RESUMEN
Proteolipid protein 1 (Plp1) is highly expressed in enteric glia, labeling cells throughout the mucosa, muscularis, and the extrinsic innervation. Plp1 is a major constituent of myelin in the central and peripheral nervous systems, but the absence of myelin in the enteric nervous system (ENS) suggests another role for Plp1 in the gut. Although the functions of enteric glia are still being established, there is strong evidence that they regulate intestinal motility and permeability. To interrogate the role of Plp1 in enteric glia, we investigated gut motility, secretomotor function and permeability, and evaluated the ENS in mice lacking Plp1. We studied two time points: â¼3 mo (young) and >1 yr (old). Old Plp1 null mice exhibited increased fecal output, decreased fecal water content, faster whole gut transit times, reduced intestinal permeability, and faster colonic migrating motor complexes. Interestingly, in both young and old mice, the ENS exhibited normal glial and neuronal numbers as well as glial arborization density in the absence of Plp1. As Plp1-associated functions involve mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Mapk/Erk1/2) signaling and Mapk/Erk1/2 are reported to have a regulatory role in intestinal motility, we measured protein expression of Erk1/2 and its active form in the small intestine. Old Plp1 null mice had reduced levels of phosphorylated-Erk1/2. Although Plp1 is not required for the normal appearance of enteric glial cells, it has a regulatory role in intestinal motility and barrier function. Our results suggest that functional changes mediated by Plp1-expressing enteric glia may involve Erk1/2 activation.NEW & NOTEWORTHY Here, we describe that Plp1 regulates gut motility and barrier function. The functional effects of Plp1 eradication are only seen in old mice, not young. The effects of Plp1 appear to be mediated through the Erk1/2 pathway.
Asunto(s)
Motilidad Gastrointestinal , Mucosa Intestinal , Proteína Proteolipídica de la Mielina , Animales , Ratones , Sistema Nervioso Entérico/fisiología , Motilidad Gastrointestinal/fisiología , Ratones Noqueados , Neuroglía/metabolismo , Neuronas/metabolismo , Proteolípidos/metabolismo , Proteolípidos/farmacología , Proteína Proteolipídica de la Mielina/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiologíaRESUMEN
ABSTRACT: Neurogastroenterology and motility (NGM) disorders are common in childhood and are often very debilitating. Although pediatric gastroenterology fellows are expected to obtain training in the diagnosis and management of patients with these disorders, there is an ongoing concern for unmet needs and lack of exposure and standardized curriculum. In the context of tailoring training components, outcome and expressed needs of pediatric gastroenterology fellows and programs, members of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and American Neurogastroenterology and Motility Society (ANMS) developed guidelines for NGM training in North America in line with specific expectations and goals of training as delineated through already established entrustable professional activities (EPAs). Members of the joint task force applied their expertise to identify the components of knowledge, skills, and management, which are expected of NGM consultants. The clinical knowledge, skills and management elements of the NGM curriculum are divided into domains based on anatomic regions including esophagus, stomach, small bowel, colon and anorectum. In addition, dedicated sections on pediatric functional gastrointestinal (GI) disorders, research and collaborative approach, role of behavioral health and surgical approaches to NGM disorders and transition from pediatric to adult neurogastroenterology are included in this document. Members of the NASPGHAN-ANMS task force anticipate that this document will serve as a resource to break existing barriers to pursuing a career in NGM and provide a framework towards uniform training expectations at 3 hierarchical tiers corresponding to EPA levels.
Asunto(s)
Gastroenterología , Enfermedades Gastrointestinales , Adulto , Niño , Competencia Clínica , Curriculum , Gastroenterología/educación , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Humanos , América del Norte , Sociedades Médicas , Estados UnidosRESUMEN
Although still controversial, there is increasing agreement that postnatal neurogenesis occurs in the enteric nervous system (ENS) in response to injury. Following acute colitis, there is significant cell death of enteric neurons and evidence suggests that subsequent neural regeneration follows. An enteric neural stem/progenitor cell population with neurogenic potential has been identified in culture; in vivo, compensatory neurogenesis is driven by enteric glia and may also include de-differentiated Schwann cells. Recent evidence suggests that changes in the enteric microenvironment due to injury-associated increases in glial cell-derived neurotrophic factor (GDNF), serotonin (5-hydroxytryptamine [HT]), products from the gut microbiome, and possibly endocannabinoids may lead to the transdifferentiation of mature enteric glia and may reprogram recruited Schwann cells. Targeting neurogenic pathways presents a promising avenue toward the development of new and innovative treatments for acquired damage to the ENS. In this review, we discuss potential sources of newly generated adult enteric neurons, the involvement of GDNF, 5-HT, endocannabinoids, and lipopolysaccharide, as well as therapeutic applications of this evolving work. Stem Cells 2019;37:1136-1143.
