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PubMed2004

Imaging data in autism: from structure to malfunction.

During the last two decades, neuroimaging studies have improved our knowledge of brain development and contributed to our understanding of disorders involving the developing brain. Differences in cerebral anatomy have been determined in autism spectrum disorder (ASD). Morphological studies by magnetic resonance imaging have provided evidence of structural differences in ASD compared with the normal population. This has enhanced our view of autism as a neurobiological disorder corresponding with different stages and events in brain development. Alterations in volume of the total brain and specifically the cerebellum, frontal lobe, and limbic system have been identified. There appears to be a pattern of increased and then decreased rate of brain growth over time. We integrate these observations with neurobehavioral findings to provide a developmental hypothesis of the pathophysiology of autism.

Autistic Disorder↗
PubMed2004

Neurologic treatment strategies in autism: an overview of medical intervention strategies.

Child neurologists are likely to be caring for an increasing number of patients with autistic spectrum disorder (ASD). ASD may occur in as many as 1/100 to 1/200 births. It appears to be a multifactorial disease, with many phenotypes or subgroups. No simple treatment is currently approved for curing or managing core symptoms of autism. We rationally propose a symptom-based review of what treatments may offer relief to specific subtypes of clinical behaviors seen in autism. There is a lack of clinically based evidence on which to universally recommend a rational clinical algorithm for treatment; we suggest that rational pharmacotherapy may offer symptomatic relief to core areas of dysfunction in the autistic population. Future research into rational medical treatment options is desperately needed.

Aggression↗
PubMed2006

Seeing it differently: visual processing in autism.

Several recent behavioral and neuroimaging studies have documented an impairment in face processing in individuals with Autism Spectrum Disorder (ASD). It remains unknown, however, what underlying mechanism gives rise to this face processing difficulty. One theory suggests that the difficulty derives from a pervasive problem in social interaction and/or motivation. An alternative view proposes that the face-processing problem is not entirely social in nature and that a visual perceptual impairment might also contribute. The focus of this review is on this latter, perceptual perspective, documenting the psychological and neural alterations that might account for the face processing impairment. The available evidence suggests that perceptual alterations are present in ASD, independent of social function.

Autistic Disorder↗
PubMed1993

Mitral restenosis and mitral regurgitation 1 year after Inoue mitral balloon valvotomy in a population of patients with pliable mitral valve stenosis.

To determine the rate of mitral restenosis and mitral regurgitation increase 1 year after mitral valvotomy using the Inoue balloon catheter, 66 consecutive patients with severe, pliable mitral stenosis had their mitral valve area (MVA) calculated by two-dimensional echocardiography (2DE) and Doppler before, immediately after balloon valvotomy, and at 1-year follow-up. Color Doppler studies were also done to detect small atrial septal defects (ASDs) and mitral regurgitation. The mean age of the patients was 31 +/- 12 years. Three patients were in New York Heart Association (NYHA) class II and 63 patients were in NYHA class III to IV. Sixty-two of the 66 patients had an echo score (Boston) of < or = 8. After Inoue balloon valvotomy (IBV), the MVA (2DE) increased from 0.8 +/- 0.2 to 1.9 +/- 0.3 cm2 (p < 0.001), and the Doppler MVA increased from 0.8 +/- 0.2 to 1.8 +/- 0.3 cm2 (p < 0.001). We detected 4 of 66 cases (6%) with significant residual mitral stenosis (MVA < 1.5 cm2). Mitral regurgitation increased in 14 of 66 patients (21%), but no patient developed severe mitral regurgitation. Fourteen out of 66 patients (20%) had ASDs that were detected on color Doppler. At 1-year follow-up the mean Doppler MVA was maintained at 1.8 +/- 0.4 cm2, with 6 of 66 patients (9%) exhibiting significant mitral valve restenosis. Residual significant mitral stenosis must be differentiated from mitral restenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2000

Usefulness of the myocardial performance index for assessing right ventricular function in congenital heart disease.

