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Biomedical subjects

C H Tamburro

Publications and source records attributed to C H Tamburro.

At least 19 recordsLinked to original sources
PubMed1997

Activity and tolerance of a continuous subcutaneous infusion of interferon-alpha2b in patients with chronic hepatitis C.

We administered interferon-alpha2b (IFN-alpha2b) by continuous subcutaneous infusion (60,000 IU/h, or 10 million IU/week) over 3 months to 7 patients with chronic hepatitis C. All had previously responded, as assessed by normalization of transaminases to the same dose of IFN administered by intermittent injection over 6 months, but had relapsed after cessation of therapy. The continuous infusion was tolerated well at the site of infusion, and the systemic side effects were similar in type but were lesser in intensity than with intermittent dosage. Four of 7 subjects had normalization of transaminase at the end of week 12 of therapy. Serum HCV RNA and HCV by PCR decreased with treatment, and there was a prompt and sustained increase in serum beta2-microglobulin and of 2', 5' OAS activity. The level of the latter appeared to correlate with response of the transaminase. Serum IFN concentrations were low but detectable throughout therapy. After stopping IFN administration, the transaminases in responders increased again to pretreatment levels.

Administration, Cutaneous↗
PubMed1996

Response to higher doses of interferon alfa-2b in patients with chronic hepatitis C: a randomized multicenter trial. Hepatitis Interventional Therapy Group.

To evaluate response rates to 3, 5, or 10 million units (MU) of interferon alfa-2b, given thrice weekly, and to determine whether higher doses of interferon increase the likelihood or durability of the response, a multicenter, randomized trial was performed at nine academic medical centers in the United States. Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of interferon alfa-2b thrice weekly for 12 weeks. Based on the alanine aminotransferase (ALT) response at treatment-week 12, the patients were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study. Serum ALT concentrations and liver histology were measured. The overall complete response rates to 3, 5, or 10 MU were not different at treatment-week 12 (31% vs. 42% vs. 40%, not significant). The majority of week-12 responders continued to respond during additional treatment. When the treatment was discontinued, 15.4% to 19.0% of patients maintained their response. Of the nonresponders to 3 MU at week 12, who were continued on 3 MU for an additional 12 weeks, none responded. However, response to additional therapy occurred in 12% of week-12 nonresponders, whose dose was escalated from 3 or 5 MU to 10 MU. The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment liver biopsy and viral genotype. We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug. Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose; however, a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses. Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis C.

Adolescent↗
PubMed1993

A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study.

A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo-treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen.

Alcohol Drinking↗
PubMed1993

Cell-mediated hepatic injury in alcoholic liver disease. Veterans Affairs Cooperative Study Group 275.

BACKGROUND: The mechanism responsible for the initiation and perpetuation of alcoholic liver disease (ALD) remains poorly understood. This investigation attempted to elucidate the role of cell-mediated immune phenomena in the pathogenesis of ethanol-induced liver injury. METHODS: Frozen liver biopsy specimens from 144 patients with moderate to severe ALD were examined by the avidin-biotin immunoperoxidase technique for the expression of antigenic markers of T and B lymphocytes, natural killer cells, and class I and II MHC molecules in the tissue. RESULTS: Expression of CD3 by lymphocytes correlated significantly with regenerating nodules, intralobular inflammation, central sclerosis, and abnormalities of Kupffer cells. B cells were rarely present, and natural killer cells were absent. CD3+ lymphocytes expressed either CD4 or CD8 surface molecules. Enhanced class I MHC expression correlated significantly with portal inflammation, limiting plate erosion, vascular abnormalities, and hemosiderosis. Expression of class II MHC molecules correlated significantly with necrosis, bile stasis, and Mallory bodies. CONCLUSIONS: The distribution and persistence of CD4+ and CD8+ cells in actively advancing ALD, the enhanced MHC expression on hepatocytes, and their relationship to alcoholic hyalin and necrosis lend support to the hypothesis that a cytotoxic T lymphocyte-hepatocyte interaction plays a role, perhaps via lymphokine production, in the genesis or perpetuation of ALD.

CD3 Complex↗
PubMed1993

Polychlorinated biphenyl exposure and human disease.

Polychlorinated biphenyls (PCBs) continue to be of great environmental and occupational health interest. This review summarizes the major clinical findings reported in individuals incurring the greatest PCB exposure--those persons working in the manufacture or repair of electrical capacitors or transformers. The potential target organs addressed in the studies reviewed include the liver, lungs, skin, cardiovascular system, nervous system, certain endocrine systems, the blood/immune system, and the gastrointestinal and urinary tracts. After careful analysis, the weight of evidence suggests the only adverse health effects attributable to high, occupational PCB exposures are dermal. This review confirms and extends the observations of others, ie, that the collective occupational experience with PCB fluids provides no evidence for adverse PCB effects on any other organ systems.

