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Biomedical subjects

W C Maddrey

Publications and source records attributed to W C Maddrey.

At least 37 records · Page 2Linked to original sources
PubMed1995

A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis.

One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure.

Hepatic injury in alcoholics due to intake of acetaminophen (APAP or acetylparaaminophenol) with therapeutic intent has been reported, but the extent of the phenomenon is not clear, pertinent details of the association remain insufficiently clarified, and the importance of the phenomenon is not widely appreciated. The present report describes 67 patients who developed hepatic injury after ingestion of APAP with therapeutic intent. All were regular users of alcohol. Sixty-four percent of the patients were considered to be "alcoholic" or reported intakes greater than 80 g/d, 35% took 60 g/d or less, and the remainder were vague in their reporting. Doses of APAP were in the "nontoxic" range ( < 6 g/d) in 60% of the group, within the recommended range ( < 4 g/d) in 40%, and at 4.1 to 6 g/d in 20%. Characteristic feature was the towering level reached by aspartate transaminase (AST) with figures ranging from 3,000 to 48,000 IU in more than 90% of cases. Almost 20% of the patients died. The data on these patients were similar to 94 cases of injury from APAP taken with therapeutic intent reported in the literature. This study provides further evidence of hepatic injury in regular uses of alcohol, especially chronic alcoholics, who take APAP with therapeutic intent. Susceptibility is presumably caused by induction of cytochrome P-4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well. The syndrome of liver injury is distinctive, marked by uniquely elevated levels of AST, and poses a significant threat.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1994

Chronic viral hepatitis: diagnosis and management.

Most patients with chronic hepatitis are infected with the B or C virus. Diagnosis has been simplified with the advent of increasingly accurate assays. Treatment, however, is still less than ideal; only about 50% of patients respond to alpha-interferon, and the rate of relapse is particularly high in hepatitis C. Refinements in patient selection criteria and treatment modalities are on the horizon.

Autoimmune Diseases↗
PubMed1994

Limonene in expired lung air of patients with liver disease.

As part of an effort to examine the relationship between chemosensory disturbance and oral chemistry, we analyzed expired lung air samples from a series of 24 patients with liver disease and 24 healthy controls using gas chromatography-mass spectrometry. Compared to samples from controls, lung air from patients with liver disease contained unusually high levels of limonene, a monoterpene that is a major component of the essential oil of citrus fruits (0.1 vs 7.0 micrograms/20 liters for controls and patients). Only half the patients showed high levels of limonene. Patients with noncholestatic liver disease were significantly more likely to have elevated lung air limonene levels than those with cholestatic liver disease (0.2 vs 13.8 micrograms/20 liters). Responses to food frequency and dietary behavior questionnaires indicated a pattern of diet selection and food preferences that were consistent with a dietary origin for the limonene in these patients.

Air↗
PubMed1994

Relationship between liver biochemical tests and dietary intake in patients with liver disease.

Relationships between liver biochemical test values and reported frequency of consumption of various foods were examined using a principal-component analysis of data from 42 patients with chronic liver disease. The statistical procedure identified relationships among biochemical and dietary variables. One relationship included the variables albumin, bilirubin, and frequency of intake of fruits and vegetables, starch, and meats. A relationship was also found between serum alkaline phosphatase (ALP) levels and fat/oil intake. Data from patients with primary biliary cirrhosis (PBC) and noncholestatic liver disease were compared using a correlational analysis. In patients with PBC, serum ALP levels were positively correlated with frequency of intake of fat/oil (r = 0.59, p < 0.01) and meats (r = 0.46, p < 0.05), whereas serum bilirubin (Bili) and aspartate aminotransferase (AST) levels were significantly correlated with frequency of intake of dairy products (rs = 0.48 and 0.45, ps < 0.05 for Bili and AST, respectively), meats (rs = 0.59 and 0.65, ps < 0.01), and fat/oil (r = 0.54, p < 0.02 and r = 0.48, p < 0.05). In patients with noncholestatic liver disease, Bili levels were correlated with frequency of intake of fat/oil (r = 0.58, p < 0.01), and fruits and vegetables (r = 0.68, p < 0.01). These results suggest that the degree of elevation of some liver biochemical tests in patients with liver disease may be affected by dietary intake.

