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PubMed2005

Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention.

OBJECTIVE: Our previous study indicated an association between cellular immune reactivity to common dietary proteins (DPs) and excessive proinflammatory cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant of innate immunity in the gut mucosa, in a subset of autism spectrum disorder (ASD) children. However, it is unclear whether such abnormal LPS responses are intrinsic in these ASD children or the results of chronic gastrointestinal (GI) inflammation secondary to immune reactivity to DPs. This study further explored possible dysregulated production of proinflammatory and counter-regulatory cytokines with LPS in ASD children and its relationship to GI symptoms and the effects of dietary intervention measures. METHODS: This study includes ASD children (median age 4.8 years) on the unrestricted (n = 100) or elimination (n = 77) diet appropriate with their immune reactivity. Controls include children with non-allergic food hypersensitivity (NFH; median age 2.9 years) on the unrestricted (n = 14) or elimination (n = 16) diet, and typically developing children (median age 4.5 years, n = 13). The innate immune responses were assessed by measuring production of proinflammatory (TNF-alpha, IL-1beta, IL-6, and IL-12) and counter-regulatory (IL-1ra, IL-10, and sTNFRII) cytokines by peripheral blood mononuclear cells (PBMCs) with LPS. The results were also compared to T-cell responses with common DPs and control T-cell mitogens assessed by measuring T-cell cytokine production. RESULTS: ASD and NFH PBMCs produced higher levels of TNF-alpha with LPS than controls regardless of dietary interventions. However, only in PBMCs from ASD children with positive gastrointestinal (GI(+)) symptoms, did we find a positive association between TNF-alpha levels produced with LPS and those with cow's milk protein (CMP) and its major components regardless of dietary interventions. In the unrestricted diet group, GI(+) ASD PBMCs produced higher IL-12 than controls and less IL-10 than GI(-) ASD PBMCs with LPS. GI(+) ASD but not GI(-) ASD or NFH PBMCs produced less counter-regulatory cytokines with LPS in the unrestricted diet group than in the elimination diet group. There was no significant difference among the study groups with regard to cytokine production in responses to T-cell mitogens and other recall antigens. CONCLUSION: Our results revealed that there are findings limited to GI(+) ASD PBMCs in both the unrestricted and elimination diet groups. Thus our findings indicate intrinsic defects of innate immune responses in GI(+) ASD children but not in NFH or GI(-) ASD children, suggesting a possible link between GI and behavioral symptoms mediated by innate immune abnormalities.

Autistic Disorder↗

PubMed1983

[Evaluation of left ventricular function in patients with atrial septal defect by exercise echocardiography].

In order to evaluate left ventricular function in atrial septal defect (ASD), 12 cases with ASD, 18 postoperative cases of ASD and 27 normal controls were examined by means of exercise echocardiography using supine bicycle ergometer (50 watts and 3 min). M-mode echocardiograms and left ventricular (LV) short-axis views by two-dimensional echocardiography were subjected to the observation. M-mode echocardiographic studies: ASD group showed an increased stroke dimension (SD) during exercise mainly due to a marked increase of left ventricular end-diastolic dimension ( LVDd ) and a slight decrease of left ventricular end-systolic dimension ( LVDs ). Postoperative ASD group showed an increased SD during exercise mainly due to a marked decrease of LVDs and a slight decrease of LVDd . On the other hand, in normal control group exercise increased SD only by a significant decrease of LVDs . Right ventricular dimension was decreased during exercise in ASD group, but did not change significantly in postoperative ASD and normal control groups. During exercise in ASD group, peak velocity of circumferential fiber shortening (VCF) was increased most markedly, and negative peak VCF was decreased most strikingly. Eight of 12 patients with ASD who showed abnormal interventricular septal motion demonstrated remarkable improvement of the motion during exercise. Two-dimensional echocardiographic studies: Left ventricular short-axis views demonstrated that the shape of the left ventricular cavity changed from flattened to more circular configuration during exercise at end- and early-diastole in ASD group. The shape of the left ventricular cavity at late-systole did not change significantly during exercise in this group. In postoperative ASD group, the left ventricular short-axis view demonstrated circular configuration of the left ventricle at end-diastole both in rest and during exercise. The shape of the left ventricular cavity did not change by exercise. It was concluded that in ASD group cardiac output is increased during exercise by decreasing a left to right shunt at the atrial level and increasing left ventricular filling rate. Therefore, the left ventricular function was found to be good in ASD.

