Alvin M. Gelb

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 groups II and III (moderate and mild chronic liver disease, P < 0.01) and the contrast group (P < 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 all 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.

Tissue culture of human epithelial cells from benign colonic tumors

SummaryHuman 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.

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.

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.

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.

Treatment of Malignant Biliary Obstruction with a High‐Dose‐Rate Remote Afterloading Device Using a 10 Fr Nasobiliary Tube

Abstract: The role of intracavitary radiation therapy for palliative treatment of malignant biliary obstruction has been previously described, incorporating both preloading and afterloading techniques. We present an approach which combines nasobiliary intubation with the use of a remote afterloader unit, the Microselectron HDR (Nucletron Corp, The Netherlands), which is capable of delivering high‐dose radiation treatments in a matter of minutes. This method offers decreased treatment time, thus reducing the hospitalization period, and minimizes problems associated with conventional intracavitary radiation therapy such as potential radiation exposure to hospital personnel, drifting of the iridium source, and risk of nosocomiai infection. The combined endoscopic‐radiation technique has been used in 5 seriously ill Patients without complications. To date all patients are alive, (follow‐up range 2–6 months). This safer, more efficient method of brachytherapy has not only improved the delivery of intracavitary therapy, but may offer longer term benefits. Further follow‐up is needed.