Crespo C.S.,University of Alcalá |
Cachero A.P.,University of Alcalá |
Jimenez L.P.,University of Alcalá |
Barrios V.,Hospital Infantil Universitario Nino Jesus |
And 2 more authors.
Frontiers in Endocrinology | Year: 2014
The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food intake, whereas the other subpopulation coexpresses pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript that inhibits food intake. AgRP antagonizes the effects of the POMC product, a-melanocyte-stimulating hormone (a-MSH). Both populations project to areas important in the regulation of food intake, including the hypothalamic paraventricular nucleus, which also receives important inputs from other hypothalamic nuclei. © 2014 Sobrino Crespo, Perianes Cachero, Puebla Jiménez, Barrios and Arilla Ferreiro.
Rubio-Cabezas O.,University of Exeter |
Rubio-Cabezas O.,Hospital Infantil Universitario Nino Jesus |
Minton J.A.L.,University of Exeter |
Kantor I.,Josa Andras Hospital |
And 3 more authors.
Diabetes | Year: 2010
OBJECTIVE - NEUROD1 is expressed in both developing and mature β-cells. Studies in mice suggest that this basic helix-loop-helix transcription factor is critical in the development of endocrine cell lineage. Heterozygous mutations have previously been identified as a rare cause of maturity-onset diabetes of the young (MODY). We aimed to explore the potential contribution of NEUROD1 mutations in patients with permanent neonatal diabetes. RESEARCH DESIGN AND METHODS - We sequenced the NEUROD1 gene in 44 unrelated patients with permanent neonatal diabetes of unknown genetic etiology. RESULTS - Two homozygous mutations in NEUROD1 (c.427-428del and c.364dupG) were identified in two patients. Both mutations introduced a frameshift that would be predicted to generate a truncated protein completely lacking the activating domain. Both patients had permanent diabetes diagnosed in the first 2 months of life with no evidence of exocrine pancreatic dysfunction and a morphologically normal pancreas on abdominal imaging. In addition to diabetes, they had learning difficulties, severe cerebellar hypoplasia, profound sensorineural deafness, and visual impairment due to severe myopia and retinal dystrophy. CONCLUSIONS - We describe a novel clinical syndrome that results from homozygous loss of function mutations in NEUROD1. It is characterized by permanent neonatal diabetes and a consistent pattern of neurological abnormalities including cerebellar hypoplasia, learning difficulties, sensorineural deafness, and visual impairment. This syndrome highlights the critical role of NEUROD1 in both the development of the endocrine pancreas and the central nervous system in humans. © 2010 by the American Diabetes Association.
Trindade F.,Hospital Of Cascais Dr Jose Of Almeida |
Kutzner H.,Dermatohistopathologische Gemeinschaftslabor |
Tellechea O.,Hospital Universitario Of Coimbra |
Requena L.,Fundacion Jimenez Diaz |
Colmenero I.,Hospital Infantil Universitario Nino Jesus
Journal of the American Academy of Dermatology | Year: 2012
Background: Hobnail hemangioma (HH) is currently classified as a benign vascular tumor, although it is not well understood whether this lesion differentiates toward blood or lymphatic endothelial cells. Immunostaining with the endothelial marker Wilms tumor 1 (WT1) helps distinguish between vascular neoplasms and malformations, being positive in the former and negative in the latter. Objective: We sought to investigate WT1, human herpesvirus 8 latent nuclear antigen, D2-40, and Ki-67 immunoprofile in HH, to gain further insight into its histogenesis. Methods: We evaluated 52 HHs collected in Dermatohistopathologische Gemeinschaftslabor, Friedrichshafen, Germany. Immunohistochemical expression of WT1 was performed in all cases. Ten of 52 lesions were also studied for D2-40 and Ki-67 staining and 12 lesions were stained for human herpesvirus 8 latent nuclear antigen. Results: All 52 HHs were completely negative for WT1 immunostaining. Immunohistochemistry performed in 10 HHs showed diffuse and strong positive staining for D2-40 in 8 lesions and focal positivity in two. All cases tested showed negative staining for Ki-67 and human herpesvirus 8 latent nuclear antigen. Limitations: There are no limitations. Conclusions: Although the exact histogenesis of HH is unknown, most of the performed immunohistochemical studies support a lymphatic line of differentiation. However, on the basis of the WT1 negativity, we believe that HH is better considered as a lymphatic malformation rather than a lymphatic neoplasm. © 2010 by the American Academy of Dermatology, Inc.
