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Biomedical subjects

Christine Edwards

Publications and source records attributed to Christine Edwards.

At least 19 recordsLinked to original sources
PubMed2006

Quantification of Parkinson's disease-related network expression with ECD SPECT.

PURPOSE: Spatial covariance analysis has been used with FDG PET to identify a specific metabolic network associated with Parkinson's disease (PD). In the current study, we utilized a new, fully automated voxel-based method to quantify network expression in ECD SPECT images from patients with classical PD, patients with multiple system atrophy (MSA), and healthy control subjects. METHODS: We applied a previously validated voxel-based PD-related covariance pattern (PDRP) to quantify network expression in the ECD SPECT scans of 35 PD patients, 15 age- and disease severity-matched MSA patients, and 35 age-matched healthy control subjects. PDRP scores were compared across groups using analysis of variance. The sensitivity and specificity of the prospectively computed PDRP scores in the differential diagnosis of individual subjects were assessed by receiver operating characteristic (ROC) analysis. RESULTS: PDRP scores were significantly increased (p < 0.001) in the PD group relative to the MSA and control groups. ROC analysis indicated that the overall diagnostic accuracy of the PDRP measures was 0.91 (AUC). The optimal cutoff value was consistent with a sensitivity of 0.97 and a specificity of 0.80 and 0.71 for discriminating PD patients from MSA and normal controls, respectively. CONCLUSION: Our findings suggest that fully automated voxel-based network assessment techniques can be used to quantify network expression in the ECD SPECT scans of parkinsonian patients.

Algorithms↗
PubMed2006

Network modulation in the treatment of Parkinson's disease.

It has been proposed that deep brain stimulation (DBS) of the subthalamic nucleus (STN DBS) and dopaminergic therapy ameliorate the symptoms of Parkinson's disease through similar functional mechanisms. We examined this notion using PET to compare the metabolic effects of these treatment approaches. Nine Parkinson's disease patients (age 61.7 +/- 11.1 years) were scanned ON and OFF STN stimulation and nine others (age 60.0 +/- 9.3 years) were scanned ON and OFF an individual titrated intravenous levodopa infusion. The two treatment groups were matched for baseline disease severity as well as clinical response to therapy. Similarities and differences in the effects of treatment on regional metabolism were assessed using statistical parametric mapping (SPM). In addition, we used network analysis to assess the effect of therapy on the expression of an abnormal Parkinson's disease-related spatial covariance pattern (PDRP). We found that both STN DBS and levodopa therapy were associated with significant (P < 0.001) metabolic reductions in the putamen/globus pallidus, sensorimotor cortex and cerebellar vermis, as well as increases in the precuneus (BA 7). The metabolic effects of the two interventions differed in the STN and medial prefrontal cortex, with relative increases with stimulation in the former structure and decreases in the latter. Network quantification disclosed reductions in PDRP activity with both interventions, which correlated with clinical improvement (P < 0.05). The degree of network modulation by therapy did not differ significantly for the two treatment approaches (P > 0.6). These findings support the results of previous imaging studies indicating that effective symptomatic therapies for Parkinson's disease involve a common mechanism. The modulation of pathological brain networks is a critical feature of the treatment response in parkinsonism.

Adult↗
PubMed2006

Enhanced porphyrin accumulation using dendritic derivatives of 5-aminolaevulinic acid for photodynamic therapy: an in vitro study.

Intracellular porphyrin generation following administration of 5-aminolaevulinic acid has been widely used in photodynamic therapy for a range of malignant and certain non-malignant lesions. However, cellular uptake of 5-aminolaevulinic acid is limited by its hydrophilic nature and improved means of delivery are therefore being sought. Highly branched polymeric drug carriers known as dendrimers are a promising new approach to drug delivery. The aim of this study was to investigate the efficacy of dendrimers conjugated with 5-aminolaevulinic acid for porphyrin production in the transformed PAM 212 keratinocyte cell line and skin explants. Each dendritic derivative incorporated three 5-aminolaevulinic acid residues which were conjugated as esters via methyl or propyl linkers to a central tertiary carbon whose remaining terminal bore an amino, aminobenzyloxycarbonyl or nitro group. In the cell line, all compounds were more efficient at low concentrations compared to equimolar 5-aminolaevulinic acid for porphyrin production, with the most efficient incorporating the longer propyl linker. This compound was also the most lipophilic according to partition coefficient measurements. The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure for all the compounds, together with minimal dark toxicity. Our findings indicate that the key factors influencing the efficacy of the dendritic derivatives are lipophilicity and steric hindrance within the dendritic structure which could restrict access to intracellular esterases for liberation of 5-aminolaevulinic acid. These findings should be taken into account in the design of larger dendrimers of 5-aminolaevulinic acid.

