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OBJECTIVES: To explain what a clinical academic career can be, what it can lead to for the individual, profession and most importantly the patient, and why these roles are so important to radiography. KEY FINDINGS: Multiple challenges to the adoption of clinical academic careers exist, including achievable measurable outcomes, visibility & senior support, and balancing different time demands. Equally the rewards are wide ranging and can advance both the individual and profession through role extension opportunities, increased career progression, patient benefits, and academic and research skills. CONCLUSION: Clinical academic careers can provide advantages for the individual, department, profession and most importantly the patient with advanced clinical practice through evidenced based research. IMPLICATIONS FOR PRACTICE: Improving clinical academic careers within Radiography will promote research participation and increase radiographic roles in patient-centred research delivery and development. Combining evidenced based research with academic skills will lead to improved patient care and better clinical outcomes.
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Técnicos Medios en Salud , Recompensa , HumanosRESUMEN
Aim To describe the healthcare needs of adolescent patients inhabiting the 'seventh age of childhood' in our region with a view towards future workforce and infrastructure planning. Methods This is a retrospective descriptive study of patients aged between 14 and 16 years presenting to each of the six hospitals in our hospital group over a 10 year period (01.07.2006-1.07.2016) using electronic databases. Results There were 10,992 hospital admissions, 41,456 outpatient appointments and an average of 1,847 attendances per year at our Emergency Department in this age group. Seventeen percent (n=1,873) of patients were admitted to age appropriate wards. Only 11.3% (n=1,242) of our cohort were admitted under the care of a Paediatrician. Conclusion The Irish healthcare agenda needs to be advanced to ensure the optimal health for this valuable, yet vulnerable generation. Further investment will help shape the fledgling discipline of 'adolescent health' in Ireland.
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Salud del Adolescente , Atención Ambulatoria/estadística & datos numéricos , Atención a la Salud , Necesidades y Demandas de Servicios de Salud , Pacientes Ambulatorios/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Atención al Paciente/estadística & datos numéricos , Adolescente , Factores de Edad , Estudios de Cohortes , Bases de Datos Factuales , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Humanos , Irlanda/epidemiología , Masculino , Pediatras , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) share many symptoms but underlying mechanisms may be different. We have developed a magnetic resonance imaging (MRI) technique to measure intestinal volumes, transit, and motility in response to a laxative, Moviprep(®) . We aim to use these biomarkers to study the pathophysiology in IBS-C and FC. METHODS: Twenty-four FC and 24 IBS-C were studied. Transit was assessed using the weighted average position score (WAPS) of five MRI marker pills, taken 24 h before MRI scanning. Following baseline scan, participants ingested 1 L of Moviprep(®) followed by hourly scans. Magnetic resonance imaging parameters and bowel symptoms were scored from 0 to 4 h. KEY RESULTS: Weighted average position score for FC was 3.6 (2.5-4.2), significantly greater than IBS-C at 2.0 (1.5-3.2), p = 0.01, indicating slower transit for FC. Functional constipation showed greater fasting small bowel water content, 83 (63-142) mL vs 39 (15-70) mL in IBS-C, p < 0.01 and greater ascending colon volume (AC), 314 (101) mL vs 226 (71) mL in IBS-C, p < 0.01. FC motility index was lower at 0.055 (0.044) compared to IBS-C, 0.107 (0.070), p < 0.01. Time to first bowel movement following ingestion of Moviprep(®) was greater for FC, being 295 (116-526) min, compared to IBS-C at 84 (49-111) min, p < 0.01, and correlated with AC volume 2 h after Moviprep(®) , r = 0.44, p < 0.01. Using a cut-off >230 min distinguishes FC from IBS-C with low sensitivity of 55% but high specificity of 95%. CONCLUSION & INFERENCES: Our objective MRI biomarkers allow a distinction between FC and IBS-C.
