Pro re nata medications in mental health: Results of a transversal study.

BACKGROUND: Pro re nata are frequent in psychiatry. The risks engendered by this treatment requires that their prescription and administration be made safer. The frequency of administration of pro re nata depends mainly on the nurse's clinical judgment. AIMS: Our first objective was to assess nurses' satisfaction about the quality of doctors' pro re nata prescriptions. Our second objective was to assess the nurses' self-reported practices for administering pro re nata treatments as written in the prescription. METHOD: Self-administered questionnaires were sent by the hospital's internal mail between November 13, 2014, and December 10, 2014 to all nurses in our psychiatric establishment in France. The questionnaire included multiple-choice questions and questions based on clinical vignettes. RESULTS: The response rate was 51.9% (124/239). Overall, 75.6% considered that the quality of the prescriptions in terms of dosage was satisfactory. However, regardless of the quality of the doctor's pro re nata prescription, nurses did not contact the doctor even when the prescription quality was poor. Unexpectedly, we found that 88.7% have administered medication "as needed" without a doctor's prescription and sometimes acted without consulting doctors. CONCLUSIONS: The nurses appeared globally satisfied with doctors' prescriptions of pro re nata medications. On the other hand, most administered some medications without any prescription, that is, illegally. Physicians must be rigorous in the quality of their PRN prescriptions. At the same time, nurses must comply with the medical prescription or contact the physician if the quality of the PRN prescription appears poor.

Stigma resistance is associated with advanced stages of personal recovery in serious mental illness patients enrolled in psychiatric rehabilitation.

BACKGROUND: Stigma resistance (SR) is defined as one's ability to deflect or challenge stigmatizing beliefs. SR is positively associated with patient's outcomes in serious mental illness (SMI). SR appears as a promising target for psychiatric rehabilitation as it might facilitate personal recovery. OBJECTIVES: The objectives of the present study are: (i) to assess the frequency of SR in a multicentric non-selected psychiatric rehabilitation SMI sample; (ii) to investigate the correlates of high SR. METHODS: A total of 693 outpatients with SMI were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluation included standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, and personal recovery and a large cognitive battery. SR was measured using internalized stigma of mental illness - SR subscale. RESULTS: Elevated SR was associated with a preserved executive functioning, a lower insight into illness and all recovery-related outcomes in the univariate analyses. In the multivariate analysis adjusted by age, gender and self-stigma, elevated SR was best predicted by the later stages of personal recovery [rebuilding; p = 0.004, OR = 2.89 (1.36-4.88); growth; p = 0.005, OR = 2.79 (1.30-4.43)). No moderating effects of age and education were found. CONCLUSION: The present study has indicated the importance of addressing SR in patients enrolled in psychiatric rehabilitation. Recovery-oriented psychoeducation, metacognitive therapies and family interventions might improve SR and protect against insight-related depression. The effectiveness of psychiatric rehabilitation on SR and the potential mediating effects of changes in SR on treatment outcomes should be further investigated in longitudinal studies.

[Early intervention in bipolar affective disorders: Why, when and how]. / Intervenir précocement dans les stades débutants du trouble bipolaire : pourquoi, quand et comment.

