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Objective: A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and efficacy of OROS MPH in a multicenter, randomized, clinical trial., Methods: Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward., Results: Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively., Conclusions: For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS, Concerta.

Background: Antecedents to human immunodeficiency virus-dementia (HIV-D) are poorly understood., Objective: To identify risk factors for HIV-D., Methods: Subjects who are positive for HIV who have CD4+ counts either below 200/microL or below 300/microL with evidence of cognitive impairment were enrolled in this study. Neurologic, cognitive, functional, and laboratory assessments were done semiannually for up to 30 months. Human immunodeficiency virus-dementia was diagnosed using American Academy of Neurology criteria for probable HIV-1-associated dementia complex., Results: One hundred forty-six nondemented patients were enrolled, 45 of whom subsequently met criteria for incident HIV-D. In univariate analyses using the Cox proportional hazards regression model, the following variables were significantly associated with time to develop dementia: cognitive: abnormal scores on Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol tests; attention-memory, psychomotor, and executive function domain scores; and the diagnosis of minor cognitive/motor disorder; neurologic and medical: increased abnormalities on the neurologic examination, extrapyramidal signs, history of HIV-related medical symptoms; functional: higher reported role or physical function difficulties. Depression was also a strong risk factor, along with sex, hematocrit, hemoglobin, and beta2-microglobulin levels. In a multivariate model that used cognitive domain scores, covariates with significant hazard ratios included depression, executive dysfunction, and the presence of minor cognitive/motor disorder., Conclusion: Cognitive deficits, minor cognitive/motor disorder, and depression may be early manifestations of HIV-D.

Cognitive and functional outcomes are of primary interest in the design of efficacy trials in HIV-associated cognitive impairment. In a longitudinal cohort study, weak associations were found between measures of cognitive performance and commonly used measures of daily functioning (mostly self-report measures) in HIV-infected individuals. Modifications of current functional scales or new functional instruments are needed to assess the clinical relevance of cognitive changes in clinical trials of HIV-associated cognitive impairment.

A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.

Methylmercury (MeHg) is a neurotoxicant whose high-dose effects first became known following a number of poisoning outbreaks that occurred worldwide. The primary human exposure is low dosage from fish consumption. Studies of fish-eating populations have not found a consistent pattern of association between exposures and outcomes. Therefore, examining specific areas of cognitive functioning has been suggested as an important approach to determine whether more subtle effects of MeHg exposure are present. In the Seychelles longitudinal study of prenatal and postnatal MeHg exposure from fish consumption and development, the McCarthy Scales of Children's Abilities (MSCA) were administered to children at age 66 months. No association between MeHg exposure and performance on the MSCA General Cognitive Index was identified. We analyzed these data further to determine whether associations were present on specific subscales of the MSCA. The standard MSCA subscales were analyzed. Then, more specific subscales of the MSCA were defined and analyzed utilizing a neuropsychological approach. The subscales were recombined to approximate the domains of cognitive functioning evaluated in the Faroes and New Zealand studies. Analyses of both the standard and the recombined MSCA subscales showed no adverse associations with MeHg exposure and neuropsychological endpoints. A positive association between postnatal MeHg exposure and performance on the MSCA Memory subscale was found. These findings are consistent with previous reports from the Seychelles study in that no adverse effects of MeHg exposure from fish consumption can be detected in this cohort.

Human exposure to methylmercury (MeHg), a known neurotoxin, is primarily from fish consumption. As part of a large study examining the association between MeHg exposure and child development in a population with high fish consumption we examined school-age behavior using the Achenbach Child Behavior Checklist (CBCL). The CBCL Total T score was a primary endpoint and was reported earlier to show no adverse association with prenatal or postnatal MeHg exposure. In this study we analyzed the T scores of the CBCL subscales to determine if more discrete aspects of measured behavior were associated with exposure. The Seychelles Child Development Study (SCDS) is a prospective, double blind, longitudinal evaluation of over 700 children. The index of prenatal exposure was maternal hair total mercury (T-Hg) in a segment growing during gestation. Postnatal exposure was T-Hg in the child's hair taken at 66 months of age. The child's primary caregiver completed the CBCL during the 66-month evaluation. No association between prenatal or postnatal MeHg exposure and the CBCL subscales was found. In Seychellois children exposed to MeHg from consumption of ocean fish we found no association between either prenatal or postnatal MeHg exposure and behavior as measured by the CBCL subscales., (Copyright 2000 Academic Press.)