Neurocognitive dysfunction in electrical status epilepticus during slow-wave sleep syndrome: Can the natural course of the syndrome be modified with early pharmacological treatment? [Disfunción neurocognitiva en el síndrome de estado de mal eléctrico durante el sueño lento: ¿Podemos modificar la evolución natural del síndrome con un tratamiento farmacológico precoz?]
Garcia-Penas J.J.,Hospital Infantil Universitario Nino Jesus
Revista de Neurologia | Year: 2010
Introduction. Epileptic syndromes with continuous spike wave in slow-wave sleep (CSWS), including electrical status epilepticus in sleep (ESES) and Landau-Kleffner syndrome, are true epileptic encephalopathies where sustained epileptic activity is related to cognitive and behavioural decline. Aims. To review the natural course of ESES, to define the general principles of treatment of epileptic syndromes with CSWS, to delineate the different options that are currently available for treating these epileptic encephalopathies, and to analyze the prognostic factors linked to pharmacological treatment of ESES. Development. Epileptic syndromes with CSWS are initially treated with a pharmacologic intervention with polytherapy of antiepileptic drugs in most cases. However, due to the poor response that CSWS often have to antiepileptic drugs, non-pharmacologic treatment options are an important part of a comprehensive treatment plan for this group of children. This article discusses the use of corticosteroids, intravenous immunoglobulins, ketogenic diet, vagus nerve stimulation, and epilepsy surgery in the treatment of patients with epileptic syndromes with CSWS. Conclusions. Treatment of ESES extends beyond just control of the seizures; amelioration of the continuous epileptiform discharge must occur to improve neuropsychological outcome. There is a significant correlation between the length of the ESES period and the extent of residual intellectual deficit at follow-up. According to this knowledge, there is a well defined therapeutic interval where our different strategies of treatment may be useful, and the upper limits of this time frame to a critical period of 12-18 months. © 2010 Revista de Neurología.
Ruiz-Falco Rojas M.L.,Hospital Infantil Universitario Nino Jesus
Revista de neurologia | Year: 2012
Tuberous sclerosis complex is an autosomal dominant disease, with variable expressivity and multisystemic involvement, which is characterised by the growth of benign tumours called hamartomas. The organs that are most commonly affected are the brain, skin, kidneys, eyes, heart and lungs. Of all the children with this disease, 85% present neurological manifestations that, due to their severity, are the main cause of morbidity and mortality. The most significant neurological manifestations are epilepsy, autism spectrum disorders and mental retardation. It has been shown that in tuberous sclerosis complex the genes TSC1 and TSC2 alter the mTOR enzyme cascade, which sets off inhibition of this pathway. The possibility of resorting to treatments applied at the origin, thus inhibiting this pathway, is currently being evaluated.
Sanchez Bayle M.,Hospital Infantil Universitario Nino Jesus
Revista Espanola de Pediatria | Year: 2011
There are essentially four health determinants of the persons: health care system (11%), the setting, that is the environment, equipments, work conditions, etc. (19%), genetic inheritance (27%) and individual habits or style of life (43%). Risk factor is considered to be an aspect of behavior or style of life, environmental exposure or innate or hereditary characteristic which, on the basis of the epidemiological evidence, is known to be associated with a related health condition whose prevention is considered important. The cardiovascular risk factors (CVR) totally fall within this category of determinants, either because they have a genetic origin or because of bad the result of the styles and habits of life. There is much evidence regarding the positive effects of preventive activities in relationship with cardiovascular risk, especially regarding primordial prevention which is of most interest in the pediatric age. The actions having the most evidence are along the lines of avoiding smoking and obesity, promoting regular physical exercise and a healthy diet (rich in fruits, vegetables and fiber, and low in salt and saturated fats) and controlling blood pressure, hyperlipidemia and hyperglycemia.
