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Biomedical subjects

R P Perrillo

Publications and source records attributed to R P Perrillo.

At least 73 records · Page 4Linked to original sources

Different operating conditions affect risk of hepatitis B virus infection at two residential institutions for the mentally disabled.

The prevalence of hepatitis B virus markers was determined in two residential institutions for the mentally disabled which exhibited major differences in operating policies. Eighty per cent of 91 clients and 16% of 92 employees at institution A had positive tests for hepatitis B virus markers, including two staff members and one client with serologic evidence of recent infection (immunoglobulin M antibody to hepatitis B core antigen). In contrast, 34% of 395 clients and 8% of 294 workers at institution B were positive for hepatitis B virus markers, and none of the staff demonstrated evidence of recent infection. The observed differences in seroprevalence were likely to have been influenced by substantial disparities in living conditions, staff-to-client ratios in critical areas, and level of employee experience. In addition to significant institutional differences, seroprevalence was associated with severity of mental retardation in clients and duration of employment in staff. This study emphasizes the importance of local policies in the prevention of hepatitis B virus infection at residential institutions for the mentally disabled.

Adolescent↗

Rosette inhibitory factor (RIF) augments cyclic AMP generation by helper T lymphocytes.

The effect of Rosette Inhibitory Factor (RIF) on cyclic AMP generation by peripheral blood mononuclear cells (PBMC) and lymphocyte subpopulations (OKT4+ or helper T cells, OKT8+ or suppressor T cells, B lymphocytes) was analyzed. The results were compared to those observed with isoproterenol, an agent which is known to inhibit erythrocyte rosette (ER) formation and increase cyclic AMP levels in T cells. RIF elevated cyclic AMP levels in PBMC, an effect which was observed to be confined to helper T cells. Isoproterenol also elevated levels of cyclic AMP in PBMC but non-selectively augmented levels of the cyclic nucleotide in all lymphocyte subpopulations. Whereas isoproterenol increased cyclic AMP levels within 30 min, RIF did so after a lag period of 4 hr, a delay which is necessary for inhibition of ER formation. These studies reaffirm the selective effect of RIF on helper T cells. We conclude that inhibition of ER formation and possibly other immunoregulatory effects associated with RIF may be mediated via modulation of the adenyl cyclase-cyclic nucleotide network.

Cell Separation↗

Comparative efficacy of adenine arabinoside 5' monophosphate and prednisone withdrawal followed by adenine arabinoside 5' monophosphate in the treatment of chronic active hepatitis type B.

Thirty-eight patients with chronic active hepatitis type B received antiviral therapy. In one trial, 22 patients were randomized to either no treatment or treatment with a 28-day cycle of adenine arabinoside 5' monophosphate (ARA-AMP); in a second trial, 13 patients were randomized to no treatment or treatment with two 28-day cycles of ARA-AMP separated by a 4-wk rest interval; during a third trial, 11 individuals were treated with 8 wk of prednisone therapy followed by 28 days of ARA-AMP therapy. The response rate (73%) to the regimen with prednisone was significantly greater than that achieved in the first or second trial (0% and 15%, respectively). The data indicate that the combination of short-term prednisone and ARA-AMP therapy may offer more promise for successful treatment of chronic active hepatitis type B than does ARA-AMP alone. Synergism may possibly occur by the combined effects of immune rebound provided by corticosteroid withdrawal and the inhibition of viral proliferation by ARA-AMP.

Adult↗

Clinical and immunologic features of chronic dialysis patients who fail to respond to hepatitis B vaccine.

Eighteen patients on chronic dialysis (15 haemodialysis, three peritoneal) were evaluated to determine whether certain clinical features and/or in vitro indicators of immune function correlated with the response to hepatitis B vaccine. Only 44% of patients developed antibody to hepatitis B surface antigen (anti-HBS) following vaccination and neither duration of dialysis, history of renal transplant, peripheral T cell numbers, T4/T8 ratios, nor mitogen induced lymphocyte proliferation correlated with response to vaccination. Advanced age, history of multiple blood transfusions and depressed levels of IgM may be associated with a poor antibody response to the vaccine. Future studies need to consider these variables when evaluating immunogenicity of new hepatitis B vaccine preparations.

Adult↗

Prevalence of hepatitis B antibodies in personnel at a children's hospital.

