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1.
Phys Rev Lett ; 131(4): 041002, 2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37566836

ABSTRACT

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

2.
Parkinsonism Relat Disord ; 70: 36-41, 2020 01.
Article in English | MEDLINE | ID: mdl-31809948

ABSTRACT

INTRODUCTION: Bi-allelic mutations in the gene for glucocerebrosidase (GBA) cause Gaucher disease, an autosomal recessive lysosomal storage disorder. Gaucher disease causing GBA mutations in the heterozygous state are also high risk factors for Parkinson's disease (PD). GBA analysis is challenging due to a related pseudogene and structural variations (SVs) that can occur at this locus. We have applied and refined a recently developed nanopore DNA sequencing method to analyze GBA variants in a clinically assessed New Zealand longitudinal cohort of PD. METHOD: We examined amplicons encompassing the coding region of GBA (8.9 kb) from 229 PD cases and 50 healthy controls using the GridION nanopore sequencing platform, and Sanger validation. RESULTS: We detected 23 variants in 21 PD cases (9.2% of patients). We detected modest PD risk variant p.N409S (rs76763715) in one case, p.E365K (rs2230288) in 12 cases, and p.T408 M (rs75548401) in seven cases, one of whom also had p.E365K. We additionally detected the possible risk variants p.R78C (rs146774384) in one case, p.D179H (rs147138516) in one case which occurred on the same haplotype as p.E365K, and one novel variant c.335C > T or p.(L335 = ), that potentially impacts splicing of GBA transcripts. Additionally, we found a higher prevalence of dementia among patients with GBA variants. CONCLUSION: This work confirmed the utility of nanopore sequencing as a high-throughput method to identify known and novel GBA variants, and to assign precise haplotypes. Our observations may contribute to improved understanding of the effects of variants on disease pathogenesis, and to the development of more targeted treatments.


Subject(s)
Dementia/genetics , Glucosylceramidase/genetics , Nanopore Sequencing/standards , Parkinson Disease/genetics , Aged , Aged, 80 and over , Cohort Studies , Dementia/etiology , Female , Humans , Male , Middle Aged , New Zealand , Parkinson Disease/complications , Reproducibility of Results , Sequence Analysis, DNA
3.
Proc Natl Acad Sci U S A ; 116(33): 16186-16191, 2019 Aug 13.
Article in English | MEDLINE | ID: mdl-31350347

ABSTRACT

Spin-orbit coupling (SOC), the interaction between the electron spin and the orbital angular momentum, can unlock rich phenomena at interfaces, in particular interconverting spin and charge currents. Conventional heavy metals have been extensively explored due to their strong SOC of conduction electrons. However, spin-orbit effects in classes of materials such as epitaxial 5d-electron transition-metal complex oxides, which also host strong SOC, remain largely unreported. In addition to strong SOC, these complex oxides can also provide the additional tuning knob of epitaxy to control the electronic structure and the engineering of spin-to-charge conversion by crystalline symmetry. Here, we demonstrate room-temperature generation of spin-orbit torque on a ferromagnet with extremely high efficiency via the spin-Hall effect in epitaxial metastable perovskite SrIrO3 We first predict a large intrinsic spin-Hall conductivity in orthorhombic bulk SrIrO3 arising from the Berry curvature in the electronic band structure. By manipulating the intricate interplay between SOC and crystalline symmetry, we control the spin-Hall torque ratio by engineering the tilt of the corner-sharing oxygen octahedra in perovskite SrIrO3 through epitaxial strain. This allows the presence of an anisotropic spin-Hall effect due to a characteristic structural anisotropy in SrIrO3 with orthorhombic symmetry. Our experimental findings demonstrate the heteroepitaxial symmetry design approach to engineer spin-orbit effects. We therefore anticipate that these epitaxial 5d transition-metal oxide thin films can be an ideal building block for low-power spintronics.

