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BACKGROUND: Obstetric anal sphincter injury is the most frequent cause of fecal incontinence (FI) in young women. However, the relationship between the extent of anal sphincter defects and the severity of long-term FI (at least 1 year after delivery) has been poorly studied. The aim of the present study was to determine if, in the long term, the extent of anal sphincter defects graded at anal endosonography was linked with the severity of FI. METHODS: A retrospective study was conducted on women with a history of vaginal delivery, who presented with FI and had three-dimensional anorectal high-resolution manometry and endoanal ultrasound in our center from January 2015 to 2016. The detailed clinical history of each patient was obtained from the institutional database. The severity of FI was assessed with the Jorge and Wexner continence scale. RESULTS: There were 250 women with a mean age of 60 ± 14 years. Seventy-six (30.4%) had an isolated defect of the internal anal sphincter, 21 (8.4%) had an isolated defect of the external anal sphincter, and 150 (60%) had both internal and external sphincter defects. The extent of IAS and EAS defects was proportionally correlated with the decrease in mean resting anal pressure (p < 0.01) and the decrease in mean squeeze pressure (p = 0.013) measured by 3DHRAM. No significant correlation was found between the extent and location of the defect (IAS, EAS or both) on endoanal ultrasound and the severity of FI. Menopause was the only independent factor significantly associated with the severity of FI. CONCLUSIONS: In our study, no significant correlation was observed between the extent of the anal sphincter defect and the severity of FI. Menopause was the only identified and independent risk factor for FI. These data confirm that, in the long-term, FI is often multifactorial.
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Canal Anal , Incontinencia Fecal , Anciano , Canal Anal/diagnóstico por imagen , Canal Anal/patología , Parto Obstétrico/efectos adversos , Endosonografía , Incontinencia Fecal/complicaciones , Incontinencia Fecal/diagnóstico por imagen , Incontinencia Fecal/etiología , Femenino , Humanos , Manometría , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , UltrasonografíaRESUMEN
Membrane receptors regulate numerous intracellular functions. However, the molecular underpinnings remain poorly understood because most receptors initiate multiple signaling pathways through distinct interaction interfaces that are structurally uncharacterized. We present an integrated computational and experimental approach to model and rationally engineer membrane receptor-intracellular protein systems signaling with novel pathway selectivity. We targeted the dopamine D2 receptor (D2), a G-protein-coupled receptor (GPCR), which primarily signals through Gi, but triggers also the Gq and beta-arrestin pathways. Using this approach, we designed orthogonal D2-Gi complexes, which coupled with high specificity and triggered exclusively the Gi-dependent signaling pathway. We also engineered an orthogonal chimeric D2-Gs/i complex that rewired D2 signaling from a Gi-mediated inhibitory into a Gs-dependent activating pathway. Reinterpreting the evolutionary history of GPCRs in light of the designed proteins, we uncovered an unforeseen hierarchical code of GPCR-G-protein coupling selectivity determinants. The results demonstrate that membrane receptor-cytosolic protein systems can be rationally engineered to regulate mammalian cellular functions. The method should prove useful for creating orthogonal molecular switches that redirect signals at the cell surface for cell-engineering applications.
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Simulación por Computador , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/química , Complejos Multiproteicos/química , Ingeniería de Proteínas , Receptores de Dopamina D2/química , Transducción de Señal , Línea Celular , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Humanos , Complejos Multiproteicos/genética , Receptores de Dopamina D2/genéticaRESUMEN
The presence of Shiga toxin-producing Escherichia coli (STEC) in food is a major concern for food safety authorities and industries. Methods for detecting these pathogenic bacteria are crucial. Enrichment of foods for STEC identification has been optimized, but selective concentration of bacteria before isolation still needs to be improved. In the present study, we tested the performance of the VIDAS ESPT detection method against that of the immunomagnetic separation (IMS) method. A preenrichment inoculation was performed to provide a realistic scenario of the contamination that occurs in foods, and the methods were then compared. Results obtained were then confirmed in naturally contaminated foods. Preenrichment inoculation assays revealed that the novel concentration method using phage recombinant proteins or the selective capture of the target top seven STEC serogroups is as specific and sensitive as IMS. Subsequent evaluation of naturally contaminated samples confirmed that the novel concentration method and IMS are equivalent in performance under the conditions tested.
