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Biomedical subjects

Anthony J Freeman

Publications and source records attributed to Anthony J Freeman.

11 recordsLinked to original sources
PubMed2005

Damage control surgery and angiography in cases of acute mesenteric ischaemia.

BACKGROUND: Acute mesenteric arterial occlusion typically presents late and has an estimated mortality of 60-80%. This report examines the evolution of a novel management approach to this difficult surgical problem at a teaching hospital in rural Australia. METHODS: A retrospective review of 20 consecutive cases that presented to Lismore Base Hospital, Lismore, New South Wales, between 1995 and 2003 was performed. RESULTS: Of the 16 patients who were actively treated, 10 survived. Mortality was associated with attempting an emergency operative revascularisation and not performing a second-look laparotomy. All three patients who had a damage control approach at the initial operation survived and in four cases endovascular intervention successfully achieved reperfusion of acutely ischaemic bowel. CONCLUSIONS: Evidence from the series of patients described suggests that damage control surgery and early angiography improve survival in patients suffering acute mesenteric ischaemia. A damage control approach involves emergency resection of ischaemic bowel with no attempt to restore gastrointestinal continuity and formation of a laparostomy. Patients are stabilised in the intensive care unit (ICU) and angiography can be arranged to either plan a definitive bypass procedure or alternatively endovascular therapies can be carried out in an attempt to arrest gastrointestinal infarction. Definitive surgery is then considered after 2-3 days. This approach is particularly attractive if immediate specialist vascular expertise is not available.

Acute Disease↗
PubMed2004

Prevalence of production of virus-specific interferon-gamma among seronegative hepatitis C-resistant subjects reporting injection drug use.

This report describes subjects who were highly likely to have been repeatedly exposed to hepatitis C virus (HCV) through injection drug use and who remained negative for anti-HCV antibody. Production of virus-specific interferon- gamma by peripheral blood mononuclear cells was seen in the majority of subjects (72%) and was associated with higher-risk behavior. For 92% of the subjects, results of recombinant immunoblot assays demonstrated faint bands against nonstructural proteins. The immune responses described are likely to have been primed and maintained by episodes of subclinical infection without classic seroconversion and may indicate a hepatitis C-resistant phenotype. Vaccine strategies to mimic this response may provide protection against persistent HCV infection.

Adolescent↗
PubMed2004

Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort.

Understanding the earliest virological and immunological events in acute hepatitis C virus (HCV) infection may provide insight into the determinants of protective immunity. Four cases of HCV viremia with subsequent viral clearance, but without biochemical hepatitis or anti-HCV seroconversion, are reported from a prospective cohort study of prison inmates. Two of the subjects who developed sustained viremia were assessed for production of interferon (IFN)- gamma, by use of the enzyme-linked immunospot (ELISPOT) method and by assessment of HCV cytotoxic T lymphocyte (CTL) activity, CD4 lymphocyte proliferative responses, HCV load, and genotype. After 2-6 months of viremia, all 4 subjects cleared serum HCV RNA. Specific cellular responses were detected in both of the subjects who were assessed, and production of IFN- gamma was demonstrated in one subject. All subjects had weak, but consistent, serological reactivity against HCV nonstructural proteins on immunoblot testing, despite repeatedly nonreactive HCV ELISA tests. These cases highlight the potential for cellular immune responses against HCV to facilitate viral clearance, responses that may model those required for effective HCV vaccination.

Adult↗
PubMed2003

The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection.

BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.

Adult↗
PubMed2003

Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation.

The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.

Adult↗
PubMed2003

Natural history models for hepatitis C-related liver disease: different disease progression parameters for different settings.

An understanding of the natural history of hepatitis C virus (HCV) infection has improved in recent years. Estimates of liver disease progression among people with chronic hepatitis C have been developed from various study populations, including liver clinics, post-transfusion hepatitis C cohorts and community-based cohorts. These estimates can be used in hepatitis C natural history models; however, they need to be matched to differing requirements. Estimation and projection of liver disease burden at the population level requires estimates of HCV prevalence and incidence, and disease progression among all people with chronic hepatitis C. Liver disease progression based on community cohorts would appear the most appropriate for a population level model. In contrast, models that examine the cost-effectiveness of antiviral therapy for people with chronic hepatitis C require disease progression estimates from the treatment setting. Further models are required to determine individual prognosis and should be based on an assessment of cofactors for liver disease progression.

Antiviral Agents↗
PubMed2002

Is severe liver disease a common outcome for people with chronic hepatitis C?

For people with chronic hepatitis C, an assessment of their risk of progression to advanced liver disease is a major priority. Early studies of the natural history of chronic hepatitis C suggested that development of cirrhosis was a relatively common outcome, even in the first 20 years of infection. These studies were either cross-sectional liver clinic series of people referred for assessment to specialist clinics, or longitudinal cohorts of people with post-transfusion hepatitis. More recent studies (particularly longitudinal community-based cohorts) indicate that liver disease progression is generally slow, and that a minority of people with chronic hepatitis C will develop advanced liver disease. Based on an extensive review of studies reporting on chronic hepatitis C natural history, we have developed a Markov model of liver disease progression. This model estimates that the risk of progression to cirrhosis is 7% and 20% after 20 and 40 years of infection, respectively. Corresponding estimates for hepatitis C-related mortality are 1% and 4%. However, liver disease progression is highly variable, and certain subgroups of people with chronic hepatitis C are at increased risk of advanced liver disease. Those groups include people with a heavy alcohol intake, those who have coinfection with HIV or HBV, and those who have already progressed to moderate to severe hepatic fibrosis.

Disease Progression↗
PubMed2002

Quantification of hepatitis C virus in human liver and serum samples by using LightCycler reverse transcriptase PCR.

A highly sensitive, non-probe-based, real-time quantitative reverse transcriptase PCR was developed for viral load measurements in both serum and liver samples from patients with hepatitis C virus (HCV) infection. With synthetic RNA, the linearity of the approach was conserved over a wide range of HCV copy numbers. There was a strong correlation between hepatic and serum viral load measurements (r = 0.689, P = 0.004, n = 15), indicating that the level of viremia reflected the amount of virus present in the liver.

Hepacivirus↗