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1.
Epidemiol Infect ; 149: e45, 2021 01 29.
Article in English | MEDLINE | ID: mdl-33509310

ABSTRACT

We present the comparative characterisation of 195 non-aureus staphylococci (NAS) isolates obtained from sheep (n = 125) and humans (n = 70) in Sardinia, Italy, identified at the species level by gap gene polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis with AluI. Isolates were tested phenotypically with a disc diffusion method and genotypically by PCR, for resistance to 11 antimicrobial agents including cationic antiseptic agents. Among the ovine isolates, Staphylococcus epidermidis (n = 57), S. chromogenes (n = 29), S. haemolyticus (n = 17), S. simulans (n = 8) and S. caprae (n = 6) were the most prevalent species, while among human isolates, S. haemolyticus (n = 28) and S. epidermidis (n = 26) were predominant, followed by S. lugdunensis and S. hominis (n = 4). Of the 125 ovine isolates, 79 (63.2%) did not carry any of the resistance genes tested, while the remainder carried resistance genes for at least one antibiotic. The highest resistance rates among ovine isolates were recorded against tetracycline (20.8%), and penicillin (15.2%); none was resistant to methicillin and two exhibited multidrug resistance (MDR); one of which was positive for the antiseptic resistance smr gene. By contrast, most human isolates (59/70, 84.3%) were resistant to ⩾1 antimicrobials, and 41 (58.6%) were MDR. All 52 (74.3%) penicillin-resistant isolates possessed the blaZ gene, and 33 of 70 (47.1%) harboured the mec gene; of these, seven were characterised by the Staphylococcal Chromosomal Cassette (SCCmec) type IV, 6 the type V, 5 of type III and one representative each of type I and type II. The majority (57.1%) was erythromycin-resistant and 17 isolates carried only the efflux msrA gene, 11 the methylase ermC gene and an equal number harboured both of the latter genes. Moreover, 23 (32.8%) were tetracycline-resistant and all but one possessed only the efflux tetK gene. qacA/B and smr genes were detected in 27 (38.6%) and 18 (25.7%) human NAS, respectively. These results underline a marked difference in species distribution and antimicrobial resistance between ovine and human-derived NAS.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Sheep/microbiology , Staphylococcus/isolation & purification , Animals , Female , Humans , Italy/epidemiology , Milk , Staphylococcus/classification , Staphylococcus/genetics
2.
Biotech Histochem ; 96(3): 197-201, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32552083

ABSTRACT

Cell blocks and fine needle aspirations can be used for cytopathological diagnosis. Conventional fine needle aspiration smears provide limited material for diagnosis. The cell block technique provides more tissue, which improves diagnostic accuracy. We compared a modified cell block cytology to fine needle aspiration for providing optimal preservation of histochemical and immunocytochemical properties. We used 30 fine needle aspirates from oral lesions in two groups: group 1, fine needle aspiration cytology; group 2, cell block cytology. Smears of fine needle aspirates were stained with Papanicolaou. For the modified cell block technique, aspirated material was centrifuged to create a cell pellet, which then was fixed with Nathan alcohol formalin substitute. After routine histopathological processing, cell pellets were embedded in paraffin, then sectioned and stained with hematoxylin and eosin. Sections were compared to Papanicolaou stained smears of fine needle samples. Cellular morphology and staining quality of modified cell block samples were superior to fine needle aspiration cytology; both methods exhibited distinct nuclear morphology. Modified cell blocks provide excellent cytopathologic features compared to fine needle aspiration cytology.