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Separación Inmunomagnética , Escherichia coli Shiga-Toxigénica , Bacteriófagos , Microbiología de Alimentos , Humanos , Separación Inmunomagnética/métodos , Carne/microbiología , Serogrupo , Escherichia coli Shiga-Toxigénica/aislamiento & purificaciónRESUMEN
BACKGROUND: 3D-high definition anorectal manometry (3DARM) may aid the diagnosis of functional anorectal disorders, but data comparing asymptomatic and symptomatic subjects are scarce. We aimed to describe 3DARM values in asymptomatic volunteers and those with fecal incontinence (FI) or chronic constipation (CC), and identify which variables differentiate best these groups. METHODS: Asymptomatic subjects were stratified by sex, age, and parity. Those with FI or CC were included according to anorectal symptom questionnaires. Endoanal ultrasound examination and 3DARM were performed the same day. Anal pressures were analyzed at rest, during voluntary squeeze, and during push maneuver, and compared between the 3 groups. Anal pressure defects were defined and compared to ultrasound defects. KEY RESULTS: A total of 126 subjects (113 female, mean age 52 years, range 18-83) were included; 36 asymptomatic, 38 FI, 42 CC. Anal resting and squeeze pressures, and rectal sensitivity values were lower in FI women than in the other groups. Typical anal sphincter asymmetry during squeezing was less frequently observed in FI women. A dyssynergic pattern during push maneuver was found in 70% of asymptomatic subjects, and with a similar frequency in the 2 symptomatic groups. There was slight concordance between 3D-pressure defects and ultrasound defects. CONCLUSIONS & INFERENCES: 3D anal pressures in asymptomatic women were significantly lower than in men, and in FI compared to asymptomatic women. The classical dyssynergic pattern during push maneuver was found as frequently in asymptomatic and symptomatic patients. Further studies should try to identify 3DARM variables that could reliably identify dyssynergic defecation.
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Estreñimiento/diagnóstico , Incontinencia Fecal/diagnóstico , Manometría , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/fisiopatología , Enfermedad Crónica , Estreñimiento/fisiopatología , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recto/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce. METHODS: A prospective, longitudinal, web-based survey of 'real-life' respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified. RESULTS: A total of 4316 patients (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs, but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were as follows: the use of natural extracts (odds ratio, OR) [95% confidence interval (CI)] = 2.74 [1.61-4.87], P = 0.001), the absence of symptomatic allergy medications (1.707 [1.008-2.892], P = 0.047), asthma diagnosis (1.74 [1.05-2.88], P = 0.03), sensitization to animal dander (1.93 [1.21-3.09], P = 0.006) or pollen (1.16 [1.03-1.30], P = 0.012) and cluster regimens (vs rush) (4.18 [1.21-14.37], P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR [95% CI] = 17.35 [1.91-157.28], P = 0.01). CONCLUSION: AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.
