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1.
J Paediatr Child Health ; 56(11): 1708-1718, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33197982

RESUMEN

Constipation is a common problem in childhood. The most common type of constipation is functional, accounting for 90-95% of all cases. The aim of this review is to provide clinical scenarios with treatment using evidence-based information, and management strategies and a clinical algorithm to guide the management of constipation in children. Recent guidelines and online information sites are detailed. Clinical red flags and organic causes of constipation are included. Four clinical scenarios are presented: case (1) 4-month-old child with constipation since birth and likely Hirschsprung disease; case (2) 6-month-old infant with infant dyschezia; case (3) 4-year old with functional constipation; and; case (4) 9-year old with treatment resistant constipation. Children with functional constipation need a thorough history and physical exam to rule out the presence of any 'red flags' but do not require laboratory investigations. Management includes education and demystification, disimpaction followed by maintenance therapy with oral laxatives, dietary counselling and toilet training. Treatment options differ between infants and children. Disimpaction and maintenance regimens for common laxatives are presented. On treatment failure or on suspicion of organic disease the patient should be referred for further evaluation. The radionuclide intestinal transit study (scintigraphy) is a useful modality for evaluation and planning of management in treatment-resistant children. Treatment options for treatment-resistant patients are presented. High-level evidence (meta-analyses) for pharmalogical and non-pharmalogical treatment modalities are reviewed and an algorithm for assessment and treatment are presented.


Asunto(s)
Estreñimiento , Enfermedad de Hirschsprung , Niño , Preescolar , Estreñimiento/tratamiento farmacológico , Estreñimiento/terapia , Humanos , Lactante , Recién Nacido , Laxativos/uso terapéutico , Pediatras , Insuficiencia del Tratamiento
2.
Neuromodulation ; 23(8): 1061-1081, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32017319

RESUMEN

BACKGROUND: In the last 20 years, studies have shown that large bowel function can be modified by neural stimulation. While still in its infancy, this area of research is beginning to show promise. METHODS: This overview brings together systematic reviews and meta-analyses of electrical stimulation used to treat colonic disorders (fecal incontinence, constipation, slow transit constipation [STC], irritable bowel syndrome [IBS-C], and spina bifida-neurogenic bowel). Different methods of electrical stimulation including through sacral nerves, paraspinal, transabdominal, and using electroacupuncture over the ankle or knee and direct stimulation of the bowel are reviewed. RESULTS AND DISCUSSION: Most evidence is low level (pilot and small cohort studies) but with more RCTs appearing. Sacral nerve stimulation (SNS) does improve urinary dysfunction and fecal incontinence but not constipation. It is expensive with high rates of reoperation. Transcutaneous stimulation with interferential current (IFC, alternating current at KHz frequency with 2 channels out of phase) does improve constipation and may provide benefit as an adjuvant to behavioral or exercise therapies. Acupuncture and electro-acupuncture (low/very low-level evidence) may have a benefit for constipation. CONCLUSION: SNS is effective but expensive and limited to extreme patients. Transcutaneous stimulation is noninvasive and cheap and IFC may be effective for constipation, but many parameters need to be optimized and higher level evidence provided from studies (sham, blinding, and larger patient numbers). The next 20 years should be exciting in the field as higher level studies are performed.


Asunto(s)
Colon/fisiopatología , Estreñimiento , Terapia por Estimulación Eléctrica , Incontinencia Fecal , Estreñimiento/terapia , Estimulación Eléctrica , Electroacupuntura , Incontinencia Fecal/terapia , Humanos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Nervios Espinales , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
3.
Neuromodulation ; 21(7): 669-675, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29498773

