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1.
Pharmacogenomics J ; 16(3): 231-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26169577

RESUMO

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Tosse/induzido quimicamente , Tosse/genética , Proteínas Interatuantes com Canais de Kv/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Biologia Computacional , Tosse/etnologia , Bases de Dados Genéticas , Registros Eletrônicos de Saúde , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fenótipo , Medição de Risco , Fatores de Risco , Escócia , Estados Unidos
2.
Genes Immun ; 16(1): 1-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25297839

RESUMO

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Herpes Zoster/genética , Herpesvirus Humano 3/fisiologia , RNA não Traduzido/genética , Idade de Início , Idoso , Algoritmos , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Herpes Zoster/epidemiologia , Herpes Zoster/etnologia , Herpes Zoster/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante , Estudos Retrospectivos , Estados Unidos/epidemiologia , Estados Unidos/etnologia
3.
Prev Med Rep ; 36: 102517, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38116283

RESUMO

Prior research suggests COVID-19 has amplified stress on Academic Clinician Frontline-Workers (ACFW). The aim of this paper is: (1) to better understand the experiences of ACFW during the COVID-19 pandemic including their mental-emotional wellbeing, academic productivity, clinical experiences, and (2) to examine any gender differences. A cross-sectional survey was administered to University of Minnesota/M Health Fairview systems' faculty February-June 2021. Of the 291 respondents, 156 were clinicians, with 91 (58 %) identifying as Frontline-Workers (ACFW). Faculty wellbeing was assessed using validated measures in addition to measures of productivity and sociodemographics. For example, ACFW reported a higher Work-Family Conflict (WFC) scores compared to non-ACFW (26.5 vs. 24.1, p = 0.057) but did not report higher Family-Work Conflict (FWC) scores (17.7 vs. 16.3, p = 0.302). Gender sub-analyses, revealed that women ACFW compared to men ACFW reported higher WFC scores (27.7 vs. 24.1, p = 0.021) and FWC (19.3 vs. 14.3, p = 0.004). Academically, ACFW reported submitting fewer grants and anticipated delays in promotion and tenure due to the COVID-19 (p = 0.035). Results suggest COVID-19 has exacerbated ACFW stress and gender inequities. Reports of anticipated delay in promotion for ACFW may pose a challenge for the long-term academic success of ACFW, especially women ACFW. In addition, women may experience higher FWC and WFC as compared to men. Schools of academic medicine should consider re-evaluating promotion/tenure processes and creating resources to support women ACFW as well as ACFW caregivers.

4.
Osteoporos Int ; 21(3): 467-77, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19506792

RESUMO

SUMMARY: A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) -634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction. INTRODUCTION: A nested case-control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women. METHODS: Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology. RESULTS: Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 -634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction. CONCLUSION: Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Osteoporose Pós-Menopausa/etiologia , Fumar/efeitos adversos , Idoso , Índice de Massa Corporal , Densidade Óssea/genética , Métodos Epidemiológicos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-6/genética , Proteínas Relacionadas a Receptor de LDL/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/fisiologia , Fumar/epidemiologia , Wisconsin/epidemiologia
5.
Br J Cancer ; 101(1): 178-84, 2009 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-19513076

RESUMO

BACKGROUND: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. METHODS: Among 52 158 women (aged 55-74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. RESULTS: Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00-1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03-1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02-1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. CONCLUSION: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.


