Epilepsy Research in the Institute of Physiology of the Czech Academy of Sciences in Prague.

Starting from simple clinical statistics, the spectrum of methods used in epilepsy research in the Institute of Physiology of the Czechoslovak (now Czech) Academy of Sciences progressively increased. Professor Servít used electrophysiological methods for study of brain activity in lower vertebrates, neuropathology was focused on electronmicroscopic study of cortical epileptic focus and ion-sensitive microelectrodes were used for studies of cortical direct current potentials. Developmental studies used electrophysiological methods (activity and projection of cortical epileptic foci, EEG under the influence of convulsant drugs, hippocampal, thalamic and cortical electrical stimulation for induction of epileptic afterdischarges and postictal period). Extensive pharmacological studies used seizures elicited by convulsant drugs (at first pentylenetetrazol but also other GABA antagonists as well as agonists of glutamate receptors). Motor performance and behavior were also studied during brain maturation. The last but not least molecular biology was included into the spectrum of methods. Many original data were published making a background of position of our laboratory in the first line of laboratories interested in brain development.

[Management of vulvovaginal atrophy: Physical therapies. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Traitements physiques de l'atrophie vulvovaginale. RPC Les femmes ménopausées du CNGOF et du GEMVi.

INTRODUCTION: For some patients, local hormonal or non-hormonal treatments for genitourinary syndrome of menopause (SGUM) are contraindicated or insufficiently effective. Different physical therapies such as vaginal laser therapy, radiofrequency therapy, photobiomodulation therapy and local injection of hyaluronic acid, autologous fat (lipofilling) and platelet rich plasma (PRP) have been proposed as alternatives. OBJECTIVE: The objective of this review was to elaborate guidelines for clinical practice regarding the physical therapies proposed for management of vulvovaginal atrophy (AVV). METHODS: A systematic review of the literature on AVV management with physical therapies was conducted on Medline between January 2014 and December 2020. RESULTS: Regarding vaginal laser therapy, there are few randomized controlled trials and no formal conclusions can be drawn. The fractional CO2 laser did not demonstrate its superiority over local estrogen therapy. The ERBIUM:YAG laser has not been studied in randomized controlled trials. The lack of follow-up on the vaginal laser and the series of cases reporting risks of vaginal stenosis or chronic pain do not encourage recommending it as a first-line treatment. The literature concerning other physical treatments of AVV is weak concerning the genital area. CONCLUSION: CO2 or ERBIUM:YAG vaginal lasers are not the first-line treatment for AVV (grade C). In patients with a contraindication to local hormonal treatments, treatment with vaginal CO2 laser or ERBIUM:YAG may be considered after information about the risks (burn, stenosis, pain) (expert opinion). The other physical treatments of SGUM have to be evaluated.

[Optimizing training in limited obstetric ultrasound for midwives through a combination of e-learning and simulation]. / E-learning et simulation en échographie focalisée pour la formation continue des sages-femmes en salle de naissance.

OBJECTIVE: To evaluate a training program in limited obstetric ultrasound, combining e-learning and simulation. METHODS: This a descriptive cohort study in Single-center study conducted in a French university hospital. Thirty-three practicing midwives who had not received basic training in ultrasonography had unlimited access to an e-learning platform offering interactive theoretical instruction modules. Then, they attended a one-day simulator-based obstetric ultrasound workshop. A theoretical competency test was taken before the e-learning component (T1), then before (T2) and after (T3) the simulation workshop. Their competency in specific practical tasks was assessed before and after the workshop. A learner satisfaction questionnaire was completed after the program. RESULTS: The mean score obtained in the theoretical competency test was 46.6% (range 8.3-83.3%) at T1, 87.2% (66.6-100%) at time T2, and 91.6% (66.6-100%) at T3. Significant improvements were observed between times T1 and T2 (P<0.001) or T3 (P<0.001), as well as in the performance of certain practical tasks, such as placental location (P=0.02) and visualization of the cervix (P=0.03). The mean number of logins to the e-learning platform during the program was 11.2 per participant (6-24). Most participants were satisfied with the training and reported an improvement in their daily practice. CONCLUSION: Training in limited obstetric ultrasound, combining e-learning to acquire theoretical knowledge and a hands-on simulation workshop, appears to meet the needs of practicing midwives. Most participants were satisfied with the proposed teaching and the rapid acquisition of ultrasound skills applicable to their clinical practice.

[Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review]. / Intérêt de la toxine botulinique A dans le traitement des troubles pelvi-périnéaux de la personne âgée.

