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1.
Disabil Rehabil ; 45(3): 469-482, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35142243

RESUMO

PURPOSE: To evaluate a dog-walking program (called "Dog Buddies") designed to address the need for evidence-based programs that create opportunities for people with cognitive disabilities to be more socially included in mainstream society. The research question was: Does community dog walking foster social interaction for people with cognitive disabilities? MATERIALS AND METHODS: Single-case experimental design was used with four individuals (three with intellectual disability; one with Acquired Brain Injury (ABI)) recruited via two disability service providers in Victoria. Target behaviours included frequency and nature of encounters between the person with disability and community members. Change was measured from baseline (five community meetings with a handler but no dog) to intervention period (five meetings minimum, with a handler and a dog). Semi-structured interviews, audio-recorded and transcribed verbatim, provided three participants' subjective experiences of the program. RESULTS: Dog Buddies increased the frequency of encounters for all participants. The presence of the dog helped to foster convivial encounters, community members were found to be more welcoming, and some participants were recognised or acknowledged by name over time in the intervention phase. CONCLUSIONS: The dog-walking program offered a simple means of influencing the frequency and depth of community-based social interactions for people with cognitive disabilities.IMPLICATIONS FOR REHABILITATIONThe co-presence of people with disabilities in the community with the general population does not ensure social interaction occurs.Both disability policy, and the programs or support that is provided to people with disabilities, needs to have a strong commitment to the inclusion of people with disabilities in mainstream communities.Dog Buddies is a promising example of a program where the presence of a pet dog has been demonstrated to support convivial, bi-directional encounters of people with cognitive disabilities and other community members.Dog-walking offers a simple means of influencing the frequency and depth of community-based social interactions for people with cognitive disabilities.


Assuntos
Pessoas com Deficiência , Deficiência Intelectual , Humanos , Animais , Cães , Caminhada , Deficiência Intelectual/psicologia , Cognição
4.
JACC Cardiovasc Imaging ; 5(1): 38-45, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22239891

RESUMO

OBJECTIVES: A prospective, multicenter (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging study was performed to estimate the correlations among arterial FDG uptake and atherosclerotic plaque biomarkers in patients with peripheral artery disease. BACKGROUND: Inflammation within atherosclerotic plaques is associated with instability of the plaque and future cardiovascular events. Previous studies have shown that (18)F-FDG-PET/CT is able to quantify inflammation within carotid artery atherosclerotic plaques, but no studies to date have investigated this correlation in peripheral arteries with immunohistochemical confirmation. METHODS: Thirty patients across 5 study sites underwent (18)F-FDG-PET/CT imaging before SilverHawk atherectomy (FoxHollow Technologies, Redwood City, California) for symptomatic common or superficial femoral arterial disease. Vascular FDG uptake (expressed as target-to-background ratio) was measured in the carotid arteries and aorta and femoral arteries, including the region of atherectomy. Immunohistochemistry was performed on the excised atherosclerotic plaque extracts, and cluster of differentiation 68 (CD68) level as a measure of macrophage content was determined. Correlations between target-to-background ratio of excised lesions, as well as entire arterial regions, and CD68 levels were determined. Imaging was performed during the 2 weeks before surgery in all cases. RESULTS: Twenty-one patients had adequate-quality (18)F-FDG-PET/CT peripheral artery images, and 34 plaque specimens were obtained. No significant correlation between lesion target-to-background ratio and CD68 level was observed. CONCLUSIONS: There were no significant correlations between CD68 level (as a measure of macrophage content) and FDG uptake in the peripheral arteries in this multicenter study. Differences in lesion extraction technique, lesion size, the degree of inflammation, and imaging coregistration techniques may have been responsible for the failure to observe the strong correlations with vascular FDG uptake observed in previous studies of the carotid artery and in several animal models of atherosclerosis.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Artérias/diagnóstico por imagem , Artérias/imunologia , Fluordesoxiglucose F18 , Imagem Multimodal , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/imunologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Idoso , Aorta/diagnóstico por imagem , Aorta/imunologia , Biomarcadores/análise , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/imunologia , Estudos de Viabilidade , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/imunologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Estados Unidos
5.
Neurourol Urodyn ; 31(1): 69-74, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21905086

