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Biomedical subjects

K E Sherman

Publications and source records attributed to K E Sherman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Tests of the liver: use and misuse.

Physicians frequently order batteries of tests that are used to assess liver injury or function. These tests are frequently ordered to screen for disease. However, a lack of understanding of the nature of the assays and the laboratory assignment of normal versus abnormal often leads to unnecessary workup or missed disease. We attempt to describe the nature of the most commonly used laboratory tests for liver disease, including alanine and aspartate aminotransferases, alkaline phosphatase, bilirubin, and gamma glutamyl transpeptidase. In addition, the role of functional tests of the liver, including prothrombin time, and metabolite clearance tests, such as aminopyrine and monoethylglycinexylidine, are examined.

Albumins↗
PubMed1997

Hepatitis C serotypes in nonalcoholic and alcoholic patients.

Genotyping of the hepatitis C virus (HCV) RNA can be performed by a variety of methods following polymerase chain reaction amplification of a stable RNA portion of the genome. The gold standard is amplification of the RNA from the NS5 region, followed by direct sequencing and homology comparison. This method is extremely labor intensive. In this study, we compared an immunoblot serotyping technique (HCV SIA) to a reverse-hybridization line-probe assay (LiPA) for genotype classification among non-alcoholic HCV infected patients. We then compared and contrasted the response in this cohort to a population of alcoholic patients with HCV infection. To validate the serotype assay, sera from 110 patients with chronic HCV infection was utilized. Serotyping (Chiron SIA) and genotyping by the LiPA (Line Probe Assay, Innogenetics) reverse-hybridization technique was performed. Additionally, both methods were compared to sequence-derived genotyping in 26 patients based on PCR amplification of the NS5 region. After the validation phase, sera from 105 alcoholic patients was genotypically classified by the serologic method. The nonalcoholic and alcoholic groups were then compared with regard to serotype, demographics, and frequency of untypable test results. Among typable pairs, the overall concordance rate between serotyping and LiPA-based genotyping was 93.75%. Patients with genotype 1 by reverse hybridization demonstrated a 95.8% concordance with serotype. Untypable samples were present for both techniques, but since they occurred in different patients, the techniques were complementary. Alcoholic patients were significantly more likely to be infected with untypable serotypes than those without a pattern of alcohol abuse. These patients were also more likely to be HCV RNA negative than sera from typable patients. Serotype 1 was associated with high HCV RNA titer and poor interferon treatment response among both nonalcoholic and alcoholic patients. An immunoblot method for the evaluation of genotype classification was rapid and easily performed compared to sequence-based genotyping. There was a high degree of concordance compared to reverse-hybridization and sequence-based genotype characterization methods. Failure to detect HCV RNA in the serum is associated with a higher likelihood of classification failure. This problem was particularly prevalent in the alcoholic population. HCV RNA titers and treatment outcomes were strongly associated with serotype classification results, demonstrating clinical utility of this assay technique.

Adult↗
PubMed1996

Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope coding domain.

Patients coinfected with the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) were studied with regard to nucleotide sequence variability in the E2/NS1 first hypervariable region of the HCV genome. The nucleotide variability within individual patients was compared to patients infected only with HCV. The proportion of predicted synonymous and nonsynonymous amino acid changes, and the relationship to putative high-antigenicity sites, were evaluated in the hypervariable envelope domain. Ninety-one clones from 10 patients with HCV/HIV coinfection were sequenced, following polymerase chain reaction (PCR) amplification of the hypervariable region. The control HCV group included 53 clones from 7 patients. Sequence analysis encompassed the region coding for amino acids 384 to 414. Consensus sequences from each patient were used as the internal standard for nonsynonymous amino acid codon variability. Cumulative proportional comparison at each amino acid site revealed increased variability in HCV RNA from patients with HCV/HIV coinfection versus HCV alone (P < .05). The greatest variability was observed at amino acids 386, 397, 400, 402, 405, 407, and 414, with >l0 percent clonal variation at these sites. Jameson-Wolf plots were used to predict putative high-antigenicity domains. Nonsynonymous clonal variation resulted in alteration of putative antigenic sites within the hypervariable region. All clones had at least one high-probability site. Clones with unique predicted antigenic domains were observed more frequently in HIV/HCV coinfected patients, and, independent of viral titer, were consistent with increased sequence variability. These data suggest an accumulation of envelope variants in the HCV/HIV coinfected patients, which could be related to ineffective viral clearance, and may help explain prior reports of interferon (IFN) resistance in this patient group.