INTRODUCTION: The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly. METHODS: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated. RESULTS: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended. CONCLUSION: BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.

Do stereoisomers of homocysteic acid exhibit different convulsant action in immature rats?

Mechanism of ictogenesis of D- and L-stereroisomers of homocysteic acid was studied in 12-day-old rats by means of antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. There was no qualitative difference between the two stereoisomers in generation of emprosthotonic (flexion) as well as generalized tonic-clonic seizures. Moderate differences were observed in the first, nonconvulsive effects of the two isomers. As generation of the two types of seizures is concerned, NMDA and AMPA participate in generalized tonic-clonic seizures whereas NMDA receptors play a dominant role in generation of flexion seizures.

[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review]. / Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue.

AIM: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. METHODS: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. CONCLUSION: Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

Ontogenetic development of sensitivity of the cerebral cortex to an antagonist of GABA(A) receptor bicuculline.

Local application of four concentrations of bicuculline methiodide (a specific antagonist of GABA(A) receptors) was used to study a sensitivity of somatosensory cortex in four age groups of immature rats with implanted electrodes. Presence and latencies of two epileptic phenomena (focal discharges and seizures) were evaluated. Focal discharges exhibited moderate tendency to a decrease of sensitivity to bicuculline methiodide with maturation. Concentration-effect relation of incidence of focal discharges was observed only in 7- and 12-day-old but not in older animals. Results with incidence and latencies of seizures did not show relations to age or concentration of bicuculline. Neither of the epileptic phenomena can be used as a reliable index of cortical maturation.

[Pathophysiology of detrusor underactivity in the elderly]. / Physiopathologie de l'hypoactivité détrusorienne de la personne âgée.

AIM: The aim of this study was to review the evidence regarding the pathophysiology of detrusor underactivity in the elderly. METHODS: A literature review was conducted in July 2016 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: The prevalence of detrusor underactivity has been reported to range from 8% to 48% depending on the definition used and the age of the population studied. Current data suggest that aging may itself be a causative factor of detrusor underactivity through myogenic dysfunctions (ultrastructural degeneration of the detrusor muscle) and neurogenic dysfunctions (by degeneration of efferent but mostly afferent innervation mechanisms). Beyond these inherently age-related mechanisms, many comorbidities whose prevalence increase with age (diabetes, bladder outlet obstruction, estrogen deficiency, atherosclerosis, etc.) may be implicated in the development of detrusor underactivity in the elderly. The role played by detrusor overactivity in the appearance of detrusor underactivity must be considered separately as both seem to be the expression of the same condition of the lower urinary tract responding to different stages and secondary to numerous etiopathogenic factors which modulate its progression and clinical expressions. CONCLUSION: Pathophysiology of detrusor underactivity remains poorly understood but seems to imply myogenic and neurogenic factors which are favored, besides the aging per se, by various and numerous comorbidities which prevalence increase with age (diabetes, bladder outlet obstruction…).

Influence of early life status epilepticus on the developmental expression profile of the GluA2 subunit of AMPA receptors.

AMPA receptors (AMPARs) are responsible for fast excitatory neurotransmission, and their prolonged activation can result in the generation and spread of epileptic seizures. At early stages of postnatal development, the majority of AMPARs are permeable to both Na(+) and Ca(2+) ions. This permeability, which increases neuronal excitability, is due to the lack of the GluA2 subunit, encoded by the GRIA2A gene, and/or the presence of an unedited GluA2 subunit Q/R site (glutamine instead of arginine). Lithium chloride- and pilocarpine-induced status epilepticus (LiCl/Pilo-SE) in rodents represents a model of severe seizures that result in development of temporal lobe epilepsy (TLE). The aim of this study was to determine how LiCl/Pilo-SE induced early in life (at postnatal day 12; P12) alters normal expression of the GRIA2A gene and GluA2 protein. SE was interrupted by an injection of paraldehyde (Para). Control groups were 1) naïve animals, and 2) siblings of SE rats receiving only LiCl and paraldehyde (LiCl/Para). The expression profile of GRIA2A mRNA was determined via qPCR, and GluA2 protein levels were measured by western blotting. The analysis was performed at 3h (protein levels), and then 3-, 6-, 13-, and 60days, following LiCl/Pilo-SE or LiCl/Para injection (i.e. at P12, P15, P18, P25, P72 respectively). Six different brain regions were analyzed: frontal (CXFR), parietal (CXPAR), and occipital (CXOC) cortex, dorsal (HD) and ventral (HV) hippocampus, and thalamus (TH). There was a significant increase in GRIA2A mRNA expression in the CXFR, CXPAR, and CXOC of P18 SE animals. In CXFR and HD, increased expression of GluA2 AMPAR subunit protein was detected, as well as a surge in GRIA2A mRNA and GluA2 protein expression especially at P18. In HD the surge was detected not only during development (P18), but also later in life (P72). Since high levels of GluA2 can be neuroprotective (by decreasing Ca(2+) permeability), our data suggest that the neocortex and dorsal hippocampus are able to activate endogenous antiepileptic mechanisms. A marked decrease in the overall expression of GluA2 protein in the HV in the LiCl/Pilo-SE and LiCl/Para rats, suggests that the HV is predisposed to excitotoxicity, not only during development, but even in adulthood. Interestingly, LiCl in combination with paraldehyde can also strongly alter the normal ontogeny of GRIA2A mRNA as well as GluA2 subunit protein expression.