RESUMEN

BACKGROUND: Transcutaneous electrical stimulation (TES) using interferential current (IFC) is a new therapeutic treatment for constipation. Clinical studies show that TES-IFC for 3-6 months improves colonic transit, but it is not clear if short-term stimulation affects transit or the effect requires longer to develop. The aim of this study was to determine if TES-IFC for only four days affects oral-rectal transit time in healthy pigs. METHODS: Twenty-two 4-5-week old large white female piglets had transit studies during week 4 and week 5 by placing a capsule containing 18 radiopaque plastic markers in the esophagus under anesthetic followed by x-rays at 6, 30, 54, and 78 hours. Animals were randomly assigned to active or control groups. The active group received TES for 30 min daily for four days. Interferential current was applied through four electrodes (4 × 4 cm), with two para-spinal just below the last rib and two on the belly at the same level. Stimulation was at 4000 Hz and 4080-4160 Hz with currents crossing through the abdominal cavity. RESULTS: Whole bowel transit times ranged from 7.7 to 72.2 hours, stomach transit from <1 to 63 hours, and bowel with rectum transit time from 5 to 53 hours. Transit times were the same for the control (median 28.4 hours) and TES-IFC (23.0 hours) groups in the prestimulation and stimulation weeks (control 23.0, TES-IFC 19.8 hours) with no change within or between groups. CONCLUSION: Four days of half-hour TES-IFC daily in healthy 5-week-old piglets did not change oral-rectal transit time.


Asunto(s)
Abdomen/inervación , Tránsito Gastrointestinal/fisiología , Boca/fisiología , Recto/fisiología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Abdomen/diagnóstico por imagen , Animales , Femenino , Boca/diagnóstico por imagen , Boca/inervación , Distribución Aleatoria , Recto/diagnóstico por imagen , Recto/inervación , Porcinos , Factores de Tiempo
4.
Pediatr Surg Int ; 32(8): 773-7, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27392639

RESUMEN

BACKGROUND/PURPOSE: Long-term problems with faecal incontinence occur in up to 50 % of patients after pull-through for Hirschsprung disease (HSCR). The cause often remains unknown, leading to empirical treatments. Using nuclear transit study, we found some patients surprisingly had rapid proximal colonic transit, suspicious of occult diarrhoea. We aimed to assess whether these patients had unrecognized adverse reactions to food. METHODS: Patients (n = 10, all males, 9.6 year; 4.25-15.5 years) with persistent faecal incontinence following pull-through for HSCR referred to the senior author and after exclusion of anatomical defects, underwent nuclear transit studies. Most (8) subsequently underwent breath hydrogen tests for sugar malabsorption and were tested for adverse reactions to food. Exclusion diets for protein allergens, lactose or fructose were then trialed. RESULTS: Of the 10 patients with rapid intestinal transit proven on nuclear transit study, breath hydrogen tests for fructose and/or lactose malabsorption were done in 8, and were positive in 7/8 patients. Exclusion diets contributed to either resolution or improvement in faecal incontinence in 9/10 patients. CONCLUSIONS: Rapid transit in the proximal, ganglionated colon may be present in children with faecal incontinence following pull-through for HSCR, possibly secondary to adverse reactions to food. This study suggests that children with post-operative soiling may benefit from a transit study and hydrogen breath tests to diagnose adverse reactions to food caused by sugar malabsorption.


Asunto(s)
Incontinencia Fecal/fisiopatología , Hipersensibilidad a los Alimentos/fisiopatología , Tránsito Gastrointestinal/fisiología , Enfermedad de Hirschsprung/cirugía , Síndromes de Malabsorción/fisiopatología , Adolescente , Pruebas Respiratorias , Niño , Preescolar , Fructosa/metabolismo , Humanos , Hidrógeno/análisis , Lactosa/metabolismo , Masculino , Complicaciones Posoperatorias
5.
Neuromodulation ; 19(5): 515-21, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27293084

RESUMEN

AIM: As transcutaneous electrical stimulation (TES) increased defecation in children and adults with Slow-Transit Constipation (STC), we performed a pilot study to test if TES can improve symptoms (defecation and soiling) in children with chronic constipation without STC and transit delay in the anorectum. METHODS: Children with treatment-resistant constipation presenting to a tertiary hospital had gastrointestinal nuclear transit study (NTS) showing normal proximal colonic transit and anorectal holdup of tracer. TES was administered at home (1 hour/day for 3 months) using a battery-powered interferential stimulator, with four adhesive electrodes (4 × 4 cm) connected so currents cross within the lower abdomen at the level of S2-S4. Stimulation was added to existing laxatives. Daily continence diary, and quality-of-life questionnaires (PedsQL4.0) were compared before and after TES. RESULTS: Ten children (4 females: 5-10 years, mean 8 years) had holdup in the anorectum by NTS. Nine had <3 bowel motions (BM)/week. After three months TES, defecation frequency increased in 9/10 (mean 0.9-4.1 BM/week, p = 0.004), with 6/9 improved to ≥3 BM/week. Soiling reduced in 9/10 from 5.9 to 1.9 days/week with soiling, p = 0.004. Ten were on laxatives, and nine reduced/stopped laxative use. Quality-of-life improved to within the normal range. CONCLUSION: TES improved symptoms of constipation in >50% of children with treatment-resistant constipation with isolated holdup in the anorectum. Further studies (RCTs) are warranted in these children.