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Colon/diagnóstico por imagen , Estreñimiento/diagnóstico por imagen , Síndrome del Colon Irritable/diagnóstico por imagen , Laxativos/administración & dosificación , Imagen por Resonancia Magnética , Polietilenglicoles/administración & dosificación , Adulto , Colon/efectos de los fármacos , Estreñimiento/fisiopatología , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Tránsito Gastrointestinal/efectos de los fármacos , Tránsito Gastrointestinal/fisiología , Humanos , Síndrome del Colon Irritable/fisiopatología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study introduces the large 'Nottingham Test Meal' (NTM) for assessment of gastric motor and sensory function by non-invasive imaging. METHODS: NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and 12 solid agar-beads (0 kcal) with known breaking strength. Gastric fullness and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gastric emptying (GE) were measured in 24 healthy volunteers (HVs) by gastric scintigraphy (GS) and magnetic resonance imaging (MRI). The contribution of secretion to gastric volume was assessed. Parameters that describe GE were calculated from validated models. Inter-observer agreement and reproducibility were assessed. KEY RESULTS: NTM produced moderate fullness (VAS ≥30) but no more than mild dyspeptic symptoms (VAS <30) in 24 HVs. Stable binding of meal components to labels in gastric conditions was confirmed. Distinct early and late-phase GE were detected by both modalities. Liquid GE half-time was median 49 (95% CI: 36-62) min and 68 (57-71) min for GS and MRI, respectively. Differences between GS and MRI measurements were explained by the contribution of gastric secretion. Breaking strength for agar-beads was 0.8 N/m(2) such that median 25 (8-50) % intact agar-beads and 65 (47-74) % solid material remained at 120 min on MRI and GS, respectively. Good reproducibility for liquid GE parameters was present and GE was not altered by agar-beads. CONCLUSIONS & INFERENCES: The NTM provided an objective assessment of gastric motor and sensory function. The results were reproducible and liquid emptying was not affected by non-nutrient agar-beads. The method is potentially suitable for clinical practice.
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Gastroenterología/métodos , Gastropatías/diagnóstico , Adulto , Anciano , Femenino , Vaciamiento Gástrico/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Cintigrafía , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: Recently, cine magnetic resonance imaging (MRI) has shown promise for visualizing movement of the colonic wall, although assessment of data has been subjective and observer dependent. This study aimed to develop an objective and semi-automatic imaging metric of ascending colonic wall movement, using image registration techniques. METHODS: Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland-Altman analysis calculated from two separate observations on a subset of data. KEY RESULTS: All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55-0.86), p < 0.001 (Spearman Rho). Bland-Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (-0.039 to 0.052 intra-observer and -0.051 to 0.054 inter-observer, range of measurement 0-0.353). CONCLUSIONS & INFERENCES: The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink.
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Colon/fisiología , Motilidad Gastrointestinal/fisiología , Imagen por Resonancia Cinemagnética/métodos , Adulto , Colon/efectos de los fármacos , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Humanos , Imagenología Tridimensional/métodos , Masculino , Polietilenglicoles/farmacología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Cushing's disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing's syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing's disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia. CASE PRESENTATION: The case is that of a 13-year old boy, presenting with a long history of symptoms and signs suggestive of hypercortisolism, who was found to have cyclical ACTH-dependent hypercortisolism following dynamic pituitary testing and serial late-night salivary cortisol measurements. The patient underwent endoscopic transsphenoidal resection of the pituitary. Early surgical remission was confirmed by undetectable post-operative morning plasma cortisol levels. Histology and immunocytochemistry of the resected pituitary tissue showed extensive corticotroph cell hyperplasia. CONCLUSION: This report describes a rare case of cyclical Cushing's disease secondary to corticotroph hyperplasia in a paediatric patient. This highlights the challenging and varied nature of Cushing's disease and its diagnosis, and the need to keep a differential diagnosis in mind during the diagnostic process.
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Corticotrofos/patología , Hidrocortisona/metabolismo , Periodicidad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Enfermedades de la Hipófisis/diagnóstico , Adolescente , Humanos , Hiperplasia/diagnóstico , Masculino , Saliva/químicaRESUMEN
BACKGROUND: Symptoms of irritable bowel syndrome (IBS) are frequently reported to be exacerbated by stress. Animal studies suggest that corticotrophin releasing hormone (CRH) mediates the effect of stress on the bowel. We have shown that stressed IBS patients with diarrhea have constricted small bowels. We hypothesized that we could mimic this effect by applying experimental stress in the form of either hand immersion in ice water or CRH injection in healthy volunteers (HV). METHODS: The postprandial effect of the cold pressor test (repeated hand immersion in ice cold water) and injection of CRH, were assessed vs control in two groups of 18 HVs. KEY RESULTS: CRH produced a significant rise from baseline salivary cortisol levels (p = 0.004) not seen with the cold pressor test. Small bowel water content (SBWC) fell postprandially on all four treatments. SBWC was significantly reduced by both stressors but CRH caused a greater effect (anova, p < 0.003 vs p = 0.02). Ascending colon (AC) volume was greater after CRH injection compared with saline (p = 0.002) but no differences were seen with the cold pressor test vs warm water. Postprandial increase in colon volume was also reduced by CRH which also increased the sensations of distension and bloating. CONCLUSIONS & INFERENCES: Two experimental stressors were shown to constrict the small bowel, mimicking the effect previously seen in IBS-D patients. CRH increased the volume of the AC. We speculate that stress accelerates transfer of water from the small bowel to the AC.