Adolescent↗

PubMed2005

Left ventricular conditioning in the elderly patient to prevent congestive heart failure after transcatheter closure of atrial septal defect.

Transcatheter closure of atrial septal defects (ASDs) is a safe and effective treatment. Over the past years, an increasing number of elderly patients (age > 60 years) have been admitted for transcatheter closure to prevent ongoing congestive heart failure from volume overload. However, recent data point to the risk of serious acute left ventricular dysfunction leading to pulmonary edema immediately after surgical or transcatheter ASD closure in some patients. In this study, we used a technique described before to recognize in advance patients at risk of left heart failure after ASD closure. Those patients at risk were then treated with preventive conditioning medication for 48-72 hr before definitive transcatheter ASD closure was performed. Fifty-nine patients aged over 60 years (range, 60-81.8 years; median, 68 years) were admitted to our institution for transcatheter closure of an atrial septal defect. All patients received evaluation of atrial pressures before and during temporary balloon occlusion of the ASD. Patients with left ventricular restriction due to increased mean atrial pressures (> 10 mm Hg) during ASD occlusion received anticongestive conditioning medication with i.v. dopamine, milrinone, and furosemide for 48-72 hr before definitive ASD closure with an Amplatzer septal occluder was performed. In 44 patients without any signs of left ventricular restriction, ASD closure was performed within the first session. Fifteen (25%) out of 59 patients showed left ventricular restriction. In the majority of patients with LV restriction, the mean left atrial pressures with occluded ASD were significantly decreased after 48-72 hr of conditioning medication. Definitive ASD closure was then performed in a second session. Only two patients received a fenestrated 32 mm Amplatzer occluder due to persistent increased atrial pressures > 10 mm Hg even after conditioning medication. There were no significant differences in shunt, device size, or defect size between the two groups. Balloon occlusion of atrial septal defects identifies patients with left ventricular restrictive physiology before ASD closure. Intravenous anticongestive conditioning medication seems to be highly effective in preventing congestive heart failure after interventional closure of an ASD in the elderly patient with a restrictive left ventricle.

Aged↗

PubMed1987

Usefulness of anatomic parameters derived from two-dimensional echocardiography for estimating magnitude of left to right shunt in patients with atrial septal defect.

The ability of two-dimensional echocardiography (2DE) to quantitate the atrial septal defect size and left-to-right shunt magnitude was examined in 75 adult patients with simple ostium secundum atrial septal defect (ASD) with left-to-right shunts of 19-92% of systemic flow as determined by oximetry. The ASD was visualized in 71 of 75 (95%) patients utilizing subcostal 2DE, and the end-systolic atrial septal defect diameters in subcostal 2DE (ASDe) were measured. The maximal diameters of ASD measured during operation (ASDop) were obtained in 45 of these patients, who then underwent surgical ASD repair. The correlation between ASDe and ASDop was high (r = 0.91, p less than 0.001), indicating accuracy of quantitating defect size via subcostal 2DE approach. However, the correlation between the left-to-right shunt magnitude and ASDe was only fair (r = 0.76, p less than 0.01). In large ASDe the shunts varied greatly, while in small ASDe the shunts increased proportionally with increasing sizes of ASD. In addition, the ratio of left-to-right ventricular diameter (RVD/LVD) was determined. The RVD/LVD correlated relatively well with the shunt magnitudes (r = 0.83, p less than 0.001). Using the two new echocardiographic parameters of ASDe and RVD/LVD, a high percentage (85%) of patients with a large left-to-right shunt requiring surgical closure can be identified. All 43 patients with ASDe greater than 2.0 cm and RVD/LVD greater than 1.1 had a left-to-right shunt greater than 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Measurement of atrial septal defect size: a comparative study between three-dimensional transesophageal echocardiography and the standard balloon sizing methods.

