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Following ingestion, disulfiram is rapidly excreted in the urine and breath, with 90% of the dose gone in 3 days. In some subjects, the enzymes in the liver that oxidized diethyldithiocarbamate to carbon disulfide are very active, making this the principal metabolic pathway. However, if this pathway is not active, there is an increased excretion of DDC into the urine.

Persons with non-A, non-B hepatitis (cases) identified in 5 transfusion studies in the early 1970s have been followed ever since and compared for outcome with matched, transfused, non-hepatitis controls from the same studies. Previously, we reported no difference in all-cause mortality but slightly increased liver-related mortality between these cohorts after 18 years follow-up. We now present mortality and morbidity data after approximately 25 years of follow-up, restricted to the 3 studies with archived original sera. All-cause mortality was 67% among 222 hepatitis C-related cases and 65% among 377 controls (P = NS). Liver-related mortality was 4.1% and 1.3%, respectively (P = .05). Of 129 living persons with previously diagnosed transfusion-associated hepatitis (TAH), 90 (70%) had proven TAH-C, and 39 (30%), non-A-G hepatitis. Follow-up of the 90 TAH-C cases revealed viremia with chronic hepatitis in 38%, viremia without chronic hepatitis in 39%, anti-HCV without viremia in 17%, and no residual HCV markers in 7%. Thirty-five percent of 20 TAH-C patients biopsied for biochemically defined chronic hepatitis displayed cirrhosis, representing 17% of all those originally HCV-infected. Clinically evident liver disease was observed in 86% with cirrhosis but in only 23% with chronic hepatitis alone. Thirty percent of non-A, non-B hepatitis cases were unrelated to hepatitis viruses A,B,C, and G, suggesting another unidentified agent. In conclusion, all-cause mortality approximately 25 years after acute TAH-C is high but is no different between cases and controls. Liver-related mortality attributable to chronic hepatitis C, though low (

Total parenteral nutrition (TPN), now widely used, is successful in preventing and reversing malnutrition in individuals with various diseases and conditions. However, hepatic and biliary complications of TPN are encountered in both adult and pediatric patients. Certain complications, such as sepsis and TPN-associated cholestasis, occur more frequently in very young infants. Continuing problems commonly seen in adults are steatosis and steatonecrosis. Reasons for the development of these complications are multifactorial. Etiologies of hepatic complications, especially the role of deficiency/excess of nutrients in the pathogenesis of hepatobiliary disorders, are summarized. Complications caused by the duration of TPN are discussed with emphasis on prevention and management. Evidence now suggests that prompt enteral feeding, even in minimal amounts, may prevent many of the metabolic complications associated with TPN. TPN should be used only in amounts meeting needs and for a duration essential to survival.

Both acute and chronic ethanol consumption may cause esophageal dysmotility. In order to systematically evaluate the effect of ethanol on esophageal motility, we studied esophageal motility in 13 healthy subjects before and following acute intravenous administration of 0.8 g/kg ethanol and in chronic alcoholics within 6 hr of their last drink (n = 6) and following 24 to 48 hr of abstinence when signs of withdrawal were present (n = 13). Withdrawing alcoholics were also restudied after intravenous administration of 0.8 g/kg ethanol. Ethanol transiently decreased lower esophageal sphincter pressure (LESP) and inhibited LES relaxation in all control subjects; this inhibitory effect of ethanol on LESP in alcoholics was significantly less, indicating the development of tolerance. Ethanol moderately decreased esophageal contraction amplitude (ECA) in 10 of 13 controls and prolonged duration of contractions in all but had no effect on velocity of esophageal contractions. In contrast, ECA was significantly elevated in both groups of alcoholics, but this was significantly more marked in withdrawing alcoholics. Ethanol infusion returned ECA toward normal values in withdrawing alcoholics. Abnormal motility was noted in three intoxicated alcoholics and 10 (77%) withdrawing alcoholics. This included nutcracker esophagus in five and hypertensive LES in two. These data indicated that (1) esophageal motor dysfunction is common in alcoholics; (2) acute ethanol administration decreases LESP and esophageal contraction amplitude, whereas chronic ethanol consumption and withdrawal from ethanol increases ECA. This suggests development of a compensatory mechanism in chronic alcoholics leading to high pressure esophageal contractions during withdrawal.

