Haptic and visuo-haptic impairments for object recognition in children with autism spectrum disorder: focus on the sensory and multisensory processing dysfunctions.

Dysfunctions in sensory processing are widely described in individuals with autism spectrum disorder (ASD), although little is known about the developmental course and the impact of these difficulties on the learning processes during the preschool and school ages of ASD children. Specifically, as regards the interplay between visual and haptic information in ASD during developmental age, knowledge is very scarce and controversial. In this study, we investigated unimodal (visual and haptic) and cross-modal (visuo-haptic) processing skills aimed at object recognition through a behavioural paradigm already used in children with typical development (TD), with cerebral palsy and with peripheral visual impairments. Thirty-five children with ASD (age range: 5-11 years) and thirty-five age-matched and gender-matched typically developing peers were recruited. The procedure required participants to perform an object-recognition task relying on only the visual modality (black-and-white photographs), only the haptic modality (manipulation of real objects) and visuo-haptic transfer of these two types of information. Results are consistent with the idea that visuo-haptic transfer may be significantly worse in ASD children than in TD peers, leading to significant impairment in multisensory interactions for object recognition facilitation. Furthermore, ASD children tended to show a specific deficit in haptic information processing, while a similar trend of maturation of visual modality between the two groups is reported. This study adds to the current literature by suggesting that ASD differences in multisensory processes also regard visuo-haptic abilities necessary to identify and recognise objects of daily life.

Prevalence of Autism Spectrum Disorder in a large Italian catchment area: a school-based population study within the ASDEU project.

AIMS: This study aims to estimate Autism Spectrum Disorders (ASD) prevalence in school-aged children in the province of Pisa (Italy) using the strategy of the ASD in the European Union (ASDEU) project. METHODS: A multistage approach was used to identify cases in a community sample (N = 10 138) of 7-9-year-old children attending elementary schools in Pisa - Italy. First, the number of children with a disability certificate was collected from the Local Health Authority and an ASD diagnosis was verified by the ASDEU team. Second, a Teacher Nomination form (TN) to identify children at risk for ASD was filled in by teachers who joined the study and the Social Communication Questionnaire (SCQ) was filled in by the parents of children identified as positive by the TN; a comprehensive assessment, which included the Autism Diagnostic Observation Schedule-Second Edition, was performed for children with positive TN and SCQ⩾9. RESULTS: A total of 81 children who had a disability certificate also had ASD (prevalence: 0.79%, i.e. 1/126). Specifically, 66 children (57 males and nine females; 62% with intellectual disability -ID-) were certified with ASD, whereas another 15 (11 males and four females; 80% with ID) were recognised as having ASD among those certified with another neurodevelopmental disorder. Considering the population of 4417 (children belonging to schools which agreed to participate in the TN/SCQ procedure) and using only the number of children certified with ASD, the prevalence (38 in 4417) was 0.86%, i.e. one in 116. As far as this population is concerned, the prevalence rises to 1% if we consider the eight new cases (six males and two females; no subject had ID) identified among children with no pre-existing diagnoses and to 1.15%, i.e., one in 87, if probabilistic estimation is used. CONCLUSIONS: This is the first population-based ASD prevalence study conducted in Italy so far and its results indicate a prevalence of ASD in children aged 7-9 years of about one in 87. This finding may help regional, national and international health planners to improve ASD policies for ASD children and their families in the public healthcare system.

Targeting the EWS-FLI1 transcription factor in Ewing sarcoma.

PURPOSE: Preclinical data indicate there is strong synergism of action against Ewing sarcoma in sequential treatment with trabectedin followed by irinotecan and it appears to be related to a selective blockade of the transcription factor EWS-FLI1. This combination was evaluated in Ewing sarcoma patient who was progressing with standard therapies. METHODS: Trabectedin was given as a 24-h iv infusion on day 1 at the dose of 1 mg/sqm, and irinotecan 75 mg/sqm on day 2 and then on days 2 and 4, every 3 weeks from the seventh course. RESULTS: The therapy was well tolerated with transient hematological toxicity and transaminitis and induced stabilization of the disease lasting for 11 courses, with clinical improvement and marked reduction of the need for opioids. However, shortly before the 12th course, sudden death occurred, possibly due to cerebral stroke, presumably not related to the drug treatment. CONCLUSIONS: The encouraging clinical benefit observed with the combination and its good tolerability deserves further investigation in Ewing sarcoma.

