Annie Dupuis

Unified Criteria for Ultrasonographic Diagnosis of ADPKD

Individuals who are at risk for autosomal dominant polycystic kidney disease are often screened by ultrasound using diagnostic criteria derived from individuals with mutations in PKD1. Families with mutations in PKD2 typically have less severe disease, suggesting a potential need for different diagnostic criteria. In this study, 577 and 371 at-risk individuals from 58 PKD1 and 39 PKD2 families, respectively, were assessed by renal ultrasound and molecular genotyping. Using sensitivity data derived from genetically affected individuals and specificity data derived from genetically unaffected individuals, various diagnostic criteria were compared. In addition, data sets were created to simulate the PKD1 and PKD2 case mix expected in practice to evaluate the performance of diagnostic criteria for families of unknown genotype. The diagnostic criteria currently in use performed suboptimally for individuals with mutations in PKD2 as a result of reduced test sensitivity. In families of unknown genotype, the presence of three or more (unilateral or bilateral) renal cysts is sufficient for establishing the diagnosis in individuals aged 15 to 39 y, two or more cysts in each kidney is sufficient for individuals aged 40 to 59 y, and four or more cysts in each kidney is required for individuals > or = 60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged > or = 40 yr is sufficient to exclude the disease. These unified diagnostic criteria will be useful for testing individuals who are at risk for autosomal dominant polycystic kidney disease in the usual clinical setting in which molecular genotyping is seldom performed.

The Effect of Chronic Infection With Aspergillus fumigatus on Lung Function and Hospitalization in Patients With Cystic Fibrosis

BACKGROUND The relevance of Aspergillus fumigatus in patients with cystic fibrosis (CF) not affected by allergic bronchopulmonary aspergillosis is unclear. Our aim was to determine the effect of persistent infection with A fumigatus on pulmonary exacerbations and lung function in children with CF. METHODS This was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children from 1999 to 2006. Persistent A fumigatus infection was defined as the presence of two or more positive sputum or bronchoalveolar cultures for A fumigatus in a given year. The primary outcome measure was the annual number of hospitalizations for pulmonary exacerbations. RESULTS Two hundred thirty patients with CF were included in the analysis. The FEV(1) of patients persistently infected with A fumigatus was 3.61% (P< or =.0001) lower during the study period compared with uninfected patients. There was a significant interaction between A fumigatus and Pseudomonas aeruginosa on lung function (P=.0006). Patients not infected with either organism had the highest pulmonary function. Persistent A fumigatus infection (relative risk [RR]=1.94, P=.0002) and CF-related diabetes (RR=1.64, P=.028) were associated with an increased risk of pulmonary exacerbations requiring hospitalization, whereas there was no increased risk of pulmonary exacerbations among patients with allergic bronchopulmonary aspergillosis (RR=1.02, P=.94). When adjusted for baseline pulmonary function, none of these variables were associated with a significantly increased risk of pulmonary exacerbations, with only chronic A fumigatus infection trending toward significance (RR=1.40, P=.065). CONCLUSIONS Persistent A fumigatus infection is an independent risk factor for hospital admissions in patients with CF.

A Comparison of Inhaled Fluticasone and Oral Prednisone for Children with Severe Acute Asthma

BACKGROUND Inhaled corticosteroids are effective in the treatment of children with asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in the management of severe acute disease. METHODS We performed a double-blind, randomized trial involving 100 children five years of age or older who had severe acute asthma (indicated by a forced expiratory volume in one second [FEV1] that was less than 60 percent of the predicted value) and in whom the results could be evaluated. All were treated with an aggressive bronchodilator regimen and received one dose of either 2 mg of inhaled fluticasone through a metered-dose inhaler with a spacer or 2 mg of oral prednisone per kilogram of body weight. They were assessed hourly for up to four hours. RESULTS The mean (+/-SD) base-line FEV1 as a percentage of the predicted value was 46.3+/-12.5 in the fluticasone group (51 subjects) and 43.9+/-9.9 in the prednisone group (49 subjects). The FEV1 increased by a mean of 9.4+/-12.5 percentage points in the fluticasone group and by 18.9+/-9.8 percentage points in the prednisone group four hours after therapy (P< 0.001). None of the children in the prednisone group had a reduction in FEV1 as a percentage of the predicted value from base line to four hours, as compared with 25 percent of those in the fluticasone group (P<0.001). Sixteen (31 percent) of the children treated with fluticasone were hospitalized, as compared with five (10 percent) of those treated with prednisone (P=0.01). CONCLUSIONS Children with severe acute asthma should be treated with oral prednisone and not with inhaled fluticasone or a similar inhaled corticosteroid.