Atrial septal defect (ASD) size measurement is of paramount importance for the successful deployment of a transcatheter septal occluder. The stretched balloon diameter (SBD) has long been regarded as the gold standard for selection of the size of any device. Three-dimensional (3-D) transesophageal echocardiography (TEE) can visualize the overall structure of the atrial septum, therefore rendering an accurate size of the ASD. In this study we aimed to validate the accuracy of ASD size measurement by 3-D TEE and to elucidate the reason for the difference between balloon sizing and 3-D measurement. Forty-one consecutive patients were enrolled in this protocol for ASD device closure using the Amplatzer septal occluder. Thirty-nine patients were diagnosed by 2-D transthoracic echocardiography as secundum ASD and 2 patients were diagnosed as patent foramen ovale. Two measurements of the balloon size were sequentially obtained by 2-D TEE after the balloon was fully inflated in the left atrium. First, no residual shunt across the septum could be seen while the balloon was pulled back against the septum. This measurement was called the balloon occlusive diameter (BOD). Second, with balloon deflation, a slight deformity of the balloon was seen just prior to its popping through the septum. This measurement was called the stretched balloon diameter (SBD). Three-dimensional TEE was performed in all patients at the beginning of the procedure before device deployment and within 15 minutes after device release. Three-dimensional TEE provided superior views of the ASDs, showing the spatial relationship between the ASD and the neighboring structures. For maximal ASD size measurement, balloon sizing was larger than 3-D TEE examination, whereas 2-D was smaller than the other two methods. The best correlation was found between 3-D TEE measurements and the BOD (r = 0.98, p < 0.0001). Three-dimensional TEE provides en face view of ASD; thus, it can accurately measure the size of ASD. Three-dimensional TEE measurement of ASD can be used instead of balloon sizing for the selection of transcatheter ASD occluder size.

Adolescent↗

PubMed2004

Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10.

A lymphocytic enterocolitis has been reported in a cohort of children with autistic spectrum disorder (ASD) and gastrointestinal (GI) symptoms. This study tested the hypothesis that dysregulated intestinal mucosal immunity with enhanced pro-inflammatory cytokine production is present in these ASD children. Comparison was made with developmentally normal children with, and without, mucosal inflammation. Duodenal and colonic biopsies were obtained from 21 ASD children, and 65 developmentally normal paediatric controls, of which 38 had signs of histological inflammation. Detection of CD3+ lymphocyte staining for spontaneous intracellular TNFalpha, IL-2, IL-4, IFNgamma, and IL-10, was performed by multicolor flow cytometry. Duodenal and colonic mucosal CD3+ lymphocyte counts were elevated in ASD children compared with noninflamed controls (p<0.03). In the duodenum, the proportion of lamina propria (LP) and epithelial CD3(+)TNFalpha+ cells in ASD children was significantly greater compared with noninflamed controls (p<0.002) but not coeliac disease controls. In addition, LP and epithelial CD3(+)IL-2+ and CD3(+)IFNgamma+, and epithelial CD3(+)IL-4+ cells were more numerous in ASD children than in noninflamed controls (p<0.04). In contrast, CD3(+)IL-10+ cells were fewer in ASD children than in noninflamed controls (p<0.05). In the colon, LP CD3(+)TNFalpha+ and CD3(+)IFNgamma+ were more frequent in ASD children than in noninflamed controls (p<0.01). In contrast with Crohn's disease and non-Crohn's colitis, LP and epithelial CD3(+)IL-10+ cells were fewer in ASD children than in nondisease controls (p<0.01). There was a significantly greater proportion of CD3(+)TNFalpha+ cells in colonic mucosa in those ASD children who had no dietary exclusion compared with those on a gluten and/or casein free diet (p<0.05). There is a consistent profile of CD3+ lymphocyte cytokines in the small and large intestinal mucosa of these ASD children, involving increased pro-inflammatory and decreased regulatory activities. The data provide further evidence of a diffuse mucosal immunopathology in some ASD children and the potential for benefit of dietary and immunomodulatory therapies.