Alkaline Phosphatase↗
PubMed1994

Viral hepatitis: a 1994 interim report.

A variety of viruses cause many of the disorders that are recognized as acute and chronic liver diseases. Remarkable scientific advances achieved during the past two decades have lead to readily available accurate diagnostic tests for hepatitis viruses designated A through E. Effective vaccines have been developed to prevent hepatitis B and, more recently, hepatitis A. Heightened understanding of the pathogenesis of chronic hepatitis caused by hepatitis B and C suggests several promising therapeutic approaches. Interferon is the sole drug yet proven to be effective in the treatment of some patients with chronic hepatitis B and C. Newer antiviral agents that will be used alone or in combination are under development.

Acute Disease↗
PubMed1993

Chemosensory function, food preferences and appetite in human liver disease.

We evaluated chemosensory function, food preferences, and appetite in 88 patients with liver disease including those with hepatitis, cirrhosis, primary biliary cirrhosis, and sclerosing cholangitis. Reported chemosensory disturbances were common in the patients with liver disease: over 40% reported recent taste changes, and 27% reported recent changes in smell, compared to only 6% of healthy, age- and gender-matched controls with no history of marked chemosensory malfunction. Compared to controls, a greater proportion of liver patients reported food cravings (47 vs. 17%) and food aversions (33 vs. 16%). Foods with a predominantly bitter taste were specifically less preferred in patients with liver disease compared to healthy controls. Patients were also more likely to report poor to fair appetite than controls (37 vs. 5%). Groups of patients with different types of liver pathology showed varying patterns of food preferences, suggesting that dietary recommendations to liver patients might be tailored to the altered preferences associated with a particular type of hepatic dysfunction.

Adult↗
PubMed1993

Serum amino acids following human orthotopic liver transplantation.

Our findings indicate that serum amino acid changes after OLT are complex and influenced by multiple factors including sepsis and use of parenteral hyperalimentation with exogenous amino acids. Additional factors which may influence the rate of normalization of amino acids after OLT include the presence of malnutrition (frequently observed before OLT) and the extent of pretransplant portal-systemic shunting. Our results demonstrate that the presence of septic complications and the use of CPN are important determinants of the postoperative levels of several amino acids, including the BCAA/AAA ratio. Our logistic regression model using the BCAA/AAA ratio predicted the occurrence of sepsis after OLT 77% of the time. Prospective assessment and validation of this model is under way.

Amino Acids↗
PubMed1993

Chronic hepatitis.

Evaluation, management and treatment of patients with chronic inflammation of the liver is an important task for the clinician. Almost every ongoing liver injury has an element of inflammation. In those disorders grouped as chronic hepatitis, the brunt of the liver injury is borne by the hepatocyte and continues until either the stimulus is removed or the inflammatory response is blunted. Chronic viral infection is by far the most important cause of chronic hepatitis. Hepatitis B and hepatitis C infections are both frequent causes and may result in cirrhosis. Interferon therapy has proven useful in the treatment of some patients with bone disorders. Idiopathic autoimmune chronic hepatitis is an important contributor to the diagnosis of chronic hepatitis and usually responds to corticosteroid therapy. Because of the availability of effective therapy, Wilson's disease, which is a quite rare but important cause of chronic hepatitis, should be considered. Even more rarely, an ongoing reaction to the continued administration of a therapeutic drug leads to chronic hepatitis. Advances in diagnosis, increased understanding of the courses followed by each of the major disorders, and the availability of effective treatment for many patients has heightened interest in the syndrome of chronic hepatitis.

Autoimmune Diseases↗
PubMed1992

Antitumor effect of deferoxamine on human hepatocellular carcinoma growing in athymic nude mice.