Subject(s)
Cytodiagnosis , Biopsy, Fine-Needle , Cytological Techniques , Formaldehyde , Staining and Labeling
3.
Biosens Bioelectron ; 87: 607-614, 2017 Jan 15.
Article in English | MEDLINE | ID: mdl-27616286

ABSTRACT

Serious brain disorders, such as the Alzheimer's Disease (AD), are associated with a marked drop in the levels of important neurotransmitters, such as acetylcholine (ACh). Real time monitoring of such biomarkers can therefore play a critical role in enhancing AD therapies by allowing timely diagnosis, verifications of treatment effectiveness, and developments of new medicines. In this study, we present the first acetylcholine/oxygen hybrid enzymatic fuel cell for the self-powered on site detection of ACh in plasma, which is based on the combination of an enzymatic anode with a Pt cathode. Firstly, an effective acetylcholinesterase immobilized electrode was developed and its electrochemical performance evaluated. Highly porous gold was used as the electrode material, and the enzyme was immobilized via a one step rapid and simple procedure that does not require the use of harsh chemicals or any electrode/enzyme pre-treatments. The resulting enzymatic electrode was subsequently used as the anode of a miniature flow-through membrane-less fuel cell and showed excellent response to varying concentrations of ACh. The peak power generated by the fuel cell was 4nW at a voltage of 260mV and with a current density of 9µAcm-2. The limit of detection of the fuel cell sensor was 10µM, with an average response time as short as 3min. These exciting results open new horizons for point-of-care Alzheimer diagnosis and provide an attractive potential alternative to established methods that require laborious and time-consuming sample treatments and expensive instruments.


Subject(s)
Acetylcholine/blood , Acetylcholinesterase/metabolism , Alzheimer Disease/diagnosis , Biosensing Techniques/instrumentation , Electrochemical Techniques/instrumentation , Enzymes, Immobilized/metabolism , Acetylcholine/metabolism , Alzheimer Disease/blood , Alzheimer Disease/metabolism , Bioelectric Energy Sources , Biomarkers/blood , Biomarkers/metabolism , Electrodes , Equipment Design , Gold/chemistry , Humans , Platinum/chemistry , Point-of-Care Systems , Porosity
4.
Diabet Med ; 33(7): 985-91, 2016 07.
Article in English | MEDLINE | ID: mdl-26937608

ABSTRACT

AIMS: To test the hypothesis that soluble cellular adhesion molecules would be positively and independently associated with risk of diabetes. METHODS: Soluble levels of six cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1, E-cadherin, L-selectin and P-selectin) were measured in participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study. Participants were then followed for up to 10 years to ascertain incident diabetes. RESULTS: Sample sizes ranged from 826 to 2185. After adjusting for age, sex, race/ethnicity, BMI and fasting glucose or HbA1c , four cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1 and E-cadherin) were positively associated with incident diabetes and there was a statistically significant trend across quartiles. Comparing the incidence of diabetes in the highest and lowest quartiles of each cellular adhesion molecule, the magnitude of association was largest for E-selectin (hazard ratio 2.49; 95% CI 1.26-4.93) and ICAM-1 (hazard ratio 1.76; 95% CI 1.22-2.55) in fully adjusted models. Tests of effect modification by racial/ethnic group and sex were not statistically significant for any of the cellular adhesion molecules (P > 0.05). CONCLUSIONS: The finding of significant associations between multiple cellular adhesion molecules and incident diabetes may lend further support to the hypothesis that microvascular endothelial dysfunction contributes to risk of diabetes.


Subject(s)
Cadherins/blood , Diabetes Mellitus, Type 2/epidemiology , E-Selectin/blood , Intercellular Adhesion Molecule-1/blood , L-Selectin/blood , P-Selectin/blood , Vascular Cell Adhesion Molecule-1/blood , Antigens, CD , Cohort Studies , Diabetes Mellitus, Type 2/blood , Female , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk , United States/epidemiology
5.
Pharmacogenomics J ; 14(4): 309-15, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24394200