Assuntos
Ferro da Dieta/administração & dosagem , Carne , Mutagênicos/administração & dosagem , Neoplasias/epidemiologia , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Culinária , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Modelos de Riscos Proporcionais , Neoplasias da Próstata/epidemiologia , Inquéritos e Questionários
6.
Br J Ophthalmol ; 90(4): 407-10, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16547314

RESUMO

AIM: To study the prevalence and causes of blindness in a rural south Indian population. METHODS: 3924/4800 enumerated (81.75%) subjects, aged 40 years or more from rural Tamil Nadu, underwent comprehensive ophthalmic examination-visual acuity, refraction, intraocular pressure, gonioscopy, cataract grading (LOCS II), retinal examination, and SITA Standard where indicated. Blindness was defined using WHO criteria as best corrected visual acuity of less than 3/60 and/or visual field of less than 10 degrees in the better eye. The influence of age, sex, literacy, and occupation was assessed using multiple logistic regression. RESULTS: 753 subjects (19.2%; 321 males, 432 females) presented with a visual acuity of <3/60; 132 subjects (3.36%, 95% CI: 2.80 to 3.93) were diagnosed to be blind. Cataract was responsible in 74.62% of eyes; glaucoma, cystoid macular oedema, optic atrophy, and corneal scars accounted for 3.79% each. Bilateral causes of blindness were cataract (78.63%), glaucoma (4.29%), optic atrophy (3.42%), cystoid macular oedema, and corneal scars (2.56% each). In 19 eyes (7.2%) the blindness was probably related to cataract surgery. Blindness was positively associated with increasing age (p<0.0001). CONCLUSION: 3.36% of the studied rural population was bilaterally blind, with cataract being the single most important cause.


Assuntos
Cegueira/epidemiologia , Cegueira/etiologia , Adulto , Distribuição por Idade , Idoso , Catarata/complicações , Catarata/epidemiologia , Extração de Catarata/efeitos adversos , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Saúde da População Rural/estatística & dados numéricos , Acuidade Visual
7.
Clin Pharmacol Ther ; 100(2): 160-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26857349

RESUMO

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.


Assuntos
Bases de Dados Genéticas , Variação Genética , Genômica , Farmacogenética , Idoso , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos
8.
Br J Ophthalmol ; 89(3): 360-3, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15722319

RESUMO

AIM: To investigate whether unilateral vision loss reduced any aspects of quality of life in comparison with normal vision and to compare its impact with that of bilateral vision loss. METHODS: This study used cluster stratified random sample of 3271 urban participants recruited between 1992 and 1994 for the Melbourne Visual Impairment Project. All predictors and outcomes were from the 5 year follow up examinations conducted in 1997-9. RESULTS: There were 2530 participants who attended the follow up survey and had measurement of presenting visual acuity. Both unilateral and bilateral vision loss were significantly associated with increased odds of having problems in visual functions including reading the telephone book, newspaper, watching television, and seeing faces. Non-correctable by refraction unilateral vision loss increased the odds of falling when away from home (OR = 2.86, 95% CI 1.16 to 7.08), getting help with chores (OR = 3.09, 95% CI 1.40 to 6.83), and becoming dependent (getting help with meals and chores) (OR = 7.50, 95% CI 1.97 to 28.6). Non-correctable bilateral visual loss was associated with many activities of daily living except falling. CONCLUSIONS: Non-correctable unilateral vision loss was associated with issues of safety and independent living while non-correctable bilateral vision loss was associated with nursing home placement, emotional wellbeing, use of community services, and activities of daily living. Correctable or treatable vision loss should be detected and attended to.


Assuntos
Atividades Cotidianas , Cegueira/psicologia , Qualidade de Vida , Acidentes por Quedas , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Segurança
9.
Br J Ophthalmol ; 89(6): 699-703, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15923505

