PubMed Health⌕ Search

Biomedical subjects

C L Lau

Publications and source records attributed to C L Lau.

At least 19 recordsLinked to original sources
PubMed2003

Current status of lung transplantation.

Two decades have passed since the first successful clinical lung transplant was performed in 1983, and, in the interim, lung transplantation has become the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has been made in the field through refinement of technique and improved understanding of transplant immunology and microbiology. Unfortunately, donor shortages continue to limit the more widespread application of lung transplantation. In order to address this issue, marginal donors, living lobar and split lung donor techniques, and nonheartbeating donors have been used clinically to increase the number of donor lungs available. Chronic rejection of the lung allograft is currently the major hurdle limiting longterm survival. To date, prevention of known risk factors and treatment strategies have not lessened the devastating toll this process has on lung transplant survival. Better understanding of the cause of chronic rejection is needed in order to develop novel strategies for its treatment. Promotion of immune tolerance is a promising area that could potentially eliminate chronic rejection. The present article discusses recent advances in lung transplantation. It also details the major issues facing the field today. Only through continued clinical and experimental investigation will lung transplantation eventually reach its full potential.

Bronchiolitis Obliterans↗
PubMed2002

Laparoscopic antireflux surgery in the lung transplant population.

BACKGROUND: Lung transplantation has emerged as a viable therapeutic option for patients with a variety of end-stage pulmonary diseases. As immediate posttransplant surgical outcomes have improved, the greatest limitation of lung transplantation remains chronic allograft dysfunction. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in allograft dysfunction. GERD is prevalent in end-stage lung disease patients, and it is even more common in patients after transplantation. We report here on the safety of laparoscopic fundoplication surgery for the treatment of GERD in lung transplant patients. METHODS: Eighteen of the 298 lung transplants performed at Duke University Medical Center underwent antireflux surgery for documented severe GERD. The safety and benefit of laparoscopic fundoplications in this population was evaluated. RESULTS: The antireflux surgeries included 13 laparoscopic Nissen fundoplications, four laparoscopic Toupets, and one open Nissen (converted secondary to extensive adhesions). Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). There were no deaths from the antireflux surgery. After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). CONCLUSIONS: GERD occurs commonly in the posttransplant lung population. Laparoscopic fundoplication surgery, when indicated, can be done safely with minimal morbidity and mortality. In addition to the resolution of reflux symptoms, improvement in pulmonary function may be seen in this population after fundoplication. Lung transplant patients with severe GERD should be strongly considered for antireflux surgery.

Adolescent↗
PubMed2002

Effects of pneumoperitoneum on hemodynamic and systemic immunologic responses to peritonitis in pigs.

BACKGROUND: Experimental evidence supporting the safety of laparoscopic intervention during sepsis is limited. The purpose of this study was to evaluate the effects of pneumoperitoneum on immunologic and hemodynamic responses to peritoneal sepsis. MATERIALS AND METHODS: A porcine model of peritonitis was created using an intraperitoneal autologous fecal inoculum. Pigs were then subjected to one of four procedures 24 h postinoculation (n = 6 per group): laparotomy, CO(2) laparoscopy, helium laparoscopy, and anesthesia only (1.5% isoflurane in 100% O(2), mechanical ventilation). Venous blood samples were obtained prior to inoculation, and at 24 (prior to procedure), 30, 48, 72, and 96 h postinoculation to determine white blood count (WBC) with differential, C-reactive protein (CRP), tumor necrosis factor, and bacteremia. Heart rate, end-tidal CO(2) (ETCO(2)), mean arterial blood pressure (MAP), and arterial blood gas variables were also measured at baseline and every 30 min throughout the procedure. RESULTS: Postoperative blood cultures confirmed systemic bacteremia in all groups at all time periods postinoculation. Following inoculation, WBC, band cell count, and CRP remained elevated above baseline in all groups throughout the study (P < 0.01). However, no significant differences in these parameters were observed among groups. In the CO(2) laparoscopy group, MAP, ETCO(2), and arterial pCO(2) were increased above baseline, while pH was decreased throughout the procedure (P < 0.01). CONCLUSIONS: In this animal model of peritonitis, CO(2) pneumoperitoneum induced hypercapnia, acidemia, and systemic hypertension intraoperatively, without a discernable effect on systemic immune function.

Acidosis↗
PubMed2001

Immune complex formation after xenotransplantation : evidence of type III as well as type II immune reactions provide clues to pathophysiology.

