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Biomedical subjects

M McCarron

Publications and source records attributed to M McCarron.

At least 19 recordsLinked to original sources

A measure of subjective burden for dementia care: the Caregiving Difficulty Scale--Intellectual Disability.

BACKGROUND: It has been suggested in the literature on family caregiving for persons with Alzheimer's dementia (AD) that levels of objective and subjective burden among carers often predict institutionalization of the persons with AD. There is a paucity of measures to assess whether perceived burden among formal caregivers may also predict movement to more restrictive settings for persons with intellectual disabilities (ID) and AD. This study focused upon the development of a measure of subjective burden, The Caregiving Difficulty Scale - Intellectual Disability (CDS-ID) as a first step in addressing this measurement deficit. METHODS: An existing caregiver subjective burden scale, the Caregiving Hassles Scale (CHS) was adapted for use with 203 staff caregivers of persons with ID and AD. Preliminary testing of existing CHS items and proposed new items was carried out in two countries, Ireland and the USA. Confirmatory factor analysis with the existing items and exploratory factor analysis with existing and proposed new items for the scale was used to establish the content and test the psychometric properties of a revised scale, the CDS-ID. RESULTS: On the existing CHS items, staff carers appeared to experience greater subjective burden than has been reported for family caregivers. However, the psychometric properties of the CHS found with this population were poor. Factor analysis produced a revised scale, the CDS-ID with three subscales with Cronbach alphas ranging from 0.75 to 0.93 and 38 items overall. CONCLUSIONS: This new scale when used with objective burden and other scales offers an opportunity to more systematically measure the difficulties staff experience when caring for persons with ID who present with symptoms of AD.

Adult↗

Health co-morbidities in ageing persons with Down syndrome and Alzheimer's dementia.

BACKGROUND: Consideration of the relationship between physical and mental health co-morbidities in ageing persons with Down syndrome (DS) and Alzheimer's dementia (AD) is of clinical importance both from a care and resource perspective. AIM To investigate and measure health co-morbidities in ageing persons with Down syndrome with and without AD. METHODS: Recorded physical and mental health needs were ascertained for 124 persons with DS>35 years through a systematic and detailed search of individual medical and nursing case records. Differences in persons with and without AD were investigated, by stage of dementia and by level of intellectual disability (ID). A summed score for health co-morbidities was created and compared using t-tests. RESULTS: Persons with AD had significantly higher co-morbidity scores than persons without AD (t=-8.992, d.f.=121, P<0.0001). There was also a significant difference in summed co-morbidity scores for persons at end-stage vs. persons at mid-stage AD (t=-6.429, d.f.=56, P<0.0001). No differences were found by level of ID. CONCLUSIONS: Increasing health co-morbidities in persons with DS and AD have important implications for care and resources. Appropriate environmental supports combined with competent skilled staff are crucial and will have an important impact on the quality of life for this increasingly at risk population.

Aging↗

Novel employment of lactate dehydrogenase release from porcine aortic endothelial cells (PAEC) as a quantitative marker of cytotoxic activity in thermophilic Campylobacter spp. from human faecal isolates, poultry and environmental sources.

The aim of this study was to employ a novel cytotoxicity assay based on primary porcine aortic endothelial cells in combination with a lactate dehydrogenase release assay to quantitatively determine differences in cytotoxin production between Campylobacter jejuni, C. coli, C. lari and urease-positive thermophilic campylobacters (UPTC), isolated from human faeces, animals and environmental sources. Campylobacter isolates totalling 34 and comprising of C. jejuni (n = 24) C. coli (n = 5) and UPTC (n = 4) and C. lari (n = 1) were analysed. The cytotoxic response ranged from 32.15 to 64.47% and 33.08 to 59.41%, for C. jejuni from chicken and human isolates, respectively and there was no statistically significant difference (P > 0.05) in cytotoxic response between C. jejuni isolated from humans and chicken isolates (50.78% versus 50.55% cytotoxicity, respectively). However, there was a difference in response between C. jejuni and C. coli isolated from chickens (50.78% versus 33.22% cytotoxicity, respectively). The greatest cytotoxic response was obtained with the UPTC group of organisms examined (n = 4 isolates) (mean cytotoxic response = 57.11% cytotoxicity. Employment of this cytotoxin assay may help identify virulent strains in poultry that could potentially proceed to cause clinical problems for humans and thus intervention measures targeted at the reduction or elimination of such specific strains, may be sought.