Antibody to hepatitis B core antigen and antibody to hepatitis B surface antigen were measured in serum samples from 825 personnel at St Louis Children's Hospital (702 were possibly at high risk of occupational hepatitis B virus (HBV) exposure and 123 were office personnel); 5.6% had positive findings for both antibodies, 5.6% had findings for antibody to hepatitis B surface antigens alone, and 1.3% had positive findings for antibody to hepatitis B core antigens alone. The group with positive findings for antibody to hepatitis B surface antigens alone did not have traditional risk factors for HBV infection, suggesting that this serologic finding may not be a reliable indicator of past HBV infection. After accounting for the effects of age, sex, and ethnicity, it was found that no occupational group had a significantly increased prevalence of HBV antibodies compared with prevalence in other personnel. In comparison with volunteer blood donors, only physicians older than 40 years of age had an increased HBV antibody prevalence. It is concluded that St Louis Children's Hospital has not been a high-risk environment for HBV exposure in recent years. However, caution is advised in generalizing these conclusions because other children's hospitals may serve a patient population at higher risk of HBV infection. Decisions regarding HBV immunization policy should take into consideration the fact that personnel at different hospitals may face markedly different risks of HBV exposure.

Adult↗

Immune globulin and hepatitis B immune globulin. Prophylactic measures for intimate contacts exposed to acute type B hepatitis.

We studied the relative prophylactic efficacies of recently derived immune globulin containing antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B immune globulin in 60 intimate contacts exposed to acute type B hepatitis. Forty susceptible contacts were randomly assigned to treatment with either a single intramuscular dose of immune globulin or hepatitis B immune globulin (0.06 mL/kg of body weight), following which observation was maintained over a 12-month period. Twenty additional contacts received the equivalent of twice the dose of immune globulin given to the first group, and follow-up was maintained for six months. Neither the hepatitis B virus (HBV) attack rates (11% to 19%) nor the frequency of clinical illness (0% to 4.8%) was substantially different in the three groups. When compared with average frequencies reported in the literature, significantly lower illness rates were noted for immune globulin recipients. These data indicate that currently derived immune globulin as well as hepatitis B immune globulin may confer protection from illness (le, passive-active immunity) in the setting of intimate exposure to HBV.

Acute Disease↗

Survey of hepatitis B viral markers at a public day school and a residential institution sharing mentally handicapped students.

The prevalence of hepatitis B virus markers was studied among employees and clients at a nonresidential public school for the mentally handicapped and at a privately operated residential facility. In the residential institution, 73 (80%) of 91 clients and 15 (16%) of 92 workers had positive tests for hepatitis B virus markers. Twenty-three clients, including six carriers of hepatitis B surface antigen (subtype ayw), received their education their education at the public school. Only two students (4%) who did not live at the residential institution and one employee (2%) had positive tests for hepatitis B virus markers. One of these students had acute hepatitis B infection, with hepatitis B surface antigen subtype ayw; the subtyping suggested that he had acquired the infection from one of the six carriers from the residential institution. Testing for IgM antibody to hepatitis B core antigen in single serum samples facilitated the identification of acute and chronic hepatitis B infection in children and staff of both facilities. The results show hepatitis B can be transmitted in this setting, and vaccination may be warranted for susceptible students and staff.

Adolescent↗

Spontaneous clearance and reactivation of hepatitis B virus infection among male homosexuals with chronic type B hepatitis.

Abrupt increases of alanine transaminase were observed in 6 of 23 non-treated, male homosexuals with chronic hepatitis associated with hepatitis B virus. Before this occurrence, all subjects had hepatitis B e antigen (HBeAg) and elevated DNA polymerase activity. Within 3 months, HBeAg was nondetectable in 3 subjects and elevated DNA polymerase disappeared in 4. These serologic events were not always sustained, however. In 3 subjects, reactivation of hepatitis B virus infection occurred within the subsequent 6-month period. Serologic testing for cytomegalovirus, Epstein-Barr virus, delta agent, and hepatitis B surface antigen (HBsAg) subtype showed that episodes of clearance and reactivation were not explainable by secondary infection with these agents or infection with a different HBsAg subtype. Spontaneous clearance and reactivation of hepatitis B virus infection may commonly occur among male homosexuals with chronic type B hepatitis. These phenomena should be considered when evaluating the need for treatment or interpreting the results of investigations that use anti-viral therapy.

Adult↗

Prevaccination screening of medical and dental students. Should low levels of antibody to hepatitis B surface antigen preclude vaccination?

