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1.
Phys Rev Lett ; 125(1): 014801, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32678646

RESUMO

We report observations of coherent optical transition radiation interferometry (COTRI) patterns generated by microbunched ∼200-MeV electrons as they emerge from a laser-driven plasma accelerator. The divergence of the microbunched portion of electrons, deduced by comparison to a COTRI model, is ∼9× smaller than the ∼3 mrad ensemble beam divergence, while the radius of the microbunched beam, obtained from COTR images on the same shot, is <3 µm. The combined results show that the microbunched distribution has estimated transverse normalized emittance ∼0.4 mm mrad.

2.
Int Nurs Rev ; 66(2): 290-298, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30729518

RESUMO

BACKGROUND: For older men with hypertension living in rural areas, non-adherence to treatment is a common phenomenon. The experience on risk perception of individuals with their condition is recognized as playing a critical role in promoting treatment adherence. However, the experience on risk perception in a cohort of older men with hypertension seems unclear. AIM: To develop a theory concerning risk perception experience in a cohort of older men with hypertension from a rural area of Thailand. METHODS: A grounded theory approach was used. Semi-structured, face-to-face interviews with 29 hypertensive older men were conducted in Thailand using purposive and theoretical sampling methods. The grounded theory analytical method that included initial and focused coding, and constant comparison was used to analyse the data. FINDINGS: 'Developing a personal sense of risk' emerged as a core category, which incorporated the related four subprocesses: comparing healthcare provider information with stories of people with hypertension, comparing one's own situation with stories of people with hypertension, changing personal sense of risk and changing risk-related behaviour. Older men selected to focus on one particular outcome, using the selected outcome to monitor their risk. CONCLUSION: This investigation provides a theory for healthcare providers to understand older men's perceptions of personal risk for complications of hypertension. A personal sense of risk influences risk-related behaviour change. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The findings can be used in assessing a personal sense of risk and promoting treatment adherence in older men with hypertension. Effective storytelling intervention, a standard tool for assessment personal sense of risk in older men with hypertension, should be developed. Hypertension care policy needs to be developed for individualized approaches.


Assuntos
Atitude Frente a Saúde , Hipertensão/psicologia , Saúde do Homem , Senso de Coerência , Idoso , Teoria Fundamentada , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Tailândia
3.
Int Nurs Rev ; 63(4): 547-554, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27682150

RESUMO

AIM: This study explored Turkish nursing students' perceptions of providing care to patients culturally different from themselves. BACKGROUND: Increasing migration will increase the need for nurses to provide care across cultural groups. METHODS: Twenty one students in the second year of a 4-year nursing programme participated in 3 focus groups. Data were analysed using directed content analysis. Research questions were based on Campinha-Bacote's model. RESULTS: Three themes were identified: perceived cultural barriers, perceived cultural facilitators and identifying culturally sensitive actions. Generally, students were able to define culture but were unable to say how culture would affect nursing practice. DISCUSSION: Students were unprepared to practice in a multicultural setting. Cultural awareness is insufficient for determining how to respond to cultural differences. LIMITATIONS: The study is limited by its restriction to a single school of nursing and a single curriculum. CONCLUSIONS: The multiple, ongoing political, religious and ethnic conflicts will require nurses to provide care to patients from other cultural groups, in some instances to people identified as adversaries to the group the nurse may represent. Understanding cultural differences is insufficient to do this effectively. IMPLICATIONS FOR NURSING EDUCATION: Learning culturally competent care requires opportunities to provide, be guided through and reflect on care to individuals from different cultural groups. IMPLICATIONS FOR ORGANIZATIONAL AND PUBLIC POLICIES: Standards for culturally competent care should be adopted by all care delivery settings. Public and organizational policies openly declaring healthcare settings as cultural safe zones, and explicit organizational commitment to culturally safe care, would set clear expectations for providers and help ensure a positive patient experience.


