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PubMedDate not supplied

Acute stress disorder after burn injury: a predictor of posttraumatic stress disorder?

OBJECTIVES: The principal goals of this study were to determine whether ASD predicted chronic PTSD and whether dissociation is more characteristic of the acute-trauma period than PTSD symptoms. METHODS: Eighty-three hospitalized adult burn patients were assessed with structured interviews and self-report measures within 2 weeks of injury and again at least 6 months postburn. RESULTS: Nineteen percent had ASD. Dissociative symptoms were not more common or more severe than PTSD symptoms. Thirty-six percent had chronic PTSD. While ASD predicted chronic PTSD, meeting the symptom criteria for PTSD within 2 weeks postburn also predicted chronic PTSD. CONCLUSIONS: Our data support the inclusion of an ASD diagnosis in the DSM, which would allow the diagnosis of symptoms in the first month posttrauma as a psychiatric disorder but questions whether dissociation is more characteristic of the acute trauma period than the PTSD symptom clusters.

Adult↗
PubMed2005

Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.

Children with autistic spectrum disorders (ASDs) tend to suffer from severe gastrointestinal problems. Such symptoms may be due to a disruption of the indigenous gut flora promoting the overgrowth of potentially pathogenic micro-organisms. The faecal flora of patients with ASDs was studied and compared with those of two control groups (healthy siblings and unrelated healthy children). Faecal bacterial populations were assessed through the use of a culture-independent technique, fluorescence in situ hybridization, using oligonucleotide probes targeting predominant components of the gut flora. The faecal flora of ASD patients contained a higher incidence of the Clostridium histolyticum group (Clostridium clusters I and II) of bacteria than that of healthy children. However, the non-autistic sibling group had an intermediate level of the C. histolyticum group, which was not significantly different from either of the other subject groups. Members of the C. histolyticum group are recognized toxin-producers and may contribute towards gut dysfunction, with their metabolic products also exerting systemic effects. Strategies to reduce clostridial population levels harboured by ASD patients or to improve their gut microflora profile through dietary modulation may help to alleviate gut disorders common in such patients.

Autistic Disorder↗
PubMed2023

Rare variation in noncoding regions with evolutionary signatures contributes to autism spectrum disorder risk.

Little is known about the role of noncoding regions in the etiology of autism spectrum disorder (ASD). We examined three classes of noncoding regions: Human Accelerated Regions (HARs), which show signatures of positive selection in humans; experimentally validated neural Vista Enhancers (VEs); and conserved regions predicted to act as neural enhancers (CNEs). Targeted and whole genome analysis of >16,600 samples and >4900 ASD probands revealed that likely recessive, rare, inherited variants in HARs, VEs, and CNEs substantially contribute to ASD risk in probands whose parents share ancestry, which enriches for recessive contributions, but modestly, if at all, in simplex family structures. We identified multiple patient variants in HARs near IL1RAPL1 and in a VE near SIM1 and showed that they change enhancer activity. Our results implicate both human-evolved and evolutionarily conserved noncoding regions in ASD risk and suggest potential mechanisms of how changes in regulatory regions can modulate social behavior.

Human Accelerated Regions↗
PubMed2024

De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.

Three-dimensional genome organization plays a critical role in gene regulation, and disruptions can lead to developmental disorders by altering the contact between genes and their distal regulatory elements. Structural variants (SVs) can disturb local genome organization, such as the merging of topologically associating domains upon boundary deletion. Testing large numbers of SVs experimentally for their effects on chromatin structure and gene expression is time and cost prohibitive. To address this, we propose a computational approach to predict SV impacts on genome folding, which can help prioritize causal hypotheses for functional testing. We developed a weighted scoring method that measures chromatin contact changes specifically affecting regions of interest, such as regulatory elements or promoters, and implemented it in the SuPreMo-Akita software (Gjoni and Pollard 2024). With this tool, we ranked hundreds of de novo SVs (dnSVs) from autism spectrum disorder (ASD) individuals and their unaffected siblings based on predicted disruptions to nearby neuronal regulatory interactions. This revealed that putative cis-regulatory element interactions (CREints) are more disrupted by dnSVs from ASD probands versus unaffected siblings. We prioritized candidate variants that disrupt ASD CREints and validated our top-ranked locus using isogenic excitatory neurons with and without the dnSV, confirming accurate predictions of disrupted chromatin contacts. This study establishes disrupted genome folding as a potential genetic mechanism in ASD and provides a general strategy for prioritizing variants predicted to disrupt regulatory interactions across tissues.

