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Biomedical subjects

M A Gerber

Publications and source records attributed to M A Gerber.

At least 55 records · Page 3Linked to original sources

Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation.

Recurrent infection with hepatitis C virus (HCV) is almost universal following orthotopic liver transplantation although clinical severity varies. Data on 135 patients who underwent transplantation for hepatitis C cirrhosis were reviewed. We describe a progressive, severe cholestatic form of hepatitis occurring in a subgroup of patients with recurrent hepatitis C. Ten patients with severe recurrent hepatitis C were identified; 1 has died, 1 awaits retransplantation, and 8 have undergone retransplantation. All 10 developed severe progressive cholestatic hepatitis, with a mean rise in bilirubin to 24.7 mg/dL at the time of retransplantation. Histology at initial recurrence was of mild hepatitis without evidence of rejection. The failed grafts showed either cirrhosis or confluent hepatic necrosis. The onset of cholestasis preceded retransplantation by less than 5 months. Our study suggests that a minority of patients with recurrent hepatitis C after undergoing liver transplantation develop a severe progressive cholestatic hepatitis and liver failure.

Adult↗

Iron overload in patients with chronic hepatitis C: a clinicopathologic study.

Recent studies suggest that increased hepatic iron may impair the response to interferon therapy in patients with chronic hepatitis C. We reviewed the records and liver biopsies of 72 patients with chronic hepatitis C to determine the prevalence of iron overload and to evaluate whether there is a correlation between serum and hepatic iron concentrations and activity of liver disease. Patients with other causes of liver disease or iron overload were excluded. Necroinflammatory activity and fibrosis were evaluated using modified Knodell score. Hepatic iron was assessed using Brissot's grading system. Increased serum iron and ferritin levels were found in 29% and 43% patients, respectively. Hepatic iron grades 0, I, II, III, and IV were present in 37%, 35%, 25%, 3%, and 0% of patients, respectively. A significant correlation was found between hepatic iron grade and serum ferritin (P = .0001). There was no correlation between hepatic iron grade and histological activity index or fibrosis score. In summary, we found a high proportion of patients with chronic hepatitis C had mild to moderate increase in hepatic iron content even when patients with alcoholism and recurrent transfusions were excluded. However, very few patients had severely increased iron load.

Adolescent↗

Hepatocellular carcinoma in long-term oral contraceptive use.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in certain parts of the world, particularly in Africa and Asia, but it is less commonly encountered in the United States. It is closely associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and almost always develops in a cirrhotic liver. In non-cirrhotic livers, HCC is found in about 20% of asymptomatic carriers of HBV and rarely in patients taking androgenic-anabolic or oral contraceptive (OC) steroids. We report four patients, who developed HCC after prolonged use of OC steroids. Whether OC steroids act as mutagen or co-carcinogen in hepatocarcinogenesis is not clear. To exclude latent HCV and HBV infections which may occur in the absence of their serological markers, we employed polymerase chain reaction for the detection of HBV and HCV sequences in the tumor and non-tumorous liver tissue. Viral sequences of HBV and HCV were undetectable in all four cases. These findings suggest OC use as the only known risk factor in these cases and, therefore, strengthen its possible role in hepatocarcinogenesis.

Adult↗

Evaluations of enzyme-linked immunosorbent assay procedure for determining specific Epstein-Barr virus serology and of rapid test kits for diagnosis for infectious mononucleosis.

Using the results of Epstein-Barr virus-specific immunofluorescence serology as the "gold standard," we found that the sensitivities of the five rapid test kits varied from 78 to 84% and specificities varied from 89 to 100%. Enzyme-linked immunosorbent assay-determined specific Epstein-Barr virus antibody profiles had a sensitivity and specificity of 98.6 and 95.5%, respectively.

Antibodies, Viral↗

Antibiotic resistance: relationship to persistence of group A streptococci in the upper respiratory tract.