Assuntos
Competência Cultural , Assistência à Saúde Culturalmente Competente , Estudantes de Enfermagem , Diversidade Cultural , Feminino , Grupos Focais , Humanos , Masculino , Turquia , Adulto Jovem
4.
Mucosal Immunol ; 6(6): 1110-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23462909

RESUMO

Antimicrobial peptides are secreted by the intestinal epithelium to defend from microbial threats. The role of human ß defensin-1 (hBD-1) is notable because its gene (beta-defensin 1 (DEFB1)) is constitutively expressed and its antimicrobial activity is potentiated in the low-oxygen environment that characterizes the intestinal mucosa. Hypoxia-inducible factor (HIF) is stabilized even in healthy intestinal mucosa, and we identified that epithelial HIF-1α maintains expression of murine defensins. Extension to a human model revealed that basal HIF-1α is critical for the constitutive expression of hBD-1. Chromatin immunoprecipitation identified HIF-1α binding to a hypoxia response element in the DEFB1 promoter whose importance was confirmed by site-directed mutagenesis. We used 94 human intestinal samples to identify a strong expression correlation between DEFB1 and the canonical HIF-1α target GLUT1. These findings indicate that basal HIF-1α is critical for constitutive expression of enteric DEFB1 and support targeting epithelial HIF for restoration and maintenance of intestinal integrity.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/imunologia , Mucosa Intestinal/imunologia , beta-Defensinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células CACO-2 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Regiões Promotoras Genéticas/genética , Ligação Proteica , Ativação Transcricional , beta-Defensinas/genética
5.
J Intellect Disabil Res ; 55(8): 777-89, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20561147

RESUMO

BACKGROUND: Planning for future care after the death of parental caregivers and adapting disability support systems to achieve the best possible quality of life for people with intellectual disability as they age have been important issues for more than two decades. This study examined perceptions held by family members, group home staff and organisational managers about the future of older residents and the decisions made that a move to residential aged care was necessary. METHODS: Grounded Dimensional Analysis was used to guide data collection and analysis by an interdisciplinary research team. Three sets of interviews over a period of 18 months were conducted with a family member, house supervisor and the programme manager for each of seventeen older group home residents in Victoria. For the eight people for whom it was decided a move was necessary and the six who eventually moved focussed questions were asked about the decision-making process. RESULTS: While plans for lifelong accommodation in a group home proved unfounded, key person succession plans were effective. However, decisions to move to a residential aged care facility where necessary were made in haste and seen as a fait accompli by involved family members. CONCLUSIONS: Although family members take seriously their mandate to oversee well-being of their older relative, they have little knowledge about their rights or avenues to safeguard untimely or inappropriate decisions being made by professionals.


Assuntos
Continuidade da Assistência ao Paciente , Tomada de Decisões , Lares para Grupos , Instituição de Longa Permanência para Idosos , Deficiência Intelectual/reabilitação , Casas de Saúde , Idoso , Idoso de 80 Anos ou mais , Cuidadores , Família , Humanos , Pais , Relações Profissional-Família , Qualidade de Vida , Vitória
8.
J Intellect Disabil Res ; 52(Pt 5): 404-14, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18205755

RESUMO

BACKGROUND: Australia's national ageing policy recognises that people ageing with intellectual disability (ID) require particular attention, yet there is no policy framework concerning this population. This study describes the distribution and characteristics of people with ID in residential aged care in Victoria, provides insights into the pathways they take into aged care, and gives some indications of how facilities adapt to their needs. METHOD: A postal survey was sent to 826 residential aged care facilities in Victoria, seeking information from directors about their residents with ID. Facilities that responded were fairly representative of all facilities in Victoria. FINDINGS: Residents with ID were younger, had entered at an earlier age and remained longer than other residents. Their reported dependency profile was similar to the general aged care population, although the incidence of dementia was lower. Primary areas of concern identified by providers were: inability to fit into the resident community, lack of participation in activities and lack of meaningful relationships. CONCLUSION: This study provides a first glimpse into how older people with ID find their way into aged care and how others view their experiences once there. It suggests that further investigation is required into the accuracy of assessment undertaken prior to entry to more clearly understand whether residents with ID are inappropriately placed in residential aged as a result of a shortage of disability accommodation and inadequate resources to support aging in place for those in such accommodation.


Assuntos
Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Deficiência Intelectual/reabilitação , Instituições Residenciais/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Feminino , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/psicologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Índice de Gravidade de Doença , Vitória/epidemiologia
9.
Addict Biol ; 8(4): 399-412, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14690876

RESUMO

Null mutants of the neural-specific gamma-isotype of protein kinase C (gamma-PKC) have demonstrated differential responses to acute administration of ethanol in comparison with wild-type animals. Previous studies have shown that the mutants are less sensitive to ethanol-induced loss of righting response. Null mutants also consume more ethanol and exhibit less behavioral inhibition. In order to determine if these sensitivity differences extend to ethanol activation of locomotor activity in an open-field arena, baseline activity and the effect of two low doses of ethanol were assessed in gamma-PKC null mutants and wild-type littermates. Null mutants demonstrated higher levels of baseline activity than did their wild-type counterparts. Further analysis revealed that a 1.0 g/kg dose of ethanol increased locomotor activity in males and females of both genotypes, whereas only null mutant males were activated by a 1.25 g/kg ethanol dose. The current study demonstrates that male gamma-PKC null mutants exhibit increased sensitivity to activating doses of ethanol in contrast to previous findings of decreased sensitivity to higher, depressive doses. This reflects the pleiotropic effects of the gamma-PKC null mutation on the behavioral effects of ethanol.


