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R Sallie

Publications and source records attributed to R Sallie.

45 records · Page 3Linked to original sources

Detection of genomic and intermediate replicative strands of hepatitis C virus in liver tissue by in situ hybridization.

Nonisotopic in situ hybridization using a digoxigenin-labeled cDNA probe to the 3' nonstructural region (NS5) of hepatitis C virus (HCV) was performed on liver tissue from 33 patients. The results were compared with PCR detection of HCV RNA performed on 24 of the biopsies. Nonisotopic in situ hybridization correlated well with PCR findings. Hybridization signals were detected, within the cytoplasm and nuclei/nucleoli of hepatocytes, mononuclear, and biliary epithelial cells. In patients with clinically and histologically defined chronic active hepatitis related to active HCV infection, HCV genome was frequently detected in biliary epithelium and correlated well with biliary damage, an otherwise uncommon finding in chronic active hepatitis due to other hepatotropic viruses. Further studies using sense and antisense probes synthesized from the 5' non-coding region of the HCV genome confirmed the localization of positive strand of HCV in the above cell populations. The replicative intermediate strand was also present in all cells, although less frequently observed, apart from biliary epithelium, where negative strand of HCV was undetectable. The findings of HCV genome in liver biopsies of two patients with no significant histological abnormalities may suggest that the damage seen in chronic HCV infection is immune mediated, although the cytopathic effect of the virus may also be important.

Acute Disease↗

Detection of hepatitis "C" virus in formalin-fixed liver tissue by nested polymerase chain reaction.

Interpretation of antibody to hepatitis C virus (HCV) in patients with liver disease is difficult due to false-positive reactivity in some conditions. To evaluate the feasibility of HCV in archival material, HCV was sought in formalin-fixed, paraffin-embedded liver biopsy specimens. Nested polymerase chain reaction was used to detect hepatitis C virus in formalin-fixed, paraffin-embedded liver biopsy specimens after total RNA was extracted from tissue by proteinase K digestion and phenol/chloroform purification. The relative efficiency of amplification of HCV RNA from formalin-fixed material was estimated semiquantitatively by serial dilution of cDNA synthesised from RNA extracted from fresh and formalin-fixed sections from the same liver. Although HCV RNA could be detected in formalin-fixed liver tissue by nested PCR in 5/5 cases in which HCV was detected in serum, amplification was approximately 5-fold less efficient than when HCV was amplified from fresh tissue. Nevertheless, nested PCR of HCV from formalin-fixed liver tissue represents a useful technique in addressing some important questions related to the pathogenesis of liver disease.

Adult↗

Failure of simple biochemical indexes to reliably differentiate fulminant Wilson's disease from other causes of fulminant liver failure.

Serum, urine and tissue biochemical findings were studied in 21 cases of fulminant Wilson's disease with respect to the value of a recently described biochemical index based on serum alkaline phosphatase and total serum bilirubin levels, and these cases were compared with 193 other cases of fulminant liver failure. Serum bilirubin, alkaline phosphatase and AST levels found in fulminant Wilson's disease were significantly different from those found in other cases of fulminant liver failure, but differentiation from other causes of fulminant liver failure on the basis of these biochemical parameters was not possible. The alkaline phosphatase/bilirubin and aspartate AST/bilirubin ratios derived from the above parameters were also significantly lower in fulminant Wilson's disease than in other categories of fulminant liver failure, but distinction between diagnostic categories on this basis was not possible. When ratios that correctly identified all cases of fulminant Wilson's disease were selected, 59/190 (31%) and 84/190 (44%) cases of non-Wilsonian fulminant liver failure would erroneously be assigned a diagnosis of fulminant Wilson's disease, by alkaline phosphatase/bilirubin and AST/bilirubin ratios, respectively. A low alkaline phosphatase-to-bilirubin ratio (< 0.57) in any category of fulminant liver failure suggested a significantly worse prognosis than in cases with higher ratios (chi 2, Yates' corrected = 5.37, p = 0.02). In the Wilson's disease group, serum and hepatic copper and ceruloplasmin concentrations were normal in 4/21, 2/15 and 2/19, respectively, whereas urinary copper level was elevated in 18/18 and was the most valuable test in diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Computerized measurement of iron in liver biopsies: a comparison with biochemical iron measurement.

The measurement of stainable hepatic iron using a microcomputer image analysis system was compared with standard biochemical measurements of liver iron content in 103 liver biopsy specimens--29 of idiopathic hemochromatosis, 51 of alcoholic liver disease and 23 of various nonalcoholic liver diseases. Sections were stained using Perls' method for iron; the mean area staining positively for iron was measured and expressed as a percentage of the area of biopsy measured. Biochemical (biochemical hepatic iron [mumol/gm dry wt]/age) and morphometrical (morphometrical hepatic iron [%]/age x 100) hepatic iron indices were calculated. Patients in the idiopathic hemochromatosis group had significantly higher biochemical hepatic iron concentrations (p less than 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 284 (range = 119 to 631), 21 (range = 2 to 65) and 15 (range = 3 to 31) mumol/gm dry wt, respectively. The biochemical hepatic iron index was also significantly higher (p less than 0.001) in the hemochromatosis group compared with the alcoholic liver disease and nonalcoholic liver disease groups: 5.8 (range = 2.1 to 13.7), 0.4 (range = 0 to 1.6) and 0.4 (range = 0 to 1.1), respectively. Computerized measurements were significantly higher in the hemochromatosis group (p less than 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 9.72% (range = 1.50% to 29.26%), 0.13% (range = 0% to 1.20%) and 0.03% (range = 0% to 0.40%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Diclofenac hepatitis.

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Chemical and Drug Induced Liver Injury↗

Transplantation in primary biliary cirrhosis.

Improved immunosuppressive regimens, better postoperative intensive care and judicious patient selection have all resulted in increased patient survival following orthotopic liver transplantation (OLT), which has become the preferred option for most patients with end-stage primary biliary cirrhosis (PBC). As with most other clinical series, PBC is now the most common indication for OLT in the King's College hospital and Cambridge programmes. To date (30 July 1990), 129 patients with PBC have been transplanted, with overall actual 1 and 5 year survival rates of 65 and 63% respectively. When patients transplanted since 1985 are considered, both the 1 and 2 year survival rates are 78%. Immediate operative mortality was 4.5%, generally due to uncontrollable bleeding, while further mortality within 30 days of operation--mainly consequent upon infection and multi-organ failure--has fallen from 40% prior to 1985 to 9% since 1988. Thirteen per cent of patients have been retransplanted for vanishing bile duct syndrome, manifest in this series invariably within the first 6 months following OLT. Although rehabilitation in this series was excellent, a significant percentage of cases have continuing problems with metabolic bone disease, hypertension and renal impairment, mainly due to cyclosporin toxicity.

Humans↗