Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations. We described two novel mutations in the EIF2AK3 gene in two consanguineous families with WRS from Brazil and Morocco. We have observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398 (Gln398Stop). Both of his parents were found to be heterozygous for the mutation. We detected in both parents of case 2, a deceased Moroccan girl, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285 (p.Pro285AlafsX3). Both cases 1 and 2 had neonatal diabetes mellitus, multiple epiphyseal dysplasia, and growth delay, and presented episodes of acute hepatic dysfunction. Case 1 presented central hypothyroidism, developmental delay, and mild mental retardation. Case 2 presented a fatal episode of acute renal failure. The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis.

Is facial pattern a predisposing factor for otitis media with effusion in children?

Abnormalities in craniofacial morphology are associated with Eustachian tube dysfunction and otitis media with effusion (OME). Aim: to evaluate the relationship between facial pattern and craniofacial growth direction, and OME in children with enlarged tonsils and adenoids (ETA). Methods: Clinical prospective survey in 79 children (41 male and 38 female), ranging from 4 to 10 years of age, with tonsil and adenoid enlargement (Brodsky`s grades III and IV). Forty children presented with OME (study group) and 39 did not (control group). Cephalometric analysis was used to determine the facial pattern. Results: There was no correlation observed between facial pattern and OME (c 2 = 0.25 p = 0.88). Facial Axis was larger in the OME group (F(1.75) = 3.68 p = 0.05) and the Lower Anterior Facial height was smaller (F(1. 75) = 3.99 p = 0.05) in children with otitis media with effusion. Conclusions: There was no correlation between OME and facial pattern in children with ETA although a more horizontal facial growth direction, and a smaller lower anterior facial height was observed consistently among subjects in this group. This suggests that abnormal positioning of the eustachian tube influences the development of OME in children with ETA.

Variation of Patterns of Malocclusion by Site of Pharyngeal Obstruction in Children

Objective: To correlate the type of dental occlusion and the type of pharyngeal lymphoid tissue obstruction in children. Design: Cross-sectional study. Setting: Ambulatory ear, nose, and throat clinic of Faculdade de Medicina da Universidade de Sao Paulo. Patients: One hundred fourteen children aged 3 to 12 years presenting with mouth breathing and snoring due to tonsil and/or adenoid enlargement. Interventions: Oroscopy and nasal fiber pharyngoscopy complemented by lateral head radiography to diagnose the type of obstruction, and clinical examination to evaluate the dental occlusion. Main Outcome Measures: Tonsil and adenoid obstruction (classified from grades 1-4) and sagittal, transverse, and vertical evaluation of dental occlusion. Results: Obstructive enlargement of both tonsils and adenoids was detected in 64.9% of the sample; isolated enlargement of the adenoids, in 21.9%; isolated enlargement of the palatine tonsils, in 7.0%; and nonobstructive tonsils and adenoids, in 6.1%. All types of pharyngeal obstruction were related to a high prevalence of posterior crossbite (36.8%). Statistically significant association was found between sagittal dental occlusion and the site of lymphoid tissue obstruction (P = .02). A higher rate of class II relationship (43.2%) was detected in the group with combined adenoid and tonsil obstructive enlargement. Isolated tonsil obstruction showed a higher rate of class III relationship (37.5%). Conclusions: Different sites of obstruction of the upper airway due to enlarged lymphoid tissue are associated with different types of dental malocclusion. Findings are relevant to orthodontic and surgical decision making in these mouth-breathing patients.

