Biomedical subjects

J G Waggoner

Publications and source records attributed to J G Waggoner.

At least 37 records · Page 2Linked to original sources

PubMed1987

A serologic follow-up of the 1942 epidemic of post-vaccination hepatitis in the United States Army.

An epidemic of icteric hepatitis in 1942 affected approximately 50,000 U.S. Army personnel. This outbreak was linked to specific lots of yellow-fever vaccine stabilized with human serum. To identify the responsible virus and the consequences of the epidemic, during 1985 we interviewed and serologically screened 597 veterans who had been in the army in 1942. These subjects were selected from three groups. Group I consisted of patients who had received the implicated vaccine and had jaundice; Group II had received the implicated vaccine but remained well; Group III had received a new, serum-free vaccine, with no subsequent jaundice. Ninety-seven percent of Group I, 76 percent of Group II, and 13 percent of Group III were positive for antibodies to hepatitis B virus. Only one subject had hepatitis B surface antigen, for a carrier rate of 0.26 percent among recipients of the implicated vaccine. The prevalence of hepatitis A antibody was similar in all three groups, and no subject had antibody to hepatitis delta virus. We conclude that hepatitis B caused the outbreak, that about 330,000 persons may have been infected, that the hepatitis B virus carrier state was a rare consequence, and that the outbreak induced hepatitis B antibodies that appear to persist for life.

Aged↗

PubMed1987

Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis.

Liver biopsy specimens from 58 American patients with chronic type B hepatitis were investigated for the presence and distribution of the hepatitis B core (HBcAg) and surface (HBsAg) antigens by peroxidase-anti-peroxidase techniques. HBsAg was detected in 43 (77%) and HBcAg in 52 (90%) patients. HBcAg was present in 50 of 51 (98%) patients with hepatitis B e antigen (HBeAg) but in only two of seven (29%) of patients with antibody to HBeAg (anti-HBe). There was no correlation between severity of hepatitis or height of aminotransferase activities and the amount of HBsAg or HBcAg in hepatocytes but there was a positive correlation between amount of HBcAg and height of HBV-DNA and DNA polymerase activity in serum. Follow-up liver biopsies, taken 1 to 3 yr later, were available from 39 patients. HBcAg remained detectable in 25 of 26 patients with persistence of HBeAg but disappeared in 12 patients who had lost HBeAg. In nine patients, HBcAg was cytoplasmic as well as nuclear in distribution. Seven of these patients had an intense lobular hepatitis with marked elevations in aminotransferase activities. These findings indicate that the amount of HBcAg in liver correlates with the amount of serum hepatitis B virus as quantified by serum levels of DNA polymerase and HBV-DNA. The amount of nuclear HBcAg does not correlate with the severity of the liver disease, but the presence of cytoplasmic HBcAg usually reflects an active and severe ongoing hepatitis.

Adult↗

PubMed1987

Hepatitis B virus deoxyribonucleic acid in liver of chronic carriers. Correlation with serum markers and changes associated with loss of hepatitis B e antigen after antiviral therapy.

Patients with chronic hepatitis B receiving antiviral or immunomodulatory therapy were prospectively studied to determine the relationship between the state of hepatitis B virus deoxyribonucleic acid in liver and the levels of serum markers of hepatitis B virus infection. Hepatitis B virus deoxyribonucleic acid was quantitated and the molecular forms determined using molecular hybridization in two separate liver specimens taken at least 1 yr apart. All 30 patients initially had hepatitis B surface antigen and e antigen in serum and all had hepatitis B virus deoxyribonucleic acid, including replicative intermediate forms, present in liver. The amount of viral deoxyribonucleic acid in liver correlated significantly with the e antigen titer in serum. At the time of the second liver biopsy, e antigen was no longer detectable in the serum of 12 patients although all except 1 patient still had detectable hepatitis B surface antigen. In this group, the amount of hepatitis B virus deoxyribonucleic acid in liver had decreased significantly and replicative viral intermediates had disappeared. In contrast, among patients who remained e antigen-positive, the amount of viral deoxyribonucleic acid did not change appreciably and replicative intermediate forms were still detectable. These findings imply that in chronic hepatitis B, loss of e antigen is usually associated with resolution of hepatitis B virus replication.

Adult↗

PubMed1986

Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report.

We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.

Adult↗

PubMed1986

Immunologic effects of interferon-alpha in man: treatment with human recombinant interferon-alpha suppresses in vitro immunoglobulin production in patients with chronic type B hepatitis.