The Prevalence of Autistic Spectrum Disorder in Children Surveyed in a Tertiary Care Epilepsy Clinic

Summary:  It is well documented that children with autistic spectrum disorder (ASD) have an increased prevalence of seizures; however, studies have not been done to evaluate the prevalence of ASD in children with epilepsy. This comorbidity is important to define as early diagnosis and intervention in some children with ASD has been shown to improve outcome.

The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are associated with cystic fibrosis (CF)-related monosymptomatic conditions, including idiopathic pancreatitis. We evaluated prospectively enrolled patients who had idiopathic recurrent acute pancreatitis or idiopathic chronic pancreatitis, healthy controls, CF heterozygotes, and CF patients (pancreatic insufficient or sufficient) for evidence of CFTR gene mutations and abnormalities of ion transport by sweat chloride and nasal potential difference testing. DNA samples from anonymous blood donors were controls for genotyping. At least one CFTR mutation or variant was carried in 18 of 40 patients (45%) with idiopathic chronic pancreatitis and in 6 of 16 patients (38%) with idiopathic recurrent acute pancreatitis but in only 11 of the 50 controls (22%, P=0.005). Most identified mutations were rare and would not be identified in routine genetic screening. CFTR mutations were identified on both alleles in six patient (11%). Ion transport measurements in patients with pancreatitis showed a wide range of results, from the values in patients with classically diagnosed CF to those in the obligate heterozygotes and healthy controls. In general, ion channel measurements correlated with the number and severity of CFTR mutations. Twelve of 56 patients with pancreatitis (21%) fulfilled current clinical criteria for the diagnosis of CF, but CFTR genotyping alone confirmed the diagnosis in only two of these patients. We concluded that extensive genotyping and ion channel testing are useful to confirm or exclude the diagnosis of CF in the majority of patients with idiopathic pancreatitis.

Construct validity of a multidimensional electronic pain diary for adolescents with arthritis.

&NA; The aim of this study was to evaluate the construct validity and feasibility of a multidimensional electronic pain diary (e‐Ouch©) in adolescents with juvenile idiopathic arthritis (JIA). Two descriptive studies with repeated measures were conducted between January and December 2005. Participants were drawn from a large metropolitan rheumatology clinic in a university affiliated pediatric tertiary care centre. In Study 1, 76 adolescents with active arthritis recorded their pain three times a day for 2 weeks using the e‐Ouch©. In Study 2, 36 adolescents recorded their pain three times a day for 1 week before and 2 weeks after joint injections. Adolescents in both studies completed multiple measures to determine the construct validity and feasibility of the e‐Ouch©. Adolescents reported mild levels of pain intensity, unpleasantness, and interference as well as stiffness, and mild to moderate levels of fatigue. e‐Ouch© average weekly pain unpleasantness and interference scores were higher in adolescents with higher pain intensity scores. Correlations between average weekly pain ratings on the e‐Ouch© and scores from: (a) recalled least, average and worst weekly pain, (b) health‐related quality of life and pain coping, and (c) disease activity were as predicted. Pain ratings were significantly lower following joint injections with effect sizes in the low to moderate and moderate to high ranges at the first and second week post‐injection, respectively. These findings provide evidence of the construct validity and feasibility of the e‐Ouch© electronic diary in adolescents with JIA. Use of real‐time data capture approaches should be considered in future studies of chronic arthritis.

Intranasal oxytocin in the treatment of autism spectrum disorders: A review of literature and early safety and efficacy data in youth

BACKGROUND There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. METHODS Fifteen children and adolescents with verbal IQs≥70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. RESULTS Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. CONCLUSIONS This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav.