Quantitative assessment of ventricular function in patients with congenital heart disease is often challenging due to distorted ventricular geometry. A myocardial performance index (MPI) has been reported in adults and children that is a Doppler-derived nongeometric measure of ventricular function. The MPI measures the ratio of isovolumic time intervals (isovolumic contraction time and isovolumic relaxation time) to ventricular ejection time. The effects of altered ventricular preload or afterload on the MPI have yet to be determined. This study assesses the impact of altered preload or afterload on right ventricular (RV) function and the RV MPI in the clinical setting of congenital heart disease. Patient groups were compared with normal pediatric and adult populations before and after repair of their congenital heart lesion. Patients with large atrial septal defects (ASDs) represented the clinical setting of increased ventricular preload, whereas patients with isolated pulmonary valve stenosis represented increased RV afterload. Patients with congenitally corrected transposition of the great arteries (CC-TGA) with severe left atrioventricular valve regurgitation represented a combined increase in RV preload and afterload. The RV MPI in 152 normal children (ages 3 to 18 years) and 37 adults (ages 18 to 51 years) was 0.32 +/- 0.03 and 0.28 +/- 0.04, respectively. In pediatric patients (n = 45) and adult patients (n = 40) with ASD, the RV MPI was 0.35 +/- 0.09 (p = NS) and 0.38 +/- 0.04 (p < 0.01 compared with normal adults), respectively. Patients with pulmonary stenosis (n = 21, ages 1 day to 19 years) had a RV MPI of 0.32 +/- 0.06 (p = NS). CC-TGA patients had a RV MPI of 0.72 +/- 0.17 (p < 0.001). No significant change in the RV MPI was seen in any postoperative patient group despite relief of RV volume or pressure overload. Thus, the MPI is a quantitative measure of RV performance that is appears to be relatively independent of changes in preload or afterload in the clinical setting.

Adolescent↗
PubMed2002

Predisposing conditions for atrial fibrillation in atrial septal defect with and without operative closure.

The aims of this study were to determine the prevalence and predisposing conditions for atrial fibrillation (AF) in adults with atrial septal defect (ASD) and to evaluate the influence of age at surgical repair. The study population consisted of 286 adults with ASD (mean age 39.5 +/- 19 years). All patients had >or = 1 follow-up visit and a Doppler echocardiographic study. One hundred ninety-two of the patients underwent surgical closure 1 to 34 years before the study. Analyzed variables were entered into univariate (Mann-Whitney U) and multivariate (stepwise logistic regression) models to assess independent predictors for AF. The prevalence of AF was similar in surgically treated patients (15.6%) and in the nonsurgical group (13.8%) (p = 0.69). Multivariate analysis showed that current age (RR 1.9 per each decade of age, 95% confidence interval [CI] 1.3 to 2.7, p = 0.001), mitral regurgitation (RR 3.0 per each degree of regurgitation, 95% CI 1.6 to 5.8, p = 0.001), left atrial enlargement (RR 2.8 per each 10 mm increase in size, 95% CI 1.5 to 5.2, p = 0.001), and tricuspid regurgitation (RR 1.9 per each degree of regurgitation, 95% CI 1.0 to 3.7, p = 0.04) were independent predictors of AF; however, gender, anatomic type, defect size, Qp:Qs, pulmonary artery pressure, right ventricular dimension, left ventricular shortening fraction, and prior surgical repair were not related to late AF development. In the surgical group, age >25 years at the time of surgery was the only predictor for AF independent of age at the time of the study (p = 0.02).

Adolescent↗
PubMed1997

Balloon pulmonary valvuloplasty for pulmonary valve stenosis with atrial septal defect.

We performed successful balloon pulmonary valvuloplasty (BPV) in 6 patients with pulmonary valve stenosis and atrial septal defect (ASD) accompanied by atrial left-to-right shunt without an increase of shunting immediately after BPV. It suggests that such patients should be treated by BPV initially and the need for ASD repair can be assessed during long-term follow-up.

Catheterization↗
PubMed1999

Comparison of the Sideris and Amplatzer septal occlusion devices.

