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Biomedical subjects

J W Mosley

Publications and source records attributed to J W Mosley.

At least 73 records · Page 4Linked to original sources

Non-A, non-B hepatitis and antibody to hepatitis C virus.

Stored serum samples from the Transfusion-transmitted Viruses Study in the 1970s were tested for the presence of antibody to hepatitis C virus (anti-HCV). Single specimens from five control subjects who did not receive transfusions tested negative for anti-HCV. Of four control subjects who did not receive transfusions and who developed non-A, non-B (NANB) hepatitis after hospitalization, three remained anti-HCV negative; the fourth person with postoperative NANB hepatitis tested anti-HCV positive before the operation. Five transfusion recipients with posttransfusion hepatitis B virus infection remained seronegative; a sixth with NANB hepatitis as well as hepatitis B virus infection had seroconversion for anti-HCV. Five of nine transfusion recipients with NANB hepatitis had anti-HCV seroconversion. These results show that present anti-HCV testing demonstrates an etiologic basis for approximately half of the cases of transfusion-associated NANB hepatitis, particularly those that develop chronicity. Although cases of NANB hepatitis without seroconversion may be explained otherwise, they may be caused by another, presently unidentified, virus.

Blood Transfusion↗

Transmission of human immunodeficiency virus type 1 by dry-heated clotting factor concentrates. Transfusion Safety Study Group.

The Transfusion Safety Study monitored susceptible persons for human immunodeficiency virus type 1 (HIV-1) infections transmitted by plasma products and blood components. Through December, 1988, 6 subjects without antibody to HIV-1 (anti-HIV-1) became seropositive after receiving dry-heated factor VIII concentrate. The preparations implicated in 3 cases were derived entirely from anti-HIV-1-screened donors. In all instances, HIV-1 infection could be explained by concentrates heated at 60 degrees C for 24-30 h. Limiting consideration to concentrates and components administered after study entry showed that 4 of the seroconversions occurred among 122 subjects given 10 million units of factor VIII concentrates. No seroconversions occurred among 84 subjects given 5 million units of factor IX concentrates, or 83 who received components from over 26,000 unpaid donations. Serologic surveillance of anti-HIV-1-negative subjects provides important information, and should be routine in the management of persons receiving clotting factor concentrates.

Acquired Immunodeficiency Syndrome↗

Reproducibility in quality control of protein (Western) immunoblot assay for antibodies to human immunodeficiency virus.

The protein (Western) immunoblot assay (IB) for antibodies to human immunodeficiency virus, like other laboratory procedures, sometimes gives variable results. In the Transfusion Safety Study, indistinguishable aliquots of four quality control (QC) samples have been routinely submitted for IB with each group of patient specimens. A false negative IB result was obtained for 1.7% of 179 assays of two known positive (QC) standards and a false positive result for 2.0% of 101 assays of two known negative (QC) standards. In addition, a test panel of 24 samples was sent on a single occasion to three widely used laboratories. A false positive result was reported by one laboratory and a false negative by a second. Although generally reliable, IB results may occasionally be in error. There is much more technical variability in the relative frequencies of antigen-antibody bands than has been recognized. These interlaboratory and intralaboratory comparisons show quality control checks are essential for all laboratories, and more than one specimen should be tested if its applicability to a specific patient is questionable. Specific bands are sufficiently inconstant for the same specimen to make appearance or disappearance on successive specimens prognostically unreliable.

Blotting, Western↗

Hepatitis B virus antibody in blood donors and the occurrence of non-A, non-B hepatitis in transfusion recipients. An analysis of the Transfusion-Transmitted Viruses Study.

Patients who received transfusions and nontransfused control patients were followed to assess the incidence and cause of post-transfusion hepatitis and to identify donor factors that might relate to risk of hepatitis. We evaluated as risk factors in donors the presence of antibody to hepatitis B virus compared with elevated alanine aminotransferase (ALT) level. Units of blood that were positive for antibody to hepatitis B core antigen (anti-HBc) were associated with a twofold to threefold greater risk of non-A, non-B hepatitis in the recipients than were units without anti-HBc. In the absence of specific serologic tests for non-A, non-B agents, screening of donors for anti-HBc might be considered. Our data suggest that the incidence of non-A, non-B hepatitis might have been reduced by about one third by such screening. However, elevated ALT levels in donors had a similar association with non-A, non-B hepatitis in recipients but would have resulted in fewer units of blood being discarded than would screening for anti-HBc.