Assuntos
Análise Mutacional de DNA , Etanol/farmacologia , Genótipo , Atividade Motora/efeitos dos fármacos , Proteína Quinase C/genética , Animais , Cruzamentos Genéticos , Relação Dose-Resposta a Droga , Feminino , Marcação de Genes , Masculino , Camundongos , Camundongos Endogâmicos , Equilíbrio Postural/efeitos dos fármacos , Recombinação Genética , Reflexo/efeitos dos fármacos , Reflexo/genética
10.
J Invasive Cardiol ; 13(10): 679-83, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11731684

RESUMO

OBJECTIVE: To determine whether prophylactic, pre-operative, intra-aortic balloon counterpulsation (IABC) improves clinical outcome in stable patients with severe left main coronary artery disease. METHODS: A post-hoc analysis of 457 prospectively tracked, non-randomized patients undergoing coronary artery bypass graft surgery (CABG) for left main stenoses 50% and multivessel coronary disease, but without any hemodynamic compromise or ongoing angina, was conducted. Patients with heart failure, shock, ongoing ischemia or previous CABG were excluded. In 287 patients, pre-operative IABC was not used (Group 1), while IABC was initiated in 170 patients for "prophylaxis" (Group 2). RESULTS: Groups 1 and 2 were similar in age (67 +/- 10 years versus 67 +/- 11 years, respectively), sex (72% male versus 71% male, respectively), and body mass index (28 +/- 5.5 versus 27 +/- 5.1, respectively). However, more Group 1 patients had peripheral vascular disease (PVD) (25% versus 11%), but more Group 2 patients had diabetes (37% versus 29%), and a lower left ventricular ejection fraction. The unadjusted 30-day mortality was significantly higher in Group 1 [16 (5.6%) versus 2 (1.2%); p = 0.02]. Cardiopulmonary bypass time and post-operative length of stay did not differ between the two groups. After adjusting for PVD in the multivariate analysis, the p-value for the no IABP versus IABP comparison in the presence of PVD was 0.10, even though 0/18 patients with PVD and IABC died. CONCLUSION: While unadjusted mortality appears lower with prophylactic IABC, confounding variables such as PVD mandate a larger, randomized clinical trial in order to establish the role of IABC in stable patients with left main disease.


Assuntos
Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Estenose Coronária/mortalidade , Estenose Coronária/cirurgia , Balão Intra-Aórtico/mortalidade , Fatores Etários , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Coortes , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Ecocardiografia Transesofagiana , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças Vasculares Periféricas/complicações , Doenças Vasculares Periféricas/mortalidade , Philadelphia/epidemiologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Sistema de Registros , Volume Sistólico/fisiologia , Análise de Sobrevida , Resultado do Tratamento
11.
Res Nurs Health ; 24(4): 258-69, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11746057

RESUMO

End-of-life decision making is a complex phenomenon and providers, patients, and families often have different views about the appropriateness of treatment choices. The results presented here are part of a larger grounded-theory study of reconciling decisions near the end of life. In particular, we examined how providers (N = 15) worked near the end of patients' lives toward changing the treatment decisions of patients and families from those decisions that providers described as unrealistic (i.e., curative) to those that providers described as more realistic (i.e., palliative). According to providers, shifting patients' and families' choices from curative to palliative was usually accomplished by changing patients' and families' understanding of the patient's overall "big picture" to one that was consistent with the providers' understanding. Until patients and families shifted their understanding of the patient's condition-the big picture-they continued to make what providers judged as unrealistic treatment choices based on an inaccurate understanding of what was really going on. These unrealistic choices often precluded possibilities for a "good death." According to providers, the purpose of attempting to shift the patient or proxy's goals was that realistic goals lead to realistic palliative treatment choices that providers associated with a good death. In this article we review strategies used by providers when they believed a patient's death was imminent to attempt to shift patients' and families' understandings of the big picture, thus ultimately shifting their treatment decisions.