Cohort Studies↗
PubMed1992

Chronic liver injury in phenoxy herbicide-exposed Vietnam veterans.

Reports of hepatotoxic injury in Vietnam veterans exposed to phenoxy herbicides (mainly, 2,4-D and 2,4,5-T) initiated a retrospective cohort study of veterans self-reporting exposure to Agent Orange (AO) while serving in Vietnam from 1962 to 1971. Historical, medical, and laboratory information was obtained in a subcohort of 100 randomly selected veterans from a pool of 350 registrants. An occupational work exposure ranking system was designed to estimate individual exposure to phenoxy herbicide and its contaminant, dioxin (TCDD). Job classifications were determined by military job codes. Military application of the herbicides used in Vietnam were derived from the National Research Council Report based on the Herbs tapes. Health examination included tests of body systems affected by TCDD and similar agents, e.g., hemopoietic system, cholesterol/lipid metabolism, hepatic function, and skin lesions. Skin rash was utilized as a marker disease, since no case of true chloracne was found among the cohort. The cohort was divided into those with (R) and without (NR) a reported rash during or after the Vietnam tour. The R group had higher frequency (31%) of abnormal liver studies of all types than the NR group (18%). Of the 14 Vietnam veterans with persistent serum transaminase elevations, 86% reported a rash. Abnormal liver functions correlated with herbicide exposure index in both groups, but was more prominent in the R group. Study of the exposure index components showed that the liver abnormalities were related to the months of exposure and not to job classification or exposure rank. Viral hepatitis and alcoholism among both groups accounted for the association between liver abnormalities and cumulative exposure to AO. These data provide strong supportive evidence that chronic liver abnormalities among Vietnam veterans applying to the AO Registry are mainly due to viral or alcoholic causality and not to herbicides and their TCDD contaminant.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1992

Alcohol and cancer.

Explore the source record for details and available documents.

Alcohol Drinking↗
PubMed1986

Tests for hepatotoxicity: usefulness in screening workers.

General tests of hepatotoxicity must be selected to identify all seven different types of exposure effect--cytotoxicity, cholestasis, fibrosis, vascular injury, metabolic dysfunction, impairment of the reticuloendothelial system, and carcinogenesis--whereas specific tests need only identify one or more. The liver's multifunctional character requires using sets of tests that include blood, urine, breath, isotopic, sonic, radiological, histological, and genetic tests. In this paper, traditional studies (eg, enzymes, proteins) are reviewed for medical screening and biological monitoring for specificity, sensitivity, selectivity, and cost-effectiveness. Status of newer tests (eg, clearance, radioisotopic assay, scans) will be reviewed, and developing tests (eg, molecular, genetic) for occupational use will be introduced. Practical application of these tests will be reviewed regarding clinical evaluations, interpretation, and triage. Finally, the medical-socioeconomic implications at initial medical screening and during subsequent monitoring will be illustrated.

Breath Tests↗
PubMed1985

Use of serum bile acids in the identification of vinyl chloride hepatotoxicity.

Most previous studies proposing serum bile acids as indicators of hepatic function have been performed in hospitalized patients in whom overt symptomatic liver disease was present. The ability of fasting levels of serum bile acids to identify mild, clinically inapparent chemical liver injury in an occupational setting was compared with that of indocyanine green clearance and routine biochemical liver tests in 67 asymptomatic chemical workers in whom liver biopsies had been performed for medical indications. Histologically, 15 were found to have chemical liver injury, 27 had nonchemical liver disease, and 25 were normal. Two serum bile acids, cholylglycine and conjugates of cholic acid, were determined by radioimmunoassay, using 466 "normal" males from the same worker cohort as a reference range. The geometric mean concentrations of cholylglycine in patients with chemical liver injury, patients with nonchemical liver disease, and normal subjects were 47.9, 19.1, and 20.0 micrograms/dl, respectively (p = 0.036 by analysis of variance). Conjugates of cholic acid showed similar differences (p = 0.027), as did indocyanine green clearance with mean half-life of 4.2, 3.2, and 3.3 minutes in the three biopsy subgroups, respectively (p = 0.043). Such differences were not observed for biochemical liver tests. The fasting level of serum bile acids provided high specificity but lower sensitivity in the detection of all types of liver disease. However, serum bile acids and indocyanine green clearance provided a higher specificity and sensitivity for chemical liver injury than for nonchemical liver disease. An index of average exposure to vinyl chloride was significantly greater in the subgroup with chemical liver injury than in the other two groups, further supporting the association of chemical type injury with impaired anion uptake. These data identify the fasting level of serum bile acids as a clinically usable indicator of early chemical injury in chemically exposed asymptomatic worker populations with liver dysfunction. Further investigation is needed in other occupational hepatotoxic environments to determine if this association is limited to vinyl monomer type injury.