[Absent or hypoplastic thymus: A marker for 22q11.2 microdeletion syndrome in case of polyhydramnios]. / La dysgénésie thymique : marqueur de microdélétion 22q11.2 dans le bilan d'un hydramnios.

OBJECTIVES: In prenatal diagnosis of 22q11.2 microdeletion syndrome, without cardiac malformation or multiple associated congenital anomalies, we study the presence of polyhydramnios and its association with thymic dysgenesis. MATERIALS AND METHODS: This was a multicenter retrospective observational study. It was performed in two multidisciplinary centers for prenatal diagnosis in the south of France between January 1, 2010 and June 30, 2013. Inclusion criteria were prenatal diagnosis of 22q11.2 deletion syndrome. We excluded from the study any fetus with cardiac malformation or multiple associated congenital anomalies. RESULTS: During the inclusion period, eleven antenatal diagnoses of 22q11.2 microdeletion syndrome have been made. Six cases were excluded: 5 fetuses with cardiac malformation and one with multiple associated congenital anomalies. Therefore, five cases of isolated polyhydramnios were included. All 5 fetuses had a thymic dysgenesis: 3 had a thymic agenesis and 1 thymic hypoplasia diagnosed by sonography and 1 had a thymic agenesis diagnosed by retrospective reading of fetal MRI. CONCLUSION: When faced with a polyhydramnios, the presence of a thymic dysgenesis should be search for by ultrasound screening and would alert to the possibility of a 22q11.2 microdeletion syndrome. The confirmation of this is diagnosis by amniocentesis would enable improved antenatal support for parents and would enable early implementation of the multidisciplinary neonatal care that is required to avoid serious complications of this syndrome.

Hémorragie du post-partum immédiat : technique de méchage

Le Méchage intra-utérin (MIU) est une technique d'étape importante pour stopper l'Hémorragie du post-partum (HPP); il est pratiqué après l'inefficacité des moyens médicaux et avant l'étape chirurgicale. Les préalables pour une PEC efficace sont évoqués puis une description détaillée de la technique de méchage est faite, terminée par une étude portant sur 265 cas d'HPP sur 7 ans dont 119 cas de méchage. Avec 93,3% de taux de succès et un coût très faible, le MIU est très efficace dans la PEC de l'HPP. Aucune complication à court ou long terme n'est constatée dans la cohorte présentée. 58 cas de grossesses spontanées sont constatés par la suite

[Efficacy of a medical device containing liposomal hyaluronic acid against vulvo-vaginal dryness]. / Efficacité d'un dispositif médical à base d'acide hyaluronique liposomé contre la sécheresse vulvo-vaginale.

OBJECTIVES: Hyaluronic acid (HA) is present in the vulval and vaginal conjonctive tissue. It possesses hydrating and healing properties and is indicated to treat menopause induced vulvo-vaginal atrophy. The goal of this study is to evaluate the efficacy of a medical device containing liposomal HA upon patients of different ages suffering from vulvo-vaginal dryness (VVD). METHODS: Tested product Mucogyne® was applied 3 times a week for 84 days by 47 patients, 28 premenopausal young women (mean age: 32 years old) and 19 post-menopausal women (mean age: 57.5 years old) all suffering from VVD associated to spontaneous pain and dyspareunia. Clinical evaluations and Vaginal Health Index (VHS) were calculated at 0, 1 and 3 months. RESULTS: A significant clinical improvement (P<0.001) occurred at 1 month (-25 % for dryness and -46 % for pain) and at 3 months (respectively -86 and -79 %). VHS was significantly improved (P<0.001) from 30 % at 1 month to 72 % after 3 months. CONCLUSION: Liposomal AH significantly decreases symptoms and clinical signs of VVD at all ages and represents a safe and efficient alternative to topical and/or systemic hormonal therapy after menopause.