Rejection of renal and cardiac xenografts is initiated when natural antibodies of the recipient bind to donor endothelium, activating complement on the surface of endothelial cells. Pulmonary xenotransplants, however, reveal less evidence of antibody binding and complement activation and, in contrast to other xenografts, fare worse when the complement of the graft recipient is depleted. Accordingly, we asked whether distinct immunochemical reactions might occur after xenotransplantation of the lung and what implications such reactions might have for pulmonary pathophysiology. Analysis of serum from baboons after transplantation with porcine lungs revealed complexes containing baboon IgM and porcine von Willebrand factor. The baboon IgM in these complexes was specific for Galalpha1-3Gal. Immune complexes were also seen, albeit to a lesser extent, in the serum of kidney and heart xenotransplant recipients. Deposits of porcine von Willebrand factor and baboon C3 were detected in livers and spleens of transplanted baboons. These results indicate pulmonary xenotransplantation eventuates in formation of immune complexes and in the deposition of those complexes at distant sites. Immune complex formation could explain the peculiar fate of xenoreactive antibodies after pulmonary xenotransplantation and might contribute to the pathophysiology of the lung and systemic changes not previously considered a complication of xenotransplantation.

Animals↗
PubMed2000

The role of anti-Galalpha1-3Gal antibodies in acute vascular rejection and accommodation of xenografts.

BACKGROUND: A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute vascular rejection, which can destroy a vascularized xenograft over a period of hours to days. Acute vascular rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Galalpha1-3Gal epitopes in porcine tissue, initiate this phenomenon. METHODS AND RESULTS: Specific depletion of anti-Galalpha1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide, Galalpha1-3Galbeta1-4GlcAc, averted the development of acute vascular rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Gala1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation. CONCLUSION: These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

Acute Disease↗
PubMed2000

Noninvasive clinical staging modalities for lung cancer.

Clinical staging of lung cancer helps to determine the extent of disease and stratify patients into similar therapeutic and prognostic categories. A primary goal of clinical staging is to separate patients with potentially resectable disease from those that are unresectable. Initial assessment of the patient by history and physical examination combined with laboratory values can suggest metastatic spread of the disease. When abnormal, these clinical factors may have value in terms of predicting prognosis, but their use in early stage lung cancer is limited because of the low prevalence of symptoms, physical exam findings, and laboratory abnormalities in this group. For clinical staging, patients almost always undergo a postero-anterior and lateral chest radiograph and a computed tomography (CT) scan of the chest and upper abdomen to include the liver and adrenal glands. Although CT scanning provides exquisite anatomic information, it is less than optimal for determining lymph node status. Over the last several years, CT scanning combined with positron-emission tomography (PET) using fluorodeoxyglucose (FDG) has significantly improved the accuracy of clinical staging. The use of FDG-PET continues to be defined in the non-invasive evaluation of the primary tumor, nodal involvement, and metastatic disease. Despite the recent advancements in radiologic assessment of lung cancer, invasive sampling is still often performed for pathologic confirmation.

Diagnostic Imaging↗
PubMed2000

Influence of panel-reactive antibodies on posttransplant outcomes in lung transplant recipients.

BACKGROUND: Panel-reactive antibody (PRA) is used to estimate the degree of humoral sensitization in the recipient before transplantation. Although pretransplant sensitization is associated with increased complications in other solid organ transplant recipients, less is known about the outcome of sensitized lung transplant recipients. Therefore, we sought to determine the impact of elevated pretransplant PRA on clinical outcomes after lung transplantation. METHODS: The records of the first 200 lung transplant operations performed at Duke University Medical Center were reviewed. The outcomes of sensitized patients, PRA greater than 10% before transplantation (n = 18), were compared with the outcomes of nonsensitized patients. RESULTS: Sensitized patients experienced a significantly greater number of median ventilator days posttransplant (9 +/- 8) as compared with nonsensitized recipients (1 +/- 11; p = 0.0008). There were no significant differences between the number of episodes of acute rejection; however, there was a significantly increased incidence of bronchiolitis obliterans syndrome occurring in untreated sensitized recipients (56%) versus nonsensitized (23%; p = 0.044). In addition, there was a trend towards decreased survival in the sensitized recipients, with a 2-year survival of 58% in sensitized recipients as compared with 73% in the nonsensitized patients (p = 0.31). CONCLUSIONS: Sensitized lung transplant recipients experience more acute and chronic complications after transplantation. These patients probably warrant alternative management strategies.

Adolescent↗
PubMed2000

Molecular biologic substaging of stage I lung cancer according to gender and histology.

