Showing papers by "Hospital for Sick Children published in 2009"

Tumour-initiating cells: challenges and opportunities for anticancer drug discovery

Abstract: The hypothesis that cancer is driven by tumour-initiating cells (popularly known as cancer stem cells) has recently attracted a great deal of attention, owing to the promise of a novel cellular target for the treatment of haematopoietic and solid malignancies. Furthermore, it seems that tumour-initiating cells might be resistant to many conventional cancer therapies, which might explain the limitations of these agents in curing human malignancies. Although much work is still needed to identify and characterize tumour-initiating cells, efforts are now being directed towards identifying therapeutic strategies that could target these cells. This Review considers recent advances in the cancer stem cell field, focusing on the challenges and opportunities for anticancer drug discovery.

Comparisons of citations in Web of Science, Scopus, and Google Scholar for articles published in general medical journals.

Abstract: Context Until recently, Web of Science was the only database available to track citation counts for published articles. Other databases are now available, but their relative performance has not been established. Objective To compare the citation count profiles of articles published in general medical journals among the citation databases of Web of Science, Scopus, and Google Scholar. Design Cohort study of 328 articles published in JAMA, Lancet, or the New England Journal of Medicine between October 1, 1999, and March 31, 2000. Total citation counts for each article up to June 2008 were retrieved from Web of Science, Scopus, and Google Scholar. Article characteristics were analyzed in linear regression models to determine interaction with the databases. Main Outcome Measures Number of citations received by an article since publication and article characteristics associated with citation in databases. Results Google Scholar and Scopus retrieved more citations per article with a median of 160 (interquartile range [IQR], 83 to 324) and 149 (IQR, 78 to 289), respectively, than Web of Science (median, 122; IQR, 66 to 241) (P 10 -transformed scale, fewer citations were found in Google Scholar to articles with declared industry funding (nonstandardized regression coefficient, −0.09; 95% confidence interval [CI], −0.15 to −0.03), reporting a study of a drug or medical device (−0.05; 95% CI, −0.11 to 0.01), or with group authorship (−0.29; 95% CI, −0.35 to −0.23). In multivariable analysis, group authorship was the only characteristic that differed among the databases; Google Scholar had significantly fewer citations to group-authored articles (−0.30; 95% CI, −0.36 to −0.23) compared with Web of Science. Conclusion Web of Science, Scopus, and Google Scholar produced quantitatively and qualitatively different citation counts for articles published in 3 general medical journals.

GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice

Abstract: OBJECTIVE—Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat type 2 diabetes, and transient GLP-1 administration improved cardiac function in humans after acute myocardial infarction (MI) and percutaneous revascularization. However, the consequences of GLP-1R activation before ischemic myocardial injury remain unclear. RESEARCH DESIGN AND METHODS—We assessed the pathophysiology and outcome of coronary artery occlusion in normal and diabetic mice pretreated with the GLP-1R agonist liraglutide. RESULTS—Male C57BL/6 mice were treated twice daily for 7 days with liraglutide or saline followed by induction of MI. Survival was significantly higher in liraglutide-treated mice. Liraglutide reduced cardiac rupture (12 of 60 versus 46 of 60; P 0.0001) and infarct size (21 2% versus 29 3%, P 0.02) and improved cardiac output (12.4 0.6 versus 9.7 0.6 ml/min; P 0.002). Liraglutide also modulated the expression and activity of cardioprotective genes in the mouse heart, including Akt, GSK3, PPAR-, Nrf-2, and HO-1. The effects of liraglutide on survival were independent of weight loss. Moreover, liraglutide conferred cardioprotection and survival advantages over metformin, despite equivalent glycemic control, in diabetic mice with experimental MI. The cardioprotective effects of liraglutide remained detectable 4 days after cessation of therapy and may be partly direct, because liraglutide increased cyclic AMP formation and reduced the extent of caspase-3 activation in cardiomyocytes in a GLP-1R‐dependent manner in vitro. CONCLUSIONS—These findings demonstrate that GLP-1R activation engages prosurvival pathways in the normal and diabetic mouse heart, leading to improved outcomes and enhanced survival after MI in vivo. Diabetes 58:975‐983, 2009

Identifying patients with physician-diagnosed asthma in health administrative databases

Abstract: BACKGROUND: Asthma imposes a heavy and expensive burden on individuals and populations. A population-based surveillance and research program based on health administrative data could measure and study the burden of asthma; however, the validity of a health administrative data diagnosis of asthma must first be confirmed.

Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey

Abstract: Background: Fabry disease is a rare X-linked lysosomal storage disorder characterised by severe multisystemic involvement that leads to major organ failure and premature death in affected men and women. Over the past 7 years, the Fabry Outcome Survey (FOS) has collected data on the natural history of Fabry disease, and the long-term efficacy and safety of enzyme-replacement therapy. This paper provides an update on the first analysis of FOS data. Design: Baseline data on clinical manifestations and causes of death in a cohort of 1453 patients (699 male, 754 female) from 19 countries worldwide were analysed. Causes of death of affected relatives were analysed separately. Results: The most frequently reported signs and symptoms of Fabry disease were neurological. Cardiac, ocular, gastrointestinal, dermatological, auditory and renal manifestations were also common. The principal causes of death among 181 affected relatives of patients in FOS (most of whom had died before 2001) were renal failure in males (42%) and cerebrovascular disease in females (25%). In contrast, of the 42 patients enrolled in FOS whose deaths were reported between 2001 and 2007, cardiac disease was the main cause of death in both male (34%) and female (57%) patients. Conclusion: These data suggest that the importance of renal disease as a cause of death in patients with Fabry disease is decreasing while the importance of cardiac disease is increasing. This pattern probably reflects improvements in the management of renal disease in patients with Fabry disease.

Changing the Paradigm: Omegaven for the Treatment of Liver Failure in Pediatric Short Bowel Syndrome

Abstract: Background:Parenteral omega-3 fatty acids, such as Omegaven, may benefit patients with pediatric short bowel syndrome (SBS) who develop parenteral nutrition–associated liver disease (PNALD).Patients and Methods:Retrospective cohort describing the outcome of all 12 children with SBS and advan

Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem

Abstract: Adults with beta thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, > or =6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1-75 yr), were studied. Spine and femur BMD Z-scores < -2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.

Pediatric soft-tissue tumors and pseudo-tumors: MR imaging features with pathologic correlation: part 1. Imaging approach, pseudotumors, vascular lesions, and adipocytic tumors.

Abstract: A wide spectrum of entities may give rise to soft-tissue masses in children, including benign and malignant tumors, pseudotumors, and both neoplastic and nonneoplastic vascular lesions. Because of its excellent tissue contrast, multiplanar capability, and lack of ionizing radiation, magnetic resonance (MR) imaging has become the modality of choice in the evaluation of deep and large soft-tissue masses in children. In the vast majority of cases, however, accurate interpretation of the MR imaging findings requires correlation with the clinical findings. For example, in most posttraumatic and inflammatory pseudotumors, the clinical history is fundamental to establishing the diagnosis. In the evaluation of periarticular cysts, the location of the mass and its relationship to a joint are crucial for diagnosis, whereas in the evaluation of vascular lesions, including hemangiomas and vascular malformations, clinical findings combined with MR imaging findings are needed for accurate diagnosis in most cases. The i...

Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America.

Abstract: Summary This study aimed to determine differences in the rates of growth, endocrine- and calcium-related abnormalities in the various thalassemia syndromes in North America treated with current therapies. Medical history, physical examinations and blood and urine collections were obtained from patients with all thalassemia syndromes age 6 years and older in the Thalassemia Clinical Research Network. 361 subjects, 49% male, mean age 23·2 years (range 6·1–75 years) were studied. Approximately 25% of children and adults, regardless of the thalassemia syndrome, had short stature. Overall growth in children was mildly affected. Final height was close to midparental height (z = −0·73 ± 1·24). Patients with beta thalassemia major (TM) had higher rates of hypogonadism, multiple endocrinopathies, worse hyperglycaemia, subclinical hypoparathyroidism and hypercalciuria. Hypogonadism remained the most frequent endocrinopathy and was frequently under-treated. 12·8% of the subjects had 25 vitamin D concentrations less than 27 nmol/l and 82% less than 75 nmol/l, regardless of the thalassemia syndrome. Adolescents had lower 25 vitamin D levels than children and adults. Compared to patients with other thalassemia syndromes, those with beta TM suffered from higher rates of multiple endocrinopathies, abnormal calcium metabolism and hypercalciuria. Vitamin D abnormalities were high among adolescents.