Asunto(s)
Estreñimiento/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Niño , Preescolar , Estreñimiento/psicología , Femenino , Servicios de Atención de Salud a Domicilio , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Calidad de Vida
6.
J Paediatr Child Health ; 51(12): 1195-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26059611

RESUMEN

AIM: Constipation is a common cause of admission to hospital for disimpaction, as oral laxatives are often inadequate. High-dose oral laxative protocols are used for complete bowel clearance prior to colonoscopy, but have not been reported for treating faecal impaction. The aim of this study was to assess the effectiveness of a high-dose oral protocol using polyethylene glycol with electrolytes (PEG + E) (Movicol Rx) combined with sodium picosulphate (SP) (Dulcolax SP Rx) in faecal impaction in children presenting to a suburban clinic. METHODS: Forty-four children presented with acute/chronic faecal impaction were given six to eight sachets of PEG + E were given on day 1, with decreasing doses on subsequent 3 days, while 15-20 SP drops were given on days 2 and 3. Compliance with medication was achieved using a simple method of motivation, with the child drinking the laxatives in a race. On day 4, PEG + E was reduced to one sachet and SP to 10 drops as an ongoing maintenance dose. Defecation, soiling, diet and water intake was monitored daily for 7 days in a diary. RESULTS: Forty-four children (aged 2-17 years) seen over 8 months were reviewed retrospectively. Children began defecating within 10-12 h reaching a maximum volume of stool/day (four cups) on day 2. All patients were disimpacted successfully and in the week following disimpaction there was no reported faecal soiling or complications. CONCLUSIONS: A high-dose oral protocol combining PEG + E sachets and SP drops successfully and safely disimpacted a cohort of children with acute/chronic constipation presenting to a suburban continence clinic. This protocol appears to be useful to control faecal disimpaction in an outpatient setting, thereby avoiding hospital admission.


Asunto(s)
Citratos/uso terapéutico , Estreñimiento/tratamiento farmacológico , Electrólitos/uso terapéutico , Impactación Fecal/tratamiento farmacológico , Laxativos/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Picolinas/uso terapéutico , Polietilenglicoles/uso terapéutico , Administración Oral , Adolescente , Catárticos/uso terapéutico , Niño , Preescolar , Citratos/administración & dosificación , Combinación de Medicamentos , Quimioterapia Combinada , Electrólitos/administración & dosificación , Femenino , Humanos , Laxativos/administración & dosificación , Masculino , Compuestos Organometálicos/administración & dosificación , Picolinas/administración & dosificación , Polietilenglicoles/administración & dosificación , Solventes/uso terapéutico , Servicios de Salud Suburbana , Resultado del Tratamiento
7.
Pediatr Surg Int ; 31(5): 445-51, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25672282

RESUMEN

Slow-transit constipation (STC) is a newly described subtype of intractable constipation in children which we originally identified with deficiency of substance P in axons supplying the proximal colonic muscle. When nuclear transit studies became available, the patients were found to have slow proximal colonic transit, and responded to antegrade enemas. Using the appendicostomy, we found that there was reduced frequency in propagating sequences throughout the colon. We began testing whether transcutaneous electrical stimulation (TES) could improve motility and symptoms, and over several trials have now shown that TES is remarkably effective in treating children with STC, with long-lasting effects. TES holds promise for treating STC, as well as a range of gastrointestinal motility disorders.


