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PubMed1996

The efficacy and cost of aprotinin in children undergoing reoperative open heart surgery.

We performed a prospective, randomized, placebo-controlled, double-blind trial to assess the efficacy of aprotinin in 61 children (median age 3.7 yr) undergoing reoperative open heart surgery (OHS). Three demographically similar groups were studied: large-dose aprotinin (ALD), small-dose aprotinin (ASD), and placebo (P). Over the first 24 postoperative hours fewer patients in the aprotinin groups received packed red cells (ALD, 53%; ASD, 89%; and P, 95%; P = 0.001), platelets (ALD, 32%; ASD, 50%; and P, 65%; P = 0.04), and fresh frozen plasma (ALD, 16%; ASD, 17%; and P, 60%; P = 0.003) than placebo patients. Most importantly, aprotinin patients had fewer exposures to banked blood components (ALD, median 1 U; and ASD, median 2 U) than P (median 6 U; P = 0.001), with no difference in overall complication rate. Use of aprotinin was associated with a savings in the patient charges for blood components, operating room time, and duration of hospitalization. In conclusion, aprotinin decreased the number of units of banked blood components used during the first 24 postoperative hours in reoperative pediatric OHS. Aprotinin thus decreases the risks associated with exposure to banked blood components and reduces hospital charges.

Aprotinin↗
PubMed1996

Comparison of clinical symptoms in autism and Asperger's disorder.

OBJECTIVE: To determine what clinical symptoms clinicians have been using to distinguish between Asperger's disorder (AsD) and autistic disorder (AD). METHOD: Parents of children and adolescents with high-functioning AD (n = 48) and AsD (n = 69) were given a structured interview based on DSM-III-R and ICD-10 diagnostic criteria. Information regarding early and current symptom presentation and family, developmental, and verbal mental age information were collected. Logistic regression analyses were conducted to determine which variables best predicted clinician's diagnosis. RESULTS: A number of clinical variables predicted diagnosis. Delayed language onset was the only variable of the family and developmental variables that predicted diagnosis. The AsD group was also significantly higher than the AD group in verbal mental age. CONCLUSION: Clinicians appear to be diagnosing AsD and AD on the basis of published research and case study accounts. The findings question whether DSM-IV and ICD-10 criteria adequately describe the AsD individual, particularly in the communication domain.

Adolescent↗
PubMed2004

Outcome classification of preschool children with autism spectrum disorders using MRI brain measures.

OBJECTIVE: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. METHOD: Quantitative MRI technology was used to measure gray and white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.2 years) and 15 typically developing young children (aged 1.7-5.2 years). Diagnostic confirmation and cognitive outcome data were obtained after the children reached 5 years of age. RESULTS: A discriminant function analysis of the MRI brain measures correctly classified 95.8% of the ASD cases and 92.3% of the control cases. This set of variables also correctly classified 85% of the ASD cases as lower functioning and 68% of the ASD cases as higher functioning. CONCLUSIONS: These results indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD.

Analysis of Variance↗
PubMedDate not supplied

An approach to the timely treatment of acute stress disorder.

A convergent postburn psychopharmacologic treatment for children for acute stress disorder (ASD) symptoms has not been established. Both the application of what has been learned through treatment of similar symptoms experienced by adults with posttraumatic stress disorder and the examination of safe treatment options for children led to the clinical decision to use imipramine for 25 pediatric patients with acute burns. The treatment histories of these patients were retrospectively reviewed to see if further exploration into the efficacy of imipramine was warranted. Eighty percent of the children experienced remission of hyperarousal symptoms (eg, trouble staying asleep, trouble falling asleep) and intrusive reexperiencing symptoms (eg, nightmares). Twelve percent of the children experienced a decrease in the frequency or intensity of ASD symptoms. Eight percent had no relief of ASD symptoms. Initial findings suggest that imipramine assists children who have postburn ASD symptoms by decreasing the hyperarousal and intrusive reexperiencing symptoms of ASD.

Adult↗
PubMed2004

Autistic spectrum disorder and the fragile X premutation.

Fragile X syndrome (FXS) is the most common inherited cause of mental retardation. It is also one of the most common identifiable causes of Autism Spectrum Disorder (ASD). Carriers of FXS are often considered to be cognitively and behaviorally unaffected. However, we report here on six individuals in the premutation range who also have ASD. A comparison is made with five subjects in the premutation range who did not receive a diagnosis of ASD. The six individuals with ASD had a range of cognitive ability levels from no impairment to moderate retardation. Discussion includes the impact of molecular variables including lowered FMR1 protein and elevated FMR1 mRNA in addition to environmental factors leading to the complex neurodevelopmental disorder of ASD.