RESUMO

AIMS: To evaluate a urodynamic platform designed to identify treatment effects in small numbers of patients after a short duration of treatment using a medication with known efficacy in overactive bladder (OAB). METHODS: Twenty women with OAB were randomized in a crossover study with 7-day treatment periods with either tolterodine 4 mg long-acting (LA) or placebo and 7-day washout. Patients underwent urodynamic study (UDS) at baseline, 4-hr post-dose on Day 1 (PD1) and 4 hr post-dose on Day 7 (PD7) in each treatment period. The primary endpoint was the change from baseline in volume at maximum cystometric capacity (MCC) at PD7. As a result of dosing errors, some patients allocated to tolterodine in Period 1 mistakenly received placebo on Day 7. The data from the time points at which patients were dosed incorrectly were excluded from the per protocol (PP) analysis. RESULTS: The PP and intent to treat (ITT) mean increase in volume at MCC on PD7 for tolterodine compared with placebo was 28.9% (P = 0.038, one-sided) and 23.2% (P = 0.008, one-sided), respectively. The PD7 mean increase in volume at first desire to void was 36.5% (P = 0.054, PP) and 40.3% (P = 0.008, ITT). No volume endpoint at PD1 was statistically significant. Of all the endpoints, MCC was the least variable. CONCLUSIONS: This crossover design was able to detect a clinically meaningful and statistically significant treatment effect consistent with the previous reports of tolterodine. Despite multiple urodynamics per patient, the study was able to recruit quickly. This model is valuable for evaluating therapeutic effects for existing and novel treatments for OAB.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Cresóis/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Fenilpropanolamina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/fisiopatologia , Urodinâmica/fisiologia , Adulto , Idoso , Compostos Benzidrílicos/farmacologia , Complacência (Medida de Distensibilidade)/efeitos dos fármacos , Complacência (Medida de Distensibilidade)/fisiologia , Cresóis/farmacologia , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Antagonistas Muscarínicos/farmacologia , Fenilpropanolamina/farmacologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Tartarato de Tolterodina , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiologia , Micção/efeitos dos fármacos , Micção/fisiologia , Urodinâmica/efeitos dos fármacos
6.
Eur J Endocrinol ; 166(3): 459-67, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22180452

RESUMO

OBJECTIVE: Use of glucocorticoids for anti-inflammatory efficacy is limited by their side effects. This study examined, in the same individuals, prednisone's acute, dose-dependent effects on inflammation as well as biomarkers of glucose regulation and bone homeostasis. DESIGN: In this randomized, double-blind, parallel-design trial of healthy adults demonstrating cutaneous allergen-induced hypersensitivity, patients received placebo or prednisone 10, 25 or 60 mg daily for 7 days. METHODS: Effects on peripheral white blood cell (WBC) count, ex vivo whole blood lipopolysaccharide (LPS)-stimulated TNF-α release and response to cutaneous allergen challenge were assessed concurrently with biomarkers for glucose tolerance and bone turnover. RESULTS: Differential peripheral WBC counts changed significantly within hours of prednisone administration. Ex vivo, LPS-stimulated TNF-α was significantly reduced by all prednisone doses on days 1 and 7. The late phase cutaneous allergen reaction was significantly reduced with prednisone 60 mg vs placebo on days 1 and 7. Oral glucose tolerance tests revealed significant increases in glycaemic excursion on days 1 and 7, whereas increases in insulin and C-peptide excursions were more notable on day 7 with all doses of prednisone. The bone formation markers osteocalcin, and procollagen I N- and C-terminal peptides decreased significantly on days 1 and 7 vs placebo. CONCLUSIONS: In healthy young adults after single doses as low as 10 mg, prednisone treatment has significant effects on glucose tolerance and bone formation markers within hours of treatment, in parallel with anti-inflammatory effects.