OBJECTIVES: Bipolar disorder (BD) is a chronic and severe psychiatric disease. There are often significant delays prior to diagnosis, and only 30 to 40 % of patients will experience complete remission. Since BD occurs most often at a young age, the disorder can seriously obstruct future socio-professional development and integration. Vulnerability-stress model of BD is considered to be the result of an interaction between vulnerability genes and environmental risk factors, which leads to the onset of the disorder most often in late adolescence or early adulthood. The clinical "staging" model of BD situates the subject in a clinical continuum of varying degrees of severity (at-risk status, first episode, full-blown BD). Given the demonstrated effectiveness of early intervention in the early stages of psychotic disorder, we posit that early intervention for early stages of BD (i.e. at-risk status and first episode mania or hypomania) would reduce the duration of untreated illness and optimize the chances of therapeutic response and recovery. METHODS: We conducted a narrative review of the literature to gather updated data on: (1) features of early stages: risk factors, at-risk symptoms, clinical specificities of the first manic episode; (2) early screening: targeted populations and psychometric tools; (3) early treatment: settings and therapeutic approaches for the early stages of BD. RESULTS: (1) Features of early stages: among genetic risk factors, we highlighted the diagnosis of BD in relatives and affective temperament including as cyclothymic, depressive, anxious and dysphoric. Regarding prenatal environmental risk, we identified peripartum factors such as maternal stress, smoking and viral infections, prematurity and cesarean delivery. Later in the neurodevelopmental course, stressful events and child psychiatric disorders are recognized as increasing the risk of developing BD in adolescence. At-risk symptoms could be classified as "distal" with early but aspecific expressions including anxiety, depression, sleep disturbance, decreased cognitive performance, and more specific "proximal" symptoms which correspond to subsyndromic hypomanic symptoms that increase in intensity as the first episode of BD approaches. Specific clinical expressions have been described to assess the risk of BD in individuals with depression. Irritability, mixed and psychotic features are often observed in the first manic episode. (2) Early screening: some individuals with higher risk need special attention for screening, such as children of people with BD. Indeed, it is shown that children with at least one parent with BD have around 50 % risk of developing BD during adolescence or early adulthood. Groups of individuals presenting other risk factors, experiencing an early stage of psychosis or depressive disorders should also be considered as targeted populations for BD screening. Three questionnaires have been validated to screen for the presence of at-risk symptoms of BD: the Hypomanic Personality Scale, the Child Behavior Checklist-Paediatric Bipolar Disorder, and the General Behavior Inventory. In parallel, ultra-high risk criteria for bipolar affective disorder ("bipolar at-risk") distinguishing three categories of at-risk states for BD have been developed. (3) Early treatment: clinical overlap between first psychotic and manic episode and the various trajectories of the at-risk status have led early intervention services (EIS) for psychosis to reach out for people with an early stage of BD. EIS offers complete biopsychosocial evaluations involving a psychiatric examination, semi-structured interviews, neuropsychological assessments and complementary biological and neuroimaging investigations. Key components of EIS are a youth-friendly approach, specialized and intensive care and client-centered case management model. Pharmaceutical treatments for at-risk individuals are essentially symptomatic, while guidelines recommend the use of a non-antipsychotic mood stabilizer as first-line monotherapy for the first manic or hypomanic episode. Non-pharmacological approaches including psychoeducation, psychotherapy and rehabilitation have proven efficacy and should be considered for both at-risk and first episode of BD. CONCLUSIONS: EIS for psychosis might consider developing and implementing screening and treatment approaches for individuals experiencing an early stage of BD. Several opportunities for progress on early intervention in the early stages of BD can be drawn. Training first-line practitioners to identify at-risk subjects would be relevant to optimize screening of this population. Biomarkers including functional and structural imaging measures of specific cortical regions and inflammation proteins including IL-6 rates constitute promising leads for predicting the risk of transition to full-blown BD. From a therapeutic perspective, the use of neuroprotective agents such as folic acid has shown particularly encouraging results in delaying the emergence of BD. Large-scale studies and long-term follow-up are still needed to achieve consensus in the use of screening and treatment tools. The development of specific recommendations for the early stages of BD is warranted.

Being parent is associated with suicidal history in people with serious mental illness enrolled in psychiatric rehabilitation.

Parenting is a central life experience that could promote recovery in people with Serious Mental Illness (SMI). It could also be challenging for parents with SMI and result in poor recovery-related outcomes. Parenting is often overlooked in psychiatric rehabilitation. The objectives of the present study were to identify the characteristics and needs for care of mothers and fathers with SMI enrolled in a multicentric non-selected psychiatric rehabilitation SMI sample. We consecutively recruited 1436 outpatients from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). The evaluation included standardized scales for clinical severity, psychosocial function, quality of life and satisfaction with life, wellbeing, personal recovery and a broad cognitive battery. We found that parenting was associated to suicidal history in mothers and fathers with SMI. In the multivariate analysis, being mother was best explained by insight (p < 0.015, adjusted OR = 0.76 [0.59-0.90]), current age (p < 0.001, aOR = 1.13 [1.07-1.21]), education level (p = 0.008; aOR = 0.12 [0.02-0.53]) and family accommodation (p = 0.046, aOR = 0.19 [0.03-0.84]). Being father was best explained by suicidal history (p = 0.005, aOR = 3.85 [1.51-10.10]), marital status (in relationship, p < 0.001; aOR = 7.81 [2.73-23.84]), satisfaction with family relationships (p = 0.032, aOR = 1.22 [1.02-1.47]) and current age (p < 0.001, aOR = 1.16 [1.10-1.23]). In short, parenting was associated to increased history of suicide attempt in mothers and fathers with SMI. Mothers and fathers with SMI may have unique treatment needs relating to parenting and recovery-related outcomes. The implementation of interventions supporting the needs of parents with SMI in psychiatric rehabilitation services could improve parent and children outcomes.

