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Biomedical subjects

J E Maynard

Publications and source records attributed to J E Maynard.

At least 73 records · Page 4Linked to original sources

Non-A, non-B hepatitis: research progress and current perspectives.

Recent studies have documented the existence of at least two transmissible agents of posttransfusion non-A, non-B hepatitis. The disease frequently progresses to a state of chronic liver disease and/or persistent viremia, often in the absence of elevated liver enzymes. Difficulties encountered in the development of serologic tests for NANB antigens may be related to a lack of potent antibody coupled with low concentrations of infectious agent. The ultrastructural changes we have observed in infected chimpanzee hepatocytes are primarily confined to the cytoplasm and are, in the aggregate, most similar to those induced by a variety of RNA, but not DNA, viruses. At least one of the NANB hepatitis agents interferes with concurrent HAV or HBV infection in experimentally inoculated chimpanzees.

Animals↗

Serological markers of hepatitis B virus and alpha-fetoprotein levels preceding primary hepatocellular carcinoma in Alaskan Eskimos.

The availability of stored sera that had been obtained for other investigations permitted examination of the sequential development of hepatitis B virus (HBV) infection markers and alpha-fetoprotein (AFP) in persons who later developed primary hepatocellular carcinoma (PHC). 9 of the 11 PHC subjects had markers of HBV infection. The results showed that HBV infection could have occurred as little as 10 years before the recognition of PHC. Seroconversion from HBeAg to anti-HBe and significant rises of AFP levels occurred as long as 6 years and 2 years, respectively, before clinical onset of PHC. The finding that anti-HBe seems to precede the rise in AFP by several years suggests that in populations with a high incidence of HBV-associated PHC, or in families with high risk of PHC, the best use of AFP screening may be to monitor HBsAg carriers after seroconversion from HBeAg to anti-HBe.

Adolescent↗

Purification of acute phase anti-hepatitis A virus (HAV) IgM and development of an IgM solid-phase radioimmunoassay for the detection of HAV.

A simple two-step procedure for the purification of IgM from acute phase hepatitis A infected chimpanzee serum has been developed. The procedure involves the precipitation of the euglobulin fraction with boric acid and the fractionation of the resuspended material on Sephacryl S-300 (Pharmacia Fine Chemicals, Piscataway, NJ). The purified IgM was used to develop a solid-phase radioimmunoassay (SPRIA) in which IgM was used as capture antibody and iodinated IgM was used as a probe. This assay was compared with a conventional IgG-based SPRIA. The IgM-based assay resulted in a superior response (P/N) for the detection of antigen in crude preparations; however, endpoint analyses demonstrated similar sensitivities.

Acute Disease↗

Interruption of hepatitis B transmission by modification of a gynaecologist's surgical technique.

Between January, 1979, and January, 1980, hepatitis B developed in three women within 6 months of their undergoing gynaecological surgery at a community hospital in Mississippi. Subsequent investigation revealed another case of hepatitis B associated with gynaecological surgery. The gynaecologist who carried out all four operations (gynaecologist A) was a chronic carrier of hepatitis B. Hepatitis B surface antigen subtyping on serum from gynaecologist A and from one of the hepatitis B patients gave identical results. Patients of gynaecologist A who underwent total abdominal hysterectomies or bilateral salpingo-oophorectomies were at a greater risk of acquiring hepatitis B than were patients in whom the same procedures were carried out by a control group of gynaecologists. After gynaecologist A modified his surgical technique and began wearing two pairs of gloves during surgery, there was no further hepatitis B transmission to his surgical patients.

Carrier State↗

Excretion of hepatitis A virus in the stools of hospitalized hepatitis patients.

A study was carried out to determine whether hepatitis A virus (HAV) can be detected in the stools of patients hospitalized for HAV infection. Acute phase samples of whole blood and stool, as well as completed questionnaires, were obtained from 31 patients hospitalized at any of 13 hospitals in the Phoenix metropolitan area. Blood specimens were tested for hepatitis B surface antigen (HBsAg), IgG antibody to HAV (IgG anti-HAV), and IgM antibody to HAV (IgM anti-HAV). Stools were tested for HAV by radioimmunoassay. Five patients (16.1%) had acute hepatitis B, five (16.1%) had acute non-A/non-B hepatitis, and 21 (67.7%) had acute hepatitis A. Of these 21 patients with acute hepatitis A, 11 (52.4%) were found to have HAV in their stools. These results confirm the potential for infectivity of stools of patients hospitalized for hepatitis A and emphasizes the need for caution when dealing with such stools.

Feces↗

Dissociation of hepatitis A virus antigen-anti-HAV antibody complexes by 2-mercaptoethanol and dithiothreitol.