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Colon/metabolismo , Intestino Delgado/metabolismo , Estrés Psicológico/metabolismo , Frío , Colon/efectos de los fármacos , Hormona Liberadora de Corticotropina/administración & dosificación , Humanos , Hidrocortisona/metabolismo , Imagen por Resonancia Magnética , Periodo Posprandial , Agua/metabolismoRESUMEN
MRI can assess multiple gastric functions without ionizing radiation. However, time consuming image acquisition and analysis of gastric volume data, plus confounding of gastric emptying measurements by gastric secretions mixed with the test meal have limited its use to research centres. This study presents an MRI acquisition protocol and analysis algorithm suitable for the clinical measurement of gastric volume and secretion volume. Reproducibility of gastric volume measurements was assessed using data from 10 healthy volunteers following a liquid test meal with rapid MRI acquisition within one breath-hold and semi-automated analysis. Dilution of the ingested meal with gastric secretion was estimated using a respiratory-triggered T1 mapping protocol. Accuracy of the secretion volume measurements was assessed using data from 24 healthy volunteers following a mixed (liquid/solid) test meal with MRI meal volumes compared to data acquired using gamma scintigraphy (GS) on the same subjects studied on a separate study day. The mean ± SD coefficient of variance between 3 observers for both total gastric contents (including meal, secretions and air) and just the gastric contents (meal and secretion only) was 3 ± 2% at large gastric volumes (>200 ml). Mean ± SD secretion volumes post meal ingestion were 64 ± 51 ml and 110 ± 40 ml at 15 and 75 min, respectively. Comparison with GS meal volumes, showed that MRI meal only volume (after correction for secretion volume) were similar to GS, with a linear regression gradient ± std err of 1.06 ± 0.10 and intercept -11 ± 24 ml. In conclusion, (i) rapid volume acquisition and respiratory triggered T1 mapping removed the requirement to image during prolonged breath-holds (ii) semi-automatic analysis greatly reduced the time required to derive measurements and (iii) correction for secretion volumes provided accurate assessment of gastric meal volumes and emptying. Together these features provide the scientific basis of a protocol which would be suitable in clinical practice.
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Vaciamiento Gástrico , Imagen por Resonancia Magnética/métodos , Estómago/patología , Adulto , Algoritmos , Automatización , Calibración , Ingestión de Alimentos , Femenino , Mucosa Gástrica/metabolismo , Voluntarios Sanos , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Variaciones Dependientes del Observador , Periodo Posprandial , Cintigrafía , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Intake of food or fluid distends the stomach and triggers mechanoreceptors and vagal afferents. Wall stretch and tension produces a feeling of fullness. Duodenal infusion studies assessing gastric sensitivity by barostat have shown that the products of fat digestion have a greater effect on the sensation of fullness and also dyspeptic symptoms than carbohydrates. We tested here the hypothesis that fat and carbohydrate have different effects on gastric sensation under physiological conditions using non-invasive magnetic resonance imaging (MRI) to measure gastric volumes. SUBJECTS/METHODS: Thirteen healthy subjects received a rice pudding test meal with added fat or added carbohydrate on two separate occasions and underwent serial postprandial MRI scans for 4.5 h. Fullness was assessed on a 100-mm visual analogue scale. RESULTS: Gastric half emptying time was significantly slower for the high-carbohydrate meal than for the high-fat meal, P=0.0327. Fullness significantly correlated with gastric volumes for both meals; however, the change from baseline in fullness scores was higher for the high-fat meal for any given change in stomach volume (P=0.0147), despite the lower energy content and faster gastric emptying of the high-fat meal. CONCLUSIONS: Total gastric volume correlates positively and linearly with postprandial fullness and ingestion of a high-fat meal increases this sensation compared with high-carbohydrate meal. These findings can be of clinical interest in patients presenting with postprandial dyspepsia whereby manipulating gastric sensitivity by dietary intervention may help to control digestive sensations.
