Association between phthalates and externalizing behaviors and cortical thickness in children with attention deficit hyperactivity disorder.

BACKGROUND: Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children. METHOD: A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated. RESULTS: Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri. CONCLUSIONS: The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.

No significant association between the alpha-2A-adrenergic receptor gene and treatment response in combined or inattentive subtypes of attention-deficit hyperactivity disorder.

INTRODUCTION: Given the shortage of pharmacogenetic studies on treatment response according to subtype of attention-deficit hyperactivity disorder (ADHD), we investigated the associations between the MspI and DraI polymorphisms of the alpha-2 A-adrenergic receptor gene (ADRA2A) and treatment response to methylphenidate according to subtype of ADHD. METHODS: We enrolled 115 medication-naïve children with ADHD into an open label 8-week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical -Global Impression (CGI), ADHD rating scale, and Continuous Performance Test (CPT) pre- and post-treatment. RESULTS: There was no statistically significant association between the MspI or DraI genotypes and the relative frequency of CGI-improvement (CGI-I) 1 or 2 status among any of the groups (all types of ADHD, ADHD-C, or ADHD-I). However, among the children with ADHD-C, those subjects with the C/C genotype at the ADRA2A DraI polymorphism tended to have a CGI-I 1 or 2 status post-treatment (OR=4.45, p=0.045). DISCUSSION: The results of this study do not support the association between the the MspI or DraI genotypes and treatment response to methylphenidate in ADHD. However, our results -suggest that subtypes might influence pharmacogenetic results in ADHD.·available online at http://www.thieme-connect.de/ejournals/toc/pharmaco.

Parental perceived benefits of OROS-methylphenidate treatment for the child with attention-deficit/hyperactivity disorder and for parents themselves.

Given the shortage of studies on parental perceived benefits of OROS-methylphenidate treatment in Asian populations, we assessed parental response to OROS-methylphenidate treatment of Korean children with attention-deficit/hyperactivity disorder (ADHD), in relation to children's academic performance and behavioral symptoms as well as parental rearing stress and depressive symptoms.We enrolled 132 medication-naïve children with ADHD into a multicenter, open-label, 12-week trial of OROS-MPH. The outcome measures were the ADHD rating scale-IV (ADHD-RS), the comprehensive attention test and academic performance rating scale, and the clinical global impression (CGI)-severity/improvement instrument (for the children) and Beck depression inventory and parenting stress index (for their parents).We found parent-perceived improvements in children's ADHD-related behavioral symptoms and academic function and their parents' depressive symptoms and parenting stress. Investigator-rated ADHD symptoms and subjects' neuropsychological function were also improved (p<0.001).Parents of Korean children with ADHD perceive that OROS-methylphenidate treatment improves their children's academic function and behavior as well as their own child-rearing stress and emotional state. These findings must be interpreted with caution, due to a non-comparative open-label trial.

Association between urine cotinine levels, continuous performance test variables, and attention deficit hyperactivity disorder and learning disability symptoms in school-aged children.

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.

Human umbilical cord blood-derived mononuclear cell transplantation: case series of 30 subjects with hereditary ataxia.

BACKGROUND: The differential diagnosis for hereditary ataxia encompasses a variety of diseases characterized by both autosomal dominant and recessive inheritance. There are no curative treatments available for these neurodegenerative conditions. This open label treatment study used human umbilical cord blood-derived mononuclear cells (CBMC) combined with rehabilitation training as potential disease modulators. METHODS: 30 patients suffering from hereditary ataxia were treated with CBMCs administered systemically by intravenous infusion and intrathecally by either cervical or lumbar puncture. Primary endpoint measures were the Berg Balance Scale (BBS), serum markers of immunoglobulin and T-cell subsets, measured at baseline and pre-determined times post-treatment. RESULTS: A reduction of pathological symptoms and signs was shown following treatment. The BBS scores, IgG, IgA, total T cells and CD3+CD4 T cells all improved significantly compared to pre-treatment values (P < 0.01~0.001). There were no adverse events. CONCLUSION: The combination of CBMC infusion and rehabilitation training may be a safe and effective treatment for ataxia, which dramatically improves patients' functional symptoms. These data support expanded double blind, placebo-controlled studies for these treatment modalities.

