60 research outputs found
Bowel management in children: how to keep children clean
Objective: The term bowel management refers to an individualized program for fecal incontinent patients. The main principle is the administration of fluid to wash out the colon, either transanally or antegrade through a stoma.Method: A literature search was performed to find the best method to keep fecal incontinent children clean.Results: Bowel management with an individually determined amount of fluid, either by abdominal radiographs or hydrosonography, showed better success rates compared with transanal enemas with an estimated amount of fluid. Furthermore, transanal enemas had higher success rates compared with bowel management with antegrade continence enemas and showed fewer complications.Conclusion: To improve a childâs quality of life an antegrade continence enema can be considered. Before surgery it has to be shown that a bowel management with rectal irrigations works. The indication for a surgical approach for bowel management has to be set carefully. Conservative measures must be tried first.Keywords: anorectal malformation, antegrade continence enema, bowel management, fecal incontinenc
Metastasized pancreatic neuroendocrine tumor in a teenage girl: a case report
Introduction: Metastasized pancreatic neuroendocrine tumors are extremely rare malignancies, especially in children. Therefore, therapeutic options are limited, and few standardized therapy regimens exist. Case presentation: We report a case of a 14-year-old white girl. In 2011 she was diagnosed with a metastasized, well-differentiated pancreatic neuroendocrine tumor with expression of synaptophysin and chromogranin A. We describe her clinical course with special attention to her individual therapeutic regimens while bringing together several disciplines of medicine. Conclusions: In patients such as ours, surgical intervention may be the only therapy that will lead to long-term survival
AQP1 Is Up-Regulated by Hypoxia and Leads to Increased Cell Water Permeability, Motility, and Migration in Neuroblastoma
The water channel aquaporin 1 (AQP1) has been implicated in tumor progression and metastasis. It is hypothesized that AQP1 expression can facilitate the transmembrane water transport leading to changes in cell structure that promote migration. Its impact in neuroblastoma has not been addressed so far. The objectives of this study have been to determine whether AQP1 expression in neuroblastoma is dependent on hypoxia, to demonstrate whether AQP1 is functionally relevant for migration, and to further define AQP1-dependent properties of the migrating cells. This was determined by investigating the reaction of neuroblastoma cell lines, particularly SH-SY5Y, Kelly, SH-EP Tet-21/N and SK-N-BE(2)-M17 to hypoxia, quantitating the AQP1-related water permeability by stopped-flow spectroscopy, and studying the migration-related properties of the cells in a modified transwell assay. We find that AQP1 expression in neuroblastoma cells is up-regulated by hypoxic conditions, and that increased AQP1 expression enabled the cells to form a phenotype which is associated with migratory properties and increased cell agility. This suggests that the hypoxic tumor microenvironment is the trigger for some tumor cells to transition to a migratory phenotype. We demonstrate that migrating tumor cell express elevated AQP1 levels and a hypoxic biochemical phenotype. Our experiments strongly suggest that elevated AQP1 might be a key driver in transitioning stable tumor cells to migrating tumor cells in a hypoxic microenvironment
Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis
Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential
Virilization of a Young Girl Caused by Concomitant Ectopic and Intra-Adrenal Adenomas of the Adrenal Cortex
Background: Adenomas of the adrenal gland are rare causes ofvirilization in childhood. Case Report: A girl aged 2 years and 4 monthspresented with pubarche, distinct clitoral hypertrophy, tall stature,and increased height velocity. Plasma testosterone anddehydroepiandrosterone were elevated. Androgens remained unchanged afteradrenocorticotropic hormone, and dexamethasone administrations.Ultrasound examination and magnetic resonance imaging indicated anextra-adrenal mass adjacent to the left adrenal gland, which was removedby endoscopic surgery. However, plasma androgens remained elevated and131 I-iodomethyl-norcholesterol scintigraphy revealed tracer enhancementin the right adrenal gland, which was consecutively removed.Virilization regressed after extirpation of the adenomas and heightvelocity normalized. Results: Histology revealed a circumscribed adenomain the right adrenal gland and an epithelial mass with adrenal corticalcells in the left-sided ectopic tumor. In the ectopic tumor,melanocortin 2 receptor expression was augmented threefold compared tothe control, indicating adrenal origin. Conclusions: In this young girl,virilization is due to concomitant ectopic and intra-adrenal adenomas ofthe adrenal cortex. By melanocortin 2 receptor expression, it wasconfirmed that the ectopic adenoma derived from the adrenal cortex.Specific scintigraphy, if available, assists in allocating the source ofandrogen hypersecretion
Cholinergic Signaling Attenuates Pro-Inflammatory Interleukin-8 Response in Colonic Epithelial Cells.