Assuntos
Glicemia/metabolismo , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Mediadores da Inflamação/administração & dosagem , Prednisona/administração & dosagem , Adolescente , Adulto , Biomarcadores/metabolismo , Método Duplo-Cego , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
J Am Coll Health ; 60(1): 82-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22171733

RESUMO

OBJECTIVES: The primary objective of this study was to characterize the prevalence of overweight/obesity, metabolic syndrome (MbS) and its criteria, and nutrient intakes of college-age men and women via a large-scale screening. PARTICIPANTS AND METHODS: From August 2005 to July 2008, 2,722 subjects were recruited for the ongoing, cross-sectional Young Adult Health Risk Screening Initiative project. Anthropometric, biochemical, clinical, and dietary data were collected. RESULTS: Approximately one-half of men and more than one-quarter of women were overweight or obese. MbS was identified in 9.9% of men and 3.0% of women; 77% of men and 54% of women had at least 1 MbS criterion. Intakes of saturated fat, magnesium, and fiber, as well as body mass index and reported physical activity levels were related to MbS. CONCLUSIONS: Because of high rates of overweight/obesity and MbS, college-age adults are at risk for developing chronic diseases including diabetes mellitus and cardiovascular disease.


Assuntos
Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Biomarcadores , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etiologia , New Hampshire , Avaliação Nutricional , Obesidade/complicações , Obesidade/diagnóstico , Prevalência , Fatores de Risco , Distribuição por Sexo , Universidades , Adulto Jovem
8.
London; King's College London; June 2012. 40 p.
Monografia em Inglês | Desastres | ID: des-19064
9.
Rheumatology (Oxford) ; 49(9): 1756-61, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20525742

RESUMO

OBJECTIVES: There is a need to improve competence of musculoskeletal system (MSS) examination in medical students and junior doctors. Peer-assisted learning (PAL) is a technique whereby students learn from and with each other. This study aimed to determine whether PAL can be integrated into standard undergraduate medical curricula to improve MSS examination using the gait, arms, legs, spine (GALS) screening tool. METHODS: Fifty final-year students (trainers) were trained using GALS for MSS examination while attending a standard clinical medical attachment at Glasgow Royal Infirmary. These students delivered GALS training to a further 159 students (trainees). Pre/post-confidence questionnaire (100-mm visual analogue scale) and written feedback were obtained. Final Objective Structured Clinical Examination (OSCE) scores from an MSS station were compared with a control group of 229 students randomized to other hospitals for the standard MSS training. RESULTS: Analysis of completed trainer questionnaires (30/50) showed increased confidence in all parts of GALS after training [<47 (19) cf. >88 (12); P < 0.005]. Similarly, confidence in trainees (136/159) who answered the questionnaire increased [<43 (19) cf. >85 (15); P < 0.005]. Written comments highlighted that students would recommend PAL. OSCE results showed 84% (192/229) of students in the control group passed the MSS station, with 87% (139/159) of trainees (P = 0.3) and 100% (50/50) of trainers (P < 0.01). CONCLUSIONS: MSS examination skills are improved by integrating PAL into the undergraduate medical curriculum, with student confidence being increased, and higher OSCE scores.


Assuntos
Competência Clínica/normas , Currículo/normas , Educação de Graduação em Medicina/métodos , Avaliação Educacional/métodos , Doenças Musculoesqueléticas/diagnóstico , Reumatologia/educação , Análise de Variância , Educação de Graduação em Medicina/normas , Avaliação Educacional/normas , Humanos , Sistema Musculoesquelético , Grupo Associado , Exame Físico/métodos , Exame Físico/normas , Escócia , Estudantes de Medicina , Inquéritos e Questionários
10.
Obesity (Silver Spring) ; 18(10): 2047-54, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20448539