The CBCL 1.5-5 and the identification of preschoolers with autism in Italy.

AIMS: To study the potential use of child behaviour checklist (CBCL) 1.5-5 scales for the early identification of preschoolers at risk of autism. METHODS: CBCL scores of three groups of preschoolers were compared: (1) an experimental group of 101 preschoolers with autism spectrum disorder (ASD); (2) a control group of 95 preschoolers with other psychiatric disorders (OPD); (3) a control group of 117 preschoolers with typical development (TD). One-way analysis of variance (ANOVA), logistic regression with odds ratio (OR) and receiver operating characteristic (ROC) analyses were performed. RESULTS: ANOVA revealed that ASD and OPD had significantly higher scores in almost all CBCL scales than TD. ASD presented significantly higher scores than OPD on Withdrawn, Attention Problems and Pervasive Developmental Problems (PDP) scales. Logistic regression analysis demonstrated that these same CBCL scales have validity in predicting the presence of an ASD towards both TD and OPD. ROC analysis indicated high sensitivity and specificity for PDP (0.85 and 0.90) and Withdrawn (0.89 and 0.92) scales when ASD is compared to TD. Specificity (0.60 for PDP and 0.65 for Withdrawn) decreases when comparing ASD and OPD CONCLUSIONS: The PDP and Withdrawn scales have a good predictive validity so that they could be proposed as a first-level tool to identify preschoolers at risk of autism in primary care settings. Problems regarding the lower specificity when comparing ASD v. OPD are discussed.

Pervasive developmental disorder and epilepsy due to maternally derived duplication of 15q11-q13.

Duplications of chromosome 15 have been reported in individuals with atypical autism, varying degrees of mental retardation, and epilepsy. The authors report the molecular analysis, neurophysiologic, and clinical evaluation of a 12-year-old boy with atypical autism and epilepsy due to a maternally derived 15q11-q13 duplication. Their findings suggest that this chromosomal region harbors genes for autism and possibly for partial epilepsy that may act in a dose-dependent manner.

Pulmonary vascular disease: primary pulmonary hypertension.

Clinical and pathologic features of primary pulmonary hypertension have been well characterized, but little is known regarding the underlying cause and pathogenesis. The disorder is usually discovered in its late stage, when pulmonary vascular resistance is already severely compromised and the pathologic changes already well developed. It is not surprising, then, that most attempts at defining effective pharmacologic interventions have been disappointing. Some new approaches are clearly needed. The past decade has witnessed the rapid growth of molecular techniques in areas applied to the study of the blood vessel wall, blood coagulation, and the platelet-endothelial cell interaction. Platelet-derived growth factors and other macrophage-derived factors may play important roles in the pathogenesis of the early proliferative lesions found in the small pulmonary arterioles. Other vascular-derived mediators may be important determinants in modulating the vasoconstrictor or vasodilator response in small vessels. A recent brief but pertinent review has highlighted some of the new directions being taken. It appears that the right questions are finally being asked, and we now may have the tools to answer them.

Detection of intrapericardial hematoma after open heart surgery: the roles of echocardiography and computed tomography.

Two patients who had right atrial compression caused by intrapericardial hematomas after coronary artery bypass grafting and aortic valve replacement are described. During the course of postoperative evaluation, each patient underwent an echocardiographic examination followed by computed tomography of the chest. Two-dimensional echocardiography visualized the hematomas in both cases. Computed tomography played a useful adjunctive role by further clarifying their nature, location and extent.

Sensitivity of two-dimensional echocardiography in the direct visualization of atrial septal defect utilizing the subcostal approach: experience with 154 patients.

