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1.
Qual Life Res ; 30(7): 1803-1832, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33738710

RESUMO

INTRODUCTION: Self-report is the gold standard for measuring children's health-related outcomes. Design of such measures is complex and challenging. This review aims to systematically appraise the evidence on recall period, response scale format, mode of administration and approaches needed to enable children and young people < 19 years to participate in valid and reliable self-reporting of their health outcomes. METHOD: PsycInfo, Medline, CINAHL and Embase were searched from 1 January 1990 to 15 March 2020, and citation searching undertaken in Scopus. Articles were included if they were primary research or case reports of ≥ 3 participants reporting the following: recall period, response scale selection, administration modality. Quality was assessed using QualSyst, and results synthesised narratively. This review was conducted and reported according to PRISMA guidelines. RESULTS: 81 of 13,215 retrieved articles met the inclusion criteria. Children < 5 years old cannot validly and reliably self-report health outcomes. Face scales demonstrate better psychometric properties than visual analogue or Likert scales. Computerised and paper scales generally show equivalent construct validity. Children prefer computerised measures. Children ≤ 7 years old think dichotomously so need two response options. Those > 8 years old can reliably use a 3-point scale. CONCLUSION: The results of this review have both clinical and research implications. They can be used to inform appropriate choice of PROM for use with CYP in the clinical setting. We also give eight recommendations for future development of self-reported outcome measures for children and young people.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Medidas de Resultados Relatados pelo Paciente , Psicometria/métodos , Qualidade de Vida/psicologia , Criança , Pré-Escolar , Humanos , Lactente , Reprodutibilidade dos Testes , Autorrelato
2.
BJOG ; 126(9): 1134-1140, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30903641

RESUMO

OBJECTIVE: To determine the number of retracted articles and to examine the reasons for retraction within the obstetrics and gynaecology literature. DESIGN: Retrospective review of the PubMed database. SETTING: N/A. POPULATION: Obstetrics and gynaecology articles published from indexation until June 2018. METHODS: Articles were identified using keywords for retracted articles in obstetrics and gynaecology. Descriptive statistics were performed. MAIN OUTCOME MEASURES: Incidence of article retraction, the reasons given for retraction, and article demographics. RESULTS: A total of 176 articles were identified with a median time to retraction of 2 years; over three-quarters were retracted within the last decade (n = 136; 77.3%). The median journal impact factor was 2.5 (range of 0.26-52.67). Subspecialties with the highest number of retractions were gynaecological oncology (n = 76; 43.2%), gynaecology (n = 36; 20.5%), and obstetrics (n = 31; 17.6%). Among 176 first authors, 18 authors (10.2%) had two or more retracted articles. Clinical research articles accounted for approximately one-half of the retracted articles (n = 87; 49.4%). Among the clinical studies, 10.2% (n = 18) were randomised control trials, 16.5% (n = 29) were prospective trials and 13.1% (n = 23) were retrospective studies. Plagiarism (n = 40; 22.7%) and data falsification (n = 37; 21.0%) were the most common reasons given for retraction. CONCLUSION: Article retraction within the obstetrics and gynaecology literature is increasing. The most frequently cited reasons for article retractions were plagiarism, errors in data, fabricated results, article duplication, and compromised peer review. Consequences of article retractions to patient care and the scientific community can be significant. The thorough screening of manuscripts prior to publication should be prioritised. TWEETABLE ABSTRACT: The rate of retraction in obstetrics and gynaecology is increasing; the most common reason for retraction is plagiarism.


Assuntos
Ginecologia/estatística & dados numéricos , Obstetrícia/estatística & dados numéricos , Plágio , Retratação de Publicação como Assunto , Má Conduta Científica/estatística & dados numéricos , Humanos , Estudos Retrospectivos
3.
Clin Exp Allergy ; 48(7): 798-805, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29526044