Journal Article↗
PubMed2026

De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.

Three-dimensional genome organization plays a critical role in gene regulation, and disruptions can lead to developmental disorders by altering the contact between genes and their distal regulatory elements. Structural variants (SVs) can disturb local genome organization, such as the merging of topologically associating domains upon boundary deletion. Testing large numbers of SVs experimentally for their effects on chromatin structure and gene expression is time and cost prohibitive. To address this, we propose a computational approach to predict SV impacts on genome folding, which can help prioritize causal hypotheses for functional testing. We develop a weighted scoring method that measures chromatin contact changes specifically affecting regions of interest, such as regulatory elements or promoters, and implement it in the SuPreMo-Akita software. With this tool, we rank hundreds of de novo SVs (dnSVs) from autism spectrum disorder (ASD) individuals and their unaffected siblings based on predicted disruptions to nearby neuronal regulatory interactions. This reveals that putative cis-regulatory element interactions (CREints) are more disrupted by dnSVs from ASD probands versus unaffected siblings. We prioritize candidate variants that disrupt ASD CREints and validate our top-ranked locus using isogenic excitatory neurons with and without the dnSV, confirming accurate predictions of disrupted chromatin contacts. This study suggests that disrupted genome folding is a potential genetic mechanism in a subset of ASD cases and provides a general strategy for prioritizing variants predicted to disrupt regulatory interactions across tissues.

Humans↗
PubMed2000

A brain-controlled switch for asynchronous control applications.

Asynchronous control applications are an important class of application that has not received much attention from the brain-computer interface (BCI) community. This work provides a design for an asynchronous BCI switch and performs the first extensive evaluation of an asynchronous device in attentive, spontaneous electroencephalographic (EEG). The switch design [named the low-frequency asynchronous switch design (LF-ASD)] is based on a new feature set related to imaginary movements in the 1-4 Hz frequency range. This new feature set was identified from a unique analysis of EEG using a bi-scale wavelet. Offline evaluations of a prototype switch demonstrated hit (true positive) rates in the range of 38%-81% with corresponding false positive rates in the range of 0.3%-11.6%. The performance of the LF-ASD was contrasted with two other ASDs: one based on mu-power features and another based on the outlier processing method (OPM) algorithm. The minimum mean error rates for the LF-ASD were shown to be significantly lower than either of these other two switch designs.

Adult↗
PubMed2004

Diversion of the inferior vena cava following repair of atrial septal defect causing hypoxemia.

Atrial septal defects (ASDs) are a common congenital abnormality, and operative repair is a routine, safe procedure. Diversion of the inferior vena cava (IVC) into the left atrium is an unusual complication following ASD closure. We report a case that illustrates the problem created by this right-to-left shunt. A middle-aged woman underwent ASD repair. She developed hypoxemia postoperatively. A transthoracic echocardiogram confirmed a right-to-left shunt, found only with agitated saline injected into the femoral vein, not into the basilic vein. Surgical reexploration revealed a residual ASD diverting IVC flow into the left atrium, which was repaired with a pericardial patch. Echocardiography with agitated saline injected from the femoral vein is an easy method to diagnose this uncommon complication.

Adult↗
PubMed1978

Auricular tyrosine hydroxylase and dopamine-beta-hydroxylase activities and noradrenaline content in ischaemic heart disease.

Assessments were made of the tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities as well as the noradrenaline (NA) content of samples excised from right auricular tissue during cardiac surgery on a total of 55 patients with ischaemic heart disease (IHD), valvular heart disease (VHD), uncomplicated atrial septal defect (ASD) or congestive heart failure (CHF). The NA content was significantly higher in the IHD group than in the other three groups. The TH activity was highest in the IHD group although the difference was statistically significant only compared with the ASD and CHF groups. The DBH activity was also highest in the IHD group, but again the difference was statistically significant only compared with the ASD and CHF groups. In the whole material there was a significant positive correlation between the NA content and TH or DBH activity, as well as between TH and DBH activity. In the IHD group there was a significant positive correlation between heart volume and TH activity. The results suggest that at least compared with ASD and CHF, the sympathetic tone is relatively high in IHD, possibly involving an enhanced NA turnover.