Bilateral isolated phrenic neuropathy causing painless bilateral diaphragmatic paralysis.

The authors report four patients with a syndrome of painless bilateral isolated phrenic neuropathy. Electrophysiologic testing demonstrated active denervation restricted to the diaphragm. Long-term recovery was poor. The authors conclude that bilateral isolated phrenic neuropathy is a cause of painless diaphragmatic paralysis distinguishable from immune brachial plexus neuropathy and other neuromuscular disorders with similar clinical presentation.

Psychiatric morbidity of second and third grade primary school children in Korea.

This study was undertaken to identify psychiatric morbidity among Korean second and third elementary school children using an objective diagnostic interview tool. Data from 5,118 (2,723 boys, 2,395 girls; mean age = 8.41 years (SD = 0.66)) second and third grade schoolchildren were drawn from 28 elementary schools. After initial screening assessments using the 28-item Child Problem-Behavior Screening Test for parents, 672 primary caregivers were subjected to secondary screening using the Korean version of the CBCL. Two hundred and seventy-one high-risk children selected according to the K-CBCL results, 138 (50.9%) children and their primary caregivers were interviewed using the Korean version of K-SADS-PL for objective DSM-IV psychiatric diagnoses. Sixty-four (46.4%) of the hundred and thirty eight children were determined to have at least one psychiatric disorder. More boys were diagnosed as psychiatric patients than girls (46 males, 18 females; OR = 2.21). The most frequently diagnosed disorder was ADHD (46/64; 71.9%), followed by tic disorder, anxiety disorders, mental retardation, oppositional defiant disorder, and separation anxiety disorder. Two or more comorbid psychiatric disorders were found in 22 (34.4%) of the 64 patients. The computed crude percentage of psychiatric patients in this study was 4.12%, which is similar to previously published data.

A case of 49,XXXXX in which the extra X chromosomes were maternal in origin.

This report describes an 11 month old female baby with features of pentasomy X. A molecular and cytogenetic evaluation revealed that her karyotype was 49,XXXXX and her extra X chromosomes were of maternal origin. She has muscular hypotonia, mental retardation, a cleft palate, mild hydrocephalus as a result of dilatation of both lateral ventricles, hyperextensible elbow joints, proximal radioulnar synostosis, clinodactyly of the fifth finger, valgus of the feet, and small hands and feet. In addition, she has a persistent pupillary membrane and congenital chorioretinal atrophy. The pathogenesis of pentasomy X is not clear at present, but it is thought to be caused by successive maternal non-dysjunctions.

A prospective 2-year clinical evaluation of overdentures attached to nonsplinted implants utilizing ERA attachments.

Edentulism is a major oral healthcare issue for an ever-increasing older population in the United States. Most previous studies examined the success of overdentures supported by splinted implants utilizing clip bars and other types of attachments. This longitudinal study of 10 consecutive patients involves mandibular overdentures supported by nonsplinted implants with ERA attachments. Two-year results indicate that nonsplinted implants can be successfully used with ERA attachments to support overdentures. Each patient reported increased satisfaction with comfort, chewing, retention, and phonetics with the implant-assisted ERA-retained overdenture.

Methylphenidate increased regional cerebral blood flow in subjects with attention deficit/hyperactivity disorder.

The regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment were examined in children with attention deficit/hyperactivity disorder (ADHD). Thirty-two male children, diagnosed with ADHD by the DSM-IV diagnostic criteria, other behavioral assessment scales and neuropsychological battery, were studied using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Subjects were studied before and after MPH treatment. First, using an image subtraction method, we obtained a NDR parametric image of each patient and found increased cerebral blood flow in the frontal lobes, caudate nuclei and thalamic areas after treatment. When the changes in SPECT and clinical response were compared, the matching rate, sensitivity and specificity between them were found to be 77.1, 80.0 and 79.2%, respectively. Second, three transaxial brain slices delineating anatomically defined regions of interest (ROI) at 20, 40, and 60mm above the orbitomeatal line (OML) were used, with the average number of counts for each region of interest normalized to the area of the cerebellar maximal uptake. The left and right prefrontal areas, and caudate and thalamic areas showed significant increases in rCBF after MPH treatment. These findings suggested MPH could affect the function of the fronto-striato-thalamic circuit, which is known as the pathophysiologic site of ADHD and could be used to correct the underlying brain dysfunction of ADHD.