Aminolevulinic Acid↗
PubMed2006

Anticholinesterase effect on motor kinematic measures and brain activation in Parkinson's disease.

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson's disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity.

Analysis of Variance↗
PubMed2005

Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection.

We describe a method for the determination of the two major urinary metabolites of vitamin K as the methyl esters of their aglycone structures, 2-methyl-3-(3'-3'-carboxymethylpropyl)-1,4-naphthoquinone (5C-aglycone) and 2-methyl-3-(5'-carboxy-3'-methyl-2'-pentenyl)-1,4-naphthoquinone (7C-aglycone), by HPLC with electrochemical detection (ECD) in the redox mode. Urinary salts were removed by reversed-phase (C18) solid-phase extraction (SPE), and the predominantly conjugated vitamin K metabolites were hydrolyzed with methanolic HCl. The resulting carboxylic acid aglycones were quantitatively methylated with diazomethane and fractionated by normal-phase (silica) SPE. Final analysis was by reversed-phase (C18) HPLC with a methanol-aqueous mobile phase. Metabolites were detected by amperometric, oxidative ECD of their quinol forms, which were generated by postcolumn coulometric reduction at an upstream electrode. The assay gave excellent linearity (typically, r2 > or = 0.999) and high sensitivity with an on-column detection limit of < 3.5 fmol (< 1 pg). The interassay precision was typically 10%. Metabolite recovery was compared with that of an internal standard [2-methyl-3-(7'-carboxy-heptyl)-1,4-naphthoquinone] added to urine samples just before analysis. Using this methodology, we confirmed that the 5C- and 7C-aglycones were major catabolites of both phylloquinone (vitamin K1) and menaquinones (vitamin K2) in humans. We propose that the measurement of urinary vitamin K metabolite excretion is a candidate noninvasive marker of total vitamin K status.

Calibration↗
PubMed2005

The metabolic pathology of dopa-responsive dystonia.

We used [(18)F]-fluorodeoxyglucose and positron emission tomography to determine a discrete cerebral pattern of abnormal glucose utilization in dopa-responsive dystonia. Network analysis demonstrated that dopa-responsive dystonia is associated with a specific pattern of regional metabolic covariation, characterized by increases in the dorsal midbrain, cerebellum, and supplementary motor area, as well as reductions in motor and lateral premotor cortex and in the basal ganglia. This pattern was not expressed in mutation carriers for primary torsion dystonia. Dopa-responsive dystonia has a unique metabolic architecture that differs from other inherited forms of dystonia.

Adult↗
PubMed2005

Bottleshops and 'ready-to-drink' alcoholic beverages.

ISSUE ADDRESSED: To assess whether the strategies used to sell the 'ready-to-drink' (RTD) category of alcoholic beverages is contributing to alcohol-related harm among adolescents. METHODS: An initial investigation of bottleshops, which included an observational study designed to analyse methods employed by the liquor industry to market RTDs in bottleshops, on the central coast of New South Wales. We measured the number of glass-door display refrigerators to determine refrigerated space allocated to display RTDs compared with other alcoholic products. This measure was used to establish a quantitative baseline as an indicator for the in-store marketing of these products. We then randomly selected a dozen bottleshops from those previously visited and conducted semi-structured interviews with the staff. RESULTS: The display of colourful, youth-oriented products and packaging in glass-door display refrigerators appears to be the primary in-store method for marketing RTD products. More than 40% of all glass-door display refrigerators in bottleshops on the central coast are dedicated to the storage and display of RTDs. More than half of the staff interviewed at bottleshops reported they believed that RTD products were marketed to under 18s, particularly girls. CONCLUSION: There is already a high level of consumption of RTDs by under 18s. There is very strong marketing of these products by the liquor industry. This trend will further compound the already high-risk level of consumption of these products by young people.

Adolescent↗
PubMed2004

A middle school immunization law rapidly and substantially increases immunization coverage among adolescents.

OBJECTIVES: This study assessed the effectiveness of a middle school vaccination requirement for raising second-dose measles, mumps, and rubella vaccine and hepatitis B vaccine coverage among adolescents. METHODS: Random-digit-dialed telephone surveys were conducted before (1998) and after (1999) the implementation of a vaccination requirement for entry into the seventh grade in San Diego, Calif. RESULTS: Vaccination coverage was higher among children subject to the vaccination requirement (seventh-grade students; 60%) than among fifth- and sixth-grade students 1 year before the requirement (13%, P <.001), and 8th- through 12th-grade students not subject to the requirement (27%, P <.0001). CONCLUSIONS: Middle school-entry vaccination requirements can rapidly and substantially raise vaccination coverage among students subject to the law.