In the standard precordial echocardiographic imaging planes, there is frequent dropout of atrial septal echoes in the region of the fossa ovalis that can be minimized by use of the subcostal imaging approach. The diagnostic sensitivity of this approach was reviewed in 154 patients (mean age 31 years, range 2 months to 74 years) with documented atrial septal defect in whom a satisfactory image of the atrial septum could be obtained. Subcostal two-dimensional echocardiography successfully visualized 93 (89%) of the 105 ostium secundum atrial septal defects, all 32 (100%) ostium primum defects and 7 (44%) of the 16 sinus venosus defects. A defect was not visualized (false negative response) in 12 patients (11%) with an ostium secundum defect and in 9 patients (56%) with a sinus venosus defect. In three of the former and five of the latter, a two-dimensional echocardiographic contrast examination established the presence of the interatrial shunt. Twenty-four patients (16%) with clinical findings of uncomplicated atrial septal defect confirmed by two-dimensional echocardiography underwent surgical repair of the defect without preoperative cardiac catheterization. There were no perioperative complications. Two-dimensional echocardiographic examination of the atrial septum utilizing the subcostal approach is the preferred method for the confident, noninvasive diagnosis and categorization of atrial septal defects. Two-dimensional echocardiographic contrast and Doppler examinations complement the technique and enhance diagnostic accuracy.

Pulmonary hypertension in polymyositis.

Pulmonary hypertension is an uncommon but lethal complication of polymyositis. A 69-year-old woman is described who had a 20-month history of polymyositis and cardiac failure and in whom severe pulmonary hypertension was noted terminally when she was first seen at our clinic. She died within 24 hours of admission, and autopsy revealed severe plexogenic pulmonary vascular disease.

Cardiac involvement in polymyositis: a clinicopathologic study of 20 autopsied patients.

Cardiac involvement in polymyositis was investigated in 20 autopsied cases. Clinically, 13 of 18 patients had abnormal electrocardiograms, and 9 of the 20 patients had previous evidence of congestive heart failure. Histologically documented myocarditis was detected in 6 patients (4 with congestive heart failure and 2 without), 4 of whom also had small vessel disease of the myocardium. Patients with polymyositis may have a cardiopathy in the absence of overt myocardial inflammatory disease.

Multiple-gated acquisition cardiac blood-pool isotope imaging. Evaluation of left ventricular function correlated with contrast angiography.

Thirty-one patients were assessed by the multiple-gated acquisition cardiac blood-pool isotope-imaging technique using radiolabeled albumin within 24 hours of biplane contrast ventriculography. Data from the imaging method were analyzed by a semiautomatic technique with computer-generated edge detection and background subtraction. An excellent correlation was observed between ejection fractions determined with multiple-gated isotope imaging and those obtained by biplane contrast ventriculography (r = 0.93), and the same was true for average ejection rates (r = 0.80). For assessment of wall motion with this imaging technique, the anterior and the left anterior oblique left ventricular views were divided into nine segments, and a score was assigned to each segment based on the degree of wall motion. The cumulative anterior and left anterior oblique scores correlated well with the score from biplane contrast ventriculography (r = 0.90), and in 94% of segments in the left anterior oblique projection the assessment with multiple-gated isotope imaging was the same as or varied by only one class from the assessment by biplane contrast ventriculography. The multiple-gated acquisition cardiac blood-pool isotope-imaging technique is thus a valuable noninvasive method for assessing left ventricular function as measured by ejection fraction, ejection rates, and wall motion.

Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm.

The objects of these experiments were to determine to what extent oleic acid, removed from plasma by forearm muscles, was oxidized immediately, and to search for evidence of an intramuscular lipid pool which may be composed to triglycerides synthesized from plasma free fatty acids and which may supply substantial portions of lipid substrates for oxidation by muscle. To these ends (1-14C]oleic acid was infused at constant rate into the brachial artery of seven healthy young men at rest in the postabsorptive state. Results were: (1) muscle respiratory quotient (0.76) implied that about 80% of the oxygen consumed was for the oxidation of lipid. (2) Muscle free fatty acid uptake, had it been oxidized directly, could account for more than 100% of observed oxygen uptake. (3) There was a lag of at least 30 min before 14CO2 appeared in forearm venous blood. (4) 14CO2 release from forearm muscle tended to reach an apparent plateau after 3 h of infusion of [14C]oleic acid. (5) During the time of plateau 14CO2 release, oleic acid extracted from plasma could account for only 20% of oxygen consumption; most of the oleic acid taken up was not oxidized directly. (6) 14CO2 release persisted at a high level during the 1-3 h follow-up period after the infusion ended. (7) Neither the delay in initial appearance of 14CO2 nor its continued release after cessation of infusion was due to delay and distribution in a forearm CO2 pool, since intra-arterial infusion of NaH14CO3 in additional subjects demonstrated much more rapid distribution of 14CO2 in the forearm. Results show that most, if not all, free fatty acids taken up by resting muscle are not oxidized directly, but probably enter an intramuscular pool which has a slow turnover during resting metabolism and is the immediate source of oxidized lipid substrate.

