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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(8): 1203-1209, 2023 Aug 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-37875360

RESUMEN

OBJECTIVES: At present, there are many reports about the treatment of cricopharyngeal achalasia by injecting botulinum toxin type A (BTX-A) into cricopharyngeal muscle guided by ultrasound, electromyography or CT in China, but there is no report about injecting BTX-A into cricopharyngeal muscle guided by endoscope. This study aims to evaluate the efficacy of endoscopic BTX-A injection combined with balloon dilatation in the treatment of cricopharyngeal achalasia after brainstem stroke, and to provide a better method for the treatment of dysphagia after brainstem stroke. METHODS: From June to December 2022, 30 patients with cricopharyngeal achalasia due to brainstem stroke were selected from the Department of Rehabilitation Medicine, the First Hospital of Changsha. They were randomly assigned into a control group and a combined group, 15 patients in each group. Patients in both groups were treated with routine rehabilitation therapy, while patients in the control group were treated with balloon dilatation, and patients in the combined group were treated with balloon dilatation and BTX-A injection. Before treatment and after 2 weeks of treatment, the patients were examined by video fluoroscopic swallowing study, Penetration-aspiration Scale (PAS), Dysphagia Outcome Severity Scale (DOSS), and Functional Oral Intake Scale (FOIS) were used to assess the swallowing function. RESULTS: In the combined group, 1 patient withdrew from the treatment because of personal reasons. Two weeks after treatment, the scores of DOSS, PAS, and FOIS in both groups were better than those before treatment (all P<0.01), and the combined group was better than the control group (all P<0.001). The effective rate was 85.7% in the combined group and 66.7% in the control group, with no significant difference between the 2 groups (P>0.05). CONCLUSIONS: BTX-A injection combined with balloon dilatation is more effective than balloon dilatation alone in improving swallowing function and is worthy of clinical application.


Asunto(s)
Toxinas Botulínicas Tipo A , Infartos del Tronco Encefálico , Trastornos de Deglución , Acalasia del Esófago , Humanos , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Acalasia del Esófago/complicaciones , Acalasia del Esófago/tratamiento farmacológico , Dilatación/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Infartos del Tronco Encefálico/complicaciones , Infartos del Tronco Encefálico/tratamiento farmacológico , Resultado del Tratamiento
2.
Medicine (Baltimore) ; 102(14): e33494, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37026926

RESUMEN

RATIONALE: Idiopathic achalasia is an esophageal peristaltic dysfunction of the lower esophageal sphincter (LES). The initial symptom is progressive dysphagia. However, due to its rarity, it is often misdiagnosed as an esophageal disorder. High LES pressure on esophageal manometry is an essential finding for the diagnosis. PATIENT CONCERNS: A 55-year-old man was hospitalized with saliva-like vomitus, stuck-in-throat feeling of dysphagia, and weight loss. CLINICAL FINDINGS: On initial admission, gastrointestinal endoscopy, esophageal manometry, laboratory tests, and physical examination results were within normal limits. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Initially, the patient was diagnosed with globus sensation and recovered with medication. However, the symptoms recurred. He requested another examination on the second admission and was diagnosed with achalasia based on repeat esophageal manometry. The patient recovered after surgical treatment. LESSONS: When patients still suffer from these symptoms, there is a need to reconsider achalasia, even if it is initially excluded from the differential diagnosis. Medication is not a radical treatment; however, it sometimes ameliorates symptoms. Moreover, the psychosomatic approach can be useful in such cases.


Asunto(s)
Trastornos de Deglución , Acalasia del Esófago , Masculino , Humanos , Persona de Mediana Edad , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/tratamiento farmacológico , Benzodiazepinas , Esfínter Esofágico Inferior , Manometría/métodos
3.
Minerva Pediatr (Torino) ; 75(4): 482-489, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-30419742