ABSTRACT

In a common pharmacogenomic scenario, outcome measures are compared for treated and untreated subjects across genotype-defined subgroups. The key question is whether treatment benefit (or harm) is particularly strong in certain subgroups, and therefore the statistical analysis focuses on the interaction between treatment and genotype. However, genome-wide analysis in such scenarios requires careful statistical thought as, in addition to the usual problems of multiple testing, the marker-defined sample sizes, and therefore power, vary across the individual genotypes being evaluated. The variability in power means that the usual practice of using a common P-value threshold across tests has difficulties. The reason is that the use of a fixed threshold, with variable power, implies that the costs of type I and type II errors vary across tests in a manner that is implicit rather than dictated by the analyst. In this paper we discuss this problem and describe an easily implementable solution based on Bayes factors. We pay particular attention to the specification of priors, which is not a straightforward task. The methods are illustrated using data from a randomized controlled clinical trial in which homocysteine levels are compared in individuals receiving low and high doses of folate supplements and across marker subgroups. The method we describe is implemented in the R computing environment with code available from http://faculty.washington.edu/jonno/cv.html.


Subject(s)
Genome-Wide Association Study , Pharmacogenetics , Bayes Theorem , Humans , Polymorphism, Single Nucleotide , Probability , Randomized Controlled Trials as Topic , Stroke/prevention & control , Vitamins/administration & dosage
6.
J Thromb Haemost ; 10(4): 543-9, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22332961

ABSTRACT

BACKGROUND: Epidemiologic studies report that self-identified African Americans typically have higher hemostatic factor levels than do self-identified Caucasians or Hispanics. OBJECTIVE: To enhance understanding of phenotypic variation in hemostatic factor levels by race/ethnicity, we evaluated the relationship between genetic ancestry and hemostatic factor levels among Multi-Ethnic Study of Atherosclerosis (MESA) study participants. PATIENTS/METHODS: Our sample included 712 African American and 701 Hispanic men and women aged 45 to 84 years. Individual global ancestry was estimated from 199 genetic markers using STRUCTURE. Linear regression models were used to evaluate the relationship between ancestry and hemostatic factor levels, adjusting for age, gender, education, income and study site. RESULTS: Among African Americans, mean ± standard deviation (SD) ancestry was estimated as 79.9% ± 15.9% African and 20.1% ± 15.9% European. Each SD (16%) greater African ancestry was associated with 2.1% higher fibrinogen levels (P = 0.007) and 3.5% higher plasmin-antiplasmin (PAP) levels (P = 0.02). Ancestry among African Americans was not related to levels of factor (F)VIII or D-dimer. Mean ± SD estimated ancestry among Hispanics was 48.3% ± 23.8% Native American, 38.8% ± 21.9% European, and 13.0% ± 8.9% African. In Hispanics, each SD (19%) greater African ancestry was associated with 2.7% higher fibrinogen levels (P = 0.009) and 7.9% higher FVIII levels (P = 0.0002). In Hispanics, there was no relation between African ancestry and D-dimer or PAP levels, or between European ancestry and hemostatic factor levels. CONCLUSIONS: Greater African ancestry among African Americans and Hispanics was associated with higher levels of several hemostatic factors, notably fibrinogen. These results suggest that genetic heterogeneity contributes, albeit modestly, to racial/ethnic differences in hemostatic factor levels.


Subject(s)
Atherosclerosis/ethnology , Atherosclerosis/genetics , Black or African American/genetics , Genetic Variation , Hemostasis/genetics , Hispanic or Latino/genetics , Aged , Aged, 80 and over , Atherosclerosis/blood , Biomarkers/blood , Factor VIII/analysis , Factor VIII/genetics , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Fibrinolysin/analysis , Genotype , Humans , Linear Models , Male , Middle Aged , Pedigree , Phenotype , Prospective Studies , Risk Assessment , Risk Factors , United States/epidemiology , alpha-2-Antiplasmin/analysis
7.
Neurology ; 77(16): 1543-50, 2011 Oct 18.
Article in English | MEDLINE | ID: mdl-21975197