Adolescent↗

PubMed1992

Role of "buttoned" double-disc device in the management of atrial septal defects.

Sixteen patients seen over a 9-month period ending in August 1990 were offered transcatheter closure of their ASD with a custom-made "buttoned" double-disc device. The study was approved by the Institutional Review Board and informed consent was obtained in each case. The device consists of an occluder, a counteroccluder, and a loading wire and is delivered to the ASD site via an 8F sheath. Parents of two children elected surgical closure. In five children the stretched diameter of the ASD was too large (greater than 20 mm) and transcatheter closure was not attempted. These seven children underwent elective surgical closure without incident. In one child the defect measured 5 mm and the Qp:Qs was 1.4:1 and therefore ASD closure was not recommended. In the remaining eight children transcatheter closure was attempted. In two of the children the occluder pulled through the ASD and was successfully retrieved and the children later underwent uneventful elective surgical closure. The device was implanted across the ASD in six children. In one child the device dislodged from the ASD site within minutes after implantation and the child was sent to emergency surgery, where the device was removed and the ASD was closed. In the remaining five patients, aged 7 months to 45 years (weight 3.6 to 50 kg), with a Qp:Qs range of 1.3 to 2.3 and a stretched diameter of 10 to 19 mm, the ASD closure was successful with 25 to 40 mm size devices. Repeat echo-Doppler studies 2 weeks and 3 months after the procedure in all patients and 6 months later in two children did not reveal any residual shunt. It is concluded that (1) the custom-made "buttoned" double-disc device can be implanted across the ASD safely and effectively via an 8F sheath, thus making transcatheter ASD closure feasible even in very young infants; (2) measurement of stretched diameter of the ASD in the catheterization laboratory is a useful guide for selection of an appropriate-sized device; and (3) additional clinical trials are warranted to confirm the efficacy and safety of the device.

Adolescent↗

PubMed2024

The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder.

Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD or ASD diagnosis. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44%-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal half sibling with ASD had increased risk of AN compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk whereas a negative association was found between AN-PGS and ADHD. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and genetic associations between ASD-PGS and AN and between AN-PGS and ADHD were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.

Humans↗

PubMed2002

Ventricular septal flattening at end systole falsely predicts right ventricular hypertension in patients with ostium primum atrial septal defects.

PURPOSE: To assess the reliability of ventricular septal position in predicting elevated right ventricular pressure (RVP) in patients with ostium primum atrial septal defects (ASD 1). METHODS: Echocardiograms of 4 groups were retrospectively analyzed: Patients with ASD 1 and low RVP, patients with ASD 1 and high RVP, and 2 age-matched control groups: one with isolated ostium secundum atrial septal defects (ASD 2), and 1 with normal cardiac findings. End-systolic left ventricular sectional diameters along the midmitral diameter (D1) and a diameter orthogonal to it (D2) were measured off-line by a blinded observer. The ratio D2/D1, the eccentricity index (EI), was calculated; a higher index represents greater septal flattening. RESULTS: The mean EI in the ASD 1 with low RVP group was significantly higher than both the group with ASD 2 and the healthy control group. The mean EI of the ASD 1 group with high RVP was significantly higher than the mean EI of the ASD 1 group with low RVP, although there was a poor correlation between EI and RVP in this group, r = 0.54. CONCLUSION: The ventricular septum is flatter in the ASD 1 patients with low RVP than in an age-matched control group with ASD 2 and compared with an age-matched control group of healthy subjects, giving a false impression of elevated RVP in the ASD 1 group. Although the mean EI is significantly higher in the ASD 1 group with high RVP than in the group with low RVP, there is a poor correlation between EI and RVP, which limits the reliability of this index.

Age Factors↗

PubMed2000

Acute stress disorder symptomatology during hospitalization for pediatric injury.

