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David H Adams

Publications and source records attributed to David H Adams.

At least 73 records · Page 4Linked to original sources
PubMed2004

Peliosis of the spleen with massive recurrent haemorrhagic ascites, despite splenectomy, and associated with elevated levels of vascular endothelial growth factor.

We present the case of a 33-year-old man with isolated splenic peliosis, a rare pathological condition characterized by blood filled cystic lesions. The patient presented with recurrent massive haemorrhagic ascites, which did not resolve, despite a splenectomy. He was found to have massively elevated levels of vascular endothelial growth factor (VEGF). The clinical course of the disease was prolonged. Repeated blood transfusions for recurrent anaemia were required, in addition to repeated aspiration of reaccumulating haemorrhagic ascites and pleural effusion. The clinical course was not in keeping with previously reported cases. We have described an atypical clinical presentation in a patient with isolated splenic peliosis associated with elevated VEGF concentrations. No previously known associations for the condition were found despite thorough investigations. Management of the patient has been symptomatic and palliative. We have reviewed the various reported associations of peliosis and discussed the possible role of VEGF in this patient's condition.

Adult↗
PubMed2004

Current results of combined coronary artery bypass grafting and mitral annuloplasty in patients with moderate ischemic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: Combined coronary artery bypass grafting (CABG) and mitral annuloplasty for ischemic mitral regurgitation (MR) is historically associated with high operative mortality, and remains controversial in the setting of moderate ischemic MR. Herein, operative mortality rates in patients undergoing combined CABG and mitral annuloplasty for moderate ischemic MR were examined. METHODS: Between January 1992 and August 1999, 108 patients with moderate (grade 3+) ischemic MR and coronary artery disease underwent combined CABG and mitral annuloplasty. Univariable analysis was used to identify perioperative risk factors associated with operative mortality in patients undergoing surgery during two different time periods (1992-95 versus 1996-99). Bivariable logistic regression was used to evaluate the possible effect of era on operative mortality, while controlling for potential confounders. RESULTS: The overall operative mortality was 6.4%. During 1992-95 the operative mortality was 14% (4/28), but fell to 3.7% (3/80) during 1996-99 (p = 0.07). Patients from the earlier period were more likely to have unstable angina, worse NYHA functional class, and preoperative atrial fibrillation. Patients from the latter period were more likely to have peripheral vascular disease and chronic obstructive pulmonary disease. The unadjusted odds ratio (OR) for operative mortality associated with the earlier era was 4.3 (95% CI 9-20.8; p = 0.07). In the bivariable logistic regression models, where patient characteristics that potentially were responsible for the difference in mortality were added, the OR for operative mortality associated with the 1992-95 era ranged from 3.4 to 6.7. None of the patient characteristics appreciably reduced this risk. CONCLUSION: Recent decreased operative mortality in combined CABG and mitral annuloplasty for moderate ischemic MR suggests that a more liberal application of this approach may be warranted.

Aged↗
PubMed2003

Distinct effects of methamphetamine and cocaine on preprodynorphin messenger RNA in rat striatal patch and matrix.

We and others previously reported that equimolar doses of methamphetamine and cocaine differentially increase preprodynorphin mRNA in striatum: methamphetamine causes a patchy increase, whereas cocaine produces a more homogenous one. The current study directly examined whether this effect reflects differential induction in the patch-matrix division of striatum, as identified by micro opioid receptor immunohistochemistry. In addition, we determined whether doses of cocaine (30 mg/kg) and methamphetamine (2 mg/kg) that produced equivalent increases in extracellular dopamine differentially affected preprodynorphin mRNA expression in striatum of male, Sprague-Dawley rats. In both experiments, methamphetamine and cocaine differentially affected preprodynorphin mRNA in striatum after 3 h. The high, equimolar dose of methamphetamine selectively increased preprodynorphin mRNA in the patch division of rostral striatum, whereas cocaine increased preprodynorphin mRNA throughout patch and matrix divisions of striatum. In contrast, a dose of methamphetamine (2.0 mg/kg) that caused an increase in extracellular dopamine similar to that produced by 30 mg/kg cocaine did not significantly affect preprodynorphin mRNA in any region of striatum. These data provide further evidence that cocaine and amphetamines exert distinct effects on the patch-matrix division of striatum and suggest further that the post-synaptic consequences of elevated extracellular dopamine produced by methamphetamine and cocaine are distinct.