Asunto(s)
Sistema Nervioso Entérico/fisiología , Células-Madre Neurales/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Animales , Proliferación Celular/fisiología , Colitis/patología , Colitis/fisiopatología , Sistema Nervioso Entérico/citología , Humanos , Intestinos/patología , Intestinos/fisiopatología , Regeneración Nerviosa/fisiología , Células-Madre Neurales/citología , Neuronas/citologíaRESUMEN
OBJECTIVES: Timed barium esophagram (TBE) is a fluoroscopic study that is widely employed as an adjunctive tool for diagnosing esophageal emptying disorders in adults (eg, achalasia, esophagogastric junction outflow obstruction [EGJOO]) and for following response to treatment. We aimed to describe the characteristics and feasibility of a pediatric TBE protocol and provide a first report of the potential value of TBE for assessment of esophageal emptying in the pediatric population. METHODS: Retrospective chart review of pediatric patients at a tertiary pediatric hospital who underwent TBE from October 2017 to October 2019. Patient and test characteristics were summarized using descriptive statistics. Results from patients who had both TBE and high-resolution esophageal manometry (HRM) were used to generate ROC curves for TBE to identify esophageal emptying disorders. RESULTS: Twenty-two patients underwent 25 TBE. Fourteen of 23 (61%) received 150âmL barium volume per protocol. Nearly half (42%) of subjects could tolerate ingesting barium within 20âseconds. Nine individuals underwent HRM. The sensitivity of standard adult TBE criteria (1âcm barium column height at 5âminutes) to detect emptying disorder was 100%, specificity 40%. A modified diagnostic cutoff (1.6âcm height at 5âminutes) offered 100% sensitivity, 80% specificity. CONCLUSIONS: TBE is feasible and should be considered an adjunctive noninvasive screen for impaired esophageal emptying in children. There was heterogeneous adherence to protocol for timing and volume of barium; however, studies remained interpretable. This population may benefit from different diagnostic cutoffs than adults, and clinical judgment should be used until specific diagnostic cutoffs are determined in children.
Asunto(s)
Acalasia del Esófago , Adulto , Bario , Sulfato de Bario , Niño , Humanos , Manometría , Estudios RetrospectivosRESUMEN
OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.
Asunto(s)
Gastroenterología , Enfermedades Gastrointestinales , Niño , Esófago , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Motilidad Gastrointestinal , Humanos , América del NorteRESUMEN
OBJECTIVES: Chronic constipation is a common childhood problem and often caused or worsened by abnormal dynamics of defecation. The aim of this study was to assess the benefit of pelvic floor physical therapy (PFPT), a novel treatment in pediatrics for the treatment of chronic constipation with dyssynergic defecation. METHODS: This was a retrospective study of 69 children seen at a pediatric neurogastroenterology program of a large tertiary referral center for chronic constipation and dyssynergic defecation, determined by anorectal manometry and balloon expulsion testing. We compared the clinical outcome of patients who underwent PFPT (n = 49) to control patients (n = 20) whom received only medical treatment (laxatives/stool softeners). Additionally, characteristics of the treatment group were analyzed in relation to therapeutic response. RESULTS: Thirty-seven (76%) of the patients who received physical therapy had improvement in constipation symptoms, compared to 5 (25%) of the patients on conservative treatment (p < 0.01). Additionally, patients who received pelvic physical therapy had fewer hospitalizations for cleanouts (4 vs. 25%, p = 0.01) and -colonic surgery than those that were treated with medical therapy exclusively (0 vs. 10%, p = 0.03). Among the patients who received physical therapy, those that suffered from anxiety and/or low muscle tone had a higher response rate (100%). There were no adverse effects from the intervention. CONCLUSION: The new field of pediatric PFPT is a safe and effective intervention for children with dyssynergic defecation causing or contributing to chronic constipation, particularly in children whose comorbidities include anxiety and low -muscle tone.
