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.

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.

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.

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.

Plasma debrisoquin levels in the assessment of reduction of plasma homovanillic acid. The debrisoquin method.

Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.

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.

Role of neutrophils in lung vascular injury and edema after premature birth in lambs.

To investigate the role of neutrophils in the pathogenesis of respiratory distress after premature birth, we assessed the relationship between circulating neutrophil concentration and neutrophil accumulation in the lung, lung lymph and pleural liquid flow, and extravascular lung water in 10 chronically catheterized preterm lambs (127 +/- 1 days gestation) that were mechanically ventilated for 8 h after birth. Circulating neutrophil concentration transiently decreased within 2 h after birth and then returned to prenatal values by 6-8 h. The decrease in circulating neutrophil concentration was related directly to the accumulation of neutrophils in the air spaces, drainage of liquid and protein from the lung 6-8 h after delivery, and postmortem extravascular lung water. In additional studies, we intravenously administered mechlorethamine to 5 fetal lambs to reduce circulating neutrophils before delivery (neutrophil concentration before birth: 9 +/- 11 cells/microl). Compared with control lambs, neutrophil-depleted lambs had significantly less drainage of liquid (7.8 +/- 5.9 vs. 2.6 +/- 1.9 ml/h, respectively) and protein (116 +/- 74 vs. 42 +/- 27 mg/h, respectively) from the lung 6-8 h after birth and significantly less extravascular lung water at postmortem (6.5 +/- 0. 8 vs. 4.8 0.6 g/g dry lung, respectively). Thus neutrophils contribute to the pathogenesis of respiratory distress after premature birth by increasing lung vascular protein permeability and promoting lung edema.

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.

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.

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.

Changes of tetanus specific IgG, IgM and IgG subclasses after DPT vaccination.

We evaluated tetanus specific IgG, IgM, IgG subclasses after DPT vaccination in infants and children. Tetanus toxoid specific IgG, IgM IgG subclasses were measured to characterize the isotope profile of antibody against tetanus toxoid. The values of the tetanus specific IgG in the positive group were significantly increased compared to those of the control group, and were significantly increased after two inoculation. Tetanus specific IgG was very low in adults and neonates. In our tetanus specific IgG subclasses study, forty-five of 56 cases (80%) showed predominantly IgG1 antibody responses to tetanus toxoid, while twenty-five of 56 cases (45%) showed IgG4 responses. Both IgG1 and IgG4 responses were demonstrated in 17 cases (30%). So we suggest that IgG was mainly involved in humoral immune response after DPT vaccination, and IgG1 may play an important role among IgG subclasses. IgG4, alone or together with IgG1, can also play a role in immune response to tetanus toxoid.

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.

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.

Cell and platelet adhesions on plasma glow discharge-treated poly(lactide-co-glycolide).

Surface treatment, such as plasma glow discharge treatment, onto poly(lactide-co-glycolide) (PLGA) has been investigated to improve the cell-, tissue- and blood-compatibility. Surface-treated samples were characterized by measurement with a contact angle goniometer and electron spectroscopy for chemical analysis (ESCA). The contact angles on the plasma-treated PLGA surfaces decreased with increasing plasma exposure time from 92 degrees to about 30 degrees, i.e., increased hydrophilicity. From the results of ESCA analysis of plasma-treated films, the incorporation of oxygen molecules into plasma onto the PLGA surface was observed. Cell adhesion and growth on plasma-treated PLGA surfaces were more active than on the control. Furthermore, the maximum adhesion and growth of cells in moderate hydrophilicity were investigated. Morphology of the adhered platelets on the plasma-treated PLGA surface showed less activity than on the control, and the number of adhered platelets on the plasma-exposed PLGA sample decreased with decreasing water contact angle. It seems that surface wettability of PLGA plays an important role in cell adhesion, spreading and growth, and platelet adhesion.

A study of work injuries in eight Asian countries.

This study is based on a survey conducted in Hong Kong, Indonesia, Korea, Malaysia, the Philippines, Singapore, Sri Lanka and Thailand on occupational injuries during the years 1975-1980. The number of work accidents have risen rapidly during this period in all of the 8 countries studied. In the case of Thailand, the total number of work injuries increased four fold from 1975-1978, whereas, in Singapore it has almost doubled in 6 years. The number of permanent disablement nearly trebled in Korea, and the Philippines for the year 1967-1980. The largest percentage of accidents are lost-time injuries in all of the 8 countries. Thailand had a three fold increase in lost-time injuries whilst in Hong Kong the figure doubled. Six out of the 8 countries indicated that the building construction industry had the largest number of fatal accidents, followed by the manufacturing industry.

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.

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.