RESUMO

AIM: To determine the prevalence of glaucoma among aphakes and pseudophakes in a rural population of southern India. METHODS: 3924 subjects aged 40 years or above underwent complete ophthalmic examination. Glaucoma in aphakia/pseudophakia was diagnosed using International Society of Geographical and Epidemiological Ophthalmology criteria in aphakic/pseudophakic people. RESULTS: 54 subjects (37 aphakes, 17 pseudophakes) (1.38% of 3924 subjects, 11.2% of 482 aphakes/pseudophakes) had glaucoma in aphakia/pseudophakia. Aphakia, age, intraocular pressure (IOP), pseudoexfoliation, and peripheral anterior synechiae greater than or equal to 180 degrees of the angle were risk factors for glaucoma on univariate analysis. On multivariate analysis, IOP and aphakia were independent risk factors for glaucoma. 39 people (72.22%) with glaucoma had normal IOP at presentation. None of the people with glaucoma were aware of the disease. Blindness in one or both eyes was seen in 12 subjects (10 unilateral and two bilateral)-that is, 22.22% of people with glaucoma in aphakia/pseudophakia. CONCLUSIONS: Glaucoma is an important cause of ocular morbidity among aphakes and pseudophakes in this rural population of south India. This glaucoma, responsible for unilateral or bilateral blindness in 22.2% of those affected, was entirely undetected in this study population.


Assuntos
Afacia/complicações , Glaucoma/etiologia , Pseudofacia/complicações , Adulto , Idoso , Afacia/epidemiologia , Cegueira/epidemiologia , Cegueira/etiologia , Países em Desenvolvimento , Feminino , Glaucoma/epidemiologia , Glaucoma/fisiopatologia , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Prevalência , Pseudofacia/epidemiologia , Fatores de Risco , Saúde da População Rural/estatística & dados numéricos
10.
Br J Sports Med ; 39(9): 681-5, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16118310

RESUMO

OBJECTIVE: To evaluate the protective eyewear promotion (PEP) project, which was a comprehensive educational strategy to increase the use of appropriate protective eyewear by squash players. METHODS: An ecological study design was used. Four squash venues in one playing association were randomly chosen to receive PEP and four in another association maintained usual practice and hence formed a control group. The primary evaluation measurements were surveys of cross sectional samples of players carried out before and after the intervention. The surveys investigated players' knowledge, behaviours, and attitudes associated with the use of protective eyewear. The survey carried out after the intervention also determined players' exposure to PEP. Univariate and multivariate analyses were undertaken to describe differences at PEP venues from pre- to post-intervention and to compare these with the control venues. RESULTS: The PEP players had 2.4 times the odds (95% confidence interval, 1.3 to 4.2) of wearing appropriate eyewear compared with control group players post-intervention, relative to the groups' pre-intervention baselines. Components of PEP, such as stickers and posters and the availability and prominent positioning of the project eyewear, were found to contribute to players adopting favourable eyewear behaviours. CONCLUSIONS: Components of the PEP intervention were shown to be effective. The true success will be the sustainability and dissemination of the project, favourable eyewear behaviours, and evidence of the prevention of eye injuries long into the future.


Assuntos
Traumatismos Oculares/prevenção & controle , Dispositivos de Proteção dos Olhos , Esportes com Raquete/lesões , Adulto , Austrália , Dispositivos de Proteção dos Olhos/estatística & dados numéricos , Feminino , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Comportamento de Redução do Risco
11.
J Sci Med Sport ; 8(3): 352-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16248476

RESUMO

Self-report surveys are a common method of collecting data on protective equipment use in sport. The aim of this study was to assess the validity of self-reported use of appropriate protective eyewear by squash players. Surveys of squash players' appropriate protective eyewear behaviours were conducted over two consecutive years (2002 and 2003) at randomly-selected squash venues in Melbourne, Australia. Over the two years, 1219 adult players were surveyed (response rate of 92%). Trained observers also recorded the actual on-court appropriate protective eyewear behaviours of all players during the survey sessions. Eyewear use rates calculated from both data sources were compared. The self-reported appropriate protective eyewear use rate (9.4%; 95% CI 7.8, 11.0) was significantly higher (1.6 times more) than the observed rate (5.9%; 95%CI 4.6, 7.2). This suggests that players may over-report their use of appropriate protective equipment, though some may have incorrectly classified their eyewear as being appropriate or suitably protective. Studies that rely only on self-report data on protective equipment use need to take into account that this could lead to biased estimates.