Adult↗
PubMed2005

Incidence of and risk factors for acute stress disorder in children with injuries.

BACKGROUND: To assess the incidence of and risk factors for Acute Stress Disorder (ASD) in children with injuries. Numerous studies have documented the increased incidence of PTSD in those initially diagnosed with ASD. PTSD symptoms cause tremendous morbidity and may persist for many years in some children. METHODS: Children hospitalized with one or more injuries were interviewed and assessed with the following: Child Stress Disorders Checklist (CSDC), Family Strains Scale, Brief Symptom Inventory (BSI) and Facial Pain Scale. RESULTS: Participants included sixty-five children (ages 7-18 years). The mechanisms of injury varied (e.g. MVC, penetrating). The mean injury severity score was 8.9 +/- 7. The mean length of hospital stay was 4.6 +/- 4.6 days. Altogether, 18 (27.7%) of participants met DSM IV criteria for ASD during their acute hospital stay. Risk factors such as level of family stress, caregiver stress, child's experience of pain, and child's age were predictive of acute stress symptoms. CONCLUSION: We have identified four risk factors of ASD that have implications for the treatment, and possibly, preventative intervention for PTSD. Further investigation and greater understanding of risk factors for ASD in children with injuries may facilitate the design of acute interventions to prevent the long-term negative outcomes of traumatic events.

Adolescent↗
PubMed2005

Electroencephalogram abnormalities in children with autism spectrum disorders.

Children with an autism spectrum disorder (ASD) often are evaluated with electroencephalogram (EEG) studies to assess their risk for seizures or other underlying abnormalities. Their risk is estimated at 7% - 42%. EEG studies were conducted on a subgroup of children while following established practice parameters for evaluating children for ASD. Abnormal EEG results were obtained in 85 (27%) of the 316 children evaluatedfor ASD. Within the subset of abnormal results, 64 children had autism, 10 had an ASD or milder presentation, 6 had another developmental disorder, 3 had Rett syndrome, had Down syndrome, and 1 had Wolf-Hirshhorn syndrome. The abnormal EEG findings included epileptiform abnormalities in 55 patients (65%), and slowing in only 13 patients (15%). The focality of the epileptiformfindings included 26 (30%) in the temporal areas, 24 (28%) in the central area, 20 (23%) in the frontal area, and 7 (8%) in the occipital area. These findings confirm the importance of ongoing medicalfollow-up for children with ASDs, especially for those with abnormal EEG results.

Aftercare↗
PubMed2025

Autism spectrum disorder risk genes have convergent effects on transcription and neuronal firing patterns in primary neurons.

Autism spectrum disorder (ASD) is a highly heterogenous neurodevelopmental disorder with numerous genetic risk factors. Notably, a disproportionate number of risk genes encode transcription regulators including transcription factors and proteins that regulate chromatin. Here, we test the function of nine such ASD-linked transcription regulators by depleting them in primary cultured neurons. We then define the resulting gene expression disruptions using RNA sequencing and test effects on neuronal firing using multielectrode array recordings. We identify shared gene expression signatures across many ASD risk genes that converge on the disruption of critical synaptic genes. Fitting with this, we detect robust disruptions to neuronal firing throughout neuronal maturation. Together, these findings provide evidence that the loss of multiple ASD-linked transcriptional regulators disrupts transcription of synaptic genes and has convergent effects on neuronal firing that may contribute to enhanced ASD risk.

Autism Spectrum Disorder↗
PubMed2006

Department for Education and Skills/Department of Health Good Practice Guidance on the education of children with autistic spectrum disorder.

Currently, it is held by many that educational interventions are those most likely to make a significant difference to the prognosis and well-being of a child with an autistic spectrum disorder (ASD). Yet, decision making about educational interventions and provision in ASD is often based on beliefs, tradition and assumptions, rather than on empirical evidence. This can lead to inappropriate or ineffective provision and can cause confusion and conflict between and within professional groups and parents. Little rigorous research evidence exists to guide decisions for children with ASD. This is true for educational practice generally, and for children with other special educational needs. Practitioners and parents alike are keen for good information on how best to educate children with ASD. It was against this background that the Department for Education and Skills (DfES) and Department of Health (DoH) convened a working group of experienced practitioners and parents to produce the 'Good Practice Guidance on ASDs'. This paper explores the need for the DfES/DoH Guidance, describes its structure and content and then suggests why research evidence is sparse and how future research might be enhanced to inform practice.