OBJECTIVE: To examine and identify predictors of acute stress disorder (ASD) and ASD symptomatology (ASDS) in children hospitalized for injuries. METHOD: Fifty-four youths were assessed while hospitalized for injuries. Dependent variables were parent and nurse ratings of children's ASDS. Independent variables included children's prior trauma exposure and behavior problems, injury severity and permanence, brain injury, injury or death to family/friend(s), parental distress, and child reports of the injury/hospitalization experience as meeting criterion A for ASD. RESULTS: A total of 92.6% of children felt the current experience met criterion A, compared with 64.8% of parents. According to parent questionnaires, 4 subjects (7.4%) met DSM-IV criteria for ASD while another 12 (22.2%) had clinically significant but subsyndromal ASDS. Children's ASDS, as reported by parents, correlated highly with parental distress and ratings of children's prior psychopathology, and modestly with injury severity and family/friend(s) injured or killed. Nurses' ratings of children's ASDS correlated strictly with injury- and accident-related variables, and not with parent ratings of children's ASDS. CONCLUSIONS: Children perceive injuries and hospitalizations as stressful. ASDS is widely though divergently reported by parents and nurses in children hospitalized for injury. Parental distress, children's prior psychopathology, and injury-related factors may be useful predictors of children's postinjury ASDS.

Acute Disease↗

PubMed2004

Predicting child PTSD: the relationship between acute stress disorder and PTSD in injured children.

OBJECTIVE: To examine the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in injured children and to evaluate the utility of ASD as a predictor of PTSD. METHOD: Children hospitalized for injuries sustained in a traffic crash were enrolled in a prospective study. ASD was assessed in 243 children within 1 month after injury, and PTSD was assessed in 177 of these children 3 or more months after injury. The relationship between ASD and PTSD was examined via correlations between symptom severity scores and calculation of sensitivity, specificity, and positive and negative predictive values for categorical prediction of PTSD from ASD or subsets of ASD symptoms. RESULTS: Eight percent of children met the symptom criteria for ASD and another 14% had subsyndromal ASD; 6% met the symptom criteria for PTSD and another 11% had subsyndromal PTSD. ASD and PTSD symptom severity were associated. Sensitivity was low for prediction of child PTSD from child ASD. Subsyndromal ASD was a more effective predictor of PTSD. CONCLUSIONS: A substantial minority of injured children are affected by traumatic stress disorders. ASD in children may not be an optimal categorical predictor of PTSD. With increasing attention to early posttrauma services for children, empirically valid assessment/triage models deserve further study.

Accidents, Traffic↗

PubMed2006

Early language and communication development of infants later diagnosed with autism spectrum disorder.

It is well recognized that delayed "first words" is among the most common presenting symptoms of autistic spectrum disorders (ASD). However, data on earlier language and communication development in children with ASD are limited to retrospective reports from parents and from home videos. In this study, we prospectively collected parent report data on early communication and language development in 97 infant siblings of children with ASD and 49 low-risk controls. Parents completed the MacArthur Communicative Development Inventory--Infant Form at 12 and 18 months. Analysis compared 3 groups defined on the basis of diagnostic assessment at 24 months: (1) siblings with ASD (n = 15), (2) siblings not meeting diagnostic criteria for ASD (n = 82), and (3) low-risk controls, none of whom had ASD (n = 49). Children with ASD showed delays in early language and communication compared with non-ASD siblings and controls. At 12 months, the ASD group was reported to understand significantly fewer phrases and to produce fewer gestures. At 18 months, they showed delays in their understanding of phrases, comprehension and production of single words, and use of gestures. Siblings not diagnosed with ASD also used fewer play-related gestures at 18 months than low-risk controls, even when children with identified language delays were excluded. Overall, this prospective study confirms that delays in communication and language development are apparent early in life in children with ASD, and emphasizes that developmental surveillance should include monitoring for delays in gesture, which may be among the earliest signs of ASD.

Autistic Disorder↗

PubMed2005

The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder.