It is known that primary (swallow-induced) esophageal contractions are abnormal in alcoholics. Data concerning acid-induced esophageal contractions, which appear to be important in cleansing refluxed acid from the esophagus, are lacking. To determine whether acid-induced esophageal contractions are also affected by chronic ethanol exposure, we studied secondary (acid or saline-induced) esophageal motor events in 19 male alcoholics [6 actively drinking (ADA), 13 withdrawing (WA)]. Esophageal motility was performed in response to wet swallows (5 ml of water) and to intraesophageal injection of 5 ml of 0.1 N HCl (0.1 N) or saline. Lower esophageal sphincter pressure (LESP), amplitude (ECA), duration (ECD), and velocity (ECV) of esophageal contractions in response to swallowing and injection of acid or saline were similar in controls and alcoholics. There were more simultaneous and double-peaked contractions in response to acid and saline than to swallows in both alcoholics and controls. However, there was no difference between HCl- and NaCl-induced contractions. ECA in alcoholics was significantly higher than in controls. ECD in alcoholics was significantly more prolonged than in controls. There was no significant different between alcoholics and controls in ECV, LESP, or LES relaxation. These data indicate that similar to primary esophageal contractions, secondary esophageal contractions are also abnormal in both actively drinking and withdrawing alcoholics.

Although most free-living people over age 55 yr use alcohol occasionally, both the fraction of people drinking and the magnitude of individual alcohol consumption decrease with every decade of age. Overall, approximately 5% of drinkers over age 55 yr use alcohol at excessive levels, i.e., sufficient to interfere with health or social functioning. As age increases, the fraction of drinkers with alcohol-caused central nervous system disease and cirrhosis increases, indicating increased sensitivity to alcohol injury. Beyond age 70 yr, new-onset alcoholism is more common than long-standing alcoholism. Malnutrition in the elderly alcoholic person is rare; it usually is caused by multiple factors, including alcohol displacing nutrient-rich diet factors, disease, limited availability of food, or altered metabolism increasing nutrient requirement. The recognition of alcohol and malnutrition problems in the elderly is more difficult than in younger people.

Cases of alcoholic cirrhosis identified at necropsy were studied for the prevalence and type of gallstones, compared with age- and race-matched autopsy controls. Data were examined from 1970-1977 and 1980-1987. In the early sample of 460 cirrhotic patients, 33% had gallstone disease, contrasted with 12% in the controls. In the 1980s, among 299 patients, 46% had gallstone disease, whereas it was present in 13% of the controls. The prevalence of stones was significantly greater in the patients than in the controls for both time periods and, among the patients, was significantly greater in the 1980s than in the 1970s (p less than 0.05). A comparison of cirrhotic patients with and without gallstones indicated a significantly higher incidence of ascites in the patients with gallstones. The gallstones in cirrhotics were more frequently pigmented than in the controls in both time periods. In 100 living patients with advanced cirrhosis studied by sonography during 1987 and 1989, the prevalence of gallstones was 43%, almost the same as the autopsy sample from 1980-1987. In these cirrhotics, ascites, encephalopathy, and varices were more prevalent in the patients with stones than those without. We conclude that pigmented gallstones are increasing in cirrhosis of the liver related to the severity of the liver disease.