RESUMO

BACKGROUND: There is evidence that air pollution increases the risk of asthma hospitalizations and healthcare utilization, but the effects on day-to-day asthma control are not fully understood. OBJECTIVE: We undertook a prospective single-centre panel study to test the hypothesis that personal air pollution exposure is associated with asthma symptoms, lung function and airway inflammation. METHODS: Thirty-two patients with a clinical diagnosis of asthma were provided with a personal air pollution monitor (Cairclip NO2 /O3 ) which was kept on or around their person throughout the 12-week follow-up period. Ambient levels of NO2 and particulate matter were modelled based upon satellite imaging data. Directly measured ozone, NO2 and particulate matter levels were obtained from a monitoring station in central Leicester. Participants made daily electronic records of asthma symptoms, peak expiratory flow and exhaled nitric oxide. Spirometry and asthma symptom questionnaires were completed at fortnightly study visits. Data were analysed using linear mixed effects models and cross-correlation. RESULTS: Cairclip exposure data were of good quality with clear evidence of diurnal variability and a missing data rate of approximately 20%. We were unable to detect consistent relationships between personal air pollution exposure and clinical outcomes in the group as a whole. In an exploratory subgroup analysis, total oxidant exposure was associated with increased daytime symptoms in women but not men. CONCLUSIONS AND CLINICAL RELEVANCE: We did not find compelling evidence that air pollution exposure impacts on day-to-day clinical control in an unselected asthma population, but further studies are required in larger populations with higher exposure levels. Women may be more susceptible than men to the effects of air pollution, an observation which requires confirmation in future studies.


Assuntos
Poluição do Ar/efeitos adversos , Asma/diagnóstico , Asma/etiologia , Exposição Ambiental/efeitos adversos , Adulto , Idoso , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Avaliação de Sintomas
4.
Int J Obes (Lond) ; 40(11): 1693-1698, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27315439

RESUMO

BACKGROUND/OBJECTIVES: Consumption of high-energy beverages has been implicated as a risk factor for weight gain, yet why nutrients ingested as beverages fail to generate adequate satiety remains unclear. In general, consumers do not expect drinks to be satiating, but drinks generate greater satiety when their sensory characteristics imply they may be filling. These findings challenge traditional bottom-up models of how gut-based satiety signals modify behaviour to suggest that beliefs at the point of ingestion modify gut-based satiety signalling. SUBJECTS/METHODS: Healthy volunteers (n=23) consumed four different beverages, combining an overt sensory manipulation (thin, low sensory (LS) or thicker and more creamy, enhanced sensory (ES)) and covert nutrient manipulation (low energy (LE), 78 kcal; high energy (HE), 267 kcal) on different days. Effects on satiety were assessed through rated appetite and levels of glucose, insulin, pancreatic polypeptide (PP) and cholesystokinin (CCK) recorded periodically over 90 min, and through intake at an ad libitum test lunch. RESULTS: Intake at the test lunch and rated appetite were both altered by both the sensory and nutrient manipulations, with lowest intake and greatest suppression of hunger post-drink in the ESHE condition. Insulin increased more after HE than LE drinks, and after ES than LS drinks, whereas PP levels were higher after ES than LS versions. CCK levels only increased after the ESHE drink. CONCLUSIONS: These data confirm acute sensitivity of satiety after consuming a drink both to the sensory characteristics and nutrient content of the drink, and suggest that this may be, at least in part, due to top-down modulation of release of satiety-related gut hormones.


Assuntos
Apetite/fisiologia , Voluntários Saudáveis , Saciação/fisiologia , Resposta de Saciedade/fisiologia , Adulto , Bebidas , Colecistocinina/metabolismo , Laticínios , Carboidratos da Dieta , Proteínas Alimentares , Ingestão de Energia , Inglaterra , Glucose/metabolismo , Humanos , Insulina/metabolismo , Almoço , Masculino , Pessoa de Meia-Idade , Polipeptídeo Pancreático/metabolismo , Tamanho da Porção/psicologia , Paladar , Viscosidade , Adulto Jovem
5.
Int J Biometeorol ; 60(8): 1237-45, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26698160

RESUMO

Seabirds are subject to the influences of local climate variables during periods of land-based activities such as breeding and, for some species, moult; particularly if they undergo a catastrophic moult (complete simultaneous moult) as do penguins. We investigated potential relationships between adult penguin survival and land-based climate variables (ambient air temperature, humidity and rainfall) using 46 years of mark-recapture data of little penguins Eudyptula minor gathered at a breeding colony on Phillip Island in southeastern Australia. Our results showed that adult penguin survival had a stronger association with land-based climate variables during the moult period, when birds were unable to go to sea for up to 3 weeks, than during the breeding period, when birds could sacrifice breeding success in favour of survival. Annual adult survival probability was positively associated with humidity during moult and negatively associated with rainfall during moult. Prolonged heat during breeding and moult had a negative association with annual adult survival. Local climate projections suggest increasing days of high temperatures, fewer days of rainfall which will result in more droughts (and by implication, lower humidity) and more extreme rainfall events. All of these predicted climate changes are expected to have a negative impact on adult penguin survival.