Asunto(s)
Estreñimiento/terapia , Terapia por Estimulación Eléctrica/métodos , Tránsito Gastrointestinal/fisiología , Niño , Estreñimiento/fisiopatología , Humanos
8.
Pediatr Surg Int ; 31(4): 317-25, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25690562

RESUMEN

Testicular descent occurs in two morphologically distinct phases, each under different hormonal control from the testis itself. The first phase occurs between 8 and 15 weeks when insulin-like hormone 3 (Insl3) from the Leydig cells stimulates the gubernaculum to swell, thereby anchoring the testis near the future inguinal canal as the foetus grows. Testosterone causes regression of the cranial suspensory ligament to augment the transabdominal phase. The second, or inguinoscrotal phase, occurs between 25 and 35 weeks, when the gubernaculum bulges out of the external ring and migrates to the scrotum, all under control of testosterone. However, androgen acts mostly indirectly via the genitofemoral nerve (GFN), which produces calcitonin gene-related peptide (CGRP) to control the direction of migration. In animal models the androgen receptors are in the inguinoscrotal fat pad, which probably produces a neurotrophin to masculinise the GFN sensory fibres that regulate gubernacular migration. There is little direct evidence that this same process occurs in humans, but CGRP can regulate closure of the processus vaginalis in inguinal hernia, confirming that the GFN probably mediates human testicular descent by a similar mechanism as seen in rodent models. Despite increased understanding about normal testicular descent, the common causes of cryptorchidism remain elusive.


Asunto(s)
Conducto Inguinal/anatomía & histología , Testículo/anatomía & histología , Testículo/fisiología , Criptorquidismo/etiología , Criptorquidismo/fisiopatología , Humanos , Masculino
9.
BMC Gastroenterol ; 14: 125, 2014 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-25015386

RESUMEN

BACKGROUND: When primary care of constipation fails, the patient may need emergency hospitalisation for disimpaction. This study aimed to provide population-based data on the number of unplanned admissions and the cost to the healthcare system for constipation in Victoria, Australia in financial year 2010-11. METHODS: The Victorian Admitted Episodes Dataset was examined to find the number of emergency hospital separations coded as constipation (ICD-10-AM Code K390). An estimate of costs was determined from the number of weighted inlier equivalent separations (WIES) multiplied by the WEIS price, used by the Victorian Government for funding purposes. RESULTS: There were 3978 emergency separations for constipation in Victoria in 2010-2011, 92% in public hospitals. Fifty-five percent were female and 38% > 75 years old. One third stayed overnight and 1/3 more than 1 day. The emergency bed day rate was 7.1 per 10,000 of population. The estimate of cost, based on WEIS, was approximately $8.3 million. Potential savings could be made by reducing the number of separations in 6 Local Government Areas (LGAs). CONCLUSIONS: This study shows that the burden (in number of admissions, emergency bed days and overall direct costs) in managing emergency admissions for constipation in Victoria, Australia, is very significant and likely to be similar in other developed countries. Improved primary healthcare and alternative ways to achieve faecal disimpaction without emergency admission could save the public health system a proportion of this $8.3 million.


Asunto(s)
Estreñimiento/terapia , Costos de la Atención en Salud , Hospitalización/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estreñimiento/economía , Estreñimiento/epidemiología , Femenino , Hospitalización/economía , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Masculino , Persona de Mediana Edad , Victoria/epidemiología , Adulto Joven
10.
J Paediatr Child Health ; 50(12): 993-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24976312