Patients (N = 114) consecutively entering a medical service with ulcer, cirrhosis or pancreatitis, currently drinking and not currently active in alcoholism treatment were randomly assigned to motivational intervention (MI) or to a control group. Increased utilization of alcoholism programs and self-reported sobriety at 10 weeks were assessed. MI consisted of three separate discussions of the relationship of the patient's disease to continued drinking and the compassionate offer of treatment. Two persons skilled in treatment also met with each MI subject and discussed treatment possibilities for them, facilitating entrance if desired. Patients in both the MI and control group were treated for their medical condition by a medical team and alcoholism treatment was always recommended. Outcome was evaluated for the period from the 10th to the 16th week after return to the community by interview of patient and household contacts and by the keeping of appointments. There were no differences between the control and MI groups, with at least 38% remaining sober for the 10-week interval; the study size was sufficient to detect reliably a 30% improvement. We conclude that additional motivational intervention to this level was not beneficial to the hospitalized alcoholic with disease. There was a statistically significant increase in sobriety among patients who either undertook alcoholism therapy, accepted all parts of the study or kept clinical appointments.

Twenty-five newly admitted patients were randomly assigned to supplemental treatment with an oral fructose mineral drink or a placebo solution. Nine pints were given in a double-blinded study during the first 3 days. Observations of tremor, chlordiazepoxide requirements, patients perceptions, and observer perceptions of common withdrawal symptoms and signs and the serum levels of Zn, Mg, and potassium were made initially and after the treatment. Although the patients improved over the 4 days of observations by many of the criteria, there were no differences between those receiving active solution and placebo.

Data are presented on the rate of removal of tolbutamide from the blood from studies in heavy drinking, unemployed, male alcoholic subjects. In such subjects tolbutamide was removed faster than it was in normal subjects and faster than in patients with cirrhosis who are not drinking. This rapid removal rate persists for 4 to 9 wk after hospitalization and is reproduced with 400 gm of pure ethanol in 2 or 3 wk but cannot be reproduced with lesser amounts of beverage alcohol taken outside of the experimental study. Similar acceleration of the clearance rates was observed for warfarin and for phenytoin but could not be demonstrated for aminopyrine.

Most studies concerning the nutritional status of alcoholics have focused on the indigent alcoholic but programs now increasingly consider the working patient. The role of socioeconomic status in determining nutritional status of the alcoholic is further clarified in this study. One hundred patients from an alcoholic population were studied, 50 with low socioeconomic status and 50 with middle or higher socioeconomic status. The nutritional status of these two different socioeconomic groups was examined and compared. The middle-income alcoholic had significantly higher values in weight to height index (P less than .02), the triceps skinfold (P less than .01), the midarm muscle circumference (P less than .05), hematocrit (P less than .01), and epilation force (P less than .001) than the lower-income alcoholic group. Hair-pulling tension was compared in both groups as an index of protein malnutrition. There was a highly significant difference in the two groups.

Nine out of twelve obese patients (75%) demonstrated diminished minute ventilation volume (MVV) prior to jejunoileal bypass surgery. Seven out of the nine patients (78%) showed improvement in the MVV as weight reduction ensued following surgery. Other parameters, including arterial blood gases, did not change after weight loss. Weight reduction as a result of jejunoileal bypass surgery brings about an improvement in pulmonary function.

Significant vitamin A, E, or 25-hydroxy D deficiency occurred in 76% of 40 patients studied up to 6 years after jejunoileal bypass surgery for morbid obesity. Vitamin A was significantly lower in those who had lost 30% of their initial weight than in those who had lost less weight; however, there was no correlation of vitamin A, E, or D levels, time elapsed since surgery, or with daily intake of vitamins as subnormal values were found despite multivitamin supplementation and consumption of twice the recommended daily allowance of vitamin A. Functional derangement of retinal adaptation to darkness secondary to vitamin A deficiency was found in four of nine stable, healthy patients studied at least 18 months after surgery. There was no linear relationship between vitamin A levels and dark adapted final thresholds or with serum albumin, prothrombin time, or degree of steatorrhea. Three patients with abnormal adapted final thresholds were treated with vitamin A. Total daily intake of up to 65,000 IU of vitamin A daily for several months resulted in normalization of function in all.