Adult↗
PubMed2006

Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study.

BACKGROUND: In the recent past, psychiatrists and paediatricians have avoided prescribing stimulant medication, such as methylphenidate and dexamphetamine to patients with autism spectrum disorders (ASD) because of both doubts about efficacy and concern that these medications make stereotypies worse. Recently, a number of small trials have suggested that methyphenidate does have a role in the management of hyperactivity in children with autistic spectrum disorders. METHODS: Children with ASD and attention deficit hyperactivity disorder (ADHD), and children with ADHD without ASD received standard treatment with methyphenidate from one specialist centre. A combination of standardized and novel outcome tools was used to allow both an exploratory retrospective study of 174 children and then a prospective study of a further 52 children to be carried out. RESULTS: After treatment with stimulants, the subjects in both groups showed statistically significant improvements in target symptoms of 'hyperactivity', 'impulsivity', 'inattention', 'oppositionality', 'aggression' and 'intermittent explosive rage'. The Clinical Global Impression-Improvement and efficacy index measures also improved in each group. In both the retrospective and the prospective studies, there was no statistically significant difference in the degree of improvements between each group. Importantly, neither tics nor repetitive behaviours worsened in either group. Children in the 'ADHD-only' group who were prescribed stimulants experienced significant 'nausea', 'giddiness', 'headaches' and 'sleep difficulties', whereas sleep difficulties were the only side effect that emerged in children in the ASD with ADHD group. CONCLUSIONS: Both studies presented here support previous findings from smaller studies that show children with autism and ADHD can respond as well to stimulants as children with ADHD alone. Although randomized controlled trials remain the gold standard for efficacy studies, systems like this that allow clinicians to continue rigorous and consistent monitoring for many years have a valuable role to play. Furthermore, such monitoring systems which now exist electronically can easily accumulate large data sets and reveal details about long-term effectiveness and long-term side effects of medication that are unlikely to be discovered in short-term trials.

Adolescent↗
PubMed1990

Congenital cardiovascular malformations (CCVM) and structural chromosome abnormalities: a report of 9 cases and literature review.

Nine cases of congenital cardiovascular malformations (CCVM) with associated unbalanced structural chromosomal abnormalities were ascertained in a population-based study of heart defects, constituting 0.4% of the 2,103 cases of CCVM in the Baltimore-Washington Infant Study (BWIS). This represents a four-fold increase over the general population rate. In an effort to determine possible phenotype/karyotype correlations, the literature was searched for cases with similar karyotypic abnormalities. This comparison of 223 literature cases of karyotypic abnormalities with nine similar cases ascertained by heart malformation has provided the opportunity to review cardiac defects reported in cases of structural abnormalities of chromosomes 1, 3, 7, 8, 9, 10, 11, 15, and 18. The most common cardiac malformation present in the chromosomal cases was ventricular septal defect (VSD) (39%); similarly VSD is the most common CCVM among children with heart defects, although it is the primary defect in only 20% of the BWIS cases. Among all heart defects in the BWIS, atrial septal defect (ASD) represents 5.5% of all cases, but in cases of 8p duplication, ASD is present in 41%. In addition, 40% of cases of 9p duplication had an ASD. Similarly, 35% of cases of 11q duplication had an ASD. While the suggestion of specific karyotype/phenotype association is premature, information on additional cases might clarify the possibility that genetic determinants related to septum formation may reside on chromosome 8, 9, and/or 11. The variety of chromosomal abnormalities in cases with ventricular septal defect indicates one type of genetic heterogeneity that may be involved in this very common heart defect.

Case-Control Studies↗
PubMed1989

A new probe for affinity labelling pancreatic cholecystokinin receptor with minor modification of its structure.