RESUMEN

AIM: Constipation is common, with severe symptoms requiring hospitalisation. Constipation can be a primary (present at admission and requires treatment or investigation) or principal (first listed) diagnosis for hospitalisation. In the USA, constipation is the second most common ambulatory care digestive diagnosis with total costs >US$1.7 billion/year. Incidence of hospitalisation for constipation in children peaks at toilet-training age. This study determined the burden of paediatric constipation to hospital care in Victoria, Australia. METHOD: The Victorian Admitted Episodes Dataset was analysed retrospectively, examining hospital admissions with a primary diagnosis of constipation in the 7-year period 2002/2003 to 2008/2009. RESULTS: For children, constipation was recorded as a primary diagnosis in 8688 admissions (3.6/1000 of population). In-hospital prevalence was ∼1.0%. Mean length of stay was 4.4 days (median 1.0, range 0-993, standard deviation 16.7). There were 1121 readmissions in 668 children. Average treatment cost was A$4235/admission (median A$1461, range A$0-$278 816), with annual costs of ∼A$5 505 500. Children in the highest socio-economic area had ∼50% fewer admissions (P < 0.0001). Predictors of readmission included age 10-18, male gender, rural residence, severe socio-economic disadvantage, public hospital, planned admission, longer length of stay and association with other medical conditions. CONCLUSIONS: This study identified that constipation in children is a significant cost burden in Victoria (costing public hospitals ∼A$5.5 million/year). Hospitalisation in Victoria is 10-fold higher than in the USA with 10% readmissions within a month. We conclude that strategies aimed at reducing hospitalisation for constipation could result in significant savings for the paediatric public health system in Victoria, Australia.


Asunto(s)
Atención Ambulatoria/economía , Estreñimiento/terapia , Costo de Enfermedad , Costos de la Atención en Salud/estadística & datos numéricos , Hospitalización/economía , Clase Social , Preescolar , Estreñimiento/diagnóstico , Estreñimiento/epidemiología , Femenino , Humanos , Lactante , Tiempo de Internación , Masculino , Estudios Retrospectivos , Victoria/epidemiología
11.
J Pharmacol Exp Ther ; 340(1): 27-36, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21957267

RESUMEN

Hemokinin-1 (HK-1) is a newly identified tachykinin, originating from the immune system rather than neurons, and may participate in the immune and inflammatory response. In colonic mucosa of patients with inflammatory bowel disease (IBD), up-regulation of the TAC4 gene encoding HK-1 and increased production of prostaglandin E2 (PGE2) occur. Our aim was to examine the mechanistic link between human HK-1 and PGE2 production in normal human colon. Exogenous HK-1 (0.1 µM) for 4 h evoked an increased PGE2 release from colonic mucosal and muscle explants by 10- and 3.5-fold, respectively, compared with unstimulated time controls. The HK-1-stimulated PGE2 release was inhibited by the tachykinin receptor antagonists (S)1-2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl-4-phenyl-l azonia-bicyclo[2.2.2]octane (SR140333) [neurokinin-1 (NK1)] and N-[(2S)-4-(4-acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide (SR48968) [neurokinin-2 (NK2)] and was also inhibited by the cyclooxygenase (COX)-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) (NS-398) but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560). A parallel study with substance P showed similar results. Molecular studies with HK-1-treated explants demonstrated a stimulatory effect on COX-2 expression at both transcription and protein levels. It is noteworthy that this was coupled with HK-1-induced down-regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA and protein expression. Immunoreactivity for 15-PGDH occurred on inflammatory cells, epithelial cells, platelets, and ganglia. This finding provides an additional mechanism for HK-1-evoked PGE2 increase, in which HK-1 may interfere with the downstream metabolism of PGE2 by suppressing 15-PGDH expression. In conclusion, our results uncover a novel inflammatory role for HK-1, which signals via NK1 and NK2 receptors to regulate PGE2 release from human colonic tissue, and may further explain a pathological role for HK-1 in IBD when abnormal levels of PGE2 occur.


Asunto(s)
Colon/metabolismo , Ciclooxigenasa 2/metabolismo , Dinoprostona/biosíntesis , Inhibidores Enzimáticos/farmacología , Hidroxiprostaglandina Deshidrogenasas/antagonistas & inhibidores , Taquicininas/farmacología , Adulto , Anciano , Western Blotting , Colitis/fisiopatología , Colon/efectos de los fármacos , Colon/enzimología , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Técnicas In Vitro , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Neuroquinina-1/efectos de los fármacos , Receptores de Neuroquinina-1/fisiología , Receptores de Neuroquinina-2/efectos de los fármacos , Receptores de Neuroquinina-2/fisiología , Estimulación Química , Taquicininas/antagonistas & inhibidores
12.
J Urol ; 188(4 Suppl): 1443-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22906642