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Grasas de la Dieta/metabolismo , Digestión/fisiología , Dispepsia/psicología , Vaciamiento Gástrico , Periodo Posprandial/fisiología , Sensación , Estómago , Adulto , Dieta , Dispepsia/fisiopatología , Ingestión de Alimentos , Femenino , Humanos , Masculino , Comidas , Percepción , Saciedad , Estómago/fisiología , Estómago/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Most methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing. METHODS: Twelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes. KEY RESULTS: Small bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103). CONCLUSIONS & INFERENCES: Ingestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies.
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Catárticos/administración & dosificación , Electrólitos/administración & dosificación , Motilidad Gastrointestinal/efectos de los fármacos , Imagen por Resonancia Magnética , Polietilenglicoles/administración & dosificación , Administración Oral , Adulto , Colon/efectos de los fármacos , Colon/fisiología , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Colonic transit tests are used to manage patients with Functional Gastrointestinal Disorders. Some tests used expose patients to ionizing radiation. The aim of this study was to compare novel magnetic resonance imaging (MRI) tests for measuring orocecal transit time (OCTT) and whole gut transit time (WGT), which also provide data on colonic volumes. METHODS: 21 healthy volunteers participated. Study 1: OCTT was determined from the arrival of the head of a meal into the cecum using MRI and the Lactose Ureide breath test (LUBT), performed concurrently. Study 2: WGT was assessed using novel MRI marker capsules and radio-opaque markers (ROMs), taken on the same morning. Studies were repeated 1 week later. KEY RESULTS: OCTT measured using MRI and LUBT was 225 min (IQR 180-270) and 225 min (IQR 165-278), respectively, correlation r(s) = 0.28 (ns). WGT measured using MRI marker capsules and ROMs was 28 h (IQR 4-50) and 31 h ± 3 (SEM), respectively, correlation r(s) = 0.85 (p < 0.0001). Repeatability assessed using the intraclass correlation coefficient (ICC) was 0.45 (p = 0.017) and 0.35 (p = 0.058) for MRI and LUBT OCTT tests. Better repeatability was observed for the WGT tests, ICC being 0.61 for the MRI marker capsules (p = 0.001) and 0.69 for the ROM method (p < 0.001) respectively. CONCLUSIONS & INFERENCES: The MRI WGT method is simple, convenient, does not use X-ray and compares well with the widely used ROM method. Both OCTT measurements showed modest reproducibility and the MRI method showed modest inter-observer agreement.
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Tránsito Gastrointestinal/fisiología , Imagen por Resonancia Magnética , Adulto , Anciano , Pruebas Respiratorias , Ciego/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: The emptying of the gall bladder in response to feeding is pivotal for the digestion of fat, but the role of various food ingredients in contracting the gall bladder postprandially is not well understood. We hypothesized that different food ingredients, when consumed, will have a different effect on stimulating gall bladder emptying. To investigate this we designed two randomized, investigator-blind, cross-over studies in healthy subjects using magnetic resonance imaging (MRI) to measure gall bladder volumes serially and non-invasively. SUBJECTS/METHODS: Study 1: exploratory study evaluating the effects of 10 different food ingredients on gall bladder emptying in eight healthy subjects. The choice of ingredients varied from common items like coffee, tea and milk to actives like curcumin and potato protease inhibitor. Study 2: mechanistic study investigating the cholecystokinin (CCK) dose response to the best performer ingredient from Study 1 in 21 healthy subjects four ways. RESULTS: The largest gall bladder volume change in Study 1 was observed with fat, which therefore became the dose-response ingredient in Study 2, where the maximum % gall bladder volume change correlated well with CCK. CONCLUSIONS: These serial test-retest studies showed that the fasted gall bladder volume varied remarkably between individuals and that individual day-to-day variability had wide coefficients of variation. Improved knowledge of how to stimulate bile release using food ingredients will be useful to improve in vitro-in vivo correlation of bioavailability testing of hydrophobic drugs. It could improve performance of cholesterol-lowering plant stanol and sterol products and possibly aid understanding of some cholesterol gallstone disease.