The effect of human recombinant interferon-alpha on lymphocyte proliferation and differentiation was studied in 18 patients with chronic type B hepatitis who were participating in a randomized controlled trial of interferon-alpha therapy. Peripheral blood mononuclear cells (PBMC) were obtained by lymphopheresis before and during a 4 mo course of interferon. Pokeweed mitogen-induced immunoglobulin synthesis by PBMC obtained from patients before therapy was similar to that of PBMC from normal individuals. However, after 2 wk treatment with human recombinant interferon-alpha mitogen-induced immunoglobulin production was decreased by an average of 50%. Staining for cytoplasmic immunoglobulin revealed decreases that paralleled secreted immunoglobulin, indicating that interferon-alpha treatment inhibited immunoglobulin synthesis. Mixing autologous T and B cell enriched populations from before and during interferon treatment revealed that the decrease in immunoglobulin synthesis involved a defect in the B cell-enriched population. In contrast to immunoglobulin synthesis, pokeweed mitogen-induced lymphocyte proliferation was not significantly affected by in vivo administration of interferon-alpha. Thus a major effect of in vivo interferon-alpha on immunoregulation in patients with chronic type B hepatitis appears to be an inhibition of the late stages of B cell differentiation into immunoglobulin producing and secreting plasma cells.

Antibody Formation↗

PubMed1986

Pilot study of recombinant human alpha-interferon for chronic type B hepatitis.

Nine patients with chronic type B hepatitis were entered into a preliminary study of recombinant, human alpha-interferon therapy. Patients received one to four courses of interferon, each consisting of a fixed dose of 18, 36, 50, 68, or 100 million units given three times a week for 2 wk. Side effects including fever, chills, fatigue, myalgias, headache, and neutropenia were common and especially severe with higher doses. Serum hepatitis B virus DNA polymerase activity fell during therapy to 15%-30% of the pretreatment levels irrespective of interferon dose, but rose to the initial level by 10 days after the course ended. During follow-up, 2 patients had a sustained clinical remission in which hepatitis B virus DNA, DNA polymerase, and hepatitis B e antigen disappeared from serum and amino-transferase activities fell to normal. One patient became hepatitis B surface antigen negative. We conclude that higher doses (50 and 68 million units) of interferon have greater side effects than lower doses (18 and 36 million units), without having any greater antiviral efficacy. Further studies should be directed at therapy with lower doses given over longer periods.

Adult↗

PubMed1986

A short course of prednisolone in chronic type B hepatitis. Report of a randomized, double-blind, placebo-controlled trial.

Fifteen patients with chronic type B hepatitis were treated with corticosteroids in a randomized, double-blind, placebo-controlled trial lasting 28 days. Ten patients received prednisolone, 60 mg/d for 2 weeks, then 30 mg/d for another 2 weeks; 5 patients received placebo. Serum aminotransferase levels decreased significantly during prednisolone therapy but 4 to 10 weeks after abrupt withdrawal of the drug, they rebounded to levels greater than those before treatment. This exacerbation of disease lasted for several months and was prolonged and symptomatic in 3 patients. Hepatitis B virus levels did not change substantially during treatment. Follow-up examinations showed no improvement in biochemical or serologic features of the disease in any of the 15 patients; follow-up liver biopsies showed a worsening in 4 of 7 treated patients but in 0 of 5 control patients. Thus, a 28-day course of prednisolone produced no beneficial effects in patients with mild-to-moderate chronic type B hepatitis; on the contrary, such treatment may be harmful.

Adult↗

PubMed1985

Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate.

Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.

Adult↗

PubMed1985

Serological diagnosis of acute viral hepatitis.

Fifty cases of symptomatic acute viral hepatitis presenting at the Washington, D.C., Veterans Administration Medical Center between 1976 and 1978 were tested for serological markers of hepatitis virus infection. The etiology of the acute hepatitis appeared to be hepatitis A virus in 20%, hepatitis B virus in 52%, non-A, non-B agents in 22%, delta hepatitis in 4%, and infectious mononucleosis in 2%. The diagnosis of type B hepatitis was difficult to verify because 10% of cases were seronegative for HBsAg and another 10% were seronegative by conventional testing for IgM antibody to hepatitis B core antigen (a putative marker of acute hepatitis B virus infection). Accurate serodiagnosis of acute viral hepatitis depends upon the correct application of testing for IgM antibody to hepatitis A virus, IgM antibody to hepatitis B core antigen, HBsAg, and tests for syphilis and mononucleosis.

Adult↗

PubMed1985

The changing epidemiology of hepatitis B virus infection in the Canadian north.

