[Prolapse and urinary incontinence in women : place of the general practitioner]. / Prolapsus et incontinence urinaire chez la femme : la place du médecin généraliste.

The ageing of the population, having access to good quality of care, will result in an increase in the prevalence of pelvic floor diseases. Those persons, often in good general health, may experience difficulties in accepting functional pathologies, associated with loss in quality of life. One out of 2 women will have a pelvic floor problem and 1 out of 9 will have a surgical perineal procedure before the age of 80 years. The unitary character of the pelvic floor, a complex functional anatomic region, is often forgotten, essentially because the patients complain about one main pathology like urinary incontinence, genital prolapse, constipation and sexual disorders or chronic pain and will consult one specific specialist. Our role as health care professionals is to be aware of those associated pathologies and to obtain an optimal quality of care. The actual evolution towards specific clinical pathways with the integration of office provided care outside the hospital, needs to become the new standard of care. We try to give an overview of the different preventive, diagnostic and therapeutic options, available in a general practitioner's office. Taking care of the pelvic floor needs to be done in a global and pluridisciplinar setting. Referring towards specialised centres as well as the integration of the general practitioner, especially for the more complex cases, is essential.

Le vieillissement de la population ayant un accès à des soins de santé de qualité, mène à une augmentation de la prévalence des pathologies du périnée. Ces personnes, souvent en bonne santé, auront des difficultés à accepter des pathologies fonctionnelles associées à une perte de qualité de vie car ces pathologies du périnée représentent un large éventail de pathologies fonctionnelles. On estime qu'une femme sur 2 aura un jour un problème périnéal, 1 sur 9 devra subir une intervention chirurgicale périnéale avant l'âge de 80 ans. Le caractère unitaire du périnée, région anatomique fonctionnelle complexe, est malheureusement souvent oublié, au départ parce que les patientes se présentent chez leur médecin pour une plainte bien spécifique sans se rendre compte de cette unité et de l'association de différents symptômes comme l'incontinence urinaire, le prolapsus génital, la constipation et des troubles sexuels et douloureux. Notre rôle en tant que professionnel de santé est de ne pas négliger ces plaintes associées, afin d'avoir une qualité de soin optimale. L'évolution actuelle vers le développement des trajets de soin avec l'intégration standardisée des soins en extrahospitalier est évidente. Nous avons tenté dans cet article de donner une revue des moyens préventifs, diagnostiques et thérapeutiques applicables dans le cabinet du médecin généraliste. La prise en charge du périnée devrait toutefois avoir lieu de manière globale et de préférence pluridisciplinaire. La référence vers les centres pluridisciplinaires comme également l'intégration du médecin généraliste dans les trajets de soin, surtout pour les cas plus complexes, est essentielle.

Value of the 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. A pilot study.

OBJECTIVE: The non-invasive diagnosis of endometriosis remains challenging. Recent data suggested that somatostatin might be involved in its pathogenesis. High sensitive visualization of somatostatin receptors expression is possible using PET-CT imaging after the administration of a 68Ga-labeled somatostatin analog (DOTATATE) that will bind to the somatostatin receptor sub-types 2 and 5. The aim of the present study was to assess the usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. STUDY DESIGN: This is a prospective, single center pilot study. A pre operative 68Ga-DOTATATE PET-CT was performed in all of the patients who presented with suspected endometriosis and who were scheduled for a laparoscopy. Surgical endometriosis staging and histopathological analysis, including somatostatin receptors SST1, 2 and 5 immunohistochemistry (IHC) of removed specimens, were confronted to the results of the 68Ga-DOTATATE PET-CT. RESULTS: 12 patients were included in this study. 68Ga-DOTATATE PET-CT performed pre operatively showed increased pathologic uptake in four patients with a deep infiltrating endometriosis (DIE) recto-vaginal lesion and in another patient with an adenomyoma. Expression of SST1, 2 and 5 receptors in surgical specimens was confirmed by IHC in these five lesions. Neither superficial peritoneal endometriosis, nor ovarian endometrioma were found to show an increased pathologic uptake on 68Ga-DOTATATE PET-CT. IHC analysis confirmed that SST1, 2, and 5 receptors were not present in these lesions. CONCLUSION: The results observed in this small size series of patients seem to confirm expression of somatostatin receptors only in recto-vaginal DIE and focal adenomyosis lesions. The usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of this entity is uncertain. Future research should concentrate on studying the role of somatostatin in the pathogenesis of DIE.