RESUMEN

BACKGROUND: Intrasphincteric botulinum toxin (Botox) injection for symptomatic postoperative anal achalasia in Hirschsprung's disease (HSCR) has found wide application in the last twenty years. The aim of this study was to describe effectiveness and functional outcome of a series of patients treated over a 10-year period. METHODS: All consecutive HSCR patients who received intrasphincteric Botox injections between January 2007 and December 2016 were included. Demographic data and clinical features were collected. A detailed questionnaire focusing on outcome in the medium and long-term was administered to all families. RESULTS: In the study period 64 intrasphincteric Botox injections were performed in 31 patients. Completed questionnaires were returned by 27 out of 28 eligible patients (96%) reporting improvement or symptoms resolution in 16 (59%). The highest success rates were experienced by patients younger than 4, with long HSCR forms and with recurrent enterocolitis (75%, 100% and 100% of success rates, respectively). No major complications occurred. Minor complications were described by 7 patients (26%). CONCLUSIONS: Intrasphincteric Botox injection proved to be feasible, safe and reasonably effective in children with HSCR and postoperative anal achalasia. Infants and toddlers with long HSCR forms and recurrent bouts of enterocolitis are those who would benefit most from this treatment.


Asunto(s)
Toxinas Botulínicas Tipo A , Enterocolitis , Acalasia del Esófago , Enfermedad de Hirschsprung , Lactante , Humanos , Toxinas Botulínicas Tipo A/uso terapéutico , Enfermedad de Hirschsprung/cirugía , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/tratamiento farmacológico , Acalasia del Esófago/complicaciones , Acalasia del Esófago/tratamiento farmacológico , Resultado del Tratamiento , Enterocolitis/complicaciones , Enterocolitis/tratamiento farmacológico
4.
Am J Vet Res ; 83(4): 317-323, 2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35066488

RESUMEN

OBJECTIVE: To determine whether delivery of compounded liquid sildenafil directly to the stomach of dogs with megaesophagus (ME) would affect esophageal clearance, regurgitation frequency, body weight, or quality of life. ANIMALS: 10 client-owned otherwise healthy dogs with stable ME. PROCEDURES: A randomized crossover study was performed. Dogs received either sildenafil (1 mg/kg, PO, q 12 h) or a placebo for 14 days, followed by a 7-day washout period, then the opposite treatment for 14 days. Esophageal clearance time was assessed by means of videofluoroscopy prior to treatment and on day 1 of each treatment period. Owners maintained logs of regurgitation episodes and quality of life. RESULTS: Compounded liquid sildenafil moved into the stomach during 21 of 30 (70%) videofluoroscopy sessions. Sildenafil resulted in a significant reduction in the number of regurgitation episodes (median, 3.5 episodes/wk; range, 0 to 14.5 episodes/wk), compared with baseline (median, 6.5 episodes/wk; range, 1.5 to 19.5 episodes/wk) and the placebo (median, 4 episodes/wk; range, 0 to 28 episodes/wk), and a significant increase in body weight (median, 22.05 kg; range, 6 to 26.3 kg), compared with baseline (median, 21.55 kg; range, 5.1 to 26.2 kg) and the placebo (median, 22.9 kg; range, 5.8 to 25.9 kg). There were no differences in esophageal clearance times or quality-of life-scores between sildenafil and placebo. CLINICAL RELEVANCE: Although significant differences with placebo administration were identified, clinically relevant improvements were not seen with the use of compounded liquid sildenafil in dogs with ME.


Asunto(s)
Enfermedades de los Perros , Acalasia del Esófago , Animales , Estudios Cruzados , Enfermedades de los Perros/tratamiento farmacológico , Perros , Método Doble Ciego , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/veterinaria , Calidad de Vida , Citrato de Sildenafil/uso terapéutico
5.
J Gastroenterol Hepatol ; 37(3): 480-488, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34655450