Assuntos
Dispositivos de Proteção dos Olhos/estatística & dados numéricos , Esportes com Raquete , Adulto , Traumatismos em Atletas/prevenção & controle , Austrália , Humanos , Inquéritos e Questionários
12.
J Sci Med Sport ; 8(1): 92-100, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15887906

RESUMO

The use of appropriate eyewear in squash can protect the eyes against injury. However, few adult squash players adequately protect their eyes against potential severe injuries. We describe the characteristics of non-users of protective eyewear and examine predictors of appropriate eyewear use. Self-report surveys of adult players were conducted in metropolitan Melbourne, Australia. Information on players' knowledge, behaviours and attitudes associated with protective eyewear use was collected, in addition to player demographic data. Appropriate eyewear was defined as Standards-approved polycarbonate lens eyewear. The majority 92.2% of players did not adequately protect their eyes while playing squash. Significant predictors of reported eyewear use were: previous eye injury: playing squash on average more than 2 hr per wk: having played for more than 20 y; and having more favourable attitudes towards eye safety in squash. The significant predictors of appropriate eyewear use were: being female; previous eye injury; playing squash on average more than 2 hr per week; and having more favourable attitudes towards eye safety in squash. Understanding the characteristics of both users and non-users of appropriate eye protection in squash is essential for informing future prevention strategies.


Assuntos
Traumatismos em Atletas/prevenção & controle , Traumatismos Oculares/prevenção & controle , Dispositivos de Proteção dos Olhos/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Esportes com Raquete/estatística & dados numéricos , Equipamentos Esportivos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Traumatismos em Atletas/epidemiologia , Traumatismos Oculares/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Esportes com Raquete/lesões , Fatores de Risco , Vitória/epidemiologia
13.
Int J Pediatr Otorhinolaryngol ; 79(12): 2170-3, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26514928

RESUMO

OBJECTIVE: Tympanostomy tube insertion is the most common pediatric surgery, but it typically requires general anesthesia. To facilitate in-office tube placement without general anesthesia, two complementary technologies have recently been developed comprising an iontophoresis system for delivering local anesthesia and an integrated tube delivery system. The purpose of this study was to evaluate behavioral support techniques used during a clinical study of the new technology for pediatric in-office tube placement without general anesthesia or physical restraints. METHODS: As part of an IRB-approved, prospective, nine-center clinical study, pediatric patients requiring tube insertion underwent in-office treatment using the new procedure. The behavior management techniques included preparation, distraction, coaching, and reinforcement for cooperation. The entire procedure was videotaped and two independent coders used the validated FLACC (Face, Legs, Activity, Cry, Consolability) scale to code behavioral distress across five procedural phases. RESULTS: Seventy pediatric patients aged 8 months to 17 years (M=7.0 years; 51% female) were enrolled in the study and 68 had video recordings available for analysis. Of the 68 recordings analyzed, 63 patients completed the procedure and had tubes placed without sedation. Mean FLACC scores ranged from 0.05 to 2.38 (M=1.25, SD=0.82) and median FLACC scores ranged from 0 to 1 (Mdn=0, IQR=0.05), which indicate "mild" distress. During iontophoresis, eardrum tap (anesthesia assessment), and tube delivery, older children displayed lower distress and girls had higher FLACC scores during the eardrum tap procedural phase. CONCLUSION: When combined with the evidence-based behavioral techniques, office-based local anesthesia and tube delivery resulted in minimal distress, suggesting that the new procedure may be a viable method of conducting tympanostomy tube placement in children without having to use general anesthesia. Clinicaltrials.gov identifier: NCT01496287.