Adolescent↗
PubMed2003

Early stage Parkinson's disease patients and normal volunteers: comparative mechanisms of sequence learning.

Early-stage nondemented Parkinson's disease (PD(es)) patients can learn short but not long sequences as well as controls. We have previously shown that to achieve normal performance, PD(es) patients activated the same right-sided cortical regions as controls plus the homologous left sided cortex and bilateral cerebellum. In this study, we evaluated two related hypotheses to explain the behavioral abnormalities and the increased bilateral brain activation observed in the PD(es) group. Hypothesis 1 proposed that PD(es) patients recruit regions from a normal bilateral network specialized for sequence learning that healthy controls would activate if performing difficult tasks. Thus, PD(es) patients can learn short sequences as well as controls. Hypothesis 2 proposed that information processing within the network in the PD(es) group is impaired. Thus, PD(es) patients cannot learn as difficult a sequence as controls. To test hypothesis 1, we increased task difficulty and statistical power in the control group and showed that the control and the PD(es) groups activated the same regions. To test hypothesis 2, we analyzed the equal performance data using two partial least squares (PLS) multivariate analyses. The task-PLS analysis showed that to perform equally with controls, the PD(es) group expressed the normal bilateral network more than the control group. The behavior-PLS analysis showed that the correlation between learning performance and regional activation was significantly different between the groups. We conclude that PD(es) patients have near normal learning if task difficulty is moderate because they can recruit additional regions from a normal bilateral network specialized for sequence learning. However, when a difficult task would normally require bilateral activation, PD(es) patients fail to learn because information processing within the network is impaired. Hum. Brain Mapp. 20:246-258, 2003.

Aged↗
PubMed2003

Parallel preparative high-performance liquid chromatography with on-line molecular mass characterization.

High-throughput chemistry (HTC) is now an integral part of the lead discovery process in many pharmaceutical and related chemical companies. As this process becomes refined or improved, with the integration of systems with enhanced capabilities, and the requirement for quality compounds of high purity increases, purification is often considered a bottleneck. Although a wide range of purification techniques is available, high-performance liquid chromatography (HPLC) is usually the preferred method of purification to produce high-purity compounds. Parallel preparative HPLC with robust UV-guided fraction collection has been shown to reduce the bottleneck and complement the parallel synthesis systems. However, despite the success of this technique, post-purification analysis of fractions to identify the target compound adds an additional level of complexity. This paper describes the interfacing of the Biotage Parallex with the MUX interface on a single quadrupole mass spectrometer, thus combining robust UV-guided fractionation with on-line MS characterization.

Chromatography, High Pressure Liquid↗
PubMed2003

Implementing a seventh grade vaccination law: school factors associated with completion of required immunizations.

OBJECTIVES: We investigated school factors associated with successful implementation of a seventh grade vaccination requirement. METHODS: The proportion of students vaccinated with hepatitis B vaccine and measles containing vaccine was determined from records of schools in San Diego County, California. A school survey identified compliance strategies. Analysis identified factors associated with coverage. RESULTS: In October 1999, 67.2% of 38,875 students had received the required vaccine doses. Of 315 schools, coverage was less than 40% in 60 schools and exceeded 80% in 111 schools. Factors associated with high coverage included private schools, early and frequent notice to parents, and, for public schools, higher overall socioeconomic status of students. CONCLUSIONS: In preparation for a middle school vaccination requirement, early and frequent notification of parents improves coverage. Schools with a high percentage of low socioeconomic status students may require extra resources to support implementation.

Adolescent↗
PubMed2002

Nursing workforce. Skirting the issue.

A study of part-time nurses in three London trusts found that they were concentrated in lower grades and less likely to be involved in management than full-time nurses. While senior managers in the trusts were fully committed to flexible working, managers lower in the organisation felt that part-time working presented problems for continuity of care, and that part-time nurses were unwilling to work unsocial hours. A more strategic approach is needed to ensure that part-time nurses are employed most effectively at a time of acute nursing shortages.

Community Health Nursing↗
PubMed2002

Primary dystonia: is abnormal functional brain architecture linked to genotype?

The DYT1 dystonia mutation is associated with an abnormal metabolic brain network characterized by hypermetabolism of the basal ganglia, supplementary motor area, and the cerebellum. In this study, we quantified the activity of this network in carriers of other dystonia mutations to determine whether this functional abnormality is linked to genotype. The findings suggest that the DYT1 metabolic topography is not genotype specific and may be present in carriers of other dystonia mutations.