BACKGROUND: This study is designed to assess molecular biologic substaging according to gender and histology in patients with stage I non-small cell lung cancer (NSCLC). METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I NSCLC, with follow-up of at least 5 years. A panel of nine molecular markers was chosen for immunohistochemical analysis of the tumor: recessive oncogenes p53 and bcl-2, the protooncogene erbB-2, KI-67 proliferation index, retinoblastoma oncogene (Rb), epidermal growth factor receptor (EGFr), angiogenesis factor viii, sialyl-Tn antigen (STN), and CD-44. Cox proportional hazards regression analysis was used to construct a risk model for cancer-specific survival according to marker status, gender, and histologic subtype. RESULTS: Among men, the only molecular marker associated with decreased cancer-specific survival is erbB-2; among women, there are four markers: p53, Rb, CD-44, and factor viii. Among patients with squamous cell carcinoma, the only molecular marker associated with decreased cancer-specific survival is erbB-2; among patients with adenocarcinoma (AC), there are three markers: p53, CD-44, and factor viii. Multivariable analysis of interactions among molecular markers, gender, and histology demonstrates two important relationships (hazard ratio): p53+/women (2.269) and CD-44+/AC (2.266). CONCLUSIONS: Molecular biologic substaging of patients with stage I NSCLC demonstrates differential cancer-specific survival according to marker expression, gender, and histologic subtype.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants.

OBJECTIVE: Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model. METHODS: Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons. RESULTS: All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons. CONCLUSIONS: The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental.

Animals↗
PubMed2000

Staging techniques for lung cancer.

In summary, noninvasive clinical staging techniques aid in stratifying patients into similar prognostic and therapeutic categories. Every patient with presumed non-small cell lung cancer should undergo a thorough history and physical examination, basic routine laboratory testing, PA and lateral chest radiographs, and chest CT scan with upper abdominal cuts to allow evaluation of the liver and adrenals. Recently, FDG-PET scanning has shown tremendous promise in the noninvasive evaluation of the primary tumor, nodal involvement, and metastatic [table: see text] disease. Although valuable, clinical staging has limitations, and when pathologic confirmation of lung cancer is required, minimally invasive techniques, such as bronchoscopy, TTNA, thoracoscopy, anterior mediastinotomy, and cervical and extended mediastinoscopy, may be valuable and simple ways of obtaining tissue.

Adenocarcinoma↗
PubMed1999

Human complement regulatory proteins protect swine lungs from xenogeneic injury.

BACKGROUND: Pulmonary xenotransplantation is not possible because of hyperacute lung injury, the pathogenesis of which is unknown. This study evaluates complement-dependent pathways of pulmonary injury during heterologous perfusion of swine lungs. METHODS: Lungs from unmodified swine and swine expressing human decay-accelerating factor and human CD59 (hDAF/hCD59 swine) were perfused with either human plasma or baboon blood. Pulmonary vascular resistance and static pulmonary compliance were measured serially, and swine lung tissue were examined by light microscopy. Complement activation was assessed by serial measurements of baboon plasma C3a-desArg concentrations. RESULTS: Perfusion of unmodified swine lungs with human plasma and baboon blood resulted in hyperacute lung injury within minutes of perfusion. However, function was preserved in swine lungs expressing human decay-accelerating factor and human CD59. In both study groups, xenogeneic perfusion with baboon blood resulted in at least a sevenfold increase in plasma C3a-desArg levels suggesting transient activation of complement. CONCLUSIONS: Lungs from swine expressing human decay-accelerating factor and human CD59 were resistant to injury during perfusion with human plasma and baboon blood, indicating that complement mediated some of the features of xenogeneic acute lung injury.

Animals↗
PubMed1999

Malignant melanoma presenting as a mediastinal mass.

A case of malignant melanoma presenting as a mediastinal mass without an extrathoracic primary is reported. Microscopically the tumor appeared consistent with malignant melanoma, with the presence of focal melanin pigment in large epithelioid cells. Fontana stain confirmed the presence of melanin pigment. Immunohistochemical staining further suggested melanoma, with the tumor cells expressing a HMB45+, S100+ and cytokeratin-phenotype. Electron microscopy showed an abundance of melanosomes confirming the diagnosis of malignant melanoma.

Aged↗
PubMed1999

Mini-circuit cardiopulmonary bypass with vacuum assisted venous drainage: feasibility of an asanguineous prime in the neonate.