Adult↗
PubMed2005

Cloning and characterization of aspartate-beta-semialdehyde dehydrogenase from Mycobacterium tuberculosis H37 Rv.

AIMS: To clone and characterize the aspartate-beta-semialdehyde dehydrogenase of Mycobacterium tuberculosis H37Rv. METHODS AND RESULTS: The asd gene of M. tuberculosis H37Rv was cloned in pGEM-T Easy vector, subcloned in expression vector pQE30 having a T5 promoter, and overexpressed in Escherichia coli. The ASD enzyme was expressed to levels of 40% but was found to be inactive. Functional ASD was obtained by altering induction and growth conditions and the enzyme was purified to near homogeneity using nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. The K(m) and V(max) values for the three substrates L-ASA, NADP and Pi, the turnover number and specific activity of the enzyme were determined. CONCLUSIONS: Functional ASD enzyme of M. tuberculosis was obtained by gene cloning and protein purification using affinity chromatography. The K(cat) and specific activity of the enzyme were 8.49 s(-1) and 13.4 micromol min(-1) microg(-1) respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The ASD enzyme is a validated drug target. We characterized this enzyme from M. tuberculosis and future work would focus on deducing the three-dimensional structure of the enzyme and design of inhibitors, which could be used as drugs against TB.

Aspartate-Semialdehyde Dehydrogenase↗
PubMed2005

Adults with autism living at home or in non-family settings: positive and negative aspects of residential status.

BACKGROUND: Very little is known about the context of caregiving by parents of adults with autism or about the perceived impacts of continued patterns of co-residence vs. out-of-family living. In the present study, maternal assessments of residential status, involvement with adult children living in a non-family setting, and the impacts on mothers of their residential arrangements were examined. METHODS: Mothers from 133 families of adults (aged 22 years and older) with autism spectrum disorder (ASD) completed questionnaires as part of a longitudinal study on family caregiving. Mothers completed open-ended questions regarding the positive and negative aspects of their child's residential arrangement. Mothers also completed scaled questions regarding their satisfaction with their child's residential arrangement, the different ways in which people's lives change after a relative moves from the home, and the frequency of contact with their son or daughter. RESULTS: Mothers found co-residing with their adult child to be of greatest positive benefit to the family while those living apart found this residential arrangement of greatest benefit to the son or daughter with ASD. The greatest negative consequences for co-residing mothers were understood to fall on families, while mothers felt the majority of negative consequences for those that lived apart. There was a high level of contact and maternal involvement between the mother and adult child with ASD even after out-of-home placement. CONCLUSIONS: Residential status, as appraised by mothers, has varying impacts on the individual with ASD, on the family, and on mothers as individuals and caregivers. The present analysis suggests the multifaceted and highly contingent maternal experience associated with where her child with ASD lives. Among families whose children live elsewhere, there is an impressive amount of continued contact between these families and their son/daughter.

Adolescent↗
PubMed2006

Objective investigation of the sleep-wake cycle in adults with intellectual disabilities and autistic spectrum disorders.

BACKGROUND: Disturbances in circadian rhythm functioning, as manifest in abnormal sleep-wake cycles, have been postulated to be present in people with autistic spectrum disorders (ASDs). To date, research into the sleep-wake cycle in people with ASDs has been primarily dependant on third-party data collection. METHOD: The utilization of non-invasive objective recording technologies such as actigraphy permits investigation of both sleep and circadian rhythm functioning in people with ASDs, together with the collection of data on daytime activity. RESULTS: Data were collected from 31 participants with intellectual disabilities living in supported community-based residential provision aged between 20 and 58 years, of whom 14 had an ASD. Analysis indicated that there were no significant differences in sleep patterns and circadian rhythm function between those participants with an ASD and those without. CONCLUSIONS: The mean scores of the participants as a whole indicated abnormalities in the two key circadian rhythm parameters of interdaily stability and intradaily variability. The implications of these findings for both clinical practice and theory are discussed.

Adult↗
PubMed2004

Genetic landmarks through philately - autism spectrum disorders: a genetic update.

Autism spectrum disorders (ASD) represent a heterogeneous group of developmental disorders that present a challenge to geneticists because of their complex etiology and inheritance. This article reviews some of the advances in our understanding of causation in ASD and the role in which molecular genetic investigations have helped in unraveling the mystery of ASD. There have been few postage stamps issued relevant to ASD. Because of the need for early diagnosis and improved recognition, some countries may consider issuing stamps to highlight the importance of ASD to the population and to raise awareness and money for research funding.