RESUMEN

BACKGROUND AND AIM: The perioperative management and clinical course of per-oral endoscopic myotomy for patients receiving antithrombotic therapy remains unknown. This study aimed to clarify the status of antithrombotic therapy in per-oral endoscopic myotomy and to determine its safety and efficacy. METHODS: Patients treated with per-oral endoscopic myotomy from 2010 to 2019 in seven high-volume centers in Japan were retrospectively investigated. The patients' characteristics and antithrombotic agent management were analyzed; clinical outcomes were compared with those without antithrombotic agents. RESULTS: Of 2752 patients who underwent per-oral endoscopic myotomy, 120 patients on antithrombotic therapy (mean age 71.0 years, American Society of Anesthesiologists class II-IV [67.5%]) were identified. Antiplatelet, anticoagulant, and a combination of antithrombotic agents were used in 82, 30, and 8 patients, respectively. The perioperative management adhered to the therapeutic endoscopy guidelines published by the Japanese Society of Gastroenterological Endoscopy in most patients (88.3%). A poorer clinical baseline status (American Society of Anesthesiologists class II-IV; 67.0% vs 24.3%) and the sigmoid type (40.7% vs 22.3%) were more frequently observed in patients with achalasia on antithrombotic therapy. However, the clinical success (Eckardt score ≤ 3; 97.6% vs 94.6) and adverse event rates, such as bleeding and thromboembolic events (5.5% vs 4.7%), did not show inferiority. CONCLUSIONS: Per-oral endoscopic myotomy on antithrombotic therapy is safe and effective. However, caution is required as patients on antithrombotic therapy tend to have poorer baseline health and achalasia statuses. Our experience should help establish perioperative management with antithrombotic therapy.


Asunto(s)
Fibrinolíticos , Miotomía , Cirugía Endoscópica por Orificios Naturales , Anciano , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/cirugía , Fibrinolíticos/uso terapéutico , Humanos , Japón , Miotomía/efectos adversos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Atención Perioperativa , Estudios Retrospectivos , Resultado del Tratamiento
6.
Medicine (Baltimore) ; 100(11): e24909, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725963

RESUMEN

INTRODUCTION: Botulinum toxin (BTX) injection is a widely used treatment option for dysphagia associated with cricopharyngeal (CP) muscle achalasia, but uniform standards and protocols for administration techniques and injection sites are still lacking. This case study suggests that a unique administration technique involving a combination of ultrasound, electromyography, and balloon guidance for injecting the CP muscle can reduce inadvertent migration of BTX to non-injected tissues and increase the effectiveness and safety of BTX treatment. PATIENT CONCERNS: We describe the case of a 74-year-old man who could not swallow food or saliva for 8 months. DIAGNOSIS: The patient showed signs of true bulbar paralysis, including dizziness, hoarseness, and dysphagia. The fiberoptic endoscopic evaluation of swallowing showed massive mucilage secretion and residual materials in the postcricoid region and aspiration when swallowing 1 ml of yogurt. The video fluoroscopic swallowing study showed profoundly limited epiglottic folding and CP muscle non-relaxation, despite several unsuccessful swallow attempts. INTERVENTIONS: To manage insufficient relaxation opening of the CP muscle, BTX injection was performed using ultrasound, electromyography, and balloon catheter guidance. The narrow CP muscle situated above the balloon was identified as the target of injection by ultrasound. OUTCOMES: The patient was able to eat a soft diet. The follow-up fibrotic endoscopic swallowing study demonstrated a reduction in the amount of pharyngeal residue. The video fluoroscopic swallowing study showed that CP muscle relaxation was significantly enhanced and no penetration was shown. CONCLUSION: The unique administration technique with triple guidance holds several advantages, suggesting that it may be a promising treatment for CP muscle achalasia.


Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Cateterismo/métodos , Sistemas de Liberación de Medicamentos/métodos , Electromiografía/métodos , Acalasia del Esófago/tratamiento farmacológico , Ultrasonografía/métodos , Anciano , Deglución , Acalasia del Esófago/fisiopatología , Esfínter Esofágico Superior/fisiopatología , Humanos , Inyecciones , Masculino , Resultado del Tratamiento
7.
Hormones (Athens) ; 20(1): 197-205, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32700293

