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Biomedical subjects

J E Maynard

Publications and source records attributed to J E Maynard.

At least 55 records · Page 3Linked to original sources

Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets.

An epidemic of non-A, non-B hepatitis occurred in Kathmandu Valley, Nepal, during 1981-1982, with approximately 7.6% of households and 1.4% of individuals affected. Cases occurred preponderantly in the 15- to 34-year-old age group (70%), with most cases (75%) occurring in males. A high mortality rate (21%) occurred in pregnant women admitted to the hospital. No single water source was implicated, but epidemic peaks occurred during monsoon rains, and multiple opportunities for enteric transmission existed. One of eight patient stools examined by immune electron microscopy revealed aggregated, antibody-coated, 27-nm viruslike particles when convalescent serum samples were used as sources of antibody. Inoculation of two chimpanzees and four marmosets with a suspension of this stool resulted in elevated liver enzyme activity in three marmosets. Fecal excretion of 27-nm particles during the acute phase of disease (with temporally coincident antigen activity by radioimmunoassay) was observed in one marmoset, which also developed convalescent antibody against the particles in the original inoculum.

Adolescent↗

Hepatitis A virus: growth characteristics of in vivo and in vitro propagated wild and attenuated virus strains.

Serial passage of the MS-1 strain hepatitis A virus (HAV) in marmosets was shown to increase the yield of virus and to shorten the incubation period from approximately 55 days in the first passage to 3-7 days in the ninth and higher passages. Intravenous inoculation of susceptible chimpanzees with MS-1 HAV was found to result in a typical course of disease in two animals who had received eighth marmoset-passage virus, including the occurrence of elevated ALT activity, presence of HAV antigen in liver and stool, and seroconversion to anti-HAV. Two chimpanzees inoculated with 20th passage MS-1 HAV (M001 liver homogenate) exhibited normal or nearly normal ALT activity and had no demonstrable or significant HAV in weekly liver biopsy specimens or in serial stool suspensions obtained during 64 days of observation. However, both animals seroconverted to anti-HAV within 2 weeks after inoculation, as did the animals who had received eighth passage MS-1 HAV. These findings suggest that subpassage of the MS-1 strain of HAV in marmosets resulted in the generation of an attenuated virus strain that was still capable of inducing a vigorous antibody response in intravenously infected chimpanzees. Serial propagation of wild and attenuated strains of HAV (HAS-15 and MS-1/M001, respectively) in FRhK-4 cells was associated with a significant decrease in the growth period for both viruses. Our studies have also shown that HAS-15 HAV can be recovered in maximum yield in later passages as early as 2 to 3 days after inoculation.

Animals↗

Occurrence of hepatitis A, B, and non-A/non-B in the United States. CDC sentinel county hepatitis study I.

To determine the relative occurrence of hepatitis A, B, and non-A/non-B in the United States, serum samples and epidemiologic data were collected from patients with hepatitis in five selected counties. Overall, 41, 33, and 26 percent of the patients had hepatitis A, hepatitis B, and hepatitis non-A/non-B, respectively. The incidence, especially of hepatitis A, varied considerably. All three types of hepatitis occurred more frequently in those 15 to 44 years of age. Hepatitis A predominated in those less than 15 years of age and non-A/non-B predominated in those older than 44 years. There was a male predominance (65 to 62 percent) for hepatitis A and hepatitis B, but non-A/non-B occurred equally in both sexes. There was no seasonal pattern for any type. Risk factors for hepatitis A were previous contact with a patient with hepatitis (26 percent), homosexual (male) preference (15 percent), and day-care center contact (11 percent). For hepatitis B, risk factors included drug use (26 percent), previous contact with an infected person (22 percent), homosexual preference (12 percent), and a health-care occupation (12 percent). For hepatitis non-A/non-B, risk factors included drug use (16 percent), transfusion (12 percent), and previous contact with an infected person (12 percent). Previous hospitalization appeared to be a risk factor for both hepatitis B and hepatitis non-A/non-B.

Adolescent↗

DNA: DNA hybridization method for the diagnosis of hepatitis B infection.

Hepatitis B viral (HBV) DNA was detected in a hepatoma cell line which produces hepatitis B surface antigen (HBsAg) and in patients with acute hepatitis B. The serum of one patient with acute hepatitis B was found to be infectious when injected i.v. into a chimpanzee up to a dilution of 10(-8). Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detectable in the same serum sample by radioimmunoassay up to a dilution of 10(-5) and of 10(-3), respectively. Using DNA: DNA hybridization on nitrocellulose membranes, HBV DNA sequences were detectable up to 10(-8) dilution corresponding to the infectivity level. Based on this finding, it appears that DNA: DNA hybridization is the most sensitive method for detecting hepatitis B virus (HBV) infection. In situations with low virus levels it may be the only indicator of the presence of infectious hepatitis B virus. The use of a tritium-labelled probe makes the method economical and adaptable to hospital laboratories.

