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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.
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Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/administración & dosificación , Trastornos del Suelo Pélvico/tratamiento farmacológico , Factores de Edad , Anciano , Toxinas Botulínicas Tipo A/efectos adversos , Humanos , Inyecciones , Fármacos Neuromusculares/efectos adversos , Trastornos del Suelo Pélvico/fisiopatología , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológicoRESUMEN
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.
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Enfermedades Cardiovasculares/inducido químicamente , Antagonistas Muscarínicos/efectos adversos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Factores de Edad , Anciano , Enfermedades Cardiovasculares/fisiopatología , Humanos , Antagonistas Muscarínicos/uso terapéuticoRESUMEN
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 ).
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Enfermedades de la Vejiga Urinaria/fisiopatología , Anciano , Humanos , Enfermedades de la Vejiga Urinaria/etiologíaRESUMEN
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.
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Parto Obstétrico/métodos , Laceraciones/etiología , Laceraciones/prevención & control , Perineo/lesiones , Femenino , Humanos , EmbarazoRESUMEN
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.
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Trastornos Puerperales/diagnóstico , Retención Urinaria/diagnóstico , Adulto , Femenino , Humanos , Estudios Prospectivos , Trastornos Puerperales/epidemiología , Factores de Riesgo , Retención Urinaria/epidemiologíaRESUMEN
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.
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Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Adulto , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de NeoplasiasRESUMEN
OBJECTIVES: Provide guidelines presented as an algorithm for practical evaluation and first line therapy of urinary incontinence in elderly. PATIENTS AND METHODS: Guidelines using formalized consensus guidelines method. These guidelines have been validated by a group of 40 experts quoting proposals, subsequently reviewed by an independent group of multidisciplinary experts (urologist, general practitioner, neurologist, gynecologist, geriatrist, specialist in physical medicine and rehabilitation). RESULTS: By means of 3 rounds of interrogation of the expert panel, GRAPPPA algorithm was constructed. This algorithm take in account both evaluation and first line therapeutic options in the different type of incontinences observed in this population (urge, stress and mixed incontinence). Initial evaluation consists to track down urinary retention (and subsequently fecal stool impaction, use of anticholinergic or morphinic drugs), urinary tract infection and cognitive impairment. Haematuria, bladder-pelvic pain, history of radiotherapy or recent pelvic surgery, lead to refer the patient to a specialized unit. First line therapy is in all the cases pelvic floor training, use of local oestrogenotherapy and dietetic measures. In urge incontinence, anticholinergic drugs may be used. CONCLUSIONS: Implementation of this algorithm may promote best practice in management of urinary incontinence in elderly.
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Algoritmos , Incontinencia Urinaria/diagnóstico , Incontinencia Urinaria/terapia , Anciano , HumanosRESUMEN
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.
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Antagonistas Colinérgicos/uso terapéutico , Trastornos del Conocimiento/inducido químicamente , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Anciano , Antagonistas Colinérgicos/efectos adversos , HumanosRESUMEN
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.
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OBJECTIVE: To determine a syndrome score threshold on PFDI or PFIQ predictive of a significant improvement in post-operative functional results. DESIGN: A retrospective case review (Canadian Task Force Classification II-2). SETTING: University and research hospital. POPULATION: Women diagnosed with pelvic organ prolapse and repaired with synthetic vaginal mesh. METHODS: Quality of life was arbitrarily considered to have improved significantly if the score decreases by more than 50% between pre-operatively and 36 months post-operatively. We investigated the pre-operative cut-off score predictive of no quality of life improvement at M36 from a prospective trial for surgical pelvic organ prolapse treatment. RESULTS: The most accurate pre-operative cut-off score predicting a failure to improve quality of life at 36 months post-operatively was 62/300 (PFDI Score). This cut-off value had a positive predictive value of 83.6% and specificity of 62.1%. No significant threshold was obtained from the PFIQ score. CONCLUSION: The intensity of symptoms before surgery may interfere as a predictive factor for outcome.