RESUMEN

INTRODUCTION: Triple A (Allgrove) syndrome is a rare autosomal recessive disorder characterized by cardinal features of primary adrenal insufficiency (AI) due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrima. It is frequently associated with neurological manifestations such as autonomic dysfunction, cognitive dysfunction, cranial nerve, or motor involvement. Amyotrophy/motor neuron disease is a rare association. CASE PRESENTATION: We herein report a 19-year-old boy diagnosed with triple A syndrome (TAS), with the classic triad of ACTH-resistant adrenal insufficiency, achalasia, and alacrima. Additionally, he had distal spinal muscle amyotrophy. Alacrima was the earliest feature evident in early childhood, followed by achalasia at 12 years of age. He was diagnosed with AI at the age of 19 years, with involvement of the mineralocorticoid axis. Further evaluation showed a neurogenic pattern on electromyography, consistent with a diagnosis of motor neuron disease. A nerve conduction study revealed no significant neuropathy. Genetic analysis confirmed a pathogenic homozygous mutation in the AAAS gene c.43C>A, p.Gln15Lys. He improved with glucocorticoid and mineralocorticoid supplements for AI, and nifedipine for achalasia and artificial tears. He is planned for esophagomyotomy. CONCLUSION: In any young patient with AI not due to congenital adrenal hyperplasia, Allgrove syndrome should be ruled out. Though mineralocorticoid sparing pattern is classical, it can rarely be involved, as seen in the index case. Various components of the syndrome, as well as amyotrophy and other neurologic features, may present in a metachronous fashion. Hence, a high index of clinical suspicion can aid in early diagnosis and management.


Asunto(s)
Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/genética , Acalasia del Esófago/complicaciones , Acalasia del Esófago/genética , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patología , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismo , Corticoesteroides/uso terapéutico , Insuficiencia Suprarrenal/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Acalasia del Esófago/tratamiento farmacológico , Humanos , Gotas Lubricantes para Ojos , Masculino , Mutación , Nifedipino/uso terapéutico , Adulto Joven
8.
Am J Physiol Gastrointest Liver Physiol ; 318(1): G77-G83, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31589467

RESUMEN

BACKGROUND: Endoscopic intrasphincteric injection of Botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that the ISIB reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm, surrounds the cranial half of the LES and works like an external LES. We studied the effects of ISIB on the LES and hiatal contraction and gastroesophageal reflux (GER). Fourteen patients treated with ISIB were studied. Esophageal manometry-impedance recordings were performed before and after the ISIB. Hiatal contraction was assessed during tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise. In 6 subjects, the manometry were repeated 6-12 mo after the ISIB. The esophagogastric junction (EGJ) pressure was measured at end expiration (LES pressure) and at the peak of maneuvers (hiatal contraction). Transdiaphragmatic pressure (pdi; force of diaphragmatic contraction) was measured at the peak of forced inspiration. GER was measured from the impedance recordings. The EGJ pressure at end expiration (LES pressure) decreased significantly after the Botox injection. The peak EGJ pressure at tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise was also dramatically reduced by the ISIB. There was no effect of Botox on the pdi during forced inspiration. Seven of 10 subjects demonstrated GER during maneuvers following the ISIB. Six to 12 mo after ISIB, the LES and hiatal contraction pressure returned to the pre-ISIB levels. ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER.NEW & NOTEWORTHY The sphincter mechanism at the lower end of the esophagus comprises smooth muscle lower esophageal sphincter (LES) and skeletal muscle crural diaphragm (hiatus). Current thinking is that the endoscopic intrasphincteric injection of Botox (ISIB), used routinely for the treatment of achalasia esophagus, reduces LES pressure. Our study shows that ISIB, even though injected into the LES, diffuses into the hiatus and causes its paralysis. These findings emphasize the importance of esophageal hiatus as an important component of the antireflux barrier and that the ISIB is refluxogenic.


Asunto(s)
Inhibidores de la Liberación de Acetilcolina/efectos adversos , Toxinas Botulínicas Tipo A/efectos adversos , Diafragma/efectos de los fármacos , Acalasia del Esófago/tratamiento farmacológico , Esfínter Esofágico Inferior/efectos de los fármacos , Reflujo Gastroesofágico/inducido químicamente , Contracción Muscular/efectos de los fármacos , Parálisis Respiratoria/inducido químicamente , Inhibidores de la Liberación de Acetilcolina/administración & dosificación , Adulto , Anciano , Toxinas Botulínicas Tipo A/administración & dosificación , Diafragma/fisiopatología , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/fisiopatología , Esfínter Esofágico Inferior/fisiopatología , Femenino , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/fisiopatología , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Presión , Parálisis Respiratoria/diagnóstico , Parálisis Respiratoria/fisiopatología , Factores de Riesgo
10.
J Coll Physicians Surg Pak ; 29(6): S52-S53, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31142422

