Large Duodenal Hematoma Causing an Ileus after an Endoscopic Duodenal Biopsy in a 6-Year-Old Child: A Case Report.

Intramural duodenal hematoma (IDH) in children is a rare complication after esophagogastroduodenoscopy. It is commonly described in patients with additional disorders or risk factors, such as coagulopathy. We present a case of a previously healthy 6-year-old boy with a large obstructing intramural duodenal hematoma and concomitant pancreatitis after an elective esophagogastroduodenoscopy. The patient presented with typical symptoms of an IDH, such as abdominal pain and distension, nausea and vomiting. IDH was diagnosed using ultrasound and magnetic resonance imaging examination. Conservative management with gastric decompression using a nasogastric feeding tube, bowel rest, total parenteral nutrition and analgesia was performed. After three weeks, the patient was discharged from the hospital without any complaints. Interventional management of IDH in pediatric patients with a lack of response to conservative therapy or complicating IDH should be discussed in an interdisciplinary team.

Long-term implications of structured transition of adolescents with inflammatory bowel disease into adult health care: a retrospective study.

BACKGROUND: We aimed to evaluate the long-term clinical and socioeconomic outcome of structured transition care in adolescents with inflammatory bowel disease (IBD). METHODS: We compared the clinical long-term course of 24 patients with and 11 patients without structured transition care within 24 months before and 24 months after transfer from paediatric to adult health care. Socio-economic parameters and quality of life were assessed by IBD Questionnaire (IBDQ-32) and additional items. Treatment costs were calculated for medication, surgery and hospitalisation. RESULTS: The percentage of transfer group patients with an IBD-related intestinal complication was higher compared to the transition group (64% vs. 21%, p = 0.022). We also found a tendency towards a higher number of IBD-related surgery in the transfer group compared to the transition group (46% vs. 13%, p = 0.077). Transfer group patients received higher mean cumulated doses of radiation compared with the transition group (4.2 ± 5.3 mSv vs. 0.01 ± 0.01 mSv, p = 0.036). Delayed puberty was only noted in the transfer group (27%, p = 0.025). Mean expenditures for surgeries and hospitalisation tended to be lower in the transition group compared to transfer group patients (744 ± 630€ vs. 2,691 ± 4,150€, p = 0.050). Sexual life satisfaction was significantly higher (p = 0.023) and rates of loose bowel movements tended to be lower (p = 0.053) in the transition group. CONCLUSIONS: Structured transition of adolescents with IBD from paediatric into adult health care can lead to important clinical and economic benefits.

Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study.

BACKGROUND & AIMS: Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers. METHODS: We performed a prospective study of 1055 patients (888 adults; median age, 48 yrs and 167 children; median age, 10 yrs) referred to 8 endoscopy centers in Germany, for various indications, from January 2016 through June 2017. Patients were tested for celiac disease using Simtomax, which detects immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides (DGP). Results were compared with findings from histologic analyses of duodenal biopsies (reference standard). The primary aim was to determine the accuracy of this POCT for the detection of celiac disease, to identify candidates for duodenal biopsy. A secondary aim was to determine the prevalence of celiac disease in adult and pediatric populations referred for outpatient endoscopic evaluation. RESULTS: The overall prevalence of celiac disease was 4.1%. The POCT identified individuals with celiac disease with 79% sensitivity (95% CI, 64%-89%) and 94% specificity (95% CI, 93%-96%). Positive and negative predictive values were 37% and 99%. When we analyzed the adult and pediatric populations separately, we found the test to identify adults with celiac disease (prevalence 1.2%) with 100% sensitivity and 95% specificity. In the pediatric population (celiac disease prevalence 19.6%), the test produced false-negative results for 9 cases; the test therefore identified children with celiac disease with 72% sensitivity (95% CI 53%-86%). Analyses of serologic data revealed significantly lower DGP titers in the false-negative vs the true-positive group. CONCLUSIONS: In a study of more than 1000 adults and children, we found the Simtomax POCT to detect celiac disease with lower overall levels of sensitivity than expected. Although the test identifies adults with celiac disease with high levels of sensitivity and specificity, the prevalence of celiac disease was as low as 1.2% among adults. The test's lack of sensitivity might be due to the low intensity of the POCT bands and was associated with low serum DGP titers. Study ID no: DRKS00012499.