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Colecistoquinina/metabolismo , Dieta , Grasas de la Dieta/farmacología , Vaciamiento Vesicular/efectos de los fármacos , Vesícula Biliar/efectos de los fármacos , Adolescente , Adulto , Femenino , Alimentos , Vesícula Biliar/fisiología , Humanos , Masculino , Periodo Posprandial , Método Simple Ciego , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Postprandial bloating is a common symptom in patients with functional gastrointestinal (GI) diseases. Whole meal bread (WMB) often aggravates such symptoms though the mechanisms are unclear. We used magnetic resonance imaging (MRI) to monitor the intragastric fate of a WMB meal (11% bran) compared with a rice pudding (RP) meal. SUBJECTS/METHODS: Twelve healthy volunteers completed this randomised crossover study. They fasted overnight and after an initial MRI scan consumed a glass of orange juice with a 2267 kJ WMB or an equicaloric RP meal. Subjects underwent serial MRI scans every 45 min up to 270 min to assess gastric volumes and small bowel water content, and completed a GI symptom questionnaire. RESULTS: The MRI intragastric appearance of the two meals was markedly different. The WMB meal formed a homogeneous dark bolus with brighter liquid signal surrounding it. The RP meal separated into an upper liquid layer and a lower particulate layer allowing more rapid emptying of the liquid compared with solid phase (sieving). The WMB meal had longer gastric half-emptying times (132±8 min) compared with the RP meal (104±7 min), P<0.008. The WMB meal was associated with markedly reduced MRI-visible small bowel free mobile water content compared with the RP meal, P<0.0001. CONCLUSIONS: WMB bread forms a homogeneous bolus in the stomach, which inhibits gastric sieving and hence empties slower than the equicaloric rice meal. These properties may explain why wheat causes postprandial bloating and could be exploited to design foods that prolong satiation.
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Pan , Vaciamiento Gástrico/fisiología , Intestino Delgado/metabolismo , Comidas , Oryza , Periodo Posprandial/fisiología , Agua/fisiología , Índice de Masa Corporal , Estudios Cruzados , Femenino , Mucosa Gástrica/metabolismo , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Saciedad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: To assess the reliability of magnetic resonance imaging (MRI) to measure fetal fat volume in utero, and to study fetal growth in women with and without diabetes in view of the increased prevalence of macrosomia in the former. METHODS: We studied 26 pregnant women, 14 with pre-gestational diabetes and 12 non-diabetic controls. Fetal assessment took place at 24 weeks' gestation and again at 34 weeks by standard ultrasound biometry followed by MRI at 1.5 T. Fetal fat volume was determined from T1-weighted water-suppressed images using a semi-automated approach based on pixel intensity and taking into account partial volume effects. Fetal volume was also determined from the MRI images. Fetal weight was calculated using published fat and lean tissue densities. RESULTS: There was little fetal fat at 24 weeks' gestation, but at 34 weeks the fetal fat content was considerably higher in the women with diabetes, with a mean fat content of 1090 ± 417 cm(3) compared with 541 ± 348 cm(3) in the controls (P = 0.006). Measurements of fetal fat volume showed low intra- and interobserver variability at 34 weeks, with intraclass correlation coefficients consistently above 0.99. Birth-weight centile correlated with fetal fat volume (R(2) = 0.496, P < 0.001), percentage of fetal fat (R(2) = 0.362, P = 0.008) and calculated fetal weight (R(2) = 0.492, P < 0.001) at 34 weeks. CONCLUSIONS: MRI appears to be a promising tool for the determination of fetal fat, body composition and weight in utero during the third trimester of pregnancy.
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Tejido Adiposo/fisiología , Composición Corporal/fisiología , Peso Fetal/fisiología , Feto/fisiología , Imagen por Resonancia Magnética/métodos , Embarazo en Diabéticas , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Loperamide (LOP) is an anti-diarrhoeal agent which is thought to act largely by slowing transit with an uncertain effect on the fluid content of the small and large bowel in humans. Adding simethicone (SIM) to LOP improves its efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to assess small bowel water content (SBWC) have shown that mannitol solutions markedly increase SBWC and can be used as a model of diarrhoea. AIM: We aimed to use quantitative MRI techniques to compare the actions in the gut of LOP and LOP + SIM in a model of secretory diarrhoea using mannitol. METHODS: A total of 18 healthy volunteers ingested capsules containing placebo (PLA) or 12 mg LOP or 12 mg LOP + 125 mg SIM. After 100 min they were given a drink containing 5% mannitol in 350 mL of water. They underwent baseline fasting and postprandial serial MRI scans at 45 min intervals for 4.5 h after ingesting the drink. A range of MRI sequences was acquired to image the gut. RESULTS: LOP and LOP + SIM significantly accelerated gastric emptying (P < 0.03) and reduced SBWC during the late phase (135-270 min after mannitol ingestion), P < 0.009, while delaying arrival of fluid in the ascending colon (AC). The relaxation time T2 of the contents of the AC was reduced by both drugs (P < 0.0001). CONCLUSIONS: LOP and LOP + SIM accelerate gastric emptying, but reduce small bowel water content which may contribute to the delay in oral-caecal transit and overall anti-diarrhoeal effect.