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Desensibilización Inmunológica/efectos adversos , Hipersensibilidad/epidemiología , Vigilancia de la Población , Adolescente , Adulto , Alérgenos/administración & dosificación , Alérgenos/inmunología , Desensibilización Inmunológica/métodos , Europa (Continente)/epidemiología , Femenino , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Inmunización , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Estudios Longitudinales , Masculino , Oportunidad Relativa , Estudios Prospectivos , Factores de Riesgo , Pruebas Cutáneas , Encuestas y Cuestionarios , Evaluación de Síntomas , Adulto JovenRESUMEN
BACKGROUND: Three-dimensional high-resolution anorectal manometry (3DHRAM), used for exploring anorectal disorders, was recently developed, providing interesting topographic data for the diagnosis of pelvic floor disorders such as excessive perineal descent. The aim of our study was to define a diagnostic strategy based on selected 3DHRAM parameters to identify rectal intussusceptions (RI), considering conventional defecography (CD) as the gold standard. METHODS: All patients referred to our center in the previous 6 months for 3DHRAM to explore fecal incontinence or constipation, and who previously achieved CD, were eligible. 3DHRAM results were obtained for all classical parameters and the presence of a narrow band of high pressure in the anal canal during attempted defecation, which was recently found to be associated with RI in some studies. The sensitivity, specificity, and positive and negative predictive values were calculated for various 3DHRAM criterion in order to propose a diagnostic strategy for RI. KEY RESULTS: Twenty-six patients (66%) presented with RI on CD. On 3DHRAM, according to our diagnostic strategy, the most relevant manometric criterion for the diagnosis of RI was the association of an anterior additional high-pressure area and an excessive perineal descent, with a positive predictive value of 100% [81.5-100], a specificity of 100% [75.3-100] and a sensibility of 69.2% [48.2-85.7]. CONCLUSIONS & INFERENCES: In this study, 3DHRAM was used to diagnose RI, and we confirmed its use in the diagnosis of pelvic floor disorders. Further studies will be necessary to define classifications for these new anatomic data from 3DHRAM.
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Canal Anal/diagnóstico por imagen , Defecografía/métodos , Imagenología Tridimensional/métodos , Intususcepción/diagnóstico por imagen , Manometría/métodos , Enfermedades del Recto/diagnóstico por imagen , Adulto , Anciano , Canal Anal/fisiopatología , Estreñimiento/diagnóstico por imagen , Estreñimiento/fisiopatología , Defecación/fisiología , Incontinencia Fecal/diagnóstico por imagen , Incontinencia Fecal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Intususcepción/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedades del Recto/fisiopatología , Estudios RetrospectivosRESUMEN
We report the generation of free space terahertz (THz) pulses with energy up to 8.3 ± 0.2 µJ from an encapsulated interdigitated ZnSe Large Aperture Photo-Conductive Antenna (LAPCA). An aperture of 12.2 cm2 is illuminated using a 400 nm pump laser with multi-mJ energies at 10 Hz repetition rate. The calculated THz peak electric field is 331 ± 4 kV/cm with a spectrum characterized by a median frequency of 0.28 THz. Given its relatively low frequency, this THz field will accelerate charged particles efficiently having very large ponderomotive energy of 15 ± 1 eV for electrons in vacuum. The scaling of the emission is studied with respect to the dimensions of the antenna, and it is observed that the capacitance of the LAPCA leads to a severe decrease in and distortion of the biasing voltage pulse, fundamentally limiting the maximum applied bias field and consequently the maximum energy of the radiated THz pulses. In order to demonstrate the advantages of this source in the strong field regime, an open-aperture Z-scan experiment was performed on n-doped InGaAs, which showed significant absorption bleaching.
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Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups.
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Secuenciación de Nucleótidos de Alto Rendimiento , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Receptores Acoplados a Proteínas G/genética , Transcriptoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/genética , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Proteínas de Neoplasias/sangre , Transducción de Señal/genéticaRESUMEN
BACKGROUND AND PURPOSE: Our previous studies have shown the ß2 -adrenoceptor and its endogenous ligand, adrenaline, are required for development of the asthma phenotype in murine asthma models. Chronic administration of some, but not other, ß-blockers attenuated the asthma phenotype and led us to hypothesize that biased signalling was the basis of their differential effects, experimentally and clinically. EXPERIMENTAL APPROACH: We used mice with no detectable systemic adrenaline (PNMT(-/-) ) and wild-type (WT) mice to study the effects of four ß-blockers, alprenolol, carvedilol, propranolol and nadolol, in an ovalbumin sensitization and challenge (Ova S/C) murine model of asthma. The parameters measured were inflammatory cell infiltration, mucous metaplasia and airway hyperresponsiveness. To interpret the pharmacological action of these ligands quantitatively, we conducted computer simulations of three-state models of receptor activation. KEY RESULTS: Ova S/C PNMT(-/-) mice do not develop an asthma phenotype. Here, we showed that administration of alprenolol, carvedilol or propranolol in the absence of interference from adrenaline using Ova S/C PNMT(-/-) mice resulted in the development of an asthma phenotype, whereas nadolol had no effect. Ova S/C WT mice did develop an asthma phenotype, and administration of alprenolol, propranolol and carvedilol had no effect on the asthma phenotype. However, nadolol prevented development of the asthma phenotype in Ova S/C WT mice. Computer simulations of these four ligands were consistent with the isolated three-state receptor model. CONCLUSION AND IMPLICATIONS: ß-Blockers have different effects on the murine asthma phenotype that correlate with reported differences in activation or inhibition of downstream ß2 -adrenoceptor signalling pathways.
