Perinatal infections: HIV and co-infections in the placenta and therapeutic interventions-a workshop report.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
V Anderson
Publications and source records attributed to V Anderson.
Assessment and development of organizational ability: the Rey Complex Figure Organizational Strategy Score (RCF-OSS).
The Rey Complex Figure Organizational Strategy Score (RCF-OSS) was devised for pediatric populations to cater for developmental variability. A sample consisting of 376 children aged between 7.0 and 13.11 years was recruited for the standardization of RCF-OSS. The interrater reliability (.85 to .92) and temporal stability (.79 to .94) of the RCF-OSS are acceptable. RCF-OSS correlated moderately with RCF accuracy, memory and organization, however it seems to be measuring an independent aspect of performance, possibly strategy. Moderate linear relationships were observed with executive function and memory measures. Considerable age-related variation in strategy formation was observed with significant maturity occurring between the ages of 7 years and 11 years. Surprisingly, older children used fragmented strategies more than the younger age groups. In conclusion, the RCF-OSS is a useful adjunct to traditional accuracy scoring procedures, and the normative data indicates that organizational skills may not consolidate until middle to late adolescence.
Adolescent↗
Outcome from mild head injury in young children: a prospective study.
There is a lack of agreement regarding the long-term consequences of mild head injury (HI) at any age, with such effects rarely studied in early childhood. Given the rapid development occurring within the brain during this period, any disruption may have the potential to cause transient or permanent damage to brain structure and function. The present study sought to investigate the behavioral implications of such potential disruptions using a prospective, longitudinal design. Children aged 3-7 years at the time of injury, and suffering from mild HI, were evaluated acutely and at 6 and 30 months post-injury. Pre-injury data were collected with respect to communication, social skills, daily living skills and behavioral function. Results were compared to those from a non-injured control sample matched for age, gender, socioeconomic status, and pre-injury function. Findings showed few group differences. Children with mild HI performed similarly to controls on measures of intellectual ability, receptive language, and both everyday and spatial memory capacity. Group differences were identified for verbal fluency and story recall, with HI children failing to recover over time.
Activities of Daily Living↗
Effects of mobile phone type signals on calcium levels within human leukaemic T-cells (Jurkat cells).
PURPOSE: To test whether exposure to simulated GSM mobile phone signals (915 MHz, 2 W x kg(-1)) influences the concentration of calcium or calcium signalling patterns in a human lymphocyte cell line. MATERIALS AND METHODS: The radiofrequency (RF) energy was delivered via a coaxial applicator to a perfused chamber where cells adherent to a thin glass coverslip were imaged by laser scanning confocal microscopy. Cell calcium concentration, estimated from Fluo-3 fluorescence, was monitored over two 10-min periods; control followed by exposed/sham, with exposure status assigned in a blind and randomized fashion. Both continuous wave (CW) and pulsed wave (PW) RF (on both phytohaemagglutanin-activated and unactivated cells) were studied (with an equal number of sham exposures) on 100 cells per category (total 800 cells). RESULTS: No significant changes were noted for the following: regression slope of calcium fluorescence; mean calcium concentration; number of calcium 'spikes' in each 10 min; or mean height of these 'spikes'. The average frequency from Fourier spectra of these periods showed significant alteration in one category only: PW exposure of activated cells. CONCLUSIONS: There is no clear indication that RF emissions from mobile phones are associated with any changes in calcium levels or calcium signalling in lymphocytes.
Aniline Compounds↗
The differential assessment of children's attention: the Test of Everyday Attention for Children (TEA-Ch), normative sample and ADHD performance.
"Attention" is not a unitary brain process. Evidence from adult studies indicates that distinct neuroanatomical networks perform specific attentional operations and that these are vulnerable to selective damage. Accordingly, characterising attentional disorders requires the use of a variety of tasks that differentially challenge these systems. Here we describe a novel battery, the Test of Everyday Attention for Children (TEA-Ch), comprising nine subtests adapted from the adult literature. The performance of 293 healthy children between the ages of 6 and 16 is described together with the relationships to IQ, existing measures of attention, and scholastic attainment. This large normative sample also allows us to test the fit of the adult model of functionally separable attention systems to the observed patterns of variance in children's performance. A Structural Equation Modelling approach supports this view. A three-factor model of sustained and selective attention and higher-level "executive" control formed a good fit to the data, even in the youngest children. A single factor model was rejected. There are behavioural and anatomical grounds to believe that Attention Deficit Disorder (ADD) is particularly associated with poor self-sustained attention and behavioural control. The TEA-Ch performance of 24 boys diagnosed with ADD presented here is consistent with this view. When performance levels on WISC-III subtests were taken into account, specific deficits in sustained attention were apparent while selective attention performance was within the normal range.
