Biomedical subjects
H Popper
Publications and source records attributed to H Popper.
Early hepatic histologic alterations among chemical (vinyl monomer) workers.
Focal hepatocellular hyperplasia and focal mixed (hepatocytes and sinusoidal cells) hyperplasia are early histological alterations indicative of vinyl monomer exposure. To evaluate their uses in screening chemical workers, 93 liver biopsy specimens from 78 persons were examined in double-blind duplicative fashion. Forty-eight specimens were from exposed chemical workers, 35 of them having liver biopsy(ies) for hepatic test abnormalities and 13 for nonliver -related reasons. A comparison group consisted of 30 nonchemical workers who had undergone liver biopsy for nonliver related reasons. Twenty-three of the exposed workers (48%) had hepatic lesions consistent with exposure: 17 (35%) of these had focal hepatocytic hyperplasia, while 6 (13%) had focal mixed hyperplasia or more advanced lesions. Only five of the comparison group had like findings: four (13%) had focal hepatocytic hyperplasia; one had focal mixed hyperplasia and sinusoidal dilatation. This individual had persistent hepatic test abnormalities with the focal mixed hyperplasia and a sinusoidal dilatation, and on subsequent biopsy, angiosarcoma (and a history of using hair spray containing vinyl chloride propellant ). Ten individuals had 25 multiple biopsies also read double-blindly; 10 had two or more readings of the same biopsy. Duplicate 21 of 23 (91%) and multiple 27 of 28 (96%) biopsy interpretations in the same individual were identical. Only 6% of either duplicate and/or multiple readings disagreed. Both focal hepatocellular and mixed hyperplasia were always associated with abnormalities in hepatic test results of which indocyanine green clearance was the most sensitive and gamma-glutamyl transpeptidase the least specific.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatitis B virus, hepatitis non-A, non-B virus and hepatitis delta virus in lyophilized antihemophilic factor: relative sensitivity to heat.
Lyophilized plasma derivatives are more stable to heat than when they are in the liquid state. Commercial Factor VIII (antihemophilic factor) was seeded with a measured quantity of hepatitis B virus. The contaminated material was then lyophilized and subjected to heat of 60 degrees C for 30 hr. Chimpanzees were inoculated with the heat-treated antihemophilic factor or sham-treated antihemophilic factor that had been held at 4 degrees C. Surprisingly, hepatitis B virus survived the heating procedure with no apparent loss in titer: the incubation period to appearance of HBsAg was that expected for the challenge dose of virus. Even more surprising, one chimpanzee (the recipient of the unheated antihemophilic factor) also developed non-A, non-B hepatitis and two chimpanzees (recipients of the heated antihemophilic factor) also developed delta hepatitis. Neither of these agents was a contaminant of the hepatitis B virus challenge pool, since the purity of this hepatitis B virus pool was established previously in chimpanzees. Thus, both a non-A, non-B agent and the delta agent apparently contaminated the commercial antihemophilic factor. This is the first direct evidence for contamination of antihemophilic factor with the delta agent and confirms previous seroepidemiologic evidence for its presence in pooled plasma derivatives. Subsequent inactivation studies were performed with antihemophilic factor experimentally contaminated with the Hutchinson strain of non-A, non-B hepatitis virus. In these studies, heating at 60 degrees C for 30 hr in the dry state rendered antihemophilic factor free of detectable non-A, non-B hepatitis virus.
Specific histologic features of Santa Marta hepatitis: a severe form of hepatitis delta-virus infection in northern South America.
Stimulated by observations in an outbreak of hepatitis delta-virus infection among Yucpa Indians in Venezuela, in which unusual histologic features were found, we studied 100 cases of fatal hepatitis from Colombia, South America, which had been obtained by autopsy or viscerotomy. These cases were considered to be "Santa Marta hepatitis," or "hepatitis of the Sierra Nevada de Santa Marta," which has been observed in this region for more than 40 years. Of the 100 cases, 19 had a variety of histologic lesions or were normal, and hepatitis delta-virus antigen was not demonstrated immunocytochemically in any of them. By contrast, 81 cases had a characteristic histologic picture with intense microvesicular steatosis associated with conspicuous eosinophilic necrosis of the hepatocytes, which apparently were sluggishly removed by cytolysis. Hepatitis delta-virus antigen was detected in 70% of the 81 cases, and the absence of detection of this antigen was often associated with poor tissue preservation and more extensive hepatocyte necrosis. A smaller percentage of patients had hepatitis B virus antigens detectable in liver tissue. The characteristic lesion in these 81 cases could be distinguished from other causes of microvesicular steatosis by the extensive eosinophilic necrosis. Other variable accompanying features included intraacinar, mainly macrophagic, scavenger cell inflammation, intense portal inflammation, a parenchymal regeneration, and ductular and arteriolar proliferation. Santa Marta hepatitis as a severe form of hepatitis delta-virus infection differs markedly from fulminant delta-hepatitis in Europe and the United States in which the microsteatosis with marked eosinophilic degeneration is not found. The causes for these differences are unknown but may relate to nutritional factors or environmental toxins.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidemiologic aspects of Santa Marta hepatitis over a 40-year period.
