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Biomedical subjects

E Grant

Publications and source records attributed to E Grant.

At least 19 recordsLinked to original sources

Authoritative parenting and parental stress in parents of pre-school and older children with developmental disabilities.

BACKGROUND: Rearing a child with a developmental disability is associated with increased parental stress. Theories of stress and adjustment and bi-directional theories of child development suggest that parenting could influence these negative outcomes. METHODS: Relationships between parenting approaches and stress in parents of children with developmental disabilities (DD) (N = 53) were examined across two age groups, 3-5 years and 9-11 years and compared with a contrast group of typically developing children (TD) (N = 60). Measures used were the Parenting Stress Index-Short Form and Rickel and Biasatti's modification of Block's Child Rearing Practices Report, classified into Baumrind's parenting styles using Reitman and Gross's method. RESULTS: Parents in the older DD group used Authoritative parenting less than parents in the younger DD group, while the opposite developmental pattern was seen in the TD group. Multivariate analysis of variance showed a significant group x parenting style interaction for Parental Distress, Parent-Child Dysfunctional Interaction and Difficult Child. Stress measures were higher for the DD group and seemed to be associated with Authoritative parenting approaches, an effect that was not observed in the TD group. CONCLUSIONS: Findings suggest that the well-established effect of group on stress may be moderated by parenting style. Authoritative parenting may be highly stressful for parents of children with DD to implement, resulting in a decrease in its use across the two age groups.

Age Distribution↗

Influence of body mass index on the response to asthma controller agents.

The incidence of asthma has been positively associated with obesity. Asthma comprises diverse "phenotypes" reflecting heterogeneity in a number of characteristics, including response to therapy. The present authors examined whether body mass index (BMI) influenced the response to placebo, as well as to two asthma controller medications. A post hoc analysis was performed, pooling data from four double-blind, placebo-controlled studies randomising 3,073 moderate asthmatic adults to montelukast (n=1,439), beclomethasone (n=894) or placebo (n=740). The primary end point was asthma control days; other end points were forced expiratory volume in one second, beta-agonist use and nocturnal awakening. Analyses were conducted using BMI classification into normal (<25.0 kg.m-2; 52% of patients), overweight (25-29.9 kg.m-2; 32%) and obese (>or=30.0 kg.m-2; 16%) categories, as well as BMI as a continuous variable. The treatment groups were balanced for BMI, demographic characteristics and parameters of asthma control. The placebo response for all end points was generally lower with increasing BMI. Similarly, the response to the inhaled corticosteroid decreased, whereas the response to the leukotriene antagonist remained stable. In conclusion, post hoc data from the present study suggested that body mass index may influence the natural history of asthma control (as reflected by response to placebo) and may differentially influence response to the two active agents, warranting explicit testing in future prospective studies.

Acetates↗

The AD8: a brief informant interview to detect dementia.

BACKGROUND: Brief measures that accurately discriminate normal cognitive aging from very mild dementia are lacking. Cognitive tests often are insensitive to very mild dementia. Informant-based measures may be more sensitive in detecting early dementia. OBJECTIVE: To identify informant-reported clinical variables that differentiate cognitively normal individuals from those with very mild dementia. METHODS: A 55-item battery of informant queries regarding an individual's cognitive status was derived from a semistructured interview and a consensus panel of dementia experts. The battery was evaluated with informants for 189 consecutive participants of a longitudinal study of memory and aging and compared with an independently obtained Clinical Dementia Rating (CDR) score for the participant. Multiple regression and receiver operator characteristic curves assessed subsets of the items to discriminate between CDR 0 (no dementia) and CDR 0.5 (very mild dementia). RESULTS: The final version (AD8) querying memory, orientation, judgment, and function was administered to an additional sample of 112 CDR 0 and 68 CDR 0.5 participants. Using a cut-off of two items endorsed, the area under the curve was 0.834, suggesting good to excellent discrimination, sensitivity was 74%, and specificity was 86% (prevalence of 0.38 for very mild dementia). Inclusion of 56 additional individuals with mild to severe dementia (increasing dementia prevalence to 0.53) increased sensitivity to 85%. CONCLUSIONS: The AD8 is a brief, sensitive measure that reliably differentiates between nondemented and demented individuals. Use of the AD8 in conjunction with a brief assessment of the participant could improve diagnostic accuracy in general practice.

Aged↗

The accuracy of preoperative orthognathic predictions.