RESUMO

Precision and accuracy of the quantitative magnetic resonance (QMR) system for measuring fat in phantoms and total body fat (TBF) in humans were investigated. Measurements were made using phantoms: oil, beef with water, beef with oil, and humans with oil and water. TBF(QMR) in humans was compared with TBF by a four-compartment model (TBF(4C)). The coefficient of variation (CV) for replicate TBF(QMR) was 0.437%. QMR fat was lower at 23 °C vs. 37 °C. The fat increase in QMR phantom studies was consistent with the oil increase. When oil was added with humans, the increase in TBF(QMR) was >250 g for the initial 250 g of oil. With additional oil increments, the increase in TBF(QMR) was consistent with the amount of oil added. When water was added with humans, the TBF(QMR) increased independent of the amount of water added. TBF(QMR) was significantly less (mean ± s.e.) than TBF(4C) (females: -0.68 ± 0.27 kg, males: -4.66 ± 0.62 kg; P = 0.0001), TBF(BV) (females: -1.90 ± 0.40 kg; males: -5.68 ± 0.75 kg; P = 0.0001), and TBF(D2O) for males, but greater for females (1.19 ± 0.43 kg vs. -3.69 ± 0.81 kg for males; P = 0.0003). TBF(QMR) was lower than TBF(iDXA) with the difference greater in males (P = 0.001) and decreased with age (P = 0.011). The strong linear relationships between TBF(QMR) and TBF(4C), TBF(BV), and TBF(D2O) with slopes consistent with unity suggest that modifications are required to improve the accuracy. Should the latter be accomplished, QMR holds promise as a highly precise, rapid, and safe, noninvasive method for estimating the amount of and changes in TBF in overweight and severely obese persons.


Assuntos
Tecido Adiposo/patologia , Adiposidade , Pesos e Medidas Corporais/métodos , Espectroscopia de Ressonância Magnética/métodos , Obesidade/patologia , Adulto , Viés , Água Corporal , Pesos e Medidas Corporais/normas , Feminino , Humanos , Espectroscopia de Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Fatores Sexuais , Adulto Jovem
11.
J Am Diet Assoc ; 109(10): 1751-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19782175

RESUMO

Few comprehensive studies exist that evaluate the nutrient intake and health indicators of college-aged students. This article describes the University of New Hampshire's Young Adult Health Risk Screening Initiative and examines results from participants evaluated from September 2005 through July 2007. This cross-sectional study included 1,701 students who enrolled in an introductory nutrition course, met age requirements (18 to 24 years), agreed to participate, and completed related assessments. All evaluation components were built into the semester-long course design, thus minimizing participant burden. Anthropometric measurements, blood lipids, blood glucose, and blood pressure were measured directly by research staff. Online dietary intake was self-reported and evaluated using a software program. Health risk data indicate high rates of overweight (33%), elevated low-density lipoprotein cholesterol (53%), and elevated systolic (47%) and diastolic blood pressures (39%). Less than 30 minutes of physical activity per day was reported by 28% of respondents. The majority of males (94%) and females (73%) exceeded sodium guidelines. Although females were less likely to be overweight than males, few met recommended intakes for vitamin D (26%), calcium (25%), potassium (35%), iron (31%), and folate (32%). Undergraduate and graduate dietetics students assisted with biological assessments, data entry, and record maintenance. Data inclusion rates ranged between 84% and 94% for various measurements. The methods employed in this study could be modified by institutions interested in profiling the health status of students. Results have led to an enhanced understanding of the nutrition practices and health status of this population and will serve to inform university programs and policies.


