Detection of TMPRSS2 : ERG fusion gene in circulating prostate cancer cells

Creative Commons Attribution-NonCommercial-Share Alike 3.0 license (CC BY-NC SA)Aim: To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from prostate cancer patients and its potential in monitoring tumor metastasis. Methods: We analyzed the frequency of TMPRSS2: ERG and TMPRSS2:ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2:ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2:ERG fusion in 10 of the 15 CTC samples. Results: TMPRSS2: ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2:ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2:ERG fusion at the primary site. However, TMPRSS2:ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH. Conclusion: Although further study is required to address the association between TMPRSS2:ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis.Peer reviewedFinal Published versio

A case report of cholinergic rebound syndrome following abrupt low-dose clozapine discontinuation in a patient with type I bipolar affective disorder

Abstract Background Rebound cholinergic syndrome is a rare, but well known unwanted phenomenon occurring after abrupt clozapine discontinuation. There have been previous reported cases of cholinergic rebound in the literature; however, these reports described cholinergic rebound following cessation of high doses of clozapine in patients diagnosed with schizophrenia. Here, we report a case of rebound cholinergic syndrome and catatonia in a male patient three days after abrupt discontinuation of 50 mg of clozapine prescribed for type I bipolar affective disorder. Case presentation A 66-year old male of Spanish origin, treated for type I bipolar affective disorder for 15 years and for Crohn disease, was brought to the emergency department because of a sudden onset of mutism, dysphagia and trismus. He was described catatonic and presented hypertension, tachycardia and tachypnea. His body temperature was normal and the laboratory tests were unremarkable at presentation. A head CT and an EEG were in the normal range. While reviewing his history, it appeared the he was on clozapine 50 mg a day, first introduced 2 months ago, during a previous hospitalization for a manic episode resistant to other mood stabilizers. For an unknown reason, the patient’s psychiatrist stopped clozapine three days before the admission and replaced it by risperidone 5 mg and quetiapine 200 mg daily. A cholinergic rebound syndrome was then evoked. The patient’s ability to speak recovered dramatically and fast after the intravenous administration of 2.5 mg of biperiden supporting the diagnosis. Risperidone and quetiapine were also stopped. The patient fully recovered in 20 days after the reintroduction of 50 mg of clozapine and 2.5 mg of biperiden daily. Conclusions This case report underscores that cholinergic rebound syndrome may occur in patients suffering from bipolar affective disorders, being on clozapine as a mood stabilizer. The low dose clozapine does not preclude severe manifestations of the phenomenon. Progressive tapering should therefore be adopted in any case

Prescription d'antidépresseurs dans le traitement de la douleur : rôle de la pharmacogénétique

Antidepressants, mainly tricyclic and non-selective reuptake inhibitors of serotonin antidepressants, are part of the treatment of chronic pain. The management is complicated by a large interindividual variability of efficacy and tolerance. Important part of this variability is associated with nucleotide polymorphisms of genes encoding enzymes involved in the pharmacokinetics and pharmacodynamics of these molecules. Identification of these genetic variants could to predict clinical consequences and allowed individualized adjustments in medication or dosage. This article presents the current knowledge on the influence of genetics on the efficacy and adverse effects of antidepressants used in chronic pain treatment

Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional ECG Screening Outcome in Psychiatry study

The authors aimed to determine the prevalence of drug-induced long QT at admission to a public psychiatric hospital and to document the associated factors using a cross-sectional approach

À propos de l’accueil libre

Pourquoi l'« accueil libre » auprès des jeunes ? Y-a-t-il une spécificité professionnelle dans ce type d'accueil ? Des animatrices et animateurs de divers lieux d'accueil (groupe « Réflexion Action Jeunesse ») se sont penchés sur leur pratique et ont mis en commun leur approche. Durant plus de cinq ans, ils se sont rencontrés régulièrement afin de partager et d'analyser des situations préoccupantes de leur activité professionnelle. Une série de synthèses sur le fonctionnement complexe, les spécificités et les difficultés de l'accueil libre émane de ces rencontres et constitue le cœur de cet ouvrage. À ce noyau, deux textes théoriques de chercheur.e.s de la Haute école de travail social de Genève font écho. En amont, Laurent Wicht, souligne le caractère essentiel et institutionnalisant de la mutualisation en travail social ; en aval, Joëlle Libois et Patricia Heimgartner, prolongent la réflexion dans une perspective historique et par la tentative de définition d'une pratique fondamentale, exigeante et subtile du travail social

Regulated laminin-332 expression in human islets of Langerhans

Laminin-332 (LN-332) is a basement membrane component known to exert a beneficial effect on rat pancreatic beta cells in vitro. In this work, we analyzed the expression of LN-332 in human islets, its expression after inflammatory insults by cytokines, and the molecular mechanisms responsible for this effect. By Western blotting and RT-PCR, we showed that LN-332 was expressed in isolated human islets. By immunofluorescence on pancreas sections, we observed that labeling was confined to endocrine cells in islets. Confocal microscopy analysis on isolated islet cells revealed that labeling was granular but did not colocalize with hormone secretory granules. LN-332 was most abundant in cultured islets compared to freshly isolated islets and was found in culture medium, which suggests that it was secreted by islets. When islets were exposed to interleukin (IL)-1beta, expression and secretion of LN-332 increased as compared to control. No effect was observed with tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3-K) activity, inhibited culture- and IL-1beta-induced LN-332 expression in islets. These results show that LN-332, known to have some beneficial effect on beta cells in vitro, is produced and secreted by endocrine islet cells and is up-regulated by stressing conditions such as culture and IL-1beta-exposure