Biochemical studies on receptors for peptides are most often carried out on affinity-labelled (peptide-receptor) complexes. Necessarily, the assumption is made that a covalent (peptide-receptor) complex behaves as the native receptor. The validity of this assumption is dependent on both the affinity-labelling technique and the resolution of the analytical method used for biochemical characterization. We designed a new affinity-labelling probe in order to minimize structural modifications occurring within the affinity-labelled cholecystokinin (CCK) receptor protein. The probe was 125I-labelled 2-(p-azidosalicylamido)-1,3-dithiopropionate-[Thr28,Ahx31 ]CCK-25-33, (125I-ASD-[Thr28,Ahx31]CCK-25-33), the peptide moiety of which was released from its binding site by reduction. It was obtained by coupling a photoactivable chemical to [Thr28,Ahx31]CCK-25-33 via its N-terminus. The resulting peptide was HPLC purified and radioiodinated in the presence of chloramine T. Binding of 125I-ASD-[Thr28,Ahx31]CCK-25-33 was time- and temperature-dependent and reversible. At 25 degrees C, a steady-state level was reached after 60 min and half-maximal dissociation after 38 min. Binding was inhibited by [Thr28,Ahx31]CCK-25-33 and L-364-718 antagonist with IC50 0.4 nM and 0.9 nM, respectively. Photoaffinity labelling of pancreatic plasma membranes by 125I-ASD-[Thr28,Ahx31]CCK-25-33 identified a glycoprotein of Mr 85,000-100,000 which was retained on immobilized wheat germ agglutinin. Enzyme cleavage by endoproteinase Glu-C generated a main fragment of Mr 30,000-34,000. The same glycoprotein was photoaffinity labelled with 125I-DTyr-Gly-[Ahx28,31,pNO2Phe33]CCK-26-33 (Ahx, 2-aminohexanoic acid; pNO2Phe,p-nitrophenylalanine) an intrinsic probe having its photolabile group sited in the binding domain of cholecystokinin. 125I-ASD-[Thr28,Ahx31]CCK-25-33 is a potentially powerful tool for biologically and biochemically studying cholecystokinin receptors.

Affinity Labels↗
PubMed1994

Photolabeling of soybean microsomal membrane proteins with photoreactive acyl-CoA analogs.

Synthesis of 32P-labeled 12-azidooleoyl-CoA and 125I-labeled 12-[(azidosalicyl)amino]dodecanoyl-CoA (ASD-CoA) was achieved. The synthesized radioactive, photoreactive reagents were tested as photoaffinity labels for acyl-CoA:lysophosphatidylcholine acyltransferase from the microsomal membranes of developing soybean cotyledons. When a mixture of microsomal membranes and the azidooleoyl-CoA or ASD-CoA were incubated in the dark, the analogs were recognized as substrate and competitive inhibitor, respectively. The enzyme preferentially utilizes unsaturated acyl-CoAs rather than saturated acyl-CoAs. Incubation of microsomal membranes with acyl-CoA analogs and immediately followed by photolysis resulted in an irreversible inhibition of lysophosphatidylcholine acyltransferase activity. Analysis of photolyzed microsomal membranes by SDS/PAGE and autoradiography revealed that azidooleoyl-CoA preferentially labeled eight acyl-CoA binding proteins, but ASD-CoA labeled only three polypeptides with molecular masses of 110, 90 and 32 kDa that are commonly labeled by both the analogs. Oleoyl-CoA and dodecanoyl-CoA protect the enzyme against photoinactivation by azidooleoyl-CoA and ASD-CoA, respectively. The protection was profound in 110-kDa polypeptide indicating that this protein could be lysophosphatidylcholine acyltransferase. These results demonstrate that the photoaffinity of acyl-CoA analogs makes them potential probes to identify and characterize lipid biosynthetic enzymes.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed2006

Congenital heart diseases in the boxer dog: A retrospective study of 105 cases (1998-2005).

