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W Kirwan

Publications and source records attributed to W Kirwan.

3 recordsLinked to original sources

Tissue viral load variability in chronic hepatitis C.

OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.

Adult↗

Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome.

Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4/352.4 vs. 76.7/139.4, P < 0.001) as were endothelial E-selectin/ICAM-1 expression compared with normal EC (8.1/9 vs. 3.9/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN/EC that were not treated dopamine (174/240 vs. 252/352, P < 0.05 and 4/4.4 vs. 8.1/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium, and consequently, modulates PMN exudation. Thus, biogenic amines, including dopamine, may function as anti-inflammatory cytokines.

CD18 Antigens↗