Activities of Daily Living↗
Stability of olfactory identification deficits in neuroleptic-naive patients with first-episode psychosis.
OBJECTIVE: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. METHOD: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. RESULTS: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. CONCLUSIONS: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms.
Adolescent↗
Skin reactions to toxic plants.
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Dermatitis, Allergic Contact↗
The measurement and diagnostic utility of intrasubtest scatter in pediatric neuropsychology.
Intrasubtest scatter (ISS) is a measure of person's tendency toward inconsistency when responding to test items. It has been claimed that ISS may be suggestive of intellectual inefficiency, difficulty with recall of specific information, or fluctuating levels of arousal/attention. The research investigating these claims has been inconclusive, possibly because traditional indices of ISS may not adequately measure inconsistent responding. Item Response Theory (IRT) approaches to the detection of unusual response sequences appear to have a much firmer psychometric foundation but have been largely ignored in the neurodiagnostic literature. This study compares the utility of traditional and IRT-based indices of ISS in identifying children known to be experiencing information-processing difficulties. The WISC-R item responses of 100 children who have received cranial irradiation treatment for leukemia are compared with those of 100 healthy children. Results confirm the diagnostic utility of an IRT-based measure of unusual test behavior in this clinical group.
Adolescent↗
Attentional function in secondary school students receiving isoniazid prophylaxis for tuberculosis infection.
Reports have suggested that isoniazid treatment may be associated with poor concentration and subtle reduction in memory. This study examines attentional function and processing speed in a group of 25 adolescents who received isoniazid prophylaxis for at least 6 months. As adolescents often face major educational assessment milestones, such cognitive side effects may have important implications. Participants were assessed before treatment, 1 month into treatment and at least 1 week after treatment cessation. Measures included the Paced Auditory Serial Addition Test and subtests of the appropriate Wechsler scale sensitive to attention and speed of information processing. Isoniazid does not appear to cause significant adverse effects on attentional function in adolescents.
Adolescent↗
Evidence of a founder BRCA1 mutation in Scotland.
BRCA1 mutations have been identified in breast and ovarian cancer families from diverse ethnic backgrounds. We studied 17 different families with the BRCA1 2800delAA mutation; seven were ascertained in Scotland (Dundee, Edinburgh, Glasgow, St Andrews), five in Canada (Toronto, Victoria) and five in the United States (Chicago, Philadelphia, Seattle). Overall there was a clear preponderance of Scottish ancestry. Genotype analysis performed on key members from 17 families was consistent with a common haplotype, strongly suggesting a single ancestral origin. A possible link was established between two families by tracing their genealogies through the records of the Registrar General for Scotland. This is the first example of a BRCA1 mutation likely to be derived from a common founder in Scotland. Further studies will be necessary to estimate more accurately the population frequency of the BRCA1 2800delAA mutation among unselected cases of breast and ovarian cancer in Scotland and the UK.
Breast Neoplasms↗
Endoscopic features of smooth muscle tumors in children with AIDS.
BACKGROUND: Smooth muscle tumors are the second most common malignancy encountered in children with acquired immunodeficiency syndrome (AIDS). This study reviewed the incidence and endoscopic appearance of smooth muscle tumors in the gastrointestinal tract of children with AIDS undergoing endoscopy. METHODS: Retrospective review of all endoscopic records (n = 70) of children with AIDS from August 1988 to December 1997 at a tertiary care inner city hospital. RESULTS: Three children with advanced AIDS (4%) were found to have smooth muscle tumors, all of which had the typical appearance of submucosal nodules with central ulceration. Some were hemorrhagic. They measured less than 1 to 4 cm in diameter. Two children had multiple tumors. All lesions except for one were located in the colon. Colonic biopsies revealed a leiomyoma in one patient and a smooth muscle tumor of uncertain malignant potential in another. The forceps biopsy of the single gastric mass was not deep enough to make the diagnosis of a smooth muscle tumor. A nonmalignant smooth muscle tumor grew from less than 5 mm to more than 4 cm in 1 year and was removed surgically. All three children are alive without any evidence of local spread or distant metastases despite no specific therapy for the smooth muscle tumor. CONCLUSIONS: Smooth muscle tumors in the GI tract of children with AIDS are relatively common. Further study of the long-term outcome for children infected with the human immunodeficiency virus who have these lesions are needed to establish prognosis and management guidelines.