4.
Neuropsychologia ; 112: 66-76, 2018 04.
Article in English | MEDLINE | ID: mdl-29522760

ABSTRACT

Recent animal studies have shown that stress can profoundly affect motor behaviour and worsen motor deficits associated with Parkinson's disease (PD) by acting on the dopaminergic system, possibly due to stress-associated emotional changes. However, systematic investigation of the influence of acute emotional stressors on motor function in PD is scarce. Here we examined the effect of repeated exposure to negative emotional stimuli on grip-force control in PD. Eighteen patients with idiopathic PD (tested off-medication) and 18 healthy controls produced an isometric precision grip contraction at 15% of maximum force while viewing a series of unpleasant, pleasant, or neutral emotional images (blocked presentation; without visual feedback of force output). Force output was continuously recorded together with change in forearm muscle activity using electromyography. While viewing unpleasant images, PD participants exhibited increased variability and 4-8 Hz oscillations of force output, and greater flexor muscle activity. With feedback occluded, the decay in force amplitude was pronounced, but not modulated by emotion. In contrast, in controls, the decay in force amplitude was attenuated while viewing unpleasant images compared with pleasant and neutral images. The findings in PD may reflect an increased number of motor units discharging and reduced ability to use sensory feedback to alter the descending drive. Modulation of synaptic input to the motoneuron pool could result from acute stress-induced enhancement of sympathetic activity and/or amplification of dopamine depletion. Corroborating previous findings in animal models of PD, exposure to stress-evoking emotional stimuli can exacerbate impairments in fine motor control in individuals with PD.


Subject(s)
Emotions/physiology , Parkinson Disease/physiopathology , Psychomotor Performance/physiology , Stress, Psychological/physiopathology , Affect/physiology , Aged , Electromyography , Female , Hand Strength/physiology , Humans , Male , Middle Aged , Parkinson Disease/psychology , Reaction Time/physiology , Stress, Psychological/psychology
5.
Parkinsonism Relat Disord ; 42: 78-84, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28693940

ABSTRACT

BACKGROUND: Traditionally the risk of Parkinson's has been considered to increase monotonically with age, although there is evidence that prevalence and incidence may decrease in the oldest old. To examine this further we estimated the national prevalence and incidence of Parkinson's in New Zealand, using drug-tracing methods, to examine the relationship of Parkinson's with sex and age up to 100+. METHODS: Information on Parkinson's-related medications was extracted from the national pharmaceutical database of community-dispensed medications from 2005 to 2014. Diagnoses for a large subset of individuals were independently determined through national mortality and hospital admissions datasets. We used a Bayesian model, accommodating diagnostic uncertainty and bias, to estimate the number of people with Parkinson's. RESULTS: The 2013 prevalence of Parkinson's in New Zealand was 210 per 100 000 population (95% uncertainty interval 208-212) with age-standardized prevalence rates higher for males (ratio 1.6:1). Incidence was 31 per 100 000 person-years (95% uncertainty interval 30-32), also higher in males (ratio 1.8:1). Incidence and prevalence by age increased exponentially until 75 years, peaked at 85 years, and then dropped sharply. CONCLUSIONS: The prevalence of Parkinson's in New Zealand is expected to double over a 25-year period but then increase at a slower rate due to the drop-off in prevalence and incidence in the oldest old. The findings suggest that Parkinson's disease is not an aging-dependent but an age-dependent disorder.


Subject(s)
Aging , Parkinson Disease/economics , Parkinson Disease/epidemiology , Aged, 80 and over , Algorithms , Cost of Illness , Female , Humans , Incidence , Longitudinal Studies , Male , New Zealand/epidemiology , Parkinson Disease/classification , Prevalence , Residence Characteristics , Retrospective Studies
6.
Vet Rec ; 179(9): 229, 2016 Sep 03.
Article in English | MEDLINE | ID: mdl-27329504

ABSTRACT

Quality of life (QoL) plays a significant role in the treatment of dogs with idiopathic epilepsy (IE), yet is so far understudied. This study describes the outcome evaluation of an online questionnaire based on the carer's perception focusing on 62 QoL questions in 159 dogs with IE. Results showed that seizure frequency, but not seizure severity or presence of cluster seizures, was significantly associated with carer-perceived dog's QoL. Dogs receiving third-line antiepileptic drugs had a significantly lower perceived QoL than those that did not. Generalised linear mixed model analysis demonstrated that severity of the side effects sleeping more and ataxia were significantly associated with carer-perceived dog's QoL, with higher severities predicting lower QoL scores. The degree of carer acceptability of seizure frequency and severity was significantly associated with the dog's reported seizure frequency and severity. Moreover, there was a significant association between IE-related QoL changes of the dog and the carer, with reductions in perceived canine QoL scores associated with reductions in carer QoL, and vice versa. In conclusion, aspects of canine IE can affect both the carer and their dog's QoL. This has implications for the management and requires consideration when treatment options and outcomes are discussed.


