Methadone disposition in patients with chronic liver disease.

Chronic liver disease is common in methadone-maintained patients. We studied the disposition of this drug in 14 patients with biopsy-proved chronic liver disease and five otherwise healthy subjects receiving methadone maintenance treatment. The patients were divided into three groups based on the severity of liver disease, with group I having the most severe disease. The apparent terminal half-life of methadone was longer in group I than in group II and III (moderate and mild chronic liver disease, P less than 0.01) and the contrast group (P less than 0.05). All other kinetic indices determined for group I and all kinetic indices in groups II and III were essentially the same as those in the contrast subjects or in the other patient groups. Seven patients, including al five in group I, had flattened plasma methadone concentration-time curves. The data suggest that the maintenance dosage of methadone need not be changed in stable chronic liver disease.

Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction.

Traditionally, patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers. While bronchodilator administration with the metered dose inhaler (MDI) and reservoir or spacer attachment is as effective as administration with the nebulizer in most settings, the former has not been widely accepted for treatment of acute airway obstruction in the emergency room. We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase (reservoir spacer) in 75 patients (45 men and 30 women), ages 18-73 (chi 44 years) who presented to the emergency room with acute asthma and COPD. Subjects in each group (22 COPD and 53 asthma) were randomly assigned to treatment with three puffs of metaproterenol (0.65 mg/puff) via the MDI with InspirEase plus nebulizer with placebo, or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion. Either treatment was given three times at 30 min intervals. The FEV1 and dyspnea scores according to the Borg scale were measured at baseline, 30 min after the first treatment, and 30 min after the third. There was no significant outcome difference between the two treatments in either diagnostic group. There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L. Serum theophylline levels, the need for concomitant therapy with corticosteroids, or additional emergency room therapy after the study, hospitalizations and treatment side effects did not differ between treatment groups. We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction.

Hepatitis C virus serology in parenteral drug users with chronic liver disease.

Chronic liver disease is a common complication of parenteral drug use, and liver cirrhosis is frequently seen in users of both parenteral drugs and alcohol. In 1978-83, we studied 88 parenteral drug users with sufficient evidence of chronic liver disease to warrant liver biopsy. Current alcohol abuse was noted in 63 (72%), and six (7%) were former alcohol abusers. Cirrhosis was found in 33 (38%). Hepatitis C antibody (anti-HCV) was detected in 86 (98%). Also, 40 of the anti-HCV positive sera were tested with recombinant immunoblot assay and all of these were reactive. All but one of the 31 patients with anti-HCV and cirrhosis were alcohol abusers. We conclude that parenteral drug users with chronic liver disease almost always have evidence of HCV infection.

Aging and gastrointestinal physiology.

This article reviews the effects of aging on the immune system, specifically the role of apoptosis. Nutrition and malnutrition in the elderly and their implications are examined. The structural and functional changes that occur with aging in the gastrointestinal tract are also described. Medical care for the elderly population can significantly be improved by the understanding of the physiology of aging in the gastrointestinal tract. This improved understanding can assist in distinguishing disease states from normal changes that occur with age.

Quantitative and temporal relationships of alcohol use in narcotic addicts and methadone maintenance patients undergoing alcohol detoxification.

Evidence exists that alcohol abuse frequently coexists with narcotic addiction and methadone maintenance treatment, and it is the major factor in the development of cirrhosis and liver failure. This study of patients hospitalized for alcohol detoxification compares the quantity of alcohol consumed by alcohol abusers, addicted to narcotics or in a methadone maintenance treatment program, to that consumed by patients not involved with narcotic addiction. Mean daily alcohol consumption was not significantly different in either group using narcotics, including methadone, or in the subgroup of methadone maintenance patients, from the amount consumed by nonnarcotic abusers. Determination of temporal sequence in the use of these substances revealed that in 68% regular alcohol abuse preceded narcotic use. Alcohol abuse reportedly began after entering a methadone maintenance treatment program in 29% of our patients. Alcohol abusers who were in a methadone maintenance treatment program were significantly younger than those who did not use narcotics, including methadone. Time interval according to the patients' estimates, from onset of regular alcohol consumption to heavy drinking, was not significantly different in the two groups.

The spectrum and causes of liver diseases in narcotic addicts.

Fifty charts of patients discharged with a diagnosis of liver disease from the acute care service of a hospital for the treatment of addiction were analyzed. Among 42 active heroin users or former heroin addicts maintained on methadone, 79% were heavy alcohol abusers. Seventeen cases of cirrhosis were encountered. All occurred in those abusing alcohol. Reversible liver disease was seen in both alcohol abusers and nonalcoholics. This study suggests that alcohol is a major factor in the development of irreversible liver disease in active heroin addicts and ex-addicts on methadone maintenance.