RESUMEN

Triple A syndrome or Allgrove's syndrome is a rare autosomal recessive disorder usually manifested with three main clinical features, i.e. achalasia, alacrimation and adrenal inadequacy. Sometimes, it presents with polyneuropathy and neurological complications. Here, we report a case of a 7-year girl presenting with features of weight loss who was diagnosed with adrenal insufficiency at the age of 7 years while achalasia was diagnosed at the age of 3 years. First manifestation was achalasia and at that time, alacrimation was also defected. A 7-year XX female child presented at Endocrine Clinic of Armed Forces Institute of Pathology (AFIP) with hyperpigmentation, easy fatigue and weight loss. She had one sibling with same complaints and one brother died at the age of 3 years because of adrenal insufficiency. Her laboratory investigations revealed low cortisol level and high ACTH level, with inadequate response as well as short synacthen test (dynamic function test). This is a first case of Allgrove's syndrome reported in a tertiary hospital setting of Pakistan. Allgrove's syndrome should be considered in patients who report with adrenal insufficiency.


Asunto(s)
Insuficiencia Suprarrenal/diagnóstico , Acalasia del Esófago/diagnóstico , Enfermedades del Aparato Lagrimal/complicaciones , Pérdida de Peso , Insuficiencia Suprarrenal/tratamiento farmacológico , Niño , Acalasia del Esófago/tratamiento farmacológico , Femenino , Humanos , Hidrocortisona/uso terapéutico , Resultado del Tratamiento
11.
J Vet Intern Med ; 33(3): 1423-1433, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30968469

RESUMEN

BACKGROUND: Megaesophagus (ME) carries a poor long-term prognosis in dogs. In people, lower esophageal sphincter (LES) achalasia is a rare cause of ME that may respond to targeted intervention. Dogs with lower esophageal sphincter achalasia-like syndrome (LES-AS) have been described recently, warranting investigation of analogous targeted treatment. HYPOTHESIS/OBJECTIVES: Evaluate response of dogs with LES-AS to LES mechanical dilation and botulinum toxin A (BTA) injections, with or without surgical myotomy and fundoplication. We hypothesized that clinical and videofluoroscopic swallow study (VFSS) features of LES-AS would improve after treatment targeting functional LES obstruction. ANIMALS: Fourteen client-owned dogs with LES-AS diagnosed by VFSS. METHODS: Retrospective study. Dogs diagnosed with LES-AS underwent treatment between April 2015 and December 2017. Outcome measures included client perception of clinical severity, body weight (BW), body condition score (BCS), regurgitation frequency, and VFSS parameters (ME, esophageal motility, gastric filling). Dogs with positive responses were considered candidates for LES myotomy with fundoplication. RESULTS: By a median IQR of 21 (IQR, 14-25) days after mechanical dilation and BTA, clients reported clinical improvement in 100% of dogs, BW increased 20.4% (IQR, 12.7%-25%), pre- and post-treatment BCS was 3 (IQR, 3-4) and 5 (IQR, 4-5), respectively, and frequency of regurgitation decreased by 80% (IQR, 50%-85%). Duration of effect was 40 (IQR, 17-53) days. Despite clinical improvement, ME and abnormal esophageal motility persisted in 14 dogs. Six dogs subsequently underwent myotomy and fundoplication and maintained improvement observed after mechanical dilation and BTA. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with LES-AS experienced significant, temporary, clinical improvement after mechanical dilation and BTA. Preliminary results suggest myotomy with fundoplication provide lasting clinical benefit despite persistence of ME.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Dilatación/veterinaria , Acalasia del Esófago/veterinaria , Fundoplicación/veterinaria , Miotomía/veterinaria , Animales , Perros , Acalasia del Esófago/diagnóstico por imagen , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/cirugía , Femenino , Fluoroscopía/métodos , Fluoroscopía/veterinaria , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Grabación en Video
13.
PLoS Negl Trop Dis ; 12(9): e0006836, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30265663