Acquired Immunodeficiency Syndrome↗
Twelve year outcomes following bacterial meningitis: further evidence for persisting effects.
AIM: To determine whether intellectual and cognitive impairments observed seven years following early childhood bacterial meningitis persist into adolescence. METHODS: Blinded neuropsychological, auditory, and behaviour assessments were conducted in 109 (69%) subjects from an original cohort of 158 children, seven and 12 years after their meningitis, and in 96 controls. RESULTS: Meningitis subjects remained at greater risk than controls for any disability (odds ratio OR 4.7, confidence interval 2.2 to 9.6). Those with acute neurological complications had more sequelae than children with uncomplicated meningitis or controls (47% v 30% v 11.5% respectively; p < 0.001). Differences in intellectual, academic, and high level cognitive function between subjects and controls were maintained at the seven and 12 year assessments. In contrast, lower order skills improved, while behaviour scores deteriorated significantly (p = 0.033). CONCLUSIONS: Many of the deficits identified at the seven year follow up persist 12 years after an episode of bacterial meningitis.
Adolescent↗
Recovery of intellectual ability following traumatic brain injury in childhood: impact of injury severity and age at injury.
Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine the relationship between recovery, injury severity, age at injury and pre-injury ability. 124 children were divided according to (1) age at injury: 'young' (3-7 years) 'old' (8-12) and (2) injury severity (mild, moderate, severe). Children were evaluated acutely (T1) and at 12 months post-injury (T2), using standardized intellectual measures (IQ). Results showed a relationship between greater injury severity and poorer IQ. Age at injury was not predictive of outcome for children with mild/moderate TBI. For severe TBI, younger age at injury led to minimal recovery in IQ, while recovery from later injury was similar to that for adults. Findings suggest that children sustaining severe TBI in early childhood may be particularly at risk for residual problems post-injury.
Adaptation, Psychological↗
Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin.
PURPOSE: The epidermal growth factor (EGF) receptor is frequently overexpressed in epithelial tumors. C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor. We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors. PATIENTS AND METHODS: We treated 52 patients in three successive phase I clinical trials of C225 as a single dose (n = 13), weekly multiple dose (n = 17), and weekly multiple dose with cisplatin (n = 22). C225 dose levels were 5, 20, 50, and 100 mg/m(2). In the study combining C225 with cisplatin, limited to patients with either head and neck or non-small-cell lung cancer, C225 was further escalated to 200 and 400 mg/m(2). Cisplatin was given at a dose of 60 mg/m(2) once every 4 weeks, and treatment was continued for up to 12 weeks if no disease progression occurred. RESULTS: C225 displayed nonlinear pharmacokinetics, with antibody doses in the range of 200 to 400 mg/m(2) being associated with complete saturation of systemic clearance. C225 clearance did not change with repeated administration or with coadministration of cisplatin. Antibodies against C225 were detected in only one patient, and C225-associated toxicity was minimal. Patients experiencing disease stabilization were seen in all studies. In the study combining C225 and cisplatin, nine (69%) of 13 patients treated with antibody doses >/= 50 mg/m(2) completed 12 weeks of therapy, and two partial responses were observed. CONCLUSION: C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.
Adult↗
Attention following pediatric head injury: a developmental perspective.
This study investigated the relations between age at injury (AAI) and attentional functioning, and intellectual and academic achievement following pediatric head injury. The theoretical framework of attention proposed by Mirsky, Anthony, Duncan, Ahern, and Kellam (1991) provided the basis for this analysis, and the profile of attention found in uninjured children was evaluated for this sample. Thirty-three moderately head-injured individuals were recruited, with AAI ranging from 1 to 12 years. First, the development of attentional skills in this closed head injury (CHI) sample was found to be comparable to that of Mirsky et al.'s model. Second, AAI did not predict outcome and appeared not to be associated with the finding of mildly delayed acquisition of spelling and arithmetic skills. Also, AAI did not predict the behavioral symptoms of inattention present in this sample as indicated by parental report. It may be that AAI only influences development following severe CHI in which there is permanent cerebral pathology.