BACKGROUND: Iron is essential for the growth of all living cells. One of the important intracellular roles for iron is in the activation of ribonucleotide reductase, the enzyme that catalyzes the first step in DNA synthesis. Thus, the intracellular iron level may serve as a regulator of cell growth. The authors tested the hypothesis that lowering body iron concentration inhibits the growth of human-derived hepatocellular carcinoma (HCC) cells by depleting these cells of iron. Deferoxamine (DFO), an iron-chelating agent, was used to lower intracellular iron level. METHODS: HCC cells, PLC/PRF/5 (7 x 10(6) cells/mouse), were transplanted subcutaneously into athymic nude mice. When tumors reached 200-300 microliters in size, mice with comparable tumor sizes were paired; one was treated with DFO (300 mg/kg body weight/day, 5 days/week) intraperitoneally while the other received no treatment. RESULTS: Eight pairs of mice with HCC were observed for 5-18 weeks. Mean tumor growth rates (TGR) (mean +/- standard error) for the untreated and treated mice were 30.5 +/- 3.7 microliters/week and 11.9 +/- 1.5 microliters/week. The difference was significant (P < 0.02). In the second set of studies, DFO treatment was begun when the tumor size was smaller (100-200 microliters). Four pairs of mice were observed for 4-15 weeks; mean TGR for the four untreated mice was 18.1 +/- 5.1 microliters/week. In two mice treated with DFO, tumors regressed completely by the seventh week after initiation of treatment. The two remaining mice on DFO therapy had much slower growing tumors, with a mean TGR of 1.8 +/- 0.5 microliters/week. CONCLUSIONS: Thus, our results suggest that (1) reduction of intracellular iron concentration by DFO may be useful as antitumor therapy in HCC and (2) the favorable effects of DFO treatment are best seen when treatment is begun when the tumor is small.

Animals↗
PubMed1992

Perspective: preventive isoniazid therapy and the liver.

The preventive use of isoniazid (INH) has been controversial since 1975, but official agencies continue to advocate the procedure. Cost-effectiveness and risk benefit studies of preventive INH use have come to conflicting conclusions. A review of eight such studies indicates an increasing tendency to minimize INH hepatotoxicity and to disregard the declining tuberculosis morbidity and mortality in countries in which INH prophylaxis has not been widely adopted. We report three cases of fatal INH-associated hepatitis that illustrate that this complication of preventive INH use remains a serious problem. Current recommendations that encourage wide use of preventive INH therapy are unwise because they inflict a risk of fatal hepatitis on compliant adults and older children who have little danger of tuberculosis while being difficult to deliver to the alcohol- and drug-addicted persons whose risk is high. Health departments and physicians should severely restrict preventive INH therapy.

Adolescent↗
PubMed1991

The serum concentrations of the aminoterminal propeptide of procollagen type III and the hepatic content of mRNA for the alpha 1 chain of procollagen type III in carbon tetrachloride-induced rat liver fibrogenesis.

Serum concentrations of the aminoterminal propeptide of procollagen type III (PIIIP) are elevated in fibrogenic diseases of the liver, but the mechanism of elevation is not fully understood. To investigate the mechanism, we compared serum concentrations of PIIIP with total liver content of mRNA for the pro alpha 1 (III) chain, in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Adult male rats received CCl4 in mineral oil twice weekly for 8 weeks and were compared with age-matched controls. Serum concentrations of PIIIP were measured by a specific radioimmunoassay; molecular sizes of PIIIP in serum were also determined. Pro alpha 1 (III) mRNA content in the liver was quantitated by RNA slot-blot hybridization and chemical measurement of total hepatic RNA content. Total collagen content of the liver was estimated by hydroxyproline measurement. All CCl4-treated animals had septal fibrosis after 4 weeks, and evidence of cirrhosis (regenerative nodules, ascites) was seen after 7 weeks of treatment. Serum concentrations of PIIIP and pro alpha 1 (III) mRNA content in the liver were correlated well until cirrhosis has established. They increased simultaneously after 3 weeks of treatment, 1 week before any elevation of hepatic hydroxyproline could be detected. After cirrhosis has established, pro alpha 1 (III) mRNA content in the liver decreased markedly, but serum PIIIP levels continued to be elevated. Hepatic hydroxyproline plateaued after 5 weeks. The molecular sizes of serum PIIIP indicate the release of intact native procollagen peptide during the development of cirrhosis. In conclusion, at least in CCl4-induced liver fibrosis in the rats, serum PIIIP levels can be used as a fibrogenic marker for the period progressing to cirrhosis. But the use of the serum PIIIP levels in cirrhosis seems to be limited by factors other than liver fibrogenesis.

Actins↗