ABSTRACT

OBJECTIVES: The Vitamin Intervention for Stroke Prevention trial found an association between baseline poststroke homocysteine (Hcy) and recurrent stroke. We investigated genes for enzymes and cofactors in the Hcy metabolic pathway for association with Hcy and determined whether associated single nucleotide polymorphisms (SNPs) influenced recurrent stroke risk. METHODS: Eighty-six SNPs in 9 candidate genes (BHMT1, BHMT2, CBS, CTH, MTHFR, MTR, MTRR, TCN1, and TCN2) were genotyped in 2,206 subjects (83% European American). Associations with Hcy measures were assessed using linear regression models assuming an additive genetic model, adjusting for age, sex, and race and additionally for baseline Hcy when postmethionine load change was assessed. Associations with recurrent stroke were evaluated using survival analyses. RESULTS: Five SNPs in the transcobalamin 2 (TCN2) gene were associated with baseline Hcy (false discovery rate [FDR]-adjusted p = 0.049). TCN2 SNP rs731991 was associated with recurrent stroke risk in the low-dose arm of the trial under a recessive model (log-rank test p = 0.009, hazard ratio 0.34). Associations with change in postmethionine load Hcy levels were found with 5 SNPs in the cystathionine ß-synthase (CBS) gene (FDR-adjusted p < 0.031). CONCLUSIONS: TCN2 variants contribute to poststroke Hcy levels, whereas variants in the CBS gene influence Hcy metabolism. Variation in the TCN2 gene also affects recurrent stroke risk in response to cofactor therapy.


Subject(s)
Homocysteine/blood , Polymorphism, Single Nucleotide/genetics , Stroke/blood , Stroke/genetics , Transcobalamins/genetics , Adult , Aged , Female , Genetic Association Studies , Humans , Male , Middle Aged
8.
Rev Neurosci ; 21(1): 55-66, 2010.
Article in English | MEDLINE | ID: mdl-20458887

ABSTRACT

Learning, memory, and recovery from various neurological insults occur by a process known as neuroplasticity. Neuroplastic changes occur by a variety of physiological processes that modify central nervous system structure and function. The ability to non-invasively induce neuroplastic change in humans is developing as an exciting new field in neuroscience and may ultimately improve treatment outcomes for those suffering various neurological conditions reliant on neuroplasticity for recovery of function. The induction of neuroplastic changes is influenced by several factors, and do not occur evenly throughout the day, but appear to be under circadian control. This review will discuss the known mechanisms and techniques used to induce neuroplasticity, circadian modulation of neuroplasticity, and will discuss the potential implications of these findings for human neurorehabilitation.


Subject(s)
Circadian Rhythm/physiology , Neuronal Plasticity/physiology , Animals , Circadian Rhythm/drug effects , Humans , Neuronal Plasticity/drug effects , Neurotransmitter Agents/pharmacology
9.
J Clin Neurosci ; 17(6): 711-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20356744

ABSTRACT

Motor cortex excitability was assessed in 12 patients with Parkinson's disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated ("ON") and when immobile after medication withdrawal ("OFF"). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in "ON" and "OFF" states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either "ON" or "OFF" states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores.


Subject(s)
Motor Cortex/physiopathology , Neural Inhibition/physiology , Pallidotomy/methods , Parkinson Disease/surgery , Adult , Age Factors , Aged , Case-Control Studies , Electromyography/methods , Evoked Potentials, Motor/physiology , Functional Laterality , Humans , Middle Aged , Muscle, Skeletal/physiopathology , Parkinson Disease/pathology , Reaction Time , Sensory Thresholds/physiology , Statistics, Nonparametric , Transcranial Magnetic Stimulation , Young Adult
10.
Ann Hum Genet ; 73(2): 152-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19183347