Asunto(s)
Ataxia/fisiopatología , Estreñimiento/fisiopatología , Estreñimiento/terapia , Defecación , Diafragma Pélvico/fisiopatología , Modalidades de Fisioterapia , Adolescente , Canal Anal/fisiopatología , Ataxia/complicaciones , Niño , Preescolar , Estreñimiento/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Manometría , Recto/fisiopatología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Neurogastroenterology and motility (NGM) disorders are common and have a high health care burden. Although pediatric gastroenterology fellows are expected to obtain comprehensive training in the diagnosis and management of NGM disorders, there is ongoing concern for unmet training needs and lack of exposure in treating patients who suffer from NGM problems. METHODS: We conducted a cross-section survey of trainees listed as pediatric gastroenterology fellows in North American training programs in 2018 via direct E-mail and the pediatric gastroenterology listserv. Eighty-one pediatric gastroenterology fellows responded to the anonymous survey. RESULTS: A total of 53.1% of the fellows reported interest in NGM; however, 75.1% of the fellows believed they had not been adequately trained in NGM during their fellowship. Eighty percent of fellows with 2 weeks or less of dedicated motility training reported that they received inadequate NGM training, compared to 46.2% fellows who received 1 or more months of dedicated motility training (Pâ=â0.0148). The majority of fellows reported not being comfortable in performing gastrointestinal (GI) motility studies. The majority of fellows also reported not being comfortable in interpreting GI motility studies. CONCLUSIONS: Although most pediatric gastroenterology fellows expressed interest in NGM, the lack of exposure and dedicated training in motility during fellowship were identified as barriers to pursuing motility-focused careers. Furthermore, most fellows reported limited comfort with performing and/or interpreting motility studies. Changes are needed to encourage fellows to develop their interest and expertise in NGM.
Asunto(s)
Competencia Clínica , Becas/métodos , Gastroenterología/educación , Pediatría/educación , Estudiantes de Medicina/psicología , Adulto , Niño , Estudios Transversales , Curriculum , Educación de Postgrado en Medicina , Femenino , Gastroenterología/métodos , Motilidad Gastrointestinal , Humanos , Masculino , Pediatría/métodos , Encuestas y CuestionariosRESUMEN
Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Sistema Nervioso Entérico/patología , Tracto Gastrointestinal/patología , Enfermedad de Hirschsprung/terapia , Seudoobstrucción Intestinal/terapia , Células-Madre Neurales/trasplante , Trasplante de Células Madre , Animales , Modelos Animales de Enfermedad , Tracto Gastrointestinal/inervación , Guías como Asunto , Enfermedad de Hirschsprung/patología , Humanos , Seudoobstrucción Intestinal/patologíaRESUMEN
BACKGROUND: Enteric neural stem/progenitor cells (ENSCs) offer an innovative approach to treating Hirschsprung disease (HSCR) and other enteric neuropathies. However, postnatal-derived human ENSCs have not been thoroughly characterized and their behavior in the embryonic and postnatal intestinal environment is unknown. METHODS: ENSCs were isolated from the intestines of 25 patients undergoing bowel resection, including 7 children with HSCR. Neuronal differentiation and proliferation of ENSCs from submucosal and myenteric plexuses from patients with and without HSCR were characterized. ENSC migration and differentiation were studied following transplantation into embryonic chick neural crest, embryonic chick hindgut, and postnatal mouse aganglionic colon. RESULTS: The proliferative and neurogenic potential of ENSCs from HSCR intestine is equivalent to that of non-HSCR controls. Similarly, no difference was observed between myenteric- and submucosal-derived ENSCs. Postnatal ENSCs transplanted to embryonic neural crest pathways and to aneural hindgut migrate normally and differentiate into appropriate neural crest-derived cell types. ENSCs in postnatal mouse aganglionic colon differentiate into neurons and glia both ex vivo and in vivo. CONCLUSIONS: ENSCs isolated from the postnatal intestine of patients with and without HSCR can behave like embryonic neural crest-derived cells. These results support the feasibility of cell-based therapy for future treatment of neurointestinal disease.