The Seychelles Child Development Study has been unable to confirm any relationship between maternal exposure to MeHg during pregnancy and adverse developmental outcomes. In this report, 87 children from a pilot cohort were evaluated at 9 years of age. Each child was given a battery testing specific cognitive, visual motor, and motor skills using standardized psychometric and neuro-psychological tests. The results indicated no adverse association between maternal MeHg exposure and any developmental outcome measure. For three endpoints (Boston Naming Test and two tests of visual motor coordination), enhanced performance in males was associated with increasing prenatal MeHg exposure. A secondary analysis including both prenatal MeHg and postnatal MeHg exposure was done even though we lacked postnatal hair for about 35% of the cohort. The results of the secondary analysis mirrored the outcomes of the primary analysis regarding prenatal exposure but were less robust. The results of this study are consistent with earlier findings from the 66-month evaluations of the SCDS Main cohort. Since MeHg is neurotoxic, this effect is likely due to other factors associated with consumption of fish., (Copyright 2000 Academic Press.)

Objective: Analysis of health, neurodevelopmental, and school performance outcomes in a pilot study of term and near-term infants with respiratory failure due to pneumonia or meconium aspiration treated with surfactant., Study Design: Retrospective review of medical records, neurodevelopmental and psychosocial evaluations, and parent and teacher surveys., Results: Of the 14 patients enrolled, only one was rehospitalized, for pneumonia. Three were reported to have episodes of wheezing, two of whom required bronchodilators. One patient had unilateral hearing loss, one had a full-scale intelligence quotient that was below normal, and all but one patient for whom complete results were obtained were performing at or above grade level., Conclusion: Term and near-term newborns with moderately severe respiratory failure treated with surfactant can, in general, be expected to recover completely and have normal general health, neurodevelopmental outcome, and school performance.

Unlabelled: The Seychelles Child Development Study (SCDS) is testing the hypothesis that prenatal exposure to low doses of MeHg from maternal consumption of fish is associated with the child's developmental outcomes. No deleterious relationships between exposure to MeHg and cognitive functions have been identified in the primary analysis of the main cohort through 66 months of age. We performed secondary analyses to determine if effect modification (EM) from social and environmental factors was affecting associations between MeHg and outcomes., Methods: MeHg exposure was determined by analysis of maternal hair growing during pregnancy. Children in our Main Study cohort were evaluated at 6.5 months (N = 740) for visual recognition memory and visual attention using the Fagan Infantest, at 19 months (N = 738) and 29 months (N = 736) with the Bayley Scales of Infant Development (BSID). Interactions between MeHg and Caregiver Intelligence, Family Income and Home Environment were examined by multiple regression analysis., Results: The median prenatal MeHg exposure was 5.9 ppm (Range 0.5-26.7 ppm). No EM occurred for preferential looking or visual attention at 6.5 months, for the BSID Psychomotor Scale at either 19 or 29 months, or for activity level at 29 months as measured by the BSID Infant Behavior Record. Interactions between MeHg level and both caregiver intelligence and family income were statistically significant for the BSID Mental Scale at 19 months but not at 29 months. These showed enhancement of MDI scores with increasing maternal MeHg in higher caregiver IQ groups at several levels of family income., Conclusions: In Seychellois children, consistent major EM by social or environmental factors were not identified. The small EM by caregiver intelligence and social factors at 19 months is consistent with the enhanced performance we reported when this cohort was examined at 66 months.

To assess visual memory disturbance in different forms of schizophrenia, we compared Rey-Osterrieth Complex Figure Test (RCF) performance in acutely psychotic, chronically psychotic, and outpatient schizophrenia patients and in a control group of acutely psychotic patients with disorders other than schizophrenia. There were no group differences on the copy condition of the RCF. The chronic schizophrenia group utilized more abnormal copying strategies, however, than the outpatient or nonschizophrenia groups. Moreover, the chronic schizophrenia group demonstrated significantly poorer recall than the outpatient or nonschizophrenia groups, and a trend toward poorer performance than the acute schizophrenia group. Both groups of inpatient schizophrenia patients were characterized by a lack of relationship between copying strategies and recall accuracy. These data suggest that (a) chronic schizophrenia patients are characterized by more severe memory impairment than are nonchronic schizophrenia patients, and (b) visual memory disturbance in chronic schizophrenia is not solely a function of encoding difficulties.