Adenotonsillectomy improves the strength of respiratory muscles in children with upper airway obstruction

Objective: The aim of this paper is to study the respiratory muscle strength by evaluating the maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and lung volume before and 3 and 6 months after adenotonsillectomy. This is an interventional, before and after trial. It was set at the Department of Otolaryngology. University of Sao Paulo, School of Medicine. We included 29 children (6-13 years old), both genders, consecutively recruited from the waiting list for adenotonsillectomy. Children were submitted to maximal inspiratory pressures (MIP), maximal expiratory pressure (MEP) evaluation using an analog manovacuometer, lung volume, using incentive expirotometer and thoracic and abdominal perimeter using a centimeter tape. Children were evaluated in 3 different moments: 1 week before and 3 and 6 months after surgery. Results: MIP improved significantly 3 months (p < 0.001) after adenotonsillectomy and MEP did not change (p = 1). There were increases in lung volume (p = 000), chest (p = 0.017) and abdominal perimeter (p = 0.05). Six months after surgery, all parameters improved. MIP (p = 0), MEP (p = 0), lung volume (p = 0.02), chest (p = 0.034) and abdominal perimeter (p = 0.23). Conclusion: This study suggests that there was an improvement in respiratory muscular strength, once there was a significant improvement in maximal inspiratory pressure, lung volume and other parameters after adenotonsillectomy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Percutaneous central venous catheterization through the external jugular vein in children: improved success rate with body maneuvers and fluoroscopy assistance

Background/Purpose: Central venous catheterization is among the most common procedures performed by pediatric surgeons. Significant morbidity and even mortality can ensue from the widespread approach to the deep veins of the neck and femoral region. The external jugular vein (EJV) is a low-morbidity alternative for percutaneous catheterization in children, but it has yielded a low success rate in previous reports The authors show an improved success rate with this option. Methods: We performed an analysis of 33 patients` charts in which central venous catheterization using Seldinger technique through the EJV was attempted in 2005. Age, diagnosis, maneuvers used for success, fluoroscopy usefulness, and types of inserted catheters were evaluated. Results: The procedure was successful in 26 (78.8%) patients without complications. Diagnosis was neoplasia in almost half of the patients (42%). In half of the successful cases, body maneuvers were used, namely, twisting the head of the patient to the side of the vein and stretching the ipsilateral arm and shoulder. All but one procedure were completed under fluoroscopic guidance. In 6 (23%) patients, a long-term catheter was inserted. Conclusions: The EJV is an excellent option for central venous catheterization in children. The execution of simple maneuvers along with fluoroscopic assistance might allow for an improved success rate not only for short-term but also for long-term catheter insertion. (C) 2008 Elsevier Inc. All rights reserved.

The aversiveness of specific emotional states associated with binge-eating in obese subjects

Objective: The aim of this study was to examine the hypothesis that non-purge-related binge-eating in obesity is maintained by a 'trade-off' in which a highly aversive emotional state is exchanged for a less aversive state. Method: Ninety-eight obese binge-eaters meeting the DSM-IV criteria for binge-eating disorder [1] were contrasted with 65 non-binge-eating controls on their perceived distress associated with negative mood states usually experienced before and after binges. Results: Binge-eaters reported significantly greater distress and lower tolerance of negative mood compared to controls. Furthermore, when compared with controls, binge-eaters reported that emotions typically reported before binges (e.g. anger) were more aversive than those reported after (e.g. guilt). Conclusions: These results were interpreted as supporting the 'trade-off' theory and have implications for the treatment of binge-eating disorder.

Intraosseous Anesthesia in Hemodynamic Studies in Children with Cardiopathy

Aliman AC, Piccioni MA, Piccioni JL, Oliva JL, Auler Junior JOC - Intraosseous Anesthesia in Hemodynamic Studies in Children with Cardiopathy. Background and objectives: Intraosseous (IO) access has been used with good results in emergency situations, when venous access is not available for fluids and drugs infusion. The objective of this study was to evaluate IO a useful technique for anesthesia and fluids infusion during hemodynamic studies and when peripheral intravascular access is unobtainable. The setting was an university hospital hemodynamics unit, and the subjects were twenty one infants with congenital heart disease enrolled for elective hemodynamic study diagnosis. Methods: This study compared the effectiveness of IO access in relation to IV access for infusion of anesthetics agents (ketamine, midazolann, and fentanyl) and fluids during hemodynamic studies. The anesthetic induction time, procedure duration, anesthesia recovery time, adequate hydration, and IV and IO puncture complications were compared between groups. Results: The puncture time was significantly smaller in IO group (3.6 min) that in IV group (9.6 min). The anesthetic onset time (56.3 second) for the IV group was faster than IO group (71.3 second). No significant difference between groups were found in relation to hydration (IV group, 315.5 mL vs IO group, 293.2 mL), and anesthesia recovery time (IO group, 65.2 min vs IV group, 55.0 min). The puncture site was reevaluated after 7 and 15 days without signs of infection or other complications. Conclusions: Results showed superiority for IO infusion when considering the puncture time of the procedure. Due to its easy manipulation and efficiency, hydration and anesthesia by IO access was satisfactory for hemodynamic studies without the necessity of other infusion access.