Alanine Transaminase↗

Present knowledge of viral hepatitis.

The term viral hepatitis refers to the diseases produced by at least three, and perhaps four or five aetiologic agents that differ in their virologic characteristics, ecologic mechanisms, epidemiologic patterns, and long term consequences. These divergences are now well-defined for hepatitis A virus (HAV) and hepatitis B virus (HBV). HAV is an RNA virus dependent upon consecutive transmission in childhood, and is not associated with long term sequelae. In contrast, HBV is a DNA virus capable of producing a reservoir of chronic human infection from which spread to adults as well as children can periodically occur by a variety of methods. Chronic HBV disease is not only a continuing source of potential viral transmission in the community, but also sometimes results years later in very serious consequences. Continuing destruction of the liver leads to cirrhosis and hepatic failure; in addition, integration of viral DNA into that of the hepatocyte is probably responsible for the high incidence of carcinoma of the liver associated with HBV infection in many areas of the world. The 'third' form of viral hepatitis is termed 'non-A, non-B' (NANB), because it is identified only by serologic exclusion of HAV and HBV infection. Its epidemiologic and clinical characterization are difficult because variations in behaviour in groups of cases suggest that more than one virus is responsible for this negatively defined entity. One or more of the agents leads to chronic infection, but the relative frequency with which it causes chronic active hepatitis or hepatocellular carcinoma cannot yet be stated.

Adult↗

Hepatitis A virus infection in households.

The behavior of hepatitis A virus (HAV) infection among 980 members of 230 families in two rural districts of Costa Rica was studied prospectively from the recognition of the index case. The initial prevalence of detectable antibody (anti-HAV) ranged from 26.2% in children to 71.4% in adults. The ratio of index to household-associated infections was significantly higher among children than among adolescents and adults, indicating that children were most often responsible for the HAV introduction. The rates of household-associated cases among susceptible contacts were 70-83%; the final prevalences of anti-HAV were 90-95%. Neither index showed significant differences related to age. The ratio of clinical to silent infections in household-associated cases was uniformly 1.8:1 among children and adolescents; among adults, almost all associated infections were silent. Beginning with the 5-9-year age group, however, an immunoglobulin M response was absent in a progressively larger proportion of inapparent infections, strongly suggesting restimulation of specific immunoglobulin G antibodies by reinfection.

Adolescent↗

Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study.

To evaluate the incidence of post-transfusion hepatitis and factors influencing its occurrence, the Transfusion-Transmitted Viruses Study prospectively followed 1513 transfusion recipients from 1974 through 1979. The attack rate for non-A,non-B hepatitis was 10 per cent. The incidence of hepatitis was directly related to the alanine aminotransferase (ALT) level in blood donors. In recipients of multiple transfusions of blood that had no donor-ALT level above 29 IU per liter the attack rate was 6 per cent or less; at higher donor-ALT levels the attack rate increased progressively, reaching 45 per cent in recipients of units with an ALT of 60 IU or greater. A similar relation was observed among recipients of single units of blood. Moreover, hepatitis developed in 10 of 11 recipients of two units with an ALT level of 45 IU or greater. These data indicate that screening blood for ALT levels would reduce the incidence of non-A,non-B post-transfusion hepatitis.

Adolescent↗

Immunoglobulin M level in the diagnosis of type A hepatitis.

The serum immunoglobulin M level has often but not always been found to be higher in type A than in type B hepatitis. Studies of this question, however antedated the recognition of non-A, non-B disease, and the etiologic characterization may have been mistaken in many instances. It was appropriate, therefore, to reopen the question by an investigation of 62 serologically defined cases. IgM values above 300 U/ml occurred in 28 of 33 type A episodes, three of 24 type B, and none of ten non-A, non-B cases. Although nonspecific, the IgM assay is a generally available procedure that may provide useful evidence concerning the etiologic form of acute viral hepatitis.

Hepatitis A↗

A virologically studied epidemic of type A hepatitis in a school for the mentally retarded.