[Active surveillance of prostate cancer: treatement-free survival according to restricted or expanded eligibility criteria]. / Surveillance active du cancer de prostate : survie sans traitement curatif selon critères d'éligibilité stricts ou élargis.

AIM: Overtreatment is an actual problem in low risk localized prostate cancer (PC) management. Active surveillance (AS) is a solution to limit this problem, but eligibility criteria remained discussed. The aim was to assess possibilities of widening selection criteria for patient in AS, studying curative treatment free survival (CTFS) according to restricted or expanded eligibility criteria. METHODS: We retrospectively studied patients beginning AS between 2008 and 2014, for Gleason 6 localized PC, PSA<15ng/ml,

Self-stigma in serious mental illness and autism spectrum disorder: Results from the REHABase national psychiatric rehabilitation cohort.

BACKGROUND: Self-stigma is a major issue in serious mental illness (SMI) and is negatively associated with patient outcomes. Most studies have been conducted in schizophrenia (SZ). Less is known about self-stigma in other SMI and autism spectrum disorder (ASD). The objectives of this study are: (i) to assess the frequency of self-stigma in a multicentric nonselected psychiatric rehabilitation SMI and ASD sample; and (ii) to investigate the correlates of elevated self-stigma in different SMI conditions and in ASD. METHODS: A total of 738 SMI or ASD outpatients were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluations included sociodemographic data, illness characteristics, and standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, personal recovery, a large cognitive battery, and daily functioning assessment. RESULTS: 31.2% of the total sample had elevated self-stigma. The highest prevalence (43.8%) was found in borderline personality disorder and the lowest (22.2%) in ASD. In the multivariate analysis, elevated self-stigma was best predicted by early stages of personal recovery (moratorium, p = 0.001, OR = 4.0 [1.78-8.98]; awareness, p = 0.011, OR = 2.87 [1.28-6.44]), history of suicide attempt (p = 0.001, OR = 2.27 [1.37-3.76]), insight (p = 0.002, OR = 1.22 [1.08-1.38]), wellbeing (p = 0.037, OR = 0.77 [0.60-0.98]), and satisfaction with interpersonal relationships (p < 0.001, OR = 0.85 [0.78-0.93]). CONCLUSIONS: The present study has confirmed the importance of addressing self-stigma in SMI and ASD patients enrolled in psychiatric rehabilitation. The effectiveness of psychiatric rehabilitation on self-stigma and the potential mediating effects of changes in self-stigma on treatment outcomes should be further investigated.

[Non-tuberculous mycobacterial cervical adenitis in children: 2 cases]. / Deux cas d'adénite cervicale à mycobactéries non tuberculeuses chez l'enfant.

BACKGROUND: Cervical lymphadenitis is the most common manifestation of infection with nontuberculous mycobacteria (NTM) in immunocompetent children. Nevertheless, it is poorly known by dermatologists. Its incidence, which is currently increasing since the cessation of BCG vaccination in 2007, raises several issues regarding its pathophysiology, diagnosis and management. PATIENTS AND METHODS: We report two cases of NTM adenitis: one in a 2-year-old girl vaccinated with BCG and one in an unvaccinated 22-month-old boy, in whom a misleading presentation led to delayed diagnosis. The condition progressed to fistula formation and the diagnosis was finally made on systematic cultures of lymph node samples. The time to diagnosis was 2 and 4months, respectively. The girl was treated with erythromycin for 3 weeks and with clarithromycin for 3 weeks; the boy received clarithromycin for 7 weeks and underwent complete surgical excision. DISCUSSION: NTM adenitis preferentially affects girls under 4 years and occurs more frequently in winter and spring. First, the other differential diagnoses, including tuberculosis, must be ruled out by chest radiography. The diagnosis is oriented by the clinical picture, a positive TST and resistance to conventional antibiotics. However, it is only certified by systematic culture or PCR of lymph node biopsies, with screening for atypical mycobacteria being specified. The decrease in child protection by BCG vaccination coincides with the current increase in NTM infections, of which the most frequent is Mycobacterium avium complex (MAC) for cervical adenitis. The reference treatment is surgery. However, alternative treatments (incomplete excision, antibiotics, watchful waiting, etc.) should be considered where surgery fails or there is excessive risk of injury to a branch of the facial nerve. CONCLUSION: Atypical mycobacterial adenitis in immunocompetent children has become an increasingly common infection since the abandonment of BCG vaccination. Improved knowledge of this disease would result in complete surgical excision at an early stage with a lower rate of aesthetic sequelae.