Conventional cardiopulmonary bypass (CPB) in neonates results in increased transfusion requirements and hemodilution. There has been little advancement in CPB for the neonatal population. There is evidence that increased priming volumes and blood product transfusion enhances inflammatory response to CPB and increases myocardial and pulmonary dysfunction. We have devised a miniaturized CPB circuit that utilizes vacuum-assisted venous drainage (VAVD) in an effort to decrease priming volume and avoid transfusion requirements. The purpose of this study was to evaluate the safety and efficacy of this miniaturized CPB system and determine the feasibility of an asanguineous prime. Ten 1-week-old piglets were randomized to five mini- and five conventional CPB pump circuits. Subjects were supported with CPB at 100 ml/kg/min, cooled to 28 degrees C, exposed to 10 min aortic crossclamp with cardioplegic arrest, rewarmed to 37 degrees C, weaned from bypass, and subjected to modified-ultrafiltration (MUF) for approximately 10 min. This method was chosen to simulate a situation with all the elements of clinical CPB. Blood transfusion trigger was a hematocrit <15 on CPB. Serum samples were obtained pre-CPB, at 15 min of CPB onset, immediately post-CPB completion, and immediately post-MUF. Indices of hemolysis (SGOT, LDH), production of inflammatory mediators (interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha)), and physiologic parameters of inflammation were measured. The overall blood requirement was significantly less in the mini-circuit compared to conventional CPB (47.0+/-5.8 ml vs 314.2+/-31.6 ml; p < 0.0001). The only significant blood requirement in the mini-circuit was to replace the volume removed for samples. During the study, mean arterial pressure (MAP) (p = 0.004), static pulmonary compliance (p = 0.04), platelets (p = 0.0003), and white blood cells (p = 0.003) significantly decreased across the groups. Lung water content (p = 0.02), TNFalpha levels (p = 0.05), and SGOT (p = 0.009) increased significantly during the study, across the groups. Among all parameters tested, except for blood requirement and hematocrit post-CPB, there were no significant differences between the two circuits. VAVD makes asanguineous prime in neonates feasible. When used in this study to miniaturize a conventional-CPB circuit, VAVD with a reconfigured neonatal CPB console and circuit resulted in no detrimental effects, and allowed for markedly decreased priming volumes and blood transfusion requirements.

Animals↗
PubMed1999

Peptide growth factors in amphibian embryogenesis: intersection of modern molecular approaches with traditional inductive interaction paradigms.

Recent discoveries of the role peptide growth factors (PGFs) play in regulating embryonic patterning and differentiation have profoundly influenced research on the molecular biology of early amphibian embryogenesis. Several PGFs have been recognized to be present as endogenous components of amphibian eggs and early embryos, while other PGFs -- which are known from heterologous systems (e.g., Drosophila) -- exert remarkable effects when injected as either protein or mRNA into eggs/embryos or when added to cultured embryonic tissue. For a variety of reasons (reviewed herein) optimism abounds that an understanding in molecular terms of the classical Spemann and Nieuwkoop tissue interactions which are generally believed to drive embryonic patterning is within reach. A critical assessment of the interpretations of some of the contemporary data on PGFs (included herein) should, however, temper some of that optimism. Likely, multiple rather than single PGFs act in a combinatorial fashion to contribute to individual patterning events. As well, substantial redundancy in PGF regulatory circuits probably exists, so the heavy reliance on tissue culture assays and overexpression studies which characterize much recent research needs to be circumvented. Potential experimental approaches for "next generation" experiments are discussed.

Amphibians↗
PubMed1999

Identification of antigens on porcine pulmonary microvascular endothelial cells recognized by human xenoreactive natural antibodies.

Transplantation of organs between species is prevented in part by humoral immune responses triggered by xenoreactive natural antibodies. Although the immune barrier to xenotransplantation of the lung is thought to be qualitatively and quantitatively different than the immune barrier to xenotransplantation of the kidney or heart, the antibody-antigen reactions responsible for rejection of pulmonary xenografts have not been characterized. To begin to address this issue for porcine lungs transplanted into humans, we analyzed the porcine pulmonary endothelial antigens recognized by human xenoreactive natural antibodies. Human and baboon natural antibodies recognized glycoprotein and glycolipid antigens isolated from the membranes of porcine pulmonary microvascular endothelial cells. The antigens included the integrin chains alpha1, alpha2, alpha3, alpha5, alpha(v), beta1, beta 3, the von Willebrand Factor, and fibronectin. These glycoproteins seemed to be recognized by the same antibodies that bind to porcine kidney or cardiac xenografts. Natural antibodies also recognized at least four glycolipids containing from one to five sugar residues, although at a lower level per unit number of cells than glycoprotein antigens. The epitope recognized by natural antibodies was predominantly Gal alpha1-3Gal, a structure expressed by lower mammals but not by humans and baboons. The antigens recognized by human antibodies in the porcine lung may provide insight into the pathogenesis of the rejection reaction. Moreover, the similarity of porcine lung antigens to porcine kidney and heart antigens suggests that differences in the rejection reactions between these organs reflects the distinct responses of the organs to humoral immunity.

Animals↗