Subject(s)
Caregivers/psychology , Dog Diseases/drug therapy , Dog Diseases/psychology , Epilepsy, Generalized/veterinary , Quality of Life/psychology , Animals , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Dogs , Epilepsy, Generalized/drug therapy , Epilepsy, Generalized/psychology , Female , Humans , Male , Seizures/prevention & control , Seizures/veterinary , Severity of Illness Index , Surveys and Questionnaires , Treatment Outcome
7.
Parkinsons Dis ; 2014: 379431, 2014.
Article in English | MEDLINE | ID: mdl-24729910

ABSTRACT

Prescribing trends for medications are influenced by development of new drugs, changes in knowledge about efficacy and side effects, and priorities set by funding agencies. Changes in the utilization of antiparkinsonian agents in the outpatient community in New Zealand were investigated by using the national prescription database for the period 1995-2011. The dispensed volumes of antiparkinsonian agents were converted into number of defined daily doses per 1000 inhabitants per day for analysis. Increases in the dispensed volumes of levodopa (77%), amantadine (350%), and catechol-o-methyl transferase inhibitors (326%) occurred during the study period. Conversely, decreases in the dispensed volumes of anticholinergics (48%), selegiline (82%), and dopamine agonists (6.2%) were observed. New Zealand has seen a substantial increase of the amount of levodopa dispensed in the past 17 years. This increase appears to be related to an increase in the number of people taking the medication. We are unable to extrapolate this change to an increase in the prevalence of PD, given levodopa is used in the treatment of a number of medical conditions. The changes in other antiparkinsonian medications largely reflect changes in availability (increases in entacapone and ropinirole) and best practice treatment (declines in anticholinergics, selegiline, and tolcapone).

8.
J Vet Intern Med ; 28(2): 510-4, 2014.
Article in English | MEDLINE | ID: mdl-24612035

ABSTRACT

BACKGROUND: The impact of epilepsy and its treatment on the quality of life (QoL) is considered an important part of treatment supervision in human epilepsy. OBJECTIVES: To develop a list of key questions evaluating QoL in dogs with idiopathic epilepsy (IE) and their carers. ANIMALS: One hundred fifty-nine dogs with IE. METHODS: Cross-sectional study. An online project questionnaire was developed containing 90 QoL-associated questions that were initially allocated to 14 themes representing specific areas associated with the treatment and care of an epileptic dog. Principal component analysis was applied with the aim of refining the questionnaire to the least number of questions representing useful themes without loss of descriptive value. Carers were recruited by paper mail, primary practices, and canine epilepsy websites. Data were acquired from January to November 2011. RESULTS: Principal component analysis removed 54 questions, leaving 7 themes with 36 questions with a minimum Cronbach's alpha value of 0.7 indicating a good internal consistency: "Seizure severity and frequency", "Adverse effects of antiepileptic drug (AED)", "Restrictions on the carer's life", "Frustrations over caring for a dog with IE", "Carer distaste of AED adverse effects", "Carer anxiety around the seizure event", "Perceptions on rectal diazepam use". CONCLUSIONS AND CLINICAL IMPORTANCE: Principal component analysis successfully reduced the number of questions without loss in descriptive value. The remaining questions correlate well with each other in capturing valuable details about aspects of QoL and represent valuable key questions (EpiQoL) in the assessment of QoL for the carers of dogs with IE.