We assessed the accuracy of preoperative OPAL trade mark orthognathic predictions by retrospective analysis of 25 Class II patients who had had orthodontic treatment combined with mandibular advancement osteotomy. Preoperative and postoperative lateral cephalographs were digitised and surgical predictions generated using OPAL software. Each prediction was compared with the corresponding clinical changes. We also made a method error study by doing a random retracing of 25 cephalographs. Predictions of some of the principal OPAL values (SNA, ANB, LAFH%, OJ, OB) were reasonably accurate in terms of mean values. However, there were large individual variations for most variables and predictions of the vertical skeletal, incisor, and Wits measurements were imprecise. In particular, there was a bias towards under-prediction of the vertical skeletal changes when there was more backward mandibular rotation than anticipated. Immediate postoperative cephalographs were also affected by a 2.1mm mean downward displacement of the mandible as a result of the surgical wafer.

Adult↗

Holoprosencephaly--topologic variations in a liveborn series: a general model based upon MRI analysis.

We present an MRI-based anatomic analysis of a series of 9 human brains, representing lobar, semilobar and alobar forms of holoprosencephaly. The analysis of these variable forms of the malformation is based upon a topologic systematics established in a prior analysis of a homogeneous set of semilobar malformations. This systematics has the dual advantage that it serves both as a uniform reference for qualitative description and as a quantitative descriptive base for mathematical correlations between parameters of topology and of growth and development. Within this systematics, the prosencephalic midline is divided from caudal to rostral into diencephalic (DD-right and left, subthalamus through suprachiasmatic junction with telencephalon), telencephalic (TT-right and left, suprachiasmatic border of telencephalon midline to hippocampal commissure) and diencephalic-telencephalic (DT-right and left-hippocampal commissure through temporal limb of choroid fissure) segments. The topologic abnormality of the initial semilobar series was expressed in an orderly rostral to caudal gradient along the TT segment. In each malformation, normal midline topology began with a small posterior corpus callosum. Although the topologic anomaly in the present series invariably also involved the TT segment, this involvement was not continuous and was variably associated with anomalies of the DD in 6 and unilaterally of the DT in 1 brain. In the present as well as with the earlier series of HPE malformations but not in "normative brains," total telencephalic growth is strongly correlated with the length of the midline telencephalic segment. We propose that this system of analysis will be sensitive to the developmental stage and locus of expression of genetic and non-genetic determinants of the formal origin of HPE. For all of the present series, karyotype anlyses were normal. Mutations in the Shh and Zic2 genes were excluded in 2 cases.

Brain↗

Semilobar holoprosencephaly with midline 'seam': a topologic and morphogenetic model based upon MRI analysis.

We present an MRI-based anatomic analysis of a series of seven human brains with the semilobar form of holoprosencephaly. The analysis defines a set of common descriptors for a pattern of topological anomaly which is uniform for the set of seven brains. The core of the anomaly is a rostro-caudally aligned midline gray matter 'seam' that extends from the telencephalic-suprachiasmatic junctional region to abut the posterior aspect of the callosal commissure. The seam forms the ventricular roof throughout its extent. Rostrally it is formed by the conjoined heads of caudate/accumbens nuclei. It continues caudally as a gray matter bridge in the fundus of the interhemispheric fissure, where it bridges right and left neocortex. Fornix, septal nuclei and septal limb of the choroid plexus are absent, and the telencephalic ventricles communicate with the diencephalic via open septal limbs of the choroid fissures. By contrast, the temporal limb of hippocampal formation and the choroid plexus are normal and the temporal limb of the choroid fissure is closed. This topological anomaly of conjoined left and right cortical and nuclear gray matter into a midline seam and absent septal structures is thus confined to the region of the midline telencephalic hemisphere evagination. Total telencephalic growth is strongly correlated with the length of this topologically abnormal midline telencephalic segment. The set of findings is consistent with graded failure of induction of rostral to caudal specification in the midline rostral telencephalic zone.

Aging↗

The validity of computerized orthognathic predictions.

OBJECTIVE: utilizing OPAL cephalometric prediction software. DESIGN: A retrospective investigation involving the random selection of Class II orthognathic patients from surgical records. SUBJECTS: These 25 cases had undergone treatment aimed at producing Class I incisors. This involved fixed orthodontic appliances and a mandibular advancement osteotomy with rigid internal fixation. METHODS: Lateral cephalographs from three key stages were digitized and processed using the OPAL software. Pre-treatment predictions were generated and compared with the actual clinical changes. RESULTS: Prediction of some of the principal OPAL variables (SNA, ANB, LAFH%, OJ, OB) was reasonably accurate in terms of mean values. However, there were large individual variations for most measurements, and prediction of Wits, MxP/MnP, LAFH, and LPFH was prone to systematic error. In particular, there was a tendency towards over-prediction of the surgically-induced backward mandibular rotation. CONCLUSION: In lieu of further validation caution should be exercised with the interpretation of individual OPAL predictions, especially vertical skeletal changes, and an explanation given to patients that orthognathic predictions are based on generalizations.