Laparoscopic extended cardiomyotomy in children: an effective procedure for the treatment of esophageal achalasia

Purpose: Achalasia of the esophagus is characterized by aperistalsis and incomplete relaxation of the lower esophageal sphincter in response to swallowing. The objective of the present study is to present the experience of a modified Heller myotomy via a laparoscopic approach for the treatment of children who had this condition. Methods: A retrospective review of medical records of all patients who underwent this procedure from 2000 to 2009 was performed. The procedure consisted of an extended esophagomyotomy beginning on the lower part of the lower esophageal sphincter and continuing 5 to 6 cm above on the lower third of the esophagus, and then extended 3 to 4 cm below to the stomach, associated with an anterior 180-degree hemi-fundoplication according to Dor`s technique. Results: Fifteen patients were included in the study. There were 8 female and 7 male patients. Mean operating time was 190 minutes with no intraoperative complications and 1 conversion to open surgery because of difficulty in dissecting an inflamed distal esophagus. In a mean follow-up period of 32.3 months, 2 patients had recurrence of mild dysphagia that disappeared spontaneously, and 1 required a single botulinum toxin injection with complete resolution of symptoms. Conclusion: We conclude that the laparoscopic extended Heller myotomy with Dor fundoplication is a safe and effective method for the treatment for achalasia in the pediatric population even in advanced cases. (C) 2010 Elsevier Inc. All rights reserved.

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation

Purpose: Hepatectomy remains a complex operation even in experienced hands. The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results. Methods: The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan. Surgery was performed by surgeons competent in liver transplantation. As in liver living donor operation, vascular anomalies were investigated. The main arterial anomalies found were the right hepatic artery emerging from the superior mesenteric artery and left hepatic artery from left gastric artery. Hilar structures were dissected very close to liver parenchyma. The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe. During dissection of the suprahepatic veins, the venous infusion was decreased to reduce central venous pressure and potential bleeding from hepatic veins and the vena cava. Results: Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable. There were 31 cases of hepatoblastoma, with a 9.6% mortality rate. Ten children presented with other malignant tumors-3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma. These cases had a 50% mortality rate. Six children had benign tumors-4 mesenchymal hamartoma, 1 focal nodular hyperplasia, and a mucinous cystadenoma. All of these children had a favorable outcome. Hepatic resections included 22 right lobectomies, 9 right trisegmentectomies, 8 left lobectomies, 5 left trisegmentectomies, 2 left segmentectomies, and 1 case of monosegment (segment IV) resection. The overall mortality rate was 14.9%, and all deaths were related to recurrence of malignant disease. The mortality rate of hepatoblastoma patients was less than other malignant tumors (P = .04). Conclusion: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate. (C) 2009 Elsevier Inc. All rights reserved.

