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Biomedical subjects

D G Murphy

Publications and source records attributed to D G Murphy.

At least 19 recordsLinked to original sources
PubMed2007

Oestrogen, cognition and the maturing female brain.

Many women complain of memory and other cognitive difficulties at times that are associated with changes in ovarian steroid levels. However, the biological mechanisms through which ovarian steroids exert these effects remains poorly understood. Furthermore, the effect of hormone therapy, especially oestrogen therapy, on cognition and brain function in healthy women, and its role in the prevention of Alzheimer's disease, remains controversial. Here, we review the evidence that, in healthy women, ovarian steroids/oestrogen affects brain regions crucial to higher cognitive function at the macroscopic, microscopic, functional and neurotransmitter levels.

Aging↗
PubMed2004

SPET imaging of central muscarinic receptors with (R,R)[123I]-I-QNB: methodological considerations.

Investigations on the effect of normal healthy ageing on the muscarinic system have shown conflicting results. Also, in vivo determination of muscarinic receptor binding has been hampered by a lack of subtype selective ligands and differences in methods used for quantification of receptor densities. Recent in vitro and in vivo work with the muscarinic antagonist (R,R)-I-QNB indicates this ligand has selectivity for m(1) and m(4) muscarinic receptor subtypes. Therefore, we used (R,R)[(123)I]-I-QNB and single photon emission tomography to study brain m(1) and m(4) muscarinic receptors in 25 healthy female subjects (11 younger subjects, age range 26-32 years and 14 older subjects, age range 57-82 years). Our aims were to ascertain the viability of tracer administration and imaging within the same day, and to evaluate whether normalization to whole brain, compared to normalization to cerebellum, could alter the clinical interpretation of results. Images were analyzed using the simplified reference tissue model and by two ratio methods: normalization to whole brain and normalization to cerebellum. Significant correlations were observed between kinetic analysis and normalization to cerebellum, but not to whole brain. Both the kinetic analysis and normalization to cerebellum showed age-related reductions in muscarinic binding in frontal, orbitofrontal, and parietal regions. Normalization to whole brain, however, failed to detect age-related changes in any region. Here we show that, for this radiotracer, normalizing to a region of negligible specific binding (cerebellum) significantly improves sensitivity when compared to global normalization.

Adult↗
PubMed2001

Effects of estrogen replacement therapy on human brain aging: an in vivo 1H MRS study.

Estrogen replacement therapy (ERT) may preserve cognitive function in postmenopausal women, but the mechanism is unknown. Thus, the authors studied aging of parietal lobe and hippocampus using proton MR spectroscopy. ERT naïve postmenopausal women had a significant increase in choline-containing compounds (Cho) compared to long-term ERT users and young women. Cho reflects increased neuronal/glial membrane turnover. Thus, ERT's "neuroprotective" effect may include modulating the effects of age on neural integrity in brain regions involved in cognitive function.

Adult↗
PubMed2001

Prolactin response to d-fenfluramine in postmenopausal women on and off ERT: comparison with young women.

Estrogen is thought to have an impact on both psychological well being and cognitive function. The biological basis to this is not fully understood, but may involve estrogen's interactions with central serotonergic (5-HT) systems. Therefore, we studied the effect of long-term estrogen hormone replacement therapy (ERT) on central 5-HT tone in healthy postmenopausal women and made comparisons with young women. Prolactin (PRL) responses to the specific 5-HT releasing and re-uptake inhibiting agent, d-fenfluramine, were measured in three groups of healthy women: 11 young, 11 postmenopausal on long-term ERT, and 11 postmenopausal ERT naïve. PRL responses were significantly decreased in ERT naïve women compared to young healthy women. In contrast, PRL responses were not different between estrogen-treated and young women. Overall, there was a significant relationship between older age and lower PRL responsivity. These results suggest that central 5-HT tone is reduced in healthy postmenopausal women who are ERT naïve, but not in postmenopausal women who have received prolonged estrogen treatment. Estrogen may modulate age-related changes in 5-HT tone. This may partly explain why estrogen can decrease vulnerability to mood disorders and cognitive changes in postmenopausal women.

Adult↗
PubMed2001

Structural brain abnormalities associated with deletion at chromosome 22q11: quantitative neuroimaging study of adults with velo-cardio-facial syndrome.

BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with deletions in the qll band of chromosome 22, learning disability and psychosis, but the neurobiological basis is poorly understood. AIMS: To investigate brain anatomy in adults with VCFS. METHOD: Magnetic resonance imaging was used to study 10 patients with VCFS and 13 matched controls. We carried out three analyses: qualitative; traced regional brain volume; and measurement of grey and white matter volume. RESULTS: The subjects with VCFS had: a high prevalence of white matter hyperintensities and abnormalities of the septum pellucidum; a significantly smaller volume of cerebellum; and widespread differences in white matter bilaterally and regional specific differences in grey matter in the left cerebellum, insula, and frontal and right temporal lobes. CONCLUSIONS: Deletion at chromosome 22q11 is associated with brain abnormalities that are most likely neurodevelopmental and may partially explain the high prevalence of learning disability and psychiatric disorder in VCFS.

Adult↗
PubMed2000

Prefrontal and medial temporal correlates of repetitive violence to self and others.

BACKGROUND: The neurobiological basis for violence in humans is poorly understood, yet violent behavior (to self or others) is associated with large social and healthcare costs in some groups of patients (e.g., the mentally retarded). The prefrontal cortex and amygdalo-hippocampal complex (AHC) are implicated in the control aggression, therefore we examined the neural integrity of these regions in violent patients with mild mental retardation and nonviolent control subjects. METHODS: We used (1)H-magnetic resonance spectroscopy (MRS) to measure 1) concentrations and ratios of N-acetyl aspartate (NAA), creatine phosphocreatine (Cr+PCr), and choline-related compounds (Cho) in prefrontal lobe of 10 violent inpatients and 8 control subjects; 2) ratios of NAA, Cr+PCr, and Cho in the AHC of 13 inpatients and 14 control subjects; and 3) frequency and severity of violence in patients. RESULTS: Compared to control subjects, violent patients had significantly (p <.05, analysis of covariance-age and IQ as confounding covariates) lower prefrontal concentrations of NAA and Cr+PCr, and a lower ratio of NAA/Cr+PCr in the AHC. Within the violent patient group, frequency of observed violence to others correlated significantly with prefrontal lobe NAA concentration (r = -0.72, p <.05). CONCLUSIONS: NAA concentration indicates neuronal density, and Cr+PCr concentration high-energy phosphate metabolism. Our findings suggest that violent patients with mild mental retardation have reduced neuronal density, and abnormal phosphate metabolism in prefrontal lobe and AHC compared to nonviolent control subjects. Further studies are needed, however, to determine if these findings are regionally specific, or generalize to other groups of violent individuals.

Adult↗
PubMed2000

The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions.

Although high-functioning individuals with autistic disorder (i.e. autism and Asperger syndrome) are of normal intelligence, they have life-long abnormalities in social communication and emotional behaviour. However, the biological basis of social difficulties in autism is poorly understood. Facial expressions help shape behaviour, and we investigated if high-functioning people with autistic disorder show neurobiological differences from controls when processing emotional facial expressions. We used functional MRI to investigate brain activity in nine adults with autistic disorder (mean age +/- standard deviation 37 +/- 7 years; IQ 102 +/- 15) and nine controls (27 +/- 7 years; IQ 116 +/- 10) when explicitly (consciously) and implicitly (unconsciously) processing emotional facial expressions. Subjects with autistic disorder differed significantly from controls in the activity of cerebellar, mesolimbic and temporal lobe cortical regions of the brain when processing facial expressions. Notably, they did not activate a cortical 'face area' when explicitly appraising expressions, or the left amygdala region and left cerebellum when implicitly processing emotional facial expressions. High-functioning people with autistic disorder have biological differences from controls when consciously and unconsciously processing facial emotions, and these differences are most likely to be neurodevelopmental in origin. This may account for some of the abnormalities in social behaviour associated with autism.

Adult↗
PubMed2000

Multicenter comparison of Roche COBAS AMPLICOR MONITOR version 1.5, Organon Teknika NucliSens QT with Extractor, and Bayer Quantiplex version 3.0 for quantification of human immunodeficiency virus type 1 RNA in plasma.