Adult↗
PubMed1995

The effectiveness of simethicone in improving visibility during colonoscopy when given with a sodium phosphate solution: a double-bind randomized study.

BACKGROUND: Oral sodium phosphate solution is better tolerated than polyethylene glycol when used for colonoscopy preparation, but visibility of the lumen can be impaired because of the presence of bubbles. METHODS: We studied 86 patients receiving either simethicone (n = 42) or placebo (n = 44) in addition to oral sodium phosphate to determine if simethicone improved visibility during colonoscopy. Colonoscopy was performed by a single blinded investigator. Five areas of the colon (rectosigmoid, descending, transverse, ascending, and cecum) were assessed for the presence of bubbles on withdrawal of the endoscope. Bubbles were scored as follows: 0, minimal or none; 1, covering half the lumen; 2, covering the entire circumference; 3 filling the entire lumen. RESULTS: Thirteen patients in the placebo group and only one in the simethicone had significant bubbles ( > or = 1). Additionally, the mean bubble scores were greater in the placebo group in each region of the colon (p < or = 0.05 in rectosigmoid and ascending colon). CONCLUSIONS: This study indicates that taking simethicone with an oral sodium phosphate preparation can improve colonic visibility by diminishing the presence of bubbles. Better visualization could improve detection of mucosal pathologic lesions.

Administration, Oral↗
PubMed1995

Talc in the liver of patients with chronic hepatitis C infection.

OBJECTIVES: The presence of talc crystals in the liver has been associated with prior history of i.v. drug abuse (IVDA). Patients with hepatitis C virus (HCV) infection often deny IVDA, and many patients have no other identifiable risk factors. To evaluate the role of prior surreptitous IVDA in patients with chronic HCV infection and to assess the role of talc identification in liver tissue, an epidemiological evaluation was performed. METHODS: One hundred and nine patients with chronic HCV (ALT abnormal > 6 months, HCV ELISA and recombinant immunoblot assay positive) underwent careful evaluation for risk factors potentially associated with HCV infection. All patients then had liver biopsy. Liver biopsies were reviewed by two observers to determine histological stage and were then examined by polarized light microscopy to reveal the presence or absence of typical talc crystals. Patients with discordance between history and histological findings were re-interviewed and were confronted with the information. RESULTS: Patient interviews revealed the following risk factors: IVDA, 17.1%; blood transfusion, 24.3%; possible household/occupational exposure, 14.4%; and tattoos, 15.3%. No identifiable risk factors were noted in 28.8% of the cohort. Talc crystals were seen in 9/109 (8.3%) of liver specimens. Of this group, only two patients admitted to prior history of IVDA. Seventeen patients with an IVDA history did not have identifiable talc crystals. Follow-up phone interviews were possible with five out of seven patients with liver talc who had previously denied IVDA history. Of the five patients, three admitted to prior IVDA but only after being confronted with the liver biopsy evidence. CONCLUSIONS: The findings of talc crystals in liver biopsy specimens appears to be a specific, but not a sensitive, marker for prior IVDA. Identification of talc crystals from liver tissue may contribute to categorization of risk factors in patients with community-acquired HCV infection. Tattoos are an important, and frequently unrecognized, risk factor for HCV infection. Despite these findings, a significant proportion of patients still have no identifiable risk factor for HCV acquisition.

Adult↗
PubMed1994

Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis.

Autoimmune chronic active hepatitis is traditionally treated with corticosteroids, or corticosteroids with azathioprine. These drug therapies require long treatment periods and are associated with many debilitating drug side effects. Five patients with type I autoimmune chronic active hepatitis, and one with a probable overlap syndrome were treated with cyclosporine. All patients had previously undergone treatment with corticosteroids or corticosteroids with azathioprine and had failed to achieve total remission. In addition, all patients had significant side effects associated with therapy. Five of six patients normalized or near normalized alanine aminotransferase levels within 10 weeks of starting cyclosporine therapy. Biochemical remission was sustained for periods of up to 1 year in all primary cyclosporine responders as long as therapeutic cyclosporine levels were maintained. All responders had symptomatic improvement. Post-treatment liver biopsy was performed in three patients and histologic improvement was demonstrated in all cases. Cyclosporine appears to be a viable alternative to corticosteroid/azathioprine therapy for autoimmune chronic active hepatitis in patients who experience an incomplete response or who cannot tolerate the side effects of standard therapy.

Adult↗
PubMed1994

A 39 year old man with chronic hepatitis.