Successful treatment of a recurrent Aspergillus niger otomycosis with local application of voriconazole.

Fungal otitis (otomycosis) is a common infection encountered by otolaryngologists. Nevertheless, its management can be challenging because of its high recurrence rate and of the limited therapeutic options. A 45-year-old woman suffered from recurrent otomycosis. The ineffectiveness of successive antibiotic cures and repeated topical treatments with nystatin and then with econazole cream led to perform microbiological analyses. Culture of ear swab grew Aspergillus niger. The use of a 1% voriconazole sterile solution previously validated for treatment of eye infections was considered after ensuring the absence of known ototoxic effects of the antifungal and of the excipients. The patient was advised to apply locally this voriconazole solution daily for 14 days (3 drops, 3-4 times a day). Full recovery was obtained at the end of the treatment, and no relevant side effects were noticed. More than one year after completion of therapy, there was no recurrence. Our observation shows that voriconazole 1% solution is an interesting option for treating otomycosis which failed to respond to usual therapeutic options. Further prospective studies are now warranted to confirm these findings.

Health-related quality of life, anxiety and depression in parents of adolescents with Gilles de la Tourette syndrome: a controlled study.

Our objectives were to assess health-related quality of life (HRQoL), anxiety, depression of Gilles de la Tourette syndrome (GTS) adolescents' parents compared to controls; to assess GTS adolescents' HRQoL compared to controls; to investigate which parental and adolescent variables are associated with poorer parental HRQoL. The controlled study involved GTS outpatients and their parents, adolescent healthy controls matched for gender and age and their parents. Parents' HRQoL was assessed using SF-36 and WHOQOL-BREF; anxiety, depression using HADS. Adolescents' HRQoL was assessed by adolescents using VSP-A instrument and by their parents using VSP-P. A total of 75 GTS adolescents, 75 mothers, 63 fathers were compared to 75 control adolescents, 75 mothers, 62 fathers. GTS mothers had worse HRQoL than controls on 5 of the 8 SF-36 dimensions and 1 of the 4 WHOQOL-BREF dimensions, while GTS fathers had worse HRQoL on 2 of the WHOQOL-BREF dimensions. GTS mothers had poorer HRQoL than fathers. GTS mothers had more depression than control mothers and GTS fathers had more anxiety than control fathers. GTS adolescents had worse HRQoL than controls on 5 of the 9 VSP-A dimensions. Factors significantly related to parental HRQoL were anxiety, depression, GTS adolescents' HRQoL and, concerning mothers, behavioural and emotional adolescents' problems; concerning fathers, severity of vocal tics, duration since first symptoms. This study provides a better understanding of poorer HRQoL and psychiatric morbidity of GTS adolescents' parents. Clinicians should pay attention to their emotional well-being and HRQoL and be aware that mothers and fathers are differently affected.

[Psychiatrists' decision making and monitoring of antipsychotic prescription for elderly schizophrenia patients]. / Prescription et surveillance d'antipsychotiques chez les patients âgés souffrant de schizophrénie: pratiques des psychiatres et leurs déterminants.

