidity in patients with both NSCLC and esophageal cancer.

Carcinoma, Non-Small-Cell Lung↗

Non-anti-Gal alpha1-3Gal antibody mechanisms are sufficient to cause hyperacute lung dysfunction in pulmonary xenotransplantation.

BACKGROUND: Hyperacute lung dysfunction, which is always associated with pulmonary pig-to-primate xenotransplantation is not well understood. The mechanisms associated with its occurrence seem to differ from mechanisms involved in hyperacute xenograft rejection seen in porcine hearts or kidneys transplanted into primates. To determine the contribution of anti-Gal alpha1-3Gal antibodies (alphaGAb) in such a process, we performed a set of orthotopic pig lung transplants into baboons depleted of alphaGAb and compared graft function and survival with those receiving only immunosuppression. STUDY DESIGN: Pigs expressing human membrane cofactor protein served as donors. All baboons received triple immunosuppressive therapy. Depletion of alphaGAb in the experimental group (n = 4) was done by way of immunoadsorption using immunoaffinity membranes. Controls (n = 4) did not undergo immunoadsorption. Orthotopic lung transplants were performed through a left thoracotomy. Main pulmonary artery blood flow and pressure, left pulmonary artery blood flow, and left atrial pressure were recorded. RESULTS: At 1 hour after reperfusion, pulmonary artery graft flows and pulmonary vascular resistances (PVR) were better in animals depleted of alphaGAb than in controls (605 +/- 325.2 mL/min versus 230 +/- 21 mL/min; 27.1 +/- 41.3 mmHg/L/min versus 63 +/- 1 mmHg/L/min). But at 3 hours after reperfusion average graft flows in baboons depleted of alphaGAb had decreased to 277.6 +/- 302.2 mL/min and PVRs had increased 58.3 +/- 42.0 mmHg/L/min. On the other hand, controls maintained stable flows and PVRs (223 +/- 23 mL/min; 61 +/- 3 mmHg/L/min). Survival was ultimately better in control baboons when compared with alphaGAb depleted ones (12.2 +/- 3.3 h versus 4.4 +/- 3.2 h). CONCLUSION: Unlike heart and kidney xenograft transplants, hyperacute lung xenograft dysfunction seems to be mediated by factors other than alphaGAb.

Animals↗

Critical care aspects of lung transplantation.

Lung transplantation currently is the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has occurred through refinements in technique and improved understanding of transplant immunology and microbiology. As a result, recipients are surviving longer after their transplant. Despite improvements in short- and intermediate-term survival, long-term success with lung transplantation remains limited by chronic allograft rejection, also known as bronchiolitis obliterans syndrome. Despite its long-term limitations, lung transplantation remains the only hope for many with end-stage pulmonary disease, and during the past 20 years, it has become increasingly accepted and used. As a result, clinicians working in an intensive care unit (ICU) are more likely to be exposed to these patients both in the immediate postoperative period as well as throughout their remaining lives. It is thus important that the ICU team have a working knowledge of the common complications, when these complications are most likely to occur, and how best to treat them when they do arise. The main focus of this review is to address the variety of potential graft and life-threatening problems that may occur in lung transplant recipients. Because the ICU is also the most common setting where a potential donor is identified, donor issues will briefly be addressed.

Bronchiolitis Obliterans↗