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Biomedical subjects

T M Worner

Publications and source records attributed to T M Worner.

At least 37 records · Page 2Linked to original sources

Echocardiographic abnormalities in chronic asymptomatic alcoholics.

Alcohol abuse is a frequent contributor to elevated blood pressure, but the literature is ambiguous about the role of hypertension in producing left ventricular dysfunction. Fifty asymptomatic male alcoholics admitted for detoxification were studied using echocardiograms and systolic time intervals. Alcoholics were separated into Group I (28 with hypertension) and Group II (22 without hypertension). Forty-four patients had analyzable echocardiograms and were compared to 29 nonalcoholics. Group III consisted of 14 nonalcoholics with hypertension. Group IV consisted of 15 normotensive nonalcoholics (controls). The ejection fraction and shortening fraction were reduced in Group I (p less than 0.05). Hypertensive alcoholics had increased left ventricular mass indices but less than hypertensive nonalcoholics. Left ventricular wall stress was compared to mass as an index of ventricular compensation. The wall stress to mass index for hypertensive alcoholics was 1.65 as compared to 1.43 for the controls. Alcoholics without hypertension had a wall stress to mass ratio of 1.54. Hypertensive patients had a reduced wall stress to mass ratio of 1.38 when compared to controls. These data suggest an inappropriate compensatory response to afterload. Alcohol and hypertension combined may be more harmful to left ventricular function than either disease alone.

Adult↗

Urine toxicology as a predictor of continuation in outpatient alcoholism treatment.

Urine for toxicology was obtained from 93% of 62 alcoholics (60 males, 2 females) applying for alcoholism treatment. Fourteen urines were positive, with cocaine (35%) and minor tranquilizers (35%) being most common. History of drug use did not correlate with toxicology results nor was there an association with simultaneously obtained alcohol levels. Treatment outcome was analyzed retrospectively at 4 months. Subjects were more likely to remain in outpatient therapy if the screening urine toxicology was negative.

Adult↗

Vitamin A treatment of sexual dysfunction in male alcoholics.

Thirty abstinent male alcoholics with sexual dysfunction were randomized to treatment with 3 mg RE (10,000 IU) vitamin A or placebo daily for 4 mo. Age, drinking history, period of abstinence before enrollment, and base-line laboratory indices were comparable in both groups at entry. Of the 15 subjects given placebo, 13 had a partial or full recovery of sexual functioning. By contrast, of those given vitamin A, 10 had a partial response. There were no complete responders. Six subjects (1 placebo, 5 vitamin A) who developed liver abnormalities during treatment underwent liver biopsies; five had fibrosis or cirrhosis. A significant decrease in luteinizing hormone was noted in the group given vitamin A compared with the placebo-treated group. Thus vitamin A therapy did not improve sexual functioning in male alcoholics and may have been associated with toxicity.

Alcoholism↗

Increase in tryptophan oxygenase activity in alcoholic patients.

This study was conducted in order to assess whether chronic excessive alcohol consumption affects the activity of the liver enzyme tryptophan oxygenase which is rate limiting along the most important pathway of tryptophan catabolism. Five alcoholics were studied twice, once shortly after admission to an inpatient unit and the second time 1 month later. On each study day patients were given a tryptophan load of 50 mg/kg. Kynurenine in the urines (which reflects tryptophan oxygenase activity) was measured for a period of 6 hr following the load and showed a significantly enhanced activity of the enzyme shortly after cessation of drinking. This increased activity could explain the lowered tryptophan levels we have previously reported in alcoholics. The increase in enzyme activity may have been mediated by a rise in glucocorticoid hormones. In all instances, plasma cortisol measured hourly for 6 hr after the start of the experiment, was higher shortly after cessation of drinking than 1 month later.

Adult↗

Carbohydrate-deficient transferrin, a marker for chronic alcohol consumption in different ethnic populations.

Serum levels of carbohydrate-deficient transferrin (CDT) were determined in a racially mixed population of 107 alcoholics, 18 healthy, nonalcoholic control subjects, 62 abstinent alcoholics, and in 64 Caucasian patients with various nonalcoholic liver diseases. The upper limit of normal CDT levels was 80 mg/liter (2 SD above the mean). CDT values exceeding this level were found in more than 80% of Black, Puerto Rican, and Caucasian alcoholics who had consumed greater than or equal to 50 g of alcohol/day for 1 month or longer prior to testing. Puerto Rican alcoholics had higher CDT values than the Black and Caucasian ethnic groups; however, these differences were significant only when compared to the Black population. Of 64 patients with nonalcoholic liver diseases, one individual with chronic active hepatitis (CAH) with an alcohol consumption of 20 g/day, and 10 of 26 subjects with primary biliary cirrhoses (PBC), who claimed to consume either no or only occasional moderate amounts of alcohol, had CDT levels ranging from 81 to 144 mg/liter. Seven of these individuals were in advanced stages of PBC. Total transferrin levels were variable and not significantly different in all subject groups studied. CDT/total transferrin ratios were increased in most patients with abnormal amounts of CDT, and there was a significant correlation between these ratios and CDT levels in all study groups. Serum enzyme parameters as well as red blood cell mean corpuscular volumes did not correlate with CDT values.(ABSTRACT TRUNCATED AT 250 WORDS)

Black or African American↗

Changes in carbohydrate-deficient transferrin levels after alcohol withdrawal.