DNA, Viral↗

Early detection of primary hepatocellular carcinoma by screening for alpha-fetoprotein in high-risk families. A case-report.

Serum levels of alpha-fetoprotein (AFP) may be raised for up to 2 years before clinical presentation of primary hepatocellular carcinoma (PHC). A group of people judged to be at high risk of PHC because of long-term serological positivity for hepatitis B surface antigen, ethnicity, location of residence, and a strong family history of PHC were screened for increasing levels of AFP. After 1 1/2 years of twice-yearly screening, one of them, a 19-year-old Eskimo man, had a raised AFP level, which continued to rise rapidly over the next 3 months, although the patient remained symptomless and ultrasonography, 99mTc-scan, and computerised tomography of the liver were negative. Hepatic angiography suggested a small tumour in the periphery of the right lobe of the liver, but at laparotomy the right lobe was normal. Instead a tumour was found in the lateral tip of the left lobe. The tumour, a PHC, was resected surgically, and the patient has been well in the 11 months since his operation. His serum AFP level returned to normal 2 weeks after the operation and has remained normal.

Adult↗

Effect of immunoglobulin on hepatitis A in day-care centers.

Over a 21-month interval, we investigated the effectiveness of immunoglobulin (lg) in preventing hepatitis A spread in day-care centers. Immunoglobulin was given to all center and employees whenever hepatitis occurred in one center child or employee or parents in two families. Immunoglobulin programs were completed in 91 centers during the trial within an average of 17 days of onset of illness in the index case. Immunoglobulin intervention caused significant reduction in the average size of a day-care hepatitis outbreaks, from 7.3 cases in historically untreated centers to 6.0 cases in Ig-treated centers. Cases in center children and employees virtually ceased two weeks after Ig intervention, while those in household contacts decreased significantly within six weeks. Reported cases of hepatitis type A or unspecified in the community decreased 75%, and the number of new hepatitis outbreaks decreased 77% during the trial. A decrease occurred not only in day-care-associated cases, but in cases not directly associated with centers, probably due to decreased tertiary spread from day-care families into the community. Use of Ig to prevent hepatitis spread in day-care centers seems to be an excellent means of controlling this disease, both within the centers and the general community.

Arizona↗

Unrelatedness of factor VIII-derived non-A/non-B hepatitis and hepatitis B virus.

A DNA hybridization assay was used to detect hepatitis B virus (HBV)-specific DNA sequences in extracted sera obtained from chimpanzees infected with HBV, hepatitis A virus (HAV), and a factor VIII-derived non-A/non-B (NANB) agent. The results did not reveal any HBV-DNA homology with sera obtained from animals infected with HAV or factor VIII-derived NANB. Sera obtained from two HBV-infected chimpanzees demonstrated that HBV-specific DNA could be detected during the acute phase of the disease. In addition, an HBV-specific DNA-dependent DNA polymerase assay did not demonstrate any statistically significant activity in 12 of 12 NANB acute-phase specimens or in 6 of 6 NANB chronic-phase specimens. These results suggest that the factor VIII-derived NANB agent is unrelated to HBV.

Animals↗

Non-A, non-B hepatitis in chimpanzees: interference with acute hepatitis A virus and chronic hepatitis B virus infections.

Two chimpanzees with persistent non-A, non-B (NANB) hepatitis were superinfected with marmoset-passaged MS-1 HAV. Two control chimpanzees were also infected with marmoset-passaged HAV. Neither animal with persistent NANB hepatitis developed elevated alanine aminotransferase (ALT) activity, whereas both control chimpanzees exhibited ALT elevations within 3 weeks after inoculation. In addition, both NANB-infected chimpanzees demonstrated a delayed anti-HAV antibody response in which one animal failed to produce detectable IgM anti-HAV. With the exception of one stool, all serial liver biopsy specimens and daily stool suspensions from the superinfected chimpanzees were negative for HAV antigen. One chimpanzee with a chronic HBV infection was superinfected with non-A, non-B hepatitis and was shown to develop elevated ALT activity and hepatocyte ultrastructural alterations accompanied by a marked reduction in the titer of serum HBsAg. Our combined findings indicate that acute and persistent non-A, non-B hepatitis infections are capable of interferring with two distinctly different hepatotropic viruses. These results also suggest that in vitro detection of non-A, non-B hepatitis infection or virus(es) may be achieved by antibody-independent methodologies that employ the basic principle of viral interference.