ABSTRACT

Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extension analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic ESRD. The original and replication analyses confirmed association with four SNPs in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in intron 1 (P = 0.004) and one in intron 5 (P = 0.002) with T2DM-associated ESRD. In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160 controls, an additional 7 intron 13 SNPs produced evidence of association (P = 3.5 x 10(-5)- P = 0.05). No associations were seen with these SNPs in those with T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Black or African American/genetics , Diabetic Nephropathies/ethnology , Diabetic Nephropathies/genetics , Genetic Predisposition to Disease , Aged , Diabetes Mellitus, Type 2/complications , Female , Humans , Introns , Male , Middle Aged , Polymorphism, Single Nucleotide
11.
Arch Dis Child ; 93(9): 760-7, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18456686

ABSTRACT

OBJECTIVE: To examine whether the inverse association between birth weight and blood pressure varies by skin pigmentation and/or related genotypes. STUDY DESIGN: 671 children from a predominantly caucasian birth cohort were followed-up to adolescence (mean (SD) age 14.4 (0.64)). METHODS: Data on birth weight, socioeconomic status, maternal antenatal smoking, adolescent blood pressure and polymorphisms of candidate genes were obtained and analysed by multiple linear regression. RESULTS: An increase in birth weight of 1 kg was associated with an non-significant difference in adolescent systolic blood pressure of -0.53 mm Hg (95% CI -1.72 to 0.66) per kg after adjustment for child age and cohort entry criteria. The inverse association between birth weight and systolic blood pressure was stronger for those with darker skin (> or =2% melanin) (difference in effect, p = 0.02), those with more copies of the C allele of corticotropin-releasing hormone (CRH) +T1273C (p = 0.06), and those with more copies of the short (< or =236 bp) form of the 11beta-HSD2{CA}n(repeat) microsatellite (p = 0.03). CONCLUSIONS: These findings add to the evidence that cortisol-related pathways may account for at least part of the observed birth weight-blood pressure associations.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics , Birth Weight/physiology , Blood Pressure/physiology , Corticotropin-Releasing Hormone/genetics , Infant, Low Birth Weight/physiology , Skin Pigmentation , Adolescent , Anthropometry , Birth Weight/genetics , Blood Pressure/genetics , Child , Child, Preschool , Female , Genotype , Humans , Infant, Newborn , Male , Polymorphism, Genetic/genetics , Pregnancy , Skin Pigmentation/genetics , Systole/genetics , White People/ethnology , White People/genetics
12.
Ann Hum Genet ; 69(Pt 5): 517-27, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16138910

ABSTRACT

Height and body mass index (BMI) have high heritability in most studies. High BMI and reduced height are well-recognized as important risk factors for a number of cardiovascular diseases. We investigated these phenotypes in African American families originally ascertained for studies of linkage with type 2 diabetes using self-reported height and weight. We conducted a genome wide scan in 221 families containing 580 individuals and 672 relative pairs of African American descent. Estimates of heritability and support for linkage were assessed by genetic variance component analyses using SOLAR software. The estimated heritabilities for height and BMI were 0.43 and 0.64, respectively. We have identified major loci contributing to variation in height on chromosomes 15 (LOD = 2.61 at 35 cM, p = 0.0004), 3 (LOD = 1.82 at 84 cM, p = 0.0029), 8 (LOD = 1.92 at 135 cM, p = 0.0024) and 17 (LOD = 1.70 at 110 cM, p = 0.0044). A broad region on chromosome 4 supported evidence of linkage to variation in BMI, with the highest LOD = 2.66 at 168 cM (p = 0.0005). Two height loci and two BMI loci appear to confirm the existence of quantitative trait loci previously identified by other studies, providing important replicative data to allow further resolution of linkage regions suitable for positional cloning of these cardiovascular disease risk loci.