BACKGROUND: Intestinal mucosal pathology, characterized by ileo-colonic lymphoid nodular hyperplasia (LNH) and mild acute and chronic inflammation of the colorectum, small bowel and stomach, has been reported in children with autistic spectrum disorder (ASD). AIM: To assess ileo-colonic LNH in ASD and control children and to test the hypothesis that there is an association between ileo-colonic LNH and ASD in children. PATIENTS AND METHODS: One hundred and forty-eight consecutive children with ASD (median age 6 years; range 2-16; 127 male) with gastrointestinal symptoms were investigated by ileo-colonoscopy. Macroscopic and histological features were scored and compared with 30 developmentally normal (non-inflammatory bowel disease, non-coeliac disease) controls (median age 7 years; range 1-11; 25 male) showing mild non-specific colitis in 16 cases (13 male) and normal colonic histology in 14 cases (12 male). Seventy-four ASD children and 23 controls also underwent upper gastrointestinal endoscopy. The influence on ileal LNH of dietary restriction, age at colonoscopy, and co-existent LNH elsewhere in the intestine, was examined. RESULTS: The prevalence of LNH was significantly greater in ASD children compared with controls in the ileum (129/144 (90%) vs. 8/27 (30%), P < 0.0001) and colon (88/148 (59%) vs. 7/30 (23%), P = 0.0003), whether or not controls had co-existent colonic inflammation. The severity of ileal LNH was significantly greater in ASD children compared with controls, with moderate to severe ileal LNH present in 98 of 144 (68%) ASD children versus 4 of 27 (15%) controls (P < 0.0001). Severe ileal LNH was associated with co-existent colonic LNH in ASD children (P = 0.01). The presence and severity of ileal LNH was not influenced by either diet or age at colonoscopy (P = 0.2). Isolated ileal LNH without evidence of pathology elsewhere in the intestine was a rare event, occurring in less than 3% of children overall. On histopathological examination, hyperplastic lymphoid follicles are significantly more prevalent in the ileum of ASD children (84/138; 61%) compared with controls (2/23; 9%, P = 0.0001). CONCLUSION: Ileo-colonic LNH is a characteristic pathological finding in children with ASD and gastrointestinal symptoms, and is associated with mucosal inflammation. Differences in age at colonoscopy and diet do not account for these changes. The data support the hypothesis that LNH is a significant pathological finding in ASD children.

Adolescent↗

PubMed2005

Role of transthoracic Doppler pulmonary venous flow pattern in large atrial septal defects.

OBJECTIVE: Large uncomplicated atrial septal defect (ASD) alters the pulmonary venous flow (PVF) pattern. We aimed to study the role of transthoracic echocardiography (TTE) in estimating the PVF Doppler abnormalities in ASD. By repeating the study soon after ASD closure, we correlated the hemodynamics of atrial shunting with PVF patterns. METHODS: This study was performed in a tertiary care referral teaching hospital in 2003. The TTE PVF patterns of 34 patients with ASD were studied. TTE study was reported by two blinded investigators independently. Surgical closure of ASD was done on eleven patients and the early postoperative PVF Doppler pattern was also studied with TTE. RESULTS: PVF patterns were adequately recorded in 34 of 38 (90%) subjects with ASD with equal male: female ratio (n = 17 each). The mean age of the study group was 21.4 +/- 8.7 years. ASD ranged from 10 to 38 mm in diameter with a mean of 18 +/- 4.2 mm. Continuous antegrade wave (CAW, mean 68.45 +/- 13.6 cm/s) replaced normally occurring S and D waves in all ASD patients. The atrial reversal wave was reduced or absent (mean 20.18 +/- 3.28 cm/sec). After ASD closure, the CAW was replaced by the S (46.18 +/- 7.5 cm/sec) and D waves (57.72 +/- 9.7 cm/sec) with increase in atrial reversal wave to 27.81 +/- 5.1 cm/sec. CONCLUSIONS: The S and D antegrade waves normally seen in PVF are replaced by a continuous antegrade wave in ASD. Atrial reversal wave is also reduced. PVF waveform becomes normal after ASD closure. TTE PVF Doppler pattern can help estimate ASD hemodynamics.