Intravenous inoculation of two marmosets and one chimpanzee with hepatitis A virus (HAV) resulted in the replication of virus in liver, excretion of HAV particles in stool, and the appearance of circulating antibodies specific for hepatitis A. The development of an early antibody response in the chimpanzee and in one of the two infected marmosets was shown to interfere with the serologic detection of HAV antigen (HAV Ag) in homogenates of acute phase liver tissue obtained from these animals. Treatment of HAV Ag-positive and IgM anti-HAV-positive liver homogenates with thiol reducing compounds was shown to release HAV Ag from in vitro formed immune complexes. The increased RIA response for HAV Ag in homogenates treated with 2-mercaptoethanol (2-ME) or dithiothreitol (DTT) was further shown not to be due to activation of HAV Ag itself or to a nonspecific effect on the RIA coating antibody, radiolabeled probe, or homogenized liver tissue. IgG and IgM double-antibody sandwich RIAs for HAV Ag were also compared for their ability to detect HAV Ag under reducing and nonreducing conditions. Application of the 2-ME or DTT treatment procedure to the serologic detection of other viral antigens or viruses whose presence in blood, stool, tissue macerate, or other milieu may be masked by specific antibody appears to be feasible.

Animals↗

Risk factors for hepatitis A in day-care centers.

Outbreaks of hepatitis in day-care centers in Maricopa County, Arizona, were studied over a two-year period to learn which center characteristics affected the spread of hepatitis A. Of the 279 licensed center, 85 (30%) had outbreaks of hepatitis affecting three or more families. Outbreaks occurred in 63% of centers enrolling infants younger than one year of age, 32% of centers enrolling children one year of age or older, and 2.5% of centers enrolling children two years of age or older (P less than 0.0001). Outbreaks were also significantly more frequent in large centers enrolling greater than or equal to 51 children, centers open greater than 15 hours per day, and centers operated for profit. The introduction of hepatitis into a center was related strongly to the number of hours open and to the size and age enrollment, but the spread of hepatitis was related solely to the presence of children younger than two years of age. These data strongly link the spread of hepatitis A in day-care centers to the presence of very young children and provide a framework for designing disease-control strategies.

Age Factors↗

Transmission of hepatitis B by an oral surgeon.

An outbreak of hepatitis B in southeastern Connecticut was traced to an oral surgeon. In a serosurvey of his 754 noninstitutionalized patients, 511 (68%) participated. The rates of seropositivity for hepatitis B surface antigen (HBsAg) or antibody to HBsAg by year of oral surgery were 4.8% in 1977, 7.4% in 1978, and 14.8% in 1979. The transmission of hepatitis B, as measured by seropositivity, occurred between November 1978 and August 1979; the peak transmission was in February (31.2% seropositivity). Seropositivity was strongly correlated with the extent of surgical trauma (P less than 0.0001). HBsAg subtyping revealed that the oral surgeon and all four subtypable patients demonstrated both d and y reactivity, as did the patient from whom it was most likely the oral surgeon acquired his infection: a mentally retarded patient who had 24 extraction in March 1978. This study demonstrates that the transmission of hepatitis B between dental practitioners and their patients frequently results in subclinical infections.

Adolescent↗

Temporal patterns of ultrastructural alterations in hepatocytes of chimpanzees with experimental non-A, non-B hepatitis.

Non-A, non-B hepatitis was transmitted to eight chimpanzees by intravenous inoculation with antihemophilic materials (factor VIII) that had been implicated in transmission of the disease, with acute-phase liver homogenate from an infected chimpanzee, with acute-phase from an infected chimpanzee, or with chronic-phase plasma from infected chimpanzees. All eight animals developed elevated alanine aminotransferase activity, and all demonstrated unique hepatocyte cytoplasmic tubules at some time during the acute phase of disease. The temporal patterns for tubule appearance in hepatocyte cytoplasm, however, were highly variable, even between chimpanzees given similar inocula. Convoluted membranous structures were found occasionally in early or pre-acute-phase liver biopsy specimens. Aggregates of microtubules were also found in hepatocyte cytoplasm in some acute-phase biopsy specimens. No disease-specific nuclear changes or structures, including clusters or crystalline arrays of virus-like particles, were found in any of the serial liver biopsy specimens from chimpanzees with experimental non-A, non-B hepatitis.

Alanine Transaminase↗

Hepatitis B in homosexual men: prevalence of infection and factors related to transmission.

Of 3,816 homosexual men examined in five sexually transmitted disease clinics in the United States, 6.1% had hepatitis B surface antigen, 52.4% had antibody to hepatitis B surface antigen, and 3.0% of the men who had no other indicator of infection with hepatitis B virus (HBV) had antibody to hepatitis B core antigen. The rate of seropositivity for HBV indicated by the presence of one or more of these serologic markers was 61.5%; seropositivity was significantly related to the duration of regular homosexual activity and to the number of nonsteady male sexual contacts in the four months before the patients were interviewed. Anal-genital intercourse, oral-anal intercourse, and rectal douching were significantly related to evidence of HBV infection, but oral-oral contact and oral-genital contact were not. Trauma to the rectal mucosa is a feature common to the practices that were significantly related to seropositivity for HBV.