Subject(s)
Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Black People , Body Height , Body Mass Index , Cardiovascular Diseases/genetics , Chromosome Mapping , Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 4 , DNA Primers/chemistry , Family Health , Female , Genetic Linkage , Genome , Genotype , Humans , Lod Score , Male , Quantitative Trait Loci , Risk Factors , Software
13.
Diabetologia ; 48(4): 661-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15747111

ABSTRACT

AIMS/HYPOTHESIS: The heritability of fasting serum insulin and glucose concentrations in non-diabetic members of multiplex hypertensive families is unknown. METHODS: We calculated the familial aggregation of fasting serum glucose and insulin concentrations and performed a genome-wide scan to assess whether quantitative trait loci contribute to these phenotypes in 2,412 non-diabetic individuals from 1,030 families enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) in the Family Blood Pressure Program. RESULTS: The heritability (+/-SE) of fasting serum insulin was 0.47+/-0.085 in European Americans and 0.28+/-0.08 in African Americans (p<0.0001 for both), after adjusting for age, sex, and BMI. A genome-wide scan for fasting serum insulin yielded a maximum log of the odds (LOD) score of 2.36 on chromosome 5 at 20 cM (p=0.0004) in European Americans, and an LOD score of 2.28 on chromosome 19 at 11 cM (p=0.0004) in African Americans. The heritability of fasting serum glucose was 0.5109+/-0.08 in the former and 0.29+/-0.09 in the latter (p<0.0003 for both) after adjusting for age, sex and BMI. A genome-wide scan for fasting serum glucose revealed a maximum LOD score of 2.07 on chromosome 5 at 26 cM (p=0.0009) in European Americans. CONCLUSIONS/INTERPRETATION: These analyses demonstrate the marked heritability of fasting serum insulin and glucose concentrations in families enriched for the presence of members with hypertension. They suggest that genes associated with fasting serum insulin concentration are present on chromosomes 19 and 5, and that genes associated with fasting serum glucose concentration are on chromosome 5, in families enriched for hypertension.


Subject(s)
Blood Glucose/metabolism , Genome, Human , Hypertension/genetics , Insulin/blood , Quantitative Trait Loci/genetics , Adult , Black or African American/genetics , Aged , Analysis of Variance , Chromosomes, Human, Pair 19/genetics , Chromosomes, Human, Pair 5/genetics , Family Health , Fasting , Female , Genetic Linkage/genetics , Genotype , Humans , Hypertension/blood , Insulin Resistance/genetics , Male , Markov Chains , Middle Aged , Pedigree , Phenotype , Quantitative Trait, Heritable , United States , White People/genetics
15.
Diabet Med ; 21(2): 165-70, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14984452

ABSTRACT

AIMS: To compare diabetes management practices in 2001 among individuals from Tasmania, Australia, with a previous management survey conducted in 1995-7. METHODS: Subjects were ascertained through the Tasmanian Insulin-Treated Diabetes Register. General demographic data were collected by telephone interview, and participants mailed a questionnaire on their diabetes management practices. RESULTS: The response rate in 2001 was 80.8% (n=1336). There was a trend to more frequent blood glucose self-monitoring, notably in those less than 25 years (P<0.001 for monitoring >2 times/day), together with continued uptake of the pen system of insulin administration. More intensive shared management by general practitioner and diabetes specialist was noted, including a greater proportion visiting their doctor more than five times per year (P=0.006 for those <50 years). Most patients continue to be appropriately screened for hypertension and retinopathy. Dietitian visits declined overall (P=0.03 for at least annual visits), and there appeared to be an inadequate level of foot examination by patients and doctors. CONCLUSIONS: The survey indicated that most patients were taking greater responsibility for their metabolic control, and intensive management practices and more convenient methods of administration may be contributors. Two areas of possible concern are access to dietitian services, and patient and health provider education on appropriate foot care.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Adolescent , Adult , Age Factors , Aged , Blood Glucose Self-Monitoring , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Self Care
16.
Br J Ophthalmol ; 88(1): 79-83, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14693780