OBJECTIVE: Advancing age entails specific treatment modalities for patients with schizophrenia. The choice of appropriate antipsychotic therapy (AP) and the monitoring of treatment is a major challenge. However, little is known about the real-world prescribing practices of psychiatrists for elderly schizophrenia patients. The aim of this study was to assess prescribing practices and treatment monitoring in elderly schizophrenia patients and whether socio-professional psychiatrists' characteristics are related to their practices. METHODS: We contacted by mail 190 psychiatrists to take part in an observational survey of their AP prescribing practices for elderly (aged over 65) schizophrenia patients. RESULTS: The response rate was 44.2%, and of the psychiatrists who replied 75% were treating elderly schizophrenia patients. A second-generation AP (SGAP) was prescribed as first-line of treatment by 87.7% of the psychiatrists. The most frequently used SGAPs were risperidone and olanzapine (respectively preferred by 54.4% and 19.3% of the psychiatrists taking part). At the beginning of treatment, 91.1% of the psychiatrists prescribed a lower dose than for middle-aged patients. Of the psychiatrists taking part, 64.9% prescribed monotherapy; and among these psychiatrists, 65% cited insufficient control of the disease as the reason for their choice, while 48.7% of those who elected not to prescribe combined AP did so in order to limit the side-effects. Of the psychiatrists taking part, 54.4% prescribed long-acting injectable AP (LAAP); better therapeutic compliance and alliance was the main argument in the choice of LAAP given by the psychiatrists taking part who prescribed the drug, whereas the absence of indications and problems of tolerance were arguments against for those who did not. "Personal experience" emerged as the governing factor in the choice of AP. The AP side-effect profile was the main criterion of choice of the AP agent for 3.5% of the psychiatrists taking part, and the most frequently chosen secondary criterion (29.8%). Monitoring of treatment was partly performed according to professional recommendations: pre-treatment and post-prescription assessments of waist circumference and ophthalmological monitoring were very infrequent (8.8 to 18.5%) as were pre-treatment and early post-prescription assessments of prolactinaemia (14.8 to 20.4%); long-term cardiac monitoring was infrequent (43.9%). The psychiatrists taking part whose first-line drug was SGAP were more familiar with professional recommendations than those who prescribed first generation antipsychotic (FGA) drugs (72% as against 14.3%, P=0.006). Of the psychiatrists taking part in the study, 64.9% reported they commonly use professional recommendations. Psychiatrists who declared they commonly use professional recommendations measured pulse rate and blood pressure significantly more often over the long-term than those who did not (74.3% as against 41.2%, P=0.0315). They also measured waist circumference over the long-term significantly more often than psychiatrists who did not commonly use professional recommendations (22.9% as against 0%, P=0.0420). Psychiatrists treating more than ten of these patients yearly measured significantly more often over the long-term pulse rate and blood pressure than those treating fewer patients (80% as against 50%, P=0.0399). Over the long-term monitoring, psychiatrists with a larger number of elderly schizophrenia patients in their care also performed more often fasting blood glucose test, lipid profile and referral for cardiac consultation with ECG (respectively, 95.5% as against 70.8%, P=0.0489; 90.9% as against 58.3%, P=0.0182; 81.8% as against 29.2%, P<0.0001). CONCLUSIONS: The results of this survey need to be confirmed in a larger population sample. The antipsychotic prescribing practices were broadly in agreement with current recommendations except for the tolerance profile which was not the first element taken into account in the choice of the AP agent. Some clinical and paraclinical medical examinations were carried out infrequently, in particular cardiac monitoring over the long-term, which is essential in this elderly patient population. One important element to emerge from our results was that common use of professional recommendations is associated with better monitoring.

[pT3N0 prostate cancer treated with radical prostatectomy as sole treatment: Oncological results and predictive factors of recurrence]. / Cancer de la prostate de stade pT3N0 traité par prostatectomie radicale en monothérapie : résultats carcinologiques et facteurs prédictifs de récidive.

