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Biomedical subjects

M A Gerber

Publications and source records attributed to M A Gerber.

At least 19 recordsLinked to original sources
PubMed1992

The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Adolescent↗
PubMed1992

A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites.

BACKGROUND: Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern United States. Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten. METHODS: To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic. Children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days. Subjects were followed for one year for clinical manifestations of Lyme disease. Serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi. RESULTS: Of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo. Of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with B. burgdorferi. Erythema migrans developed in two subjects, both of whom had received placebo. There were no asymptomatic seroconversions and no late manifestations of Lyme disease. The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (P = 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent). CONCLUSIONS: Even in an area in which Lyme disease is endemic, the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated.

Adult↗
PubMed1992

Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease.

To determine if antibodies to Borrelia burgdorferi persist after antibiotic treatment, we recalled 32 patients with Lyme disease from a primary care practice a mean of 16 months after treatment and analyzed initial and follow-up serum samples by ELISA and immunoblot assays. Of the eight patients whose initial serum specimens were positive for IgM antibody by ELISA, three had positive titers of IgM antibody at follow-up; of the 23 patients whose initial serum specimens were positive for IgG antibody by ELISA, 19 had positive titers of IgG at follow-up. Of the five patients whose initial serum specimens were positive for IgM antibody by immunoblot, two had positive titers of IgM antibody at follow-up; of the 30 patients whose initial serum specimens were positive for IgG antibody by immunoblot, 29 had positive titers of IgG antibody at follow-up. The bands on the IgG immunoblot remained remarkably constant during the period from analysis of the initial specimen to that of the follow-up specimen. Nine of the 32 patients had persistent or recurrent symptoms, and ELISA and immunoblot were not helpful for identifying these nine patients.

Adult↗
PubMed1992

Colour thresholding and objective quantification in bioimaging.

Computer imaging is rapidly becoming an indispensable tool for the quantification of variables in research and medicine. Whilst its use in medicine has largely been limited to qualitative observations, imaging in applied basic sciences, medical research and biotechnology demands objective quantification of the variables in question. In black and white densitometry (0-256 levels of intensity) the separation of subtle differences between closely related hues from stains is sometimes very difficult. True-colour and real-time video microscopy analysis offer choices not previously available with monochrome systems. In this paper we demonstrate the usefulness of colour thresholding, which has so far proven indispensable for proper objective quantification of the products of histochemical reactions and/or subtle differences in tissue and cells. In addition, we provide interested, but untrained readers with basic information that may assist decisions regarding the most suitable set-up for a project under consideration. Data from projects in progress at Tulane are shown to illustrate the advantage of colour thresholding over monochrome densitometry and for objective quantification of subtle colour differences between experimental and control samples.

Animals↗
PubMed1992

Detection of replicative hepatitis C virus sequences in hepatocellular carcinoma.

Several serologic studies suggest that infection by hepatitis C virus (HCV) may be associated with the development of hepatocellular carcinoma (HCC). Therefore, we examined tumor tissue and/or the surrounding liver of 20 patients for viral sequences by the polymerase chain reaction (PCR). In 12 cases, liver and tumor tissues were separable for extraction. RNA was extracted from frozen tissues and used as a template for reverse transcription followed by double PCR with nested primers for the 5'-untranslated (NT) and nonstructural NS3 regions of HCV. In addition, the tissue extracts were tested by single PCR for X gene and S gene sequences of hepatitis B virus (HBV). NT region sequences of HCV were detected in the available tumor tissue of all anti-HCV-positive patients except for one. Negative (replicative) strands of HCV RNA were found in the same tissues as positive (genomic) strands at almost the same relative amounts, suggesting replication of HCV in the tumor tissue rather than contamination by HCV-positive blood. HBV X and S sequences were demonstrated in two tumors, but were absent from three tumors that were surrounded by liver tissues with HBV X sequences. One patient had nucleic acids of both viruses in tumor tissue. These observations suggest that in addition to HBV, HCV may play a role in the development of hepatocellular carcinoma.

Adolescent↗
PubMed1992

Histopathology of community acquired chronic hepatitis C. The Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team.

As part of a study of community-acquired non-A, non-B hepatitis, liver biopsy specimens of 29 anti-HCV positive and four anti-HCV negative patients were evaluated in order to characterize the histopathologic changes of chronic hepatitis C. Liver biopsies were performed 6 to 46 mo after onset of the disease and repeat biopsies were obtained in 10 anti-HCV positive patients. The histologic diagnoses were chronic persistent hepatitis (45%), chronic active hepatitis (35%), and chronic lobular hepatitis (21%). Irrespective of the tissue diagnosis, the majority of the patients showed characteristic histologic abnormalities in the liver, particularly damage of the small and medium-sized bile ducts (76%), lymphoid aggregates in portal tracts (45%), enlarged macrophages (48%), and steatosis (31%). In 59% of the patients, two or more of these histologic abnormalities were combined. Similar histologic changes have previously been observed in non-A, non-B hepatitis, but only uncommonly in hepatitis A or hepatitis B. We conclude that the histopathologic findings in chronic hepatitis C are highly characteristic, although not pathognomonic.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1992

Detection of hepatitis C virus RNA sequences by polymerase chain reaction in fixed liver tissue.