The prevalence of hepatitis B virus (HBV) markers in 484 medical and 329 dental students was studied. Three students (0.9%) were hepatitis B surface antigen (HBsAg) reactive, and 46 students (5.7%) were reactive for antibody to HBsAg (anti-HBs). There was no difference in anti-HBs frequency between medical and dental students, and the prevalence of this marker was not associated with year in school. Of the 46 reactors, eight (17%) were nonreproducible and 38 (83%) were reproducibly reactive when the same samples were reanalyzed. Of note, all nonreproducible reactors exhibited anti-HBs sample-negative control (S/N) ratios of less than 10, and none were positive for antibody to hepatitis B core antigen (anti-HBc). Nineteen (50%) of the reproducible reactors had anti-HBs S/N ratios equal to or greater than 10, and only 15 (39%) were anti-HBc positive. In view of these observations, we do not recommend HBV screening in a vaccine program for health students. Due to the frequency with which low-level anti-HBs reactors without anti-HBc are found to be nonreproducibly positive, we are concerned by the potential overinterpretation of such results before the formulation of decisions about the need for vaccination.

Hepatitis B↗

Anti-hepatitis B core immunoglobulin M in the serologic evaluation of hepatitis B virus infection and simultaneous infection with type B, delta agent, and non-A, non-B viruses.

The clinical value of an enzyme-linked immunosorbent assay for the detection of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc IgM) was evaluated by testing serum samples from the following groups of patients: (a) 27 individuals who had been diagnosed as having acute hepatitis B virus (HBV) infection, (b) 29 hepatitis B surface antigen (HBsAg) carriers, (c) 6 subjects with acute non-B hepatitis, and (d) 10 HBsAg-negative but anti-HBc-positive subjects who were suspected of being index cases for the intimate transmission of HBV. Whereas 24 of the 27 individuals with presumed acute HBV infection exhibited anti-HBc IgM, only 2 of 29 HBsAg carriers were found to be positive. Hepatitis B surface antigen persisted during an 8-mo observation period in 3 anti-HBc IgM-negative subjects with acute HBsAg-positive hepatitis. Before anti-HBc IgM testing, it was considered that these cases had evolved to the HBsAg carrier state. However, the regular demonstration of anti-HBc IgM in acute type B hepatitis, as well as the failure to detect this antibody in the majority of HBsAg carriers, led to reclassification of these cases as probable instances of acute non-A, non-B or delta-agent hepatitis superimposed on the HBsAg carrier state. Through additional testing, the diagnosis of non-A, non-B (NANB) infection was confirmed in 2 of these cases, and delta-agent infection was identified in the third. None of the non-B hepatitis cases exhibited anti-HBc IgM. However, 5 of the 10 suspected type B index cases were anti-HBc IgM-positive, indicating that they were very recently infected and most likely had infected their cohabiting sexual partners. The results from this study indicate that testing for anti-HBc IgM may improve serodiagnostic accuracy when acute NANB and delta-agent hepatitis occur in previously unrecognized HBsAg carriers. Moreover, it may be a useful test in defining potential high risk sources of exposure to HBV.

Antibodies, Viral↗

Acute non-A, non-B hepatitis with serum sickness-like syndrome and aplastic anemia.

We treated a patient in whom acute non-A, non-B hepatitis was complicated by a serum sickness-like syndrome (rash, arthralgias). Serum from this patient demonstrated a fall in C3, C4, and total hemolytic complement levels during the syndrome, in association with circulating IgM immune complexes. Fatal aplastic anemia developed later in the patient. This case illustrates that non-A, non-B hepatitis may be complicated by immune complex features that have previously been emphasized to occur with acute hepatitis B. Additional evidence supporting the occurrence of this clinical picture in non-B forms off viral hepatitis is presented.

Acute Disease↗

Quantitative temporal analysis of 99mTechnetium p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and disease.

Excretory liver function was analyzed in 10 healthy volunteers and 28 subjects with acute or chronic liver injury following intravenous administration of 99mtechnetium p-isopropyl iminodiacetic acid. Hepatobiliary transit of this agent was quantitated at 5-min intervals for a total of 60 min. Indices of total liver activity, liver cell uptake, liver parenchymal clearance, and bile duct clearance of 99mtechnetium p-isopropyl iminodiacetic acid were calculated from time--activity curves over heart, liver, extrahepatic bile ducts, and gallbladder. Seven subjects with acute viral hepatitis, 15 with extrahepatic biliary obstruction, and 6 with intrahepatic cholestasis were evaluated. Compared with healthy volunteers, a significant (p less than 0.0001) reduction in total liver activity and liver parenchymal clearance was demonstrated in all patient groups. Major resolution in all liver-derived indices, particularly total liver activity, occurred during convalescence from hepatitis and after biliary drainage. Nonmeasurable bile duct clearance always indicated a diagnosis of extrahepatic obstruction in cholestatic subjects, and this index normalized in subjects following biliary drainage. Whereas visual assessment of 99mtechnetium p-isopropyl iminodiacetic acid scans provided limited, useful information about the functional status of the liver, quantitative temporal analysis proved to be a much more effective technique.

Biliary Tract↗