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PubMed2003

Acute psychophysiological arousal and posttraumatic stress disorder: a two-year prospective study.

This study investigated the role of acute arousal in the development of posttraumatic stress disorder (PTSD). Hospitalized motor vehicle accident survivors (n = 146) were assessed for acute stress disorder (ASD) within 1 month of the trauma, 6 months later, and reassessed for PTSD 2 years posttrauma (n = 87). Heart rates (HR) were assessed on the day of hospital discharge. Participants who had PTSD 2 years posttrauma had higher HR at hospital discharge than those without PTSD. A diagnosis of ASD or a resting HR of 95 beats per minute had moderate sensitivity (74%) and specificity (91%) in predicting PTSD. These findings suggest that caution is required in using acute HR as a predictor of longer-term PTSD following trauma.

Accidents, Traffic↗
PubMed2004

Right atrial 'thrombus in transit' and atrial septal defect in a 70-year-old man: cardioembolic source of pulmonary and paradoxical cerebral embolization.

A 70-year-old man was admitted with sudden onset of dyspnea, near syncope and left hemiparesis. Clinical examination, blood gas analysis, ECG and the chest X-ray were consistent with pulmonary embolism. Transthoracic echocardiography (TTE) revealed right atrial free-floating thrombus, large atrial septal defect (ASD), right heart enlargement and pulmonary artery hypertension. Anticoagulation therapy was initiated immediately, soon after thrombolytic therapy was started but the patient died due to possible pulmonary or cerebral embolization. We underscore rapid diagnosis by TTE that revealed right heart thrombus in transit and large ASD.

Aged↗
PubMed2003

The symptoms of autism spectrum disorders in adolescence and adulthood.

This article describes the symptoms of autism spectrum disorders (ASD) manifested by 405 individuals between the ages of 10 and 53 years, all of whom had an ASD diagnosis. Data were collected using the Autism Diagnostic Interview-Revised (ADI-R) to assess the pattern of autism symptoms in adolescence and adulthood. Findings include that although virtually all sample members met the criteria for Autistic Disorder earlier in their childhood, just over half (54.8%) would have met autism criteria if current scores were used to complete the diagnostic algorithm; that adolescents were more likely to improve in the Reciprocal Social Interaction domain than the adults, whereas the adults were more likely to improve in the Restricted, Repetitive Behaviors and Interests domain, and there were no differences in severity of symptoms between cohorts in the Communication domain; and that individual symptoms showed unique trajectories, with greatest symptom abatement between lifetime and current ADI-R ratings for speaking in at least three-word phrases and the least symptom improvement for having friendships. Findings were interpreted in the context of life course development, reformulations of diagnostic criteria, and changing service contexts for individuals with autism spectrum disorders.

Adolescent↗
PubMed2005

The additive benefit of hypnosis and cognitive-behavioral therapy in treating acute stress disorder.

This research represents the first controlled treatment study of hypnosis and cognitive- behavioral therapy (CBT) of acute stress disorder (ASD). Civilian trauma survivors (N=87) who met criteria for ASD were randomly allocated to 6 sessions of CBT, CBT combined with hypnosis (CBT-hypnosis), or supportive counseling (SC). CBT comprised exposure, cognitive restructuring, and anxiety management. CBT-hypnosis comprised the CBT components with each imaginal exposure preceded by a hypnotic induction and suggestions to engage fully in the exposure. In terms of treatment completers (n=69), fewer participants in the CBT and CBT-hypnosis groups met criteria for posttraumatic stress disorder at posttreatment and 6-month follow-up than those in the SC group. CBT-hypnosis resulted in greater reduction in reexperiencing symptoms at posttreatment than CBT. These findings suggest that hypnosis may have use in facilitating the treatment effects of CBT for posttraumatic stress.

Adolescent↗
PubMed2005

The course of psychological disorders in the 1st year after cancer diagnosis.

This study investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) and comorbid anxiety, depressive, and substance use disorders over the first 12-month period following a cancer diagnosis. Individuals recently diagnosed with 1st onset head and neck or lung malignancy were assessed for ASD within the initial month following their diagnosis and reassessed for PTSD and other psychological disorders at both 6 months and 12 months following their cancer diagnosis. The incidence for PTSD at 12 months (14%) was lower than the incidence for other anxiety (20%) and depressive (20%) disorders. This study points to the need for the development of valid therapeutic interventions to assist this population in the 1st year following their diagnosis.