RESUMEN

PURPOSE: Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic genitofemoral nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the genitofemoral nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the genitofemoral nerve in control and antiandrogen treated rats. MATERIALS AND METHODS: A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, nerves (Tuj1), calcitonin gene related peptide (marker for genitofemoral nerve) and cell nuclei (DAPI). RESULTS: The inguinal mammary bud, its adjacent androgen receptor and genitofemoral nerve mammary branch (containing calcitonin gene related peptide) persisted from embryonic day 17 to postnatal day 2 in all antiandrogen treated males, yet regressed in all control males by postnatal day 2. CONCLUSIONS: Antiandrogens resulted in the persistence of the mammary branch and inguinal mammary bud. Persistent genitofemoral nerve mammary branches may arrest or slow down gubernacular migration by releasing calcitonin gene related peptide in the mammary inguinal fat pad, thus reducing the chemotactic gradient to calcitonin gene related peptide from genitofemoral nerve branches in the distal scrotum. We hypothesize that this process may be related to antiandrogen induced cryptorchidism in the rodent.


Asunto(s)
Péptido Relacionado con Gen de Calcitonina/fisiología , Testículo/embriología , Testículo/inervación , Animales , Masculino , Ratas , Ratas Sprague-Dawley
13.
J Urol ; 186(4 Suppl): 1606-13, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21855918

RESUMEN

PURPOSE: Cryptorchidism is a common abnormality and normal testicular descent is controlled by the gubernaculum. The cremaster may originate from abdominal muscles during gubernacular eversion or alternatively it may develop inside the gubernaculum. We studied cremaster myogenesis to determine how it develops. MATERIALS AND METHODS: Coronal sections of the pelvis were prepared from male Sprague-Dawley® rats and from males treated prenatally with the antiandrogen flutamide at embryonic day 19, and postnatal days 10, 19 and 35 after receiving ethical approval. Immunohistochemical stains were prepared for Ki67, Pax-7, myogenin, myosin heavy chain 7, Myh1, Myh2, Myh4, embryonic myosin, and slow and cardiac troponin T. Cell counts of the 1) gubernacular tip, 2) proximal gubernaculum/cremaster muscle and 3) adjacent abdominal wall are shown as a percent of positive fibers or positive cells per area. RESULTS: Throughout embryonic day 19, and postnatal days 10 and 19 proliferation (Ki67) was maximal at the gubernacular tip (p <0.001), as were muscle stem cells markers (Pax-7 p <0.05), early myogenesis (myogenin p <0.001) and immature muscle (Myh7, and slow and cardiac troponin T p <0.0001). In contrast, secondary (fast twitch, Myh1, 2 and 4) fibers were more common in abdominal muscles (p <0.0001). Differences in muscle maturity and composition decreased with time. Flutamide treated rats showed more cellular proliferation than controls postnatally on postnatal day 10 (p <0.001) as well as persistent immature embryonic myosin at the tip from postnatal day 19 (p <0.05). CONCLUSIONS: Results show that the rat cremaster muscle is more immature at the gubernacular tip, consistent with myogenesis occurring in the gubernaculum during migration to the scrotum, as proposed in humans.


Asunto(s)
Criptorquidismo/embriología , Conducto Inguinal/embriología , Desarrollo de Músculos , Músculo Liso/embriología , Escroto/embriología , Testículo/embriología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-Dawley
14.
Pediatr Surg Int ; 27(7): 699-704, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21287181

RESUMEN

PURPOSE: Adult slow-transit constipation (STC) occurs predominantly in females and is associated with low numbers of substance P (SP)-containing nerves in colonic circular muscle. AIM: To determine if reduced SP nerves is female predominant in paediatric STC. METHODS: Children with STC were identified from records of more than 600 nuclear transit studies (NTS) and intestinal biopsies done for intractable chronic constipation between November 1998 and March 2009. Colonic seromuscular biopsies collected from hepatic and splenic flexures, and sigmoid colon were processed for immunohistochemistry. Nerve fibre density in circular muscle containing SP was measured qualitatively by a pathologist. RESULTS: Eighty-eight children with chronic constipation had both NTS and intestinal biopsies. Seventy-eight children (52 M; age 2-15.5 years; mean 7.7 years) had STC diagnosed by NTS. SP was reduced in 10/26 girls, but only 11/52 boys. CONCLUSION: In this sample, STC was more common in boys than girls. However, in girls with STC, SP deficiency occurred in 40%, when compared with 20% of boys. During puberty, the percentage of girls with reduced SP decreased, whilst the percentage of boys increased. These results suggest that STC is heterogeneous and that there are some gender differences, the implication of which requires further investigation.