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Antagonistas Adrenérgicos beta/farmacología , Asma , Alérgenos , Alprenolol/farmacología , Animales , Asma/inmunología , Asma/metabolismo , Asma/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Carbazoles/farmacología , Carvedilol , Recuento de Células , Epinefrina/deficiencia , Femenino , Masculino , Ratones Noqueados , Modelos Biológicos , Mucinas/metabolismo , Nadolol/farmacología , Ovalbúmina , Fenotipo , Propanolaminas/farmacología , Propranolol/farmacologíaRESUMEN
AIM: Anorectal manometry is the most common test used to explore anorectal disorders. The recent three-dimensional high-resolution anorectal manometry (3D-HRAM) technique appears to be able to provide new topographic information. Our objective was to develop an automated analysis of 3D-HRAM images to diagnose anal sphincter defects and compare the results with those of endoanal ultrasonography (EUS), which is considered to be the gold standard. METHOD: All patients being tested in our department for faecal incontinence or dyschezia by 3D-HRAM and EUS were eligible for the study. 3D-HRAM was used to record resting and squeeze pressure, reflecting internal and external anal sphincter function, respectively. A software platform was designed to automatically analyse the 3D-HRAM images and calculate a diagnostic score for any anal sphincter defect compared with EUS. RESULTS: A total of 206 (91% female) patients of mean age of 54 years were included in the study. A sphincter defect was diagnosed by EUS in 130 (63%). The diagnostic scores from the 3D-HRAM automated analysis for an internal anal sphincter defect showed a sensitivity of 65% and a specificity of 65%. For an external anal sphincter defect, the sensitivity was 43% and the specificity 87%. CONCLUSION: Our study developed a method based on 3D-HRAM to automatically diagnose sphincter defects, allowing a systematic and comprehensive analysis of the test recordings. Compared with EUS, the 3D-HRAM image analysis procedure revealed poor sensitivity and specificity.
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Canal Anal/diagnóstico por imagen , Automatización/instrumentación , Incontinencia Fecal/diagnóstico , Imagenología Tridimensional , Manometría/métodos , Adulto , Anciano , Canal Anal/fisiopatología , Estudios de Cohortes , Estreñimiento/diagnóstico , Endosonografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
Antipsychotic drugs are known to have sex-dependent effects on metabolic homeostasis. Liver plays a crucial role in drug degradation as well as in glucose and lipid metabolism. The present study examines the influence of clozapine and haloperidol on metabolic liver parameters. Over 12 weeks, male and female Sprague-Dawley rats were fed ground pellets containing clozapine or haloperidol. Liver mass was weighed and liver index calculated. Liver transaminases (ALAT, ALP), malondialdehyde, glucose, triglycerides, total cholesterol, HDL-cholesterol, and glycogen were determined. Finally, SREBP-1 and SREBP-2 as well as neutral fat deposits were examined. In male rats fed with clozapine, we found increased liver mass correlated with an increased liver index, high triglyceride levels, a high ratio of SREBP-1, and an elevated neutral fat distribution. Male and female haloperidol treated rats showed decreased liver mass and increased neutral fat deposition. Malondialdehyde was increased in all rats receiving antipsychotic medication indicating elevated oxidative stress. In both male and female clozapine treated rats, we found glycogen depletion related to decreased glucose levels in females. While liver transaminases were unchanged in the clozapine group, ALAT was elevated after haloperidol treatment in both sexes. Chronic clozapine intake exerts sex-dependent effects on hepatic metabolism. Although haloperidol has been shown to change fewer metabolic parameters, it causes oxidative stress and neutral fat deposits in liver tissue in both sexes.