Background: Exogenous surfactant replacement has improved survival and reduced pulmonary complications of prematurity. Improved early outcomes for infants of <30 weeks' gestation treated with a strategy of prophylactic versus rescue surfactant, if needed, were demonstrated in a multicenter, randomized trial conducted between 1985 and 1988. We reevaluated a subset of survivors from this trial to determine the pulmonary and neurodevelopmental outcomes at school age., Methods: At 4.5 to 8 years of age, all survivors from one of the three centers were located, and 96% were evaluated. The original randomization included stratification by center and followed an intention-to-treat methodology in assessing the efficacy of prophylactic versus rescue treatment with surfactant. The follow-up test battery included a health-assessment questionnaire, spirometry, 88% saturation test, neurologic examination, and the McCarthy Scales of Children's Abilities (MSCA) and the Conners' Parent Rating Scale-48. Educational achievement was determined by school class placement and teachers' reports of achievement., Results: Of the 192 children originally enrolled, 154 survived. Evaluations were performed on 148 of these infants. An abnormal pulmonary history was found in 45 (30%) of the children: 16 (22%) in the prophylactic group and 29 (39%) in the rescue group. Formal pulmonary function was evaluated in 81 children; 29 (78%) in the prophylactic group and 33 (75%) in the rescue group were considered abnormal. No significant differences were found between the two groups on either cognitive or motor subscales of the MSCA, the Conners' Parent Rating Scale-48, the neurologic examination, the education services received in school, or the teacher ratings of below-average academic performance. Intelligence scores measured on the MSCA were low-normal for both groups. Some level of educational assistance was being provided to 72 (49%) of the cohort studied, and both groups had below average educational performance and increased needs for educational assistance., Conclusions: Prophylactic surfactant administration to infants of <30 weeks' gestation was associated with fewer long-term clinical pulmonary complications than assignment to rescue administration. Formal pulmonary testing at school age did not reveal significant differences between treatment groups in those infants who could be tested. There also were no group differences found on neurologic, cognitive, behavioral, or educational assessments at school age.

Tourette syndrome (TS) is a hereditary condition characterized by the presence of chronic, multiple motor tics and is commonly associated with obessive-compulsive behavior, attentional and executive dysfunction, and aggressive behavior. A wide range of other genetic and environmental conditions that interfere with normal basal ganglia developmental processes can produce a clinical syndrome that we call the developmental basal ganglia syndrome (DBGS), and which closely resembles TS. Failure to distinguish TS from other causes of DBGS has probably hampered research efforts aimed at clarifying the neurobiological mechanisms, localizing the genetic defect, assessing therapy, and establishing accurate prevalence rates for TS.

Two interrelated cross-sectional studies were conducted to expand earlier findings about correlates of outwardly directed aggressive behavior in children with mental retardation. In Study 1 we compared children with mental retardation, 27 with and 23 without aggression. Aggression was best predicted by concurrent self-injurious behavior (SIB). In Study 2 we examined the likelihood that aggression was predicted by concurrent SIB and other nondestructive maladaptive behaviors in an archival cohort of 701 children younger than 21 with IQs below 70. Self-injurious behavior significantly predicted outwardly directed aggression for all children regardless of age. Additional predictors besides SIB showed only minimal improvements in model R2 values. Results were discussed in light of recent research proposing a common basis for aggression and SIB.

Patients with neurodevelopmental syndromes often receive numerous psychiatric diagnoses before the true nature of their disorder becomes apparent. We present a case in which the neuropsychological evaluation played a significant role in reconceptualizing a patient who had received, at various times, diagnoses of schizotypal personality disorder, schizoaffective disorder, and schizophrenia. The identification of specific cognitive deficits in executive functioning, perceptual organization, visual-spatial problem solving, and abstraction led to: 1) a diagnosis of nonverbal perceptual-organization-output disabled; 2) the adoption of a rehabilitative treatment model; and 3) a greater understanding of the way in which the patient's social deficits represented adaptations to her cognitive impairments. Research data and theoretical models relating cognitive deficits to psychiatric symptoms are discussed, and evidence is presented that schizophrenia and certain neurodevelopmental syndromes may share commonalities of pathophysiology. Diagnostic issues arising from similarities between these disorders are discussed. It is suggested that direct comparisons between these groups can aid in clarifying the specific nature of cognitive deficit-symptom relationships, as well as leading to improvements in the understanding, diagnosis and treatment of schizophrenic and neurodevelopmental syndromes.