OBJECTIVES: To evaluate biological free survival in patients with locally advanced prostate cancer treated with radical prostatectomy (RP) as sole treatment, and to analyse predictive factors of recurrence. PATIENTS AND METHOD: We retrospectively studied patients treated between 1996 and 2006 for a pT3N0 prostate cancer with RP without any adjuvant treatment. The main endpoint was PSA relapse, defined as two successive elevations of PSA>0.2 ng/mL. An association between PSA free survival and PSA, Gleason score, pathological stage and surgical margins status was statistically assessed. RESULTS: A total of 147 patients were included. Median preoperative PSA was of 10 ng/mL. Pathological stage was pT3b in 30% of the cases and surgical margins showed cancer involvement in 63% of the cases. Gleason score was ≥3+4 in 74% of the cases. Postoperative PSA was undetectable in 121 (82%) patients. Median follow up following RP was of 5 years. The 5-year-PSA free survival was of 48%. Multivariate analysis showed that preoperative and postoperative PSA, as well as Gleason score were predictors of PSA relapse (P<0.05). In patients with undetectable postoperative PSA, 5-year-PSA free survival was of 56%. Seminal vesicle involvement and Gleason score ≥3+4 were the only independent predictors of PSA relapse. CONCLUSIONS: After RP for pT3N0 prostate cancer, the only predictive factors of recurrence were postoperative PSA and Gleason score. In case of undetectable postoperative PSA, surveillance seems acceptable if Gleason score is <3+4 and in the absence of seminal vesicle involvement.

[Therapeutic efficacy and safety of repetitive Transcranial Magnetic Stimulation in depressions of the elderly: a review]. / Efficacité et tolérance de la stimulation magnétique transcrânienne (SMTr) dans le traitement des dépressions chez le sujet âgé: revue de la littérature.

INTRODUCTION: During the past 15 years, therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) have been studied in psychiatric diseases, particularly in the treatment of depressive disorders. There are more and more data suggesting its efficacy in the treatment of depression in older patients. Thus, the authors found it useful to conduct an up-to-date review of studies that examined the efficacy and safety of rTMS to treat depressive disorders in the aged. METHOD: After an exhaustive consultation of databases (Medline/PubMed and the Avery-George-Holtzheimer Database of rTMS Depression Studies), supplemented by a manual research, the authors retained studies evaluating the therapeutic efficacy of rTMS on depressive disorders in the aged. RESULTS: Fifteen studies were retained. Four open studies using high frequency rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), demonstrated a decrease in the mean Hamilton Depression Rating Scale (HDRS) scores; however, only a quarter of the aged patients studied experienced a significant remission of depression. Five parallel arm double-blind versus placebo studies concluded in contradicting results: two studies confirmed a significantly greater efficacy of rTMS compared to placebo, whereas three studies did not; but the sham procedure (positioning coil at 90 degrees from the scalp) was disputable in most studies. One study concluded in therapeutic efficacy by inhibiting the right DLPFC. Three controlled parallel arm studies compared rTMS and electroconvulsive-therapy (ECT); one study concluded in greater efficacy of ECT at end of treatment, but the number of ECT treatments depended on the patients' response, whereas a 15-day course of rTMS was systematically administered; additionally HDRS scores were similar in two groups of patients (rTMS and ECT) at 6 months. Lastly, three studies focused on aged patients with cerebrovascular disease. They showed the efficacy of rTMS, although older age and smaller frontal gray mater volumes were associated with a poorer response to rTMS. DISCUSSION: Thus, although some studies concluded contradicting results, literature data globally sustain an efficacy of rTMS for depression in the elderly. Several parameters might be associated with greater antidepressant efficacy (higher intensity pulses of rTMS of the left DLPFC; higher number of stimulations or higher number of rTMS sessions). Poorer responsiveness to rTMS may be related to several patients' factors including older age and smaller frontal gray matter volumes; lesions of the white matter pathways connecting the left DLPFC and the left anterior cingulate cortex might explain a poor response to rTMS. Literature data globally confirm that rTMS is safe and does not produce cognitive deficits, even among highly vulnerable patients with clinical evidence of cerebrovascular disease. CONCLUSION: Many questions remain concerning the optimal stimulation parameters, administration protocol, and privileged indications. Thus, the next rTMS studies should be carefully designed to clarify these questions.

[Primary metastatic urethral melanoma: a case study]. / Mélanome primitif de l'urètre découvert au stade métastatique: à propos d'un cas.

PURPOSE: Primary urethral melanoma is a rare pathology for which treatment strategies are controversial. The aim of this work was to report a case of metastatic primary urethral melanoma, and to discuss recent data available from literature. MATERIAL AND METHOD: Case study was summarized from the patient's medical chart. Review of literature was performed using the National Center for Biotechnology Information (NCBI) database. RESULTS: We reported the case of an 89-year-old woman who died from a primary metastatic melanoma of the urethra. This pathology encounters for less than 1% of melanomas and has an adverse prognosis. In case of metastasis, specific survival is only of a few months. When localized to the urethra, treatment relies on radical urethrectomy, followed by adjuvant chemo- and immunotherapy. CONCLUSIONS: The modalities of treatment of primary urethral melanoma rely only on reported case studies. When diagnosed at the metastatic stage, reported specific survival does not exceed a few months.