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Clozapina/farmacología , Haloperidol/farmacología , Hígado/metabolismo , Caracteres Sexuales , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Biomarcadores/metabolismo , HDL-Colesterol/metabolismo , Femenino , Glucosa/metabolismo , Glucógeno/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Malondialdehído/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Triglicéridos/metabolismoRESUMEN
Faecal incontinence is common and significantly affects quality of life. Its treatment involves dietary manipulation, medical treatments, perineal rehabilitation or surgery. In this paper, the French National Society of Coloproctology offers recommendations based on the data in the current literature, including those on recently developed treatments. There is a lack of high quality data and most of the recommendations are therefore based either on grade of recommendation B or expert recommendation (Level 4). However, the literature supports the construction of an algorithm based on the available scientific evidence and expert recommendation which may be useful in clinical practice. The French National Society of Coloproctology proposes a decision-making algorithm that includes recent developments of treatment. The current recommendations support sacral nerve modulation as the key treatment for faecal incontinence. They do not support the use of sphincter substitutions except in certain circumstances. Transanal irrigation is a novel often successful treatment of faecal incontinence due to neurological disorders.
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Canal Anal/cirugía , Antidiarreicos/uso terapéutico , Dietoterapia/métodos , Terapia por Estimulación Eléctrica/métodos , Terapia por Ejercicio/métodos , Incontinencia Fecal/terapia , Resina de Colestiramina/uso terapéutico , Fibras de la Dieta/uso terapéutico , Medicina Basada en la Evidencia , Humanos , Loperamida/uso terapéutico , Plexo Lumbosacro , Mucílago de Planta/uso terapéutico , Irrigación Terapéutica/métodos , Nervio Tibial , Resultado del TratamientoRESUMEN
AIM: Three-dimensional high-resolution anorectal manometry (3DHRAM) is a new technique that can simultaneously provide physiological and topographical data on the terminal part of the digestive tract. Our object was to assess whether 3DHRAM is able to reliably diagnose excessive perineal descent already diagnosed with conventional defaecography, which is considered to be the gold standard. METHOD: All patients referred to our centre for anorectal manometry and conventional defaecography were evaluated with a maximum of 6 months between the two examinations. Anorectal manometry was performed using the 3D High-Resolution Given Imaging® probe. Excessive perineal descent was defined as the downward movement of the anal high-pressure zone during straining. At the end of the straining effort, the high-pressure zone regained its initial position, thereby indicating that the probe had not moved. RESULTS: Nineteen female patients of median age 53 (21-70) years were included in the study. All cases with excessive perineal descent diagnosed using defaecography were visualized with 3DHRAM. The degree of perineal descent determined by 3D and conventional defaecography was compared (Spearman correlation 0.726, P = 0.01). In contrast, the averages measured were significantly different; the average was 11.68 ± 3.3 mm for 3DHRAM but 34.21 ± 13.3 mm for conventional defaecography (P = 0.002). CONCLUSION: The results of the study demonstrate that 3DHRAM can diagnose excessive perineal descent with the same degree of reliability as defaecography. Quantitative measures were not correlated, however, possibly because of methodological differences. The study confirms the value of the morphological data provided by 3DHRAM.
