Primary hepatic cancer in alcoholics.
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Adult↗
Biomedical subjects
C H Tamburro
Publications and source records attributed to C H Tamburro.
Evidence for endothelial cell origin of vinyl chloride-induced hepatic angiosarcoma.
Previous reports of hepatic angiosarcoma have not clearly defined the cellular type from which this tumor arises, as evidenced by the terminology of endothelioma, Kupffer cell sarcoma, endothelial cell sarcoma, and hemangioendothelial sarcoma, etc., which have been used interchangeably. In addition, there has been no consensus on the separate entity of Kupffer and sinusoidal endothelial cells. In the work presented here, evidence for the endothelial cell origin of this tumor is provided by the demonstration of factor VIII, a known endothelial cell marker, in the tumor cells. Fluorescence due to the presence of factor VIII appeared intense in the tumor sinusoidal cells of all four vinyl chloride-associated angiosarcomas studied, whereas normal liver sinusoidal lining cells showed negligible fluorescence.
Endothelium↗
Exposure indices for epidemiological surveillance of carcinogenic agents in an industrial chemical environment.
A prospective system for establishing chemical exposure indices was developed and implemented for 22 chemicals used at a Louisville chemical plant. Validation of the indices was done statistically using industry-related cancer (liver angiosarcoma) and worker-matched controls. A rank ordered system for exposures was used to identify a relationship between the occurrence of disease and the presence of a suspect chemical used in the industrial environment.
Carcinogens↗
Identification of human toxicity and carcinogenicity by ethylene derivatives.
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Carcinogens, Environmental↗
Chemical hepatitis: pathogenesis, detection and management.
The toxic effects of many nonmedicinal chemicals include serious hepatic injury, often accompanied by various degrees of damage to other organs. Some chemicals produce only mild damage. Others are capable of producing injury only after ingestion of large amounts, after severe exposure, or in combination with another agent such as alcohol.
Acute Disease↗
Biochemical alterations in livers of rats exposed to vinyl chloride.
Sprague-Dawley rats were exposed to vinyl chloride to determine the earliest sequential biochemical changes occurring with liver injury before anglosarcoma development. Activity of glucose-6-phosphatase, a key gluconeogenic enzyme in the liver microsomal fraction, decreased 25% with respect to controls after 70 h of exposure. Glucose-6-phosphate dehydrogenase activity increased twofold after more than 100 h of exposure. Nonprotein sulfhydryl levels (glutathione and/or cysteine) showed a slight but progressive elevation, whereas glutathione reductase activity increased 50-60% during exposure to vinyl chloride.NADPH-cytochrome c reductase and mixed function oxidase were unchanged in the same microsomal fraction. There markers of liver mitochondrial, cytosol, and microsomal function. No significant histological changes were found on light microscopic examination during this exposure period. However, with electron microscopy, dilation of rough endoplasmic reticulum was seen in the animals exposed for more than 137 h. These enzymatic changes are considered to reflect early hepatocellular adaptation to vinyl chloride exposure with very mild or limited hepatocellular injury in its earliest stage.
Animals↗
Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.
Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.
Adolescent↗
Health effects of vinyl chloride.
Vinyl chloride is a basic chemical for plastics manufacturing and has been used as an anesthetic agent. Vinyl chloride's previously unknown carcinogenic capability appears to be related to the body's ability to convert it from a non-toxic or minimally toxic chemical to a toxic and, with prolonged exposure, cancer-forming agent. Early exposure in animals causes body cells to make adaptive changes which may prepare them for malignant transformation and appear to precede evidence of morphological injury. These findings appear to occur before a low-grade chemical injury occurs. Vinyl chloride chemical injury in man appears to follow the same pattern. Present clinical data in humans now demonstrate evidence of pre-cancer injury and cancer transformation of various types of cells in different organs of the body. Manifestations of pre-cancerous injury to organs other than the liver (such as the lung, heart, spleen, brain and lymphatic system) may also be occurring and require further investigation. Early detection of these pre-cancerous chemical injuries requires a prospective ongoing system of surveillance and the development of diagnostic methods which can identify specific causal agents in the presence of non-specific injury. Such a systematic approach has been developed and is now in operation. Its initial achievements appear to be the foundation for future success in controlling the health effects of industrial chemicals.
Animals↗
Urinary glycosaminoglycan patterns in angiosarcoma of the liver.
Glycosaminoglycans extracted from 24-hour urine specimens from patients with hepatic angiosarcoma and from normal/controls were separated as cetylpyridinium complexes into "hyaluronic acid," "chondroitin sulfate," and "heparin" fractions, then further separated and characterized by anion-exchange chromatography and hyaluronidase susceptibility. The chromatographic pattern of the urinary chondroitin sulfate fraction in patients with angiosarcoma of the liver differed from those of controls in that there was a relative increase in the total amount of uronic acid in a hyaluronidase-resistant fraction and a decrease in a fraction susceptible to hyaluronidase digestion. These changes appeared to become more pronounced with advancing disease. Chromatographic patterns and determinations of hyaluronidase susceptibility indicated that the resistant fraction was heparan sulfate and that the susceptible fraction was chondroitin-4-sulfate and/or chondroitin-6-sulfate.