Assuntos
Assistência Ambulatorial , Comportamento Infantil , Ventilação da Orelha Média/métodos , Adolescente , Comportamento do Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Dor/prevenção & controle , Medição da Dor , Estudos Prospectivos
14.
Equine Vet J ; 47(6): 715-20, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25237779

RESUMO

REASONS FOR PERFORMING STUDY: To add to the existing data on impact loading of the metacarpophalangeal (MCP) joint as a precursor to assessing the potential role of impact in joint disease. OBJECTIVES: To examine the effect of impact loading on contact areas of the first phalanx (P1) and proximal sesamoids (PS) with the third metacarpal (McIII) under 3 hoof-strike conditions (toe-first, flat, heel-first). STUDY DESIGN: Randomised, repeated controlled experiment using cadaver material. METHODS: Eight cadaver limbs were subjected to randomised, repeated controlled trials where the hoof was struck by a pendulum impact machine (impact velocity 3.55 m/s) under 3 strike conditions. Data from pressure sensitive film placed over medial and lateral McIII condyles and lateromedially across the dorsal aspect of McIII were quantified: total areas of P1 and PS contact (cm(2) ) at maximum recorded pressure; centroid locations of contact areas relative to the sagittal ridge (cm) and transverse ridge (cm) and dispersion of pixels (cm(4) ) for each McIII condyle (medial/lateral). The effect of the strike conditions on each variable were statistically tested using repeated-measures ANOVA (α = 0.05). RESULTS: Contact area between P1 and McIII condyles fell in well-defined areas bounded by the sagittal and transverse ridge, contact areas from PS were smaller and widely dispersed across McIII palmar border. Ratio of contact area of P1 to PS was 2.83 (P<0001). Hoof strike had no significant effect on contact area (P>0.54) CONCLUSIONS: Contact at impact (primarily from P1 and distally situated on McIII), contrasts with contact areas at midstance from both P1 and PS, symmetrically placed. Under impact, the greatest contact area was on the dorsal aspect of the medial condyle and coincides with the area subjected to the greatest increase in subchondral bone stiffening in joint disease.


Assuntos
Casco e Garras/anatomia & histologia , Cavalos/fisiologia , Articulações/fisiologia , Animais , Fenômenos Biomecânicos , Cadáver , Pressão
15.
Equine Vet J ; 47(2): 223-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24580552

RESUMO

REASONS FOR PERFORMING STUDY: We wished to add to the existing baseline data on impact loading of the distal limb as a precursor to assessing the potential role of impact in injury and joint disease. OBJECTIVES: To examine the effect of 3 hoof-strike conditions (toe first, flat and heel first) and 2 specimen masses (with and without a ballast of ∼2% body mass) on impact deceleration and vibration frequencies and energies at the hoof, first phalanx and third metacarpal. STUDY DESIGN: Biomechanical experiments in cadaver material. METHODS: Eight cadaver limbs were subjected to randomised, repeated controlled trials, in which the hoof was struck by a pendulum impact-testing machine (impact velocity, 3.55 m/s) in the 3 strike and 2 mass conditions. Data from triaxial accelerometers on the hoof, first phalanx and third metacarpal quantified, for all trials, the peak impact acceleration, frequencies in the first 6.4 ms following impact, the frequency with the most energy, 95% of the total energy and the frequency at 95% cumulative energy. The effects of the strike and mass conditions on each variable were statistically tested using repeated-measures ANOVA (α = 0.05). RESULTS: Signal energy reaching the third metacarpal was 6-31% of that at the hoof. A heel-first strike produced the largest peak accelerations and highest frequencies among all strike conditions, and changing the mass had no effect regardless of strike condition. CONCLUSIONS: Large accelerations that occur upon impact of the hoof with the ground are attenuated by the distal structures of the equine limb, but still carry considerable energy within the signal that could be damaging to tissue and are dependent on hoof-strike condition but not ballast. Our results suggest that impact loading on the hoof could be a factor in contributing to bone injury and joint disease in the distal limb.