[Methods of pushing at vaginal delivery and pelvi-perineal consequences. Review]. / Mode de poussée à l'accouchement et conséquences pelvi-périnéales. Revue de la littérature.

INTRODUCTION: The main objective of that review was to evaluate the pelvi-perineal consequences of the different methods of pushing at vaginal delivery. METHODS: A review on PubMed, the Cochrane Library and EM-Premium was performed from 1984 to 2014. Among 29 manuscripts analysed, only nine randomised controlled trials (including one meta-analysis of three trials) comparing Valsalva and spontaneous pushing were selected. A 10 th study, secondary analysis of a randomized controlled trial comparing different methods of perineal protection (warm compresses, massage and manual protection), was also selected. RESULTS: Two trials have shown that spontaneous pushing reduces the risk of perineal tears, but studies were heterogeneous and discordant results do not allowed definitive conclusions. Results on the duration of the second stage of labour are conflicting. The method of pushing does not seem to affect the rate of episiotomy, instrumental delivery and cesarean section. Maternal satisfaction seems to be better after spontaneous pushing. It seems that there is no negative effect of spontaneous pushing on neonate well-being, and one study has shown a significant improvement of prenatal fetal parameters during the expulsive phase. CONCLUSION: According to current knowledge, both techniques of pushing during the expulsive phase at delivery seem comparable in terms of duration, risk of perineal tears and neonatal outcome.

[Assessment of gynecology obstetric interns training on birth simulator]. / Évaluation de la formation des internes de gynécologie obstétrique sur simulateur d'accouchement.

OBJECTIVE: The aim of this study was to assess the gynecology obstetric residents training on a birth simulator. MATERIALS AND METHODS: This is a prospective monocentric study, which had included residents at the beginning of their formation and performed on SIMone™, 3B SCIENTIFIC(®) birth simulator. It had included four sessions (supervised by two seniors registrar): two on instrumental extraction (vacuum and forceps) and two on labor monitoring. The two sessions were performed at one month. A theoretical formation was accomplished after the first assessment. Three assessments were performed based on two score scales (extraction and labor monitoring). A free training was allowed at each extraction session. RESULTS: Twelve interns were included in this study. There was a significant scores improvement between first and third session for instrumental extraction (2.4 points on 11 [±1.8] vs. 8 [±0.9]; [P<0.05]) and for labor monitoring (5.2 [±1.4] points on 9 vs. 6.6 [±1.3]; [P<0.05]). Interns considered this training improved their theoretical and practical knowledge for respectively 11 and 12 interns on 12. For 9 interns, a most important debriefing with teachers was desirable. CONCLUSION: Training on birth simulator allows an improvement of knowledge and skill of gynecology obstetric interns. A structured debriefing should be instituted after the sessions.

[Evaluation of urine postvoid residuals in post-partum period: a prospective and descriptive clinical study]. / Évaluation des résidus postmictionnels du postpartum: étude prospective descriptive.

INTRODUCTION: Few studies have evaluated urine postvoid residuals (PVRs) and their risk factors during the post-partum (PP) period. The aim of this prospective study was to screen postvoid residuals in a cohort of patients in PP, and to identify the risk factors. MATERIALS AND METHODS: For three months, patients in PP were given an evaluation of their PVR (ultrasounds method) after a spontaneous urination. Clinical data as regards delivery were collected. RESULTS: One hundred and sixty-eight patients were included. Among them, 61% had a urine volume at the first urination over 500 mL, and 52% presented with a pathological PVR (PVR over 150 mL for a urine volume over 150 mL). The median PVR was 153.50 mL. The median volume of the first spontaneous urination was 400 mL. Among patients with a pathological PVR, the total duration of the labor and the duration of its second phase were significantly longer (P=0.003 and P<0.05, respectively), and the volume of the first urination was higher. Indwelling catheterization during the delivery decreased the volume of the first spontaneous urination (volume over 500 mL in 28% vs 72% of patients, P=0.017) but was not associated with a decreased PVR in non-pathological deliveries. Instrumental deliveries were associated with higher PVRs than caesarean or physiological deliveries (244 mL, 180 mL et 156 mL; P=0.033). A bacteriuria was not significantly associated with PVR (54% vs 49%, P>0.05). CONCLUSION: We were able to identify risk factors for PVR in the PP, such as the duration of labor, instrumental delivery and elevated volume of the first urination after delivery.