Adult↗
PubMed2002

MOET: Bangladesh--an initial experience.

OBJECTIVES: To summarize the quantitative and qualitative immediate assessments of the Managing Obstetric Emergencies and Trauma (MOET) course and to examine the individual changes in score obtained for each of the scenarios. METHODS: Students' knowledge before and after the course was evaluated with a standardized comprehensive questionnaire. RESULTS: All candidates showed an improvement in postcourse, compared to precourse, scores. In the individual score analysis only one scenario showed a non-significant change. The majority of other scenarios showed highly significant improvement between the two scores. CONCLUSION: This paper summarises the development of the first MOET course to be run outside the UK. It demonstrates the reliability of the model-based scenario foundation with a highly significant improvement in knowledge about obstetric emergency management. Further evaluation of longer term practice changes is now required.

Clinical Competence↗
PubMed2002

Antibacterial characteristics in the feces of breast-fed and formula-fed infants during the first year of life.

BACKGROUND: Human milk is known to protect infants from a number of infectious diseases. Much less is known about the bioactivity of milk-derived factors in the intestine. In this study, potentially protective characteristics in the feces of breast-fed and formula-fed infants were compared. METHODS: The feces of 26 breast-fed and 18 formula-fed infants were collected during the first year of life. In each sample, the concentrations of total protein, immunoglobulin A, and sialic acid were measured. In addition, the effect of the fecal samples was measured on the adhesion of enteropathogenic Escherichia coli (EPEC) to Caco-2 cells and on transepithelial electrical resistance (TER) during an infection. RESULTS: In the first month, sialic acid and immunoglobulin A were found in the feces of breast-fed infants in substantially higher concentrations than in the feces of formula fed infants (sialic acid, 1197 +/- 370 microg/ mL versus 31 +/- 19 microg/ mL; immunoglobulin A, 0.11 +/- 7 mg/mL versus 0.3 +/- 1 mg/mL) and thereafter decreased to similar levels in half a year. Adhesion of EPEC to Caco-2 cells was inhibited between 65% and 85% by stools from both groups. The decrease of TER during EPEC infection was unaffected by fecal samples of any origin or age. CONCLUSION: Potentially protective factors are present in higher concentrations in the stools of breast-fed infants than in stools of formula-fed infants. Interestingly, feces from breast-fed and formula-fed infants inhibited bacterial adhesion to a similar level, but neither was able to preserve epithelial barrier function.

Age Factors↗
PubMed2002

Relationships among the metabolic patterns that correlate with mnemonic, visuospatial, and mood symptoms in Parkinson's disease.

OBJECTIVE: A multivariate analysis of baseline brain metabolism was used to investigate the relationships among pathophysiological mechanisms responsible for cognitive dysfunction and dysphoria in nondemented patients with Parkinson's disease. METHOD: Using [(18)F]fluorodeoxyglucose positron emission tomography and neuropsychological tests, the authors studied 15 nondemented patients who had Parkinson's disease without major depression (DSM-III-R). Their mean age was 59.2 years (SD=9.2), the mean rating of Parkinson's disease stage (Hoehn and Yahr scale) was 3.3 (SD=0.9), and all had Mini-Mental State Examination scores of 24 or higher. To identify specific regional patterns of brain metabolism associated with abnormal cognitive and mood functioning, the data were analyzed by using brain-behavior partial least squares. This multivariate voxel-based analysis allowed detection of significant topographic patterns of metabolic activity and quantification of the extent to which each topographic pattern correlated with scores on mnemonic, visuospatial, and dysphoric tests. RESULTS: Two significant, independent topographic patterns were identified. Pattern 1 included parieto-occipito-temporal and medial temporal brain regions, and pattern 2 included the lateral frontal and anterior limbic cortex. Patterns 1 and 2 exhibited a double dissociation in their behavioral correlates: pattern 1 correlated with both visuospatial and mnemonic functioning but not with dysphoria; pattern 2 correlated with dysphoria but not with the cognitive measures. CONCLUSIONS: The authors used the independence of topographic patterns and the size of correlations between topographic patterns and behavior to infer relationships among the pathophysiological processes responsible for the correlations. The finding that mildly abnormal mnemonic and visuospatial functioning correlated with the same topographic pattern suggests that a common pathophysiology underlies this marker of cognition in Parkinson's disease. By contrast, the independence of the two topographic patterns supports the notion that different mechanisms underlie cognitive and dysphoric symptoms in nondemented patients with Parkinson's disease.

Adult↗