[The treatment of female urinary incontinence]. / Le traitement de l'incontinence urinaire chez la femme.

Urinary incontinence isn't a fatality anymore. This pathology, which handicaps a large majority of the female population, should be treated in a global approach of the pelvic floor pathologies. Up to 25% of women over 65 years will suffer from urinary incontinence but age is not a discriminating factor in the appearance of this pathology. Comportemental and physiotherapeutical treatments are primordial. In case of lack of good results, surgery may offer good results in urinary incontinence and pharmacological treatment for urge urinary incontinence. In this text, the most common treatment options will be discussed.

[Toxic dermatitis caused by pseudoephedrine: apropos of a case]. / Toxidermie à la pseudoéphédrine: à propos d'un cas.

Allergy to pseusoephedrine seems to be rare and has been described as responsible of urticaria, contact dermatitis, fixed non-pigmenting erythema or pseudoscarlatina. We report the case of a male patient who presented a recurrent erythema after administration of different treatments including pseudoephedrine. A cutaneous biopsy was compatible with erythema multiform. Patch tests confirmed the diagnosis of allergy to pseudoephedrine but resulted in a reappearance of symptoms.

Pathological tau phenotypes. The weight of mutations, polymorphisms, and differential neuronal vulnerabilities.

In tauopathies, comparative biochemistry of tau aggregates shows that they differ in both phosphorylation and content of tau isoforms. Six tau isoforms are found in human brain that contain either three (3R) or four microtubule-binding domains (4R). In Alzheimer's disease, all six of the tau isoforms are phosphorylated and aggregate into paired helical filaments. They are detected by immunoblotting as a major tau triplet (tau 55, 64, and 69). In corticobasal degeneration and progressive supranuclear palsy, only phosphorylated 4R-tau isoforms aggregate and appear as a major tau doublet (tau 64 and 69). In Pick's disease, only phosphorylated 3R-tau isoforms aggregate into filaments and are characterized by another major tau doublet (tau 55 and 64). Finally, recent findings provide a direct link between a genetic defect in tau and its abnormal aggregation into filaments in frontotemporal dementia with parkinsonism linked to chromosome 17. In the present study, the question of a relationship between tau isoforms and cell morphology is raised. To answer this question, stably transfected human neuroblastoma SY5Y cell lines with either 3R- or 4R-tau isoforms are established. Cell morphology and tau phosphorylation were modified, suggesting that cells undergo profound changes in their metabolism and viability.

Synthesis and ligand binding of nortropane derivatives: N-substituted 2beta-carbomethoxy-3beta-(4'-iodophenyl)nortropane and N-(3-iodoprop-(2E)-enyl)-2beta-carbomethoxy-3beta-(3',4'-disubstituted phenyl)nortropane. New high-affinity and selective compounds for the dopamine transporter.