RESUMEN

BACKGROUND: Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders, including megaesophagus. Treatment focuses on improving symptoms, and isosorbide and nifedipine may be used for this purpose. METHODOLOGY: We conducted a systematic review to evaluate the effectiveness of pharmacological treatment for Chagas' megaesophagus. We searched MEDLINE, Embase and LILACS databases up to January 2018. We included both observational studies and RCTs evaluating the effects of isosorbide or nifedipine in adult patients with Chagas' megaesophagus. Two reviewers screened titles and abstracts, selected eligible studies and extracted data. We assessed the risk of bias using NIH 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group' and RoB 2.0 tool. Overall quality of evidence was assessed using GRADE. PRINCIPAL FINDINGS: We included eight studies (four crossover RCTs, four before-after studies). Three studies evaluated the effect of isosorbide on lower esophageal sphincter pressure (LESP), showing a significant reduction (mean difference -10.52mmHg, 95%CI -13.57 to-7.47, very low quality of evidence). Three studies reported the effect of isosorbide on esophageal emptying, showing a decrease in esophageal retention rates (mean difference -22.16%, 95%CI -29.94 to -14.38, low quality of evidence). In one study, patients on isosorbide reported improvement in the frequency and severity of dysphagia (moderate quality of evidence). Studies evaluating nifedipine observed a decrease in LESP but no effect on esophageal emptying (very low and low quality of evidence, respectively). Isosorbide had a higher incidence of headache as a side effect than nifedipine. CONCLUSIONS: Although limited, available evidence shows that both isosorbide and nifedipine are effective in reducing esophageal symptoms. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile. TRIAL REGISTRATION: PROSPERO CRD42017055143. ClinicalTrials.gov CRD42017055143.


Asunto(s)
Enfermedad de Chagas/complicaciones , Acalasia del Esófago/tratamiento farmacológico , Isosorbida/administración & dosificación , Nifedipino/administración & dosificación , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
15.
Sci Rep ; 7(1): 3563, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28620185

RESUMEN

The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl -/- mice developed megaesophagus and rectal prolapse. Inhibition of c-Abl with imatinib mesylate, an anti-CML drug, or ablation of c-Abl using Prx1-Cre, which marks smooth muscle cells, recapitulated most of the muscularis propria phenotypes. The pathogenesis of rectal prolapse was attributable to overproliferation of smooth muscle cells, which was caused by enhanced ERK1/2 activation. Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Genes abl , Homeostasis , Mucosa Intestinal/metabolismo , Animales , Proliferación Celular , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/etiología , Acalasia del Esófago/metabolismo , Acalasia del Esófago/patología , Esófago/efectos de los fármacos , Esófago/metabolismo , Genes p16 , Predisposición Genética a la Enfermedad , Homeostasis/efectos de los fármacos , Mesilato de Imatinib/farmacología , Mucosa Intestinal/efectos de los fármacos , Ratones , Ratones Noqueados , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Fenotipo , Prolapso Rectal/etiología , Prolapso Rectal/metabolismo , Prolapso Rectal/patología
16.
Semin Pediatr Surg ; 26(2): 116-120, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28550869

RESUMEN

Achalasia is a rare neurogenic motility disorder of the esophagus, occurring in approximately 0.11 cases per 100,000 children. The combination of problems (aperistalsis, hypertensive lower esophageal sphincter (LES), and lack of receptive LES relaxation) results in patients having symptoms of progressive dysphagia, weight loss, and regurgitation. Treatment modalities have evolved over the past few decades from balloon dilation and botulinum toxin injection to laparoscopic Heller myotomy and endoscopic myotomy. Most data on achalasia management is extrapolated to children from adult experience. This article describes understanding of the pathogenesis and discusses newer therapeutic techniques as well as controversies in management.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Acalasia del Esófago/cirugía , Niño , Acalasia del Esófago/tratamiento farmacológico , Humanos
17.
Horm Res Paediatr ; 88(2): 167-171, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28395280

RESUMEN

INTRODUCTION: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients' fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. PATIENT AND RESULTS: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient's growth pattern. CONCLUSIONS: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The long-term effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS.