The results of transcatheter atrial septal defect (ASD) occlusion with 2 different devices (Sideris adjustable buttoned device vs Amplatzer Septal Occluder) were compared in 2 consecutive series of patients. Comparative outcomes were assessed by whether a device was implanted or not, by complications and fluoroscopy time of implantation, and by the incidence of residual shunting on transthoracic echocardiography at follow-up. The patient and defect characteristics were similar in both groups. Twenty-eight of 33 Sideris devices and 37 of 39 Amplatzer devices were implanted. The fluoroscopy time for the Amplatzer implants was 13.4 minutes (range 8 to 41) compared with 23.7 minutes (range 11 to 60.6) for the Sideris implants (p <0.001). The complete occlusion rate for the Amplatzer device was 93% compared with 44% for the Sideris device at 1 year (p <0.001). In conclusion, the Amplatzer device produces higher occlusion rates of ASDs with shorter fluoroscopy times.

Adolescent↗
PubMed1999

Minimally invasive surgery with cardioscopy for congenital heart defects.

BACKGROUND: Minimally invasive cardiac surgery remains a burgeoning discipline lacking adequate instrumentation and perfusion circuitry, particularly for the pediatric population. Cardioscopy, utilizing first generation imaging equipment with a variety of different angled lenses, provides a unique opportunity to expand the realm for the diagnosis and treatment of congenital heart disease. METHODS: Sixty-eight children with a mean weight of 23 +/- 11 kg (range 8-62 kg) who underwent repair of atrial septal defects (ASD) using a minimally invasive approach (MINI group) were compared to 25 consecutive children undergoing ASD repair via a full median sternotomy (CONT group). In addition, mini-sternotomy with or without cardioscopy allowed for the diagnosis and treatment of more complex congenital lesions in 24 children. RESULTS: The mean age in the MINI group was 7 +/- 3 years (range 1-15 years) compared to 4 +/- 4 years in the CONT group (p = 0.009). The mean body surface area of the MINI group (0.8 +/- 0.2 m2; range 0.4-1.6 m2) was larger than the CONT group (mean 0.6 +/- 0.3 m2; range 0.2-1.6 m2; p = 0.04). Ischemic times and cardiopulmonary bypass times were similar in both groups. Postoperative hospital stay was shorter in the MINI group (3 +/- 2 versus 4 +/- 1 days; p = 0.014). CONCLUSIONS: Minimally invasive cardiac surgery can be performed safely even in small children with congenital heart defects. In addition to improved cosmetic results, these techniques can reduce the utilization of hospital resources. Future advances in cardioscopic technology should permit minimally invasive repair of most complex congenital heart lesions and should obviate the need for full sternotomy in the majority of children undergoing cardiac surgery.

Adolescent↗
PubMed2000

A new, safe, and easy technique of atrial septal defect creation.

We created an atrial septal defect (ASD) using a Ferris-Smith-Kerrison bone punch under transesophageal echocardiographic monitoring for infants with complex congenital heart diseases, eg, transposition of the great arteries. We describe a safe and easy technique of ASD creation instead of Blalock-Hanlon operation.

Echocardiography, Transesophageal↗
PubMed2000

Attempting suppression of traumatic memories over extended periods in acute stress disorder.

This study investigated the influence of attempted suppression and thought control strategies on traumatic memories. Survivors of civilian trauma with acute stress disorder (ASD; n = 20) and without ASD (n = 20) monitored their trauma-related thoughts for three 24-h periods. In period 1, participants were instructed to think about anything. In period 2, participants were administered suppression or nonsuppression instructions relating to thoughts of the trauma. In period 3, participants were again instructed to think about anything. The results revealed no evidence for an increase in trauma-related thoughts following suppression instructions. Punishment and worry thought control strategies correlated significantly with both anxiety and suppression ratings. Frequency of intrusions was associated with a distraction cognitive strategy. These findings point to the importance of traumatised individuals' cognitive strategies in mediating the management and occurrence of posttraumatic intrusions.

Accidents, Occupational↗
PubMed2002

Differential inhibition of 30S and 70S translation initiation complexes on leaderless mRNA by kasugamycin.