Stenting of the right ventricular outflow tract in the symptomatic infant with tetralogy of Fallot.

Abstract: Background: Repair of neonatal tetralogy of Fallot (TOF) has low mortality. Debate continues regarding the initial management of cyanotic or duct-dependent infants with TOF and adverse risk factors. While repair can and has been performed in these patients, it is associated with increased morbidity. Objective: We review the effectiveness of right ventricular outflow tract (RVOT) stenting in the symptomatic young infant with TOF. Methods: Clinical, echocardiographic, angiographic and haemodynamic data were reviewed for nine patients who underwent 11 RVOT stenting procedures from October 1994 to August 2007. Results: The pulmonary valve was deemed unsalvageable in all patients (median valve diameter 3.7 mm (range 2.7–4.2), Z-score −6.7 (range −9.7 to −5.4). RVOT stenting improved arterial oxygen saturation from a median of 73% (60–85%) to 94% (90–98%) (p = 0.008). Median Z-score for the left pulmonary artery increased from −4.9 (−7.8 to −2.4) before stent implantation to −1.5 (−4.2 to −0.2) (p = 0.02) before surgical repair. Median Z-score for the right pulmonary artery increased from −3.7 (−6.8 to −1.9) to −0.8 (−2.5 to 0.1) (p = 0.008). Median Nakata index increased from 56 mm 2 /m 2 (21–77) to 150 mm 2 /m 2 (123–231) (p = 0.008). There were no procedural complications. Six patients have undergone successful repair. There were no deaths. Conclusions: In the symptomatic young infant with TOF, stenting of the RVOT provides a safe and effective management strategy, improving arterial oxygen saturation and encouraging pulmonary artery growth.

Does echocardiography facilitate determination of hemodynamic significance attributable to the ductus arteriosus

Abstract: The assignment of hemodynamic significance to a patent ductus remains a challenge for neonatal intensivists. The impact is medical uncertainty and ongoing debate as to when treatment should be provided if ever. Patent ductus arteriosus is associated with significant neonatal morbidities including necrotizing enterocolitis and brain injury; causality has not been proven. In addition, there are limited data suggesting a beneficial effect of therapeutic intervention. The inability to accurately differentiate the pathological ductus arteriosus from the innocent ductus arteriosus may contribute, in part, to the lack of scientific evidence of benefit or causality. Our group has previously proposed the need for a staging system to characterize the clinical and echocardiography impact of the ductus arteriosus. This approach requires comprehensive echocardiography evaluation to assess ductal size and the degree of pulmonary overcirculation/systemic hypoperfusion related to the transductal shunt. In this review, we will highlight the evidence for echocardiography markers of hemodynamic significance and speculate as to how they may facilitate improved decision making in the neonatal intensive care unit.

Expressed sequence tags: an overview.

Abstract: Expressed sequence tags (ESTs) are fragments of mRNA sequences derived through single sequencing reactions performed on randomly selected clones from cDNA libraries. To date, over 45 million ESTs have been generated from over 1400 different species of eukaryotes. For the most part, EST projects are used to either complement existing genome projects or serve as low-cost alternatives for purposes of gene discovery. However, with improvements in accuracy and coverage, they are beginning to find application in fields such as phylogenetics, transcript profiling and proteomics. This volume provides practical details on the generation and analysis of ESTs. Chapters are presented which cover creation of cDNA libraries; generation and processing of sequence data; bioinformatics analysis of ESTs; and their application to phylogenetics and transcript profiling.

An experimental study on imitation of alcohol consumption in same-sex dyads.

