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Biomedical subjects

M A Gerber

Publications and source records attributed to M A Gerber.

At least 91 records · Page 5Linked to original sources
PubMed1993

Hepatitis C RNA in liver of chronic hepatitis C patients before and after interferon alfa treatment.

BACKGROUND: Successful treatment of chronic hepatitis C with interferon alfa is frequently followed by relapse. Because loss of hepatitis C viral RNA (HCV-RNA) in serum is not predictive of sustained response, the loss of HCV-RNA in liver as a predictor of sustained response was investigated. METHODS: Twenty-one patients with chronic hepatitis C treated with recombinant interferon alpha had HCV-RNA sequences determined in frozen liver tissue before and after treatment and in serum at the end of treatment. Reverse double polymerase chain reaction was used to detect sequences to the 5' nontranslated region of the HCV genome using double nested primers. RESULTS: HCV-RNA disappeared in the liver in 10 of 11 (91%) complete responders whereas it remained detectable in the liver or serum of 7 of 8 (87%) nonresponders. Five complete responders relapsed biochemically during 6 month's follow-up; 4 of these had no detectable HCV-RNA in liver at end of treatment. CONCLUSIONS: Disappearance of HCV-RNA in liver correlates with initial clinical outcome, but as previously reported with serum HCV-RNA, this loss does not necessarily allow prediction of a sustained response.

Base Sequence↗
PubMed1993

Long-term outcome of Lyme disease in children given early treatment.

Sixty-three patients treated with appropriate antimicrobial therapy between 1985 and 1990 for physician-documented erythema migrans were identified. A telephone interview program 1 to 6 years after the initial episode of Lyme disease revealed that none of the patients had evidence of carditis, arthritis, or neurologic complications attributable to Lyme disease. A new episode of erythema migrans was reported in 7 (11%) of the patients 1 to 4 years after the initial episode.

Anti-Bacterial Agents↗
PubMed1993

Relation of hepatitis C virus to hepatocellular carcinoma.

Hepatitis C virus is an enveloped, single-stranded RNA virus with a positive stranded genome of about 9400 nucleotides. It probably belongs to the family of Flaviviridae which replicate via full-length, complementary, negative-stranded RNA. Hepatitis C virus is the predominant etiologic agent of non-A, non-B hepatitis around the world. It frequently leads to chronic hepatitis which may progress to cirrhosis and hepatocellular carcinoma. The currently available antibody assay for hepatitis C virus cannot distinguish between current and past hepatitis C virus infection. We developed a strand-specific reverse double polymerase chain reaction for detection of hepatitis C virus RNA (non-translated and non-structural sequences) in extracts of hepatocellular carcinoma tissues and the surrounding liver. Negative (replicative) and positive (genomic) strands of hepatitis C virus RNA were detected in both liver and tumor tissues in almost equal frequency and relative amounts. These data suggest that hepatitis C virus replicates in hepatocellular carcinoma cells and supports the epidemiologic evidence for an association between chronic hepatitis C virus infection and hepatocarcinogenesis.

Base Sequence↗
PubMed1993

Persistence of hepatitis B virus DNA in the liver after loss of HBsAg in chronic hepatitis B.

To determine whether patients with chronic hepatitis B who lose hepatitis B virus DNA and HBsAg from the serum completely resolve the hepatitis and virus infection, we evaluated serum and liver tissue from 11 patients who had lost HBsAg. These patients were evaluated for clinical, histological and serological features and for hepatitis B virus DNA by use of hybridization and polymerase chain reaction techniques. Liver biochemical test results were normal in all except two patients who had mild aminotransferase elevations. All sera were negative for hepatitis B virus DNA by direct hybridization, and only one was positive transiently by polymerase chain reaction. Liver histology was abnormal in all patients, but the changes were mild and markedly improved compared with biopsy specimens taken before loss of HBsAg. Liver tissue from 10 patients was positive for hepatitis B virus DNA by polymerase chain reaction but not by direct hybridization. These findings indicate that loss of HBsAg is associated with marked improvements in clinical and serum biochemical features of chronic hepatitis B, yet mild degrees of hepatitis and low levels of viral DNA may persist in the liver.