Despite the use of penicillin for more than 40 years in treating GABHS infections, there has been no significant change in the in vitro susceptibility of GABHS to penicillin. Reported failures to eradicate GABHS from the upper respiratory tracts of patients with pharyngitis and the apparent resurgence of serious Group A streptococcal infections and their sequelae probably are not related to the emergence of penicillin resistance. Although erythromycin resistance in GABHS had been a major problem in Japan and continues to be a major problem in Finland, it has not been a problem in this country. The susceptibility of GABHS to the newer macrolide antibiotics appears to be similar to that of erythromycin. Comprehensive, community-wide programs to continuously monitor for erythromycin resistance in GABHS would be difficult to justify. However, because little is known about how erythromycin resistance in GABHS is acquired or spread, it would be reasonable to periodically monitor isolates of GABHS for erythromycin resistance. A substantial proportion of GABHS are currently resistant to tetracyclines and these agents are inappropriate for treating GABHS infections. Although little recent information is available about the susceptibility of GABHS to sulfonamides, these agents have been shown to be ineffective in eradicating GABHS from the upper respiratory tract regardless of the in vitro sensitivities. GABHS have not been shown to be resistant to any of the commonly used oral cephalosporins; however, there is a great deal of variability among these agents in their activity against GABHS. Clindamycin resistance in GABHS has remained unusual. This agent is an alternative for treating GABHS infections due to macrolide-resistant strains in patients who cannot be treated with beta-lactam antibiotics. There is no reason, based on the in vitro susceptibilities of GABHS, to change the current recommendations for treating GABHS infections with penicillin and for using erythromycin for patients who are allergic to penicillin.

Anti-Bacterial Agents↗

Lupus aortitis: a case report and review of the literature.

Systemic lupus erythematosus is a complex immunological and rheumatological disease that has numerous complications. Central to the pathogenesis of systemic lupus erythematosus is immune complex formation and deposition in blood vessels and end organs. This is a case report of an autopsy of a patient with systemic lupus erythematosus, end stage renal disease, peripheral vascular occlusive disease, pancreatitis, and aortitis. The aortitis was found to be immune complex mediated with deposition of IgG, C3, as well as fibrinogen in the wall of the aorta as shown by immunofluorescence. The hypercoagulable state of the patient is discussed with particular emphasis on the role of anticardiolipin antibodies, antiphospholipid antibodies, and anti-beta-2-glycoprotein I in the pathogenesis. This case is unique in that the immune complex mediated aortitis has not been described in the literature over the past 25 years. We recommend that the diagnosis of immune complex mediated aortitis be considered in the differential diagnosis of aortitis, particularly in the background of a patient with systemic lupus erythematosus.

Adult↗

Identification of bipotential progenitor cells in human liver regeneration.

Recent studies, including our own, suggest that intermediate filament proteins, particularly bile duct-specific cytokeratin 19 (CK19) and the hepatocyte-specific HepPar1 antigen define the developmental stages of hepatic progenitor cells during liver morphogenesis. We hypothesized that the HepPar1+ CK19+ progenitor cells are activated during human liver regeneration after massive hepatic necrosis and proliferate with the formation of so-called ductular hepatocytes or neocholangioles. We demonstrated previously that the ductular hepatocytes proliferate and share phenotypic characteristics with hepatocytes and biliary epithelial cells. In this investigation, we compared the expression pattern of intermediate filament proteins and HepPar1 antigen in ductular hepatocytes with that of bipotential hepatic progenitor cells. CK14, CK19, vimentin, and HepPar1 antigen were localized by immunoperoxidase staining in 13 human livers with regeneration after massive hepatic necrosis. Double immunostaining of three cases for CK14/CK19 and HepPar1/CK19 was also performed. CK19 reaction exhibited diffuse staining of the cytoplasm of many ductular hepatocytes and bile ducts in all cases. CK14 was expressed in the cytoplasm of ductular hepatocytes and few bile ducts in 5 of 12 specimens. HepPar1 staining was positive in many ductular hepatocytes in 11 of 13 cases. Vimentin was detected in the perinuclear cytoplasm of ductular hepatocytes and some bile duct epithelial cells in all regenerating livers. Double immunostaining for HepPar1/CK19 demonstrated that the ductular hepatocytes contained either HepPar1 or CK19 and that some ductular hepatocytes coexpressed both antigens. CK14, CK19, vimentin, and HepPar1 expression in ductular hepatocytes in human liver regeneration resembles the pattern seen in the developing human liver from 4 to 16 weeks' gestation. This suggests that the ductular hepatocytes recapitulate the developmental stages of bipotential liver progenitor cells and differentiate in steps marked by the acquisition or loss of specific phenotypic characteristics.