Assuntos
Tomada de Decisões , Cuidados Paliativos/psicologia , Equipe de Assistência ao Paciente , Doente Terminal/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Teoria de Enfermagem
12.
J Neurosci ; 21(21): RC180, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11606660

RESUMO

Etiological factors influencing the development of alcoholism are complex and, at a minimum, include an interaction between polygenic factors and personality and biological traits. Human and animal studies suggest that some genes may regulate both the traits associated with alcohol abuse, such as decreased sensitivity or anxiety, and vulnerability to alcoholism. The identification of these genes could elucidate neurochemical pathways that are important in the development of alcohol abuse. Results from the present study indicate that the gene encoding the neuronal-specific gamma subtype of protein kinase C (PKCgamma) influences both ethanol consumption and behavioral impulsivity, a personality characteristic associated with Type II alcoholics, in a pleiotropic manner. Mice lacking PKCgamma consume more ethanol in a two-bottle choice paradigm and also demonstrate increased behavioral impulsivity in an appetitive-signaled nosepoke task when compared with wild-type littermate control mice. Therefore, PKCgamma may be an important mechanism within the cell that mediates one or more neurochemical pathways relevant to an increased predisposition to alcoholism.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Comportamento Animal/fisiologia , Comportamento de Escolha/fisiologia , Comportamento Impulsivo/genética , Isoenzimas/deficiência , Proteína Quinase C/deficiência , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Etanol/administração & dosagem , Feminino , Isoenzimas/genética , Masculino , Camundongos , Camundongos Mutantes , Nicotina/administração & dosagem , Proteína Quinase C/genética , Sacarina/administração & dosagem , Fatores Sexuais
13.
J Adv Nurs ; 36(1): 102-11, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11555054

RESUMO

AIM: The aim of the study was to gain an understanding of cultural competence from the perspectives of non-mainstream nurse educators, specifically those of Latin heritage. BACKGROUND/RATIONALE: Although the theoretical concepts of 'cultural diversity' and 'culturally competent care' have been supported and promoted by the largest professional nursing organizations, the practical application of these concepts has often created difficulties for nurse researchers, educators, and clinicians. The lack of progress in teaching and evaluating cultural competence suggested the need to 'center the margins' and explore cultural competence from the margins of one particular non-mainstream nursing group, Latina nurse educators. DESIGN/METHODS: A grounded theory research design was employed. A group of 10 doctoral, prepared, self-identified, Latina nurse educators participated in face- to-face audiotaped interviews. Data collection, analysis, and theoretical sampling decisions occurred concurrently, strengthening theory generation. Institutional review board approval was received for all steps of the study. The major limitation of the study was the omission of student voices. RESULTS/FINDINGS: The analysis suggests that the Latina participants shared the common purpose of teaching students how to think about difference. The teaching practices of this group of Latina educators was based on a belief that 'difference' is not solely about specific cultural groups. For example, content about 'Hmongs' or 'Latinos'. Rather, Latina faculty focused on teaching students how to directly connect with anyone perceived as different from oneself. CONCLUSION: Latina faculty did not distinguish between competent care and culturally competent care; for them, competence necessarily includes cultural competence. They conceptualize the provision of competent care to all persons who are perceived as different, rather than focusing only on those who are perceived as 'culturally' different. These conceptualizations have the potential to shed new light on how nurses and nurse educators think about, develop, and integrate cultural competence into nursing education, practice, and research.


Assuntos
Educação em Enfermagem , Docentes de Enfermagem , Enfermagem Transcultural/educação , Diversidade Cultural , Hispânico ou Latino , Humanos , Entrevistas como Assunto , Pesquisa em Educação em Enfermagem , Vermont
14.
J Eval Clin Pract ; 7(3): 261-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11555085