Asunto(s)
Acetilcisteína/uso terapéutico , Insuficiencia Suprarrenal/tratamiento farmacológico , Antioxidantes/uso terapéutico , Acalasia del Esófago/tratamiento farmacológico , Trastornos del Crecimiento/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Acetilcisteína/farmacología , Insuficiencia Suprarrenal/sangre , Antioxidantes/farmacología , Niño , Preescolar , Acalasia del Esófago/sangre , Trastornos del Crecimiento/sangre , Humanos , Lactante , Masculino , Especies Reactivas de Oxígeno/sangre , Resultado del Tratamiento
18.
Vet Rec ; 180(16): 404, 2017 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-28188161

RESUMEN

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty-one puppies were randomly assigned to two groups (treatment and control). The dogs were given sildenafil oral suspension 1 mg/kg every 12 hours for 14 days or placebo in a masked fashion. Clinical signs (frequency of regurgitation and weight gain) and oesophagrams (relative oesophageal diameter, ROD) were evaluated in order to assess the efficacy of drug treatment, by examiners who were unaware of the study protocol. In addition, a set of in vitro experiments on isolated samples of canine lower oesophageal sphincter (LOS) was performed, and the effects of increasing concentrations of sildenafil on basal tone and electrically-stimulated motility were assessed. Sildenafil administration significantly reduced the number of regurgitation episodes (0.88±1.40 v 2.65±1.56, P<0.0001) and significantly increased weight gain in the treated dogs compared to controls (79.76±28.30 per cent v 53.40±19.30 per cent, P=0.034). ROD values, at the end of the treatment period, were significantly decreased in the sildenafil group, compared to pre-treatment values (0.97±0.19 v 0.24±0.14, P<0.0001), in contrast to control subjects (0.98±0.17 v 1.10±0.25, P=0.480). In accordance with the in vivo findings, sildenafil dose-dependently reduced basal tone and increased electrically-induced relaxation of dog LOS samples. These results suggest that sildenafil citrate helps ameliorate clinical and radiographic signs in dogs with CIM by reducing LOS tone, and could represent a novel therapeutic tool for the treatment of this disease.


Asunto(s)
Enfermedades de los Perros/congénito , Enfermedades de los Perros/tratamiento farmacológico , Acalasia del Esófago/veterinaria , Citrato de Sildenafil/uso terapéutico , Animales , Enfermedades de los Perros/diagnóstico por imagen , Perros , Acalasia del Esófago/congénito , Acalasia del Esófago/diagnóstico por imagen , Acalasia del Esófago/tratamiento farmacológico , Femenino , Masculino , Radiografía/veterinaria , Resultado del Tratamiento
19.
Dis Esophagus ; 30(3): 1-5, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-27337985

RESUMEN

In achalasia and spastic esophageal motility disorders, botulinum toxin (botox) injection is considered an effective and low-risk procedure for short-term symptom relief. It is mainly offered to medically high-risk patients. However, no analysis of risks of botox injections has been performed. To determine the incidence and risk factors of procedure-related complications after esophageal botox injections, we analyzed the records of all patients undergoing botox injection therapy for esophageal motility disorders at four university hospitals in Europe and North America between 2008 and 2014. Complications were assigned grades according to the Clavien-Dindo classification. In 386 patients, 661 botox treatments were performed. Main indications were achalasia (51%) and distal esophageal spasm (DES) (30%). In total, 52 (7.9%) mild complications (Clavien-Dindo grade I) were reported by 48 patients, the majority consisting of chest pain or heartburn (29 procedures) or epigastric pain (5 procedures). No ulceration, perforation, pneumothorax, or abscess were reported. One patient died after developing acute mediastinitis (Clavien-Dindo grade V) following injections in the body of the esophagus. In univariate logistic regression, younger age was associated with an increased risk of complications (OR 1.43, 95%CI 1.03-1.96). Treatment for DES, injections into the esophageal body, more injections per procedure, more previous treatments and larger amount of injected botulinum toxin were no risk factors for complications. Esophageal botox injection seems particularly appropriate for high-risk patients due to low complication rate. However, it should not be considered completely safe, as it is associated with rare side effects that cannot be predicted.


Asunto(s)
Toxinas Botulínicas/efectos adversos , Trastornos de la Motilidad Esofágica/tratamiento farmacológico , Inyecciones/efectos adversos , Neurotoxinas/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Toxinas Botulínicas/administración & dosificación , Dolor en el Pecho/inducido químicamente , Acalasia del Esófago/tratamiento farmacológico , Espasmo Esofágico Difuso/tratamiento farmacológico , Esófago , Europa (Continente) , Femenino , Pirosis/inducido químicamente , Hospitales Universitarios , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neurotoxinas/administración & dosificación , América del Norte , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
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