Animals↗
PubMed2003

Mechanisms of Gal(alpha)1-3Gal(beta)1-4GlcNAc-R (alphaGal) expression on porcine valve endothelial cells.

OBJECTIVE: We have previously reported that porcine valve endothelium does not express immunodetectable levels of the carbohydrate Gal(alpha)1-3Galbeta1-4GlcNAc-R (known as alphaGal), suggesting that fresh porcine valve may be immunoprivileged. In this study, we further investigated the mechanisms of alphaGal expression on porcine valve endothelial cells. METHODS: Primary cultures of porcine valvular endothelial cells were established and compared with porcine aortic endothelial cells and human vein endothelial cells. Immunoblotting, reverse transcriptase-polymerase chain reaction, and flow cytometry were used to compare the expression of alphaGal at both the protein and messenger RNA levels. RESULTS: Porcine valvular endothelial cells grew rapidly on a gelatin substrate. Similar to our previous in vivo results, valve endothelial cells expressed alphaGal much less intensely than did aortic endothelial cells. Porcine aortic endothelial cells expressed an isolectin B4 (isolectin B4 lectin Bandeiraea simplicifolia) immunodetectable band at 135 kd that was not visible on porcine valve endothelial cells or on human vein endothelial cells. Reverse transcriptase-polymerase chain reaction documented three transcripts of the alphaGal gene that were identically expressed on porcine valve and aortic endothelial cells. Furthermore, flow cytometry showed an almost identical surface profile between porcine aortic and valve endothelial cells, in contrast with human vein endothelial cells. CONCLUSIONS: Cultures of primary valve endothelial cells were established and exhibited similar phenotypic patterns in vitro to those we have previously documented in vivo. RNA and flow cytometric analyses documented no difference between the RNA expression and surface protein profile for alphaGal, although whole-cell extracts demonstrated an immunodetectable band on Western blotting that was present on aortic endothelial cells but not on valve endothelial cells. These findings clarify the mechanism of expression of alpha1,3galactosyltransferase gene expression in valve endothelial cells, suggesting that delayed rejection of fresh porcine cardiac valves may occur.

Animals↗
PubMed2003

Differential induction of nuclear factor-kappaB and activator protein-1 activity after CD40 ligation is associated with primary human hepatocyte apoptosis or intrahepatic endothelial cell proliferation.

CD40, a tumor necrosis factor receptor superfamily member, is up-regulated on intraheptatic endothelial cells (IHEC) and epithelial cells during inflammatory liver disease, and there is evidence that the functional outcome of CD40 ligation differs between cell types. Ligation of CD40 on cholangiocytes or hepatocytes results in induction of Fas-mediated apoptosis, whereas ligation of IHEC CD40 leads to enhanced chemokine secretion and adhesion molecule expression. We now report that differential activation of two transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), in primary human hepatocytes or IHEC, is associated with and may explain, in part, the different responses of these cell types to CD40 ligation. CD40 ligation induced a rise in NF-kappaB activity in hepatocytes,which peaked at 2 h and returned to baseline by 24 h; however, IHEC CD40 ligation resulted in a sustained up-regulation of NF-kappaB (>24 h). In hepatocytes, CD40 ligation led to sustained up-regulation of AP-1 activity >24 h associated with increased protein levels of RelA (p65), c-Jun, and c-Fos, whereas no induction of AP-1 activity was observed in IHECs. Analysis of mitogen-activated protein kinase phosphorylation (phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH(2)-terminal kinase 1/2) and expression of inhibitor kappaBalpha were entirely consistent, and thus confirmed the profiles of NF-kappaB and AP-1 signaling and the effects of the selective inhibitors assessed using electrophoretic mobility shift assay or Western immunoblotting. CD40 ligation resulted in induction of apoptosis in hepatocytes after 24 h, but on IHECs, CD40 ligation resulted in proliferation. Inhibition of (CD40-mediated) NF-kappaB activation prevented IHEC proliferation and led to induction of apoptosis. Selective extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase inhibitors reduced levels of apoptosis in (CD40-stimulated) hepatocytes by approximately 50%. We conclude that differential activation of these two transcription factors in response to CD40 ligation is associated with differences in cell fate. Transient activation of NF-kappaB and sustained AP-1 activation is associated with apoptosis in hepatocytes, whereas prolonged NF-kappaB activation and a lack of AP-1 activation in IHECs result in proliferation.

