Interactions with T cells induce expression of VCAM-1 by human intrahepatic endothelial cells in vitro.
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Biomedical subjects
Publications and source records attributed to D H Adams.
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OBJECTIVE: This study compares the quality of valve replacement and repair performed through minimally invasive incisions as compared to the standard operation for aortic and mitral valve replacement. SUMMARY BACKGROUND DATA: With the advent of minimally invasive laparoscopic approaches to orthopedic surgery, urology, general surgery, and thoracic surgery, it now is apparent that standard cardiac valve operations can be performed through very small incisions with similar approaches. METHODS: Eighty-four patients underwent minimally invasive aortic (n = 41) and minimally invasive mitral valve repair and replacement (n = 43) between July 1996 and April 1997. Demographics, procedures, operative techniques, and postoperative morbidity and mortality were calculated, and a subset of the first 50 patients was compared to a 50-patient cohort who underwent the same operation through a conventional median sternotomy. Demographics, postoperative morbidity and mortality, patient satisfaction, and charges were compared. RESULTS: Of the 84 patients, there were 2 operative mortalities both in class IV aortic patients from multisystem organ failure. There was no operative mortality in the patients undergoing mitral valve replacement or repair. The operations were carried out with the same accuracy and attention to detail as with the conventional operation. There was minimal postoperative bleeding, cerebral vascular accidents, or other major morbidity. Groin cannulation complications primarily were related to atherosclerotic femoral arteries. A comparison of the minimally invasive to the conventional group, although operative time and ischemia time was higher in minimally invasive group, the requirement for erythrocytes was significantly less, patient satisfaction was significantly greater, and charges were approximately 20% less than those in the conventional group. CONCLUSIONS: Minimally invasive aortic and mitral valve surgery in patients without coronary disease can be done safely and accurately through small incisions. Patient satisfaction is up, return to normality is higher, and requirement for postrehabilitation services is less. In addition, the charges are approximately 20% less. These results serve as a paradigm for the future in terms of valve surgery in the managed care environment.
PURPOSE: To study results of foveal cone electroretinography (ERG) in patients with nonproliferative diabetic retinopathy (NPDR), with and without clinically significant macular edema (CSME). METHODS: Electroretinograms of foveal cones were elicited, with a dual-beam stimulator-ophthalmoscope, from 18 consecutive patients with bilateral NPDR and unilateral CSME. RESULTS: Analysis of resulting data revealed that mean amplitude was significantly lower in eyes with CSME and in eyes without CSME., compared with that in normal eyes. Mean implicit time was significantly longer in eyes with CSME compared with that in normal eyes, but in eyes of diabetic patients without CSME., mean implicit time was the same as that in normal eyes. Amplitudes were directly correlated and implicit times were inversely correlated with best-corrected Snellen visual acuity in eyes with and without CSME. Eyes with CSME had significantly lower amplitudes and longer implicit times than their fellow eyes without CSME. In addition, eyes with NPDR, with or without CSME, did not exhibit the normal rise in amplitude with increasing duration of light exposure. CONCLUSIONS: Electroretinographic findings showed abnormalities in foveal cone responses in eyes with NPDR, particularly in the presence of CSME. These results may support a functional role for outer retinal dysfunction in patients with diabetic retinopathy and loss of central vision.
Biliary epithelial cells are the focus of inflammatory damage in several liver diseases, including allograft rejection wherein intrahepatic bile ducts are infiltrated and damaged by T cells and neutrophils. Locally secreted chemotactic cytokines (chemokines) are important signals for leukocyte recruitment to an inflammatory site and include interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1), potent chemotactic agents for neutrophils and monocyte or T cells, respectively. In this study, we demonstrate that primary cultures of human biliary epithelial cells (BECs) express and secrete IL-8 and MCP-1, both of which are upregulated rapidly and markedly in response to the proinflammatory cytokines IL-1 and tumor necrosis factor-alpha. Interferon-gamma had a differential effect by reducing IL-8 secretion but stimulating MCP-1 secretion. BECs cocultured in transwell chambers below confluent monolayers of endothelial cells promoted the transendothelial migration of neutrophils, which was blocked by antibodies to CD18 or CD11b but only partially inhibited by blocking antibodies to IL-8. We conclude that human BECs produce and secrete potent, functional chemokines when stimulated by proinflammatory cytokines. The ability of BECs to secrete chemokines and thus to promote leukocyte infiltration into portal tracts seems likely to be an important cause of bile duct damage in such conditions as liver allograft rejection and may explain the involvement of intrahepatic bile ducts in a number of inflammatory liver diseases.
Aortic valve replacement has proven reliable, relieves life-threatening symptoms, and improves long-term survival of patients with aortic stenosis and aortic regurgitation. Minimally invasive aortic valve replacement uses small incisions; reduces exposure of the patient to surgical trauma, blood utilization, and operative dissection; although still using cardiopulmonary bypass and achieving the same general quality as with the open operation. Early and medium term results for minimally invasive aortic valve replacement approaches show a reduction in pain, improved patient satisfaction, and improved mobility and return to full-time activity. Concomitantly, there should be decreased cost and a decreased reliance on post-hospital rehabilitation.