Sequential serum levels of carbohydrate-deficient transferrin (CDT) were determined in 72 alcoholics at various intervals during detoxification. Before treatment, 57 patients (79%) had increased CDT values (Group A), whereas in 15 individuals (21%) (Group B), CDT levels were within the normal range. In 51 Group A patients, CDT decreased progressively after cessation of alcohol intake (half-life, 16 +/- 5 days), but fluctuated and remained abnormal in the remaining six. Nine Group B patients maintained normal CDT values throughout the follow-up period, but slightly or moderately increased levels were recorded on one occasion in the other six Group B subjects. Patients whose CDT levels had reached normal values after treatment, showed a recurrent increase in CDT after a relapse. gamma-Glutamyl transferase activities, which were elevated in 56% of Group A and in 80% of Group B alcoholics, showed a decrease after cessation of alcohol consumption in most patients with initially elevated values (Group A, 30 of 32; Group B, 10 of 12). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as mean corpuscular volumes (MCV) were normal in the majority of patients. CDT/total transferrin ratios correlated positively with CDT levels. CDT proved to be the most sensitive marker for chronic alcoholism (79%), whereas GGT activity levels were more useful only in patients with normal CDT levels before alcohol withdrawal. In the assessment of treatment outcome, the combination of CDT and GGT as markers yielded a sensitivity of 95%.

Adult↗

Effects of fasting and chronic alcohol consumption on the first-pass metabolism of ethanol.

The present investigation was undertaken to evaluate what fraction of alcohol ingested in amounts during usual "social drinking" does not enter the systemic circulation. To that effect, on consecutive days, either peroral or intravenous ethanol was administered in both fed and fasted states to 7 nonalcoholic and 18 alcoholic subjects. In nonalcoholics consuming 0.15 g/kg body wt ethanol, the magnitude of first-pass metabolism of ethanol was 3.94 +/- 0.15 mmol/L X h, calculated as the difference of the areas under the curve obtained after oral and intravenous alcohol administration. The first-pass metabolism accounted for 73% of the latter. When the administered dose was increased to 0.3 g/kg body wt ethanol, the corresponding values were 6.46 +/- 0.50 mmol/L X h and 44%. Fasting decreased this effect. When alcoholics consumed 0.15 g/kg body wt ethanol, the corresponding values were 0.92 +/- 0.65 mmol/L X h and 23%. When these alcoholics were fasted, the first-pass metabolism again decreased and it was significantly lower than in the nonalcoholics tested under the same conditions. We conclude that in humans a significant fraction of ingested alcohol undergoes first-pass metabolism but that this effect is reduced in alcoholics and by fasting. The magnitude of this process determines the bioavailability of alcohol and thus modulates its potential toxicity.

Administration, Oral↗

Effect of abstinence on the blood acetaldehyde response to a test dose of alcohol in alcoholics.

Following an acute dose of alcohol (0.15 g/kg intravenously), blood levels of acetaldehyde were significantly higher in nonabstinent alcoholics than in controls. After 2 weeks of abstinence, this blood acetaldehyde response significantly decreased in alcoholics and the acetaldehyde returned towards levels comparable to those observed in nonalcoholics. These results suggest that elevated blood acetaldehyde levels in the alcoholics are secondary to the chronic alcohol consumption rather than reflecting a primary preexisting defect.

Acetaldehyde↗

Serum procollagen type III N-terminal peptides and laminin P1 peptide in alcoholic liver disease.

The appearance of perivenular fibrosis on liver biopsy reflects the beginning of the fibrotic process that ultimately results in liver cirrhosis. To examine whether the fibrogenic activity can be detected by blood tests, we evaluated whole antibody radioimmunoassay (RIA) of procollagen type III N-terminal peptides (P-III-P), RIA of these peptides using Fab fragments (Fab-P-III-P), and RIA of the laminin P1 peptide in alcoholics within 1 week of alcohol abstinence. The Fab-P-III-P levels in subjects with perivenular fibrosis were significantly higher than those in patients with simple fatty liver. Values in 63% of subjects with perivenular fibrosis exceeded the upper limit of the fatty liver group. Patients with simple fatty liver had significantly lower values than nonalcoholic controls. Serum levels of P-III-P and laminin were elevated in patients with alcoholic hepatitis and correlated well with the degree of inflammation. With abstinence, Fab-P-III-P levels increased in all alcoholics. P-III-P values increased in patients with normal P-III-P values on admission. By contrast, the values of laminin decreased during abstinence. Therefore, to interpret serum levels of Fab-P-III-P, P-III-P, and laminin, the duration of abstinence must be taken into consideration. P-III-P, Fab-P-III-P and laminin measurements in the serum within 1 week of abstinence can contribute to the detection of alcoholic liver disease and the determination of its stage.