Animals↗

Responding to the challenges of ageing and dementia in intellectual disability in Ireland.

The intellectual disability (ID) population in Ireland is ageing and the number of older persons with the dual disability of ID and dementia is increasing. In spite of these demographic trends, as in other countries adequate policy and service provision for this population are lacking. This paper draws upon data available on the population with ID and dementia, reviews both generic and ID specific literature, considers the policy context and argues for a specific model of service provision. A service model is proposed for the development of multidisciplinary specialist teams within ID, delivered through mobile regional ID dementia clinics.

Adult↗

A pilot study of the reliability and validity of the Caregiver Activity Survey - Intellectual Disability (CAS-ID).

BACKGROUND: People with Down's syndrome (DS) are at increased risk of Alzheimer-type dementia (AD) when compared to the general population. Despite AD being a serious progressive disorder, little attention has been paid to the impact of the illness on formal caregivers. In the general population, the Caregiver Activity Survey (CAS) is used to measure time spent by family caregivers assisting people with AD in their day-to-day activities of living. In order to plan appropriate models of health and social care effectively for people with AD and DS, it is imperative that the care requirements of individuals at different stages of dementia are realized. An amended version of this survey, the Caregiver Activity Survey - Intellectual Disability (CAS-ID), was developed and tested for use by professional caregivers in the present study. METHODS: The CAS-ID was administered to 30 people with DS and their caregivers. Convergent validity was tested by comparing the results of the CAS-ID to other validated tests for cognitive and functional impairment in individuals with DS. Test-retest and inter-rater reliability were investigated. RESULTS: The final version of the CAS-ID consists of eight items: dressing, bathing/showering, grooming, toileting, eating and drinking, housekeeping, nursing care-related activities, and supervision/ behaviour management. The scale had excellent test-retest reliability, and correlated strongly with the Down Syndrome Mental Status Examination (DSMSE; r = -0.770), the Test for Severe Impairment (TSI; r = -0.881) and the Daily Living Skills Questionnaire (DLSQ; r = -0.855). CONCLUSIONS: The present authors provide preliminary evidence for the validity and reliability of the CAS-ID. This instrument offers a means of identifying and measuring care and resources requirements as this population experiences symptoms of dementia. Such information may help assist healthcare professionals in planning supports and services to address the care challenges evidenced at different stages of the disease process.

Activities of Daily Living↗

Temporal lobe-oriented CT scanning and dementia in Down's syndrome.

BACKGROUND: Although individuals with Down's syndrome (DS) are uniquely at risk of developing Alzheimer's disease, the diagnosis of dementia in DS is problematic because of the difficulty in detecting cognitive decline in individuals with pre-existing learning disability. AIM: To determine if dementia in DS is associated with Medial Temporal Lobe (MTL) atrophy as measured by temporal lobe-oriented CT scanning. METHOD: Ten individuals with DS who were experiencing functional decline had CT scans with temporal lobe-oriented views. All individuals were assessed for the presence of dementia according to modified DSM-IIIR criteria. The minimal thickness of the MTL, corrected for age-related atrophy was measured using a computer calipers at the level of the mid-brainstem by a radiologist blind to the dementia diagnosis. RESULTS: All six individuals who met modified DSM-IIIR criteria for dementia showed significant MTL atrophy. CONCLUSIONS: The utility of temporal lobe-oriented CT scanning as an adjunct to the diagnosis of dementia in DS appears promising and warrants further study.