Adult↗
PubMed1983

The identification of hepatic injury and hepatic angiosarcoma among vinyl chloride workers--the epidemiological approach.

The Occupational Health Surveillance System described herein has provided the experience and data to clearly demonstrate that prospective, epidemiological application to the problem of health surveillance in the occupational environment is feasible and economical. It has demonstrated that the approach is implementable in industries of any size or type, can be operated without interference with industrial productivity, is extremely cost-effective at the epidemiological surveillance program level, provides the best means to identify and characterize agents which may produce occupationally-related disease in the human population, provides an ongoing means of assessing the effectiveness of intervention or preventive measures and be provided through the expertise of health sciences centers with economic benefit to the universities and industry and a significant social benefit to the community.

Health Promotion↗
PubMed1981

Chemotherapy of vinyl chloride-associated hepatic angiosarcoma.

The use of systemic chemotherapy was studied in a group of four patients who had hepatic angiosarcoma in association with exposure to vinyl chloride. All of the patients received Adriamycin 60 mg/m2 i.v. q3-4 weeks and in three patients this was combined with Cytoxan 600 mg/m2 and methotrexate 20 mg/m2. Three patients had an objective response lasting four, nine, and ten months. One patient had stable disease for ten months. Responding patients maintained an excellent performance status during therapy. Following evidence of progressive disease, patients died in three, four, and six months. Survival from the time of diagnosis was 11, 13, 15 and 53+ months. Sufficient data are not available from these patients to recommend a specific drug or combination for use in hepatic angiosarcoma, but our data indicate that chemotherapy can improve quality and duration of survival.

Adult↗
PubMed1981

Occupational carcinogenesis: the Louisville experience with vinyl chloride-associated hepatic angiosarcoma.

Hepatic angiosarcoma in man was first associated with exposure to vinyl chloride in Louisville, Kentucky, where it was identified in 10 persons from a single vinyl chloride polymerization plant; clinical manifestations are summarized herein. Following prolonged exposure to vinyl chloride, the onset of this disease is insidious and the clinical picture is that of nonspecific hepatic injury with mildly abnormal biochemical liver test results. Carcinoembryonic antigen and alpha fetoprotein are undetectable. Radionuclide and angiographic studies of liver show characteristic but nondiagnostic abnormalities. A definite diagnosis is usually made only by open liver biopsy. Treatment is unsatisfactory but chemotherapy seems to prolong survival. Average survival from diagnosis is about 12 months. Overt liver failure usually occurs only as a preterminal event and was the major cause of death in all of our patients. Preventive measures are now in effect in the plant. This experience illustrates the importance of the clinician in occupationally-related cancer.

Hemangiosarcoma↗
PubMed1981

Effectiveness of federally required medical laboratory screening in the detection of chemical liver injury.

The increasing concern of industrialized societies over the potential health hazard of synthetic chemicals in the occupational environment has led to government requirements for medical laboratory screening of workers. The specific tests for such screening programs are most often selected on the basis of medical experience which utilized them in symptomatic or hospitalized populations. Required screening tests for hepatic injury including cancer in vinyl chloride workers has been systematically and prospectively studied in an industrial population working with synthetic rubber and plastics. Approximately 1300 employees were studied over a five-year period. A cohort of 969 male employees, for the purposes of analysis, were divided into a "standard" and "nonstandard" population based upon the absence or presence of significant medical disease (including liver disease). A subcohort of 120 individuals was further identified based on availabiliity of liver biopsy. Evaluation of federally required studies included alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP), alanine aminotranserase (ALT, SGPT), aspartic aminotransferase (AST, SGOT) and bilirubin (BR). Also studied were indocyanine green clearance (ICG) and radioisotopic liver spleen scans (L-S scans). The GGTP provided the highest positive predicted value as a screening test for identifying "nonstandard" individuals (individuals with all types of medical disease) followed by ICG, AST, ALT, L-S scan, AP, and BR. In the identification of asymptomatic liver disease the GGTP had the least specificity due to a high false positive rate, while the AP provided the highest specificity. The ICG clearance however, provided the best combination of positive predictive value and sum of specificity and sensitivity. The AP provided additional increase in specificity as a follow-up study. There was no evidence that any of the other federally required tests added any additional benefit and did add significant increase in the false positive rate. These studies support the need for evaluating screening tests as to their sensitivity, specificity and positive predictive value, in asymptomatic individuals, before they are made established requirements.

Adolescent↗