Adolescent↗

Antibiotic resistance in group A streptococci.

Although erythromycin resistance in GABHS has been a major problem in Japan and in Finland, it has not been a problem in the United States. The susceptibility of GABHS to the newer macrolide antibiotics seems to be similar to that of erythromycin. Comprehensive, community-wide programs to continuously monitor for erythromycin resistance in GABHS would be difficult to justify; however, because little is known about how erythromycin resistance in GABHS is acquired or spread, it would be reasonable to periodically monitor isolates of GABHS for erythromycin resistance. Despite more than four decades of use of penicillin in treating GABHS infections, no significant change has occurred in the in vitro susceptibility of GABHS to penicillin. The resurgence of severe, invasive GABHS infections and of acute rheumatic fever is not attributable to the emergence of strains of GABHS with increased resistance to penicillin. A substantial proportion of GABHS are currently resistant to tetracyclines, and these agents are inappropriate for treating GABHS infections. Although little recent information is available about the susceptibility of GABHS to sulfonamides, these agents have been shown to be ineffective in eradicating GABHS form the upper respiratory tract regardless of the in vitro sensitivities. GABHS have not been shown to be resistant to any of the commonly used oral cephalosporins; however, a great deal of variability exists among these agents in their activity against GABHS. Clindamycin resistance in GABHS has remained unusual. This agent is an alternative for treating GABHS infections due to macrolide-resistant strains in patients who cannot be treated with beta-lactam antibiotics.

Anti-Bacterial Agents↗

Detection of hepatitis B and hepatitis C viral sequences in fulminant hepatic failure of unknown etiology.

In a significant number of patients, the etiology of fulminant hepatic failure (FHF) is unknown. To determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) play a role in patients without serologic markers of HBV and HCV infection, the authors examined tissue samples from 15 liver explants with massive hepatic necrosis for the presence of viral sequences by the polymerase chain reaction (PCR). The specimens were derived from nine patients with FHF of unknown etiology; two with serum hepatitis B surface antigen (HBsAg); two with antibodies to HCV; one with antibodies to hepatitis A virus (HAV) and anti-HBc of the IgM class; and one with isoniazid toxicity. Nucleic acids were extracted from frozen liver samples. RNA was used as a template for reverse transcription, followed by double PCR with nested primers for the 5'-untranslated region of HCV. DNA was tested by single PCR for S gene sequences of HBV. Hepatitis B virus sequences were detected in the specimens of the two HBsAg positive patients, the anti-HAV/anti-HBc positive patient, and three of nine patients with FHF of unknown etiology. Hepatitis C virus sequences were present in the explant of one patient with FHF of unknown etiology, but not in the two patients with antibodies to HCV. In two specimens with molecular findings of HBV infection (1 from a patient with serum HBsAg and 1 without), there was immunohistochemical evidence of coinfection or superinfection with hepatitis delta virus (HDV). In conclusion, in this patient population, HBV, alone or with HDV or HAV, causes fulminant hepatic failure more often than HCV infection. However, in the majority of patients, the etiology of fulminant hepatic failure remains unknown.

Adult↗

Recombinant outer surface protein C ELISA for the diagnosis of early Lyme disease.