Adolescent↗

PubMed2005

The functional neuroanatomy of spatial attention in autism spectrum disorder.

This study investigated the functional neuroanatomical correlates of spatial attention impairments in autism spectrum disorders (ASD) using an event-related functional magnetic resonance imaging (FMRI) design. Eight ASD participants and 8 normal comparison (NC) participants were tested with a task that required stimulus discrimination following a spatial cue that preceded target presentation by 100 msec (short interstimulus interval [ISI]) or 800 msec (long ISI). The ASD group showed significant behavioral spatial attention impairment in the short ISI condition. The FMRI results showed a reduction in activity within frontal, parietal, and occipital regions in ASD relative to the NC group, most notably within the inferior parietal lobule. ASD behavioral performance improved in the long ISI condition but was still impaired relative to the NC group. ASD FMRI activity in the long ISI condition suggested that the rudimentary framework of normal attention networks were engaged in ASD including bilateral activation within the frontal, parietal, and occipital lobes. Notable activation increases were observed in the superior parietal lobule and extrastriate cortex. No reliable activation was observed in the posterior cerebellar vermis in ASD participants during either long or short ISI conditions. In addition, no frontal activation during short ISI and severely reduced frontal activation during long ISI was observed in the ASD group. Taken together, these findings suggest a dysfunctional cerebello-frontal spatial attention system in ASD. The pattern of findings suggests that ASD is associated with a profound deficit in automatic spatial attention abilities and abnormal voluntary spatial attention abilities. This article also describes a method for reducing the contribution of physical eye movements to the blood-oxygenation level dependent activity in studies of ASD.

Adolescent↗

PubMed2000

Endocrine responses to chronic androstenedione intake in 30- to 56-year-old men.

In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investigated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n = 28), or placebo (n = 27) for 28 days. Serum ASD, dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplementation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1-4 in ASD (P < 0.05). There was no relationship between age and changes in serum ASD (r2 = 0.024), free testosterone (r2 = 0.00), or estradiol (r2 = 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 = 0.244; P < 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplementation period (P < 0.05). These results suggest that the ingestion of 100 mg ASD, three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations.

Administration, Oral↗

PubMed2005

[Applying interventional treatment for the atrial septal defect in 165 children under five years of age].

OBJECTIVE: To study the clinical technology of transcatheter closure of secundum atrial septal defects (ASD) with Amplatzer device in younger and lower body weight children. METHODS: The transcatheter closure of ASD using Amplatzer septal occluder (ASO) was performed in 165 children under 5 years of age (75 boys and 90 girls) with secundum ASD from Aug 1998 to May 2004. The age of the cases ranged from 2 to 5 (mean 3.7 +/- 1.1) years. The body weight ranged from 9 to 18 (mean 12.6 +/- 2.3) kg. The ratio of pulmonary circulation quantity to the systemic circulation quantity (Qp/Qs) was 3.2 +/- 1.9. All the patients underwent clinical examination, X-ray, electrocardiography (ECG) and echocardiography (Echo) for diagnosis of secundum ASD. The transthoracic echocardiography (TTE) was used to detect and measure the defect of the patients and even trans-esophageal echocardiography (TEE) had to be used when it was necessary. With Echo and X-ray guidance, the measuring balloon was used in the body and outside the body to determine the balloon-stretch diameters of ASD, and proper occluders were selected accordingly for the patients for interventional treatment of ASD. RESULTS: The devices were implanted successfully in 163 (98.8%) cases. One failure occurred in a case in whom the device moved into the left atrium after release, and the other failure was that the position of the device was uncertain because of temporary unavailability of a special transducer for TEE. Surgical operations were performed for these two cases. The stretch diameter of ASD was from (8 - 30) mm, (mean 18.3 +/- 5.1) mm. The size of device was selected according to the stretch diameter of ASD. The diameter of the occluders selected was from (8 - 30), (mean 18.6 +/- 5) mm in this series. The occlusion procedure was monitored by fluoroscopy and TTE and in 5 cases (3%) by TEE. The diameter of right ventricle was improved within 2 days after occlusion from (mean 16.4 +/- 4.9) mm to (mean 12.6 +/- 3.8) mm, (p < 0.01). One hundred and forty seven cases belonged to the simple secundum ASD(89%). Thirteen cases who were complicated with other cardiac deformity were treated successfully with different interventional procedure. Six cases had multiple openings and three of these cases had tumour-like changes of the atrial septum which were closed completely just by one occluder. In only one case small quantity of residual shunt remains. No other severe complication was found in this group. About 100 cases (60%) had large ASD, so the procedure was more difficult in those cases. CONCLUSION: The clinical effectiveness of treatment of ASD in children under 5 years of age with Amplatzer occluders was satisfactory and therefore this therapeutic procedure is feasible for this age group of patients. Nevertheless, we do not recommend to use the technique for infants and children under 2 years of age. Strict selection of indications and proper size of occluder and good cardiologic and surgical settings are among the basic factors for successful interventional occlusion of ASD in young children.