Hepatitis B virus infections are common in the Eskimo (Inuit) populations of the world. In this study, serologic markers of hepatitis B infection were measured in 172 inhabitants (78%) of an isolated Canadian Inuit settlement. Evidence of hepatitis B infection was found in 22% of residents. The prevalence increased with age, being uncommon under the age of 20 (7%), yet present in the majority of inhabitants over the age of 40 (64%). Sera from four individuals (2.3%) were hepatitis B surface antigen- (HBsAg) positive. All four HBsAg carriers were negative for immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc), hepatitis B e antigen (HBeAg), and DNA polymerase, but positive for antibody to hepatitis B e antigen (anti-HBe). These data suggest that hepatitis B infection has become relatively uncommon in the inhabitants of this community born during the past 20-30 years. The apparent decline in prevalence did not appear to be related to recent demographic or socioeconomic changes in the area.

Adolescent↗

PubMed1984

Acute type A hepatitis during chronic hepatitis B virus infection: association of depressed hepatitis B virus replication with appearance of endogenous alpha interferon.

Two patients with chronic type B hepatitis and intercurrent episodes of acute type A hepatitis are presented. Serological markers of hepatitis B virus replication decreased or became undetectable in both patients during the acute illness, while interferon activity was transiently detected in serum. The presence of serum leukocyte (alpha) interferon was confirmed by neutralization with specific antisera and tests of pH2 stability. These observations suggest a role for natural leukocyte (alpha) interferon in the modulation and control of hepatitis B virus infection and provide further evidence to support trials of exogenous leukocyte (alpha) interferon in the chronic infection.

Acute Disease↗

PubMed1984

Spontaneous reactivation of chronic hepatitis B virus infection.

Studies on the natural history of chronic type B hepatitis have shown that loss of hepatitis B e antigen and seroconversion to antibody to hepatitis B e antigen are usually accompanied by remission of disease activity and improvement in serum aminotransferase levels. Twenty-five symptomatic patients with biopsy-documented chronic type B hepatitis were followed for 25 +/- 2 mo (mean +/- SEM) after disappearance of hepatitis B e antigen, hepatitis B virus-deoxyribonucleic acid, and deoxyribonucleic acid polymerase activity from the serum. Twenty-four patients developed the antibody to hepatitis B e antigen. All 25 patients demonstrated a decrease in serum aminotransferase levels, and most became asymptomatic. However, during subsequent follow-up, 8 of the 25 patients (32%) exhibited reactivation of chronic type B hepatitis manifested by abrupt elevation of serum aminotransferase levels and reappearance of serum hepatitis B virus-deoxyribonucleic acid, deoxyribonucleic acid polymerase activity, and, in 7 patients, hepatitis B e antigen. All 8 patients developed symptoms: 3 became icteric, 3 developed ascites, and 2 bled from esophageal varices. One of these patients died. Episodes of reactivation invariably occurred within 1 yr of loss of hepatitis B e antigen and lasted for up to 13 mo. These observations suggest that loss of hepatitis B e antigen and seroconversion to the antibody to hepatitis B e antigen do not necessarily imply permanent remission of chronic type B hepatitis, and subsequent spontaneous reactivation may be an important cause of progression of hepatic injury.

Adult↗

PubMed1983

Gamma-aminobutyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure.

Hepatic encephalopathy (HE) is a syndrome of generalized neural inhibition, which complicates both acute and chronic liver failure. Since gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter of the brain and HE is associated with increased responsiveness to certain drugs (benzodiazepines and barbiturates) that mediate neural inhibition by binding to the GABA receptor complex on postsynaptic neural membranes, the status of this receptor complex in HE was investigated. Fulminant hepatic failure was induced in rabbits by the intravenous injection of galactosamine hydrochloride. Neural membranes were isolated from the brains of normal rabbits, rabbits in hepatic coma, and rabbits with another type of metabolic encephalopathy, uremic coma. To characterize GABA and benzodiazine receptors, measurements were made of the specific binding to neural membranes of 3H-GABA and 3H-flunitrazepam, respectively. Computer-assisted Scatchard plot analysis of the binding data suggested the presence of two independent receptors for GABA and a single class of receptor for benzodiazepines. Hepatic coma was associated with no changes in the affinities of these receptors but with significant increases in their densities: 0.34 vs. 0.60; 1.1 vs. 2.2; and 4.6 vs. 7.3 pmol/mg of membrane protein for the high-affinity GABA, low-affinity GABA and benzodiazepine receptors, respectively. Uremic coma was associated with no changes in the affinities or densities of GABA receptors. On the basis of these findings, it is suggested that (1) increased numbers of GABA receptors in liver failure may potentiate neural inhibition by increasing the sensitivity of the brain to GABA and (2) increased responsiveness to the sedative-hypnotic effects of benzodiazepines in liver failure may be mediated by increased numbers of receptors for this class of drug, permitting increased drug effect.

Animals↗

PubMed1983

Antibody to hepatitis B surface antigen in nonprimate animal species.