Animals↗
PubMed2004

Young children with autism show atypical brain responses to fearful versus neutral facial expressions of emotion.

Evidence suggests that autism is associated with impaired emotion perception, but it is unknown how early such impairments are evident. Furthermore, most studies that have assessed emotion perception in children with autism have required verbal responses, making results difficult to interpret. This study utilized high-density event-related potentials (ERPs) to investigate whether 3-4-year-old children with autism spectrum disorder (ASD) show differential brain activity to fear versus neutral facial expressions. It has been shown that normal infants as young as 7 months of age show differential brain responses to faces expressing different emotions. ERPs were recorded while children passively viewed photos of an unfamiliar woman posing a neutral and a prototypic fear expression. The sample consisted of 29 3-4-year-old children with ASD and 22 chronological age-matched children with typical development. Typically developing children exhibited a larger early negative component (N300) to the fear than to the neutral face. In contrast, children with ASD did not show the difference in amplitude of this early ERP component to the fear versus neutral face. For a later component, typically developing children exhibited a larger negative slow wave (NSW) to the fear than to the neutral face, whereas children with autism did not show a differential NSW to the two stimuli. In children with ASD, faster speed of early processing (i. e. N300 latency) of the fear face was associated with better performance on tasks assessing social attention (social orienting, joint attention and attention to distress). These data suggest that children with ASD, as young as 3 years of age, show a disordered pattern of neural responses to emotional stimuli.

Autistic Disorder↗
PubMed2004

Regression and word loss in autistic spectrum disorders.

BACKGROUND: For many years, researchers and clinicians have described parent reports of an unusual developmental phenomenon in a substantial minority of children with Autistic Spectrum Disorders (ASD), the acquisition and then loss of communication skills during the second year of life. METHODS: As part of a longitudinal study of 110 children referred for assessments of possible autism at age 2 years or younger, 21 developmentally delayed children and 33 typically developing controls, 19 children were described by their parents at age 2 as having gained and lost spontaneous, meaningful words, and 12 children as having a history of less specific loss of imitated words or nonword vocalizations. A battery of diagnostic and cognitive tasks was administered to all children at study entrance, at ages 3 (for the referral children only) and 4 or 5 (for referral and developmentally delayed children). RESULTS: Results indicated that the acquisition of a small number of spontaneous words used meaningfully and consistently followed by loss of all words, often associated with other social changes, was unique to children diagnosed at 5 years with ASD. Few differences, besides those that defined the pattern of word loss, emerged between children with ASD with and without word loss. Loss of less specific, nonword vocalizations was associated with cognitive delay, with or without autism. CONCLUSIONS: Word loss is a reliably identifiable phenomenon in early childhood that appears to be unique, but not universal to, ASD. Histories and outcome of children with word loss were not in keeping with a sudden change from normal to abnormal functioning, but did suggest that this type of loss in the second year of life may be a useful 'red flag' for ASD in a significant minority of cases.

Autistic Disorder↗
PubMed2001

Intervention in the critically ill neonate and infant with hypoplastic left heart syndrome and intact atrial septum.