BACKGROUND: Atrial fibrillation (AF) after coronary artery bypass surgery (CABG) is the most common sustained arrhythmia. Its pathophysiology is unclear, and its prevention and management remain suboptimal. The aim of this prospective study was to determine the current incidence of AF, identify its clinical predictors, and examine its impact on resource utilization. METHODS AND RESULTS: Over a 12-month period ending July 31, 1994, a CABG procedure was performed on 570 consecutive patients (age range, 32 to 87 years; median age, 67 years; 232 [41%] were > or = 70 years; 175 [31%] were women; 173 [30%] were diabetics; 364 [65%] required nonelective surgery; 86 [15%] had had a prior CABG; and 86 [15%] had had prior percutaneous transluminal coronary angioplasty). AF occurred in 189 patients (33%). The median age for patients with AF was 71 years compared with 66 for patients without (P = .0001). Multivariate logistic regression analysis (odds ratio, +/- 95% CI, P value) was used to identify the following independent predictors of postoperative AF: increasing age (age 70 to 80 years [OR = 2; CI, 1.3 to 3; P = .002], age > 80 years [OR = 3; CI, 1.6 to 5.8; P = .0007]), male gender (OR = 1.7; CI, 1.1 to 2.7; P = .01), hypertension (OR = 1.6; CI, 1.0 to 2.3; P = .03), need for an intraoperative intraaortic balloon pump (OR = 3.5; CI, 1.2 to 10.9; P = .03), postoperative pneumonia (OR = 3.9; CI, 1.3 to 11.5; P = .01), ventilation for > 24 hours (OR = 2; CI, 1.3 to 3.2; P = .003), and return to the intensive care unit (OR = 3.2; CI, 1.1 to 8.8; P = .03). The mean length of hospital stay after surgery was 15.3 +/- 28.6 days for patients with AF compared with 9.3 +/- 19.6 days for patients without AF (P = .001). The adjusted length of hospital stay attributable to AF was 4.9 days, corresponding to > or = $10 055 in hospital charges. CONCLUSIONS: AF remains the most common complication after CABG and consequently is a drain on hospital resources. Concerted efforts to reduce the incidence of AF and the associated increased length of stay would result in substantial cost saving and decrease patient morbidity.
Two local events that are crucial for T cell emigration into tissue are (1) activation of T cell integrins to permit binding to endothelial counter-receptors and (2) directed migration through the endothelium and into tissue in response to chemotactic factors. Because the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta can activate adhesion and induce migration of T cells in vitro, we investigated their expression in human liver allografts to determine whether they might be involved in regulating the recruitment of T cells to allografts in vivo. Both chemokines were expressed strongly by infiltrating leukocytes during rejection and could be detected immunohistochemically on biliary epithelium, an important target for T cell mediated graft damage. Both chemokines, but particularly MIP-1 beta, were detected on the vascular and sinusoidal endothelium of rejecting liver allografts, where they were coexpressed with the T cell beta 1-integrin receptor vascular cell adhesion molecule-1. In situ hybridization with complementary ribonucleic acid probes showed no MIP-1 alpha or MIP-1 beta mRNA in normal liver but dramatic expression of both chemokines in infiltrating leukocytes and graft endothelium during rejection. Expression was reduced after successful corticosteroid treatment of rejection but persisted in patients progressing to chronic rejection. Increased MIP-1 alpha and MIP-1 beta mRNA expression was already found in biopsies taken at the end of the transplant operation, suggesting that early induction of chemokines, possibly in response to graft reperfusion, might promote the subsequent development of graft rejection. These data demonstrate for the first time that MIP-1 alpha and MIP-1 beta are (1) expressed in human liver allografts, (2) produced by endothelial cells in vivo, and (3) induced early after transplantation. They suggest that MIP-1 alpha and MIP-1 beta produced by graft infiltrating leukocytes and graft endothelium might play a crucial role in regulating T cell recruitment to liver allografts in vivo.
The macroglide immunosuppressant FK506 is effective at preventing and reversing hepatic allograft rejection. The establishment of graft rejection is dependent upon an influx of lymphocytes from the circulation into the graft in response to locally secreted chemotactic factors. Thus, inhibition of lymphocyte migration might be an additional mode of action of FK506 that could block lymphocyte recruitment to rejecting liver allografts. In the present study, we provide evidence to support this hypothesis because we have demonstrated, using in vitro migration assays, that FK506 can inhibit the migration of lymphocytes, including CD4+ and CD8+ T-cells, to structurally diverse chemotactic factors that are present during human liver allograft rejection. In addition, FK506 acts on lymphocytes in patients with graft rejection to inhibit migration and to block the secretion of chemotactic factors in vitro. Thus, FK506 might reverse established graft rejection by inhibiting lymphocyte recruitment to the graft in vivo.
