Combining medical treatment and CBT in treating alcohol-dependent patients: effects on life quality and general well-being.

AIMS: The aim of the study was to examine how the combination of medication and a brief cognitive behavioral intervention for alcohol dependency can affect patients' quality of life (QL), symptoms of depression and smoking habits. METHODS: We conducted a randomized, open-label, multicenter naturalistic study for 243 voluntary-treatment-seeking alcohol-dependent adult outpatients in two phases: first, 12 weeks with continuous medication followed by targeted medication for up to 52 weeks, and second, a follow-up period of 67 weeks (altogether 2.5 years). The subjects were randomized 1:1:1 to receive supervised naltrexone, acamprosate or disulfiram, plus a brief manual-based cognitive behavioral intervention (CBT). RESULTS: All three study groups showed a significant reduction in drinking from baseline to the end of the study. In the QL test EQ-5D, patients exhibited significant positive changes in sleeping, action, pain and mood dimensions. Severity of depression decreased during the whole study. Smoking decreased more in the disulfiram group than in the naltrexone and acamprosate groups. CONCLUSION: A combination of medical treatment (naltrexone, acamprosate or disulfiram) with the CBT-booklet (patient guide) appears to help reduce patients' symptoms of depression and improve their QL. Treatment is also associated with success at quitting smoking, especially among patients using disulfiram.

N-ras gene mutations in acute myeloid leukemia: accurate detection by solid-phase minisequencing.

Mutations in the N-ras gene are found in one-third of patients with acute myeloid leukemia. The N-ras mutations could serve as markers for residual cells, if a highly sensitive method for detecting the mutations was available. We applied a new method, solid-phase minisequencing, to analyze bone-marrow cells from 16 patients with acute myeloid leukemia for mutations in codon 12, 13 and 61 of the N-ras gene. In the solid-phase minisequencing technique the mutations are identified by a primer extension reaction, in which a single labelled nucleoside triphosphate is incorporated into an immobilized DNA fragment previously amplified by the polymerase chain reaction. We identified N-ras mutations in 5 of the patients (30%). In one patient, we observed 2 mutations that were shown to be located in different alleles. With the solid-phase minisequencing method, we were able to determine the proportion of mutated cells in the samples. We found that in 4 of the samples only a fraction (7-64%) of the blasts carried an N-ras mutation, and in one sample practically all blast cells were mutated. The method was highly sensitive, allowing us to identify N-ras mutations even when the sample consisted of 99.7% normal cells and only 0.3% mutated blasts.

Temperature-sensitive mutants for steroid-sensitive growth of S115 mouse mammary tumor cells.

We have generated temperature-sensitive (ts) mutants for steroid-regulated anchorage-independent cell growth. Androgen-responsive S115+A mouse mammary tumor cells were mutagenized with ethyl methane sulfonate and the variants which were growth-arrested in suspension at the nonpermissive temperature of 41 degrees C were selected by killing dividing wild-type cells with the DNA synthesis inhibitors 5-fluoro-2'-deoxyuridine or cytosine arabinoside. Fifteen clones were isolated and characterized for morphology and growth properties. Three (ts21, ts27, ts33) of the phenotypic variants were ts for androgen-maintained anchorage-independent growth, two of them (ts27 and ts33) also for growth in monolayer. Growth arrest at 41 degrees C was not due to a defect in androgen receptor function in any of the mutant cell lines as shown by steroid binding assays and by the androgen-stimulated expression of both endogenous MMTV RNA and the transiently transfected LTR-CAT gene at the nonpermissive temperature. It remains to be determined for clone ts33 whether the defect is in postreceptor events of steroid action or in genes affecting general mechanisms of cell growth. However, since in clones ts21 and ts27 general cell growth remains functional at 41 degrees C under serum stimulation, defects may be in postreceptor steroid-related pathways. It is hoped that these mutants will provide a useful tool for study of steroid regulation of cell growth and in particular of the property of anchorage-independent growth.