Asunto(s)
Movimiento Celular , Proliferación Celular , Enfermedad de Hirschsprung/patología , Intestino Grueso/inervación , Plexo Mientérico/patología , Células-Madre Neurales/patología , Neurogénesis , Nicho de Células Madre , Plexo Submucoso/patología , Adolescente , Animales , Células Cultivadas , Embrión de Pollo , Niño , Preescolar , Modelos Animales de Enfermedad , Femenino , Enfermedad de Hirschsprung/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Ratones Endogámicos C57BL , Células-Madre Neurales/trasplante , Esferoides Celulares , Trasplante de Células Madre , Adulto JovenRESUMEN
OBJECTIVES: Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. METHODS: Retrospective review (2005-2013) children (5-21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. RESULTS: Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (Pâ=â0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (Pâ=â0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (Pâ=â0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (Pâ=â.01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (Pâ=â.07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (Pâ=â0.24) did. CONCLUSIONS: Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.
Asunto(s)
Dolor Abdominal/tratamiento farmacológico , Antidepresivos Tricíclicos/uso terapéutico , Síndrome del Colon Irritable/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Dolor Abdominal/fisiopatología , Dolor Abdominal/psicología , Adolescente , Antidepresivos Tricíclicos/efectos adversos , Niño , Preescolar , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Gastroenterología , Humanos , Síndrome del Colon Irritable/fisiopatología , Síndrome del Colon Irritable/psicología , Modelos Logísticos , Masculino , Rol del Médico , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: A major area of unmet need is the development of strategies to restore neuronal network systems and to recover brain function in patients with neurological disease. The use of cell-based therapies remains an attractive approach, but its application has been challenging due to the lack of suitable cell sources, ethical concerns, and immune-mediated tissue rejection. We propose an innovative approach that utilizes gut-derived neural tissue for cell-based therapies following focal or diffuse central nervous system injury. RESULTS: Enteric neuronal stem and progenitor cells, able to differentiate into neuronal and glial lineages, were isolated from the postnatal enteric nervous system and propagated in vitro. Gut-derived neural progenitors, genetically engineered to express fluorescent proteins, were transplanted into the injured brain of adult mice. Using different models of brain injury in combination with either local or systemic cell delivery, we show that transplanted enteric neuronal progenitor cells survive, proliferate, and differentiate into neuronal and glial lineages in vivo. Moreover, transplanted cells migrate extensively along neuronal pathways and appear to modulate the local microenvironment to stimulate endogenous neurogenesis. CONCLUSIONS: Our findings suggest that enteric nervous system derived cells represent a potential source for tissue regeneration in the central nervous system. Further studies are needed to validate these findings and to explore whether autologous gut-derived cell transplantation into the injured brain can result in functional neurologic recovery.
Asunto(s)
Encéfalo/fisiopatología , Trasplante de Células/métodos , Sistema Nervioso Entérico/fisiología , Células-Madre Neurales/fisiología , Trasplante de Células Madre/métodos , Animales , Encéfalo/efectos de la radiación , Encéfalo/cirugía , Lesiones Encefálicas/cirugía , Lesiones Encefálicas/terapia , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Sistema Nervioso Entérico/citología , Ratones , Ratones Endogámicos C57BL , Células-Madre Neurales/trasplante , Neurogénesis , Traumatismos Experimentales por Radiación/cirugía , Traumatismos Experimentales por Radiación/terapiaRESUMEN
OBJECTIVES: This study aimed to examine the long-term clinical outcomes of children with severe constipation, as defined by need for rectal biopsy (RB), and to determine which baseline characteristics were predictors of successful outcome. METHODS: Children with severe constipation who underwent RB for evaluation of Hirschsprung disease at a tertiary medical center were eligible. A cohort of children with constipation without a history of RB served as controls (matched 2:1 by sex and age). Retrospective chart review of clinic visits was performed at baseline, 3, 6, 12, 18, and 24 months. Successful clinical outcomes were defined as ≥3 bowel movements weekly for ≥4 weeks, with ≤2 fecal incontinence episodes monthly, irrespective of laxative use. RESULTS: A total of 175 RB children (90 boys, mean age: 6.7 years) were matched to 350 controls. Mean duration of constipation symptoms before intake in the RB group was significantly longer compared with controls (3.7 vs 0.4 years, Pâ<â0.001). By 24 months, the cumulative percentage of children achieving at least 1 period of successful outcome was significantly higher in the control group compared with RB population (73% vs 24%, Pâ<â0.001). Multivariate analysis revealed that younger age (Pâ=â0.001, odds ratio 0.87) and shorter duration of constipation before RB (Pâ=â0.03, odds ratio 0.45) were significant predictors of successful outcome. CONCLUSIONS: Only one-quarter of patients with severe constipation achieved successful outcome during 2-year follow-up. Younger age and shorter duration of constipation at time of biopsy were predictors of successful outcomes, emphasizing the importance of early diagnosis and initiation of treatment in this population.