Assuntos
LDL-Colesterol/sangue , Dieta , Nível de Saúde , Hipertensão/epidemiologia , Sobrepeso/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Antropometria , Estudos Transversais , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Hipertensão/diagnóstico , Estilo de Vida , Masculino , New Hampshire , Política Nutricional , Sobrepeso/diagnóstico , Medição de Risco , Fumar , Estudantes/psicologia , Universidades/estatística & dados numéricos , Adulto Jovem
12.
Med Teach ; 29(6): 577-82, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17978969

RESUMO

BACKGROUND: This study evaluates whether peer-assisted learning (PAL) can be used to improve students' clinical examination skills. METHODS: Four year 4 students trained in PAL techniques and musculoskeletal (MSS) examination used the Gait, Arms, Legs and Spine (GALS) system in a five-week student selected module. These students then recruited and trained 28 second-year trainees. Trainees were evaluated using pre/post confidence questionnaires (100 mm visual analogue scale), a course experience questionnaire (five-point Likert scales) and end-of-year objective structured clinical examination (OSCE) scores. RESULTS: Baseline data from the experimental group were no different from a separate control group, but after training a statistically significant difference in confidence levels was observed in all parts of GALS, <38 to >73 (p < 0.0001). Course experience questionnaires demonstrated benefits in all parameters including communication skills and group work with all students recommending PAL training. In end-of-year OSCE 93% of PAL-trained students passed the MSS examination station compared with 67% for those participating in the standard curriculum alone (p < 0.0001). Examination results for other clinical skill stations showed no difference in performance between the two groups. CONCLUSIONS: This study shows that PAL is a useful adjunct to MSS training, and could be incorporated into medical curricula to enhance clinical skills.


Assuntos
Competência Clínica , Educação de Graduação em Medicina/métodos , Aprendizagem , Doenças Musculoesqueléticas , Grupo Associado , Ensino/métodos , Adulto , Currículo , Avaliação Educacional , Feminino , Humanos , Masculino , Estatísticas não Paramétricas , Inquéritos e Questionários
13.
Med Educ ; 41(4): 411-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17430287

RESUMO

OBJECTIVE: This study aimed to determine whether peer-assisted learning (PAL) can enhance clinical examination skills training. METHODS: Three student trainers studied small-group theory and clinical examination and provided PAL as extra tuition for 86 trainees. Trainees watched an examination video, were videotaped practising the examination and, after constructive feedback, repeated the examination. Responses to PAL were evaluated to attain an overview of trainee and trainer performance using visual analogue and Likert scale analyses. Year-group review was undertaken using questionnaires. RESULTS: Trainees evaluated all aspects of PAL highly, including their post-training confidence in examination skills (mean > 7.7 on a 10-cm scale), indicating that the PAL was effective. Written comments confirmed the students perceived the sessions as well structured and of high quality. Compared with trainees in the first groups, those from later groups gave all parameters similar or higher gradings. Those for interest (P = 0.03) and appropriateness (P = 0.01) were significantly higher, suggesting that trainers may improve their technique with time. Students with previous degrees gave similar or lower gradings than standard entry students, with answers about post-training confidence and recommendation to friends being statistically lower (P < 0.006). Six months later, year-group analysis showed that 90% of trainees rated PAL highly, and 86% wished to become trainers. Of the trainers' year group, 79% perceived that PAL training could improve examination skills. CONCLUSIONS: In the context of clinical skills training, PAL was highly evaluated across many parameters, including confidence after training. Student interest and enthusiasm supports suggestions that PAL could be a useful adjunct to clinical skills training.


Assuntos
Competência Clínica/normas , Educação de Graduação em Medicina/métodos , Grupo Associado , Estudantes de Medicina/psicologia , Ensino/métodos , Adolescente , Adulto , Atitude do Pessoal de Saúde , Feminino , Humanos , Aprendizagem , Masculino , Escócia
14.
J Clin Pharmacol ; 46(3): 321-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16490808