Assuntos
Aceleração , Membro Anterior/fisiologia , Casco e Garras/fisiologia , Cavalos/fisiologia , Vibração , Animais , Fenômenos Biomecânicos , Cadáver
16.
J Med Chem ; 44(6): 988-1002, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11300880

RESUMO

A critical early event in the inflammatory cascade is the induced expression of cell adhesion molecules on the lumenal surface of vascular endothelial cells. These adhesion molecules include E-selectin, ICAM-1, and VCAM-1, which serve to recruit circulating leukocytes to the site of the inflammation. These adhesive interactions allow the leukocytes to firmly adhere to and cross the vascular endothelium and migrate to the site of tissue injury. Pharmaceutical agents which would prevent the induced expression of one or more of the cell adhesion molecules on the endothelium might be expected to provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A thieno[2,3-d]pyrimidine, A-155918, was identified from a whole-cell high-throughput assay for compounds which inhibited the tumor necrosis factor-alpha (TNFalpha)-induced expression of E-selectin, ICAM-1, or VCAM-1 on human vascular endothelial cells. Traditional medicinal chemistry methods were applied to this low-micromolar inhibitor, resulting in the 2,4-disubstituted thieno[2,3-c]pyridine A-205804, a potent and selective lead inhibitor of E-selectin and ICAM-1 expression (IC(50) = 20 and 25 nM, respectively). The relative position of the nitrogen atom in the thienopyridine isomer was shown to be critical for activity, as was a small amide 2-substituent.


Assuntos
Selectina E/metabolismo , Endotélio Vascular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Pirimidinas/síntese química , Administração Oral , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Depressão Química , Selectina E/genética , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Genes Reporter , Humanos , Molécula 1 de Adesão Intercelular/genética , Luciferases/genética , Regiões Promotoras Genéticas , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/toxicidade , Ratos , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
17.
Invest Ophthalmol Vis Sci ; 41(12): 3720-5, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11053268

RESUMO

PURPOSE: Cataract is the most common cause of blindness in the world. The purpose of this study was to estimate the population attributable risk associated with identified risk factors for cortical, nuclear, and posterior subcapsular (PSC) cataract in a representative sample of the Victorian population aged 40 years and older. METHODS: Cluster, stratified sampling was used and participants were recruited through a household census. At locally established test sites, standardized clinical examinations were performed to assess cataract and personal interviews were conducted to quantify potential risk factors. Multivariate logistic regression was used to determine the independent risk factors associated with the three types of cataract, and the population attributable risk was calculated. RESULTS: A total of 3271 (83% of eligible) of the urban residents and 1473 (92%) rural residents participated. The urban residents ranged in age from 40 to 98 years (mean, 59 years), and 1511 (46%) were men. The rural residents ranged in age from 40 to 103 years (mean, 60 years), and 701 (48%) were men. The overall prevalence of cortical cataract was 12.1% (95% CL 10.5, 13.8), nuclear cataract 12.6% (95% CL 9.61, 15.7), and PSC cataract 4.93% (95% CL 3.68, 6.17). Significant risk factors for cortical cataract included age, female gender, diabetes for greater than 5 years, gout for greater than 20 years, arthritis, myopia, average annual ocular UV-B exposure, and family history of cataract (parents or siblings). Significant risk factors for nuclear cataract included age, female gender, rural residence, age-related maculopathy, diabetes for greater than 5 years, smoker for greater than 30 years, and myopia. The significant risk factors for PSC cataract were age, rural residence, thiazide diuretic use, and myopia. Of the modifiable risk factors, ocular UV-B exposure explains 10% of the cortical cataract in the community, and cigarette smoking accounts for 17% of the nuclear cataract. CONCLUSIONS: Because of the near universal exposure to UV-B in the environment, ocular protection has one of the highest modifiable attributable risks for cortical cataract and would therefore be an ideal target for public health intervention. Quit smoking campaigns can be expanded to incorporate information about the excess cataract in the community associated with long-term smoking. Nonmodifiable risk factors such as age, gender, and long-term medication use have implications for the timely referral and treatment for those at higher risk of cataract.