Neonates that present with hypoplastic left heart syndrome (HLHS) and intact atrial septum (IAS) pose a major management problem for the pediatric cardiac team. They are critically ill newborns with profound hypoxemia and acidosis that require immediate attention. Controversy exists as to the most appropriate management strategy. In one series where a primary and emergent surgical-staged reconstructive procedure was performed, the in-house hospital mortality was 65% and the overall survival was 17%. With equal abysmal results, transcatheter creation of an atrial septal defect (ASD) using conventional balloon atrial septostomy (BAS) with or without the combination of blade atrial septotomy had an unacceptable high risk of cardiac perforation leading to tamponade and death. However, using more modern transcatheter techniques of transseptal perforation of the atrial septum followed by progressive and serial balloon septoplasty, creating an ASD, significantly reduced the risk of the procedure. In one series, 16 consecutive neonates underwent this type of interventional procedure without procedural mortality. The management strategy of creating an ASD in the catheterization lab followed by Stage I reconstructive surgical repair 3-5 days after the initial catheterization procedure improved the in-house survival to 57%. Unfortunately, there continues to be significant attrition of these patients undergoing Stage II and III reconstructive repair, which supports cardiac transplantation as an alternative strategy. There have been echocardiographic and histopathologic studies of these neonates, and an important echo classification of left atrial morphology has been described with perhaps some prognostic implication. In addition, autopsy specimens have demonstrated significant "arterialization" of the pulmonary venous architecture that likely dooms the patient with single ventricle physiology to a poor outcome. Future improvement in transcatheter techniques and materials offer promise in palliating these critically ill neonates. The concept of radiofrequency energy perforating catheters has great merit and may reduce the risk of cardiac perforation as compared with the rigid and long transseptal needle. Echocardiographic imaging at the time of entry through the IAS may improve the safety as well. The novel concepts of "butterfly" or "dog-bone" stents placed across the atrial septum creates a precisely sized ASD that may be more conducive to effectively lower left atrial hypertension, yet avoids excessive pulmonary blood flow associated with large atrial communications. In addition, new materials, such as the Cutting Balloon Catheter, may offer promise in creating ASDs in these patients. A more aggressive approach would be to consider intrauterine fetal transcatheter opening of the IAS using modified techniques that have been attempted for left ventricular outflow tract obstruction. Unfortunately to date, the results of attempted relief of aortic valve stenosis have been extremely poor. Finally, we as interventionalists need to continue to improve our skills to help in the complex management of these critically ill neonates and infants. Only through continued efforts of the entire cardiac team of intensivists, cardiologists, cardiothoracic surgeons, and interventionalists will our management strategy be defined to maximize the future outcome in this group of patients.

Angiography↗
PubMed2001

Transcatheter closure of atrial septal defects in children & adults using the Amplatzer Septal Occluder.

We are reporting the worldwide experience in closing atrial septal defects (ASDs) in children and adults using the Amplatzer Septal Occluder (ASO) as of July 2000. The outcome measures were safety and efficacy with special emphasis on: (1) immediate success of the ASD closure as measured by transesophageal echocardiography (TEE), (2) short- and medium-term follow-up at 24 hours and 1 and 3 months and long-term follow-up at 1, 2, and 3 years as assessed by transthoracic echocardiography (TTE); and (3) the incidence of complications. In all, 3580 procedures were performed in 3535 patients. In 75 patients, the device was not implanted for variety of reasons; 3460 patients received a single ASO device and 45 received two devices for multiple ASDs. The median age of the patients was 12.1 year, (range, 10 days-88 years, the median weight was 41.0 kg (range, 2.4-137 kg) and the median Qp/Qs ratio was 2 (range, 0.3-10). The median size of ASD by TEE was 14 mm (range, 1-38 mm) and the median stretched diameter was 18 mm (range, 4-44 mm). The median size of device implanted was 18 mm (range, 4-40 mm). The median fluoroscopy time was 17.1 minutes (range, 0.0-194.0 minutes). The immediate success rate including those patients with complete closure, trivial residual shunt, or with small residual shunt was 97.4%. This increased to 99.2% and 100% at 3 months and 3 years, respectively. Minor complications were encountered in 2.8% of procedures, while serious complications occurred in less than 0.3% of the cases. There were no device related deaths. We conclude that the ASO is a safe and effective device for catheter closure of small to large ASDs up to a stretched diameter of 40 mm in children and adults with very high short-, medium, and long-term success rates.

Adolescent↗
PubMedDate not supplied

Acute stress disorder symptoms in gunshot-injured youth.

PROBLEM: The prevalence of acute stress disorder symptoms (ASDS) and other psychiatric comorbidities in youth with recent gunshot injuries. METHODS: Children (n=20) admitted to an urban hospital ER for gunshot injuries over a 4-year period were evaluated for ASDS, co-morbid DSM-III-R diagnoses, legal and gang involvement, and psychiatric history; medically hospitalized children (n=36) similar in age, sex, race, and socioeconomic status served as a control group. FINDINGS: Gunshot-injured youth reported a 75% rate of ASDS compared to a 14% rate in medically ill youth (OR 18.6; chi2 = p < .0001). Parent ratings of ASDS closely corresponded with youth ratings. Youth rated reexperiencing the event as the most frequent distressing symptom. Gunshot injury was associated with legal problems, gang involvement, marijuana/alcohol dependence, conduct disorder, social phobia, and agoraphobia compared to youth with medical illness. CONCLUSIONS: Compared to youth with medical illness, gunshot-injured youth were 18.6 times (p = .0001) more likely to show symptoms of ASDS. Further research, developmentally appropriate assessment, prevention, and treatment are needed in this area.

Adolescent↗