Alanine Transaminase↗

Dialysis encephalopathy and aluminum exposure: an epidemiologic analysis.

We identified 55 patients with dialysis encephalopathy in six dialysis centers studied by means of a uniform clinical classification. Dialysis encephalopathy was the direct cause of death in most cases, and the disease appeared to significantly shorten survival. The overall attack rate of dialysis encephalopathy was 4% and varied among dialysis centers from 2.2% to 14.7%. In two centers with adequate data, the attack rate for dialysis encephalopathy rose significantly with increasing cumulative aluminum exposure via dialysate, and the mean cumulative aluminum exposure for patients with the disease was significantly higher than that for all other patients at risk. We further demonstrated that the cumulative level of aluminum tolerated by the patient before onset of symptoms was inversely related to the average aluminum concentration of dialysate water.

Aluminum↗

Posttransfusion non-A, non-B hepatitis: physicochemical properties of two distinct agents.

Two separate and distinct episodes of non-A, non-B hepatitis were induced in each of two chimpanzees by two inocula: one containing a chloroform-resistant agent and the other containing a chloroform-sensitive agent. Both agents were recovered from liver tissue and plasma obtained from a single chimpanzee during the acute and chronic phases of infection with a factor VIII concentrate, respectively. The chloroform-resistant agent did not cause unique changes in hepatocytes; in contrast, the chloroform-sensitive agent did induce the formation of cytoplasmic tubules, convoluted endoplasmic reticulum, and dense reticular inclusion bodies. The latter changes are similar in character to those induced in infected cells by some enveloped mammalian RNA viruses.

Animals↗

Prevalence of hepatitis B in selected Alaskan Eskimo villages.

Sera collected in 1973-1975 from 3053 residents of 12 selected Alaskan Eskimo villages were tested for evidence of hepatitis B virus infection. Overall, hepatitis B surface antigen (HBsAg) was found in 6.4% of those tested. Evidence of hepatitis B infection (positive for HBsAg or antibody to hepatitis B surface antigen (anti-HBs] varied considerably by village, from 4.6% to 69.9%, and increased with advancing age. The proportion with HBsAg was significantly higher in those under the age of 13 years, and the male/female ratio varied from 0.9 to 1.5 to 1.5 in the prepubertal, postpubertal-premenopausal, and postmenopausal age groups, respectively. The prevalence of hepatitis B e antigen (HBeAg) in HBsAg-positive persons decreased with advancing age, and conversely, the prevalence of antibody to hepatitis B e antigen (anti-HBe) increased with age. Hepatitis B infection was found to be sporadically distributed, with great village-to-village variation and further variation by household within most villages. The high HBsAg and HBeAg seropositivity observed in children suggests that children are both more recently infected with hepatitis B and are more involved in hepatitis B transmission in these villages.

Adolescent↗

Hepatitis B virus transmission associated with a multiple-dose vial in a hemodialysis unit.

Ten of sixty-one patients in a maintenance hemodialysis center seroconverted to hepatitis B surface antigen (HBsAg)-positive in August 1981. All but one were negative for antibody to hepatitis B core antigen, indicating early infection, and all received dialysis on the same days. Findings of case-control study showed that all "cases" received dialysis after the early morning shift, compared to 50% of controls (p = 0.01), and all cases used a multiple-dose vial of local anesthetic (bupivacaine), compared to 58% of controls (p = 0.03). At a common area used to prepare medications, an HBsAg carrier apparently stuck herself with a needle before drawing up bupivacaine, thus contaminating the vial that then served as the vehicle of transmission. Ten of eleven susceptible patients (those negative for antibody to HBsAg) who subsequently used bupivacaine and received dialysis seroconverted to HBsAg-positive, giving an attack rate of 91%. Serum samples from six of the ten cases were subtype Ad (or Adw), as was the implicated carrier's serum.

Bupivacaine↗

Experimental conditions affecting the sensitivity of enzyme-linked immunosorbent assay (ELISA) for detection of hepatitis B surface antigen (HBsAg).

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) for the detection of hepatitis B surface antigen (HBsAg) was improved 16 to 32 times after examination of various solid-phase supports, different antibody preparations as capture antibody, and different conditions for adsorbing capture antibody to the solid-phase. Comparisons were made by checkerboard titration analysis and by sensitivity studies, both of which demonstrated essentially equivalent results. Endpoints were determined by visual inspection and by spectrophotometry using o-phenylenediamine as substrate. The assay was as sensitive as commercially available radioimmunoassays without the requirement of affinity chromatography purified reagents, expensive instrumentation, or radioisotopes.

Animals↗