Aged↗
PubMed2005

Predictors of posttraumatic stress disorder following cancer.

This study investigated the predictors of posttraumatic stress disorder (PTSD) following a diagnosis of cancer. Individuals who were recently diagnosed with 1st onset head and neck or lung malignancy (N = 82) were assessed within 1 month of diagnosis for acute stress disorder (ASD) and other psychological responses including depression; individuals were reassessed (N = 63) for PTSD 6 months following their cancer diagnosis. At the initial assessment ASD was diagnosed in 28% of participants, and 22% met criteria for PTSD at 6-months follow-up. Peritraumatic dissociative symptoms at the time of receiving one's cancer diagnosis was the sole predictor of PTSD severity at 6-months follow-up. Elevated dissociative symptoms and greater distress at the initial assessment were the best predictors of PTSD caseness at 6-months follow-up. This study provides evidence for identifying recently diagnosed cancer patients who may benefit from psychological assistance in order to prevent chronic psychopathology.

Adult↗
PubMed2000

A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2.

Tricuspid atresia (TA) is a common form of congenital heart disease, accounting for 1-3% of congenital cardiac disorders. TA is characterized by the congenital agenesis of the tricuspid valve connecting the right atrium to the right ventricle and both an atrial septal defect (ASD) and a ventricular septal defect (VSD). Some patients also have pulmonic stenosis, persistence of a left-sided superior vena cava or transposition of the great arteries. Most cases of TA are sporadic, but familial occurrences with disease in multiple siblings have been reported. Gata4 is a zinc-finger transcription factor with a role in early cardiac development. Gata4-deficient mice fail to form a ventral heart tube and die of circulatory failure at embryonic day (E) 8.5 (refs 6,7). Zfpm2 (also known as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the developing heart beginning at E8.5 (refs 8-10). Zfpm2 interacts specifically with the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription. Here we use targeted mutagenesis to explore the role of Zfpm2 in normal cardiac development. Zfpm2-deficient mice died of congestive heart failure at E13 with a syndrome of tricuspid atresia that includes an absent tricuspid valve, a large ASD, a VSD, an elongated left ventricular outflow tract, rightward displacement of the aortic valve and pulmonic stenosis. These mice also display hypoplasia of the compact zone of the left ventricle. Our findings indicate the importance of Zfpm2 in the normal looping and septation of the heart and suggest a genetic basis for the syndrome of tricuspid atresia.

Animals↗
PubMed2006

Transgenic alternative-splicing reporters reveal tissue-specific expression profiles and regulation mechanisms in vivo.

Alternative splicing of pre-mRNAs allows multicellular organisms to create a huge diversity of proteomes from a finite number of genes. But extensive studies in vitro or in cultured cells have not fully explained the regulation mechanisms of tissue-specific or developmentally regulated alternative splicing in living organisms. Here we report a transgenic reporter system that allows visualization of expression profiles of mutually exclusive exons in Caenorhabditis elegans. Reporters for egl-15 exons 5A and 5B showed tissue-specific profiles, and we isolated mutants defective in the tissue specificity. We identified alternative-splicing defective-1 (asd-1), encoding a new RNA-binding protein of the evolutionarily conserved Fox-1 family, as a regulator of the egl-15 reporter. Furthermore, an asd-1;fox-1 double mutant was defective in the expression of endogenous egl-15 (5A) and phenocopied egl-15 (5A) mutant. This transgenic reporter system can be a powerful experimental tool for the comprehensive study of expression profiles and regulation mechanisms of alternative splicing in metazoans.

Alternative Splicing↗
PubMed2005

A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism.

Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.9+/-4.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

Administration, Oral↗
PubMed2005

Interaction of SP-A (surfactant protein A) with bacterial rough lipopolysaccharide (Re-LPS), and effects of SP-A on the binding of Re-LPS to CD14 and LPS-binding protein.