Distribution of metamitron-resistant Chenopodium album L. in Belgian sugar beet.

Chenopodium album L. (fat-hen) with a Ser264-Gly mutation is resistant to photosystem II-inhibiting herbicides like the triazinone metamitron, a key herbicide in sugar beet. In recent years, this resistant biotype may cause unsatisfactory weed control in Belgian sugar beet. However, the dimension of the problem was yet unknown. Therefore, a survey was conducted in 2008 covering the whole Belgian sugar beet area. In randomly selected fields, C. album plants surviving weed control were counted and sampled. First, the number of surviving plants was used to estimate the prevalence of fields with unsatisfactory control and to classify the surveyed fields. Then, the share of the resistant biotype in each field was determined with cleaved amplified polymorphic sequence-analysis (CAPS-analysis) on sampled leaves. Finally, all results were visualised on the map of Belgium. Twenty percent of the fields had more than 500 surviving plants per hectare and were thus classified as fields with unsatisfactory C. album control. The resistant biotype was present in 95% of these fields and even in 74% of the sampled fields with good weed control. No pattern was found during mapping. These results indicate that the metamitron-resistant biotype has spread over the whole sugar beet area but that it is not (yet) causing severe problems in every field. To get a more accurate estimation of the portion of resistant plants in the field and the effect of herbicide treatment on this biotype, an elaborate survey will be conducted in 2010 on fields that have both untreated and treated plots installed.

Epidermal growth factor-induced neuroendocrine differentiation and apoptotic resistance of androgen-independent human prostate cancer cells.

Neuroendocrine differentiation (NED) has been implicated in prostate cancer progression and hormone-therapy failure. Neuroendocrine cells are non-proliferating and escape apoptotic cell death, although their origin and the causes of their apoptotic resistance have as yet been poorly elucidated. This study demonstrates a new mechanism involved in controlling NED. We report that epidermal growth factor (5-50 ng/ml) promotes neuroendocrine-like differentiation of androgen-independent DU145 prostate cancer cells. This differentiation is associated with an increase in the expression of Neuron Specific Enolase (NSE) and a reduction in cell proliferation and is blocked by inhibiting tyrosine kinase activity with genistein and with compound 56 (C56). An increase in the cAMP level, using dibutryl cAMP (db-cAMP) (1 mM) and isobutylmethylxanthine (100 microM), does not promote NED by itself, but does increase the effect of EGF on NED. In addition, EGF-induced NED protects cells from apoptosis induced with thapsigargin (1 microM) by reducing the thapsigargin-induced cytosolic calcium overload. In order to describe how EGF-induced NED protects cells against thapigargin-induced calcium overload we investigated the spatiotemporal calcium signalling linked to apoptosis. By using thapsigargin in various conditions on DU145 cells and using micro-fluorimetric calcium measurements, we show that depletion of intracellular calcium store induces apoptosis and that the amplitude and duration of the capacitive calcium entry are two apoptosis-modulating parameters. We show that protection against thapsigargin-induced apoptosis conferred by NED is achieved by reducing the amount and the speed of calcium that can be released from calcium pools, as well as modulating the amplitude of the subsequent calcium entry.

Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control.

The present study demonstrates for the first time that intracellular calcium-ATPases and calcium pool content are closely associated with prostate cancer LNCaP cell growth. Cell growth was modulated by changing the amount of epidermal growth factor, serum, and androgene in culture media. Using the microspectrofluorimetric method with Fura-2 and Mag Fura-2 as probes, we show that in these cells, the growth rate is correlated with intracellular calcium pool content. Indeed, an increased growth rate is correlated with an increase in the calcium pool filling state, whereas growth-inhibited cells show a reduced calcium pool load. Using Western blotting and immunocytochemistry, we show that endoplasmic reticulum calcium pump expression is closely linked to LNCaP cell growth, and are a common target of physiological stimuli that control cell growth. Moreover, we clearly demonstrate that inhibition of these pumps, using thapsigargin, inhibits LNCaP cell growth and prevents growth factor from stimulating cell proliferation. Our results thus provide evidence for the essential role of functional endoplasmic reticulum calcium pumps and calcium pool in control of prostate cancer LNCaP cell growth, raising the prospect of new targets for the treatment of prostate cancer.