Incidence and susceptibility of Campylobacter jejuni in pediatric patients: Involvement in bacteremia [Incidencia y sensibilidad de Campylobacter jejuni en pacientes pediátricos: Implicación en bacteriemia]
Gonzalez-Abad M.J.,Hospital Infantil Universitario Nino Jesus |
Alonso-Sanz M.,Hospital Infantil Universitario Nino Jesus
Revista Espanola de Quimioterapia | Year: 2013
Introduction. Invasive disease as a result Campylobacter spp. is rarely reported. Bloodstream infections have been reported in patients with immune deficiency or other serious underlying conditions. We conducted a prospective study to know the incidence of Campylobacter jejuni bacteremia in pediatric patients and its susceptibility to erythromycin and ciprofloxacin. Methods. The identification of Campylobacter isolates was based on routine culture methods. Antimicrobial susceptibility was performed using a disk diffusion method. Results. During April 2010-June 2012, at Hospital Niño Jesús of Madrid, Campylobacter spp. was isolated from 171 stool specimens in 154 patients. The median age was 2 years (3 months-21 year). One hundred and one (66%) isolates were identified as C. jejuni. Nine patients with enteritis due C. jejuni (9%) were immunocompromised. Erythromycin resistance was observed in 5% of the isolates. The resistance to ciprofloxacin was 88%. Blood cultures were obtained of 19 patients infected with C. jejuni (19%). Of these, one had C. jejuni bacteremia. During the study period, other episode of C. jejuni bacteremia was detected in one patient different without positive stool culture for C. jejuni (0.34% of all bloodstreams infections). Both patients were immunocompromised. Conclusions. Campylobacter spp. is an uncommon cause of bloodstream infection in our serie occurring in pediatric patients with immune deficiency as predisposing factor. In our institution, empirical use of fluoroquinolones for Campylobacter infections should not be recommended by the high rate of resistance. Moreover in our study the resistance to erythromycin is low, however is advisable its surveillance.
Rubio-Cabezas O.,Hospital Infantil Universitario Nino Jesus |
Rubio-Cabezas O.,University of Exeter |
Ellard S.,University of Exeter
Hormone Research in Paediatrics | Year: 2013
Over the last decade, we have witnessed major advances in the understanding of the molecular basis of neonatal and infancy-onset diabetes. It is now widely accepted that diabetes presenting before 6 months of age is unlikely to be autoimmune type 1 diabetes. The vast majority of such patients will have a monogenic disorder responsible for the disease and, in some of them, also for a number of other associated extrapancreatic clinical features. Reaching a molecular diagnosis will have immediate clinical consequences for about half of affected patients, as identification of a mutation in either of the two genes encoding the ATP-sensitive potassium channel allows switching from insulin injections to oral sulphonylureas. It also facilitates genetic counselling within the affected families and predicts clinical prognosis. Importantly, monogenic diabetes seems not to be limited to the first 6 months but extends to some extent into the second half of the first year of life, when type 1 diabetes is the more common cause of diabetes. From a scientific perspective, the identification of novel genetic aetiologies has provided important new knowledge regarding the development and function of the human pancreas. Copyright © 2013 S. Karger AG, Basel.
Robledillo J.C.L.,Hospital Infantil Universitario Nino Jesus
Pediatria Integral | Year: 2013
Musculoskeletal symptoms are common in children and adolescents. Most of the cases are benign but a number of children develop a chronic pain syndrome and become quite disable. The focus of the review is on chronic or recurrent musculoskeletal complaints. Chronic pain in childhood can be caused by a wide variety of conditions, several of which are discussed here: growing pains, hypermobility syndrome, fibromyalgia, chronic fatigue syndrome and reflex sympathetic dystrophy. The aetiology of the majority of cases is unknown. Differential diagnosis is broad, then when evaluating a child meticulous history taking and a careful examination is required in order to avoid misdiagnosis. Only a small proportion has an inflammatory or systemic origin. Various treatments have been propose but effective managing is based on interdisciplinary approach to reverse pain associated disability with education, simple analgesics and psycologic intervention.
Garcia-Penas J.J.,Hospital Infantil Universitario Nino Jesus
Revista de Neurologia | Year: 2015
Introduction. School failure, learning and behavioral problems are more common in children with epilepsy than the general population. The aim of this study is to examine the different factors which can affect the school performance of children with epilepsy. Development. Various psychosocial, medication-related, and epilepsy-related factors may be associated with learning disorders in epilepsy. The age of onset of epilepsy, the type of syndrome, its aetiology, and the response to treatment are some of the most important epilepsy-related factors. All of the established antiepileptic drugs can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. Conclusions. Judicious management of all related factors is essential for an optimal outcome. Recent onset of educational problems in a child with epilepsy deserves immediate and exhaustive evaluation and management. © 2015 Revista de Neurología.