One-stage transanal Swenson procedure for rectosigmoid Hirschsprung’s disease in infants and children

Objective: This study aimed to present the outcome of transanal one-stage Swenson pull-through procedure in the management of rectosigmoid Hirschsprung’s disease (HD).Background: HD is a common cause of intestinal obstruction in pediatric age. Several pull-through procedures have been used to treat this pathology.Patients and methods: Between June 2008 and June 2015, 84 children with biopsy-proven HD underwent transanal one-stage Swenson pull-through procedure. Intraoperative details, postoperative complications, and bowel habits were recorded. Follow-up period ranged from 6 to 42 months.Results: The age at the time of surgery ranged from 3 months to 2 years. The length of the resected aganglionic segment ranged from 12 to 34 cm. The operating time ranged from 72 to 180 min. Postoperative hospital stay ranged from 3 to 6 days. There were no anastomotic leaks, no perianal infection, or postoperative bowel obstruction. Twelve patients (14.28%) developed postoperative enterocolitis. Six patients (7.14%) required a posterior internal sphincter myectomy despite repeated dilatations. All patients had less than four times bowel motions per  day, 3 months after surgery. No voiding disturbances were encountered at the end of the follow-up period and none of the patients complained of recurrent constipation. Six patients developed perianal dermatitis, which was treated conservatively within 3 months after surgery. Anastomotic circumference could not be felt at digital examination in 78 patients 3 months after surgery.Conclusion: One-stage transanal Swenson pull-through procedure is a safe alternative and simpler procedure for rectosigmoid HD with low morbidities and accepted outcome as regards postoperative bowel habits.Keywords: Hirschsprung’s disease, rectosigmoid Hirschsprung’s, Swenson procedure, transanal pull-throug

Structure and in vitro digestibility of grass pea (Lathyrus sativus L.) flour following transglutaminase treatment

The impact of transglutaminase (TG) modification on microstructure and in vitro protein and starch digestibility of grass pea flour was investigated. Results demonstrated that grass pea flour proteins act as effective substrate of TG. Microstructural results showed that the addition of TG produced a more compact structure likely due to TG-catalyzed heteropolymers. Nutritional properties such as slowly digestible starch and expected glycemic index values followed the order: grass pea flour incubated in the absence of TG>grass pea flour incubated in the presence of TG>raw flour. The TG-catalyzed heteropolymers were easily digested as demonstrated by in vitro oral and gastric digestion carried out under physiological conditions. Therefore, TG-modified grass pea flour can be considered as a new source of starch and proteins suitable for feeding a large spectrum of population

Gastrografin in the management of adhesive small bowel obstruction in children: a pilot study

Background/purpose Adhesive small bowel obstruction (ASBO) is a common emergency problem in children with previous abdominal surgery. Management protocols usually start with a conservative approach that may be successful in some cases, whereas in others it will end eventually by laparotomy with its associated morbidity and mortality. Our aim was to assess the role of water-soluble contrast, gastrografin, in the conservative management of ASBO. Patients and methods During the period January 2009 to July 2010, 33 patients with ASBO were presented at the Pediatric Surgery Unit at the Ain Shams University Hospitals. Patients who failed to improve after 48 h of conservative management in the absence of signs of strangulation were subjected to gastrografin administration. Patients were evaluated clinically and radiologically to determine the resolution of the adhesive attack, with estimation of hospital stay time. Results An oral administration of gastrografin successfully completed the conservative management in eight of 12 patients (66.6%), thus avoiding surgery and subsequently reducing hospital stay. Conclusion Gastrografin may have a valuable role in the management of ASBO, whether diagnostic or therapeutic, but a randomized controlled trial is needed to prove its effectiveness in reducing surgical intervention rate and hospital stay time.Keywords: adhesive, bowel obstruction, gastrografi

Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia

AbstractBackgroundTardive dyskinesia (TD) is a potentially irreversible consequence of long term treatment with antipsychotic drugs which is according to a well-known theory believed to be related to oxidative stress induced neurotoxicity. Dehydroepiandrosterone (DHEA) is an endogenous antioxidant with neuroprotective activity. The biosynthesis of DHEA depends upon the activity of cytochrome P450c17α (CYP17). The gene that encodes for CYP17 has a (T34C) single nucleotide polymorphism which enhances CYP17 transcription and expression.ObjectiveTo test the hypothesis that carriership of a more active CYP17 variant would result in higher DHEA(S) levels and protect against neurotoxicity which results in orofaciolingual TD (TDof), limb-truncal TD (TDlt) or both (TDsum).MethodTardive dyskinesia was assessed cross-sectionally in 146 Caucasian psychiatric inpatients from Siberia.ResultsPatients who are carriers of the Cyp17 genotype CC have less chance of developing TD compared to patients who are carriers of the Cyp17 genotypes TC or TT (p<0.05). However, these carriers have significant lower circulating DHEAS levels compared to carriers of the Cyp17 genotypes TC and TT (p<0.05). Conversely, carriers of the CYP17 T-allele have significant elevated DHEAS levels. After correcting for gender and age no significant relationship between Cyp17 genotype CC, the T-allelle and the C-allele and the DHEAS concentration of patients was observed.ConclusionsAlthough an association between the CYP17 CC genotype and TD is indicated, our findings do not support the hypothesis that this is mediated through increased DHEA(S) levels. We believe that the relationship between this polymorphism and neuroprotective effects of steroids is more complex and cannot be elucidated without taking the posttranslational regulation of the enzyme into account

Assessment of aortic stiffness by cardiovascular magnetic resonance following the treatment of severe aortic stenosis by TAVI and surgical AVR

Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV).A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m.Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved

Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate—a validated assay for the clinic

The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5–1,500 ng/mL for oseltamivir and 20–1,500 ng/mL for the oseltamivircarboxylate metabolite. As a proof of concept, oseltamivir and oseltamivircarboxylate levels were determined in DBS obtained from healthy volunteers who received a single oral dose of Tamiflu®

Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia:A comparison of genetic variants in two independent patient populations

Objectives: An established theory for the pathogenesis of tardive dyskinesia is disturbed dopaminergic receptor sensitivity and/or dopaminergic intracellular signaling. We examined associations between genetic variants of neurotransmitter receptors and tardive dyskinesia. Methods: We assessed tardive dyskinesia in Caucasian psychiatric inpatients from Siberia (N = 431) and a long-stay population from the Netherlands (N = 168). These patients were genotyped for 43 tag single nucleotide polymorphisms in five neurotransmitter receptor genes, and the results for the two populations were compared. Results: Several significant associations with tardive dyskinesia were identified, but only GRIN2A (rs1345423) was found in both patient populations. This lack of agreement was probably due to the small effect size of the associations, the multiple testing and the small sample size of the Dutch patient population. After reviewing the literature, we propose that the constitutive stimulatory activity of serotonergic type 2 receptors may be relevant. Conclusions: Inactivity of the serotonergic, type 2C receptor or blockade of these receptors by atypical antipsychotic drugs may decrease the vulnerability to develop tardive dyskinesia

TET1 is a tumor suppressor of hematopoietic malignancy

The methylcytosine dioxygenase TET1 (‘ten-eleven translocation 1’) is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted the development of B cell lymphoma in mice. TET1 was required for maintenance of the normal abundance and distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation of the B cell lineage and of genes encoding molecules involved in chromosome maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in which TET1 was hypermethylated and transcriptionally silenced. Our findings provide in vivo evidence of a function for TET1 as a tumor suppressor of hematopoietic malignancy.National Institutes of Health (U.S.) (5RO1HD045022)National Institutes of Health (U.S.) (5R37CA084198