RESUMO

This single-center, open-label, 2-period crossover study investigated the effects of multiple-dose ezetimibe (EZE) on a single dose of cyclosporine (CyA). Healthy subjects received 2 treatments in random order with a 14-day washout: (1) CyA 100 mg alone and (2) EZE 20 mg for 7 days with CyA 100 mg coadministered on day 7; EZE 20 mg alone was administered on day 8. AUC(0-last) and Cmax geometric mean ratios (90% confidence interval) for ([CyA + EZE]/CyA alone) were 1.15 (1.07, 1.25) and 1.10 (0.97, 1.26), respectively. Tmax (approximately 1.3 hours) was similar with and without EZE (P >.200). Mean CyA exposure slightly increased (approximately 15%) with multiple-dose EZE 20 mg; however, this value was contained within (0.80, 1.25). The implications for chronic EZE dosing within the usual clinical paradigm of chronic CyA dosing have not been established; caution is recommended when using these agents concomitantly. CyA concentrations should be monitored in patients receiving EZE and CyA.


Assuntos
Anticolesterolemiantes/farmacologia , Azetidinas/farmacologia , Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Adulto , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos , Ezetimiba , Feminino , Humanos , Masculino
15.
J Clin Pharmacol ; 46(3): 328-36, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16490809

RESUMO

This open-label, single-period study evaluated the single-dose pharmacokinetics of ezetimibe (EZE) 10 mg in the setting of steady-state cyclosporine (CyA) dosing in renal transplant patients. A single 10-mg dose of EZE was coadministered with the morning dose of CyA (75-150 mg twice a day). Total EZE (sum of unconjugated, parent EZE and EZE-glucuronide; EZE-total) AUC(0-last) and Cmax were compared to values derived from a prespecified database of healthy volunteers. Geometric mean ratios (90% CIs) for (EZE + CyA)/EZE alone for EZE-total AUC((0-last)) and Cmax were 3.41 (2.55, 4.56) and 3.91 (3.13, 4.89), respectively. Compared to healthy controls, EZE-total AUC((0-last)) was 3.4-fold higher in transplant patients receiving CyA; similar exposure levels were seen in a prior multiple-dose study in which EZE 50 mg was administered to healthy volunteers without dose-related toxicity. Because the long-term safety implications of both higher EZE exposures and undetermined effect on CyA are not yet understood, the clinical significance of this interaction is unknown.


Assuntos
Anticolesterolemiantes/farmacocinética , Azetidinas/farmacocinética , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Transplante de Rim , Adulto , Idoso , Anticolesterolemiantes/sangue , Área Sob a Curva , Azetidinas/sangue , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos , Ezetimiba , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Nutr ; 135(5): 1208-14, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15867305

RESUMO

The dietary carotenoids lutein (L) and zeaxanthin (Z) are the principal components of macular pigment (MP). Protection of the central retina by MP is suggested, but data are limited. Dietary practices and serum carotenoid concentrations were investigated in 98 adults, 45-73 y old, in relation to MP. Macular pigment optical density (MPOD) was measured at 4 loci: 10 min (10', 30 min (30'), 60 min (60'), and 120 min (120') retinal eccentricity. Serum L + Z concentrations in fasting subjects were correlated with MPOD: 10' (r = 0.29, P = 0.008), 30' (r = 0.342, P = 0.0006), and 60' (r = 0.73, P = 0.001) eccentricity. Dietary L + Z was positively correlated with MPOD: 10' (r = 0.24, P = 0.02), 30' (r = 0.237, P = 0.02), 60' (r = 0.27, P = 0.009), and 120' (r = 0.25, P = 0.02) eccentricity. The lowest fruit and vegetable consumers had lower MPOD at 30' (P = 0.01), 60' (P = 0.03), and 120' (P = 0.006) eccentricity compared with the highest consumers. Based on age quartiles (45-49 y), (50-55 y), (56-61 y), and (62-74 y), the youngest and oldest had higher MPOD than those 56-61 y at 60' (P < 0.05). Compared with those with a BMI (kg/m(2)) >/= 27, those with a BMI < 27 had higher serum concentrations of beta-carotene (P = 0.002), and higher MPOD at 60' (P = 0.04) and 120' (P = 0.01). These findings suggest that carotenoid-rich diets and serum carotenoids positively contribute to MP status.