Abstract: Aim: In order to study the role of imitation in relation to drinking, alcohol consumption among two peers was examined with experiments in a naturalistic drinking setting. Method: In a bar lab, 135 young adults (52% women) were exposed to either a non-drinking, a light-drinking or a heavy-drinking same-sex model (i.e. a confederate) in a 30-min time-out session. Instead of using a taste task (Quigley and Collins, 1999. The modeling of alcohol consumption: a meta-analytic review. J Stud Alcohol 60:90–8) in which participants were obliged to consume alcohol, in the current study, a design was used in which participants were allowed to drink alcohol but could also choose non-alcoholic beverages. Results: Craving for alcohol was included as a covariate in ANCOVAs. Results showed that the participants consumed substantially more alcohol when exposed to heavy-drinking models compared to light- and non-drinking models. Craving levels were positively related to alcohol consumption during the experiment. Conclusion: Both men and women imitated same-sex peers’ drinking behavior in an ad lib naturalistic bar setting.

Mammographic density: a heritable risk factor for breast cancer.

Abstract: The appearance of the breast on mammography varies among women, reflecting variations in tissue composition. Stroma and epithelium attenuate x-rays more than fat and appear light on a mammogram, which we refer to here as " mammographic density, " while fat appears dark. We show evidence that mammographic density is a strong risk factor for breast cancer, and that risk of breast cancer is four to five times greater in women with density in more than 75% of the breast, compared with those with little or no density. Density in more than 50% of the breast may account for a large proportion of breast cancers. Density is influenced by age, parity, body mass index, and menopause but these factors account for only 20 - 30% of the variation in density in the population. Twin studies have shown that percent mammographic density, at a given age, is highly heritable, and that inherited factors explain 63% of the variance. Mammographic density has the characteristics of a quantitative trait, and may be influenced by genes that are easier to identify than those associated with breast cancer itself. The genes that influence mammographic density may also be associated with risk of breast cancer, and their identification is also likely to provide insights into the biology of the breast, and to identify potential targets for preventive strategies.

What controls the timing of puberty? An update on progress from genetic investigation.

Abstract: Purpose of reviewPuberty is an important developmental stage during which reproductive capacity is attained. Genetic and environmental factors both influence the timing of puberty, which varies greatly among individuals. However, although genetic variation is known to influence the normal spectrum o

Use and limitations of malaria rapid diagnostic testing by community health workers in war-torn Democratic Republic of Congo

Abstract: Background Accurate and practical malaria diagnostics, such as immunochromatographic rapid diagnostic tests (RDTs), have the potential to avert unnecessary treatments and save lives. Volunteer community health workers (CHWs) represent a potentially valuable human resource for expanding this technology to where it is most needed, remote rural communities in sub-Saharan Africa with limited health facilities and personnel. This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo, a tropical African setting ravaged by human conflict.

The effect of heartburn and acid reflux on the severity of nausea and vomiting of pregnancy.

Abstract: BACKGROUND: Heartburn (HB) and acid reflux (RF) in the non-pregnant population can cause nausea and vomiting; therefore, it is plausible that in women with nausea and vomiting of pregnancy (NVP), HB/RF may increase the severity of symptoms

Decomposing the relation between Rapid Automatized Naming (RAN) and reading ability.

Abstract: The Rapid Automatized Naming (RAN) test involves rapidly naming sequences of items presented in a visual array. RAN has generated considerable interest because RAN performance predicts reading achievement. This study sought to determine what elements of RAN are responsible for the shared variance between RAN and reading performance using a series of cognitive tasks and a latent variable modelling approach. Participants performed RAN measures, a test of reading speed and comprehension, and six tasks, which tapped various hypothesised components of the RAN. RAN shared 10% of the variance with reading comprehension and 17% with reading rate. Together, the decomposition tasks explained 52% and 39% of the variance shared between RAN and reading comprehension and between RAN and reading rate, respectively. Significant predictors suggested that working memory encoding underlies part of the relationship between RAN and reading ability.