SP-A (surfactant protein A) is a lipid-binding collectin primarily involved in innate lung immunity. SP-A interacts with the bacterial rough LPS (lipopolysaccharide) Re-LPS (Re595 mutant of LPS from Salmonella minnesota), but not with smooth LPS. In the present study, we first examined the characteristics of the interaction of human SP-A with Re-LPS. Fluorescence intensity and anisotropy measurements of FITC-labelled Re-LPS in the presence and absence of SP-A indicated that SP-A bound to Re-LPS in solution in a Ca2+-independent manner, with a dissociation constant of 2.8x10(-8) M. In the presence of calcium, a high-mobility complex of SP-A and [3H]Rb-LPS (Rb mutant of LPS from Escherichia coli strain LCD 25) micelles was formed, as detected by sucrose density gradients. Re-LPS aggregation induced by SP-A was further characterized by light scattering. On the other hand, human SP-A inhibited TNF-alpha (tumour necrosis factor-alpha) secretion by human macrophage-like U937 cells stimulated with either Re-LPS or smooth LPS. We further examined the effects of human SP-A on the binding of Re-LPS to LBP (LPS-binding protein) and CD14. SP-A decreased the binding of Re-LPS to CD14, but not to LBP, as detected by cross-linking experiments with 125I-ASD-Re-LPS [125I-labelled sulphosuccinimidyl-2-(p-azidosalicylamido)-1,3-dithiopropionate derivative of Re-LPS] and fluorescence analysis with FITC-Re-LPS. When SP-A, LBP and CD14 were incubated together, SP-A reduced the ability of LBP to transfer 125I-ASD-Re-LPS to CD14. These SP-A effects were not due to the ability of SP-A to aggregate Re-LPS in the presence of calcium, since they were observed in both the absence and the presence of calcium. These studies suggest that SP-A could contribute to modulate Re-LPS responses by altering the competence of the LBP-CD14 receptor complex.

Acute-Phase Proteins↗
PubMed1991

Pentraxin binding to isolated rat liver nuclei.

The interaction of human C-reactive protein (CRP) and serum amyloid P-component (SAP) with isolated rat liver nuclei was studied to identify nuclear ligands for each pentraxin using the iodinatable heterobifunctional thiol-cleavable cross-linking reagent sulphosuccinimidyl-2-(p-azidosalicylamido)-1,3'-dithiopropio nate (SASD). Nuclei (100 micrograms of DNA) bound 21 pmol of 125I-labelled CRP Ca(2+)-dependently at saturation with half-saturation occurring at 200 pmol of 125I-CRP. By contrast, only 2.7 pmol of 125I-labelled SAP was bound at saturation, with half-saturation at 50 pmol. The binding of pentraxins to nuclei is, in addition to putative chromatin binding, due to nuclear-envelope binding, where 3.2 pmol 125I-labelled CRP binds Ca2+ dependently to nuclear envelopes (25 micrograms) at saturation, but only 0.62 pmol SAP is required to saturate. Specific photocross-linking of 125I-2-(p-azidosalicylamido)-1,3'-dithiopropionate (125I-ASD)-CRP and 125I-ASD-SAP to nuclei revealed transfer of 125I-photoreactive azides to nuclear-envelope proteins of 43, 46, 52 and 70 kDa. In addition, SAP binding to histones H2A, H2B, H3 and H4 was detected, whereas CRP bound only to H4. Neither pentraxin cross-linked to histone H1.

Animals↗
PubMed1995

The biosynthesis of threonine by mammalian cells: expression of a complete bacterial biosynthetic pathway in an animal cell.