Verapamil inhibits proliferation of LNCaP human prostate cancer cells influencing K+ channel gating.

The mechanisms of verapamil and tetraethylammonium (TEA) inhibition of voltage-gated K+ channels in LNCaP human prostate cancer cells were studied in whole-cell and outside/inside-out patch-clamp configurations. Rapidly activating outward K+ currents (I(K)) exhibited neither C-type, nor rapid (human ether á go-go-related gene-type) inactivation. With 2 mM [Mg(2+)](o), I(K) activation kinetics was independent of holding potential, suggesting the absence of ether á go-go-type K+ channels. Extracellular applications of TEA and verapamil (IC(50) = 11 microM) rapidly (12 s) inhibited I(K) in LNCaP cells. Blocking was also rapidly reversible. Intracellular TEA (1 mM), verapamil (1 mM), and membrane-impermeable N-methyl-verapamil (25 microM) did not influence whole-cell I(K), although both phenylalkylamines inhibited single-channel currents in inside-out patches. Extracellular application of N-methyl-verapamil (25 microM) had no influence on I(K). Our results are compatible with the hypothesis that, in LNCaP cells expressing C-type inactivation-deficient voltage-activated K+ channels, phenylalkylamines interact with an intracellular binding site, and probably an additional hydrophobic binding site that does not bind charged phenylalkylamines. The inhibiting effects of verapamil and TEA on I(K) were additive, suggesting independent K+-channel blocking mechanisms. Indeed, TEA (1 mM) reduced a single-channel conductance (from 7.3 +/- 0.5 to 3.2 +/- 0.4 pA at a membrane potential of +50 mV, n = 6), whereas verapamil (10 microM) reduced an open-channel probability (from 0.45 +/- 0.1 in control to 0.1 +/- 0.09 in verapamil-treated cells, n = 9). The inhibiting effects of verapamil and TEA on LNCaP cell proliferation were not multiplicative, suggesting that both share a common antiproliferative mechanism initiated through a K+ channel block.

Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence.

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg. kg(-1). day(-1)). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.

Store depletion and store-operated Ca2+ current in human prostate cancer LNCaP cells: involvement in apoptosis.

1. In the present study, we investigated the mechanisms involved in the induction of apoptosis by the Ca2+-ATPase inhibitor thapsigargin (TG), in androgen-sensitive human prostate cancer LNCaP cells. 2. Exposure of fura-2-loaded LNCaP cells to TG in the presence of extracellular calcium produced an increase in intracellular Ca2+, the first phase of which was associated with depletion of intracellular stores and the second one with consecutive extracellular Ca2+ entry through plasma membrane, store-operated Ca2+ channels (SOCs). 3. For the first time we have identified and characterized the SOC-mediated membrane current (Istore) in prostate cells using whole-cell, cell-attached, and perforated patch-clamp techniques, combined with fura-2 microspectrofluorimetric and Ca2+-imaging measurements. 4. Istore in LNCaP cells lacked voltage-dependent gating and displayed an inwardly rectifying current-voltage relationship. The unitary conductance of SOCs with 80 mM Ca2+ as a charge carrier was estimated at 3.2 +/- 0.4 pS. The channel has a high selectivity for Ca2+ over monovalent cations and is inhibited by Ni2+ (0.5-3 mM) and La3+ (1 microM). 5. Treatment of LNCaP cells with TG (0.1 microM) induced apoptosis as judged from morphological changes. Decreasing extracellular free Ca2+ to 200 nM or adding 0.5 mM Ni2+ enhanced TG-induced apoptosis. 6. The ability of TG to induce apoptosis was not reduced by loading the cells with intracellular Ca2+ chelator (BAPTA-AM). 7. These results indicate that in androgen-sensitive prostate cancer cells the depletion of intracellular Ca2+ stores may trigger apoptosis but that there is no requirement for the activation of store-activated Ca2+ current and sustained Ca2+ entry in induction and development of programmed cell death.