"Santa Marta" hepatitis has been recognized as an unusual type of severe hepatitis occurring in northern Colombia since 1930. Liver specimens from a historic viscerotomy series, used by Gast-Galvis to identify cases and describe epidemiologic features of this disease, were available for review and histopathologic staining for delta-virus. Of 86 liver specimens examined from cases of fulminant Santa Marta hepatitis, 81 showed a distinct histopathologic picture, in various stages of progression, with features of eosinophilic necrosis, microvesicular fat infiltration of the liver parenchyma and morula cells; 69% were positive for delta-antigen by immunoperoxidase staining. This disease occurred predominantly in several small towns within 50 km of Santa Marta, with mortality reaching 1.25 per 1,000 inhabitants per year during the 1940's. Children under age 15 were most commonly affected and males affected twice as frequently as females. Liver specimens obtained from children, or within 15 hr of death, or which showed early histologic stages of disease were most likely to be positive for delta-antigen. This and the accompanying study confirm the existence of a distinct type of fulminant hepatitis in Colombia for over 50 years. The epidemiologic and histopathologic features are comparable to severe hepatitis in Venezuela Indians and in the Amazon basin of Brazil, suggesting that all are caused by delta-superinfection of hepatitis B virus carriers.
Regulatory modulation in hepatology.
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Chronic type B hepatitis and the "healthy" HBsAg carrier state.
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Relation of the hepatitis B virus carrier state to hepatocellular carcinoma.
The attempt to divide the large group of chronic HBsAg carriers into "healthy" vs. those with chronic hepatitis of various intensities is sometimes difficult. The major problems are overlap in clinical manifestations, hepatic test results and histologic as well as virologic features. Nevertheless, this separation is not only conceptually important, but may also be useful in patient management, particularly because of the risk of transition to cirrhosis and HCC. Although at least 75% of patients with HCC associated with HBV have cirrhosis, the time point at which the cirrhosis developed is not established, particularly since the vast majority of chronic HBsAg carriers fall into the "healthy" category. Important unanswered questions are, therefore: how often do "healthy" carriers develop cirrhosis and/or HCC, including the time relations between the two? Does the transformation to HCC result from one or several identifiable acute events in the "healthy" carrier (or in mild CPH) or is it a gradual process of progressing chronic hepatitis B in which intercurrent exacerbations may still play a role? Do the quantitative observations as to the relation between persistent HBV infections and HCC in the East apply to Western countries? Our hypothesis concerning pathogenesis is based on pathologic, molecular, clinical and epidemiologic observations and concepts, and is supported by studies of hepadna virus-infected animals. This thesis proposes that integration of HBV DNA into host chromosomes in acute or chronic hepatitis or during the "healthy" carrier state corresponds to an initiation event similar to that described in chemical carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Serial passage of hepatitis delta virus in chronic hepatitis B virus carrier chimpanzees.
Five consecutive passages of hepatitis delta virus in hepatitis B virus carrier chimpanzees were performed in order to further characterize the infectious and pathogenic nature of this naturally occurring defective virus. Three animals received identical inocula at fourth passage in order to assess individual animal variation as a factor in the course of infection and disease. Acute hepatitis delta virus infection occurred in all hepatitis B virus carrier chimpanzees as demonstrated by coincident intrahepatic hepatitis delta antigen, serum hepatitis delta antigen and serum hepatitis delta virus RNA followed by seroconversion to antibody to hepatitis delta antigen. In all animals, acute hepatitis was temporally associated with hepatitis delta virus infection and was self-limited. The incubation period to hepatitis shortened with passage, whereas biochemical and histologic evidence of liver diseases increased. The marked increase in liver disease with passage was not associated with increasing markers of hepatitis delta virus replication or expression, thus indicating that adaptation to the chimpanzee by serial passage resulted in increased hepatitis delta virus virulence. The duration of hepatitis due to hepatitis delta virus infection in three chimpanzees which received the same inoculum varied from 1 to 8 months. The observations of passage adaptation and individual host variation in this experimental model of hepatitis delta virus disease parallel known pathogenic variations in human hepatitis delta virus infection.
Photochemical decontamination of blood components containing hepatitis B and non-A, non-B virus.
Diluted plasma samples containing 10(2), 10(3), 10(4), and 10(5) chimpanzee infectious doses (CID) of a human non-A, non-B hepatitis virus (NANBV) were treated with a combination of two psoralen compounds, 4'-aminomethyl-4,5',8-trimethylpsoralen and 4,5',8-trimethylpsoralen, and exposed to long wavelength ultraviolet. Each dilution was then transfused into one of four chimpanzees. In a second experiment, three samples containing 10(4.5) CID of hepatitis B virus (HBV) and two samples containing 10(4) CID of NANBV were treated with 8-methoxypsoralen (8-MOP) and ultraviolet irradiation. Two chimpanzees were each transfused with both a treated HBV and a treated NANBV sample. The third chimpanzee was inoculated with a treated HBV sample alone. In the six months after inoculation none of the animals showed biochemical or histological evidence of hepatitis. In experiments involving NANBV inocula, the susceptibility of the animals was confirmed by subsequent challenge with untreated NANBV. Factor VIII concentrate containing virus and photochemically treated as in the first experiment retained an average of 91% of its activity while that in the second experiment retained 94% of its activity.
Adverse drug reactions involving the liver: probable mechanisms.
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In memoriam Joseph Klingenstein 1891-1976.
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Gustave L. Levy and the development of the medical school.
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The current challenge to medical education in the United States.
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Eulogies delivered at the funeral service of Dr. George James.
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The role of the medical school in the delivery of health care.
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Isidore Snapper, M.D. 1889-1973.
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