The coding regions for the Escherichia coli gene for aspartokinase I/homoserine dehydrogenase I (thrA) and the Corynebacterium glutamicum gene for aspartic semialdehyde dehydrogenase (asd) have been subcloned into a Simian Virus 40 (SV40)-based mammalian expression vector. Both enzyme activities are expressed in mouse 3T3 cells after transfer of the corresponding chimaeric gene. The kinetic parameters are similar to those of the native bacterial enzymes, and aspartokinase I/homoserine dehydrogenase I retains its allosteric regulation by threonine. An extract of the cells expressing aspartokinase I/homoserine dehydrogenase I, mixed with one from cells expressing aspartic semialdehyde dehydrogenase, produced homoserine when the mixture was incubated with aspartic acid, ATP and NADPH. The thrA and asd expression cassettes were combined into a single plasmid which, when transfected into 3T3 cells, enabled them to produce homoserine from aspartic acid. Homoserine-producing 3T3 cells were transfected with the plasmid pSVthrB/C (homoserine kinase and threonine synthase) and selected for growth on homoserine. Cell lines isolated from these cells expressed the complete bacterial threonine pathway, were independent of threonine for growth and could be maintained in medium which contained no free threonine. The threonine in the proteins of these cells became enriched in 15N when the culture medium contained [15N]aspartic acid. The production of homoserine and the growth of cells was at a maximum when there was more than 2.5 mM aspartate in the medium. Below this concentration the high Km of aspartokinase limited the flux through the pathway. In the presence of additional aspartic acid the new pathway could sustain a cell cycle time close to that of the same cells cultured in threonine-containing medium.

3T3 Cells↗
PubMed2006

Predicting lexical density growth rate in young children with autism spectrum disorders.

PURPOSE: The purpose of this longitudinal correlational study was to test whether an environmental variable and 4 child variables predicted growth rate of number of different nonimitative words used (i.e., lexical density). METHOD: Thirty-five young (age range = 21-54 months) children with autism spectrum disorders (ASD) who were initially nonverbal or low verbal participated in the study. Lexical density was measured at 3 times: at entry into the study as well as 6 months and 12 months after entry into the study. Growth curve analysis was used to test the associations. The predictive value of the putative predictors in the model was tested after controlling for initial expressive language impairment. RESULTS: Initial frequency of intentional communication and diversity of object play were predictors of lexical density growth above and beyond initial expressive language impairment (both pseudo R(2)s = .14). CONCLUSIONS: Intentional communication and diversity of object play may represent important prelinguistic goals for young children with ASD. These skills not only have been shown to be malleable through treatment, but they also provide a context for linguistic input from others that may facilitate language development.

Autistic Disorder↗
PubMed2002

An audit of referrals of children with autistic spectrum disorder to the dietetic service.

UNLABELLED: Autistic spectrum disorder (ASD) is a developing area for dietetic referrals. There is little published data on current dietetic practice. Some children with ASD are referred for gluten/casein free diet. The theory is that abnormal metabolites in the urine may be a result of incomplete breakdown of gluten and casein in the gut. There are some published open studies that support the efficiency of such a diet [Knivsberg et al. (1995) Scand. J. Educ. Res.39: 223; Lucarelli et al. (1995) Panminerva Med.37: 137; Whiteley et al. (1999) Int. J. Res. Practice 3: 45] and also that there are many anecdotal reports that the diet helps some children. AIMS AND OBJECTIVES: This study aimed to audit the types of referral made to the dietetic service to identify key dietetic issues and to describe factors which may influence outcome/disease management. METHODS: Dietetic records were used to audit the referrals to the dietetic service over a 3-month period. Seven-day diet histories were assessed using computer food composition tables and topics of interest recorded against a draft protocol agreed within the profession. RESULTS: Requests for gluten-free and casein-free dietetic advice, and/or the management of food selectivity and dysfunctional feeding behaviour constituted the majority of referrals. In many cases, child's environment was rarely simple. CONCLUSIONS: Despite the limitations of this small study, the findings suggest that the management of these referrals is highly complex. A dietitian's input should ensure that the nutritional adequacy of the diet is maintained or restored.

Autistic Disorder↗
PubMed2001

Outcome following surgical closure of secundum atrial septal defect.

OBJECTIVE: To assess the current outcome of surgical closure of secundum atrial septal defects (ASD) in an Australian paediatric population. METHODOLOGY: A retrospective chart review of 87 children, aged 2 months to 15 years, was performed for surgery between August 1995 and March 1999. RESULTS: There were no deaths in the patients studied. Approximately one in four patients (24.1%) experienced complications requiring further management. Complication rates were similar to those published previously. However, one in nine patients (11.5%) required surgical drainage of a pericardial effusion. A total of five of 87 (5.7%) patients developed post-pericardiotomy syndrome (PPS), of whom four required pericardiocentesis. The risk for developing a pericardial effusion requiring drainage or PPS was more than twice in children older than 5 years of age at the time of surgery compared to those aged under 5 years, although there was an insufficient number of subjects in the study to prove this statistically (Odds ratio 2.31). CONCLUSIONS: Most patients have an uncomplicated postoperative course following surgical closure of secundum ASD. However, a significant minority (24.1%) do develop complications requiring further management and have a correspondingly longer period of hospitalization. Patients older than 5 years of age were identified as being potentially at greater risk for the development of PPS or a pericardial effusion requiring drainage. Further research needs to be performed to clarify this.