Apoptosis↗
PubMed2002

Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells.

Vascular adhesion protein-1 (VAP-1) is an amine oxidase and adhesion receptor that is expressed by endothelium in the human liver. The hepatic sinusoids are perfused by blood at low flow rates, and sinusoidal endothelium lacks selectin expression and has low levels of CD31, suggesting that VAP-1 may play a specific role in lymphocyte recruitment to the liver. In support of this we now report the constitutive expression of VAP-1 on human hepatic sinusoidal endothelial cells (HSEC) in vitro and demonstrate that VAP-1 supports adhesion and transmigration of lymphocytes across these cells under physiological shear stress. These are the first studies to report the function of VAP-1 on primary human endothelial cells. Under static conditions lymphocyte adhesion to unstimulated HSEC was dependent on VAP-1 and ICAM-2, whereas adhesion to TNF-alpha-stimulated HSEC was dependent on ICAM-1, VCAM-1, and VAP-1. Under conditions of flow, blocking VAP-1 reduced lymphocyte adhesion to TNF-alpha-treated HSEC by 50% and significantly reduced the proportion of adherent lymphocytes that transmigrated across cytokine or LPS-activated endothelium. In addition, inhibition of the amine oxidase activity of VAP-1 reduced both adhesion and transmigration of lymphocytes to a level similar to that seen with VAP-1 Ab. Thus, VAP-1 can support transendothelial migration as well as adhesion, and both functions are dependent on its enzymatic activity. In the absence of selectins and CD31, VAP-1 may play a specific role in lymphocyte recruitment via hepatic sinusoidal endothelium. Moreover, since VAP-1 is induced on nonhepatic endothelium in response to inflammation, its ability to support lymphocyte transendothelial migration may be an important systemic function of VAP-1.

Amine Oxidase (Copper-Containing)↗
PubMed2002

The role of cholangiocytes in the development of chronic inflammatory liver disease.

Cholangiocytes constitute the biliary epithelium, an important barrier to infection entering the liver via the gastrointestinal tract. These cells have developed mechanisms to respond to infection by recruiting and interacting with effector leukocytes to clear bacterial or viral pathogens. Cholangiocytes are also targets of immune mediated damage in several liver diseases and under these circumstances protective mechanisms, for example the secretion of chemokines and expression of adhesion molecules, become harmful and promote the inappropriate recruitment and retention of effector cells within portal tracts. In chronic inflammatory biliary diseases such as primary biliary cirrhosis and primary sclerosing cholangitis, infiltrating leukocytes destroy bile ducts by killing cholangiocytes via complex molecular mechanisms involving Fas-dependent apoptosis and autocrine and paracrine interactions with other members of the TNF superfamily including CD40. A better understanding of these processes may lead to novel therapeutic approaches aimed at switching off the chronic inflammatory response and protecting bile ducts from apoptosis.

Animals↗
PubMed2002

Analysis of the control of the anti-gal immune response in a non-human primate by galactose alpha1-3 galactose trisaccharide-polyethylene glycol conjugate.