Alcohol use in methadone maintenance clinics.

A study was undertaken to determine the frequency of alcohol use and the amount consumed by methadone maintenance patients. In four clinics of the Beth Israel Medical Center Methadone Maintenance Treatment Program, every fifth patient from an alphabetical clinic list was selected for interview. Among the 101 patients who were interviewed, mean alcohol consumption was 1.2 ounces per day. Among those who drank, there was a continuum in terms of amount consumed. Forty-three percent had totally abstained from alcohol during the prior 3 months, and an additional 30% drank one or less ounces per day. Independently obtained staff rankings generally approximated interview results, and thus supported the reliability of the interview. Since staff rankings for participants and nonparticipants in the interview were similar, it appears that those who participated were typical of the group selected for study.

Venereal transmission of enteric pathogens in male homosexuals. Two case reports.

In two cases there was simultaneous or sequential occurrence of amebiasis, shigellosis, and giardiasis in male homosexuals. Enteric pathogens may, under the proper conditions, be venereally transmitted. In particular, the sexual practices of male homosexuals, most significantly, oral-anal contact, appear to provide the necesseary link for transmission. Evidence suggests that this is a growing problem.

Sexual transmission of enteric protozoa and helminths in a venereal-disease-clinic population.

We examined the prevalence of enteric protozoan and helminthic infections and the associations between infection and gender, sexual preference, and sexual practices in 180 consecutive patients at a venereal-disease clinic. Of 163 men, 29 were infected with one or more enteric parasites. None of the 17 women had an enteric infection. The prevalence of infections with Entamoeba histolytica or Giardia lamblia (or both) was 21.5 per cent in homosexual men, 6.2 per cent in bisexual men, and 0 in heterosexual men. There were significant associations between oral-anal sex and infection with E. histolytica (P less than 0.01) or with helminths (P less than 0.05). Homosexuality and oral-anal sex were the most important risk factors in E. histolytica, G. lamblia, and helminthic infections. We conclude the "hyperendemic" enteric protozoan infection rates in homosexual men are related to three factors: the original endemic level in the general population; the prevalence of sexual acts that facilitate transmission; and the frequency of exposure to an infected person.

Primary smooth muscle tumors of venous origin.

Vein tumors are rare, difficult to diagnose, and usually malignant. We have encountered three: a leiomyoma of the jugular vein and leiomyosarcomas of the saphenous vein and inferior vena cava (IVC). The leiomyoma was lost to follow-up, the saphenous vein leiomyosarcoma survived nine years, and the leiomyosarcoma of the IVC is six months without recurrence. Half of venous leiomyosarcomas arise in the IVC, predominately in women over 50 years of age. Surgical excision is the treatment of choice since malignant or benign status cannot be determined operatively. Resection should include a segment of the original vessel. This poses problems in the IVC when the renal veins require sacrifice. Right renal vein interruption mandates nephrectomy. Edema following IVC resection is evaluated. The incidence is lower than anticipated when resection is for tumor if there is no history of phlebitis. The IVC was reconstructed with a composite autograft but this is not now recommended. Despite significant local recurrences or distal metastases, cure or long-term palliation can often be achieved. Radiation and chemotherapy do not improve survival or prevent recurrence.

Tissue bile acids in patients with colon cancer and colonic polyps.

The purpose of this study was to determine whether in man unusual types of concentrations or bile acids were present in colonic polyps, colon carcinomas, or the adjacent, apparently normal tissue. Methods for the determination of soluble and tissue-bound bile acids were validated. Of 14 polyps analyzed, eight contained detectable levels of bile acid, predominantly chenodeoxycholic acid; no lithocholic acid was observed in either the tissue-bound or soluble bile acid fractions. Bile acids were found in four of nine samples of colon carcinoma; in one tumor, tissue-bound lithocholic acid was present. Bile acids were similarly found in seven of 10 samples of normal bowel taken adjacent to the carcinoma. In the soluble bile acid fraction, cholic acid was more abundant than chenodeoxycholic acid. There was no correlation between tissue histology and bile acid composition or concentration. Under the conditions used, this study did not disclose a relationship between tissue bile acids and colorectal histology.

Tumors of the ampulla of Vater: early diagnosis by intraampullary biopsy during endoscopic cannulation. Two case presentations and a review of the literature.