Intestinal transit time of lactulose and malabsorption of lactose were measured by hydrogen excretion in breath following ingestion of 20 g lactulose or 25 g lactose. Patients were 20 recently drinking, adequately nourished, chronic, male alcoholics. Many (65%) complained of diarrhea while drinking actively. Small bowel transit was significantly shorter in alcoholics with diarrhea (62 +/- 8.6 min) than in normal controls (93 +/- 10.4 min, p less than 0.05). It increased significantly after 8-10 days abstinence, to a value of 101.5 +/- 11 min, not significantly different from normal controls. Following lactulose 75% of alcoholics developed diarrhea after 1-2 days compared with only 15% after 8-10 days of abstinence; 40% had diarrhea after lactose in the initial study, whereas no subjects had diarrhea from the same dose after a period of sobriety. These data suggest that drinking alcoholics have an increased sensitivity to osmotic loads, which is associated with diarrhea, shortened transit time, and lactose intolerance. Abnormalities disappeared 8-10 days following cessation of drinking and normal diet.

At 3 and 6 months after discharge no differences in abstinence rates were found between patients who completed a 9-day inpatient alcoholism treatment program and those who participated in a 21-day treatment program.

T HIAMINE-DEFICIENCY SYNDROMES lfl the United States occur almost exclusively in alcoimolic patients (1-2) anti can usually be attributeti to poor dietary intake of the vitamin (3). However, it seemed to the authors that some alcoholics may manifest thiamine deficiency while consunming a�)parently adequate quantities of thiamine-containing foods. The possibility of impairetl thiamine absorption in alcoholism diti not appear to imave been investigated. Time present controlled study was, therefore, undertaken to determine the absorption of radioactive timiamine in a hospitalized group of severely alcoholic patients.

This prospective, double-blind, parallel, two clinic study compared fenoprofen calcium, 200 mg; ibuprofen, 400 mg; and placebo in the treatment of pain due to primary dysmenorrhea. By various criteria, the treatment groups, prior to treatment, were not significantly different (P greater than 0.05) in paired comparisons. However, after oral administration of the study medications, the pain scores were significantly greater (P less than 0.05) for the placebo group than for either other group. The posttreatment pain scores for the fenoprofen and ibuprofen treated groups were not significantly different (P greater than 0.05).

Status of thiamin in the elderly North American population is reviewed. Most Americans eat sufficient thiamin but about 5% of those over 60 yr old show impaired thiamin status. This is more marked in the poor, those confined in institutions, or those with illness. Thiamin responsive heart disease and Wernicke Korsakoff CNS syndromes occur in the elderly but there is no increased prevalence. Minor heart or neurological syndromes related to thiamin deficiency cannot be identified. The Recommended Dietary Allowance of thiamin provides at least 50% excess thiamin for those over 60 yr old--this amount is adequate. There is no known toxicity for thiamin.

Ten normal subjects were given 0.8 mg/kg warfarin orally, and daily blood samples were taken for one week to test for prothrombin activity and warfarin levels, the latter determined specifically by a high-performance liquid chromatography method. Bumetanide at a dose of 1 mg/day was then administered for 14 days. A second dose of warfarin was given on the eighth day of bumetanide administration. The curves showing disappearance of warfarin from the blood were identical before and during bumetanide administration. The prothrombin times were similar in both studies. It is concluded that bumetanide does not influence anticoagulant activity or its duration when warfarin and bumetanide are given simultaneously.

Intestinal transit was assessed in 25 insulin-requiring male diabetics and 15 healthy controls by measuring the breath hydrogen appearance time after the ingestion of both the liquid and the solid meal containing nonabsorbable carbohydrate. Three groups of patients were studied: nine patients without peripheral or autonomic neuropathy or retinopathy; nine patients with peripheral neuropathy; and seven patients with peripheral and autonomic neuropathy. Eight patients complained of gastrointestinal symptoms, including three with watery diarrhea. Intestinal transit of the solid meal was more prolonged than the liquid meal in normal and diabetic subjects. There was no significant difference in intestinal transit between normal controls and any group of diabetics; however, one-third of the diabetics had abnormal intestinal transit of the liquid test meal (four rapid, four delayed); only one patient with diarrhea had rapid intestinal transit. These data suggest that abnormal intestinal transit is common in diabetics. Altered intestinal transit is not a prerequisite of diabetic diarrhea.