BACKGROUND: The current limitation to the clinical application of xenotransplantation using pig organs is a rejection process that has been termed delayed xenograft rejection or acute vascular rejection. It is thought that acute vascular rejection may be mediated at least in part by both the continued synthesis, of preexisting, and the induction, posttransplantation, of antibodies against the carbohydrate moiety galalpha1-3gal that is present on glycoproteins and glycolipids of the pig endothelium. The synthesis of these antibodies has proven difficult to control with currently available immunosuppressive agents. METHODS: We have synthesized galalpha1-3gal conjugated polyethylene glycol polymers that can bind to anti-galalpha1-3gal antibodies and tested their activity in non-human primates. RESULTS: These conjugates when administered to non-human primates can substantially reduce the levels of preexisting and control the induction of anti-galalpha1-3gal antibodies. The level of circulating antibody-secreting cells that make anti-galalpha1-3gal antibodies is also reduced. CONCLUSION: These alpha-gal polyethylene glycol conjugates may have the potential to control the anti-gal antibody response in a pig to primate organ transplant setting and may be a useful therapeutic agent in prolonging graft survival.

Animals↗
PubMed2002

The liver: a model of organ-specific lymphocyte recruitment.

The liver is constantly exposed to gut-derived antigens that enter via the portal vein, and it must modulate immune responses so that harmful pathogens are cleared but necessary food antigens are ignored. The liver contains a large resident and migratory population of lymphocytes and macrophages that provide immune surveillance against foreign antigen. This population of cells can be rapidly expanded in response to infection or injury by recruiting leukocytes from the circulation, a process that is dependent on the ability of lymphocytes to recognise, bind to and migrate across the endothelial cells that line the vasculature. Lymphocytes can enter the liver at several sites: the vascular endothelium in the portal tracts (comprising the hepatic artery, portal vein and bile ductule), the sinusoids (through which the blood percolates past the hepatocytes) or the central hepatic veins (through which the blood exits). The requirements and physical conditions at each site vary and there is evidence that different combinations of adhesion proteins are involved at these different sites. This article discusses the expression and function of adhesion molecules within the liver and demonstrates how specific populations of effector lymphocytes can be selectively recruited to the liver.

Animals↗
PubMed2002

Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease.

Primary sclerosing cholangitis is strongly linked to inflammatory bowel disease, but any model to explain the development of primary sclerosing cholangitis must take into account the fact that it usually runs a course independent from inflammation in the bowel, illustrated by the fact that this disease can develop many years after proctocolectomy. Thus, liver disease can develop in the absence of a diseased colon and cannot be explained solely by release of toxic factors from the inflamed gut. We propose the existence of an enterohepatic circulation of lymphocytes, whereby some mucosal lymphocytes generated in the gut during active inflammatory disease subsequently persist as longlived memory cells capable of recirculation through the liver. Under the right conditions, these dual-homing lymphocytes might become activated in the liver resulting in hepatic inflammation that is independent from inflammation in the gut. Recent reports that some lymphocyte homing-receptors are shared by the liver and gut provide a molecular basis for this hypothesis and explain the distribution of extraintestinal disease in inflammatory bowel disease.

Cell Adhesion Molecules↗
PubMed2002

Hepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease.

The chronic inflammatory liver disease primary sclerosing cholangitis (PSC) is associated with portal inflammation and the development of neolymphoid tissue in the liver. More than 70% of patients with PSC have a history of inflammatory bowel disease and we have previously reported that mucosal addressin cell adhesion molecule-1 is induced on dendritic cells and portal vascular endothelium in PSC. We now show that the lymph node-associated chemokine, CCL21 or secondary lymphoid chemokine, is also strongly up-regulated on CD34(+) vascular endothelium in portal associated lymphoid tissue in PSC. In contrast, CCL21 is absent from LYVE-1(+) lymphatic vessel endothelium. Intrahepatic lymphocytes in PSC include a population of CCR7(+) T cells only half of which express CD45RA and which respond to CCL21 in migration assays. The expression of CCL21 in association with mucosal addressin cell adhesion molecule-1 in portal tracts in PSC may promote the recruitment and retention of CCR7(+) mucosal lymphocytes leading to the establishment of chronic portal inflammation and the expanded portal-associated lymphoid tissue. This study provides further evidence for the existence of portal-associated lymphoid tissue and is the first evidence that ectopic CCL21 is associated with lymphoid neogenesis in human inflammatory disease.