The hepatitis B virus infects only humans and higher apes. Viruses similar to the human hepatitis B virus (hepadna viruses) have been discovered in several nonprimate species including woodchucks, ground squirrels, and domesticated ducks. To search for other models of hepatitis B virus infection, we screened serum specimens from 64 exotic animals (24 species), 56 domesticated animals (6 species), and 52 laboratory animals (3 species). Samples were tested for deoxyribonucleic acid polymerase by enzymatic assay and for hepatitis B surface antigen and antibody and antibody to hepatitis B core antigen by radioimmunoassays. All sera were negative for deoxyribonucleic acid polymerase, hepatitis B surface antigen, and antibody to hepatis B core antigen suggesting that none of these animals harbored hepadna viruses in serum. However, 48% of the sera from 58% of the 33 species were reactive for antibody to hepatitis B surface antigen. This reactivity was blocked by human serum positive for hepatitis B surface antigen but not by control human serum. The antibody to hepatitis B surface antigen was generally present in low titer (95% were less than or equal to 1:16) and was often directed against subdeterminants of hepatitis B surface antigen (anti-d, anti-y, or anti-w). Characterization of the antibody to hepatitis B surface antigen by gel chromatography, sucrose density ultracentrifugation, affinity chromatography, and chemical inactivation suggested that it was entirely or predominantly immunoglobulin M antibody. Thus, many animals species have naturally occurring immunoglobulin M antibody to hepatitis B surface antigen detectable by radioimmunoassay. This antibody could arise as a result of either the intermittent spontaneous maturation of clones of antibody to hepatitis B surface antigen forming lymphocytes or exposure to environmental antigens that share epitopes with hepatitis B surface antigen. Similar naturally occurring antibody to hepatitis B surface antigen may be present in some humans.

Animal Population Groups↗

PubMed1982

Prevalence of antibody to hepatitis A virus in a Canadian Inuit community.

To determine the prevalence of hepatitis A in a Canadian Inuit population, serum from 85% of the 850 inhabitants of Baker Lake, Northwest Territories, was tested by radioimmunoassay for antibody to the hepatitis A virus (anti-HAV). The overall prevalence of anti-HAV in the community was 71%. Exposure to the virus occurred early in life, such that by the age of 6 years 53% of the children had anti-HAV in their serum. The rate approached 100% by the age of 50 years. These findings document the ubiquitous nature of the hepatitis A virus in this northern Inuit settlement and suggest that immunoprophylaxis be considered for individuals taking short-term employment in such places.

Adolescent↗

PubMed1982

Pipetter's thumb.

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Allied Health Personnel↗

PubMed1982

Hepatitis virus infection in an isolated Canadian Inuit (Eskimo) population.

The epidemiology of Hepatitis A virus (HAV) and hepatitis B virus (HBV) infection was studied in a northern Canadian Inuit (Eskimo) settlement. Sera from 720 of the 850 inhabitants of Baker Lake, Canada, were tested for markers of HAV and HBV infection. Anti-HAV was present in 71% of the residents and its prevalence increased with age. Serologic evidence of HBV infections was found in 27% of residents. The prevalence increased with age, being uncommon under the age of 20 (6%) and almost universal over the age of 60 (93%). Among the 29 hepatitis B surface antigen (HBsAg) carriers identified, all were adults, all had low levels of HBsAg, and all were negative for hepatitis B e antigen (HBeAg) and DNA polymerase but positive for antibody to HBeAg. These data demonstrate a high prevalence of HAV and HBV infection in this population. Further, they suggest that a dramatic decrease in the transmission of HBV infection has occurred over the past 20-30 years.

Adolescent↗

PubMed1981

Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis.

Twenty-five patients with chronic type B hepatitis documented by liver biopsy were followed for 1 to 6 years with serial measurements of aminotransferase levels, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), and hepatitis B virus DNA polymerase. Initially, all were positive for HBsAg and HBeAg and had elevations in serum aminotransferases. In follow-up, only one lost HBsAg reactivity. In 13, however, elevated aminotransferase levels spontaneously fell to normal and have remained normal. These 13 also had a seroconversion from HBeAg to anti-HBe, and all became negative for serum DNA polymerase. Most had a fall in HBsAg titer. This seroconversion occurred concurrently with or several months before the fall in aminotransferase levels. In contrast, the 12 persons who remained HBeAg positive continued to have elevated aminotransferase levels. All 10 of these patients who were initially positive for DNA polymerase remained positive. These data suggest that many patients with chronic type B hepatitis eventually have a spontaneous remission in clinical and biochemical evidence of active disease, usually heralded or accompanied by the disappearance of HBeAg and DNA polymerase.

Adult↗