Adult↗

Liver fibrosis in alcoholics. Detection by Fab radioimmunoassay of serum procollagen III peptides.

Radioimmunoassays were used to measure serum levels of laminin and of procollagen III peptides, both with the intact antibody and with the Fab fragments, within one week of alcohol withdrawal in 83 alcoholics admitted for detoxification and/or treatment of concomitant medical problems. All patients underwent a diagnostic liver biopsy, which revealed simple fatty liver in 22, perivenular fibrosis in 20, septal fibrosis in 21, and cirrhosis in 20. Although all three serum measurements correlated significantly with the degree of fibrosis, only the Fab radioimmunoassay of procollagen III peptides discriminated between simple fatty liver and perivenular fibrosis in a significant number of subjects.

Adult↗

Pharmacokinetics of mezlocillin in patients with hepatobiliary dysfunction.

The pharmacokinetics of mezlocillin were investigated in 26 patients with alcoholic liver disease. Serum concentrations of mezlocillin were measured following intravenous administration of 3 g doses over 30 min. The mean peak serum concentration (+/- standard deviation) of mezlocillin at the end of infusion was 138.8 +/- 55.7 mg/l and the mean terminal half-life (T 1/2 beta) was 2.10 +/- 0.9 h. The 24 h urinary recovery of mezlocillin was 35.4 +/- 12.4% of the administered dose. Serum clearance was found to be inversely correlated with alkaline phosphatase and with total bilirubin. The T 1/2 beta was related to the following clinical measurements: age, SGOT and prothrombin time. This relationship suggests it may be prudent to adjust the dosage and the dosage interval of mezlocillin in patients with hepatobiliary dysfunction.

Adult↗

Esophageal function in chronic alcoholics.

We determined whether there are abnormalities in esophageal motility or acid clearance in chronic alcoholics since alterations in these parameters have been implicated in the pathogenesis of esophagitis after chronic ingestion of ethanol. In addition to esophageal manometry, we also performed acid-clearance studies and examined salivary output, acid-neutralizing capacity, and bicarbonate concentration. We found an increased lower esophageal sphincter pressure which reverted to normal after withdrawal from ethanol. Except for a significantly larger number of tertiary contractions, no other abnormality of esophageal motility was found. Salivary flow, acid-neutralizing capacity, and bicarbonate concentration were not significantly different from that in control subjects. However, in contrast to findings in controls, there was no correlation between salivary bicarbonate concentration and acid-neutralizing capacity in the alcoholics. Our results indicate that chronic ethanol ingestion alters some aspects of esophageal function and salivary composition but that these alterations are unlikely to explain the increased risk of esophagitis in alcoholics.

Adult↗

Perivenular fibrosis as precursor lesion of cirrhosis.

Thirty-four male alcoholics underwent sequential liver biopsies as part of their evaluation. Of 19 subjects with simple fatty livers, only three showed progression of liver disease: one developed perivenular fibrosis after two years; a second showed no progression after three years, but developed perivenular fibrosis after four years; the third subject likewise showed no progression after one year, but developed incomplete cirrhosis after six years. In contrast, of 15 subjects with perivenular fibrosis at the time of the initial biopsy, 13 progressed to more severe stages of liver disease during a one- to four-year follow-up interval. Nine developed fibrosis, one developed incomplete cirrhosis and three developed cirrhosis. Thus, patients with perivenular fibrosis at the fatty liver stage are likely to progress to more severe stages of alcoholic liver disease if they continue to consume alcohol.

Adult↗

Balloon cytology in screening of asymptomatic alcoholics for esophageal cancer, Part I.

We assessed the feasibility of using balloon cytology to screen an asymptomatic group of alcoholics at increased risk for esophageal cancer. The results indicate that this group can be studied with minimal morbidity and that useful material can be obtained in 85% of subjects. Keratinization was present in 68% of specimens and fungus was noted in 9%. Individuals with moderate to large amounts of keratinization consumed significantly more alcohol than those without cytologic evidence of keratin. We speculate that keratinization and fungus may represent markers of enhanced malignant potential in this population.

Adult↗

Association between amino acid alterations and hallucinations in alcoholic patients.

Because available evidence suggests that alterations in the serotonergic as well as dopaminergic tones underlie hallucinatory activity, we decided to investigate whether serotonin and dopamine pathways are modified in alcoholics with a history of hallucinosis. Brain serotonin has been shown to depend on the plasma ratio of its precursor tryptophan over other amino acids competing with it for brain entry. Similarly, brain dopamine depends on the plasma ratio of its precursors phenylalanine and dopamine over their competitors. Amino acid abnormalities are common in alcoholics. For this reason, we assessed whether alcoholics who had experienced hallucinations have alterations in amino acids believed to be associated with neurotransmitter modifications. Patients with a history of hallucinations were found to have a tryptophan ratio significantly lower than that of patients without such a history, and a tyrosine + phenylalanine ratio significantly higher. These data suggest that amino acid abnormalities believed to result in decreased brain serotonin and in increased brain dopamine render certain individuals more vulnerable to hallucinatory experiences.

Adult↗