RESUMO

The increasing economic burden of asthma care is incurred partly by patients with more severe symptoms. However, little is known about the characteristics of these severe asthma patients. This study examined sociodemographic, disease-specific characteristics and health care utilization that are related to asthma disease severity, for the purpose of identifying areas for treatment improvement. A total of 2927 asthma patients (12 years or older), who were continuously enrolled in one of three participating health plans for a 6-month study period and who responded to an asthma survey, were included in the study. Univariate and multivariate analyses were performed to examine the sociodemographic, disease-specific characteristics and health care utilization by asthma severity. About 25% of the patients reported experiencing severe asthma symptoms. They were more likely to be African-Americans, Hispanics, women, patients with less than a college education, residents in the south-west, current smokers, and those receiving care from non-specialists. Severe asthmatics reported having less of an understanding of the clinical manifestation of asthma and the means to manage asthma exacerbation. Outpatient contacts did not differ significantly between severe and other patients, although their utilization of emergency room and inpatient care was significantly greater. This study suggests that a significant proportion of asthma patients is experiencing severe symptoms and barriers other than access to care prevent appropriate control of asthma. Poor control appears to be related to smoking, deficits in knowledge about self-care, not receiving medical care from a specialist, and inadequate use of medications.


Assuntos
Asma/terapia , Qualidade da Assistência à Saúde , Adolescente , Adulto , Asma/fisiopatologia , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de Doença , Inquéritos e Questionários , Estados Unidos
15.
Am J Manag Care ; 7(9): 913-22, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11570024

RESUMO

OBJECTIVES: To compare a combination of salmeterol and fluticasone with common asthma pharmacologic regimens used in real-world clinical practice, and to evaluate the associated costs and outcomes of care. STUDY DESIGN: Cross-sectional examination of medical and pharmacy claims. METHODS: The study population included 33,939 adult asthmatics (at least 12 years of age) continuously enrolled in 1 of 4 participating health plans for the 6-month study period. Every subject was in 1 of 10 different pharmacotherapy treatment groups. Univariate and multivariate analyses were used to compare the rates and costs of pharmaceutical prescriptions and medical care services between patients on salmeterol plus fluticasone and patients with other pharmacologic therapies. RESULTS: About 60.4% of the patients were on single controllers; the balance was on short-acting beta 2-agonists alone (23%) or double controllers (16.8%). The average overall cost of asthma care was approximately $228 per patient over the 6 months of the study. Pharmaceutical cost was the major cost driver, which was significantly lower for single-controller (mean = $134) than for double-controller therapies (mean = $325). However, total costs were $50-$200 lower (P < .029) for patients on salmeterol plus fluticasone and inhaled steroids plus mast cell stabilizing agents than for those on other double controllers. CONCLUSIONS: Single-controller regimens and short-acting beta-agonists were less costly than double-controller regimens. Within the double-controller groups, salmeterol plus fluticasone appeared to be less costly than other double controllers, except inhaled steroids plus mast cell stabilizing agents.


Assuntos
Albuterol/uso terapêutico , Androstadienos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Custos de Cuidados de Saúde/estatística & dados numéricos , Resultado do Tratamento , Adulto , Albuterol/administração & dosagem , Albuterol/análogos & derivados , Albuterol/economia , Androstadienos/administração & dosagem , Androstadienos/economia , Antiasmáticos/administração & dosagem , Antiasmáticos/economia , Asma/economia , Asma/epidemiologia , Efeitos Psicossociais da Doença , Quimioterapia Combinada , Feminino , Fluticasona , Humanos , Masculino , Xinafoato de Salmeterol , Estados Unidos/epidemiologia
16.
Gerontologist ; 41(4): 539-45, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11490052

RESUMO

PURPOSE: This study explored how nursing home residents define quality of care. DESIGN AND METHODS: Data were collected through in-depth interviews and were analyzed using grounded dimensional analysis. RESULTS: Residents defined quality in three ways: (a) Care-as-service residents focused on instrumental aspects of care. They assessed quality using the parameters of efficiency, competence, and value. (b) Care-as-relating residents emphasized the affective aspects of care, defining quality as care that demonstrated friendship and allowed them to show reciprocity with their caregivers. (c) Care-as-comfort residents defined quality as care that allowed them to maintain their physical comfort, a state that required minute and often repetitive adjustments in response to their bodily cues. IMPLICATIONS: Residents' perceptions of care quality have implications for long-term care practice. The integration of these perceptions into quality assurance instruments could improve the usefulness of tools designed to obtain resident input.


Assuntos
Doença Crônica/enfermagem , Comportamento do Consumidor , Instituição de Longa Permanência para Idosos , Casas de Saúde , Indicadores de Qualidade em Assistência à Saúde , Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/psicologia , Feminino , Humanos , Masculino , Relações Enfermeiro-Paciente
17.
J Fam Pract ; 50(7): 595-602, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11485708

RESUMO

OBJECTIVE: The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma. STUDY DESIGN: In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo. POPULATION: We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone. OUTCOMES: measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results. RESULTS: After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%). CONCLUSIONS: Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.