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Canal Anal/fisiopatología , Defecación/fisiología , Manometría/métodos , Recto/fisiopatología , Adulto , Anciano , Canal Anal/diagnóstico por imagen , Estreñimiento/fisiopatología , Defecografía , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Imagenología Tridimensional , Persona de Mediana Edad , Proyectos Piloto , Presión , Recto/diagnóstico por imagen , Estudios Retrospectivos , Transductores de Presión , Adulto JovenRESUMEN
The roles of G-protein-coupled receptors (GPCRs) in the control of food intake and energy expenditure are being increasingly recognized, and new drug candidates targeting these receptors are making their entry into the clinic. GPCRs exert their action along the various sites of regulation of energy homeostasis control including the central nervous system, the pancreas, the gut and fat cells. Exciting new data about GPCRs recognizing and mediating the effects of lipid mediators and concerning receptors for which no endogenous ligands have been identified yet open new exciting avenues for the validation of additional drug targets. In addition, recently developed paradigms around the concepts of cross-talk regulation and functional selectivity should lead to the development of drugs with improved therapeutic efficacy and reduced undesirable effects. Some of these promising discoveries are discussed in the present article and accompanying papers.
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AIM: Our aim was to compare for the first time measurements obtained with water-perfused catheter anorectal manometry and three-dimensional (3D) high-resolution manometry in patients with anorectal disorders. METHOD: Consecutive patients referred to our centre for anorectal manometry (ARM) were recruited to undergo the two procedures successively. Conventional manometry was carried out using a water-perfused catheter (WPAM) and high-resolution manometry was achieved with a 3D probe (3DHRAM). For each procedure, parameters recorded included the following: anal canal length, resting pressure, squeeze pressure and rectal sensitivity. RESULTS: Two hundred and one patients were included in this study. The mean values for resting and squeeze pressures were correlated and found to be significantly higher when measured with 3DHRAM than with WPAM. However, the length of the anal canal was not significantly different when measured by the two techniques without correlation between the two mean values obtained. The presence of the rectoanal inhibitory reflex was systematically assessed by both WPAM and 3DHRAM and anismus was also systematically diagnosed by both WPAM and 3DHRAM. CONCLUSION: The pressure values obtained with 3DHRAM are correlated with those measured with conventional manometry but are systematically higher. 3DHRAM has the advantage of providing a pressure recording over the entire length and circumference of the anal canal, allowing a more useful physiological assessment of anorectal function.
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Enfermedades del Ano/diagnóstico , Manometría/métodos , Adulto , Anciano , Canal Anal/fisiopatología , Enfermedades del Ano/complicaciones , Enfermedades del Ano/fisiopatología , Estreñimiento/etiología , Incontinencia Fecal/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Presión , Enfermedades del Recto/complicaciones , Enfermedades del Recto/diagnóstico , Enfermedades del Recto/fisiopatología , Recto/fisiopatologíaRESUMEN
AIM: Three-dimensional high-resolution anorectal manometry (3D HRAM) is a new technique that can simultaneously provide physiological and topographical data. Our aim was to assess whether it can identify anal sphincter defects by comparing it with endoanal ultrasonography (EUS) considered as the gold standard. METHOD: An anal defect on 3D HRAM was defined as a continuous circumferential area over which the pressure was < 10 mmHg during the measurement of anal resting and voluntary contraction pressure. Inter-observer agreement was also assessed. RESULTS: A total of 100 patients (93 females) with a mean age of 53.5 ± 15.3 years were included. The positive diagnosis of an anal sphincter defect using 3D HRAM and EUS was in agreement (59.3%) (κ = 0.419) of the time for the internal anal sphincter (IAS) and (55.9%) (κ = 0.461) for the external anal sphincter (EAS). The inter-observer agreement for a diagnosis of an anal sphincter defect was (100%) (κ = 0.937) for the IAS and (95%) (κ = 0.751) for the EAS. The intra-class correlation coefficient for the extent of the defect was 0.853 for the IAS and 0.651 for the EAS. CONCLUSION: The preliminary results demonstrate some level of agreement in the diagnosis of anal sphincter defects between 3D HRAM and EUS but insufficient for 3D HRAM to be adequately reliable using the criteria chosen. The excellent inter-observer agreement, however, demonstrates that 3D HRAM is reproducible and provides a new dimension for the evaluation of sphincter function.