Adult↗

Sustained attention in young people at high risk for schizophrenia.

BACKGROUND: Sustained attention has been found to be impaired in individuals suffering from schizophrenia and their close relatives. This has led to the hypothesis that impaired sustained attention is an indicator of vulnerability to schizophrenia. METHODS: The Edinburgh High Risk Study used the Continuous Performance Test-Identical Pairs version (CPT-IP) to assess sustained attention in 127 high risk participants, 30 controls and 15 first-episode schizophrenic patients. A second assessment was completed by 59 high risk and 18 control participants 18 months to 2 years after the first. RESULTS: No differences in attentional capacity were found between the high risk and control groups and there was no association between genetic liability to schizophrenia and poor performance on the CPT-IP. Additionally, no association between occurrence of psychotic symptoms in the high risk group and impaired attentional capacity was found. CONCLUSIONS: The results suggest that deficits in sustained attention are not indicative of a genetic vulnerability to schizophrenia, and are not associated with the occurrence of psychotic symptoms.

Adult↗

Edinburgh high risk study--findings after four years: demographic, attainment and psychopathological issues.

This study reports findings of the Edinburgh High Risk Study four years after it began. This study is designed to explore the pathogenesis of schizophrenia by examining a large sample of young adults aged 16-25 years who are at enhanced risk of developing schizophrenia by having two close relatives with the disorder, and comparing them with matched controls. This paper presents comparisons of the high risk subjects, well controls and subjects with first-episode schizophrenia in terms of demographic, childhood, psychopathological, educational and employment, forensic and social work variables. High risk subjects have more psychological difficulties, poorer educational and employment attainment, and more social work contact than controls. The enhanced social work involvement related to the presence of a schizophrenic parent (especially a mother) but the other difficulties could not be attributed to that situation. Neurotic, partially held psychotic and fully held psychotic symptoms all occurred in both subjects and controls, but all were significantly more common in high risk subjects. Clinical schizophrenia has so far developed in 10 high risk subjects and in no controls. Possible confounding effects of drug or alcohol misuse were considered but were found unlikely to be important.

Adolescent↗

CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection.

T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) alpha and beta chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria.

Animals↗

CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection.

The discovery of the CD1 antigen presentation pathway has expanded the spectrum of T-cell antigens to include lipids, but the range of natural lipid antigens and functions of CD1-restricted T cells in vivo remain poorly understood. Here we show that the T-cell antigen receptor and the CD1c protein mediate recognition of an evolutionarily conserved family of isoprenoid glycolipids whose members include essential components of protein glycosylation and cell-wall synthesis pathways. A CD1c-restricted, mycobacteria-specific T-cell line recognized two previously unknown mycobacterial hexosyl-1-phosphoisoprenoids and structurally related mannosyl-beta1-phosphodolichols. Responses to mannosyl-beta1-phosphodolichols were common among CD1c-restricted T-cell lines and peripheral blood T lymphocytes of human subjects recently infected with M. tuberculosis, but were not seen in naive control subjects. These results define a new class of broadly distributed lipid antigens presented by the CD1 system during infection in vivo and suggest an immune mechanism for recognition of senescent or transformed cells that are known to have altered dolichol lipids.

Adult↗

Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study.

BACKGROUND: Studies of groups of individuals who have a genetically high risk of developing schizophrenia, have found neuropsychological impairments that highlight likely trait markers of the schizophrenic genotype. This paper describes the change in neuropsychological function and associations with psychiatric state of high risk participants during the first two assessments of the Edinburgh High Risk Study. METHODS: Seventy-eight high risk participants and 22 normal controls, age and sex matched completed two neuropsychological assessments 18 months to 2 years apart. The areas of function assessed include intellectual function, executive function, learning and memory, and verbal ability and language. RESULTS: The high risk participants performed significantly worse on particular tests of verbal memory and executive function over the two assessments than matched controls. Those high risk participants who experienced psychotic symptoms were found to exhibit a decline in IQ and perform worse on tests of verbal memory and executive function than those without symptoms. An increase in psychotic symptoms between the two assessments in the high risk group was found to be associated with an apparent decline in IQ and memory. CONCLUSIONS: The results suggest that the development of psychotic symptoms is preceded by a decline in IQ and memory. This may reflect a general and a more specific disease process respectively.