Assuntos
Catarata/epidemiologia , Prioridades em Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/patologia , Catarata/prevenção & controle , Feminino , Humanos , Cápsula do Cristalino/patologia , Córtex do Cristalino/patologia , Núcleo do Cristalino/patologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/organização & administração , Prevalência , Saúde Pública , Fatores de Risco , População Rural , População Urbana , Vitória/epidemiologia
18.
Invest Ophthalmol Vis Sci ; 40(12): 2810-8, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10549640

RESUMO

PURPOSE: To assess the prevalence, distribution, and demographic associations of refractive error in an urban population in southern India. METHODS: Two thousand five hundred twenty-two subjects of all ages, representative of the Hyderabad population, were examined in the population-based Andhra Pradesh Eye Disease Study. Objective and subjective refraction was attempted on subjects >15 years of age with presenting distance and/or near visual acuity worse than 20/20 in either eye. Refraction under cycloplegia was attempted on all subjects < or =15 years of age. Spherical equivalent >0.50 D in the worse eye was considered as refractive error. Data on objective refraction under cycloplegia were analyzed for subjects < or =15 years and on subjective refraction were analyzed for subjects >15 years of age. RESULTS: Data on refractive error were available for 2,321 (92.0%) subjects. In subjects < or =15 years of age, age-gender-adjusted prevalence of myopia was 4.44% (95% confidence interval [CI], 2.14%-6.75%), which was higher in those 10 to 15 years of age (odds ratio, 2.75; 95% CI, 1.25-6.02), of hyperopia 59.37% (95% CI, 44.65%-74.09%), and of astigmatism 6.93% (95% CI, 4.90%-8.97%). In subjects >15 years of age, age-gender-adjusted prevalence of myopia was 19.39% (95% CI, 16.54%-22.24%), of hyperopia 9.83% (95% CI, 6.21%-13.45%), and of astigmatism 12.94% (95% CI, 10.80%-15.07%). With multivariate analysis, myopia was significantly higher in subjects with Lens Opacity Classification System HI nuclear cataract grade > or =3.5 (odds ratio, 9.10; 95% CI, 5.15-16.09), and in subjects with education of class 11 or higher (odds ratio, 1.80; 95% CI, 1.18-2.74); hyperopia was significantly higher in subjects > or =30 years of age compared with those 16 to 29 years of age (odds ratio, 37.26; 95% CI, 11.84-117.19), in females (odds ratio, 1.86; 95% CI, 1.33-2.61), and in subjects belonging to middle and upper socioeconomic strata (odds ratio, 2.10; 95% CI, 1.09-4.03); and astigmatism was significantly higher in subjects > or =40 years of age (odds ratio, 3.00; 95% CI, 2.23- 4.03) and in those with education of college level or higher (odds ratio, 1.73; 95% CI, 1.07-2.81). CONCLUSIONS: These population-based data on distribution and demographic associations of refractive error could enable planning of eye-care services to reduce visual impairment caused by refractive error. If these data are extrapolated to the 255 million urban population of India, among those >15 years of age an estimated 30 million people would have myopia, 15.2 million hyperopia, and 4.1 million astigmatism not concurrent with myopia or hyperopia; in addition, based on refraction under cycloplegia, 4.4 million children would have myopia and 2.5 million astigmatism not concurrent with myopia or hyperopia.


Assuntos
Erros de Refração/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Erros de Refração/diagnóstico , População Urbana/estatística & dados numéricos
19.
Invest Ophthalmol Vis Sci ; 42(5): 908-16, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11274066