Adult↗

Dementia in people with Down's syndrome.

OBJECTIVES: To determine the prevalence of dementia in an Irish sample of people with Down's syndrome (DS) and to examine associated clinical characteristics of dementia in this group. METHOD: 285 people with DS (Age 35-74 years, mean age +/- SD 46.5 +/- 8.2 years) were included in this cross-sectional study. The diagnosis of dementia was made using modified DSMIV criteria. Cognitive tests used were the Down's syndrome Mental Status Examination (DSMSE), Test for Severe Impairment (TSI) and adaptive function was measured by the Daily Living Skills Questionnaire (DLSQ). RESULTS: The overall prevalence of dementia was 13.3%. The presence of dementia was associated with epilepsy, myoclonus, and head injury. The demented DS group were significantly older (n = 38, mean age 54.7 years SD +/- 7.5) than the non-demented (n = 246, mean age 45.6, SD +/- 7.3). The TSI and DLSQ had a satisfactory spread of scores without 'floor' or 'ceiling' effects in people with moderate and severe learning disability. Median scores in demented versus the non-demented groups were significantly different for each measure of function. CONCLUSIONS: Dementia had a prevalence of 13.3% and occurred at a mean age of 54.7 years. The combination of DLSQ score, age and presence of epilepsy were found to predict presence of dementia.

Activities of Daily Living↗

Dopa decarboxylase gene polymorphisms and attention deficit hyperactivity disorder (ADHD): no evidence for association in the Irish population.

Dopa decarboxylase (DDC) is an enzyme which catalyses the decarboxylation of both dopa to dopamine and L-5 hydroxytryptophan to serotonin. Both catecholamines are major neurotransmitters of the mammalian nervous system. It has been suggested that genes involved in the dopaminergic system play a primary role in predisposing to attention deficit hyperactivity disorder (ADHD). In this study, the 4-bp insertion/deletion variant mapped to the first neuronally expressed exon 1 at the dopa decarboxylase gene and two microsatellite markers flanking the gene were investigated for possible association with ADHD. Using HHRR, we observed an increased transmission (though not significant) of the 4-bp insertion (allele 1) to ADHD cases (chi(2) = 2.72, P = 0.1, RR = 1.25). However marginally significant excess transmission of allele 10 (213 bp) of the 3' microsatellite D7S2422 ( approximately 0.75 cM distal to dopa decarboxylase gene) was found (chi(2) = 4.2, P = 0.04, RR=1.48). Interestingly, a haplotype containing both alleles is transmitted more frequently (chi(2)= 5, P = 0.025). Analysing data by the sex of transmitting parent showed a greater relative risk for paternal transmission of the 4-bp insertion allele and allele 10 of the D7S2422 (RR = 1.48 and 1.63 respectively). This provides preliminary evidence that this locus or a closely mapped DNA variant may be involved in the genetic susceptibility to ADHD. However, further studies are required to either confirm or refute these observations.

Alleles↗

No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population.

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset syndromes affecting 3%-6% of school-age children worldwide. Although the biological basis of ADHD is unknown, a dopaminergic abnormality has long been suggested. The dopamine D4 receptor gene (DRD4) has been mapped to chromosome 11p15.5 and has been implicated in predisposition to ADHD. Several independent genetic association studies have demonstrated increased frequency of the DRD4 7-repeat allele in ADHD cases compared with controls or excess transmission of the 7-repeat allele from parents to affected offspring. However, there have also been few negative studies. In this study we investigated 78 ADHD parent proband trios and 21 parent proband pairs for the transmission of the DRD4 alleles in HHRR and case control design. We found no significant differences in the frequency of the DRD4 alleles transmitted or not transmitted to ADHD cases from their parents nor when comparing case allele frequencies to ethnically matched controls. Therefore, it is unlikely that the DRD4 7-repeat allele is associated with ADHD in the Irish population.