Subject(s)
Dog Diseases/diagnosis , Epilepsy, Generalized/veterinary , Animals , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Cross-Sectional Studies , Dog Diseases/drug therapy , Dog Diseases/psychology , Dogs , Epilepsy, Generalized/diagnosis , Epilepsy, Generalized/drug therapy , Epilepsy, Generalized/psychology , Female , Male , Quality of Life/psychology , Surveys and Questionnaires
9.
J Neural Transm (Vienna) ; 121(4): 371-8, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24306276

ABSTRACT

C-type natriuretic peptide (CNP) is a neurotrophic factor widely expressed in the central nervous system including the basal ganglia, limbic system and hypothalamus. Nothing is known of CNP's role in the human brain but in rodents CNP promotes axon growth and branching, and interacts with dopaminergic function in models of addiction. Because preliminary evidence showed reduced levels in Parkinson's disease (PD), we examined concentrations of CNP peptides in cerebrospinal fluid (CSF) in 146 PD patients from the DATATOP study to determine changes over time in relation to medication status and cognitive function. CNP and an aminoterminal product of proCNP (NTproCNP) were measured in extracts from stored CSF by radioimmunoassay. CSF samples were obtained twice-at enrolment and at the study's endpoint (requirement for levodopa treatment) after treatment with placebo or deprenyl. At enrolment, median baseline concentration of CSF NTproCNP (776 pmol/L, n = 146) was significantly lower than that in a reference group without neurological disorder (1,010 pmol/L, p < 0.001). Concentrations declined significantly during placebo (p = 0.02) and lower values at enrolment were associated with more rapid functional decline (p < 0.01). In contrast, deprenyl-a treatment which delayed the need for levodopa-nullified the time-dependent decline in CSF NTproCNP. In conclusion subnormal CSF NTproCNP which declines with time and associates with increasing functional disability implicates CNP in PD. Concordant clinical and peptide responses to deprenyl suggest that some of the benefits of monoamine oxidase inhibitors in PD are mediated by preserving tissue CNP activity.


Subject(s)
Antiparkinson Agents/therapeutic use , Natriuretic Peptide, C-Type/cerebrospinal fluid , Parkinson Disease/cerebrospinal fluid , Parkinson Disease/drug therapy , Selegiline/therapeutic use , Adult , Aged , Aged, 80 and over , Cognition Disorders/etiology , Female , Humans , Male , Middle Aged , Parkinson Disease/complications , Retrospective Studies , Severity of Illness Index , Time Factors
10.
Diabetologia ; 56(7): 1494-502, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23568273

ABSTRACT

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.


Subject(s)
Cardiovascular Diseases/epidemiology , Carotid Intima-Media Thickness , Diabetes Mellitus/epidemiology , Humans , Myocardial Infarction/epidemiology , Risk Factors , Stroke/epidemiology
11.
J Small Anim Pract ; 53(6): 344-51, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22647213

ABSTRACT

OBJECTIVES: Evoked otoacoustic emission testing is the preferred test in human patients for sensorineural deafness screening in neonates and cochlear outer hair cell function monitoring in adults. This study evaluated evoked otoacoustic emission testing for cochlear function assessment in dogs within a clinical setting. METHODS: Two populations of anaesthetised dogs were included. In group 1 the evoked otoacoustic emission response was compared to the brainstem auditory evoked response in 10 dogs having hearing assessment. Group 2 comprised 43 presumed normal dogs, in which the suitability of two types of evoked otoacoustic emissions, transient-evoked and distortion product otoacoustic emissions, were evaluated (brainstem auditory evoked response was not performed in this group). RESULTS: Valid transient-evoked otoacoustic emission and distortion-product otoacoustic emission responses were successfully recorded within the clinical setting and correctly identified deaf and hearing ears. Within presumed healthy dogs, normal otoacoustic emission response was demonstrated in more than 80% of dogs using a single, short distortion-product otoacoustic emission run and in 78% of dogs with valid transient-evoked otoacoustic emission responses using a series of three repeated transient-evoked otoacoustic emission short runs. CLINICAL SIGNIFICANCE: Transient-evoked otoacoustic emission and distortion-product otoacoustic emission testing provided a rapid, non-invasive frequency-specific assessment of cochlear function. Transient-evoked otoacoustic emission and distortion product otoacoustic emission testing is suitable as a screening procedure to detect loss of cochlear function in dogs, although further investigation is needed.