The fault-tolerance characteristics of time-continuous, recurrent artificial neural networks (ANNs) that can be used to solve optimization problems are investigated. The performance of these networks is illustrated by using well-known model problems like the traveling salesman problem and the assignment problem. The ANNs are then subjected to up to 13 simultaneous stuck-at-1 or stuck-at-0 faults for network sizes of up to 900 neurons. The effect of these faults on the performance is demonstrated, and the cause for the observed fault-tolerance is discussed. An application is presented in which a network performs a critical task for a real-time distributed processing system by generating new task allocations during the reconfiguration of the system. The performance degradation of the ANN under the presence of faults is investigated by large-scale simulations and the potential benefits of delegating a critical task to a fault-tolerant network are discussed.

Disturbances in neural circuitry including the basal ganglia and prefrontal cortex have been hypothesized to be a cause of obsessive-compulsive disorder (OCD). Because eye movements are often impaired in neurologic diseases affecting these brain areas, oculomotor functioning was assessed in 17 unmedicated patients with OCD and in 25 normal controls. As compared with control subjects, patients with OCD demonstrated low-gain (slow) pursuit eye movements and an increased frequency of square wave jerk intrusions, but no increase in anticipatory saccades. In addition, several OCD patients showed an unusual pattern of intrusive, brief epochs of high-gain (fast) pursuit lasting on the order of 50 to 130 msec. These epochs of fast pursuit moved the eyes ahead of the target being tracked, and were terminated by corrective reversal saccades. Studies of eye movement abnormalities may provide an informative neurophysiologic approach for studying disturbances in basal ganglia and frontal cortical function that have been observed in functional neuroimaging and neuropsychological studies of OCD.

Four stimulus elements configured as a notional diamond were flashed in pairs to elicit apparent motion. When the elements were identical (4 Zs), the direction of apparent motion was ambiguous. When the elements were pairs of different letters (Cs and Os, Es and Zs), letters of different sizes (Zs and zs), or oppositely oblique lines, the direction of apparent motion tended to be between identical elements. This was true, however, only for an initial, brief observation period. Subsequently, the direction of apparent motion tended to be determined by the direction of motion perceived at first, regardless of the character of the elements. This quickly established directional set (within 10 sec) largely swamped any tendency to resolve correspondence in terms of a feature of the stimulus. It appears to be based on spatial rather than retinal or egocentric coordinates.

A relationship between the amount of available estradiol receptors in uteri of inbred mice and their H-2 genotype is suggested by study in congenic animals.

Antinuclear antibodies are almost always found in sera of patients with systemic lupus erythematosus. To differentiate antinuclear antibodies from antibodies to DNA in the recently described Crithidia luciliae assay, we developed an immunoperoxidase technique for detecting antibodies to native, double-stranded DNA and compared results by it with those by the Farr assay. Smears of cultured Crithidia luciliae were incubated with human sera, peroxidase-labeled anti-human IgG serum, and diaminobenzidine. The peroxidase stain was examined by conventional light microscopy, which facilitated differentiation between the kinetoplast and the nuclear staining. The Crithidia assay appeared to be specific for double-stranded DNA antibodies, seemed to be more sensitive than the Farr assay, and allowed us to determine the immunoglobulin classes of antibodies to native DNA. Some patients with systemic lupus erythematosus had only IgM or IgA antibodies to DNA.

Contrary to an earlier report [Anstis and Gregory, Q. Jl exp. Psychol. 17, 173-174 (1965)], we find that the sustained retinal motion caused by tracking a moving target over a stationary grating does not result in a motion aftereffect (MAE) which is equivalent to that resulting from comparable retinal motion caused by actual motion of a grating. The MAE associated with tracking generally occurs in elements falling on areas not previously exposed to retinal motion. It is in the same direction as the previous retinal motion in the display and is apparently an induced MAE caused by a weak, below threshold MAE in the elements stimulating areas that were previously exposed to retinal motion. Based on an analysis of eye movement records, we do not believe that the weakness of the tracking MAE is primarily a function of the poor quality of the tracking eye movements. Other possible reasons for the weakness of the MAE are suggested.