Adolescent↗

Conformational preferences in 2-nitrophenylthiolates: interplay between intra- and intermolecular forces; structures of (E)-1-(4-methyl-2-nitrobenzenethiolato)-2-phenylethene, S-(2-nitrophenyl)-benzenecarbothiolate and 1-(2-nitrophenylthio)-2,5-pyrrolidinedione

In (E)-1-(4-methyl-2-nitrobenzenethiolato)-2-phenylethene, C15H13NO2S (1) (orthorhombic Pbca), the nitro group is almost coplanar with the adjacent aryl ring, but the dihedral angles between the nitro-aryl and styryl fragments is approximately 121 degrees. The molecules are linked by paired C-H...O hydrogen bonds in a chain of rings. In S-(2-nitrophenyl)benzenecarbothiolate, C13H9NO3S (2) (monoclinic P2(1)/a), the nitro group is rotated by 33.0 (2) degrees out of the plane of the adjacent aryl ring and the thiobenzoate group is strongly twisted away from the plane of the disubstituted aryl ring. The molecules of (2) are linked into chains by C--H...O hydrogen bonds, and each chain is linked to two neighbouring chains by means of aromatic pi... pi stacking interactions. In 1-(2-nitrophenylthio)-2,5-pyrrolidinedione, C10H8N2O4S (3) (monoclinic P2(1)/a), the nitro group is again almost coplanar with the adjacent aryl ring, but the pyrrolidinedione unit is almost orthogonal to the O2NC6H4SN plane. There are three types of C-H...O hydrogen bond in the structure, and these link the molecules into a two-dimensional net. The conformations of these molecules have been investigated by SCF calculations and two energy minima have been identified for each: the molecules of (1) and (3) adopt conformations in their crystals which are close to those at the overall energy minima calculated for isolated molecules, while molecules of (2) adopt a conformation in the crystal close to that calculated for the local energy minimum. Comparisons are made with the structures of some related compounds and it is concluded that, while the nature of the two conformational minima is determined by intramolecular forces, the choice between them is determined primarily by intermolecular forces.

Journal Article↗

Age at onset of dementia and age of menopause in women with Down's syndrome.

Menstrual status and the age of menopause were investigated in 143 Irish females with Down's syndrome (DS). The average age of menopause in 42 subjects (44.7 years) was younger than in the general population. The age at onset of dementia correlated with the age of menopause. This finding may be a manifestation of accelerated ageing in DS or point to oestrogen deficiency being an independent risk factor for the development of Alzheimer's dementia in DS. The implications of this finding for possible treatments are discussed.

Adult↗

Determinants of aggression, and adaptive and maladaptive behaviour in older people with Down's syndrome with and without dementia.

In a cross-sectional study of aggression, and adaptive and maladaptive behaviour in 128 subjects with Down's syndrome (DS), 29 of whom had dementia, the current authors found that the presence of dementia was not predictive of aggression or maladaptive behaviour. However, the level of adaptive behaviour was shown to be lower in subjects with dementia, and in those with lower levels of cognitive functioning, as measured on a rating instrument, the Test for Severe Impairment. Although the presence of aggressive behaviours is not higher in subjects with dementia and DS on cross-sectional review, it remains to be seen whether aggression will increase in individual cases with the onset or progression of dementia. The decline in adaptive behaviour shown in the present study confirms the findings of previous studies and indicates a direction for service development for persons with the dual diagnosis of dementia and DS.

Adult↗

Cognitive decline in Down syndrome: a validity/reliability study of the test for severe impairment.

The utility of the Test for Severe Impairment was studied with 60 older persons who had Down syndrome. Construct validity, test-retest reliability, and interrater reliability were established for the full study group and for subgroups based on degree of mental retardation and dementia status. There was no difference in scores by gender. There were some interesting findings for the group with moderate mental retardation and dementia and the group with severe mental retardation without dementia that may signal specific applications and limitations of the test for use with individuals who have Down syndrome. The internal consistency of the instrument was satisfactory. Results suggest that this test is a useful performance-based task for persons with Down syndrome.