ABSTRACT

AIMS: Mutations of seven crystallin genes have been shown to cause familial cataract. The authors aimed to identify disease causing crystallin mutations in paediatric cataract families from south eastern Australia. METHODS: 38 families with autosomal dominant or recessive paediatric cataract were examined. Three large families were studied by linkage analysis. Candidate genes at regions providing significant LOD scores were sequenced. Single stranded conformational polymorphism (SSCP) analysis was used to screen five crystallin genes in the probands, followed by direct sequencing of observed electrophoretic shifts. Mutations predicted to affect the coding sequence were subsequently investigated in the entire pedigree. RESULTS: A LOD score of 3.72 was obtained at the gamma-crystallin locus in one pedigree. Sequencing revealed a P23T mutation of CRYGD, found to segregate with disease. A splice site mutation at the first base of intron 3 of the CRYBA1/A3 gene segregating with disease was identified by SSCP in another large family. Five polymorphisms were also detected. CONCLUSIONS: Although mutations in the five crystallin genes comprehensively screened in this study account for 38% of paediatric cataract mutations in the literature, only two causative mutations were detected in 38 pedigrees, suggesting that crystallin mutations are a relatively rare cause of the cataract phenotype in this population.


Subject(s)
Cataract/genetics , Crystallins/genetics , Eye Diseases, Hereditary/genetics , Mutation , Cataract/congenital , Child , Female , Genetic Predisposition to Disease , Humans , Lod Score , Male , Pedigree , Polymorphism, Single-Stranded Conformational
17.
Ann Rheum Dis ; 61(12): 1081-4, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12429539

ABSTRACT

BACKGROUND: Previous studies have suggested a strong genetic component to osteoarthritis (OA), especially that of the hand, and three linkage studies have suggested the existence of susceptibility loci in disparate regions of chromosome 2q. OBJECTIVE: To examine for linkage to 2q in a Tasmanian population of women and men with familial hand OA. METHODS: Hand OA (distal interphalangeal, carpometacarpal, and Heberden's nodes) was assessed by a combination of hand photographs and radiographs. A non-parametric linkage (NPL) analysis was performed on chromosome 2q of 69 members in 22 families with severe distal interphalangeal joint OA using Genehunter. A quantitative trait linkage analysis of a larger group of 456 members in 68 families was also performed using SOLAR. RESULTS: The maximum non-parametric linkage score was 1.05 (p=0.15) at marker IL1R1, close to the centromere. All components of hand OA scores had significant heritability in this dataset (28%-35%, all p<0.001). Despite this, the quantitative trait analysis (after adjustment for age and, where appropriate, sex) yielded maximum LOD scores of 0.90 for Heberden's nodes (both sexes combined), and 1.19 for carpometacarpal OA score (women only). CONCLUSIONS: These results do not provide confirmation of linkage on chromosome 2q in the larger white population with hand OA. They suggest that there are regional variations in the genetic cause of hand OA and that other loci not on 2q may be important in this disease.


Subject(s)
Chromosomes, Human, Pair 2/genetics , Genetic Linkage/genetics , Hand , Osteoarthritis/genetics , Adult , Aged , Analysis of Variance , Disease Susceptibility , Family , Female , Finger Joint/diagnostic imaging , Hand/diagnostic imaging , Humans , Lod Score , Male , Middle Aged , Phenotype , Radiography , Tasmania
18.
Arch Dis Child Fetal Neonatal Ed ; 87(2): F78-82, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12193510

ABSTRACT

Retinopathy of prematurity (ROP) has been recognised as an important cause of childhood visual impairment and blindness since the 1940s when improved facilities and treatment increased the survival rate of premature infants. Although its incidence and severity have been decreasing in developed countries over the past two decades, both are increasing in developing nations. ROP is consequently targeted as an important but avoidable disease. This review provides an updated summary and discussion of much of the work that has been produced through population, animal, cell culture, and genetic research. The authors examine the prevalence, risk factors, and possible causes of the disease with a particular focus on genetic studies. They conclude that while significant reductions in the disease have occurred in developed countries, further research is required to fully understand and prevent the disease. In the meantime, development and implementation of appropriate screening and treatment strategies will be critical in reducing blindness in developing countries.