Adolescent↗
PubMedDate not supplied

Pathology-related troponin I release and clinical outcome after pediatric open heart surgery.

BACKGROUND: Perioperative myocardial injury is determined by the ischemic duration, pathology, and preoperative myocardial status. Our aim was to evaluate pathology-related differences in troponin I (TnI) release, a sensitive and specific marker of myocardial injury, and its relation to clinical outcome after pediatric open heart surgery. METHODS: Troponin I was measured serially postoperatively in 133 children undergoing repair of atrial (ASD, n = 41) and ventricular septal defects (VSD, n = 46), and tetralogy of Fallot (TOF, n = 46). The length of the right ventricular outflow tract (RVOT) incision in the latter was classified as either minimum(n = 33) or extended(n = 13). RESULTS: Postoperative TnI levels were lesion specific and did not correlate with clinical outcome for ASDs. Peak TnI correlated with inotropic duration for VSD (r = 0.69, p < 0.0001) and TOF (r = 0.51, p = 0.0004). Significant correlations were also observed for the durations of ventilation (r = 0.64 and 0.36, respectively) and ICU stay (r = 0.60 and 0.55). Younger age (<1 year old) in children with VSDs and an extended incision into the RVOT in TOF were associated with greater TnI release and worse clinical outcome. CONCLUSIONS: Postoperative TnI release is pathology related and reflects myocardial damage from both ischemia-reperfusion injury and direct myocardial trauma.

Child, Preschool↗
PubMed2005

Caudal anesthesia in pediatric cardiac surgery: does it affect outcome?

OBJECTIVE: The purpose of this study was to examine the influence of caudal anesthesia on outcomes (pediatric intensive care unit [PICU] length of stay, hospital length of stay, ventilatory time, early extubation rate) in pediatric patients undergoing congenital heart disease repair requiring cardiopulmonary bypass (CPB). DESIGN: Retrospective. SETTING: University teaching hospital. PARTICIPANTS: Pediatric patients undergoing surgery to treat congenital heart disease between 1999 and 2002. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Thirty-four patients with atrial septal defect (ASD), 37 with ventricular septal defect, and 46 with tetralogy of Fallot (TOF) were included in the analysis. No differences were found in preoperative and intraoperative data between caudal and noncaudal group for each disorder. There was no difference between caudal and noncaudal groups in PICU and hospital stay. A statistically significant difference was found in the postoperative ventilatory time in patients with ASD and TOF between caudal and noncaudal groups. The early extubation rate was higher in the TOF caudal group compared with the noncaudal group. CONCLUSIONS: This retrospective study demonstrated that postinduction placement of caudal anesthesia does not affect PICU or hospital length of stay. A well-controlled prospective study is needed to confirm these findings.

Analgesics, Opioid↗
PubMed2005

The case against minimally invasive cardiac surgery.

Stellar outcomes have been achieved for patent ductus arteriosus (PDA), atrial septal defect (ASD), and ventricular septal defect (VSD) repairs by using the traditional surgical methods. Over the last decade, minimally invasive procedures have been introduced that promise excellent results with an improved cosmetic appearance, shorter rehabilitation period, less pain, and decreased hospital cost. We reviewed various minimally invasive procedures that are used in PDA, ASD, and VSD to assess their safety and efficacy. These techniques use limited approaches to the heart (partial sternotomies, transxiphoid, anterolateral thoracotomy, and mini-thoracotomy) that reduce the surgeons access and control of the cardiac structures. Cannulation sites for the establishment of cardiopulmonary bypass have been altered. Minimally invasive therapies for congenital heart surgery cannot be adopted until evidence-based data has proven them to be equal or better than the traditional procedure.

Cardiac Surgical Procedures↗