Adult↗

Drosophila P element transposase induces male recombination additively and without a requirement for P element excision or insertion.

P element dysgenesis-associated male recombination in Drosophila was examined with a selective system focused upon a section of the third chromosome divided into eight recombination segments. Tests compared crossing over in the presence of none, one and two doses of P(delta 2-3)(99B), a non-mobile transposase source, in the absence of a mobilizable P element target in the genome. In the presence of the P transposase source, and without a P element target, significant male recombination occurred in genomic regions physically separated from the P(delta 2-3) site. Using two doses of P(delta 2-3) without a P element target, the male recombination rate doubled, and 90% of the crossovers occurred in the pericentric region. The distribution of recombination events, in the absence of P element targets approximates that seen in studies of radiation induced mitotic crossing over and the metaphase chromosome map. Another experiment examined the effects of one dose of P(delta 2-3) on a genome with a single P element target, P(lArB)(87C9), in the third recombination segment. Crossovers increased 58-fold in the immediate region of the P element target.

Animals↗

In vivo human somatic mutation: frequency and spectrum with age.

The number and molecular nature of in vivo mutations in relation to age was studied at the autosomal HLA-A locus in human lymphocytes. Mutant lymphocytes were isolated by immunoselection, cloned at limiting dilution and enumerated, and the HLA-A gene and other polymorphic gene loci on chromosome 6 were studied by Southern blotting to determine gene dosage and loss of heterozygosity. Results of 167 assays in 73 individuals showed that the total number of mutant lymphocytes increased significantly with age from a geometric mean frequency of 0.71 x 10(-5) in neonates to 6.53 x 10(-5) in elderly individuals. Analysis of rearrangement of T lymphocyte receptor beta or gamma chain genes gave a best estimate of 3.3% for the proportion of mutant lymphocytes detected which are clonally related. Molecular study of 434 mutants from 31 individuals showed no change on Southern blotting in 64.7%, gene deletion in 2.8% and mitotic recombination in 32.5%. Two mutants due to gene conversion but no mutants due to non-disjunction were detected. The number of 'no change' and recombination mutants increased significantly with age. There was a significant difference between individuals in the proportion of mutants which resulted from mitotic recombination and the data suggested that the proportion was bimodally distributed. The point of crossing-over in recombination mutants was predominantly randomly distributed between the HLA-A locus and the centromere.

Adolescent↗

Clove oil ingestion in an infant.

A case is presented in which a 7-month-old child developed central nervous system depression, urinary abnormalities and a large anion-gap acidosis after the accidental oral administration of clove oil. Supportive care and gastric lavage were sufficient for total recovery of the patient. Possible mechanisms of the depression and acidosis are discussed, and suggestions for treatment are presented.

Acidosis↗

The relationship between P elements and male recombination in Drosophila melanogaster.

P element dysgenesis associated male recombination in Drosophila was examined with a selective system focused upon 5% of the standard female genetic map divided into eight recombination segments. We found no correspondence between P element mobilization events and recombination in males in the intervals monitored. We defined two adjacent short genetic and molecular regions, one devoid of male recombination and the other acting as a "hot spot" for exchange in the absence of supporting P element insertion and excision activity. These data suggest that, even in the presence of mobilizing P elements, transposase may be active at non-P element sites, and that the genome may harbor sequences ranging from highly responsive to completely unresponsive to transposase action. A viewpoint is presented wherein P elements, with sequences that bind transposase, serve to focus the recombination action of transposase to encompass a region of DNA radiating outward from the initial binding site. We suggest that this region is measured in terms of chromosomal segments rather than limited to P element sequences.

Animals↗