Chronic lung injury in preterm lambs: abnormalities of the pulmonary circulation and lung fluid balance.

Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124+/-3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of 15+/-5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6+/-2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic lung injury, documented by serial chest radiographs and postmortem pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during the month after birth at term, did not change significantly from the first to the last week of study. Lung lymph flow, an index of net transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in lung vascular protein permeability. Postmortem studies showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.

The effect of inter-implant distance on the height of inter-implant bone crest.

BACKGROUND: The biologic width around implants has been well documented in the literature. Once an implant is uncovered, vertical bone loss of 1.5 to 2 mm is evidenced apical to the newly established implant-abutment interface. The purpose of this study was to evaluate the lateral dimension of the bone loss at the implant-abutment interface and to determine if this lateral dimension has an effect on the height of the crest of bone between adjacent implants separated by different distances. METHODS: Radiographic measurements were taken in 36 patients who had 2 adjacent implants present. Lateral bone loss was measured from the crest of bone to the implant surface. In addition, the crestal bone loss was also measured from a line drawn between the tops of the adjacent implants. The data were divided into 2 groups, based on the inter-implant distance at the implant shoulder. RESULTS: The results demonstrated that the lateral bone loss was 1.34 mm from the mesial implant shoulder and 1.40 mm from the distal implant shoulder between the adjacent implants. In addition, the crestal bone loss for implants with a greater than 3 mm distance between them was 0.45 mm, while the implants that had a distance of 3 mm or less between them had a crestal bone loss of 1.04 mm. CONCLUSIONS: This study demonstrates that there is a lateral component to the bone loss around implants in addition to the more commonly discussed vertical component. The clinical significance of this phenomenon is that the increased crestal bone loss would result in an increase in the distance between the base of the contact point of the adjacent crowns and the crest of bone. This could determine whether the papilla was present or absent between 2 implants as has previously been reported between 2 teeth. Selective utilization of implants with a smaller diameter at the implant-abutment interface may be beneficial when multiple implants are to be placed in the esthetic zone so that a minimum of 3 mm of bone can be retained between them at the implant-abutment level.

Histologic and clinical comparison of bilateral sinus floor elevations with and without barrier membrane placement in 12 patients: Part 3 of an ongoing prospective study.

In 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. One of the parameters under evaluation in this study is the effect of barrier membrane placement on the creation of vital bone in the grafted sinus cavity. This report presents a histologic and histomorphometric evaluation of healing with and without the placement of an expanded polytetrafluoroethylene (e-PTFE) barrier membrane over the lateral window at the time of sinus grafting. The data were collected from 12 patients who underwent bilateral sinus elevation surgery. In each of these 12 patients the same grafting material was used in both sinuses, making the presence or absence of an e-PTFE barrier membrane the only controlled variable. Under the conditions of this study, the results indicate that (1) placement of the barrier membrane tends to increase vital bone formation; (2) placement of a barrier membrane has a positive effect on implant survival; and (3) membrane placement should be considered for all sinus elevation procedures.

Chronic lung injury in preterm lambs. Disordered respiratory tract development.