In 2 cases of ampullary tumor, the diagnosis was made by intraampullary biopsy after an abnormality was discovered via the fluoroscope during endoscopic retrograde cholangiopancreatography. One case was a villotubular adenoma with dysplasia and carcinoma in situ, and the other, a polypoid adenocarcinoma of the ampulla of Vater. These tumors were not visualized on upper gastrointestinal barium studies and conventional duodenoscopy nor by direct vision during endoscopic retrograde cholangiopancreatography. In the past the diagnosis of ampullary neoplasm has been most often made of surgery and on autopsy. Only in 11 of 538 patients reviewed was the diagnosis made by biopsy of a tumor visible at endoscopy. As demonstrated by the two cases we report, intraampullary biopsy of lesions visualized on fluoroscopy during endoscopic retrograde cholangiopancreatography may facilitate early diagnosis.

A case of chronic liver disease due to tolazamide.

Although chlorpropamide and tolbutamide are well recognized as causes of hepatotoxicity, there are only 3 reported cases of hepatic injury caused by a third oral hypoglycemic agent, tolazamide. In 2 of these cases, the liver-function tests returned to normal when the drug was discontinued. In the third case, the patient had cholestasis from chlorpropamide before administration of tolazamide and developed chronic liver disease. We are reporting the second instance of chronic liver disease induced by tolazamide. Our patient had been taking chlorpropamide, but she had no evidence of liver disease before administration of tolazamide. Tolazamide should be considered as a drug capable of producing hepatotoxicity that on occasion may be chronic.

Tissue culture of human epithelial cells from benign colonic tumors.

Human colonic epithelial cells from three classes of benign tumors have been reproducibly cultured free of fibroblasts for 8 wk using a supplemented Medium 199 (M 199S). The cultured colonic cells were identified as epithelial by the presence of junctional complexes (tight junctions, gap junctions, and desmosomes), a brush border on the apical surface, keratin fibrils, and by both a close-packed columnar or cuboidal morphology and the capability to transport water and ions to form hemicysts. Colony formation was initiated by groups of epithelial cells, not by single cells, and was inhibited by cocultivation with either lethally irradiated 3T3 cells or human diploid fibroblasts. Enhancement of epithelial colony formation was observed following culture on nonadherent, "floating" substrates compared with substrates attached directly to the bottom of the culture dish. Replication of epithelial cells in M 199S from the class of benign colonic tumors least prone to malignancy, the tubular, was significantly enhanced by epidermal growth factor (EGF). In contrast, EGF did not stimulate the growth of cells in M 199S from the other classes of benign tumors, the villotubular and the villous, which exhibit more malignant potential. These data imply that premalignant colonic epithelial cells lose responsiveness to growth modulation by EGF as they progress toward frank carcinoma.

Effect of severe alcoholic liver disease on the disposition of methadone in maintenance patients.

We studied methadone disposition in 11 maintenance patients with alcoholic liver disease of such severity that liver biopsy was contraindicated. Nine methadone-maintained patients with recent alcohol abuse but minimal or no evidence of liver disease served as controls. Most kinetic indices, including the apparent oral clearance and area under the concentration-time curves, were similar in patients and controls. Although the apparent terminal half-life of methadone was longer (p = 0.04) in the patients with liver disease, the peak plasma methadone level was lower (p = 0.03). None of the patients had signs or symptoms of methadone overdosage or abstinence at the time of study. Six patients and one control had flattened plasma methadone concentration-time curves. We hypothesize that, in severe liver disease, damage to hepatic drug-metabolizing systems is offset by damage to the capacity of the liver to store and release unchanged methadone. The usual methadone maintenance dose may be continued in stable patients with severe alcoholic cirrhosis.

Chronic liver disease in abusers of alcohol and parenteral drugs: a report of 204 consecutive biopsy-proven cases.

We studied a consecutive series of 204 patients who were admitted to a hospital for addictive diseases during 40 months and who had a liver biopsy. Parenteral drug abusers (n = 34) were significantly younger than alcohol abusers (n = 23) or abusers of both (n = 147) and had lower levels of serum alkaline phosphatase, total bilirubin, and aspartate aminotransferase than the other two groups. Chronic active hepatitis and chronic persistent hepatitis were more frequent (p less than 0.001) in abusers of parenteral drugs alone, whereas cirrhosis was found most often (p less than 0.001) in abusers of both alcohol and parenteral drugs. Cirrhosis was present in 10 of 39 (26%) simultaneous abusers of alcohol and parenteral drugs compared with 58 of 96 (60%) alcohol-abusing former parenteral drug abusers (p less than 0.001). Methadone maintenance treatment was not associated with cirrhosis. Thus, methadone-maintained patients who abuse alcohol and develop cirrhosis should remain in methadone maintenance treatment and receive concomitant alcoholism treatment. Also, these data further support the hypothesis that abusers of both alcohol and parenteral drugs have an increased risk of developing cirrhosis.