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Diafragma Pélvico/fisiopatología , Diafragma Pélvico/cirugía , Prolapso de Órgano Pélvico/fisiopatología , Prolapso de Órgano Pélvico/cirugía , Calidad de Vida , Vagina/cirugía , Anciano , Canadá , Colposcopía/métodos , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Prolapso de Órgano Pélvico/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Procedimientos de Cirugía Plástica/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Mallas Quirúrgicas , Encuestas y Cuestionarios , Resultado del Tratamiento , Prolapso Uterino/fisiopatología , Prolapso Uterino/cirugíaRESUMEN
OBJECTIVE: We sought to validate a sequence of ultrasonographic mesh measurements to determine the relevant time points in the postoperative monitoring of mesh size. METHODS: Mesh was measured preoperatively ex vivo, prior to insertion, in 25 patients scheduled to undergo vaginal repair of cystocele involving insertion of a Ugytex™ transobturating polypropylene mesh. A 2D/3D perineal ultrasound scan was performed at the end of the surgical procedure (D0), then on third day after surgery (D3) and 6 weeks (W6) after the operation. Medio-sagittal view was used to measure mesh total length and the sagittal arc (length between the most distant points of the mesh). RESULTS: Time-course changes in sagittal arc were marked by a 8% increase on D3 (with respect to D0) and a 20% decrease at W6 (with respect to D3). Mesh total length at W6 on average corresponded to 74% (±20) of mesh total length measured on D3. CONCLUSION: This study showed the changes in the mesh ultrasonographic measurements following vaginal placement by vaginal route. The D3 ultrasound scan should appear to be suitable as a reference for subsequent ultrasonographic monitoring.
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Cistocele/diagnóstico por imagen , Cistocele/cirugía , Mallas Quirúrgicas , Anciano , Femenino , Estudios de Seguimiento , Humanos , Periodo Posoperatorio , Estudios Prospectivos , UltrasonografíaRESUMEN
The purpose of our study was to determine whether a single administration of anticonvulsant doses of two ligands of benzodiazepine receptors, clonazepam and Ro 19-8022, leads to development of rebound phenomena in immature 12-day-old rats. Three tests were used: pentylenetetrazole (PTZ)-induced seizures, isolation-induced ultrasonic vocalizations, and motor performance. Susceptibility to the convulsant effects of PTZ decreased 24 hours, but increased 48 hours, after clonazepam administration. Ultrasonic vocalizations were completely suppressed 30 minutes and 3 hours after clonazepam; a moderate inhibitory effect persisted even at 48 hours. Motor abilities were slightly compromised up to 3 hours. Similar effects of Ro 19-8022 on PTZ-induced seizures and ultrasonic vocalizations were observed 24 and 48 hours after administration; motor performance was not affected. Rebound proconvulsant effects followed different time courses after administration of the two benzodiazepine receptor ligands in developing animals. Anxiolytic-like effects of these drugs were still present at the time when animals exhibited rebound proconvulsant effects.
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Clonazepam/farmacología , Susceptibilidad a Enfermedades/inducido químicamente , Moduladores del GABA/farmacología , Actividad Motora/efectos de los fármacos , Pirrolidinas/farmacología , Quinolizinas/farmacología , Convulsiones/inducido químicamente , Vocalización Animal/efectos de los fármacos , Análisis de Varianza , Animales , Animales Recién Nacidos , Masculino , Pentilenotetrazol , Ratas , Ratas Wistar , Receptores de GABA-A/metabolismo , Convulsiones/metabolismoRESUMEN
1. Four diets were offered to broiler chickens from 7 to 17 d of age; these included a phosphorus-adequate positive control (PC) (4·7 g/kg available P), a sub-optimal P negative control (NC, 2·5 g/kg available P) with (500 and 12500 FTU/kg) and without phytase. Dietary apparent metabolisable energy (AME), dietary net energy for production (NEp), the efficiency of AME retention (Kre), heat production and total tract amino acid digestibility coefficients were determined. The determination of NEp involved a comparative slaughter technique in which growing chickens were fed the experimental diets ad libitum. 2. Feed intake, weight gain and feed conversion efficiency increased significantly in a dose dependent manner in response to dietary phytase activity. Overall, the NEp of the phytase supplemented diets significantly improved by approximately 15·6% compared with the negative control, while dietary AME was unaffected. Although phytase did not affect AME, the large increase in the NEp demonstrated that dietary phytases improves energy utilisation, i.e. diverting more energy, not accounted for in the AME procedure, for production. This is largely a result of the stimulatory effect that phytase has on feed intake rather than on digestibility of the diet. 3. Overall, the diet supplemented with 12500 FTU had 6·4% significant improvement in total tract digestibility coefficients of the total amino acids compared with the negative control. With regard to individual amino acids, the impact of phytase was far more pronounced for threonine, an important component of the gastrointestinal mucin, than for other amino acids. 4. Dietary NEp was more highly correlated with performance criteria than dietary AME and seems to be a more sensitive way to evaluate broiler response to phytase supplementation.