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Enfermedades del Ano/diagnóstico por imagen , Enfermedades del Ano/fisiopatología , Endosonografía , Imagenología Tridimensional , Manometría/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , PresiónRESUMEN
INTRODUCTION: An increased risk for metabolic syndrome has been described for patients with psychotic disorders. Antipsychotic drugs possibly contribute to metabolic changes. METHODS: Haloperidol or clozapine was orally fed to male and female Sprague Dawley rats for 12 weeks, and body weight gain, food and water intake were measured. The serum levels of fasting glucose, HbA1c, triglycerides, cholesterol, HDL and LDL, insulin, leptin, adiponectin and ghrelin were determined. Gonadal and perirenal fat pads were removed and weighed. RESULTS: We found increased body weight in the male clozapine group, but decreased ones in the male haloperidol group. Clozapine-treated male and female animals had higher fasting glucose, adiponectin, leptin, ghrelin, cholesterol, HDL and LDL levels, whereas haloperidol caused increased levels of insulin and decreased values of HbA1c, cholesterol, HDL and LDL. CONCLUSION: Both antipsychotic drugs cause sex-dependent metabolic changes, which are risk factors for the metabolic syndrome, be it hyperinsulinemia under haloperidol treatment or hyperglycemia, hyperleptinemia and hyperlipidemia under clozapine.
Asunto(s)
Antipsicóticos/farmacología , Clozapina/farmacología , Haloperidol/farmacología , Síndrome Metabólico/metabolismo , Adiposidad/efectos de los fármacos , Animales , Antipsicóticos/sangre , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Clozapina/sangre , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Haloperidol/sangre , Hormonas/sangre , Insulina/metabolismo , Lípidos/sangre , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Caracteres Sexuales , Aumento de Peso/efectos de los fármacosRESUMEN
AIM: The study aimed to assess, for the first time, the effectiveness of interferential therapy (IFT) in the treatment of slow transit constipation in adults and its impact on the quality of life. METHOD: All consecutive patients with slow transit constipation diagnosed by symptomology and a colonic transit time (CTT) of > 100 h measured with radiopaque markers were included in this prospective study. IFT was performed for 1 h/day over 3 months. Clinical improvement was based on the stool diary and the Knowles-Eccersley-Scott Symptom and Cleveland Clinic Constipation Scores. Quality of life was assessed with the Gastrointestinal Quality of Life Index questionnaire. RESULTS: Eleven patients with a median age of 51 years were included. At the end of the follow-up period, seven (63.6%) had significantly improved after IFT with a median of 0.66 stools per week [interquartile range (IQR) 0.33-0.66] before treatment and 1.66 (IQR 1.33-1.66) after (P = 0.007). The Knowles-Eccersley-Scott Symptom score changed from 30 (IQR 27-33) before treatment to 19 (IQR 17-26) after treatment (P = 0.005) and the Cleveland Clinic Constipation Score from 26 (IQR 25-28) to 17 (IQR 13-24; P = 0.005). The CTT improved from 103 h (IQR 101-113) to 98 h (IQR 94-107; P = 0.02). The Gastrointestinal Quality of Life Index score improved from 60 (IQR 57-63) to 95 (IQR 68-100; P = 0.005). CONCLUSION: IFT is a new non-invasive treatment for slow transit constipation. Further studies to confirm these results with longer follow-up are necessary.
Asunto(s)
Estreñimiento/terapia , Defecación , Terapia por Estimulación Eléctrica , Calidad de Vida , Enfermedad Crónica , Femenino , Tránsito Gastrointestinal , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVES: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials. METHODS: In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events. RESULTS: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P=0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P=0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b). CONCLUSIONS: We failed to demonstrate any benefit of TENS on our primary end-point.