Subject(s)
Evoked Potentials, Auditory, Brain Stem/physiology , Hearing Loss, Sensorineural/veterinary , Hearing Tests/veterinary , Otoacoustic Emissions, Spontaneous/physiology , Animals , Dogs , Female , Hearing Loss, Sensorineural/diagnosis , Hearing Tests/methods , Male
12.
Pharmacogenomics J ; 12(1): 10-21, 2012 Feb.
Article in English | MEDLINE | ID: mdl-20697427

ABSTRACT

The study aim was to identify early (within 14 days) and late changes (by 3 months) in breast cancer gene expression profiles associated with neoadjuvant therapy with letrozole. RNA from sequential tumour biopsies in 54 patients was analyzed on microarrays; changes were determined by frequency, magnitude and significance analyses. Substantially more genes were changed at 3 months (1503) than at 14 days (237). Early changed genes were associated with cell cycle (downregulation), blood vessel development and extracellular matrix (upregulation); late changes included 'cellular metabolic process', 'generation of precursor metabolites and energy' (decreased) and 'cell adhesion' 'biological adhesion' (increased). A striking difference between the early and late changes was the general location of downregulated genes-nuclear structures at 14 days and mitochondria after 3 months. These changes in gene expression profiles provide a new and important database by which to understand molecular mechanisms of letrozole in breast cancers.


Subject(s)
Aromatase Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Nitriles/therapeutic use , Transcriptome , Triazoles/therapeutic use , Aromatase Inhibitors/pharmacology , Cluster Analysis , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Letrozole , Nitriles/pharmacology , Prospective Studies , Time Factors , Treatment Outcome , Triazoles/pharmacology
13.
J Parasitol ; 98(1): 205-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21830937

ABSTRACT

We conducted cross-sectional surveys of parasites infecting a large free-living colony of baboons at the Southwest National Primate Research Center in San Antonio in October 2003 and April 2004, immediately before, and 6 mo after, treatment with ivermectin. Trichuris sp. was the predominant species present, infecting 79 and 69% of individual animals in the 2 surveys, with fecal egg counts (FEC) of up to 60,200 eggs per g (epg) (mean = 1,235 in October 2003 and 1,256 in April 2004). Prevalence remained fairly stable across age groups, and intensity was highest in animals <1 or >15 yr old, in contrast to patterns observed in humans, where school-age children show the heaviest infections. Strongyloides sp. was also identified, but the species identity remains uncertain. Small subunit ribosomal DNA sequences differed from published sequences of Strongyloides fuelleborni at multiple sites, but resided in a monophyletic group with other Strongyloides species with 92% bootstrap support. This may reflect a recent acquisition from a local host, or that the published sequence of S. fuelleborni is incorrect. Widespread infections with 2 nematode genera in a free-ranging baboon colony that are an important source of morbidity in human populations provide a useful model system for work on the epidemiology, control, pathology, and genetics of these parasites in a host species that is physiologically, immunologically, and genetically similar to humans.


Subject(s)
Monkey Diseases/parasitology , Papio/parasitology , Strongyloidiasis/veterinary , Trichuriasis/veterinary , Age Distribution , Animals , Cross-Sectional Studies , DNA, Helminth/chemistry , DNA, Ribosomal/chemistry , Feces/parasitology , Female , Male , Monkey Diseases/epidemiology , Parasite Egg Count/veterinary , Phylogeny , Prevalence , RNA, Ribosomal, 18S/genetics , Sequence Alignment/veterinary , Strongyloides/classification , Strongyloides/genetics , Strongyloides/growth & development , Strongyloides/isolation & purification , Strongyloidiasis/epidemiology , Strongyloidiasis/parasitology , Texas/epidemiology , Trichuriasis/epidemiology , Trichuriasis/parasitology , Trichuris/growth & development , Trichuris/isolation & purification
14.
Neurology ; 75(19): 1717-25, 2010 Nov 09.
Article in English | MEDLINE | ID: mdl-21060094

ABSTRACT

OBJECTIVE: To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease-Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks. METHODS: A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N). RESULTS: Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%). CONCLUSIONS: The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/psychology , Parkinson Disease/diagnosis , Parkinson Disease/psychology , Psychiatric Status Rating Scales , Aged , Aged, 80 and over , Cognition Disorders/complications , Female , Humans , Longitudinal Studies , Male , Middle Aged , Neuropsychological Tests/standards , New Zealand , Parkinson Disease/complications , Psychiatric Status Rating Scales/standards , ROC Curve
16.
J Psychopharmacol ; 24(10): 1465-72, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19460872