Subaortic stenosis (SAS) is one of the most common congenital heart diseases (CHD) in dogs with Boxers being predominantly affected. However, the increasing availability of modern diagnostic imaging systems now allows a better assessment of cardiac morphology and function, thereby facilitating early detection of CHD in awake animals. In this context, the case records of Boxer dogs diagnosed with CHD using echocardiography combined with Doppler mode, were retrospectively reviewed (1998-2005). One hundred and five Boxers exhibiting either a single CHD (53/105, 50.5%) or association of several CHD (52/105, 49.5%) were included. The most common CHD was atrial septal defect (ASD) observed in 56.2% of these animals (59/105), followed by mitral dysplasia (58/105, 55.2%), and SAS (49/105, 46.7%). SAS was associated with one or two CHD in 29.5% of cases (31/105). Most of the dogs with a low intensity left heart base systolic murmur had an isolated ASD whereas most of the dogs with a similar but high intensity murmur had SAS, either isolated or associated with a concurrent CHD. The incidence of ASD and mitral dysplasia in Boxer dogs is higher than previously assumed, and ASD is a common cause of left heart base systolic murmur in this breed of dog. This confirms that the detection of such a murmur should not be used as the unique criterion for diagnostic confirmation of SAS.

Animals↗
PubMed2004

Childhood autism spectrum disorder in the Barwon region: a community based study.

OBJECTIVE: To establish a community database for children with autism spectrum disorder (ASD) to determine prevalence and identify subgroups based on key intellectual, clinical and family parameters. METHODS: Data were collected for children previously diagnosed with an ASD in the Barwon region using parental interview and review of the child's paediatric and psychological records. Preschool diagnoses were typically made by specialist psychologists and school-age diagnoses made by a multidisciplinary team. RESULTS: One hundred and seventy-seven children in the Barwon region were identified as having ASD (82% response rate). The prevalence of ASD was one per 255 children aged two to 17 years. The prevalence increased 10 fold over a 16-year period and this increase was relatively even across all levels of child intellectual functioning. Forty-two percent of children were intellectually disabled (IQ < 70) and performance IQ was significantly higher than verbal IQ but typical block design-comprehension subtest patterns were not common. Nine sibling pair families were identified, 24% were labelled as having attention deficit hyperactivity disorder (ADHD), 6% had epilepsy, and 18.3% were macrocephalic where data were available. Family difficulty was associated with the degree of obsessions/rituals, frequency and intensity of anger/aggression, and ADHD but overall was not associated with the child's intellectual status. CONCLUSIONS: The relatively rapid increase in prevalence is consistent with overseas studies and suggests significant changes in diagnostic criteria, increasing community awareness and the need for support at all levels of intellectual functioning. Increased occurrence in siblings and relatives gives further evidence for a genetic cause.

Adolescent↗
PubMed1989

Two-dimensional pulsed Doppler echocardiographic technique for estimating pulmonary to systemic blood flow ratio in children with atrial septal defect and patent ductus arteriosus.

A two-dimensional pulsed Doppler echocardiographic method was evaluated for quantifying the pulmonary (Qp) to systemic (Qs) blood flow ratio. Twenty six patients were studied, 15 with atrial septal defect (ASD) and 11 with patent ductus arteriosus (PDA). An apical four-chamber view was used to measure the maximal Doppler flow velocities in the right and left ventricular inflow regions (RVIR and LVIR) and the maximal diameters of the tricuspid and mitral anuli at diastole. The two-dimensional pulsed Doppler pulmonary to systemic blood flow ratio (Qp/Qs) estimation involved calculating the area of the Doppler flow velocity signal along the time scale multiplied by the diameter of either the tricuspid or mitral anulus as measured on the apical four-chamber view. In ASD patients, Qp was measured at RVIR and Qs at LVIR. In PDA patients, Qp was calculated at LVIR and Qs at RVIR. Twenty-six healthy children comprised the control group. The areas of the Doppler flow velocity signals along the time scales of RVIR and LVIR were also quantified and the diameters of the tricuspid and mitral anuli were measured. In the control group, the linear correlation of the trans-mitral M(d)*M(a) to trans-tricuspid T(d)*T(a) value was r = 0.909, n = 26. The correlations between Doppler Qp/Qs ratio estimates and those obtained at cardiac catheterization were r = 0.902, n = 15 in ASD and r = 0.967, n = 11 in PDA. These results suggest a clinical application of this Doppler echocardiographic method in the noninvasive estimation of the cardiac shunt in ASD and PDA.