Lymphocyte recruitment to tissue is regulated by homing molecules expressed on subsets of leukocytes that bind to endothelial adhesion molecules termed addressins in target tissues. The addressins and homing molecules involved in recruiting lymphocytes to inflamed human liver are not known. E-selectin, which acts as an addressin for a subset of skin-infiltrating T cells that express a distinct E-selectin ligand called the cutaneous lymphocyte antigen (CLA), can be detected on endothelium in inflammatory liver diseases suggesting it might also act as an addressin for liver-infiltrating lymphocytes. To determine whether E-selectin does play such a role we looked for concomitant expression of E-selectin on hepatic endothelium and E-selectin ligands on infiltrating lymphocytes in liver sections from patients with primary biliary cirrhosis (PBC), acute allograft rejection, alcoholic liver disease, and normal liver. E-selectin was detected on vascular endothelium in association with lymphocytic infiltrates in all three liver diseases but not on normal endothelium. However, less that 10% of infiltrating lymphocytes expressed the only known lymphocyte E-selectin ligand, CLA. We used E-selectin chimeric fusion proteins to probe for novel E-selectin ligands on liver-infiltrating lymphocytes; however, less than 10% of lymphocytes had t he ability to bind the fusion proteins. Thus, E-selectin is unlikely to act as an addressin for liver-infiltrating lymphocytes, suggesting that other molecules are involved in lymphocyte recruitment to the liver. Despite the lack of binding to lymphocytes other structures in the liver expressed CLA and bound the E-selectin fusion proteins. Inflamed, but not normal, intrahepatic bile ducts expressed CLA and bound E-selectin, suggesting that they express activation dependent carbohydrate binding receptors. Furthermore, Kupffer cells did not express CLA but bound to both E-selectin fusion proteins, suggesting that they express potentially novel E-selectin ligands.
Until recently, treatment options for patients with cystine calculi were not favorable. Using holmium:yttrium-aluminum-garnet (YAG) lasers to fragment cystine calculi, however, may provide a minimally invasive and cost-effective alternative to current treatments. This article describes cystine calculi and the diagnostic methods and current medical and surgical interventions used to treat patients and discusses the differences between flash lamp pulsed dye lasers and holmium:YAG lasers. Preoperative, intraoperative, and postoperative considerations for laser ureterolithotripsy of cystine calculi also are discussed.
Increasingly, patients undergoing coronary artery bypass grafting (CABG) are elders, have had previous CABG, and have poor left ventricular function. To evaluate determinants of perioperative myocardial infarction (PMI) after isolated CABG, 499 consecutive patients were reviewed. Definite PMI (total peak creatine kinase [CK] > 700 U/L, creatine kinase MB [CK-MB] > 30 ng/ml, and new pathologic electrocardiographic Q waves) occurred in 25 patients (5.0%) and probable PMI (total peak CK > 700 U/L, CK-MB > 30 ng/ml, and a new wall-motion abnormality) occurred in 10 (2.0%) patients. According to multivariate logistic regression analysis, independent risk factors for definite or probable PMI (adds ratios; 95% confidence intervals) were emergency surgery (3.1; 1.1 to 8.4; p = 0.003), aortic cross-clamp time > 100 minutes (4.2; 1.6 to 11.2; p = 0.004), myocardial infarction in the preceding week (2.6; 1.0 to 6.4; p = 0.04), and previous revascularization (2.4; 1.1 to 5.2; p = 0.02). In conclusion, both preoperative and intraoperative factors influence the risk of PMI after CABG. Despite changes in the profile of patients undergoing CABG, the incidence of PMI in this tertiary center is comparable with that found in earlier series, probably because of improvements in surgical techniques and postoperative care.
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BACKGROUND & AIMS: Molecules that regulate T-cell adhesion to hepatic endothelium and thereby recirculation of T cells to the liver are poorly understood. Because the adhesion molecule vascular adhesion protein-1 (VAP-1), which mediates lymphocyte binding to lymph node endothelium, is expressed on hepatic endothelium, it could play a role in regulating T-cell recruitment to the liver. The aim of this study was to investigate the distribution of VAP-1 expression in human liver and the ability of VAP-1 to support T-cell binding to hepatic endothelium in vitro. METHODS: Hepatic VAP-1 expression was investigated using immunohistochemistry and specific monoclonal antibodies, and VAP-1-mediated adhesion to hepatic endothelium was investigated with a tissue-binding adhesion assay using human liver sections. RESULTS: VAP-1 was expressed on sinusoidal and vascular endothelium in non-inflamed liver and in inflamed liver from patients with either allograft rejection or primary biliary cirrhosis. T cells from healthy donors bound to hepatic endothelium when added to noninflamed liver sections; this binding was inhibited by a specific anti-VAP-1 antibody but not by antibodies to intercellular adhesion molecule 1, lymphocyte function--associated antigen 1, or very late after activation (antigen) 4. VAP-1--mediated adhesion was unaffected by T-cell activation with phorbol ester. CONCLUSIONS: VAP-1 is constitutively expressed on hepatic endothelium and mediates T-cell adhesion to hepatic endothelium in vitro. VAP-1 could play a critical role in regulating T-cell recirculation to the liver in vivo.
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