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6-Fitasa/farmacología , Aminoácidos/metabolismo , Alimentación Animal , Pollos/metabolismo , Suplementos Dietéticos , Digestión/efectos de los fármacos , Proteínas de Escherichia coli/farmacología , Crianza de Animales Domésticos/métodos , Animales , Pollos/crecimiento & desarrollo , Metabolismo EnergéticoRESUMEN
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.
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Posmenopausia , Vagina , Atrofia/patología , Constricción Patológica/patología , Femenino , Humanos , Modalidades de Fisioterapia , Vagina/patologíaRESUMEN
Potentiation of adenosinergic inhibitory modulation is one of possible strategies to develop new antiepileptic drugs. Nonspecific receptor agonist 2-chloroadenosine was tested against pentetrazol-induced convulsions in immature (7, 12, 18 and 25 days old) and adult rats. Doses of 1-15 mg/kg i.p. suppressed tonic phase of generalized tonic-clonic seizures (GTCS) in the two youngest groups, whereas GTCS were abolished in older rats. Minimal clonic seizures in 18-day and older rats were suppressed by high doses of 2-chloroadenosine. The role of A1 and A2A adenosine receptors was studied in 12- and 25-day-old rats. Action of an agonist of A1 receptors CCPA is similar to that of 2-chloroadenosine. An agonist of A2A receptors CGS 21680 exhibits an anticonvulsant action only in the dose-inducing catalepsy; an A2A antagonist ZM 241385 moderately suppressed tonic phase of GTCS only in 12-day-old animals. Anticonvulsant action of adenosine agonists is due to their effects on A1 receptors.
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2-Cloroadenosina/farmacología , Anticonvulsivantes/farmacología , Receptor de Adenosina A1/efectos de los fármacos , Receptor de Adenosina A1/metabolismo , Convulsiones/metabolismo , Animales , Convulsivantes/toxicidad , Masculino , Pentilenotetrazol/toxicidad , Ratas , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
OBJECTIVE: To assess the effects of an oral soy isoflavone extract (Phytosoya) on endometrium and breast in postmenopausal women treated for 3 years. METHODS: A total of 395 postmenopausal women were included in this international prospective, open-label study. The number of patients who completed the 3-year study was 197. The women were treated for 3 years with a specific, standardized soy isoflavone extract (total 70 mg/day). Endometrial biopsy, transvaginal ultrasonography and mammography were performed before and after 3 years of treatment. RESULTS: No case of hyperplasia/cancer was diagnosed among the 192 interpretable biopsies at 3 years. Only one case of simple hyperplasia was diagnosed among 197 post-baseline interpretable biopsies. The endometrial safety of this extract has been demonstrated (point estimate 0.5%). There was no statistically significant change in endometrial thickness after 3 years (98.4% inactive or atrophic and 0.3% proliferative endometrium at 1 year). Mammography results showed no notable change from baseline. No patient in any set developed an ACR classification of 4 or 5 after 3 years of treatment. The global safety was rated as either 'excellent' or 'good' by 99.1% of investigators and 99.0% of patients after 3 years of treatment. The adverse events were as follows: eight patients had metrorrhagia and seven patients had at least one breast adverse event: three patients had 'breast pain', two patients reported 'breast tenderness' and two patients had 'hypertrophic breast' (most of them were possibly treatment-related). CONCLUSIONS: As no case of hyperplasia was diagnosed among the 301 interpretable biopsies at 1 year and there was only one case of simple hyperplasia in the 197 post-baseline biopsies at 3 years, the endometrial safety of this extract has been demonstrated. Furthermore, as demonstrated by the lack of change in endometrial thickness associated with the histologic results, we suggest that this extract does not exert a mitogenic effect on the endometrium. These results suggest that daily administration of 70 mg of a specific, standardized isoflavone extract for 3 years could be a safe treatment for both endometrium and breast.