Infants affected by Hirschsprung disease (HSCR), a neurodevelopmental congenital disorder, lack ganglia of the intrinsic enteric nervous system (aganglionosis) in a variable length of the colon, and are prone to developing severe Hirschsprung-associated enterocolitis (HAEC). HSCR patients typically show abnormal dense innervation of extrinsic cholinergic nerve fibers throughout the aganglionic rectosigmoid. Cholinergic signaling has been reported to reduce inflammatory response. Consequently, a sparse extrinsic cholinergic innervation in the mucosa of the rectosigmoid correlates with increased inflammatory immune cell frequencies and higher incidence of HAEC in HSCR patients. However, whether cholinergic signals influence the pro-inflammatory immune response of intestinal epithelial cells (IEC) is unknown. Here, we analyzed colonic IEC isolated from 43 HSCR patients with either a low or high mucosal cholinergic innervation density (fiber-low versus fiber-high) as well as from control tissue. Compared to fiber-high samples, IEC purified from fiber-low rectosigmoid expressed significantly higher levels of IL-8 but not TNF-ι, IL-10, TGF-β1, Muc-2 or tight junction proteins. IEC from fiber-low rectosigmoid showed higher IL-8 protein concentrations in cell lysates as well as prominent IL-8 immunoreactivity compared to IEC from fiber-high tissue. Using the human colonic IEC cell line SW480 we demonstrated that cholinergic signals suppress lipopolysaccharide-induced IL-8 secretion via the alpha 7 nicotinic acetylcholine receptor (a7nAChR). In conclusion, we showed for the first time that the presence of a dense mucosal cholinergic innervation is associated with decreased secretion of IEC-derived pro-inflammatory IL-8 in the rectosigmoid of HSCR patients likely dependent on a7nAChR activation. Owing to the association between IL-8 and enterocolitis-prone, fiber-low HSCR patients, targeted therapies against IL-8 might be a promising immunotherapy candidate for HAEC treatment
Quantitative Histomorphometry of the Healthy Peritoneum
The peritoneum plays an essential role in preventing abdominal frictions and
adhesions and can be utilized as a dialysis membrane. Its physiological
ultrastructure, however, has not yet been studied systematically. 106
standardized peritoneal and 69 omental specimens were obtained from 107
patients (0.1â60 years) undergoing surgery for disease not affecting the
peritoneum for automated quantitative histomorphometry and
immunohistochemistry. The mesothelial cell layer morphology and protein
expression pattern is similar across all age groups. Infants below one year
have a thinner submesothelium; inflammation, profibrotic activity and
mesothelial cell translocation is largely absent in all age groups. Peritoneal
blood capillaries, lymphatics and nerve fibers locate in three distinct
submesothelial layers. Blood vessel density and endothelial surface area
follow a U-shaped curve with highest values in infants below one year and
lowest values in children aged 7â12 years. Lymphatic vessel density is much
lower, and again highest in infants. Omental blood capillary density
correlates with parietal peritoneal findings, whereas only few lymphatic
vessels are present. The healthy peritoneum exhibits major thus far unknown
particularities, pertaining to functionally relevant structures, and subject
to substantial changes with age. The reference ranges established here provide
a framework for future histomorphometric analyses and peritoneal transport
modeling approaches
Research perspectives in the etiology of congenital anorectal malformations using data of the International Consortium on Anorectal Malformations: evidence for risk factors across different populations
Contains fulltext :
89406.pdf (publisher's version ) (Closed access)PURPOSE: The recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities. METHODS: The consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case-parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data. RESULTS: Currently, 701 ARM cases have been recruited throughout Europe. Clinical data are available from all cases, and DNA samples and questionnaire data mainly from the Dutch and German cases. Preliminary analyses on environmental risk factors in the Dutch and German cohort found associations between ARM and family history of ARM, fever during first trimester of pregnancy and maternal job exposure to cleaning agents and solvents. CONCLUSION: First results show that both genetic and environmental factors may contribute to the multifactorial etiology of ARM. The International Consortium on Anorectal Malformations will provide possibilities to study and detect important genes and environmental risk factors for ARM, ultimately resulting in better genetic counseling, improved therapies, and primary prevention.1 november 201
Whole exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association
Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum-stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henleâs loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or CAKUT in VACTERL association
No association between the common calcium-sensing receptor polymorphism rs1801725 and irritable bowel syndrome
Background
The calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca2+/Mg2+- homeostasis and senses interstitial Ca2+ levels and thereby controls downstream signalling cascades. Due to its expression in the gut epithelium, the enteric nervous system and smooth muscles and its key function in regulation and coordination of muscular contraction and secretion, it represents an excellent candidate gene to be investigated in the pathophysiology of irritable bowel syndrome (IBS). Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and consequently contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity.
Methods
We have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA.
Results
Genotype frequencies showed no association in the three genotyped caseâcontrol samples, neither with IBS nor with IBS subtypes.
Conclusions
Although we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca2+ levels and disturbed secretion and gut motility which were unfortunately not assessed in the patients genotyped. This underlines the necessity of a more detailed phenotyping of IBS patients and control individuals in future studies
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