Adolescent↗

Late radiation injury following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor.

PURPOSE: To document the late radiographic change following hyperfractionated craniospinal radiotherapy for primitive neuroectodermal tumor. METHODS AND MATERIALS: We reviewed long-term MRI scans on 21 patients with standard risk and high risk primitive neuroectodermal tumor treated with hyperfractionated radiotherapy following surgical resection. High risk patients also received adjuvant chemotherapy. Long-term scans were defined as scan obtained at least 1 year from diagnosis. Clinical follow-up data was available on all patients. RESULTS: Twelve of 21 patients had MRI evidence of necrosis, telangiectasia, white matter changes, basal ganglia change, or cerebral atrophy consistent with radiation injury. No patient required treatment for the radiographic change. CONCLUSIONS: Slightly over half of the patients had evidence of long-term radiation effect following craniospinal axis radiotherapy. However, no patient had frank clinical symptoms related to the radiographic findings.

Adolescent↗

Dielectric behaviour of frozen DNA in solution.

In this article, measurements are reported on ice and frozen DNA solutions between 100 Hz-10 MHz. Pure ice is shown to exhibit single relaxation behaviour, which confirms previous work taken over a more restricted frequency range. The frozen DNA solution displays double-dispersion behaviour. One dispersion centred around 3 kHz is due to a defect mechanism while the other, centred around 2 MHz, may be attributed to counterion flow through the water immediately adjacent to the DNA molecule.

Animals↗

Neuropsychological assessment of young people at high genetic risk for developing schizophrenia compared with controls: preliminary findings of the Edinburgh High Risk Study (EHRS).

BACKGROUND: Finding risk indicators for schizophrenia among groups of individuals at high genetic risk for the disorder, has been the driving force of the high risk paradigm. The current study describes the preliminary results of a neuropsychological assessment battery conducted on the first 50% of subjects from the Edinburgh High Risk Study. METHODS: One hundred and four high risk subjects and 33 normal controls, age and sex matched, were given a neuropsychological assessment battery. The areas of function assessed and reported here include intellectual function, executive function, perceptual motor speed, mental control/ encoding, verbal ability and language, learning and memory measures, and handedness. RESULTS: The high risk subjects performed significantly more poorly than the control subjects in the following domains of neuropsychological function: intellectual function, executive function, mental control/encoding and learning, and memory. Controlling for IQ, high risk subjects made significantly more errors on the Hayling Sentence Completion Test (HSCT), took longer to complete section A of the HSCT, had lower scores on the delayed recall condition of the visual reproductions subtest of the Wechsler Memory Scale-Revised, and had significantly poorer Rivermead Behavioural Memory Test (RBMT) standardized scores. The presence of significant group by IQ interactions for the RBMT and time to complete section A of the HSCT suggested that differences among the groups were more marked in the lower IQ range. Performance on the HSCT was found to be related to the degree of family history of schizophrenia. CONCLUSIONS: High risk subjects performed more poorly than controls on all tests of intellectual function and on aspects of executive function and memory.

Adult↗

People at risk of schizophrenia. Sample characteristics of the first 100 cases in the Edinburgh High-Risk Study.

BACKGROUND: The Edinburgh High-Risk Study is designed to explore the underlying pathogenesis of schizophrenia. AIMS: To establish the sample characteristics of the first 100 subjects in this study of young adults at risk of schizophrenia for genetic reasons, and to compare them with appropriate controls. METHOD: Details of the recruitment of the first 100 high-risk subjects aged 16-25 years into a prospective Scotland-wide study are given. Subjects and 30 age- and gender-matched normal controls were interviewed using the PSE, SADS-L and SIS and an unstructured psychiatric interview. RESULTS: Some significant differences emerged between the high-risk group and the control group, namely in previous psychiatric history (31 v. 6.3%), forensic contacts (19 v. 3.1%) and delinquent behaviour (20 v. 3.1%). There were also differences in some parameters from the SIS: childhood social isolation, interpersonal sensitivity, social isolation, suicidal ideation, restricted affect, oddness and disordered speech. CONCLUSIONS: These differences may represent increased risk of developing schizophrenia although their true significance will not be revealed until the cohort has been followed through the at-risk years.

Adult↗