PubMed Health⌕ Search

Biomedical subjects

D A Neil

Publications and source records attributed to D A Neil.

12 recordsLinked to original sources
PubMed2001

Are parenchymal changes in early post-transplant biopsies related to preservation-reperfusion injury or rejection?

BACKGROUND: The progression of parenchymal changes in liver allograft biopsies due to preservation-reperfusion injury (PRI) and their differentiation from rejection related changes is poorly understood. The aim of this study was to determine which changes in a 1-week posttransplant biopsy could be attributed to PRI and which to acute rejection. METHODS: One week protocol liver transplant biopsies from patients with mild PRI (day 1 AST<400 IU/L) were compared with those from patients with severe PRI (day 1 AST>2000 IU/L). Parenchymal changes (cholestasis, ballooning, steatosis, necrosis) and rejection-related inflammatory features (portal tract inflammation, bile duct inflammation, portal vein endothelial inflammation, hepatic vein endothelial inflammation, and centrilobular inflammation) were blindly assessed semiquantitatively. RESULTS: Fat, cholestasis, and hepatocyte ballooning were significantly worse in the severe PRI group, and these features showed no correlation with histological features related to acute rejection. Centrilobular hepatocyte necrosis correlated with hepatic venular endothelial inflammation and centrilobular inflammation but not with rejection related features in portal tracts or with PRI. These findings suggest that centrilobular necrosis is a manifestation of a rejection-related parenchymal injury and may involve different pathogenetic mechanisms to rejection-related features in portal tracts. CONCLUSIONS: This study indicates that in early posttransplant biopsies, fat, cholestasis, and ballooning can largely be attributed to PRI. By contrast, centrilobular hepatocyte loss should be suspected as a rejection related phenomenon, even if typical portal tract changes are not prominent, and augmentation of immunosuppression should be considered.

Adolescent↗
PubMed2001

HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia.

Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated alpha subunit and a constitutively expressed beta subunit. Although HIF-1 is regulated mainly by oxygen tension through the oxygen-dependent degradation of its alpha subunit, in vitro it can also be modulated by cytokines, hormones and genetic alterations. To investigate HIF-1 activation in vivo, we determined the spatial and temporal distribution of HIF-1 in healthy mice subjected to varying fractions of inspiratory oxygen. Immunohistochemical examination of brain, kidney, liver, heart, and skeletal muscle revealed that HIF-1alpha is present in mice kept under normoxic conditions and is further increased in response to systemic hypoxia. Moreover, immunoblot analysis showed that the kinetics of HIF-1alpha expression varies among different organs. In liver and kidney, HIF-1alpha reaches maximal levels after 1 h and gradually decreases to baseline levels after 4 h of continuous hypoxia. In the brain, however, HIF-1alpha is maximally expressed after 5 h and declines to basal levels by 12 h. Whereas HIF-1beta is constitutively expressed in brain and kidney nuclear extracts, its hepatic expression increases concomitantly with HIF-1alpha. Overall, HIF-1alpha expression in normoxic mice suggests that HIF-1 has an important role in tissue homeostasis.

Animals↗
PubMed2000

Endothelium during microarterial graft procurement and transplantation.

Microarterial grafts are prone to mechanical endothelial injury that can have profound effects on the transplanted vessel, a factor neglected in studies on vascular changes post-transplantation. The aim of this study was to document the integrity of the endothelial lining after both procurement and transplantation of rat aortic grafts, using a minimal touch technique with and without the use of topical papaverine. It was found that procurement using a simple minimal touch technique preserved the endothelium and transplantation could be performed without endothelial injury. The appearance of "normal" endothelium varied with the degree of distension of the artery, suggesting a dynamic endothelial architecture to accommodate changes in the surface area of the artery during pulsation. These findings indicate that transplantation of an arterial segment without injury to the intima is possible and stress the importance of technical controls after both procurement and transplantation to prevent the use of injured grafts and misleading results.

Animals↗
PubMed2000

Coronary arteries from a single coronary ostium in the right coronary sinus: a previously unreported anatomy.

The coronary circulation originating from a single coronary ostium is rare. All possible anatomical variations were the basis of a recent classification. This case report describes a previously unreported IID(1) pattern, comprising a solitary coronary ostium in the right coronary sinus with an anatomical course of the right coronary artery. The left circumflex coronary artery arises from the proximal right coronary artery coursing behind the aorta to the left. The left anterior descending coronary artery arises from the proximal right coronary artery coursing to the left side anterior to the right ventricle.

Aortic Dissection↗
PubMed1999

Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease.

BACKGROUND: Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha). AIMS: To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease. PATIENTS: Fifty one patients with alcoholic liver disease and 12 healthy controls. METHODS: Peripheral vein (and hepatic vein in patients undergoing transjugular liver biopsy) chemokine concentrations were measured by ELISA. Chemokine secretion and transcription in isolated peripheral mononuclear cells were assessed using ELISA and in situ hybridisation in patients with severe alcoholic hepatitis. RESULTS: Serum MCP-1 concentrations were higher in alcoholic hepatitis compared with cirrhosis or healthy controls. MIP-1alpha concentrations were below the assay sensitivity in most patients. Serum MCP-1 concentrations correlated significantly with serum aspartate aminotransferase and creatinine. In severe alcoholic hepatitis, MCP-1 concentrations were higher in hepatic compared with peripheral veins; in mild alcoholic hepatitis there was no difference. Mononuclear cell secretion of both MCP-1 and MIP-1alpha was higher in severe alcoholic hepatitis compared with healthy controls, and chemokine mRNA was identified in monocytes. CONCLUSIONS: Serum MCP-1 concentrations are raised in alcoholic liver disease and reflect severity of hepatic inflammation. Monocyte secretion of both MCP-1 and MIP-1alpha is increased in severe alcoholic hepatitis. Both intrahepatic sources and peripheral mononuclear cells contribute to the raised serum MCP-1 concentrations.

Biomarkers↗
PubMed1998

Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis.

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.

Chemokine CCL2↗
PubMed1989

Vascular changes following hypothermic preservation.

This study identifies ultrastructural changes in the endothelium due to hypothermic HP-5 perfusion. These changes appear to be reversible and a manifestation of hypothermic hypoxia. This data provides a basis for improving perfusion techniques in both hypothermic preservation and cryoprotectant introduction and removal for cryopreservation.

Animals↗
PubMed1987

Caecal volvulus: ten year experience in an Australian teaching hospital.

Sixteen cases of caecal volvulus were treated surgically at a major Australian teaching hospital over a decade. Review of these cases suggests that this condition may be more common in fit people between 30 and 40 years of age than in the elderly or institutionalised. Caecal volvulus was more common in women than in men, possibly because adhesions from previous gynaecological surgery may initiate volvulus. In some other cases colonic distension due to poor muscle tone rather than distal obstruction may have been an important predisposing factor. Preoperative diagnosis was not usually made, but might have been facilitated if knowledge of the above predisposing factors had been available. This would allow colonoscopic reduction to be considered as a therapeutic alternative to laparotomy. At laparotomy, right hemicolectomy or caecal fixation (caecostomy or caecopexy) were the alternative methods of treatment.

Adult↗