Asunto(s)
Estreñimiento/epidemiología , Tránsito Gastrointestinal , Mucosa Intestinal/metabolismo , Sustancia P/deficiencia , Transporte Activo de Núcleo Celular/fisiología , Adolescente , Biopsia , Niño , Preescolar , Enfermedad Crónica , Colon Transverso/diagnóstico por imagen , Colon Transverso/inervación , Colon Transverso/metabolismo , Estreñimiento/sangre , Estreñimiento/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Masculino , Prevalencia , Cintigrafía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Distribución por Sexo , Factores Sexuales , Sustancia P/sangre , Victoria/epidemiología
15.
Pediatr Surg Int ; 27(7): 705-11, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21373802

RESUMEN

PURPOSE: Transcutaneous electrical stimulation (TES) speeds up colonic transit in children with slow-transit constipation (STC). This study examined if concurrent upper gastrointestinal dysmotility (UGD) affected response to TES. METHODS: Radio-nuclear transit studies (NTS) were performed before and after TES treatment of STC as part of a larger randomised controlled trial. UGD was defined as delayed gastric emptying and/or slow small bowel transit. Improvement was defined as increase of ≥1 Geometric Centre (median radiotracer position at each time [small bowel = 1, toilet = 6]). RESULTS: Forty-six subjects completed the trial, 34 had NTS after stimulation (21 M, 8-17 years, mean 11.3 years; symptoms >9 years). Active stimulation increased transit in >50% versus only 25% with sham (p = 0.04). Seventeen children also had UGD. In children with STC and either normal upper GI motility (NUGM) and UGD, NTS improved slightly after 1 month (57 vs. 60%; p = 0.9) and more after 2 months (88 vs. 40%; p = 0.07). However, mean transit rate significantly increased with NUGM, but not UGD (5.0 ± 0.2: 3.6 ± 0.6, p < 0.01). CONCLUSION: Transcutaneous electrical stimulation was beneficial for STC, with response weakly associated with UGD. As measured by NTS, STC children with NUGM responded slightly more, but with significantly greater increased transit compared to those with UGD. Higher numbers are needed to determine if the difference is important.


Asunto(s)
Colon/fisiopatología , Estreñimiento/terapia , Tránsito Gastrointestinal/fisiología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adolescente , Niño , Colon/diagnóstico por imagen , Estreñimiento/diagnóstico por imagen , Estreñimiento/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Proyectos Piloto , Cintigrafía , Resultado del Tratamiento
16.
Cell Tissue Res ; 341(1): 33-48, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20490865

RESUMEN

Cholinergic nerves are identified by labelling molecules in the ACh synthesis, release and destruction pathway. Recently, antibodies against another molecule in this pathway have been developed. Choline reuptake at the synapse occurs via the high-affinity choline transporter (CHT1). CHT1 immunoreactivity is present in cholinergic nerve fibres containing vesicular acetylcholine transporter (VAChT) in the human and rat central nervous system and rat enteric nervous system. We have examined whether CHT1 immunoreactivity is present in nerve fibres in human intestine and whether it is colocalised with markers of cholinergic, tachykinergic or nitrergic circuitry. Human ileum and colon were fixed, sectioned and processed for fluorescence immunohistochemistry with antibodies against CHT1, class III beta-tubulin (TUJ1), synaptophysin, common choline acetyl-transferase (cChAT), VAChT, nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP). CHT1 immunoreactivity was present in many nerve fibres in the circular and longitudinal muscle, myenteric and submucosal ganglia, submucosa and mucosa in human colon and ileum and colocalised with immunoreactivity for TUJ1 and synaptophysin confirming its presence in nerve fibres. In nerve fibres in myenteric ganglia and muscle, CHT1 immunoreactivity colocalised with immunoreactivity for VAChT and cChAT. Some colocalisation occurred with SP immunoreactivity, but little with immunoreactivity for VIP or NOS. In the mucosa, CHT1 immunoreactivity colocalised with that for VIP and SP in nerve fibres and was also present in vascular nerve fibres in the submucosa and on epithelial cells on the luminal border of crypts. The colocalisation of CHT1 immunoreactivity with VAChT immunoreactivity in cholinergic enteric nerves in the human bowel thus suggests that CHT1 represents another marker of cholinergic nerves.