Blood Flow Velocity↗
PubMed2005

Top-down attentional modulation in autistic spectrum disorders is stimulus-specific.

This study investigated top-down modulation of bottom-up attentional capture in children with autistic spectrum disorders (ASDs) and in a typically developing (TD) comparison group using a spatial-cuing task (Experiment 1) and a series of visual search tasks (Experiment 2) employing task-irrelevant distractors. The effect of color and onset singleton distractors was investigated. The TD group showed similar top-down modulation of color and onset stimuli. The ASD group showed typical top-down modulation of color stimuli, but impaired top-down modulation of onset stimuli. The results suggest that children with ASDs may be impaired at prioritizing dynamic stimuli; this has implications for social processing impairments in ASDs.

Attention↗
PubMed2001

Transcatheter closure of atrial septal defects with the STARFlex device: early results and follow-up.

BACKGROUND: The STARFlex (SF) device is a CardioSEAL (CS) double-umbrella device that has been modified by the addition of a self-centering mechanism comprised of nitinol springs connected between the two umbrellas and a flexible core wire with a pin-pivoting connection. This paper compares the results of atrial septal defect (ASD) closure with CardioSEAL and STARFlex devices. PATIENTS AND METHODS: Between December 1996 and March 2000, 117 patients underwent ASD closure with CardioSEAL (n = 79) and STARFlex (n = 38). The mean age (17 years), weight (49 kg), and ASD size (15 mm) were similar in the two groups. The procedures were performed under general anesthesia with both fluoroscopic and transesophageal echocardiographic monitoring. IMMEDIATE RESULTS: The devices were successfully implanted in all patients. Ten patients had multiple ASDs. A single device was used in four patients (CardioSEAL in three, STARFlex in one), while a simultaneous placement of two CardioSEAL (one patient) or two STARFlex (five patients) were performed in six patients. The results are summarized as follows: [table: see text] Follow-Up Results: On follow-up clinical exam, electrocardiograms, chest X-rays, and echocardiograms were obtained at 1, 6, and 12 months. [table: see text] During follow-up there were no deaths, endocarditis, rhythm disturbances, or other complications. Arm fractures were observed almost exclusively with large CardioSEAL devices (40 mm, less frequently with 33 mm), and only in one 33-mm STARFlex device. There were no clinical complications related to fractures. CONCLUSIONS: The STARFlex device seems to offer better results than the CardioSEAL, with significantly lower rates of residual shunts and arm fractures.

Adolescent↗
PubMed2001

Catheter closure of atrial septal defects and patent foramen ovale in patients with an atrial septal aneurysm using different devices.

BACKGROUND: Atrial septal aneurysm is frequently associated with patent foramen ovale (PFO) and atrial septal defects (ASD). Moreover, a relationship between atrial septal aneurysm and embolic cerebrovascular events has been suggested. The aims of this study were to analyze morphological and functional characteristics of atrial septal aneurysm in PFO and ASD patients and to assess the feasibility and efficacy of different devices for transcatheter closure and the influence of atrial septal aneurysm. METHODS: Between March 1997 and May 2000 transcatheter ASD or PFO closure was attempted in 63 patients (mean age 47 +/- 13 years) with an atrial septal aneurysm using one of the following devices: Angelwings (n = 3), Cardioseal (n = 5), Cardioseal-Starflex (n = 7), Amplatzer (n = 11), Amplatzer-PFO (n = 5), PFO-Star (n = 25), or Helex (n = 7). RESULTS: Implantation was primarily successful (after the first or second attempt) in all patients. One PFO-Star device embolized 12 hours after the procedure. During follow-up (0.6-37 months, mean 10.4 +/- 9.2) a residual shunt could be detected by transesophageal echocardiography after 2 weeks in four patients and after 6 months in one patient. Three PFO patients had cerebrovascular events after implantation. Two patients had a transient ischemic attack (TIA) and one patient a stroke. A thrombus formation on the device detected in three patients disappeared after antithrombotic therapy. CONCLUSION: We conclude that ASDs and PFOs with an associated atrial septal aneurysm can be closed with different available devices. There seem to be no additional risks compared with patients without atrial septal aneurysm.

Adult↗