Real time ultrasonography was carried out in 49 cirrhotic patients within 10 days of esophagoscopy, and in 20 normal subjects. Among the cirrhotic patients, 42 had varices and 18 of these had hematemesis within 3 months of study. The varices were graded 0 to 4+ endoscopically; the diameter of the portal vein, the splenic vein, the hepatic artery, and the maximal length of the spleen were determined on ultrasound. In addition, portal collateral veins and the sudden amputation of portal vein branches in the liver were identified when present. There was a significant correlation of the diameter of the portal vein and the maximal spleen length with the magnitude of varices on endoscopy; there was no significant relationship between the splenic vein or the hepatic artery diameter. Less than half the patients with varices had sonographically demonstrated collaterals or portal vein branch amputation. A sonoscore was derived allotting one point each for enlarged portal vein (greater than 1.3 cm), enlarged spleen, collaterals or two or more amputated veins. The sonoscore correlated better with the endoscopic grade of varices than any other marker. The sonoscore among the patients with varices who bled was significantly higher (p less than 0.01) than any of the other measures. It is concluded that real time ultrasound can be used to screen for varices and to identify the need for endoscopy.

The presence of adenomatous polyps in the colon identifies patients at increased risk of colon cancer. Removal of such polyps and undertaking repeated future examinations is proven to diminish subsequent development of the disease. Discussing with the patient, at the time of index colonoscopy, the need for repeat examination and including a note in the patient's medical record are not by themselves adequate measures of obtaining follow-up. A reminder letter mailed directly to the patient shortly before the desired appointment is a highly effective method of obtaining follow-up, when accompanied by information on the importance of repeat colonoscopy.

A breath test for carbon disulfide, a major excretion product of disulfiram, is described and evaluated. All breath excretions were standardized by collecting a fixed amount based on CO2 control. Excretion of CS2 falls rapidly (half life 8 to 18 hours), so that 20 to 30 hours following the last dose of disulfiram the test becomes negative. Approximately 300 tests in hospitalized patients taking disulfiram were positive; 40 tests in patients not taking this drug were negative. In an active disulfiram outpatient clinic more than one third of the patients who claimed to have taken disulfiram on the previous day had, as determined by this test, failed to do so. Of subjects judged by the professional staff to be almost certainly compliant 20% were not taking medication. Of the total of 52 patients tested in clinic only 25 were taking disulfiram.

Gastric emptying of technetium labeled liquid and solid meals were studied in a group of long-standing, insulin-requiring male diabetics to evaluate the relationship of gastroparesis to symptoms, diabetic control, and diabetic complications. Control subjects and three groups of diabetics were studied: A) no neuropathy; B) peripheral neuropathy; and C) peripheral and autonomic neuropathy. Nine diabetics had gastrointestinal symptoms. Gastric t1/2 liquid emptying was similar in all groups and in controls, but liquid gastric emptying in the first 15 min was significantly more rapid in the diabetics than controls. Solid emptying was prolonged in group C patients. There was a significant correlation between t1/2 solid emptying and the severity of neuropathy. The eight patients with slow solid emptying had more neuropathy and gastrointestinal symptoms than the remaining 22 patients. The type and duration of diabetes, diabetic control, and frequency of retinopathy are independent of gastroparesis. These data indicate that delayed emptying of solids is common (27%) in patients with clinically detectable neuropathy and may often be asymptomatic. Visceral autonomic neuropathy seems the most important underlying factor in diabetic gastroparesis.

In a prospective double-blind study, 27 patients with alcoholic hepatitis were randomized for 6-methylprednisolone (12 patients) or placebo treatment (15 patients). The mortality was 50% among steroid treated patients and 47% in the control group (P less than .05). The role of liver biopsy feasibility at selection is emphasized since the mortality in this group was 10% as opposed to 71% when the procedure was contraindicated (P less than .01). Complications in the steroid-treated subjects were similar quantitatively and qualitatively to those observed in the control series.