The cause of chronic lung disease of early infancy, often called bronchopulmonary dysplasia (BPD), remains unclear, partly because large-animal models that reliably reproduce BPD have not been available. We developed a model of BPD in lambs that are delivered prematurely and ventilated for 3 to 4 wk after birth to determine whether the histopathology of chronic lung injury in premature lambs mimics that which occurs in preterm infants who die with BPD, and to compare two ventilation strategies to test the hypothesis that differences in tidal volume (VT) influence histopathologic outcome. The two ventilation strategies were slow, deep ventilation (20 breaths/min, 15 +/- 2 ml/kg body weight VT; n = 5) or rapid, shallow ventilation (60 breaths/min, 6 +/- 1 ml/kg body weight VT; n = 5). Lambs were delivered at 125 +/- 4 d gestation (term = 147 d), treated with surfactant, and mechanically ventilated with sufficient supplemental oxygen to maintain normal arterial oxygenation (60 to 90 mm Hg). Quantitative histologic analysis revealed lung structural abnormalities for both groups of experimental lambs compared with lungs of control term lambs that were < 1 d old (matched for developmental age; n = 5) or 3 to 4 wk old (matched for postnatal age; n = 5). Compared with control lambs, chronically ventilated preterm lambs had pulmonary histopathology characterized by nonuniform inflation patterns, impaired alveolar formation, abnormal abundance of elastin, increased muscularization of terminal bronchioles, and inflammation and edema. Slow, deep ventilation was associated with less atelectasis, less alveolar formation, and more elastin when compared with rapid, shallow ventilation. We conclude that prolonged mechanical ventilation of preterm lambs disrupts lung development and produces pulmonary histopathologic changes that are very similar to those that are seen in the lungs of preterm infants who die with BPD. This chronic lung disease is not prevented by surfactant replacement at birth, does not appear to require arterial hyperoxia, and is influenced by VT.

Crown lengthening revisited.

Over the last 37 years, crown-lengthening procedures have been used predictably to restore teeth broken down from caries, trauma, and extensive wear. With crown lengthening, the dentogingival junction is "re-created" at a more apical level on the root to accommodate the junctional epithelium and the connective tissue attachment. Forced eruption can be used in addition, or as an alternative, to tooth lengthening. The authors discuss the indications for tooth lengthening, forced eruption, and orthodontic extrusion, as well as the treatment planning for these procedures.

Electroconvulsive shock does not induce c-fos and junB, but TIS1 and TIS8/zif-268, in neonatal rat hippocampus.

The induction in the animal brain of immediate early genes (IEGs) is known to be age-dependent, and it was suggested that, during neonatal period, signaling pathways for the induction of IEGs are immature. In this study, we investigated the induction of various IEGs in neonatal rat hippocampus after electroconvulsive shock (ECS). ECS did not induce c-fos and junB in the hippocampus of 7-day-old rat, but these genes were weakly induced at postnatal 14 days and to an adult level at postnatal 21 days; two other IEGs, TIS1 (NGFI-B, nur77) and TIS8 (zif-268, Egr-1, Krox-24, NGFI-A), were induced at postnatal 7 days, however. Our results suggested that during the neonatal period, signaling pathways for TIS1 and TIS8 induction in rat hippocampus after ECS are complete, while those for c-fos and junB are immature.

Sinus floor elevation using anorganic bovine bone matrix (OsteoGraf/N) with and without autogenous bone: a clinical, histologic, radiographic, and histomorphometric analysis--Part 2 of an ongoing prospective study.

One of the goals of the sinus elevation procedure is the creation of vital bone to effect the osseointegration of dental implants placed in the posterior maxilla. With this goal in mind, in 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. The primary parameters included the effects of graft material selection, time allowed for graft maturation, and the effect of barrier membrane placement on the creation of vital bone in the sinus cavity. The effects of these and other parameters on implant survival rates were also to be evaluated. This paper reports the data collected on a subgroup of 113 sinus elevations that used anorganic bovine bone matrix (OsteoGraf/N) alone or in combination with autogenous bone and/or demineralized freeze-dried bone as a graft material. This is the second in a proposed series of papers that will result from this ongoing research project. The results of this study indicate that: OsteoGraf/N appears to be an effective graft material with a 98.2% implant survival rate to date: vital bone formation increased with time; vital bone formation increased moderately when demineralized freeze-dried bone allograft was added, and increased substantially when intraoral autogenous bone was added or when an expanded polytetrafluoroethylene membrane was used; and the increased height achieved by the procedure was stable over a 3-year period. Because of the high overall implant survival rate, it was not possible to determine the relationship between vital bone formation or membrane usage and implant survival.