In contrast to canonical mRNAs, translation of leaderless mRNA has been previously reported to continue in the presence of the antibiotic kasugamycin. Here, we have studied the effect of the antibiotic on determinants known to affect translation of leadered and leaderless mRNAs. Kasugamycin did not affect the Shine-Dalgarno (SD)-anti-SD (aSD) interaction or the function of translation initiation factor 3 (IF3). Thus, the preferential translation of leaderless mRNA in the presence of kasugamycin can neither be attributed to an expanding pool of 30S subunits with a "blocked" aSD nor to a lack of action of IF3, which has been shown to discriminate against translation initiation at 5'-terminal start codons. Using toeprinting, we observed that on leaderless mRNA 70S in contrast to 30S translation initiation complexes are comparatively resistant to the antibiotic. These results taken together with the known preference of 70S ribosomes for 5'-terminal AUGs lend support to the hypothesis that translation of leaderless mRNAs may as well proceed via an alternative initiation pathway accomplished by intact 70S ribosomes.

Aminoglycosides↗
PubMed1995

Long-term survival of patients with argininosuccinate synthetase deficiency.

OBJECTIVE: To monitor long-term survival and outcome of patients with neonatal-onset argininosuccinate synthetase deficiency (ASD) who were treated with specific therapeutic protocols designed to activate alternative pathways of waste nitrogen excretion. DESIGN: Patients for this study included 24 infants born before 1990 and rescued from hyperammonemic coma caused by neonatal-onset ASD; they were referred to this center for enrollment in ongoing clinical studies of sodium benzoate, sodium phenylacetate, and sodium phenylbutyrate. Collaborating physicians throughout the United States and Canada provided information on survival, intellectual development, intercurrent hyperammonemic episodes, and anthropometric and biochemical measurements. RESULTS: The cumulative survival rate was 87.5% at 5 years and 72% at 10 years of age. Survivors include 15 patients currently treated with high doses of sodium phenylbutyrate; two patients have withdrawn. Among the treated group, 11 are classified as severely to profoundly mentally retarded. The remaining four patients have IQ measurements in the borderline to mentally retarded range. All patients have had intercurrent hyperammonemic episodes; our data indicate that the frequency of the episodes has decreased with implementation of the current protocol. These patients are growth retarded, but most have height-for-weight z scores within 2 SD of the mean. Laboratory studies of plasma amino acids and of hematopoietic, renal, and hepatic function are within normal limits with the exception of slightly elevated serum aminotransferase values. CONCLUSION: Our results indicate that these drugs are safe and that the current protocol improves survival rates. However, survival is accompanied by mental retardation, growth retardation, risk of hyperammonemic episodes, and the necessity of lifetime adherence to strict medication and dietary management.

Adolescent↗
PubMed1998

Acute and long-term behavioral correlates of underwater trauma--potential relevance to stress and post-stress syndromes.

As a consequence of a brief but significantly extreme stressor, an individual will experience a stress response, which may sometimes develop into Acute Stress Disorder (ASD) or Post-Traumatic Stress Disorder (PTSD). Though a rat model for ASD and PTSD is not expected to encompass the richness and complexity of the disorders in humans, it will enable the study of the common underlying mechanisms that generate the disorders, the study of pre-trauma etiological aspects of the disorders and the screening of drugs with potential relevance to the treatment of the disorders. One well-documented aspect of PTSD is the enhancing influence of contextual elements on the appearance of symptoms of the post-stress trauma. To exploit this effect, we have chosen to assess the effects of an underwater trauma in the Morris water maze since the effects of such trauma on memory and attention can be later evaluated in the context of the trauma. At both 1 h and 3 weeks after the trauma, significant behavioral deficits were observed in the water maze. The effects of the underwater trauma on the performance of rats in the water maze were context specific. Underwater trauma in a different (out-of-context) water container had no effects on the ability of rats to perform a spatial memory task in the water maze. An elevated level of anxiety was found in the plus maze test, independently of whether the trauma was performed in the water maze or in a different (out-of-context) water container. The results indicate that a within-context underwater trauma has both acute and lasting behavioral consequences which can be assessed using a spatial memory test in the context of the trauma. The results are discussed in relation to their relevance to stress and PTSD.

Analysis of Variance↗
PubMed2004

Atrial septal defect in adults > or =40 years old: negative impact of low arterial oxygen saturation.