Assuntos
Carotenoides/sangue , Dieta , Retina/fisiologia , Pigmentos da Retina/análise , Idoso , Índice de Massa Corporal , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Clin Pharmacol ; 44(9): 1054-62, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15317833

RESUMO

Simvastatin and fenofibrate are both commonly used lipid-regulating agents with distinct mechanisms of action, and their coadministration may be an attractive treatment for some patients with dyslipidemia. A 2-period, randomized, open-label, crossover study was conducted in 12 subjects to determine if fenofibrate and simvastatin are subject to a clinically relevant pharmacokinetic interaction at steady state. In treatment A, subjects received an 80-mg simvastatin tablet in the morning for 7 days. In treatment B, subjects received a 160-mg micronized fenofibrate capsule in the morning for 7 days, followed by a 160-mg micronized fenofibrate capsule dosed together with an 80-mg simvastatin tablet on days 8 to 14. Because food increases the bioavailability of fenofibrate, each dose was administered with food to maximize the exposure of fenofibric acid. The steady-state pharmacokinetics (AUC(0-24h), C(max), and t(max)) of active and total HMG-CoA reductase inhibitors, simvastatin acid, and simvastatin were determined following simvastatin administration with and without fenofibrate. Also, fenofibric acid steady-state pharmacokinetics were evaluated with and without simvastatin. The geometric mean ratios (GMRs) for AUC(0-24h) (80 mg simvastatin [SV] + 160 mg fenofibrate)/(80 mg simvastatin alone) and 90% confidence intervals (CIs) were 0.88 (0.80, 0.95) and 0.92 (0.82, 1.03) for active and total HMG-CoA reductase inhibitors. The GMRs and 90% CIs for fenofibric acid (80 mg SV + 160 mg fenofibrate/160 mg fenofibrate alone) AUC(0-24h) and C(max) were 0.95 (0.88, 1.04) and 0.89 (0.77, 1.02), respectively. Because both the active inhibitor and fenofibric acid AUC GMR 90% confidence intervals fell within the prespecified bounds of (0.70, 1.43), no clinically significant pharmacokinetic drug interaction between fenofibrate and simvastatin was concluded in humans. The coadministration of simvastatin and fenofibrate in this study was well tolerated.


Assuntos
Fenofibrato/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Hipolipemiantes/farmacocinética , Sinvastatina/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Biotransformação , Contagem de Células Sanguíneas , Estudos Cross-Over , Interações Medicamentosas , Eletrocardiografia/efeitos dos fármacos , Feminino , Fenofibrato/efeitos adversos , Meia-Vida , Humanos , Hidroximetilglutaril-CoA Redutases/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipolipemiantes/efeitos adversos , Técnicas In Vitro , Masculino , Microssomos Hepáticos/metabolismo , Pessoa de Meia-Idade , Sinvastatina/efeitos adversos
19.
J Clin Pharmacol ; 43(8): 831-9, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12953340