The occurrence of hepatitis A virus (HAV) infection in a small boarding school for mildly to moderately mentally retarded children in Umka, Yugoslavia, in the spring of 1979, six years after the last recognized occurrence, provided an opportunity to study the spread of the agent among 79 classroom and dormitory contacts. Only 51% of those who had entered subsequent to the prior outbreak had detectable antibody (anti-HAV) with immunoglobulin G predominance, and the proportion within the first six years of training did not vary. Both findings suggest a lack of endemicity during the interval. The outbreak ended spontaneously just before the summer vacation with an anti-HAV prevalence of 90%. The ratio of silent to overt cases was approximately 2:1. HAV was found in fecal samples from susceptible residents with inapparent infection as well as those with hepatitis. Among those with prior experience, there were no significant anti-HAV increases to suggest HAV reinfection in this group. Overall, 32% were seropositive for markers of past or chronic hepatitis B virus (HBV) infection, but this status did not correlate with sex, year of training, or HAV experience. Only one instance of HBV transmission was observed in the same interval as the 26 HAV infections.

Adolescent↗

Studies on the maternal-infant transmission of the viruses which cause acute hepatitis.

Eighty-three women with acute icteric hepatitis during pregnancy were followed for evidence of viral transmission to their infants. Six women had acute hepatitis A as diagnosed by appearance of anti-HAV during convalescence. Except for passively acquired antibodies which were present at birth, anti-HAV did not appear in these infants, and there was no clinical or biochemical evidence for hepatitis during follow-up. Sixty-five pregnant women had acute hepatitis B during pregnancy or in the immediate postpartum period. Transmission to infants often occurred when both maternal HBsAg and HBeAg were positive at delivery of postpartum. A majority of these infants never developed jaundice, have remained persistently HBsAg-positive, and have had periodic serum ALT elevations during follow-up. Twelve women had acute non-A, non-B hepatitis during pregnancy. Infants born to 6 of these women near term had transient elevations of serum ALT values at 4-8 wk of age, suggesting maternal transmissibility of the non-A, non-B viral agent.

Acute Disease↗

Transfusion-transmitted viruses study: experimental evidence for two non-A, non-B, hepatitis agents.

Plasma, serum, and a concentrate of factor VIII, implicated in human cases of non-A, non-B (NANB) hepatitis, were inoculated into four chimpanzees. All four animals demonstrated significant elevations of alanine aminotransferase levels within five weeks. After recovery from these NANB hepatitis episodes, the chimpanzees were cross-challenged with different inocula. A second episode of NANB hepatitis occurred after challenge in three animals. Reproducibility of the results was established by reversing the sequence of inoculation in two of the animals. A known infectious concentrate of factor VIII failed to induce hepatitis in a previously infected chimpanzee although the animal remained susceptible to a third inoculum, an event suggesting that the first inoculum might contain the same NANB hepatitis agent as the concentrate of factor VIII, which was supported by results of a subsequent cross-challenge experiment. Reinfection did not occur in two chimpanzees injected with their initial challenge strain of NANB hepatitis virus, providing evidence that strain-specific immunity had been established. Thus, experimental evidence is provided for the presence of two NANB hepatitis agents, supporting clinical and epidemiologic studies that favor the existence of more than one etiologic agent.

Alanine Transaminase↗

Hepatitis B virus exposure of hospital staff.

A patient admitted to a general medical ward for evaluation of jaundice was transferred to an intensive care unit when he developed a hemorrhagic diathesis and hepatic encephalopathy. Fifteen days elapsed before it was recognized that the patient was infected with hepatitis B virus (HBV), during which time the staff took no precautions other than routine hand washing. On subsequent evaluation of risk, it was decided that administration of an immunoglobulin preparation was not indicated despite the patient's massive contamination of his immediate environment. Of 89 persons heavily, casually, or indirectly exposed, none developed clinical illness within six months following contact. A nurse, first tested 30 days after contact, was persistently hepatitis B surface antigen-positive, but results of testing for antibody to core antigen demonstrated she was a long-term carrier. Among 61 susceptible staff members tested serially, none had serologic evidence of HBV infection. Thus, not all HBV-infected patients are highly contagious. Nonetheless, procedures to prevent such unprotected exposures are needed.

Aged↗