The diagnosis of primary sclerosing cholangitis in association with autoimmune hepatitis was made in this case after the discovery of inflammatory bowel disease prompted a cholangiogram. Immunosuppressive therapy with cyclosporine prior to ERCP resulted in a significant decrease in serum aminotransferase. Liver histology and autoimmune serologies favored a diagnosis of AIH, while cholangiographic findings suggested PSC. A review of similar cases describing the simultaneous occurrence of AIH and PSC is presented. The shared autoimmune characteristics of the two diseases, such as serum autoantibodies, peripheral lymphocyte subsets and HLA haplotypes, raises the question of whether similar mechanisms of immune dysfunction can result in both processes. The existence of a PSC-AIH overlap syndrome may help provide the linkage between the two diseases.

Adult↗
PubMed1994

The use of oral fluid for hepatitis C antibody screening.

OBJECTIVES: To assess the efficacy of oral fluid antibody testing for the detection of hepatitis C. METHODS: Paired serum and oral fluid collections were obtained from 216 subjects. A modification of the serum HCV ELISA assay was developed to improve test accuracy for an oral fluid substrate. Sensitivity was determined in 109 HCV serum ELISA-positive patients and specificity in 107 HCV serum ELISA-negative patients. RESULTS: Overall sensitivity of oral fluid collection and testing was 98.2%; specificity was 99.1%. These parameters did not seem to be altered by presence of concurrent hepatitis B infection, inflammatory state of the liver, or other factors. CONCLUSIONS: Oral fluid collection and HCV antibody testing by the modified ELISA method seems to be an effective and efficient alternatives to venipuncture and serum HCV antibody testing. Their use may facilitate epidemiological surveys and evaluation of individual patients when blood collection is not feasible.

Adult↗
PubMed1993

Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections.

Quantitation of the hepatitis C virus (HCV) provides a powerful epidemiologic and therapeutic method for the evaluation of infected patients. In this study semiquantitative reverse transcriptase polymerase chain reaction (PCR) is compared with a new branched DNA signal amplification methodology. Samples from HCV-infected patients as well as from human immunodeficiency virus-infected patients were evaluated. Reverse transcriptase PCR correlated well with the branched DNA assay (r = 0.7036, P < 0.05). HCV RNA was found to occur at significantly higher titers (P < 0.05) in patients coinfected with the human immunodeficiency virus compared with titers in those infected with HCV alone. Immune status as defined by the CD4+ count was not associated with the observed difference in viral titer.

Base Sequence↗
PubMed1992

End-stage liver disease in a 31-year-old man.

This is a case of decompensated chronic liver disease associated with FZ phenotype AAT deficiency. Histologic confirmation of the diagnosis was aided by immunostaining of the AAT globules. Liver transplantation was successful in reversing the disease process.

Adult↗
PubMed1991

Low thymosin alpha-1 concentrations in patients chronically infected with the hepatitis B virus.

Serum concentrations of thymosin alpha-1 (TA-1), an immunoregulatory peptide, were assayed in patients with chronic hepatitis B infection and volunteer blood donor controls. Coded samples were tested using a radioimmunoassay. The TA-1 concentrations in HBsAg-positive patients averaged 1555 pg/ml, whereas in the control group, the mean TA-1 in serum was 2159 pg/ml (P less than 0.001). Similar results were found for age- and sex-matched pairs. The TA-1 concentration was not associated with HBe antigen/antibody status or with values of liver-associated enzymes. Analysis of T-cell subsets in nine HBsAg carriers revealed significantly decreased CD4 (helper)-cells, both in absolute numbers and as the percentage of total lymphocytes present. These data suggest that individuals with chronic hepatitis B infection have a relative deficiency of the immunomodulatory peptide TA-1, which may contribute to the characteristics of the resultant T-cell population.

Adult↗
PubMed1991

Alanine aminotransferase in clinical practice. A review.

Alanine aminotransferase is an enzyme produced mainly in the liver. When serum activity is measured, it provides a marker of hepatic disease. This review explores the biochemistry and laboratory analysis of alanine aminotransferase in terms of its significance in human health and disease. Cut-off levels that define abnormality are rather arbitrary and this decreases the specificity of the test in apparently healthy patients. A small, but important, group of patients with alanine aminotransferase abnormality have underlying liver disease that may be treatable. Most can be diagnosed based on history, physical examination, and biochemical-serological profiles. Liver biopsy can complement the diagnostic process in selected circumstances. Literature pertaining to this is critically reviewed.

Alanine Transaminase↗