Chondroitin Sulfates↗
A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study.
A double blind, randomized, controlled trial has been conducted in 11 Veterans Administration hospitals during a 49-month period to compare the relative efficacies of immune serum globulin (ISG) and an albumin placebo for the prevention of post-transfusion hepatitis (PTH). A total of 2204 patients, of whom 1094 received ISG, participated in the study. The results indicate that ISG significantly reduced the incidence of icteric type non-B hepatitis only (inferred to be also type non-A hepatitis). Adverse reactions were rare, and the ISG did not significantly alter the incubation period or duration of the disease. The data suggest, however, that a similar reduction in type non-A, non-B hepatitis would have occurred had commercial blood been excluded from use. Analysis of the 241 patients who developed hepatitis indicates that type B hepatitis constituted less than 20% of the cases each year of the study. Furthermore, the efficacy of the ISG, manufactured in 1944, against apparent type non-A, non-B hepatitis suggests that this overlooked disease has existed from at least that time. Host- and transfusion-related factors that might have modified the development of PTH were examined. The use of commercial blood was observed to be the most important risk factor. It is concluded that the PTH incidence can be most effectively reduced by eliminating commercial donor blood, and continuing to screen volunteer donors for hepatitis B surface antigen (HBsAg) by sensitive procedures. Of prime importance is the need to define the agent(s) responsible for type non-A, non-B hepatitis.
Adult↗
Angiographic and radionuclide characteristics of hepatic angiosarcoma found in vinyl chloride workers.
Hepatic angiosarcoma, recently discovered in a large series of vinyl chloride workers, demonstrates characteristic angiographic and radionuclide changes. Tumors exhibiting central hypovascularity with puddling are usually surrounded by a peripheral stain. A negative peripheral defect is demonstrated on hepatic scan. Healing hepatic infarction secondary to wedged hepatic venography creates a false-positive lesion on angiography similar to angiosarcoma. Splenomegaly and systemic venous hypertension develop in a number of these patients.
Adult↗
Efficacy of hepatitis B immune serum globulin after accidental exposure. Preliminary report of the Veterans Administration Cooperative Study.
A randomised, double-blind, controlled trial has been undertaken to compare the efficacy of hepatitis B immune globulin (H.B.I.G.) with that of immune serum globulin (I.S.G.) for the prophylaxis of viral hepatitis. Participants in the trial were individuals exposed accidentally to material infectious for hepatitis (primarily viral B hepatitis). Preliminary evaluation of the first 302 of the 561 individuals entered into the study indicates that H.B.I.G. significantly reduced the frequencies of both clinical and subclinical hepatitis during the first 3--4 months after the injection. Less than 10% of H.B.I.G. recipients had detectable anti-HBs at the sixth month after the injection, suggesting that H.B.I.G. might need to be given every 3--4 months to continually exposed individuals. Further long-term evaluation is required in order to define more clearly those most likely to benefit from H.B.I.G.
Clinical Trials as Topic↗
Liver disease of the alcoholic.
Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.
Alcoholism↗
Hepatitis B antigen in urban-caught mosquitoes.
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Aedes↗
Hepatitis in the individual.
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Acute Disease↗
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)
Biopsy↗
Hepatic disease in asymptomatic parenteral narcotic drug abusers: a Veterans Administration collaborative study.
The Veterans Administration is currently conducting a collaborative study in three hospital-based drug treatment clinics to evaluate asymptomatic parenteral drug addicts for evidence of hepatic disease. Preliminary data are presented on 347 patients who have completed at least three months of follow-up evaluation. On admission, abnormal serum transaminase values were demonstrated in one half, HBs Ag in 7 per cent, and anti-HBs in 59 per cent. The frequency of these findings increased during the follow-up evaluation, only 19 (5.5 per cent) remaining entirely free of one or more of these abnormalities. Definable hepatologic disease (acute or chronic hepatitis, alcoholic hepatitis) developed in 46 per cent of the patients. However, among 60 of them subjected to liver biopsy, a poor correlation was noted between the clinical and histologic diagnoses. In particular, routine liver function and immunologic tests did not discriminate between histologically detected chronic active and chronic persistent hepatitis. However, HBs Ag was present significantly more frequently in those with chronic active hepatitis. Wide variability of histologic diagnoses was seen among patients subjected to more than one biopsy, apparent progression and regression of the lesion being noted. This demonstrates the hazard of attempting to assign a prognosis to the disease on the basis of a single liver biopsy specimen, and suggests that repeated biopsies should be mandatory for the evaluation of chronic liver disease in drug addicts.
Acute Disease↗