Asunto(s)
Sistema Nervioso Entérico/metabolismo , Proteínas de Transporte de Membrana/inmunología , Proteínas de Transporte Vesicular de Acetilcolina/metabolismo , Especificidad de Anticuerpos/inmunología , Biomarcadores/metabolismo , Niño , Sistema Nervioso Entérico/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Ganglios/metabolismo , Ganglios/patología , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Linfocitos/metabolismo , Linfocitos/patología , Músculos/metabolismo , Músculos/patología , Fibras Nerviosas/enzimología , Fibras Nerviosas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Transporte de Proteínas , Sustancia P/metabolismo , Sinaptofisina/metabolismo , Tubulina (Proteína)/metabolismo , Péptido Intestinal Vasoactivo/metabolismo
19.
Expert Rev Gastroenterol Hepatol ; 14(3): 163-174, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32098515

RESUMEN

Introduction: Constipation occurs in many children and can become chronic. Many grow out of it but for one third, it continues into adulthood. For most patients, there is no identifiable organic disorder and it is classified as functional constipation.Areas covered: In 2016, treatment of childhood constipation was extensively reviewed by Rome IV. This review covers meta-analyses and evidence for treatment of paediatric constipation since 2016 and new emerging treatments.Expert opinion: Since 2016, meta-analyses conclude 1) fibre should be included in a normal diet, but further supplementation does not improve constipation; 2) probiotics may increase stool frequency in children, but evidence from larger RCTs is needed; 3) comparing laxatives, polyethylene glycol (PEG) is superior to placebo, lactulose and milk of magnesia, and 4) appendix stomas are effective and should be considered before surgery. Emerging areas of study include food intolerance, electrical stimulation and faecal microbiota transplant. For research, outcome measures need standardising to allow comparison between studies and allow meta-analyses. To assist this, validated GI instruments have been developed by Rome IV and PedsQl.


Asunto(s)
Estreñimiento/terapia , Niño , Humanos , Guías de Práctica Clínica como Asunto
20.
J Urol ; 182(4 Suppl): 1744-9, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19692053

RESUMEN

PURPOSE: We evaluated long-term outcomes in boys treated for hypospadias at Royal Children's Hospital, Melbourne. MATERIALS AND METHODS: Boys who underwent hypospadias surgery were reviewed at ages 13 to 15 years. Surgical results were evaluated using the Hypospadias Objective Scoring Evaluation. Lower urinary tract function was assessed using uroflowmetry and symptom questionnaire. Self-report surveys measured quality of life, patient satisfaction, memory of surgery, psychosexual outcomes and parent satisfaction with care. RESULTS: By Hypospadias Objective Scoring Evaluation score 80% of patients had an excellent surgical outcome. Two independent reviewers assessed lower urinary tract function as normal in 82% and 86% of cases, respectively. Quality of life scores were comparable to published values in normal children. Parents rated the institution highly. Overall 90% and 81% of boys were satisfied with the body and genital appearance, respectively. Those dissatisfied with genital appearance had poorer psychosexual outcomes than satisfied patients. When surgery was completed before age 5 years, boys had no perioperative memories. An association was found between no recollection of surgery and satisfaction with body appearance. CONCLUSIONS: Objective surgical and functional outcomes are excellent after early surgery. Post-repair quality of life is comparable to published data on normal children. Parents are pleased with care. Most boys are satisfied with the body and genital appearance. However, those dissatisfied with genital appearance must be identified in the interest of psychosexual development. The association between no recollection of treatment and satisfaction with body appearance suggests that surgery should be completed before age 5 years when possible to allow the development of good body image in adolescence.


Asunto(s)
Hipospadias/cirugía , Satisfacción del Paciente , Desarrollo Psicosexual , Adolescente , Factores de Edad , Estudios Transversales , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
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