Assuntos
Androstadienos/uso terapêutico , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Antagonistas de Leucotrienos/uso terapêutico , Compostos de Tosil/uso terapêutico , Administração por Inalação , Administração Oral , Adolescente , Adulto , Idoso , Androstadienos/administração & dosagem , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Criança , Método Duplo-Cego , Feminino , Fluticasona , Humanos , Indóis , Antagonistas de Leucotrienos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Fenilcarbamatos , Testes de Função Respiratória , Sulfonamidas , Compostos de Tosil/administração & dosagem
18.
Annu Rev Neurosci ; 24: 845-67, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11520920

RESUMO

Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.


Assuntos
Comportamento Animal , Camundongos/genética , Camundongos/psicologia , Animais , Encéfalo/fisiologia , Humanos , Aprendizagem , Memória , Modelos Genéticos
19.
Cancer ; 92(2): 354-8, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11466690

RESUMO

BACKGROUND: Patients with basal cell carcinoma (BCC) demonstrate marked variation in clinical phenotype, suggesting the presence of distinct subgroups. Patients with truncal lesions comprise an interesting subgroup, because, although the pathogenesis of these tumors is unclear, there is evidence to suggest that their development is mediated by different mechanisms than the mechanisms that mediate the development of BCC on other sites. The authors now speculate that some patients inherit a predisposition to truncal BCC and develop disproportionately more BCC on this site than other patients. METHODS: The authors studied 100 patients who, at the time of initial presentation, had a truncal BCC lesion and 493 patients who had a lesion on the head and neck. The 493 patients with head and neck lesions included 36 patients who subsequently developed a truncal BCC and 457 patients who do not. RESULTS: Initial presentation with a truncal tumor was associated with significantly more subsequent BCC lesions on this site compared with patients who presented initially with a head and neck lesion. The mean truncal tumor accrual after initial presentation in patients who presented with an initial truncal BCC lesion was 0.13 BCC lesions per year compared with 0.03 BCC lesions per year in patients who presented with an initial head and neck lesion (P < 0.001). Patients with truncal lesions were significantly younger at the time of initial presentation and developed more clusters of BCC lesions (2--10 new tumors at any presentation) compared with patients who did not develop tumors on the trunk. CONCLUSIONS: These data suggest that the development of a truncal BCC is not random but, rather, is associated with a predisposition. In contrast, the accrual of nontruncal BCC lesions was similar in patients with and without initial truncal lesions, suggesting that different mechanisms determine the development of truncal BCC and nontruncal BCC.


Assuntos
Carcinoma Basocelular/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Carcinoma Basocelular/genética , DNA de Neoplasias , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/genética
20.
Pharmacol Biochem Behav ; 69(1-2): 99-110, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11420074

RESUMO

Tests of ethanol effects in PKCgamma null mutant mice have indicated that PKCgamma plays a role in initial sensitivity to ethanol-induced sedation, hypothermia, and GABA(A) receptor function and impacts neurochemical pathways mediating anxiety. The present study was undertaken to evaluate whether the decreased sensitivity to ethanol previously observed in these mice generalized to the anxiolytic effects of ethanol. PKCgamma null mutant mice and wild-type controls were tested in the elevated-plus maze, the black/white box, and the mirrored chamber after ethanol (0, 1.0, 1.25, 1.5 g/kg) or flunitrazepam (FNZ) (0, 0.015, 0.03, 0.06 mg/kg). Results indicated that although both genotypes exhibited anxiolytic responses to ethanol in the elevated plus-maze, null mutant mice were less sensitive than wild-type control mice; however, in the black/white box, PKCgamma null mutants were more sensitive than controls to the anxiolytic effects of FNZ. Neither ethanol nor FNZ produced anxiolytic responses in the mirrored chamber for either genotype. These results suggest that PKCgamma differentially mediates anxiolytic responses to ethanol and FNZ and that this relationship interacts with each drug's efficacy in reducing anxiety-related behaviors specific to each of the three mazes.


Assuntos
Ansiolíticos/farmacologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Flunitrazepam/farmacologia , Isoenzimas/fisiologia , Proteína Quinase C/fisiologia , Animais , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Isoenzimas/genética , Masculino , Camundongos , Camundongos Knockout , Proteína Quinase C/genética
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