Currently, the most reliable method for the diagnosis of hepatitis C virus (HCV) infection is the detection of viral sequences by the reverse transcription double polymerase chain reaction (RT/PCR) in serum or liver samples. We demonstrate here that noncoding region sequences (NT) of HCV were amplifiable by RT/PCR in guanidinium extracts of formalin-fixed (for 6 to 48 h), paraffin-embedded liver sections of patients with chronic hepatitis C. In contrast, core and nonstructural region sequences of HCV were not detectable in fixed tissues by PCR amplification. Boiling of routinely processed tissue sections in water containing Chelex-100, a method for extraction of amplifiable hepatitis B virus DNA, was not successful. The amount of nucleic acid extracts from fixed liver sections needed for amplification of NT region sequences was over 1000 times larger than that of extracts from frozen tissue. This method will be useful for diagnostic and investigative studies of HCV infection.

Aged↗
PubMed1991

Development and application of an in vitro model for screening anti-hepatitis B virus therapeutics.

The development of effective anti-hepatitis B virus agents has been hampered by the lack of reliable in vitro systems for the screening of new therapeutics. In an effort to circumvent this problem, we have developed an in vitro system for screening anti-hepatitis B virus drugs using hepatitis B virus DNA-transfected Hep G2 cells. The cell line designated 2.2.15 produces replicative viral DNA intermediates, mature Dane particles and high levels of viral antigens. Subconfluent 2.2.15 cells were treated with a variety of commonly used anti-hepatitis B virus therapeutics, and their efficacy was determined by analyzing changes in the replicative cellular or extracellular hepatitis B virus DNA content by Southern blotting or slot-blot hybridization. The slot-blot method was sensitive, reproducible and rapid and correlated well with Southern blotting. Analysis of the media for hepatitis B virus DNA was indicative of changes in intracellular, replicative hepatitis B virus DNA, permitting sampling of the media. Therefore 2.2.15 cells may provide a valuable method for identifying and monitoring effective anti-hepatitis B virus therapeutics. Using this system to test various agents, we confirm that 2'-deoxyguanosine strongly inhibited viral replication, whereas others tested were less effective. Correlation with in vivo systems is now needed.

Antiviral Agents↗
PubMed1991

Comparative studies on the detection of hepatitis B virus DNA in frozen and paraffin sections by the polymerase chain reaction.

The polymerase chain reaction (PCR) is an extremely sensitive technique that has been used for detection of DNA sequences in formalin-fixed, paraffin-embedded tissues. In order to verify that hepatitis B virus (HBV) DNA sequences are adequately preserved in routinely processed liver tissues, we performed PCR with five different primer pairs for HBV sequences on DNA extracted by two different methods from paraffin and frozen liver sections. The amount of PCR products obtained with DNA templates extracted by the proteinase K-SDS method from frozen sections was significantly larger than that from paraffin sections. However, boiling of deparaffinized sections in water containing Chelex-100 resulted in ample amounts of PCR products irrespective of the primers used. On Southern blots, the location of the bands of amplified DNA obtained by the different methods was consistent with the predicted size, suggesting that the viral sequences had not been altered by processing. Although freezing of fresh tissue yields quantitatively more HBV DNA, formalin fixation qualitatively preserves the viral DNA sequences adequately for detection by PCR. Therefore, formalin-fixed, paraffin-embedded tissues may be used for the detection of viral DNA sequences by PCR. Application of the described procedure to routinely processed tissues significantly broadens the applicability of this powerful diagnostic and investigative method.

Base Sequence↗
PubMed1991

Immunohistochemical studies of human immunodeficiency virus-1 in liver tissues of patients with AIDS.

A wide spectrum of hepatic lesions has been reported in AIDS, but it is not known whether the changes are related to the presence of human immunodeficiency virus type 1 (HIV-1). Therefore, we examined liver sections from 15 consecutively autopsied patients with AIDS for the presence of HIV-1 antigens p24 (core) and gp41 (envelope) by the avidin-biotin-peroxidase complex method using monoclonal antibodies. The most common histologic abnormalities noted were steatosis, portal inflammation, Kupffer cell hyperplasia, and focal hepatocellular and bile duct damage. Intra-hepatic opportunistic organisms were detected in six of 15 (40%) cases, with Mycobacterium avium-intracellulare being the commonest (four cases). Immunoreactivity for HIV-1 antigens was demonstrated in 12 of 15 cases (80%), with staining limited to Kupffer cells and other mononuclear cells characterized by a lymphoid morphology. Approximately the same number and type of cells were stained with both monoclonal antibodies and did not bear any relation to the degree of histologic abnormalities nor to the presence of opportunistic infections. The data suggest that some pathologic changes in AIDS livers are more likely the result of an indirect effect mediated by infected resident and circulating mononuclear cells than a direct cytopathic effect of HIV-1.

Acquired Immunodeficiency Syndrome↗