ABSTRACT

Interactions between the 5-HT system and the dopaminergic system and cholinergic system may be important in determining cognitive function and motor function in Parkinson's disease (PD). Previous studies have shown effects of reducing serotonin function, by acute tryptophan depletion (ATD), on neuropsychological function. In particular, an adverse effect on verbal memory has been demonstrated. This study compared with the effects of ATD on cognitive and motor function in PD and healthy control subjects. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, cross-over, randomised design in 20 patients with PD and 35 healthy controls matched for age, gender and premorbid IQ. There was a differential group effect of ATD on global cognitive function whereby the mean score on the modified mini mental state examination during ATD was lower than placebo in PD but higher in controls. There was a similar pattern of effects on verbal recognition. In a visual recognition task, ATD improved performance in the PD but not in the control group. In terms of psychomotor speed, there was also a group-specific effect with reduced latency of response during ATD in the PD group but increased latency in the control group. ATD has subtle neuropsychological effects, which differ significantly between PD and healthy control subjects. This suggests that the dopaminergic and cholinergic deficit of PD significantly modulates the effects of serotonin depletion, resulting in positive effects in some domains. Further investigation on the effects of specific serotonin antagonists may be merited in PD.


Subject(s)
Cognition/physiology , Deficiency Diseases/physiopathology , Movement Disorders/physiopathology , Parkinson Disease/physiopathology , Tryptophan/deficiency , Aged , Aged, 80 and over , Cross-Over Studies , Deficiency Diseases/blood , Deficiency Diseases/complications , Double-Blind Method , Female , Humans , Male , Memory, Short-Term , Middle Aged , Neuropsychological Tests , Parkinson Disease/blood , Parkinson Disease/complications , Psychomotor Performance , Reaction Time , Serotonin/physiology , Severity of Illness Index , Tryptophan/administration & dosage , Tryptophan/blood
17.
J Psychopharmacol ; 24(4): 615-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19625388

ABSTRACT

Reduced serotonergic tone may be a compensatory adaptation to reduced dopaminergic activity in Parkinson's disease (PD) and may result in vulnerability to depression. To test this hypothesis this study examined the effects of serotonin depletion, using the technique of acute tryptophan depletion (ATD) in PD. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, cross-over, randomised design, in 20 patients with PD and 32 healthy controls matched for age, gender and pre-morbid IQ. The primary outcome was change in scores on a modified Montgomery-Asberg Depression Rating Scale (MADRS). ATD resulted in a small but statistically significant increase in score on the MADRS, but there was no effect specific to the PD group. The results do not support the hypothesis that low serotonergic tone results in vulnerability to depression in PD and are in accord with an earlier study using the same technique in PD.


Subject(s)
Affect , Depression/etiology , Parkinson Disease/psychology , Tryptophan/deficiency , Age Factors , Aged , Antiparkinson Agents/therapeutic use , Cross-Over Studies , Depression/diagnosis , Depression/metabolism , Depression/psychology , Double-Blind Method , Humans , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnosis , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Placebo Effect , Psychiatric Status Rating Scales , Serotonin/metabolism , Severity of Illness Index
18.
Vet Rec ; 165(19): 556-8, 2009 Nov 07.
Article in English | MEDLINE | ID: mdl-19897869

ABSTRACT

The laboratory records of 1427 client-owned dogs on chronic phenobarbitone treatment were analysed. They were divided into two groups: the 918 dogs from which blood samples were collected at the trough, that is, within two hours before the next dose of phenobarbitone, and the 509 dogs from which samples were taken during the non-trough period. There were no significant differences between the mean serum concentrations of phenobarbitone in the trough and non-trough samples from dogs receiving doses ranging from 2 mg/kg per day to more than 10 mg/kg per day. However, the higher doses of phenobarbitone were associated with progressively lower phenobarbitone concentrations in the trough group relative to the non-trough group, and this difference was significant at doses of more than 10 mg/kg per day.


