A randomized trial of naltrexone for smoking cessation

Aims. To evaluate the efficacy and safety of orally administered naltrexone, alone or in combination with nicotine patches, as a treatment for cigarette smoking. Design. Randomized, partially-blinded, 2 2 factorial trial using naltrexone (active vs. placebo) and nicotine patches (active vs. none). Participants. One hundred cigarette smokers. Intervention. Twelve weeks of either placebo-only, naltrexone-only, placebo with nicotine patches or naltrexone with nicotine patches. The naltrexone dose was 50 mg taken once daily, and the nicotine patch dose was 21 mg/24-hour for the first 8 weeks and 14 mg/24-hour for the remaining 4 weeks. Brief behavioral intervention was provided at each visit. Measurements. One-week pointprevalence smoking abstinence rates confirmed by an expired air carbon monoxide level of 8 parts per million (ppm) or less, daily cigarette smoking and cigarette craving. Findings. At the end of treatment, there was no effect of naltrexone on smoking abstinence. The smoking abstinence rates were 19% and 22% for the placebo only and naltrexone only treatment groups, respectively, and 48% and 46% for the placebo with nicotine patch and naltrexone with nicotine patch groups, respectively. However, the effect of the nicotine patch at this time was significant (p=0.006), but not at the 6-month follow-up. No significant effect of naltrexone was observed on daily cigarette smoking or cigarette craving during the study. Conclusions. The opioid antagonist naltrexone was not found to be effective for smoking cessation and had no significant effect on daily cigarette consumption or craving. The results of the present study provide no support for the use of naltrexone, alone or in combination with nicotine patches, as a therapeutic treatment for smoking cessation.     

Innere Arbeitsmodelle von Bindung und aversive Kindheitserfahrungen bei Psychotherapeuten in Ausbildung

In this paper first results of a study about competence development of psychotherapists in training in Germany are presented. In particular, the current mental processing of early relationship experiences and adversive childhood experiences of 90 trainees from three psychotherapies were examined at the beginning of their training. The internal working models of attachment and adversive early childhood experiences were assessed with the Adult Attachment Interview (AAI). The quantitative data analysis was supplemented by qualitative content analysis of four interviews to examine how trainees have dealt with adversive experiences and to work out if and how those are related to their decision to become psychotherapists. The AAIs analysis with respect to the attachment representation revealed by a first analysis of 50 interviews an overrepresentation of secure attachment patterns (78?%) and thus a significantly higher proportion of secure internal working models in comparison to former studies. Psychotherapists in training seem as burdened as the general population in terms of adversive childhood experiences. The qualitative analysis suggests a high degree of self-efficacy-enhancing parentification. The results are discussed in relation to previous psychotherapy experience, therapeutic school, age and sex of trainees.     

K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung

BACKGROUND. The capability of activated oncogenes to induce malignant transformation of immortalized cells in vitro has suggested that they have a similar role in the pathogenesis of human tumors. We previously found that activation of the K-ras oncogene by a point mutation in codon 12 occurs in about one third of human lung adenocarcinomas. METHODS. We studied the clinical importance of this oncogene-activation in 69 patients with lung adenocarcinoma in whom complete resection of the tumor was possible. The polymerase chain reaction was used to amplify ras-specific sequences of DNA isolated from frozen or paraffin-embedded tumor samples. Ras point mutations were subsequently detected and classified with the use of mutation-specific oligonucleotide probes. RESULTS. Nineteen of the tumors harbored a point mutation in codon 12 of the K-ras oncogene. There was no association between the K-ras point mutation and the age at diagnosis, sex, or presence of previous or concurrent neoplasms. Tumors positive for K-ras point mutations tended to be smaller and less differentiated than those without mutations. The K-ras codon-12 point mutation was a strong (and unfavorable) prognostic factor: 12 of the 19 patients with K-ras point-mutation-positive tumors died during the follow-up period, as compared with 16 of the 50 patients with no mutation in the K-ras oncogene (P = 0.002). This difference in prognosis was also reflected in the duration of disease-free survival (P = 0.038) and in the number of deaths due to cancer (P less than 0.001). CONCLUSIONS. The presence of K-ras point mutations defines a subgroup of patients with lung adenocarcinoma in whom the prognosis is very poor and disease-free survival is not usually long despite radical resection and a small tumor load.     

Outcome of thrombus aspiration in STEMI patients: a propensity score-adjusted study

The use of thrombus aspiration (TA) prior to primary percutaneous coronary intervention (PPCI) has undergone a radical change in intervention guidelines. The clinical implications, however, are still under scrutiny. This study investigated the clinical effects and outcome of TA before PPCI in patients with ST-segment elevation myocardial infarction (STEMI). Overall 1027 patients with STEMI were analyzed in this retrospective, propensity score-adjusted, multicenter study. The primary endpoints were in-hospital and long-term mortality. There were 418 patients in the TA group and 609 in the conventional PPCI group. The in-hospital mortality rate was significantly higher in the TA group (8.7 vs. 5.0%; P?=?0.03). During long-term follow-up [median follow-up duration 689 days (IQR 405–959)] the mortality rates were similar (TA 14.3%, conventional PPCI 15.0%; P?=?0.85). Survival analysis for the complete observation period revealed no significant benefit of TA [hazard ratio (HR) 1.12; 97.5% CI 0.90–0.71; P?=?0.63]. There were also no significant differences between the groups in the following secondary endpoints: composite of cardiovascular death and non-fatal reinfarction at discharge (P?=?0.39), post-PPCI thrombolysis in myocardial infarction flow-grade-3 (P?=?0.14), left ventricular ejection fraction (P?=?0.47), and non-fatal reinfarction during follow-up (P?=?0.17). Rehospitalization rate (1.82 vs. 10.3%; P?<?0.0001) and Canadian Cardiovascular Society (CCS) grading (P?=?0.02) during follow-up were significantly lower in the TA group. In our cohort the in-hospital mortality rate was significantly higher for TA patients, but during long-term follow-up the mortality rates did not differ. The incidence of rehospitalization and CCS grading were lower in the TA-treated patients.     

Effect of estradiol on insulin secreting INS-1 cells overexpressing estrogen receptors

BACKGROUND: Estrogen has been shown to have profound effects on insulin and glucose metabolism in vivo. Indeed, estrogens were recently shown to modulate ion channel and secretory activities in endocrine cells. DESIGN AND METHODS: To investigate whether estrogenic influences are caused by direct effects on pancreatic beta-cells, we equipped INS-1 insulinoma cells with estrogen receptors and monitored insulin content and Ca(2+) fluxes as well as basal and stimulated insulin secretion upon different stimuli including glucose, the Ca(2+) ionophore ionomycin, the Ca(2+) channel agonist BayK8644, the protein kinase C activator TPA, and the adenylate cyclase activator forskolin. RESULTS AND CONCLUSION: Our data reveal that estradiol has no significant direct effect on proliferation rate, insulin content, basal and stimulated insulin output as well as Ca(2+) fluxes of insulin secreting cells in vitro, indicating that in vivo responses to estrogen on insulin and glucose metabolism result from indirect betacytotropic effects.