Attention↗
A cooperative model for Ca(++) efflux windowing from cell membranes exposed to electromagnetic radiation.
We propose a simplified version of a cooperative lattice membrane model given by Grodsky to explain observed Ca(++) efflux windowing effects from cell membranes exposed to electromagnetic radiation. Assuming that field induced conformational interactions occur only between bistable receptor sites and glycoprotein Ca(++) sites on the surface of the membrane, the model is shown to be equivalent to an Ising model. This model is known to have a phase transition to an ordered state in which a macroscopic number of Ca(++) sites are either occupied or unoccupied. We identify such states with enhanced Ca(++) efflux from cell membranes. By further assuming an averaged signal, sinusoidally varying coupling between receptor and Ca(++) sites and a power-law dependence of the characteristic time constant on the induced power-density of the applied field, we show that the model is consistent with published experimental results on power density windowing effects for particular values of model parameters. For these parameter values, the model predicts further power densities where windowing effects may be observed under appropriate conditions.
Algorithms↗
Novel mechanism of inhibition of elastase by beta-lactams is defined by two inhibitor crystal complexes.
Two structurally related beta-lactams form different covalent complexes upon reaction with porcine elastase. The high resolution x-ray structures of these two complexes provide a clear insight into the mechanism of the reaction and suggest the design of a new class of serine protease inhibitors that resist enzyme reactivation by hydrolysis of the acyl intermediate. The presence of a hydroxyethyl substituent on the beta-lactam ring provides a new reaction pathway resulting in the elimination of the hydroxyethyl group and the formation of a stabilizing conjugated double bond system. In contrast, the presence of a diethyl substituent on the beta-lactam ring leads to addition of water. The two enzyme complexes show very different binding modes in the enzyme active site.
Animals↗
OHIO-1 beta-lactamase mutants: the Arg244Ser mutant and resistance to beta-lactams and beta-lactamase inhibitors.
Mutations at residue 244 (Ambler numbering system) in the class A TEM beta-lactamase confer resistance to inactivation by beta-lactamase inhibitors and result in diminished turnover of beta-lactam substrates. The Arg244Ser mutant of the OHIO-1 beta-lactamase, an SHV family enzyme, demonstrates variable susceptibilities to beta-lactamase inhibitors and has significantly reduced catalytic efficiency. The minimum inhibitory concentrations (MICs) for Escherichia coli DH5alpha expressing the Arg244Ser beta-lactamase were reduced when compared to the strain bearing the OHIO-1 beta-lactamase: ampicillin, 512 vs. 8192 micrograms ml-1; cephaloridine, 4 vs. 32 micrograms ml-1, respectively. The MICs for the beta-lactam beta-lactamase inhibitor combinations demonstrated resistance only to ampicillin-clavulanate, 16/8 vs. 8/4 micrograms ml-1 respectively. In contrast, there was increased susceptibility to ampicillin-sulbactam, ampicillin-tazobactam, and piperacillin-tazobactam. When compared to the OHIO-1 beta-lactamase homogenous preparations of the Arg244Ser beta-lactamase enzyme demonstrated increased Km and decreased kcat values for benzylpenicillin (Km=17 vs. 50 microM, kcat=345 vs. 234 s-1) and cephaloridine (Km=97 vs. 202 microM, kcat=1023 vs. 202 s-1). Although the Ki and IC50 values were increased for each inhibitor when compared to OHIO-1 beta-lactamase, the turnover numbers (tn) required for inactivation were increased only for clavulanate. For the Arg244Ser mutant enzyme of OHIO-1, the increased Ki, decreased tn for the sulfones, and different partition ratio (kcat/kinact) support the notion that not all class A enzymes are inactivated in the same manner, and that certain class A beta-lactamase enzymes may react differently with identical substitutions in structurally conserved amino acids. The resistance phenotype of a specific mutations can vary depending on the enzyme.
Drug Resistance↗