Free fatty acid metabolism in the forearm at rest: muscle uptake and adipose tissue release of free fatty acids.

Free fatty acid (FFA) metabolism in forearm skeletal muscle at rest was studied during continuous intrabrachial arterial ininfusion of [1-14C] oleic acid in 14 normal subjects in the postabsorptive state. Total oleic acid uptake by muscle accounted for at least 65% and perhaps as much as 86% of the measured O2 consumption. The respiratory quotient (0.74) indicated predominant oxidation of lipid. Glucose was a minor substrate for oxidation. Concentrations of six individual free fatty acids were measured in arterial (A), deep venous (DV), and superficial venous (SV) plasma in 25 subjects. There were positive A-DV differences, reflecting net muscle uptake, for each FFA. The extraction ratio (A-DV)/A was greatest for oleic acid. Output of each free fatty acid from subcutaneous adipose tissue was proportional to its arterial concentration, except for stearic acid. There was no stearic acid output. Correction of (A-DV)/A to account for contribution of perimuscular adipose tissue to FFA in DV led to the conclusion that oleic acid was preferentially extracted from arterial blood by forearm muscle. It accounted for 51% of the total FFA uptake, although it comprised only 43% of total FFA in arterial plasma. Total FFA uptake by muscle was more than sufficient to account for all of the measured O2 consumption, suggesting that some of the extracted FFA may be stored in muscle for oxidation at a latter time.

Atrial septal defect: echocardiographic observations. Studies in 120 patients.

Previous studies on small numbers of patients have indicated a high incidence of increased right ventricular dimension and abnormal ventricular septal motion in patients with atrial septal defect. However, recent evidence suggests that septal motion may be normal in as many as 46% of patients with atrial septal defect when observed at proper levels. We have analyzed the echocardiograms of 120 patients with sinus venosus or secundum atrial septal defect in an attempt to define sensitivity of the foregoing two echocardiographic abnormalities. Right ventricular dimension index was increased in 98% of patients. When both sides of the ventricular septum were analyzed, abnormal ventricular septal motion was observed in 87% of patients. It is important to observe both right and left septal echoes at all levels. Other measurements and observations were made when possible and are included in the study.

Effects of brief starvation on muscle amino acid metabolism in nonobese man.

A reduction in the release of substrate amino acids from skeletal muscle largely explains the decrease in gluconeogenesis characterizing prolonged starvation. Brief starvation is associated with an increase in gluconeogenesis, suggesting increased release of amino acids from muscle. In the present studies, accelerated amino acid release from skeletal muscle induced by brief starvation was sought to account for the accompanying augmentation of gluconeogenesis. To do this amino acid balance across forearm muscles was quantified in 15 postabsorptive (overnight fasted) subjects and in 7 subjects fasted for 60 h. Fasting significantly reduced basal insulin (11.3-7.5 muU/ml) and increased glucagon (116-134 pg/ml). Muscle release of the principal glycogenic amino acids increased. Alanine release increased 59.4%. The increase in release for all amino acids averaged 69.4% and was statistically significant for threonine, serine, glycine, alanine, alpha-aminobutyrate, methionine, tyrosine, and lysine. Thus, with brief starvation, muscle release of glycogenic amino acids increases strikingly. This contrasts with the reduction of amino acid release characterizing prolonged starvation. The adaptation of peripheral tissue metabolism to brief starvation is best explained by the decrease in insulin.