[Uterine packing efficacy in postpartum hemorrhage. About 99 cases. The experience of a French hospital level 2 A]. / Le méchage intra-utérin: utilité et place dans la prise en charge de l'hémorragie du post-partum immédiat. À propos de 99 cas. L'expérience d'un centre hospitalier français de niveau 2 A.

OBJECTIVE: To show place and usefulness of intra-uterine compression in management of post-partum haemorrhage (PPH). MATERIAL AND METHODS: Retrospective cohort study, monocentric, including all consecutive cases of PPH during four years in an obstetric department of level IIa. The compression technique was the use of intra-uterine meshes, and efficacy was defined as a total and immediate bleeding interruption. Apart of meshes, patients received sulprostone then ocytocine and antibiotics. RESULTS: The rate of PPH was 3.8% on 3913 deliveries. One hundred and fifty patients with PPH were managed following CNGOF guidelines. Ninety-nine patients were also treated with intra-uterine meshes during 24hours. The rate of mesh success was 91.9%. Sixty-two cases of subsequent pregnancies were also reported. CONCLUSION: In case of PPH, intra-uterine compression using meshes is simple, cheap and efficient. That technique could avoid the use of invasive surgical procedures and a safer post-natal transfer.

[Multicentric prospective randomized and controlled study assessing effectiveness of intravaginal electrostimulation at home compared to usual care in female patients with urinary incontinence and prior perineal reeducation]. / Étude prospective multicentrique randomisée évaluant l'intérêt de l'électrostimulation intravaginale à domicile après rééducation périnéale pour incontinence urinaire.

OBJECTIVES: In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. PATIENTS AND METHODS: Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. RESULTS: A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). DISCUSSION AND CONCLUSION: Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported as worsened in 16.5% of the UC group. Using GYNEFFIK(®) favorably impacts quality of life, particularly physical activity and vitality and decreases emotional consequences of UI (i.e. anxiety and depression score as assessed by HAD scale).

Breast conserving surgery in multicentric breast cancer, preliminary data of our experience.

INTRODUCTION: It is widely supported that multicentric disease of the breast (MCDB) is a contraindication of breast conservative surgery (BCS). MATERIALS AND METHODS: This is a multicentric study (two breast cancer units from Greece, one from France) involving patients with at least two primary tumors in separate quadrants of the breast and no diffuse suspicious microcalcifications on mammography. Sixty-one patients were included in the study, but 49 were followed up to the end. Patients were randomly assigned in total mastectomy (TM) and BCS groups. End point of the study was disease-free survival rates three and five years after initial operation. RESULTS: Three years after BCS, local recurrence (LR) was observed in two patients (7%) and one after five years (total recurrence rate: 11%). A TM was performed in these patients, and in two there was no LR or distant metastasis (DM) five years after. The third patient was disease free two-years later. Three years after TM, eight patients (36.4%) had DM and 14 (63.6%) did not (p = 0.004). Five years after TM, eight patients (36.4%) had DM and 14 patients (63.6%) di not (p = 0.03). CONCLUSION: The results showed that conservative surgery was an alternative surgical option in multicentric breast cancer with good results regarding disease-free survival and recurrence.

[Impact on cognitive function of anticholinergic drugs used for the treatment of overactive bladder in the elderly]. / Traitement anticholinergique de l'hyperactivité vésicale de la personne âgée et ses impacts sur la cognition. Revue de la littérature.

OBJECTIVES: Describe the central nervous system (CNS) adverse effects of anticholinergic drugs used for the treatment of overactive bladder (OAB) in the elderly. PATIENTS AND METHODS: Relevant data from the literature were identified primarily through a Medline search of articles published through December 2013. The search terms included overactive bladder, central nervous system, elderly, anticholinergic, and antimuscarinic. Articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly. RESULTS: Several anticholinergic drugs are available for the treatment of OAB, including oxybutinin, tolterodine, trospium chloride, solifenacine, fesoterodine. Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutinin, lower for tolterodine, solifenacine, and darifenacine, and lowest for fesoterodine and trospium chloride. Unwanted CNS adverse effects depend in part on patient specific variability in pharmacokinetic parameters, blood-brain barrier permeability, degree of cholinergic neuronal degeneration, total anticholinergic drug burden and patient's baseline cognitive status. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and coma. Among the different anticholinergic agents, oxybutinin has been associated with cognitive impairment and trospium chloride and fesoterodine have shown favorable CNS tolerability. CONCLUSIONS: Anticholinergic drugs improve significatively overactive bladder symptoms in older adults. However, potential CNS adverse effects of anticholinergic agents used in OAB must lead to a full evaluation before and during the treatment in order to evaluate benefice, risks and central side effects in this frail population.