Blood Cells↗
PubMed2002

Open inferior vena caval anastomosis during bicaval heart transplantation.

Performing a precise inferior vena caval (IVC) anastomosis during bicaval orthotopic heart transplantation can sometimes be challenging because of crowding of the operative field by the venous cannula and tourniquet. We performed bicaval orthotopic heart transplantation in 10 patients using an open IVC anastomotic technique with vacuum-assisted venous drainage. A long venous cannula was passed into the IVC through the femoral vein. The IVC anastomosis was performed after removing the IVC tourniquet under vacuum-assisted venous drainage. A precise edge-to-edge IVC anastomosis was successfully performed in all patients. This technique may result in greater anastomotic precision and improved outcomes.

Anastomosis, Surgical↗
PubMed2002

Aortic valve surgery after previous coronary artery bypass grafting with functioning internal mammary artery grafts.

BACKGROUND: Aortic valve surgery after coronary artery bypass grafting (CABG) in the setting of patent pedicled internal mammary artery (IMA) grafts poses a high risk because of the underlying ischemic and valve disease. Unlike mitral valve surgery or CABG, in which aortic clamping (AoX) may be optional, aortic valve surgery uniformly requires AoX unless circulatory arrest is used. Management of the IMA graft in these circumstances has traditionally involved dissection and clamping to prevent regional myocardial warming and cardioplegia "washout" during AoX. An alternative strategy involves avoiding dissection of the IMA, leaving the IMA graft open and establishing moderate-to-deep hypothermia during AoX and cardioplegic arrest. To date, no study has been published documenting the safety and efficacy of the latter practice. METHODS: A total of 94 patients who had patent IMA graft and underwent aortic valve surgery under AoX and cardioplegia between April 1992 and March 2001 were analyzed. The IMA was avoided and left open during AoX, and the patients were cooled systemically (median 20 degrees C). Patients ranged in age from 55 to 90 years (median 73.5 years). Ejection fraction was 15% to 83% (median 50%). Of the patients, 18 (19%) underwent minimally invasive upper hemi-resternotomy. Analysis for predictors of outcome was performed. RESULTS: The operative mortality, perioperative myocardial infarction (MI), and stroke rates were 6.4%, 7%, and 11%, respectively. No significant independent predictors of operative mortality or MI could be identified in the multivariate analysis, although a trend was shown for operative mortality with urgent procedures and patients requiring concomitant surgery of the ascending or arch aorta or aortic root. Advanced age and prolonged cardiopulmonary bypass predicted stroke in the multivariate analysis. There were five (5%) IMA injuries, all occurring during reentry or mediastinal dissection, but none in the subgroup of patients who underwent minimally invasive procedures. All patients survived. CONCLUSIONS: Patients undergoing aortic valve surgery after CABG in the presence of patent IMA represent a potentially high-risk group. Because AoX is almost uniformly required, a decision regarding the management of the IMA pedicle is needed. We have found that leaving the IMA undissected and unclamped is a reasonable strategy, provided that systemic cooling for myocardial protection is established to prevent regional warming and to compensate for cardioplegia washout effect during AoX.

Aged↗
PubMed2002

Liberal use of delayed sternal closure for postcardiotomy hemodynamic instability.