Subject(s)
Anticonvulsants/blood , Anticonvulsants/pharmacokinetics , Dog Diseases/drug therapy , Phenobarbital/blood , Phenobarbital/pharmacokinetics , Animals , Dog Diseases/blood , Dogs , Dose-Response Relationship, Drug , Drug Administration Schedule , Epilepsy/drug therapy , Epilepsy/veterinary , Phenobarbital/administration & dosage , Retrospective Studies
19.
J Vet Intern Med ; 23(4): 862-70, 2009.
Article in English | MEDLINE | ID: mdl-19566851

ABSTRACT

BACKGROUND: Previous multidrug studies have identified the value of prednisolone in treating steroid responsive meningitis-arteritis (SRMA) and the potential value of acute phase proteins (APPs) and immunoglobulin A (IgA) in diagnosis and monitoring. HYPOTHESIS: (1) Prednisolone monotherapy is a successful immunosuppressive modality in the treatment of SRMA; (2) protein markers are useful in identifying the potential for relapse. ANIMALS: Twenty client-owned dogs with SRMA presented to the University of Glasgow Small Animal Hospital between May 2006 and May 2008. METHODS: A prospective, observational study: CBC, biochemistry, and cerebrospinal fluid (CSF) analyses were performed. C-reactive protein (CRP), serum amyloid-A, alpha-1-acid glycoprotein, and haptoglobin (Hp) were assessed in the serum. IgA concentrations were determined in the serum and CSF. RESULTS: Clinical resolution of SRMA was achieved in all 20 dogs. Serum CRP concentration remained increased at remission in 16/20 dogs whereas CSF cytology was within normal limits in 20/20 dogs. Serum APPs decreased significantly on treatment (P<.05) except Hp, which remained unaltered. Serum and CSF IgA concentrations remained increased for the duration of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: The prednisolone regimen presented was successful in treating SRMA without the need for additional drugs. Serum APPs are of use in the diagnosis and management of SRMA, particularly in relation to identifying relapse. Serum and CSF IgA concentrations remain increased throughout disease, aiding in diagnosis but not contributing to the management of SRMA.


Subject(s)
Arteritis/veterinary , Biomarkers , Dog Diseases/drug therapy , Meningitis/veterinary , Prednisolone/therapeutic use , Algorithms , Animals , Anti-Inflammatory Agents/therapeutic use , Arteritis/cerebrospinal fluid , Arteritis/drug therapy , Dog Diseases/cerebrospinal fluid , Dogs , Female , Immunoglobulin A , Male , Meningitis/cerebrospinal fluid , Meningitis/drug therapy , Prednisolone/administration & dosage
20.
Heredity (Edinb) ; 102(4): 357-64, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19142203

ABSTRACT

Aggregated distributions of macroparasites within their host populations are characteristic of most natural and experimental infections. We designed this study to measure the amount of variation that is attributable to host genetic factors in a pig-helminth system. In total, 195 piglets were produced after artificial insemination of 19 sows (Danish Landrace-Yorkshire crossbreds) with semen selected from 13 individual Duroc boars (1 or 2 sows per boar; mean litter size: 10.3; 5-14 piglets per litter). Starting at 10 weeks of age, piglets were repeatedly infected with the gastrointestinal helminths Trichuris suis and Ascaris suum by administering eggs in the feed for 14 weeks until necropsy. Faecal egg counts (FECs) were estimated regularly and A. suum worm burden was obtained at necropsy. Heritability calculations for log (FEC+1) at weeks 7-10 post-infection (p.i.) showed that 0.32-0.73 of the phenotypic variation for T. suis could be attributed to genetic factors. For A. suum, heritabilities of 0.29-0.31 were estimated for log (FEC+1) at weeks 7-14 p.i., whereas the heritability of log worm counts was 0.45. Strong positive genetic correlations (0.75-0.89) between T. suis and A. suum FECs suggest that resistance to both infections involves regulation by overlapping genes. Our data demonstrate that there is a strong genetic component in resistance to A. suum and T. suis infections in pigs. Identification of responsible genes would enhance our understanding of the host immune response to these common nematodes and for the closely related species (T. trichiura and A. lumbricoides) in man infecting more than a billion people.


Subject(s)
Ascariasis/veterinary , Swine Diseases/genetics , Swine Diseases/parasitology , Trichuriasis/veterinary , Animal Husbandry , Animals , Ascariasis/genetics , Ascariasis/transmission , Ascaris suum , Female , Genotype , Host-Parasite Interactions/genetics , Male , Phenotype , Sus scrofa , Swine Diseases/transmission , Trichuriasis/genetics , Trichuriasis/transmission , Trichuris
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