BACKGROUND: Although good prognosis and clinical long-term outcome have been commonly reported in minimally symptomatic adult patients with ASD, this information has been based on studies with a relatively small number of adult patients. We studied unoperated patients aged over 40 years to define the patterns of presentation, anatomical characteristics, outcome and predictive factors for free-event survival of major cardiovascular and pulmonary events. METHODS AND RESULTS: Two-hundred survivors of atrial septal defect aged over 40-yr attended from 1985 to 1998 were reviewed and followed-up from 1.6 to 22 years. Patients were classified in three groups according to age at entry: Group 1, between 40 and 49; Group 2; 50 and 59; and Group 3, > or =60 years old. The mean age at presentation was 48.8+/-9.2 years, and the most common clinical presentations were arrhythmia and dyspnea (51.4%). There were 37 (18.5%) events: 7 heart failure-related, 5 sudden death, 13 severe pulmonary infections, 5 embolisms, and 4 strokes. According to Cox's regression analysis, predictors of primary end point included age group at presentation (hazard ratio 1.71, 95% confidence limits 1.16 to 2.54), and either pulmonary hypertension (mean pulmonary pressure >35 mmHg; hazard ratio=0.65 (4.6, confidence limits 2.2 to 9.5) or, arterial oxygen saturation <80% (hazard ratio 1.71, 95% confidence limits 1.16 to 2.54). CONCLUSIONS: This study supports that long term outcome of patients aged >40 years with unoperated ASD is importantly determined by the mPAP (>35 mmHg), SaO2% (_80) and the age at diagnosis. Nevertheless we identified an inverse association between the mPAP level and SaO2% (interaction). The event-free survival expectancy may be estimated using the age at diagnosis and either SaO2% or mPAP. This prognostic stratification based on pathophysiological principles, may help in making decisions for therapeutic interventions. SaO2% should always be measured as a part of the initial clinical approach of those patients with atrial septal defect aged over 40 years.

Adult↗
PubMed2004

Atrial septal defect in apical hypertrophic cardiomyopathy associated with coronary spasm.

Apical hypertrophic cardiomyopathy (HCM) is a well-known myocardial disease, but the additional coexistence of an atrial septal defect (ASD) and coronary spasm is quite rare. We report here on a 62-year-old man suffering from congestive heart failure due to apical HCM complicated by coronary spasm and secundum-type ASD. The transthoracic, transesophageal echocardiography and cardiac catheterization were useful for diagnosing and evaluating of the patient's status. A calcium channel blocker was given to prevent coronary spasm, and a surgical patch closure operation was successfully performed. Afterwards, his symptoms were alleviated.

Calcium Channel Blockers↗
PubMed2002

[Comparative study of thoracic approaches in atrial septal defect closure].

Our early experience in approaching ASD by right thoracotomy as opposed to midline sternotomy is presented. Between July 2000 and December 2001, 15 patients (group A) were operated by right thoracotomy. Mean age of patients was 8.6 years and mean weight was 31.6 kg. In the same period, midline sternotomy was used in 16 patients (group B). Mean age was 4.7 years and weight was 16.5 kg. The duration of the procedure, by-pass, and aortic cross-clamping were similar. Bleeding was 265 ml (8.4 ml/kg) in group A, and 152 ml (9.2 ml/kg) in group B. The duration of the ICU stay and time of discharge were 2.4 days and 6 days in group A, and 2.23 days and 6.87 days in group B, respectively. No significant differences were found in ASD closure by thoracotomy and sternotomy. The cosmetic appearance acceptance of right thoracotomy was excellent.

Adolescent↗
PubMed1978

Antifibrinolytic prevention of alveolitis sicca dolorosa.

In a double-blind study dental cones containing the antifibrinolytically active propylic ester of p-hydroxybenzoic acid (PEPH), sulfanilamide and sulfathiazol or placebo were placed in dental sockets following removal of impacted mandibular third molars on 95 consecutive patients, 50 women and 45 men. The duration of the operation, the type of surgeon, preoperative symptoms and the use of peroral anticonception were recorded. The patients were asked to return to the clinic on the seventh postoperative day, and it was then noted whether the healing was disturbed by Alveolitis Sicca Dolorosa (ASD) or not. Statistical analysis showed a significantly prophylactic effect of PEPH against ASD. The prophylactic effect was most pronounced in the group of male patients without preoperative symptoms and in the group of patients operated by dental students. It could not be demonstrated that the sulfa drugs in the cones were of any benefit to the healing of the socket.

Adolescent↗