Adolescent↗

Transmission of type B viral hepatitis via eye inoculation of a chimpanzee.

To simulate a splash of infectious material in the eyes, plasma from a hepatitis B patient was placed on the corneal surfaces of a chimpanzee. The animal became infected 9 weeks later. This result indicates a need for the use of eye protection in high-risk areas, such as clinical laboratories, hemodialysis units, and dental operatories.

Animals↗

Survival of hepatitis A virus in feces after drying and storage for 1 month.

Hepatitis A virus in feces remained viable after being dried and then stored at 25 degrees C and 42% relative humidity for 30 days, as evidenced by infection of two marmosets inoculated with 1 ml of the treated fecal material. The virus was excreted in stool specimens from these animals, and seroconversion to antibody to hepatitis A virus occurred 28 and 35 days post-inoculation.

Animals↗

Serodiagnosis of acute hepatitis B virus infection by a modified competitive binding radioimmunoassay.

Using the Staphylococcus aureus absorption method, we have modified a commercial radioimmunoassay kit for the determination of total antibody to hepatitis B core antigen so that we can now determine the predominant globulin species of that antibody. One-hundred percent of acute hepatitis B sera had a predominance of immunoglobulin M antibody to hepatitis B core antigen, whereas immunoglobulin G antibody to hepatitis B core antigen was predominant in 98.2% of chronic hepatitis B surface antigen carriers. With this test and the commercially available tests for immunoglobulin M anti-hepatitis A virus, one can now reasonably differentiate acute hepatitis B from non A/non B hepatitis in a chronic hepatitis B surface antigen carrier.

Acute Disease↗

The prevention of hepatitis B with vaccine. Report of the centers for disease control multi-center efficacy trial among homosexual men.

A randomized, double-blind, vaccine/placebo trial of the Merck 20-micrograms hepatitis B virus (HBV) vaccine was done among 1402 homosexual men attending venereal disease clinics in five American cities. Vaccination was followed by only minimal side effects. Two doses of vaccine induced antibody in 80% of vaccine recipients. A booster dose 6 months after the first dose induced antibody in 85% of recipients and markedly increased the proportion of recipients who produced high antibody titers. The incidence of HBV events was markedly less in the vaccine recipients compared to that in the placebo recipients (p = 0.0004). Between month 3 and 15 after the first dose, 56 more significant HBV events (hepatitis, or hepatitis B surface antigen positive, or both) occurred in the placebo group while only 11 occurred in the vaccine group. Ten of the 11 HBV events in the vaccine recipients occurred in hypo- or nonresponders to the vaccine. This vaccine appears to be safe, immunogenic, and efficacious in preventing infection with hepatitis B virus.

Adult↗

Nosocomial viral hepatitis.

Viral hepatitis has long been recognized as a hazard in the health care environment. Nosocomial hepatitis B initially emerged in the setting of transfusion-associated infection and later in patients in dialysis units and on oncology wards. Health care workers are also at risk of acquiring nosocomial hepatitis B and more likely to acquire the infection from their patients than vice versa. Rare instances of nosocomially-transmitted hepatitis A have been documented, but hepatitis A virus excretion patterns in relation to onset of disease generally preclude significant transmission in the hospital setting. With virtual elimination of transfusion-transmitted hepatitis B, non A/non B hepatitis is the most significant cause of post-transfusion hepatitis and may occur in as high as 15 percent of the patients given multiple transfusions. Control of nosocomial viral hepatitis is based on the creation of environmental barriers specific for each viral agent. For hepatitis B, serologic surveillance of staff and patients in high risk areas, together with use of immunoglobulins for post-exposure prophylaxis and hepatitis B vaccine in susceptible persons, promises to significantly reduce nosocomial infection. Isolation procedures for patients admitted with hepatitis A or B are based on use of blood precautions for hepatitis B, modified enteric precautions for hepatitis A and a combination of both for non A/non B or etiologically unspecified hepatitis.

Cross Infection↗

Enzyme potentiated radioimmunoassay (EPRIA): a sensitive third-generation test for the detection of hepatitis B surface antigen.

A sensitive, specific immunoassay for detection of hepatitis B surface antigen (HBsAg) is described. The assay combined enzyme-linked immunosorbent assay and solid-phase radioimmunoassay and is termed enzyme potentiated radioimmunoassay (EPRIA). HBsAg was quantitated by enzymatic conversion of L[14C]glutamic acid to 14CO2 and gamma-aminobutyric acid by glutamate decarboxylase (GDC) conjugated wih goat anti-HGs IgG. Conjugation of IgG and GDC was by a thiol-disulfide bond exchange reaction after reacting N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) with each reagent. A positive/negative ratio of 2.2 was established as significant by examination of 40 normal sera negative for HBsAg. This value was the mean cpm plus 3 standard deviations. By an identical statistical analysis of sensitivity, EPRIA was found to be approximately 100-fold more sensitive than Ausria II (Abbott Laboratories, North Chicago, IL).

Animals↗