Comparison of videolaparoscopic versus open surgery for benign renal diseases in children

Introduction: Laparoscopic nephrectomy in children has become a reasonable alternative to open nephrectomy and has replaced open surgery for many renal diseases. The purpose of our study is to evaluate transperitoneal videolaparoscopic procedures in renal benign diseases in comparison to an open surgery approach. Patients and methods: 34 children aged between 17 days and 15 years old (mean 6.14) were divided into two groups in order to be submitted to nephrectomy. The first one underwent transperitoneal videolaparoscopic nephrectomy and was composed by 21 patients aged from 2 months to 15 years (mean 7.42), from which 12 were females and 9 males. The second group was submitted to open nephrectomy and was composed by 13 patients aged from 17 days to 11 years (mean 3.91), 6 females and 7 males. The groups were compared regarding anesthesic time, operative time, length of hospital stay, postoperative pain and time of reintroduction of oral intake. Short and long term complications were also evaluated. Statistical analysis was performed by Student t-test with the level of significance set at P < 0.05. The study was previously approved by the Committee on Ethics in Research of our institution. Results: Significant statistical difference was observed only for the variable length of hospital stay. No laparoscopy group case was converted to open surgery. There was no immediate or late complication. Blood loss was negligible and no transfusion was required. Conclusions: In our experience, transperitoneal videolaparoscopic nephrectomy has similar results to open nephrectomy, except for time of hospitalization. (C) 2009 AEU. Published by Elsevier Espana, S.L. All rights reserved.

Transanal endorectal pull-through in children with Hirschsprung`s disease-technical refinements and comparison of results with the Duhamel procedure

Purpose: Transanal endorectal pull-through (TEPT) has drastically changed the treatment of Hirschsprung`s disease (HD). A short follow-up of children Submitted to TEPT reveals results that are similar to the classic transabdominal pull-through procedures. However, few reports compare the late results of TEPT with transabdominal pull-through procedures with respect to complication rates and the fecal continence. The aims of the present work are to describe some technical refinements that we introduced in the procedure and to compare the short and long-term outcome of TEPT with the outcomes of a group of patients with HD who previously underwent the Duhamel procedure. Methods: Thirty-five patients who underwent TEPT were prospectively studied and compared to a group of 29 patients who were treated with colostomy followed by a classical Duhamel pull-through. The main modifications introduced in the TEPT group were no preoperative colon preparation, operation conducted under general anesthesia in addition to regional sacral anesthesia, use of only one purse-string Suture in the rectal mucosa before transanal submucosal dissection, and no use of retractors and electrocautery during file submucosal dissection. Results: The most frequent early complications of TEPT group were perineal dermatitis (22.8%) and anastomotic strictures (8.6%). The comparison with patients who underwent Duhamel procedure revealed no difference in the incidence of preoperative enterocolitis, the patients of the TEPT group were younger at the time of diagnosis and of surgery, they had shorter operating times, and they began oral feeding more quickly after the operation. The incidence of wound infection was lower in the TEPT group. Moreover, the TEPT and Duhamel groups showed no difference in the incidences of mortality, postoperative partial continence, and total incontinence. Although the incidences of complete continence and postoperative enterocolitis were not different, a tendency to the increased incidence in the TEPT group was observed. Conclusions: This study further supports the technical advantages, the simplicity, and the decreased incidence of complications of a primary TEPT procedure when compared to a classical form of pull-through. Sonic technical refinements are described, and no preoperative colon preparation was necessary for the patients studied here. The results show that the long-term outcomes of the modified TEPT procedure are generally better than those obtained with classical approaches. Published by Elsevier Inc.

Texture Image Analysis in Differentiating Malignant from Benign Adrenal Cortical Tumors in Children and Adults