To compare the sensitivity of a new ELISA for IgM antibodies to Borrelia burgdorferi that uses a recombinant outer surface protein C (rOspC) with those of a whole cell (WC) ELISA and an immunoblot assay for the diagnosis of early Lyme disease, serum specimens from 82 consecutive patients with physician-documented erythema migrans were analyzed. To compare the specificities of the three assays, serum specimens from 50 patients without a history of Lyme disease and from an area in which B. burgdorferi is not endemic were analyzed. The sensitivities of the WC ELISA, immunoblot assay, and IgM rOspC ELISA were 28%, 29%, and 46%, respectively, while the specificities were 100%, 100%, and 98%, respectively. The IgM rOspC ELISA is a convenient, readily automated, easily standardized serologic test that is significantly more sensitive for the diagnosis of early Lyme disease than either WC ELISA or immunoblot assay.

Adolescent↗

Prospective assessment of Lyme disease in a school-aged population in Connecticut.

To determine the incidence and cumulative frequency of Lyme disease in a school-aged population in an area in which Lyme disease is endemic, serum specimens were obtained before and after the 1990-1992 tick seasons from 410 middle and high school students in southeastern Connecticut. Sera were tested for serologic evidence of infection with Borrelia burgdorferi, and students were questioned about physician-confirmed episodes of clinical Lyme disease. At enrollment, 29 (7%) students had a history of Lyme disease, and of these, 12 (41%) were seropositive for B. burgdorferi infection. Seronegative students (397) were followed prospectively over a total of 796 person years. At enrollment, 381 students (93%) had no history of Lyme disease, and of these, 1 (0.3%) was seropositive. During this period, 8 students developed clinical Lyme disease and 3 had asymptomatic infections with B. burgdorferi. The incidences of clinical Lyme disease and asymptomatic B. burgdorferi infection were 10.1 and 3.8 cases/1000 person-years, respectively. Lyme disease is an important health problem in school-aged children living in southeastern Connecticut.

Adolescent↗

Chronic hepatitis C. Analysis of host immune response by immunohistochemistry.

The pathogenesis and perpetuation of hepatocellular injury in hepatitis C viral infection remains unclear. It has been proposed that a direct viropathic effect, the host immune response, or both mediate cell damage. To address this issue, the immunophenotype of the inflammatory infiltrate in the liver of 18 patients with abnormal liver function tests and serologically detectable hepatitis C virus antibodies was compared with seven control patients (three cases with hepatitis B virus infection, two with alcoholic hepatitis, and one patient each with primary biliary cirrhosis and autoimmune hepatitis). The immunohistochemical markers included UCHL1, L26, Ham-56, Mac-387, CD68, Leu-M1, and cathepsin B. We found that T cells represent the predominant cell type in both histopathologic patterns of hepatitis C, ie, chronic active hepatitis and chronic persistent hepatitis, but the intensity of the T-cell infiltrate displayed marked differences. B-cell infiltrates were only seen in the germinal centers of lymphoid follicles in portal tracts. Furthermore, significant numbers of CD68-positive macrophages/monocytes were seen in the more aggressive form of hepatitis C viral infection. These data suggest that the T-lymphocyte-mediated host immune response is similar in chronic active and chronic persistent hepatitis patterns of hepatitis C viral infection, but varies in its intensity. In addition, macrophages/monocytes may play a role in hepatocyte and bile duct injury in chronic hepatitis C.

Adult↗

Pathobiologic effects of hepatitis C.

Hepatitis C virus (HCV) is the main cause of non-A, non-B hepatitis around the world. It frequently leads to chronic hepatitis which may progress to cirrhosis and hepatocellular carcinoma (HCC). Characteristic, although not pathognomonic, histologic changes in chronic hepatitis C include bile duct damage and lymphoid aggregates in portal tracts. Hepatocyte and bile duct injury seem to be mediated by both a direct cytopathic effect of HCV and immune mechanisms, perhaps triggered by HCV. Most HCC are related to HCV, HBV, or both. HCV appears to persist and replicate in hepatocytes during malignant transformation, but it is not clear whether the virus plays a direct or indirect role in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