Adult↗
PubMed1993

HLA-DR expression in bile duct damage in hepatitis C.

Several investigations have demonstrated aberrant expression of HLA-DR on damaged bile duct epithelium of patients with primary biliary cirrhosis, liver allograft rejection, graft versus host disease, and AIDS. Since bile duct damage is a prominent feature of chronic hepatitis C, it may also be associated with HLA-DR induction. Therefore, we examined the expression of HLA-DR antigen in formalin-fixed, paraffin-embedded liver biopsy sections of 30 patients with chronic hepatitis C by the avidin-biotin peroxidase complex method using a monoclonal antibody to HLA-DR. HLA-DR was not detected on bile duct epithelium in any of the cases, although bile duct damage of varying degree was observed in 90% of the cases. HLA-DR was expressed by Kupffer cells; inflammatory infiltrates in portal tracts, and in areas of piecemeal necrosis and lobular necrosis; dendritic cells in portal and periportal areas; and occasionally hepatocytes. These observations suggest that the mechanism of bile duct injury in chronic hepatitis C may be different from that of other conditions such as primary biliary cirrhosis, liver allograft rejection, and graft versus host disease.

Antibodies, Monoclonal↗
PubMed1993

Hepatitis C in liver allografts.

Recurrent or intercurrent hepatitis C represents significant problems in patients with liver transplants and must be differentiated from hepatic allograft rejection and other conditions affecting allografts. Often, the currently available anti-hepatitis C virus (HCV) tests are not helpful in the differential diagnosis, because preexisting anti-HCV may persist after transplantation or its development may be delayed. We determined the presence of HCV RNA by the reverse double polymerase chain reaction in biopsy specimens of liver allografts from nine patients with acute or chronic hepatitis of uncertain origin and from three patients with cellular allograft rejection. The NS3 region sequences of HCV were detected in seven of nine liver allograft biopsy specimens 6 weeks to 20 months after transplantation. Hepatitis C virus RNA was not detected in two patients. One of these patients was anti-HCV positive, showing mild acute hepatitis 5 weeks after transplantation. Anti-HCV was present in three patients with detectable HCV RNA in the liver but was absent from four other patients with HCV RNA. These findings suggest that HCV is a major cause of acute and chronic hepatitis following liver transplantation, that detection of HCV RNA by polymerase chain reaction in the liver biopsy specimen represents a reliable method for the diagnosis of hepatitis C in liver allografts, and that in some patients HCV may be acquired during transplantation while in others it may represent a recurrent infection.

Hepacivirus↗
PubMed1993

Early Lyme disease: a flu-like illness without erythema migrans.

The existence of a form of early Lyme disease characterized by a flu-like illness without erythema migrans is controversial. To confirm the existence and define the clinical characteristics of the flu-like illness without erythema migrans of localized Lyme disease, the authors studied patients from a Lyme disease endemic area of Connecticut who visited their primary care physicians with an undefined flu-like illness. Patients kept a diary of their symptoms. Acute and convalescent sera were obtained. The diagnosis of Lyme disease was based on the appearance of IgM or IgG antibodies to Borrelia burgdorferi as demonstrated by both enzyme-linked immunosorbent assay and immunoblot assay. Twenty-four untreated patients were studied. In five patients acute serologic evidence of Lyme disease developed. The flu-like illness in these five patients was characterized by fever and fatigue and resolved spontaneously in 5 to 21 days. Symptoms recurred in three of these five patients. The existence of a flu-like illness without erythema migrans of early Lyme disease has been clearly established. Prospective, controlled studies are needed to better define its incidence, characteristics, and prognosis so that appropriate diagnostic and therapeutic strategies can be developed.

Acute Disease↗
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↗