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Mama/efectos de los fármacos , Endometrio/efectos de los fármacos , Isoflavonas/administración & dosificación , Isoflavonas/efectos adversos , Anciano , Enfermedades de la Mama/inducido químicamente , Enfermedades de la Mama/epidemiología , Enfermedades de la Mama/patología , Neoplasias de la Mama/epidemiología , Hiperplasia Endometrial/epidemiología , Hiperplasia Endometrial/patología , Endometrio/patología , Femenino , Humanos , Metrorragia/inducido químicamente , Metrorragia/epidemiología , Persona de Mediana EdadRESUMEN
Action of antiepileptic drugs in immature brain may differ from that in adult brain. The aim of our study was to study an anticonvulsant action of lamotrigine and phenytoin, i.e. two drugs active against partial seizures in adult experimental animals as well as human patients, in a model of simple partial seizures in immature rats. Epileptic foci were induced by local application of bicuculline methiodide on sensorimotor cortical area of 12-day-old rat pups. The animals were pretreated with lamotrigine (LTG, 10 or 20 mg/kg i.p.) or phenytoin (PHT, 15, 30 or 60 mg/kg i.p.). Control rats for LTG received saline, controls for PHT solvent composed of propyleneglycol, ethanol and water. Influence of either drug on interictal activity was negligible. High doses of both LTG and PHT suppressed the transition into ictal phases and shortened the duration of persisting seizures. The tricomponent solvent exhibited moderate activity against ictal activity if compared with saline controls. The two drugs exhibited similar action in our model, i.e. the suppression of secondary generalization from epileptic focus. This action is comparable to that described for human patients and adult experimental animals. In favor of lamotrigine speaks the absence of serious side effects.
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Epilepsias Parciales/prevención & control , Corteza Motora/efectos de los fármacos , Fenitoína/farmacología , Triazinas/farmacología , Factores de Edad , Animales , Animales Recién Nacidos , Bicuculina/análogos & derivados , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electroencefalografía , Epilepsias Parciales/inducido químicamente , Epilepsias Parciales/fisiopatología , Lamotrigina , Masculino , Corteza Motora/fisiopatología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3alpha-hydroxy-21xi,22-oxido-21-homo-5alpha-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonic-clonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology.
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Anticonvulsivantes/farmacología , Epilepsia Tónico-Clónica/tratamiento farmacológico , Pregnanolona/análogos & derivados , Pregnanolona/farmacología , Enfermedad Aguda , Factores de Edad , Animales , RatasRESUMEN
AIM: The purpose was to evaluate soft-tissue healing after poly(lactic acid) (PLA(94)) mesh implantation in a rat model. METHODS: Full-thickness abdominal wall defects were created in 108 Wistar rats, and reconstructed with 83 PLA(94) and 25 lightweight polypropylene (PPL) meshes. The meshes were previously gamma-ray sterilised with 25, 75 or 125 kGy to accelerate PLA(94) degradation. RESULTS: The inflammatory response in PLA(94) was significantly less pronounced and collagen organisation significantly better than in PPL. The higher the level of gamma-radiation, the higher the incidence of abdominal wall herniation (22.2, 31.3 and 52.6% with 25, 75 and 125 kGy, respectively). No herniation occurred in the PPL group. Tensile strength was dramatically reduced after gamma-ray-sterilised PLA(94) mesh implantation. CONCLUSION: The gamma-ray-sterilised PLA(94) mesh was poor in preventing abdominal wall hernia recurrences in a rat model.
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Inflamación/prevención & control , Ácido Láctico/uso terapéutico , Membranas Artificiales , Polímeros/uso terapéutico , Cicatrización de Heridas/fisiología , Animales , Desinfección , Rayos gamma , Hernia Abdominal/epidemiología , Hernia Abdominal/patología , Inflamación/patología , Ácido Láctico/efectos de la radiación , Poliésteres , Polímeros/efectos de la radiación , Ratas , Ratas Wistar , Heridas y Lesiones/mortalidad , Heridas y Lesiones/patologíaRESUMEN
GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentylenetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonic-clonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dose-specific suppression of the tonic phase needs further analysis.