RESUMO

Consumption of typical quantities of grapefruit juice (GFJ) increases the oral bioavailability of several CYP3A4 substrates without affecting their elimination, consistent with selective inhibition of intestinal but not hepatic CYP3A4. However, increases in the AUCs of CYP3A4 substrates recently associated with the consumption of large amounts of GFJ were similar to those observed with potent inhibitors of hepatic CYP3A4. The current study compared the effects of consuming large quantities and more typical amounts of GFJ on the activity of hepatic and intestinal cytochrome P450 3A4 in vivo, employing the erythromycin breath test (EBT) and oral midazolam pharmacokinetics. This was a two-phase, randomized, placebo-controlled crossover study, with each phase conducted with a separate panel of subjects. In Phase I, 8 male volunteers were randomized to the order of receiving one glass (240 mL) of water (placebo) or double-strength (DS) GFJ tid for 2 days and then 90, 60, and 30 minutes prior to administration of probe drugs on the 3rd day. In Phase II, 16 male volunteers were randomized to the order of receiving one glass of (1) single-strength (SS) GFJ, (2) DS GFJ, and (3) water (placebo). All treatments were administered in a fasted state. There was at least a 7-day washout period between treatments. Probe drugs, administered 30 minutes or 1 hour following each treatment in Phase I or II, respectively, consisted of oral midazolam (2 mg) coadministered with IV [14G N-methyl] erythromycin (0.03 mg). The EBT was performed 20 minutes following erythromycin administration. Blood was collected during the 24 hours following probe drug administration for the analysis of midazolam pharmacokinetics. In Phase I, consumption of one glass of DS GFJ tid for 3 days increased the Cmax of midazolam 3-fold, the AUC 6-fold, and the t1/2 2-fold and decreased the amount of exhaled 14CO2 in all 8 subjects, with a mean decrease in EBT of 18%. In Phase II, consumption of one glass of DS GFJ significantly increased the AUC and Cmax of midazolam approximately 2-fold without a significant effect on the t1/2 of midazolam or the EBT. The effects of consuming one glass of SS GFJ on midazolam pharmacokinetics and the EBT were not significantly different from those of one glass of DS GFJ. It was concluded that consumption of one glass of DS GFJ tid for 3 days significantly increased the AUC, Cmax, and t1/2 of midazolam and reduced EBT values, reflecting inhibition of both hepatic and intestinal CYP3A4. In contrast, consumption of one glass of SS or DS GFJ increased midazolam AUC and Cmax, with little effect on the midazolam t1/2 and EBT values, reflecting preferential inhibition of intestinal CYP3A4. Alterations of midazolam AUC and Cmax induced by nine glasses of DS GFJ were significantly greater than those produced by one glass of SS or DS GFJ. These data suggest that GFJ inhibits intestinal and hepatic CYP3A4 in an exposure-dependent fashion and that patients taking medications that are CYP3A4 substrates are at risk for developing drug-related adverse events if they consume large amounts of grapefruit juice.


Assuntos
Bebidas , Citrus paradisi , Inibidores das Enzimas do Citocromo P-450 , Eritromicina/farmacocinética , Fármacos Gastrointestinais/farmacocinética , Hipnóticos e Sedativos/farmacocinética , Intestinos/enzimologia , Fígado/enzimologia , Midazolam/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Testes Respiratórios , Estudos Cross-Over , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Eritromicina/metabolismo , Fármacos Gastrointestinais/metabolismo , Meia-Vida , Humanos , Hipnóticos e Sedativos/sangue , Fígado/metabolismo , Masculino , Taxa de Depuração Metabólica , Midazolam/sangue
20.
J Clin Pharmacol ; 43(9): 983-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12971030

RESUMO

Inhibition of ex vivo arachidonic acid (AA)-induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase (COX) inhibitors since platelets express COX-1 but not COX-2. At low concentrations, there is broad inter- and intrasubject variability in AA-induced aggregation of platelets ex vivo. This study defined a concentration that reliably induces aggregation without overcoming inhibition by therapeutic aspirin therapy (ASA, 81-mg) treatment. Logistic regression analysis of ex vivo aggregation, induced with increasing concentrations of AA in platelet-rich plasma (PRP), estimated that platelets from > or = 90% of subjects would aggregate at > or = 1.5 mM AA (95% confidence interval [CI], 1.1, 2.1). A concentration of 1.6 mM AA failed to aggregate platelets from 26 healthy volunteers, who had previously aggregated at this concentration, following six daily oral doses of 81 mg of ASA. These data demonstrate that 1.6 mM AA reproducibly induces platelet aggregation in PRP from healthy volunteers without overcoming the antiplatelet effect of daily low-dose aspirin therapy.


Assuntos
Ácido Araquidônico/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/sangue , Adolescente , Adulto , Ácido Araquidônico/sangue , Aspirina/administração & dosagem , Aspirina/farmacologia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacologia , Esquema de Medicação , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
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