Asunto(s)
Biopsia/métodos , Estreñimiento/diagnóstico , Enfermedad de Hirschsprung/diagnóstico , Laxativos/uso terapéutico , Recto/patología , Adolescente , Niño , Preescolar , Estreñimiento/tratamiento farmacológico , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The enteric nervous system (ENS) is composed of neural crest-derived neurons (also known as ganglion cells) the cell bodies of which are located in the submucosal and myenteric plexuses of the intestinal wall. Intramucosal ganglion cells are known to exist but are rare and often considered ectopic. Also derived from the neural crest are enteric glial cells that populate the ganglia and the associated nerves, as well as the lamina propria of the intestinal mucosa. In Hirschsprung disease (HSCR), ganglion cells are absent from the distal gut because of a failure of neural crest-derived progenitor cells to complete their rostrocaudal migration during embryogenesis. The fate of intramucosal glial cells in human HSCR is essentially unknown. We demonstrate a network of intramucosal cells that exhibit dendritic morphology typical of neurons and glial cells. These dendritic cells are present throughout the human gut and express Tuj1, S100, glial fibrillary acidic protein, CD56, synaptophysin, and calretinin, consistent with mixed or overlapping neuroglial differentiation. The cells are present in aganglionic colon from patients with HSCR, but with an altered immunophenotype. Coexpression of Tuj1 and HNK1 in this cell population supports a neural crest origin. These findings extend and challenge the current understanding of ENS microanatomy and suggest the existence of an intramucosal population of neural crest-derived cells, present in HSCR, with overlapping immunophenotype of neurons and glia. Intramucosal neuroglial cells have not been previously recognized, and their presence in HSCR poses new questions about ENS development and the pathobiology of HSCR that merit further investigation.
Asunto(s)
Colon/patología , Enfermedad de Hirschsprung/patología , Mucosa Intestinal/patología , Neuroglía/patología , Biomarcadores/análisis , Antígeno CD56/análisis , Antígenos CD57/análisis , Calbindina 2/análisis , Estudios de Casos y Controles , Diferenciación Celular , Linaje de la Célula , Forma de la Célula , Colon/química , Proteína Ácida Fibrilar de la Glía/análisis , Enfermedad de Hirschsprung/metabolismo , Humanos , Mucosa Intestinal/química , Neuroglía/química , Proteínas S100/análisis , Sinaptofisina/análisis , Tubulina (Proteína)/análisisRESUMEN
We evaluated the effect of propofol on resting anal sphincter pressure (RP) during anorectal manometry performed under general anesthesia in 20 children with chronic constipation. After propofol bolus administration, there was a significant decrease in the RP in 95% of children from a mean of 51.5 ± 15.3 to a mean nadir of 21.7 ± 10.5 mmHg (P < 0.001). The new postpropofol RP of 47.0 ± 12.4 mmHg was significantly lower compared with prepropofol RP (P < 0.0001). Propofol should be used with caution as an anesthetic agent for anorectal manometry, given the potential for confounding RP measurements.
Asunto(s)
Canal Anal/efectos de los fármacos , Anestésicos Intravenosos/farmacología , Manometría , Propofol/farmacología , Reflejo/efectos de los fármacos , Canal Anal/fisiopatología , Anestesia General , Niño , Preescolar , Estreñimiento/fisiopatología , Femenino , Humanos , Masculino , PresiónRESUMEN
Phosphatase and tensin homolog (Pten) is a key regulator of cell proliferation and a potential target to stimulate postnatal enteric neuro- and/or gliogenesis. To investigate this, we generated two tamoxifen-inducible Cre recombinase murine models in which Pten was conditionally ablated, (1) in glia (Plp1-expressing cells) and (2) in neurons (Calb2-expressing cells). Tamoxifen-treated adult (7-12 weeks of age; n = 4-15) mice were given DSS to induce colitis, EdU to monitor cell proliferation, and were evaluated at two timepoints: (1) early (3-4 days post-DSS) and (2) late (3-4 weeks post-DSS). We investigated gut motility and evaluated the enteric nervous system. Pten inhibition in Plp1-expressing cells elicited gliogenesis at baseline and post-DSS (early and late) in the colon, and neurogenesis post-DSS late in the proximal colon. They also exhibited an increased frequency of colonic migrating motor complexes (CMMC) and slower whole gut transit times. Pten inhibition in Calb2-expressing cells did not induce enteric neuro- or gliogenesis, and no alterations were detected in CMMC or whole gut transit times when compared to the control at baseline or post-DSS (early and late). Our results merit further research into Pten modulation where increased glia and/or slower intestinal transit times are desired (e.g., short-bowel syndrome and rapid-transit disorders).