Investigating the Autonomic Nervous System Response to Anxiety in Children with Autism Spectrum Disorders

Assessment of anxiety symptoms in autism spectrum disorders (ASD) is a challenging task due to the symptom overlap between the two conditions as well as the difficulties in communication and awareness of emotions in ASD. This motivates the development of a physiological marker of anxiety in ASD that is independent of language and does not require observation of overt behaviour. In this study, we investigated the feasibility of using indicators of autonomic nervous system (ANS) activity for this purpose. Specially, the objectives of the study were to 1) examine whether or not anxiety causes significant measurable changes in indicators of ANS in an ASD population, and 2) characterize the pattern of these changes in ASD. We measured three physiological indicators of the autonomic nervous system response (heart rate, electrodermal activity, and skin temperature) during a baseline (movie watching) and anxiety condition (Stroop task) in a sample of typically developing children (n = 17) and children with ASD (n = 12). The anxiety condition caused significant changes in heart rate and electrodermal activity in both groups, however, a differential pattern of response was found between the two groups. In particular, the ASD group showed elevated heart rate during both baseline and anxiety conditions. Elevated and blunted phasic electrodermal activity were found in the ASD group during baseline and anxiety conditions, respectively. Finally, the ASD group did not show the typical decrease in skin temperature in response to anxiety. These results suggest that 1) signals of the autonomic nervous system may be used as indicators of anxiety in children with ASD, and 2) ASD may be associated with an atypical autonomic response to anxiety that is most consistent with sympathetic over-arousal and parasympathetic under-arousal.

Magnetic resonance imaging to distinguish the type and severity of pediatric inflammatory bowel diseases

BACKGROUND The distinction between ulcerative colitis and Crohns disease is important, because treatment options and clinical course may vary. Magnetic resonance imaging (MRI) allows noninvasive transmural assessment of the intestine and may facilitate differentiation of ulcerative colitis from Crohns disease. The objective of this prospective study was to determine whether MRI differentiates Crohns disease from ulcerative colitis in children as effectively as colonoscopy with mucosal biopsies. METHODS Fifteen patients underwent colonoscopy with biopsies followed by abdominal MRI. The MRI diagnosis, determined by two radiologists independently completing a standardized form was compared with the gastroenterologic diagnosis. RESULTS After colonoscopy and review of histology, Crohns disease was diagnosed in nine patients, ulcerative colitis in five, and indeterminate colitis in one, who was excluded from study. Agreement of the MRI diagnosis with the gastroenterologic diagnosis was 4 of 4 (100%) for ulcerative colitis, 4 of 10 (40%) for Crohns disease considering both radiologists, and 5 of 10 (50%) for Crohns disease for each radiologist individually. Percentage of enhancement by MRI did not correlate with the severity of inflammation determined at endoscopy among the patients with Crohns disease (r = -0.3, P = 0.366). There was agreement on severity of inflammation in three of four patients with ulcerative colitis. CONCLUSIONS Current MRI interpretation of inflammatory bowel disease did not adequately recognize Crohns disease in children. Therefore, colonoscopy with biopsy remains the most accurate tool for determining the type and severity of inflammatory bowel disease in children and adolescents.

β-Adrenergic Sweat Secretion as a Diagnostic Test for Cystic Fibrosis

RATIONALE β-Adrenergically induced sweat secretion offers an expedient method to assess native cystic fibrosis transmembrane conductance regulator (CFTR) secretory function in vivo. OBJECTIVES To evaluate the sensitivity, specificity, and reliability of a test based on the activity and secretory function of CFTR in the sweat gland. METHODS Primary and validation trials with prospectively ascertained healthy control subjects, obligate heterozygotes, and patients with a CFTR-related disorder and CF (pancreatic sufficient and insufficient). MEASUREMENTS AND MAIN RESULTS Diagnostic accuracy and reliability of β-adrenergic sweat secretory rates using an evaporimeter was assessed and compared with sweat chloride concentrations. The cholinergically stimulated mean sweat rate did not differ among groups. The mean maximal β-adrenergically stimulated sweat rate in heterozygotes was about half the rate of healthy control subjects, and completely absent in pancreatic-insufficient patients with CF and pancreatic-sufficient patients with CF (P < 0.0001). Subjects with a CFTR-related disorder showed reduced or absent β-adrenergic sweat secretion. The β-adrenergic secretory response demonstrated high diagnostic accuracy (area under a characteristic receiver-operator curve = 0.99; 95% confidence interval, 0.97-1.00) and reliability (intraclass correlation, 0.90; 95% confidence interval, 0.81-0.95). The diagnostic cutoff level for CF, derived from the primary trial, correctly identified all control subjects, heterozygotes, and patients with CF in the validation cohort, whereas concurrent sweat chloride measurements misclassified one heterozygote and five subjects with CF. The cholinergic and β-adrenergic sweat secretion rates were lower in women compared with men (P < 0.001). CONCLUSIONS β-Adrenergic sweat secretion rate determined by evaporimetry is an accurate and reliable technique to assess different levels of CFTR function and to identify patients with CF.