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Antidiarreicos/uso terapéutico , Antiespumantes/uso terapéutico , Agua Corporal/metabolismo , Diarrea/tratamiento farmacológico , Loperamida/uso terapéutico , Imagen por Resonancia Magnética , Simeticona/uso terapéutico , Adulto , Estudios Cruzados , Diarrea/inducido químicamente , Diarrea/metabolismo , Método Doble Ciego , Quimioterapia Combinada , Femenino , Motilidad Gastrointestinal/fisiología , Humanos , Absorción Intestinal/fisiología , Intestino Delgado/metabolismo , Masculino , Manitol/efectos adversos , Persona de Mediana Edad , Adulto JovenRESUMEN
AIM: To evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII), and its impact on glycaemic control, insulin doses and auxological parameters in children with diabetes over a 4-year period. METHOD: A retrospective analysis of all patients treated with CSII. Data on HbA1c, height, weight, insulin doses, hypoglycaemia and diabetic ketoacidosis (DKA) were analysed. RESULTS: 67 patients, aged 1-16 years showed a mean (±SD) HbA1c pre-CSII of 8.2%, decreasing to 7.3% (±0.8%) at 6 months (p<0.01), 7.7% (±0.99) at 2 years (p<0.05), 7.4% (±0.94) at 3 years (n=9, p=0.15) and 7.6% (±0.97) at 4 years (n=4, p=1.0). Insulin doses reduced significantly with a trend towards reduced BMI SDS. Nine preschool children showed HbA1c reduction from 8.4% (±0.94) to 7.4% (±0.32, p<0.01) over 20 months with no episodes of severe hypoglycaemia or DKA. CONCLUSION: The authors demonstrate that CSII is associated with significantly improved sustained glycaemic control, especially in preschool children with diabetes in motivated families.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Adolescente , Distribución por Edad , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Cetoacidosis Diabética/prevención & control , Esquema de Medicación , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Lactante , Infusiones Subcutáneas , Insulina/efectos adversos , Insulina/uso terapéutico , Estudios Retrospectivos , Distribución por Sexo , Resultado del TratamientoRESUMEN
Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1-10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti-Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients.
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Candidiasis Mucocutánea Crónica/inmunología , Poliendocrinopatías Autoinmunes/inmunología , Receptores de Reconocimiento de Patrones/sangre , Candida albicans/inmunología , Candidiasis Mucocutánea Crónica/genética , Diferenciación Celular/inmunología , Células Cultivadas , Células Dendríticas/inmunología , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Lipopolisacáridos/inmunología , Masculino , Monocitos/inmunología , Mutación , Poliendocrinopatías Autoinmunes/genética , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/genética , Receptores de Reconocimiento de Patrones/biosíntesis , Receptores de Reconocimiento de Patrones/genética , Transducción de Señal/inmunología , Factores de Transcripción/genética , Proteína AIRERESUMEN
BACKGROUND: APECED (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) is a rare autosomal recessive disease characterised primarily by sequential immune-mediated destruction of endocrine tissues, chronic oral or mucocutaneous candidiasis and ectodermal disorders, including hypoplasia of dental enamel. AIM: This was to investigate the oral health and presence of enamel defects in a cohort of patients with APECED. METHODS: 16 patients with APECED (mean age of 13.9 years) were matched for age and gender with healthy controls. A comprehensive medical, dental and drug history was recorded, followed by a clinical assessment of oral health which was determined by assessing periodontal treatment needs, prevalence of dental caries, erosion, fluorosis and enamel defects. The estimated time of the development of the enamel defects and the contemporaneous medical diagnosis were recorded. RESULTS: Oral health of patients with APECED was poor compared with controls, with a higher prevalence of periodontal disease, caries and erosion. There was a significantly (P < 0.05) higher prevalence of enamel defects in the study group. The enamel defects were mostly hypoplastic in the form of pits, missing enamel and grooves. The enamel defects occurred in a chronological pattern. There was a strong association between the estimated time of defective enamel formation and a history of hypoparathyroidism. Gastrointestinal dysfunction and a history of chronic mucocutaneous candidiasis were also associated with the presence of enamel defects. CONCLUSION: The oral health of individuals with APECED was poor compared with controls with a higher prevalence of periodontal disease, caries, erosion and enamel defects. The enamel defects in the study population occurred in a chronological pattern and some were associated with a history of systemic disease during the period of tooth development.