Two novel series of iodinated N-substituted analogs of 2beta-carbomethoxy-3beta-(4'-iodophenyl)tropane (beta-CIT) and N-(3-iodoprop-(2E)-enyl)-2beta-carbomethoxy-3beta-(3',4'-dis ubstituted phenyl)nortropane were synthesized. They were evaluated for their inhibitory properties on dopamine (DA(T)), serotonin (5-HT(T)), and norepinephrine (NE(T)) transporters in rat brain homogenates using [3H]GBR-12935, [3H]paroxetine, and [3H]nisoxetine as specific ligands. All new N-substituted analogs of beta-CIT exhibited higher DAT selectivity over both 5-HT(T) and NE(T) than beta-CIT. Moreover compounds with the N-substituents propynyl (6), crotyl (4), 2-bromoprop-(2E)-enyl (5), and 3-iodoprop-(2E)-enyl (3d) showed similar to higher DA(T) affinities than beta-CIT (respectively 14, 15, 30, and 30 nM vs 27 nM). Compound 3d was found to be the most selective DA(T) agent of this series (5-HTT/DA(T) = 32.0 vs 0.1 for beta-CIT). The N-(3-iodoprop-(2E)-enyl) chain linked to the tropane nitrogen was therefore maintained on the tropane structure, and phenyl substitution was carried out in order to improve DA(T) affinity. K(i) values of N-(3-iodoprop-(2E)-enyl)-2beta-carbomethoxy-3beta-(3',4'-dis ubstituted phenyl)nortropanes revealed that phenyl, 4'-isopropyl, and 4'-n-propyl derivatives weakly inhibited specific binding to DA(T), whereas phenyl substitution with 4'-methyl (3c), 3',4'-dichloro (3b), and 4'-iodo (3d) yielded high-DA(T) reuptake agents with increased DA(T) selectivity compared to beta-CIT. These results demonstrate that the combination of a nitrogen and a phenyl substitution yields compounds with high affinity and selectivity for the dopamine transporter which are usable as SPECT markers for DA neurons.

Interaction of metaiodobenzylguanidine with cardioactive drugs: an in vitro study.

Metaiodobenzylguanidine (MIBG), an analogue of noradrenaline, is used to explore the functional integrity of sympathetic nerve endings in the human heart. Various drugs inhibit noradrenaline transport systems and may block the uptake of MIBG. As in vivo studies of the effect of these drugs on myocardial [123I]MIBG uptake are often difficult to perform, we used an in vitro human blood platelet model for this purpose. A platelet preparation from healthy volunteers was incubated with [125I]MIBG alone or different concentrations of drugs currently used in cardiology. Labetalol and propranolol inhibited [125I]MIBG uptake, whereas all other drugs tested (other beta-blockers, calcium inhibitors, digoxin and amiodarone) had no effect even at doses exceeding 50 microM. The labetalol dose inhibiting 50% of [125I]MIBG uptake was lower than the plasma concentration of this drug in treated patients, whereas the propranolol dose was higher. This in vitro study of the effect of drugs on MIBG uptake by human blood platelets is predictive of their in vivo effect on myocardial uptake of [123I]MIBG in treated patients, provided that plasma concentration is taken into account.

Synthesis of 4'-iodo-5-methoxy-valerophenone O-(2-aminoethyl)oxime as an agent for exploration of serotoninergic transporter.

The serotonin reuptake process is observed in the central nervous system and in cells derived from the neural crest. It would therefore be of great interest to visualize this reuptake for brain exploration and to visualize the tumors derived from these cells (Apudome). Fluvoxamine has been described as a specific uptake inhibitor for serotonin uptake and we therefore supposed that an iodinated derivative of this compound would be a suitable tracer for this purpose. We had shown by computer-assisted investigation that the trifluoromethyl group of fluvoxamine can be replaced by iodine without changing the steric hindrance of the structure. We therefore expected that this result would allow the development of a new iodinated ligand for human exploration by SPECT which would inhibit for the serotoninergic transporter. This new ligand is 4'-iodo-5-methoxyvalerophenone O-(2-aminoethyl)oxime in its E configuration. In vitro binding studies demonstrated that this iodinated ligand has a weaker affinity for the serotonin uptake sites than fluvoxamine. Steric hindrance is not sufficient to predict affinity, other structural factors such as electronic density and dipole moment must be considered to explain the biological difference between fluvoxamine and its iodinated analog.

Iodoethylspiperone, a new potential agent for exploration of central dopamine D2 receptors: synthesis and preliminary in vivo study.

We synthesized a new spiperone derivative: iodoethylspiperone (IES) to perform dopamine D2 receptor exploration by SPECT. IES was prepared from a precursor: tosylethylspiperone, and characterized by i.r. and 1H-NMR analyses. [125I]IES was obtained with 80% yield. In vivo biodistribution in rats showed a high and specific uptake in the striatum. The uptake ratio between the striatum and the cerebellum reached a maximum value 4 h after injection (10.05 +/- 2.81). IES labeled with 123I should be a promising new agent to investigate D2 receptors in the living human brain.