The Curse of Apneic Spells.

A 6-year-old girl had reduced fetal movements, numerous apneic spells, muscle hypotonia, and developmental motor delay. Her muscle biopsy tissue showed variation in myofiber diameters, small minicores by electron microscopy, and near-uniformity of type I fibers. Although no mutations were detected in RYR1, SEPN1, and DMPK genes, the RAPSN gene revealed one known mutation, p.Asn88Lys, from the mother, and one novel mutation, p.Cys366Gly, from the father. Life-saving pyridostigmine treatment suppressed her apneic spells and improved her motor development.

Inflammatory Bowel Disease in Childhood and Adolescence.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) in childhood and adolescence is 5-11 cases per 100 000 persons per year, corresponding to a new diagnosis of IBD in 800-1470 patients in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. RESULTS: Children and adolescents with IBD often have extensive involvement and an aggressive course of disease. Nonetheless, infliximab and adalimumab are the only biological agents that have been approved for this group of patients. In Crohn's disease, exclusive enteral nutrition is the treatment of first choice for inducing a remission. Patients with (peri-)anal fistulae are treated primarily with infliximab. Corticosteroids and aminosalicylates should be used with caution. In contrast, children and adolescents with ulcerative colitis are treated with either aminosalicylates or prednisolone to induce a remission. As a rule, maintenance pharmacotherapy with thiopurines in Crohn's disease and severe ulcerative colitis, or with aminosalicylates in mild to moderate ulcerative colitis, is indicated for several years, at least until the end of puberty. Patients with refractory disease courses are treated with methylprednisolone, anti-TNF-α-antibodies, and/or calcineurin inhibitors. The spectrum of surgical interventions is the same as for adults. Specific aspects of the treatment of children and adolescents with IBD include adverse drug effects, the areas of nutrition, growth, and development, and the structured transition to adult medicine. CONCLUSION: Children and adolescents with IBD or suspected IBD should be cared for by pediatric gastroenterologists in a center where such care is provided. Individualized treatment with multidisciplinary, family-oriented longterm care is particularly important. Drug trials in children and adolescents are needed so that the off-label use of drugs to patients in this age group can be reduced.

[Chronic inflammatory bowel disease: transition from pediatric to adult care]. / Chronisch entzündliche Darmerkrankungen--Transition von der Jugend- zur Erwachsenenmedizin.

Children and adolescents with inflammatory bowel diseases (IBD) are a group of patients with increasingly special health care needs. Transition from a pediatric and adolescent healthcare system into an adult medicine setting may be difficult but nevertheless is very important to ensure physiological development of adolescent patients and of the continuity of their medical treatment. Transition has shown to be a challenge for pediatricians and adult doctors as well. In Germany within the healthcare system there are no special structures established to organize and optimize transition. The German Society for Pediatric Gastroenterology and Nutrition and the German Society of Internal Medicine have founded a working group to proceed the process of transition of young patients with IBD within the german health care.

The Src homology and collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development.

Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca(2+)/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere.

Small molecule-mediated refolding and activation of myosin motor function.

The small molecule EMD 57033 has been shown to stimulate the actomyosin ATPase activity and contractility of myofilaments. Here, we show that EMD 57033 binds to an allosteric pocket in the myosin motor domain. EMD 57033-binding protects myosin against heat stress and thermal denaturation. In the presence of EMD 57033, ATP hydrolysis, coupling between actin and nucleotide binding sites, and actin affinity in the presence of ATP are increased more than 10-fold. Addition of EMD 57033 to heat-inactivated ß-cardiac myosin is followed by refolding and reactivation of ATPase and motile activities. In heat-stressed cardiomyocytes expression of the stress-marker atrial natriuretic peptide is suppressed by EMD 57033. Thus, EMD 57033 displays a much wider spectrum of activities than those previously associated with small, drug-like compounds. Allosteric effectors that mediate refolding and enhance enzymatic function have the potential to improve the treatment of heart failure, myopathies, and protein misfolding diseases. DOI: http://dx.doi.org/10.7554/eLife.01603.001.