Asunto(s)
Enfermedades de la Boca/clasificación , Poliendocrinopatías Autoinmunes/fisiopatología , Enfermedades Dentales/clasificación , Adolescente , Adulto , Candidiasis Mucocutánea Crónica/fisiopatología , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Caries Dental/clasificación , Esmalte Dental/anomalías , Hipoplasia del Esmalte Dental/clasificación , Femenino , Fluorosis Dental/clasificación , Enfermedades Gastrointestinales/fisiopatología , Humanos , Hipoparatiroidismo/fisiopatología , Masculino , Evaluación de Necesidades , Enfermedades Periodontales/clasificación , Erosión de los Dientes/clasificación , Adulto JovenRESUMEN
Patients with chronic mucocutaneous candidiasis (CMC) suffer persistent infections with the yeast Candida. CMC includes patients with autoimmune regulator (AIRE) gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, and dendritic cells (DCs), as central orchestrators, may underlie pathogenic disease mechanisms. In 29 patients with CMC (13 with APECED) and controls, we generated monocyte-derived DCs, stimulated them with Candida albicans, Toll-like receptor-2/6 ligand and lipopolysaccharide to assess cytokine production [interleukin (IL)-12p70, IL-23, interferon (IFN)-gamma, IL-2, tumour necrosis factor (TNF)-alpha, IL-6, transforming growth factor-beta, IL-10, IL-5, IL-13] and cell-surface maturation marker expression (CD83, CD86, human leucocyte antigen D-related). In both APECED and non-APECED CMC patients, we demonstrate impairment of DC function as evidenced by altered cytokine expression profiles and DC maturation/activation: (1) both groups over-produce IL-2, IFN-gamma, TNF-alpha and IL-13 and demonstrate impaired DC maturation. (2) Only non-APECED patients showed markedly decreased Candida-stimulated production of IL-23 and markedly increased production of IL-6, suggesting impairment of the IL-6/IL-23/T helper type 17 axis. (3) In contrast, only APECED patients showed DC hyperactivation, which may underlie altered T cell responsiveness, autoimmunity and impaired response to Candida. We demonstrate different pathogenic mechanisms on the same immune response pathway underlying increased susceptibility to Candida infection in these patients.
Asunto(s)
Candidiasis Mucocutánea Crónica/inmunología , Citocinas/biosíntesis , Células Dendríticas/inmunología , Poliendocrinopatías Autoinmunes/inmunología , Adolescente , Adulto , Diferenciación Celular/inmunología , Células Cultivadas , Niño , Preescolar , Susceptibilidad a Enfermedades , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-23/biosíntesis , Masculino , Persona de Mediana Edad , Células TH1/inmunología , Células Th2/inmunología , Adulto JovenRESUMEN
BACKGROUND: The Irish childhood obesity epidemic, one of the highest ranking internationally, represents a major threat to public health. We sought to perform a retrospective observational study of a clinic based cohort of obese Irish children. METHODS: Clinical data relating to gender, age, height, weight, body mass index and blood pressure were analysed, from 206 children referred to a paediatric endocrine referral centre over a 15-year period for assessment of obesity. RESULTS: Younger patients tended to have a higher standardised body mass index at initial presentation; 92% of boys and 96% of girls referred were obese (age-related BMI >/= 95th percentile). Boys (51%) and girls (49%) had initial blood pressure measurements in the hypertensive range. There was a correlation between the degree of obesity and systolic blood pressure, particularly in boys. CONCLUSIONS: Obese Irish children present with significant long-term health risks, including hypertension at baseline.