RESUMO

PURPOSE: To determine the current prevalence and causes of blindness in the Indian state of Andhra Pradesh to assess if blindness has decreased since the last survey of 1986-1989. METHODS: A population-based epidemiology study, using a stratified, random, cluster, systematic sampling strategy, was conducted in the state of Andhra Pradesh in India. Participants of all ages (n = 10,293), 87.3% of the 11,786 eligible, from 94 clusters in one urban and three rural areas representative of the population of Andhra Pradesh, underwent interview and a detailed dilated ocular evaluation by trained professionals. Blindness was defined as presenting distance visual acuity < 6/60 or central visual field < 20(o) in the better eye. RESULTS: Two hundred seventy-five participants were blind, a prevalence of 1.84% (95% confidence interval, 1.49%-2.19%) when adjusted for the age, sex, and urban-rural distribution of the population in 2000. The causes of this blindness were easily treatable in 60.3% (cataract, 44%; refractive error, 16.3%). Preventable corneal disease, glaucoma, complications of cataract surgery, and amblyopia caused another 19% of the blindness. Blindness was more likely with increasing age and decreasing socioeconomic status, and in female subjects and in rural areas. Among the 76 million population of Andhra Pradesh, 714,400 are estimated to have cataract-related blindness (615,600 cataract, 53,200 cataract surgery-related complications, 45,600 aphakia), and 228,000 refractive error-related blindness (159,600 myopia, 22,800 hyperopia, 45,600 refractive error-related amblyopia). If 95% of the cataract and refractive error blindness in Andhra Pradesh had been treated effectively, 3.4 and 7.4 million blind-person-years, respectively, could have been prevented. If 90% of the blindness due to preventable corneal disease and glaucoma had been prevented, another 2.7 million blind-person-years could have been prevented. CONCLUSIONS: The prevalence of blindness in this Indian state has increased from 1.5% in the late 1980s to 1.84% currently, as against the target of the National Program for Control of Blindness to reduce the prevalence to 0.3% by 2000. The number of people with cataract-related blindness has not reduced even with the eye care policy focus on cataract. Reduction of blindness in India will require strategies that are more effective than those that have been pursued so far.


Assuntos
Cegueira/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cegueira/etiologia , Catarata/complicações , Catarata/epidemiologia , Doenças da Córnea/complicações , Doenças da Córnea/epidemiologia , Feminino , Glaucoma/complicações , Glaucoma/epidemiologia , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Erros de Refração/complicações , Erros de Refração/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos
20.
Arch Ophthalmol ; 117(5): 658-63, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10326965

RESUMO

OBJECTIVE: To determine the prevalence and risk factors of myopia in urban and rural Victoria, Australia. PARTICIPANTS AND METHODS: The Visual Impairment Project is a population-based prevalence study of eye disease in which both urban and rural adult populations were examined. Refractive data on the participants were collected using logMAR visual acuity, corrective lens measurement, and subjective refraction. All refractive error data were converted into spherical equivalent and myopia was defined at 2 levels: worse than -0.5 diopters (D) and worse than -1.00 D. RESULTS: A total of 3271 (83%) urban and 1473 (91%) rural residents were examined. The overall prevalence of myopia worse than -0.50 D in the population was 17% (95% confidence limit = 15.8%, 18.0%). Prevalence of myopia decreased from 24% in those aged 40 to 49 years to 12% in those aged 70 to 79 years, and then increased to 17% in people older than 80 years. The younger age groups also had higher usage of myopic corrective lenses throughout their lives than the older age groups, indicating an increased use of myopic corrective lenses in recent times. Myopia was found to be significantly higher in people with higher education levels (chi2 = 119.20, P < .001), in clerks and professionals (chi2 = 132.53, P < .001), in people born in southeast Asia (chi2 = 77.62, P < .001), and in people with higher degrees of nuclear opacity (chi2 = 55.26, P < .001). CONCLUSION: Myopia rates in the Visual Impairment Project generally decrease with age and use of myopic correction has increased in recent times. Myopia was significantly related to education level, occupation, country of birth, and nuclear opacity.


Assuntos
Miopia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Lentes de Contato , Escolaridade , Óculos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/terapia , Prevalência , Fatores de Risco , População Rural , População Urbana , Vitória/epidemiologia , Acuidade Visual
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