Autophagy in Immunity Against Intracellular Bacteria

Abstract: Autophagy is an innate immune defense mechanism against various intracellular bacterial pathogens, such as Salmonella enterica serovar Typhimurium (S. typhimurium), Listeria monocytogenes and Shigella flexneri. S. typhimurium uses type three secretion systems (T3SSs) to invade mammalian cells and replicate in Salmonella-containing vacuoles (SCVs). A small population of intracellular S. typhimurium is targeted by autophagy shortly after infection. Evidence suggests that these bacteria are present within SCVs that have been damaged by high levels of T3SS activity. Autophagy limits the growth of S. typhimurium in host cells. Therefore, autophagy can be considered to protect the cytosol of eukaryotic cells from bacterial colonization. L. monocytogenes secretes the pore-forming cytolysin listeriolysin O (LLO) to disrupt the phagosome and escape into the cytosol, where it acquires actin-based motility. Autophagy can target L. monocytogenes in the cytosol under specific experimental conditions. However, L. monocytogenes utilizes several virulence factors to evade being killed by the autophagy system. A newly appreciated population of L. monocytogenes undergoes slow growth in specialized vacuoles termed spacious Listeria-containing phagosomes (SLAPs), the formation of which requires bacterial LLO and host autophagy. In the cytosol, S. flexneri can also be a target for autophagy in the absence of a T3SS effector, IcsB, that normally impairs the interaction between Atg5 and wild-type bacteria. Therefore, autophagy can recognize intracellular bacteria in a variety of ways, leading to different fates for these bacteria in host cells. The inefficient autophagy of enteric bacteria in genetically compromised individuals may contribute to the pathogenesis of Crohn’s disease.

Guidelines for submitting adverse event reports for publication

Abstract: Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation and reporting of suspected drug or other medical product adverse events.

The effect of Acid-reducing pharmacotherapy on the severity of nausea and vomiting of pregnancy.

Abstract: Background. Heartburn and acid reflux (HB/RF) are associated with increased severity of nausea and vomiting. The ability of acid-reducing drugs to reduce symptoms of nausea and vomiting of pregnancy has not been previously tested. Objective. To determine whether acid-reducing pharmacotherapy decreases the severity of NVP symptoms. Methods. We studied a cohort of women experiencing NVP, who were also experiencing HB/RF. Women were counseled to commence acid-reducing pharmacotherapy. The effectiveness of the acid-reducing medication in decreasing symptoms of both HB/RF and NVP was measured. Results. Acid-reducing drugs resulted in significant decreases in PUQE (9.6 ± 3.0 to 6.5 ± 2.5, P < .0001) and well-being scores from the initial (4.0 ± 2.0) to the follow-up interview (6.8 ± 1.6, P < .0001). After intervention with acid-reducing pharmacotherapy, a reduction in acid symptoms correlated significantly with reduction in NVP (R2 = 0.72, P < .001). Conclusion. This is the first study to demonstrate that management of HB/RF can reduce the severity of NVP.

Sleep-related breathing in children with mucopolysaccharidosis.

Abstract: Background: The mucopolysaccharidoses (MPSs), a group of genetic lysosomal storage disorders, are associated with significant morbidity. Secondarily to specific associated anatomical abnormalities, MPS is associated with sleep disordered breathing (SDB), specifically obstructive sleep apnoea (OSA) that may confer additional morbidity. Few studies have examined SDB in children with MPS using full polysomnography (PSG) and thus the exact prevalence and severity of SDB is unknown. Further, successful treatments for SDB in this population have not been explored. Objectives: This study evaluated both SDB and the efficacy of treatments offered to children with MPS using PSG data. Patients and methods: A retrospective chart review was conducted on all children with MPS and a history of suspected OSA who were referred to the Hospital for Sick Children, Toronto. Both baseline and follow up treatment PSG data were analysed. PSG data recorded included obstructive apnoea-hypopnoea index (OAHI) and central apnoea index (CAI). Results: Fourteen patients (10 male) underwent a baseline PSG. Three of 14 children on ERT were excluded from the main analyses. The median (range) baseline parameters of the population (n = 11) were recorded. The age was 5.2 years (0.8–17.8) and the body mass index (BMI) was 19.9 (13.7–22.2). The OAHI was 6.6 (0.0–54.8); the CAI was 0.6 (0.0–2.6). Seven of 11 (64%) had evidence for OSA and 3/7 children were classified as having severe OSA (OAHI > 10). Of these, 5/7 children underwent treatment for OSA with 3/5 children showing a significant reduction in their OAHI. Further, the 2 patients on ERT therapy with OSA were also both successfully treated. Conclusions: Children with MPS have a high prevalence of significant OSA and thus should be carefully screened for OSA using full polysomnography and treated accordingly.