The performance and characteristics of Roche COBAS AMPLICOR HIV-1 MONITOR version 1.5 (CA MONITOR 1.5) UltraSensitive (usCA MONITOR 1. 5) and Standard (stCA MONITOR 1.5) procedures, Organon Teknika NucliSens HIV-1 RNA QT with Extractor (NucliSens), and Bayer Quantiplex HIV RNA version 3.0 (bDNA 3.0) were compared in a multicenter trial. Samples used in this study included 460 plasma specimens from human immunodeficiency virus (HIV) type 1 (HIV-1)-infected persons, 100 plasma specimens from HIV antibody (anti-HIV)-negative persons, and culture supernatants of HIV-1 subtype A to E isolates diluted in anti-HIV-negative plasma. Overall, bDNA 3.0 showed the least variation in RNA measures upon repeat testing. For the Roche assays, usCA MONITOR 1.5 displayed less variation in RNA measures than stCA MONITOR 1.5. NucliSens, at an input volume of 2 ml, showed the best sensitivity. Deming regression analysis indicated that the results of all three assays were significantly correlated (P < 0.0001). However, the mean difference in values between CA MONITOR 1.5 and bDNA 3.0 (0.274 log(10) RNA copies/ml; 95% confidence interval, 0.192 to 0.356) was significantly different from 0, indicating that CA MONITOR 1.5 values were regularly higher than bDNA 3.0 values. Upon testing of 100 anti-HIV-negative plasma specimens, usCA MONITOR 1.5 and NucliSens displayed 100% specificity, while bDNA 3.0 showed 98% specificity. NucliSens quantified 2 of 10 non-subtype B viral isolates at 1 log(10) lower than both CA MONITOR 1.5 and bDNA 3.0. For NucliSens, testing of specimens with greater than 1,000 RNA copies/ml at input volumes of 0.1, 0.2, and 2.0 ml did not affect the quality of results. Additional factors differing between assays included specimen throughput and volume requirements, limit of detection, ease of execution, instrument work space, and costs of disposal. These characteristics, along with assay performance, should be considered when one is selecting a viral load assay.

Branched DNA Signal Amplification Assay↗
PubMed2000

Reliability and validity of the CANDID--a needs assessment instrument for adults with learning disabilities and mental health problems.

BACKGROUND: People with learning disabilities and mental health problems have complex needs. Care should be provided according to need. AIM: To develop a standardised needs-assessment instrument for adults with learning disabilities and mental health problems. METHOD: The Camberwell Assessment of Need for Adults with Developmental and Intellectual Disabilities (CANDID) was developed by modifying the Camberwell Assessment of Need (CAN). Concurrent validity was tested using the Global Assessment of Functioning (GAF) and the Disability Assessment Schedule (DAS). Test-retest and interrater reliability were investigated using 40 adults with learning disabilities and mental health problems. RESULTS: CANDID scores were significantly correlated with both DAS (P < 0.05) and GAF scores (P < 0.01). Correlation coefficients for interrater reliability were 0.93 (user), 0.90 (career), and 0.97 (staff ratings); for test-retest reliability they were 0.71, 0.69 and 0.86 respectively. Mean interview duration was less than 30 minutes. CONCLUSIONS: The CANDID is a brief, valid and reliable needs assessment instrument for adults with learning disabilities and mental health problems.

Adult↗
PubMed2000

Light energy transmission through cured resin composite and human dentin.

OBJECTIVE: This study determined the amount of light energy transmitted through various densities of cured resin composite and human dentin when 2 different light intensities were used. METHOD AND MATERIALS: The maximum light energy (mW/cm2) transmitted through disks (0.46 to 5.85 mm thick) of 7 resin composites and human dentin was measured when either a Standard or a Turbo light guide was attached to a curing light. The effects of the 2 light guides, the specimen thickness, and type of specimen dentin on light energy transmission were determined. RESULTS: The mean light energy reading at the surface of the specimens was 682.1 mW/cm2 with the Standard light guide and 1,014 mW/cm2 with the Turbo light guide. For all the specimens, there was an exponential decrease in light energy transmitted as the specimen thickness increased. The analysis of covariance showed that the specimen, thickness, and light guide all had a statistically significant effect. Significantly more light energy (about 42%) was transmitted through the specimens when the Turbo light guide was used. CONCLUSION: When the Turbo light guide was used, about 42% more light energy was transmitted through the cured composite specimens. There was an exponential decrease in the light energy transmitted through 7 resin composites and dentin as the specimen thickness increased.

Analysis of Variance↗
PubMed1999

An inpatient treatment model for adults with mild intellectual disability and challenging behaviour.