Asunto(s)
Sistema Nervioso Entérico , Animales , Ratones , Sistema Nervioso Entérico/metabolismo , Neurogénesis/fisiología , Proteolípidos/metabolismo , Tamoxifeno/farmacología , Tensinas/metabolismoRESUMEN
OBJECTIVE: To compare scintigraphic gastric emptying and antroduodenal manometry (ADM) studies with the wireless motility capsule test in symptomatic pediatric patients. STUDY DESIGN: Patients aged 8-17 years with severe upper gastrointestinal symptoms (ie, nausea, vomiting, retching, abdominal pain) referred for ADM were recruited. A standardized protocol for ADM was used. On a different day, participants were given a standardized meal and then swallowed the wireless motility capsule. A wireless receiver unit worn during the study recorded transmitted data. If not performed previously, a 2-hour scintigraphic gastric emptying study was completed at the time of ADM testing. RESULTS: A total of 22 patients were recruited, of whom 21 had complete scintigraphic gastric emptying study data and 20 had complete ADM data. The wireless motility capsule test had 100% sensitivity and 50% specificity in detecting gastroparesis compared with the 2-hour scintigraphic gastric emptying study. The wireless motility capsule test detected motor abnormalities in 17 patients, compared with 10 detected by ADM. Dichotomous comparison yielded a diagnostic difference between ADM and the wireless motility capsule test (P<.01). Migrating motor complexes were recognized in all patients by both ADM and the wireless motility capsule test. The wireless motility capsule test was well tolerated in all patients, and there were no side effects. CONCLUSION: In symptomatic pediatric patients, the wireless motility capsule test is highly sensitive compared with scintigraphic gastric emptying studies in detecting gastroparesis, and seems to be more sensitive than ADM in detecting motor abnormalities.
Asunto(s)
Endoscopía Capsular , Vaciamiento Gástrico , Enfermedades Gastrointestinales/diagnóstico , Gastroparesia/diagnóstico , Adolescente , Niño , Femenino , Enfermedades Gastrointestinales/diagnóstico por imagen , Gastroparesia/diagnóstico por imagen , Humanos , Masculino , Manometría/métodos , Cintigrafía , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Chronic constipation (CC) is a common problem in pediatrics and is often the result of obstructed defecation. The aim of the present study was to study the feasibility and efficacy of the balloon expulsion test (BET) in the diagnosis and management of children with CC. METHODS: Retrospective study comparing BET and high-resolution anorectal manometry (ARM). The BET was done together with ARM in 29 children, ages 8 to 19 years, with CC. For BET, a 60-mL balloon was used. Passage of balloon in 1 minute or less was considered normal. RESULTS: Fifteen of the 29 children had a normal BET. Of these, 14 also had an ARM, all of which were normal (except for 2 cases with a hypertonic baseline anal sphincter). Thus 12 of 14 with BET and ARM were normal on both (correlation between the tests 86%). Of the 14 children that failed BET, 10 had distal abnormalities by ARM, contrast studies, EMG, or assessment by a pelvic physical therapist. All of the patients with a nonrelaxing sphincter or outlet obstruction were treated with laxatives, anal sphincter Botox, and/or pelvic physical therapy and biofeedback. In follow-up of at least 3 months, all of the patients with a failed BET were improved. CONCLUSIONS: We found a high correlation between a normal ARM and BET. If the BET is abnormal and the ARM does not identify a cause for the distal obstruction, additional studies may be needed, including contrast enema, defecography, or electromyography. BET appears to be a safe, reliable, and useful test in the evaluation and management of CC in children.