Functional characterization of the human α-cardiac actin mutations Y166C and M305L involved in hypertrophic cardiomyopathy.

Inherited cardiomyopathies are caused by point mutations in sarcomeric gene products, including α-cardiac muscle actin (ACTC1). We examined the biochemical and cell biological properties of the α-cardiac actin mutations Y166C and M305L identified in hypertrophic cardiomyopathy (HCM). Untagged wild-type (WT) cardiac actin, and the Y166C and M305L mutants were expressed by the baculovirus/Sf9-cell system and affinity purified by immobilized gelsolin G4-6. Their correct folding was verified by a number of assays. The mutant actins also displayed a disturbed intrinsic ATPase activity and an altered polymerization behavior in the presence of tropomyosin, gelsolin, and Arp2/3 complex. Both mutants stimulated the cardiac ß-myosin ATPase to only 50 % of WT cardiac F-actin. Copolymers of WT and increasing amounts of the mutant actins led to a reduced stimulation of the myosin ATPase. Transfection of established cell lines revealed incorporation of EGFP- and hemagglutinin (HA)-tagged WT and both mutant actins into cytoplasmic stress fibers. Adenoviral vectors of HA-tagged WT and Y166C actin were successfully used to infect adult and neonatal rat cardiomyocytes (NRCs). The expressed HA-tagged actins were incorporated into the minus-ends of NRC thin filaments, demonstrating the ability to form hybrid thin filaments with endogenous actin. In NRCs, the Y166C mutant led after 72 h to a shortening of the sarcomere length when compared to NRCs infected with WT actin. Thus our data demonstrate that a mutant actin can be integrated into cardiomyocyte thin filaments and by its reduced mode of myosin interaction might be the basis for the initiation of HCM.

Cardiac deletion of the Coxsackievirus-adenovirus receptor abolishes Coxsackievirus B3 infection and prevents myocarditis in vivo.

OBJECTIVES: We investigated the role of the Coxsackievirus-adenovirus receptor (CAR) in viral myocarditis. BACKGROUND: CAR is involved in virus uptake into various cell types. It has therefore been suggested as a therapeutic target to prevent or treat Coxsackievirus B3 (CVB3)-induced diseases such as myocarditis and cardiomyopathy. Recent work in CAR-deficient animals has indicated a role in embryonic development and remodeling with cardiac malformation and lethality. METHODS: We generated a tamoxifen-inducible knockout (KO) mouse to study CAR in the adult heart after CVB3 infection. Histomorphology, virus distribution, and cardiac function were compared in CAR-KO versus noninduced littermate control animals expressing wild-type CAR (WT). RESULTS: We have demonstrated that eliminating CAR prevents signs of inflammatory cardiomyopathy, with essentially no pathology in KO hearts. Unlike CVB3-infected WT control animals, the cardiac inducible KO mice did not exhibit structural changes such as monocyte infiltration or fibrosis after CVB3 infection or increased production of markers of inflammation such as interleukin-6 and -10. Whereas CVB3 infection resulted in severe contractile dysfunction in the hearts of animals that express WT, the CAR-deficient hearts appeared normal. CONCLUSIONS: Elimination of CAR in adult hearts can efficiently block virus entry and the associated pathology including contractile dysfunction. The lack of infiltration or other morphological changes in CVB3-infected KO hearts emphasizes the contribution of direct virus-mediated pathology in enteroviral myocarditis.

The tight junction protein CAR regulates cardiac conduction and cell-cell communication.

The Coxsackievirus-adenovirus receptor (CAR) is known for its role in virus uptake and as a protein of the tight junction. It is predominantly expressed in the developing brain and heart and reinduced upon cardiac remodeling in heart disease. So far, the physiological functions of CAR in the adult heart are largely unknown. We have generated a heart-specific inducible CAR knockout (KO) and found impaired electrical conduction between atrium and ventricle that increased with progressive loss of CAR. The underlying mechanism relates to the cross talk of tight and gap junctions with altered expression and localization of connexins that affect communication between CAR KO cardiomyocytes. Our results indicate that CAR is not only relevant for virus uptake and cardiac remodeling but also has a previously unknown function in the propagation of excitation from the atrium to the ventricle that could explain the association of arrhythmia and Coxsackievirus infection of the heart.