Following the closure of the large mental handicap hospitals in the UK, the majority of people with intellectual disability (ID) are currently living in the community. However, people with ID who also exhibit challenging behaviour (CB) have been the most difficult-to-place group and use a large amount of service resources. A variety of service options have been proposed for the assessment and treatment of CBs, but there is little information on the effectiveness of these alternatives. The Mental Impairment Evaluation and Treatment Service (MIETS) is one of these service options and the aim of the present study is to describe and evaluate this service. The present authors studied the first 64 patients admitted to MIETS following its opening. A within-subject comparison research design was used. Demographic and clinical data were obtained from case records and the effectiveness of MIETS interventions was evaluated by comparing the number of incidents of challenging behaviour, the use of seclusion, and the place of residence before and after the MIETS intervention. Only 10 (17.5%) of the patients had been admitted from community facilities, but 48 (84.2%) of the patients were discharged to community placements (P < 0.000 I1). The MIETS also significantly reduced the frequency and severity of challenging behaviours (P < 0.0001). It is concluded that the MIETS is an effective treatment model for people with ID and CB, and that there is no place for therapeutic nihilism in this difficult-to-place group of patients.

Adolescent↗
PubMed1999

Premutation female carriers of fragile X syndrome: a pilot study on brain anatomy and metabolism.

OBJECTIVE: It was thought that premutation carriers of fragile X syndrome (FraX) have no neurobiological abnormalities, but there have been no quantitative studies of brain morphometry and metabolism. Thus the authors investigated brain structure and metabolism in premutation carriers of FraX. METHOD: Eight normal IQ, healthy female permutation FraX carriers aged 39 +/- 9 years (mean +/- SD) and 32 age-sex-handedness-matched controls (39 +/- 10 years) were studied; in vivo brain morphometry was measured using volumetric magnetic resonances imaging, and regional cerebral metabolic rates for glucose were measured using positron emission tomography and (18F)-2-fluoro-2-deoxy-D-glucose. RESULTS: Compared with controls, FraX premutation carriers had a significant (1) decrease in volume of whole brain, and caudate and thalamic nuclei bilaterally; (2) increase in volume of hippocampus and peripheral CSF bilaterally, and third ventricle; (3) relative hypometabolism of right parietal, temporal, and occipital association areas; (4) bilateral relative hypermetabolism of hippocampus; (5) relative hypermetabolism of left cerebellum; and (6) difference in right-left asymmetry of the Wernicke and Broca language areas. CONCLUSIONS: Premutation carriers of FraX, as defined by analysis of peripheral lymphocytes, have abnormalities in brain anatomy and metabolism. The biological basis for this is unknown, but most likely it includes tissue heterogeneity for mutation status. The findings may be of relevance to people counseling families with FraX and to understanding other neuropsychiatric disorders which are associated with expansion of triplet repeats and genetic anticipation.

Adult↗
PubMed1999

Reproducibility and performance of the second-generation branched-DNA assay in routine quantification of human immunodeficiency virus type 1 RNA in plasma.

We examined the reproducibility of a second-generation branched-DNA (bDNA) assay (Quantiplex HIV RNA 2.0) for quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma by retesting 325 specimens on separate runs and on different lots. The performance of the bDNA test was also assessed by data analysis obtained during routine testing of 15,365 specimens. Upon retesting, 96 and 86% of specimens displaying RNA levels above 5,000 and between 500 and 5, 000 copies/ml, respectively, showed less than a 0.3 log10 (twofold) difference with their initial values. Assay variability was found to increase as viral load decreased. Overall, the bDNA version 2.0 assay was found to be a reproducible and efficient test for routine quantification of HIV-1 RNA in plasma.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Primer specific and mispair extension analysis (PSMEA) as a simple approach to fast genotyping.

A simple method, primer specific and mispair extension analysis (PSMEA) with pfu DNA polymerase was developed for genotyping. PSMEA is based on the unique properties of 3'-->5' exonuclease proofreading activity. In the presence of an incomplete set of dNTPs, pfu was found to be extremely discriminative in nucleotide incorporation and proofreading at the initiation step of DNA synthesis, completely preventing primer extension when mispair(s) are found adjacent to the 3'-end of the primer. This has allowed us to accurately detect nucleotide variations, deletions and insertions for fast genotyping.

Base Pair Mismatch↗