Objective: To investigate the possible role of chromatin texture parameters, nuclear morphology, DNA ploidy and clinical functional status in discriminating benign from malignant adrenocortical tumors (ACT). Patients and Methods: Forty-eight cases of clinically benign (n=40) and clinically malignant (n=8) ACT with a minimum of 5-years` follow-up were evaluated for chromatin texture parameters (run length, standard deviation, configurable run length, valley, slope, peak and other 21 Markovian features that describe the distribution of the chromatin in the nucleus), nuclear morphology (nuclear area, nuclear perimeter, nuclear maximum and minumum diameter, nuclear shape), and DNA ploidy. Nuclear parameters were evaluated in Feulgen-stained 5 mu m paraffin-sections analyzed using a CAS 200 image analyzer. Results: Since ACTs present different biological features in children and adults, patients were divided into two groups: children (<= 15 years) and adults (>15 years). In the group of children DNA ploidy presented a marginal significance (p=0.05) in discriminating ACTs. None of the parameters discriminated between malignant and benign ACT in the adult group. Conclusion: ACTs are uncommon and definitive predictive criteria for malignancy remain uncertain, particularly in children. Our data point to DNA content evaluated by image analysis as a new candidate tool for this challenging task. Texture image analysis did not help to differentiate malignant from benign adrenal cortical tumors in children and adults.

Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal

The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a line of RIB mice transgenic for the E6 and E7 open reading frames of HPV16 driven from the alpha A crystallin promoter (FVB alpha AcryHPV16E6E7). We have transferred skin from FVB alpha AcryHPV16E6E7 mice to naive or E7-primed syngeneic NE recipients to assess whether the E7 protein of HPV16 can function as a minor transplantation antigen (MTA) and promote skin graft rejection. FVB mice did not reject E7 expressing tail or flank skin grafts. E7 immunized FVB x C57BL/6J mice recipients of FVB alpha AcryHPV16E6E7 x C57BL/6J skin generated humoral and DTH responses to E7 in vivo and E7-specific CTL precursors in the spleen, but failed to reject 57 expressing tail skin grafts by 100 days posttransfer. Thus although HPV16 E7 + ve mesenchymal and endodermal tumors can be eliminated by an E7-specific immune response, the same protein is unable to act as a MTA and promote graft rejection when expressed in skin cells. Lack of rejection of grafts expressing MTAs such as E7 may be relevant to the immunology of epithelial tumors expressing tumor-specific antigens and to our understanding of the immunology of diseases of the skin. (C) 1997 Academic Press.

Measurement of radiation dose received by the hands and thyroid of staff performing gridless fluoroscopic procedures in children

The aim of this study was to confirm that the radiation doses received by attendants who manually restrain infants during fluoroscopic procedures are low. Doses to the hands and neck of three radiologists and three nurses performing or assisting at all the fluoroscopic procedures in a children's hospital were measured for 1 month using thermoluminescent dosemeters. All fluoroscopy on children at this hospital is performed without an antiscatter grid. Total doses for the neck ranged from 20 to 50 mu Sv per week and for hands from 40 to 210 mu Sv per week. These doses were shared by the three radiologists and the three nurses. Individual doses received per staff member are very small when compared with the doses received by interventional radiology staff. Doses received by staff in this study were of the order of 5% of the limit advised by the National Health and Medical Research Council of Australia (NHMRC) for radiation workers. Nurses received larger doses than radiologists and steps will be taken to reduce this dose further.

Altered loading patterns and femoral bone mineral density in children with unilateral Legg-Calve-Perthes disease

Maximization of bone accrual during the growing years is thought to be an important factor in minimizing fracture risk in old age. Mechanical loading through physical activity has been recommended as a modality for the conservation of bone mineral in adults; however, few studies have evaluated the impact of different loading regimes in growing children. The purpose of this study was to compare bone mineral density (BMD) in weight-bearing and non-weight-bearing limbs in 17 children with unilateral Legg Calve Perthes Disease (LCPD). Children with this condition have an altered weight-bearing pattern whereby there is increased mechanical loading on the noninvolved normal hip and reduced loading on the involved painful hip. Thus, these children provide a unique opportunity to study the impact of differential mechanical loading on BMD during the growing years while controlling for genetic disposition. BMD at four regions of the proximal femur (trochanter, intertrochanter, femoral neck, total of the regions) was measured using dual energy x-ray absorptiometry (DXA), and the values were compared between the involved and noninvolved sides of the children with LCPD. The BMD of both sides also were compared with normative values based on both chronological and skeletal age data. A significantly higher BMD was found on the noninvolved side over the involved side for all regions (P