Osteoporosis in pediatric patients suffering from chronic inflammatory bowel disease with and without steroid treatment.

BACKGROUND: Children and adolescents suffering from inflammatory bowel disease (IBD) are at risk of developing osteoporosis as a result of treatment with corticosteroids as well as of nonsteroidal factors like inflammation and malnutrition. To study the impact of these factors on development of osteopathy, we compared the rate of osteoporosis in steroid-naive and steroid-treated pediatric IBD patients. METHODS: In 90 patients (50 girls) with IBD (34 steroid-naive, 53 steroid-treated, 3 not known) aged 8.8 to 19.2 (14.4 +/- 2.2) years and 52 controls (27 girls) aged 6.1 to 17.6 (12.9 +/- 3.0) years, bone mineral density (BMD) of the lumbar spine was assessed with dual energy x-ray absorptiometry. Areal BMD values were transformed into volumetric densities called bone mineral apparent density (BMAD) and expressed as standard deviation scores (SDS) on the basis of the BMAD values of the controls. RESULTS: The rate of osteoporotic patients (BMAD-SDS < -2) was 8% in girls and 20% in boys. There was a similar proportion of osteoporosis in steroid-naive (12%) and steroid-treated (11%) patients. SDS of body height showed a significant positive correlation with BMD-SDS but not with BMAD-SDS in almost all patient subgroups, indicating an interfering dependency of BMD from bone size. CONCLUSIONS: The prevalence of osteoporosis in pediatric patients with IBD is approximately the same as in adult patients. Osteoporosis is already present before steroid treatment. Data of dual energy x-ray absorptiometry measurements should be transformed into volumetric parameters to compensate for short stature. Otherwise, a lot of growth-stunted patients may be falsely diagnosed as osteopenic.

Molecular cytogenetic analysis of a de novo interstitial deletion of 5q23.3q31.2 and its phenotypic consequences.

We report a 2(3/12)-year-old boy with a constitutional interstitial deletion of 5q,46,XY,del(5)(q23.3q31.2) de novo. Clinical manifestations in this patient included failure to thrive, psychomotor retardation, mild facial dysmorphic features, and long and slender fingers and toes. The precise location and extent (9.5 Mb) of the deletion was determined by fluorescence in situ hybridization (FISH) using 19 YAC and BAC clones. Comparison of the present patient with six other patients with deletions of chromosomal bands 5q22-5q31 allowed further delineation of a constitutional del5q22q31 syndrome. The main features of this syndrome are psychomotor retardation, failure to thrive, hypotonia, hypoplastic muscles, cleft or high arched palate, low-set and dysplastic ears, flat nasal bridge, downslanting palpebral fissures, hypertelorism, anteverted nostrils, and micro- and/or retrognathia.

Determination of sterols, estrogens and inorganic ions in waste water and size-segregated aerosol particles emitted from waste water treatment.

Concentrations of steroids and inorganic ions were measured in waste water of an aerated sand trap as well as in aerosol particles emitted from this tank at the waste water treatment plant (WWTP) of Bayreuth, Germany, in January and February 2003. The investigations comprised seven sterols, two estrogens, and several inorganic ions. Since an appropriate method for the determination of sterols in waste water was not available, a new method based on solid phase extraction was developed. The concentrations of the sterols coprostanol and cholesterol amounted to 30-180 microg l(-1) in waste water and to 400-5000 pg m(-3) in aerosol particles. All other sterols were present in markedly lower concentrations. The mean concentrations of the two estrogens estrone and 17beta-estradiol were about 165 pg m(-3) in aerosol particles. The steroid concentrations in both waste water and aerosol particles varied greatly over time, however with the exception of coprostanol, no clear correlation was detected between concentrations in waste water and aerosol particles.

Report of the task force on residency training information (2001-2002), American Board of Emergency Medicine.

The American Board of Emergency Medicine gathers extensive background information on emergency medicine residents and the programs in which they train. We present the fifth annual report on the status of US emergency medicine residency programs