Child, Preschool↗

PubMed1994

[Value of biplane transesophageal echocardiography in congenital abnormalities of the heart atrium and venous-atrial connection].

BACKGROUND: Transesophageal echocardiography with transversal planes offers many advantages in the evaluation of patients with congenital anomalies of atrium, allowing visualization of obscure areas, not visualized with traditional echocardiography, as appendages, venous connections, upper interatrial defects. The aim of this paper is to check what advantages the transesophageal imaging in longitudinal plane, recently insert in biplane probes, might confer over transversal plane imaging in the evaluation of patients with congenital heart disease of atrium and venous connections. METHODS: We carried out a prospective study on 70 patients (49 adults and 22 children) with congenital heart diseases of this area. Fifty-six studies out of 71 were preoperative diagnostic, 15 were carried out in the late postoperative period. Twenty-two studies were performed under general anaesthesia during concomitant cardiac catheterisation, 49 were carried out in outpatient clinic. All the transesophageal diagnoses were subsequently confirmed at either catheterization or surgery. Lesions studied included 36 atrial septal defects (ASD) ostium secundum, 6 interatrial septal aneurysms, 1 ASD coronary sinus, 5 ASD venous sinus, 5 partial and 2 complete atrioventricular septal defects, 1 double outlet right ventricle; in operated patients 2 ASD ostium secundum, 2 ASD sinus venosus, 11 post Mustard or Senning in TGA. RESULTS: Anomalies either better defined or that obtained important additional informations by long axis scanning (vs transverse scanning) included: ASD ostium secundum 36/36, ASD multiple 1/3, caval obstruction in Mustard or Senning 4/5, anterior mitral valve cleft 2/5, left superior vena cava to coronary sinus 3/3. Features visualized by longitudinal plane alone were: ASD coronary sinus 1/1, caval obstruction in sinus venosus operated 1/1, multiple ASD 2/3, coronary artery fistula to right atrium 1/1; for associated features anterior bringing leaflets 2/2, left ventricular outflow tract obstruction 2/2, right ventricular outflow tract obstruction 1/1. Anomalies better characterized by transversal plane versus longitudinal plane were: ASD ostium primum 2/7, ASD sinus venosus sinus 3/5; for associated anomalies VSD inlet 1/1. Features visualized by transversal plane alone were: right upper pulmonary vein in superior vena cava 4/4, right upper pulmonary vein to right atrium 1/1, DIA ostium primum 5/7, ASD sinus venosus 2/5, superior vena cava obstruction in Mustard 1/5, left juxtaposition of the atrial appendages 1/1. The transversal plane alone provided the correct morphologic and hemodynamic diagnosis in 74/88 (84%) (in this group longitudinal plane gave 68% additional informations), the longitudinal planes in 69/88 (78%). However in 11% of cases longitudinal plane was the only means for identifying the congenital lesion and transversal plane in 16%. It was the combination of longitudinal and transverse scanning which gave in 97% the correct complete morphologic diagnosis. CONCLUSIONS: Thus we conclude that both planes are required for optimal transesophageal evaluation of congenital disease of atrium and venous connection.

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