Subject(s)
Retinopathy of Prematurity , Developed Countries/statistics & numerical data , Developing Countries/statistics & numerical data , Genetic Predisposition to Disease , Humans , Incidence , Infant, Newborn , Oxygen/physiology , Retinopathy of Prematurity/epidemiology , Retinopathy of Prematurity/genetics , Retinopathy of Prematurity/metabolism , Risk Factors
19.
Br J Ophthalmol ; 86(6): 696-700, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12034695

ABSTRACT

Retinopathy of prematurity (ROP) has been recognised as an important cause of childhood visual impairment and blindness since the 1940s when improved facilities and treatment increased the survival rate of premature infants. Although its incidence and severity have been decreasing in developed countries over the past two decades, both are increasing in developing nations. ROP is consequently targeted as an important but avoidable disease. This review provides an updated summary and discussion of much of the work that has been produced through population, animal, cell culture, and genetic research. The authors examine the prevalence, risk factors, and possible causes of the disease with a particular focus on genetic studies. They conclude that while significant reductions in the disease have occurred in developed countries, further research is required to fully understand and prevent the disease. In the meantime, development and implementation of appropriate screening and treatment strategies will be critical in reducing blindness in developing countries.


Subject(s)
Retinopathy of Prematurity/etiology , Developing Countries , Humans , Incidence , Infant, Newborn , Retinopathy of Prematurity/epidemiology , Retinopathy of Prematurity/genetics , Risk Factors
20.
Exp Brain Res ; 138(4): 467-76, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11465745

ABSTRACT

Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corticospinal (CS) pathway in activating the first dorsal interosseous (FDI) muscle in each hand of 16 right- (RH) and 16 left-handed (LH) subjects with varied degrees of hand preference. It was hypothesised that asymmetry in corticospinal activation of the two hands may be related to hand preference and interlimb differences in manual performance. Subjects performed isometric index finger abduction at force levels of 0.5 N, 1 N and 2 N while TMS was applied at resting threshold intensity (T), 0.9T, or 0.8T. The amount of contraction-induced facilitation of the muscle evoked potential (MEP) was used as an estimate of corticospinal involvement in the task. Patterns of MEP facilitation in each hand were compared with measures of manual performance (finger tapping speed, Purdue pegboard, maximal FDI strength). Threshold TMS intensities for an MEP in FDI at rest were similar in LH and RH subjects, and did not vary between hands. Facilitation of the MEP with voluntary activation was larger overall on the left side (P<0.05), but the asymmetry was dependent on the degree of lateralisation of hand preference. For subjects with consistent hand preference (either LH or RH), MEP facilitation in active FDI was larger for the left hand. For non-consistent RH subjects, contraction-induced MEP facilitation was larger in the right FDI muscle than the left. Asymmetry of MEP facilitation was not correlated with differences between hands in finger tapping speed or performance in the pegboard task, but was associated with relative differences in FDI strength. MEP facilitation tended to be larger in the stronger FDI muscle of the pair. We conclude that corticospinal involvement in the command for index finger abduction is generally greater when the left hand is used, although in RH subjects the asymmetry is influenced by the degree of lateralisation of hand preference. The corticospinal asymmetry is not related to speed or dexterity of finger movements, but the association with muscle strength suggests that it may be influenced in part by preferential use of one hand for tasks which strengthen the FDI muscle.


Subject(s)
Evoked Potentials, Motor/physiology , Functional Laterality/physiology , Hand/innervation , Motor Cortex/physiology , Motor Skills/physiology , Movement/physiology , Pyramidal Tracts/physiology , Adult , Electric Stimulation , Female , Hand/physiology , Humans , Magnetics , Male , Motor Cortex/anatomy & histology , Muscle Contraction/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Pyramidal Tracts/anatomy & histology , Reaction Time
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