BACKGROUND: The purpose of this retrospective study was to evaluate the current incidence, survival, and predictors of mortality for open chest management at our center. METHODS: Our database was analyzed to identify adult postcardiotomy patients who left the operating room without primary sternal closure. Medical records were reviewed to determine mortality, postoperative complications, and pertinent hemodynamic data. RESULTS: From November 1997 to June 2000, 5,177 adults underwent cardiac procedures at our center. The incidence of open chest management was 1.7% (87 of 5,177), including 0.7% (16 of 2,254) for isolated coronary artery bypass grafting, 1.6% (15 of 912) for isolated valve, and 5.6% (47 of 839) for combined valve/coronary bypass. Hospital survival was 76% (66 of 87). Major complications included deep sternal infection (n = 4), stroke (n = 8), and dialysis (n = 13). Predictors of mortality by univariate analysis included ventricular assist device insertion (p = 0.003), new onset hemodialysis (p < 0.0005), reoperation for bleeding (p = 0.002), sternal infection (p = 0.042), mean length of delay before sternal closure (survivors = 3.2 days, nonsurvivors = 6.2 days; p = 0.031), higher mean dose of epinephrine at the time of chest closure (2.5 microg versus 0.9 microg, p = 0.011), and longer duration of high dose inotropic therapy (110 hours versus 43 hours, p = 0.002). Multivariate analysis showed ventricular assistance and reoperation for bleeding as independent predictors of in-hospital death with odds ratios of 3.8 and 3.4, respectively. CONCLUSIONS: Liberal use of open chest management is useful in patients with postcardiotomy shock, and can be carried out with a relatively low incidence of sternal complications. Patients who require ventricular assistance or exploration for ongoing mediastinal bleeding continue to have a high mortality rate.

Aged↗
PubMed2002

Lymphocyte recruitment to the liver in alcoholic liver disease.

The normal liver contains a large number of lymphocytes, which include not only specialized natural killer (NK) and NKT cells but also CD4 and CD8 T cells. Whereas some of these cells are terminally differentiated effector cells that are destined to die by apoptosis, many of them are not and include immunocompetent cells that traffic through the liver to provide continuing immune surveillance as well as epithelial-associated effector T cells. In alcoholic liver disease the number of lymphocytes in the liver increases and the type and distribution of these infiltrating cells will determine the nature of the inflammation. For instance, a predominance of parenchymal inflammation is a feature of alcoholic hepatitis, whereas a predominantly portal infiltrate is a feature of cirrhosis. In this article we discuss the molecular mechanisms that regulate the entry of lymphocytes to the inflamed liver in alcoholic hepatitis. Lymphocytes play a critical role in regulating the immune/inflammatory response to alcohol, and understanding how these cells are recruited to the liver has important implications for understanding the pathogenesis of alcoholic liver disease in which parenchymal infiltration is a critical determinant of disease progression. Aberrant recruitment and retention of lymphocytes in the liver may explain why some patients with alcoholic liver disease show progressive inflammatory damage whereas in others the disease takes a more indolent course. Similarly, leukocyte recruitment may present new therapeutic targets in which lymphocyte recruitment to the specific liver compartments can be inhibited, thereby minimizing tissue damage whilst leaving generalized lymphocyte recirculation intact. Potentially the most exciting potential is to modulate the nature of the lymphocyte subsets recruited to the liver, so that harmful cells are excluded and beneficial subsets are preferentially recruited.

Animals↗
PubMed2002

Recruitment of lymphocytes to the human liver.

This review discusses the function and localisation of lymphocytes resident within the human liver, under both physiological and pathological conditions. Through description of the mechanisms that mediate lymphocyte recruitment into tissues, this article explains how hepatic endothelial and epithelial cells regulate the recruitment of specific lymphocyte subpopulations. We illustrate that the expression of adhesion molecules and chemokines is crucial to the control of lymphocyte adhesion. Thus, in the normal liver, adhesion molecules such as vascular adhesion protein-1 (VAP-1), intercellular adhesion molecule-1 (ICAM-1) and intercellular adhesion molecule-2 (ICAM-2), and chemokines such as regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), interferon gamma inducible protein-10 (IP-10), MIG and interferon inducible T-cell alpha chemoattractant (ITAC) are involved in lymphocyte binding to different endothelial compartments. However, in response to inflammation or injury, additional expression of adhesion molecules such as VCAM-1, p-selectin and e-selectin, as well as higher levels of chemokines, permits the attraction and retention of specific effector populations of lymphocytes. We also discuss the expression and function of a newly defined adhesion protein, (VAP-1), and suggest that the unique functions of this protein may provide therapeutic potential for the treatment of liver disease.

Animals↗