Optimizing the role of imaging in appendicitis

Abstract: Acute appendicitis is the most common acute abdominal condition that requires surgical intervention in childhood. From the diagnostic performance perspective, computed tomography (CT) has a significantly higher sensitivity than does ultrasound (US) for diagnosing appendicitis in children; from the safety perspective, however, one should consider the radiation associated with CT, especially in children. There is strong evidence supporting improved patient outcomes in children with suspected acute appendicitis who undergo CT scanning. Nevertheless, we should keep in mind that for a single abdominal CT study in a 5-year-old child, the lifetime risk of radiation-induced cancer would be 26.1 per 100,000 in female and 20.4 per 100,000 in male patients, based on probabilistic models designed with data from atomic bomb survivors. An integrated clinical-imaging approach, applying clinical scores that are able to predict which children with acute abdominal pain do or do not have a high probability of presenting with appendicitis may improve the effectiveness of the imaging diagnosis of appendicitis at the hospital level. Such an approach could avoid exposure of children who at low risk for appendicitis to unnecessary diagnostic tests and eventually, to radiation.

Pediatric eye injuries in a Canadian emergency department

Abstract: Objective: This study assesses the descriptive epidemiology of children with eye injuries presenting to the emergency department of a major Canadian pediatric hospital. Study Design: A retrospective cohort study. Participants: All pediatric patients (up to 18 years of age) presenting with ocular injuries to a tertiary care pediatric emergency department between January 1 and December 31, 2002. Methods: Chart review was conducted using Canadian Hospital Injury Reporting and Prevention Program forms. All injuries were classified by Birmingham Eye Trauma Terminology (BETT). Results: There were 149 patients who presented with eye injuries to the emergency department in 2002, and all of them were included in the study. Patient ages ranged from 3 months to 18 years with a median age of 8 years 8 months (interquartile range 4–11 years). Boys accounted for 73.2% of the patient total. Most of the cases (57.7%) needed some treatment and required follow-up. Eleven patients (7.3%) had vision-threatening eye injuries that required surgical management, and 3 of these required multiple surgeries. Seven of the 11 patients suffered open globe lacerations, 3 open globe ruptures, and 1 closed globe injury. Conclusions: Most eye injuries occurred at home during the summer, and over 7% of children presenting to the emergency department with eye trauma had vision-threatening injuries that required surgical management. Increasing awareness of the serious nature of ocular injuries will help to develop a comprehensive plan for educating both parents and children to minimize preventable pediatric eye injuries.

Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results.

Abstract: Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16-20% of CF newborns, providing linkage and association results from large family and case-control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provided evidence of a MI locus on chromosome 12p13.3, which was segregating in up to 80% of MI families with at least one affected offspring (HLOD = 2.9). Fine mapping of the 12p13.3 region in a large case-control sample of pancreatic insufficient Canadian CF patients with and without MI pointed to the involvement of ADIPOR2 in MI (p = 0.002). This marker was substantially out of Hardy-Weinberg equilibrium in the cases only, and provided evidence of a cohort effect. The association with rs9300298 in the ADIPOR2 gene at the 12p13.3 locus was replicated in an independent sample of CF families. A protective locus, using the phenotype of no-MI, mapped to 4q13.3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies. Our linkage approach was used to direct our fine-mapping studies, which uncovered two potential modifier genes worthy of follow-up.

Estimating the number of children exposed to parental psychiatric disorders through a national health survey

Abstract: Objective Children whose parents have psychiatric disorders experience an increased risk of developing psychiatric disorders, and have higher rates of developmental problems and mortality. Assessing the size of this population is important for planning of preventive strategies which target these children.