Assuntos
Mudança Climática , Spheniscidae , Animais , Austrália , Umidade , Modelos Teóricos , Chuva , Temperatura
6.
Vet Pathol ; 51(5): 1022-34, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24395912

RESUMO

Extremely poor growth of some individuals within a birth cohort (runting) is a significant problem in crocodile farming. We conducted a pathological investigation to determine if infectious disease is associated with runting in farmed saltwater crocodiles (Crocodylus porosus) and to look for evidence of other etiologies. In each of 2005 and 2007, 10 normal and 10 runt crocodiles, with an average age of 5.5 months and reared under identical conditions, were sampled. Laboratory testing included postmortem; histological examination of a wide variety of tissues (with quantitation of features that were noted subjectively to be different between groups); hematology; serum biochemistry (total protein, albumin, globulins, total calcium, phosphorus, and iron); bacterial culture of liver and spleen (2005 only); viral culture of liver, thymus, tonsil, and spleen using primary crocodile cell lines (2007 only); and serum corticosterone (2007 only). The only evidence of infectious disease was mild cutaneous poxvirus infection in 45% of normal and 40% of runt crocodiles and rare intestinal coccidia in 5% of normal and 15% of runt crocodiles. Bacterial and viral culture did not reveal significant differences between the 2 groups. However, runt crocodiles exhibited significant (P < .05) increases in adrenocortical cell cytoplasmic vacuolation and serum corticosterone, decreased production of bone (osteoporosis), and reduced lymphoid populations in the spleen, tonsil, and thymus. Runts also exhibited moderate anemia, hypoalbuminemia, and mild hypophosphatemia. Taken together, these findings suggest an association between runting and a chronic stress response (hyperactivity of the hypothalamic-pituitary-adrenal axis).


Assuntos
Jacarés e Crocodilos/crescimento & desenvolvimento , Estresse Fisiológico , Animais , Aquicultura , Austrália , Contagem de Células Sanguíneas/veterinária , Análise Química do Sangue/veterinária , Peso Corporal , Estudos de Coortes , Feminino , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Água do Mar , Baço/fisiopatologia
7.
Int J Palliat Nurs ; 18(3): 109-14, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22584310

RESUMO

Children's palliative care (CPC) is a specialty in itself, albeit closely related to adult palliative care (World Health Organization (WHO), 2002). However, although there are many children who require palliative care, in much of the world CPC has a poor profile and is inaccessible to those who need it (Downing et al, 2010; Knapp et al, 2011). The provision of high-quality palliative care for children is a global concern, with 27% of the world population being under the age of 15, rising to as many as 49% in countries such as Uganda (WHO, 2010). It has been estimated that as many as 7 million of these children around the world will need palliative care each year (Rushton et al, 2002), although the true figure is likely to be higher. The public health approach to palliative care is key to the development of CPC services, as is the development of models that integrate services into existing health structures.


Assuntos
Serviços de Saúde da Criança , Saúde Global , Cuidados Paliativos , Criança , Humanos
8.
Br J Pharmacol ; 153(4): 737-50, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18071294

RESUMO

BACKGROUND AND PURPOSE: Antagonist effects at the P2X(7) receptor are complex with many behaving in a non-competitive manner. In this study, the effects of N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17) and N (2)-(3,4-difluorophenyl)-N (1)-[2-methyl-5-(1-piperazinylmethyl)phenyl]glycinamide dihydrochloride (GW791343) on P2X(7) receptors were examined and their mechanism of action explored. EXPERIMENTAL APPROACH: Antagonist effects were studied by measuring agonist-stimulated ethidium accumulation in cells expressing human or rat recombinant P2X(7) receptors and in radioligand binding studies. KEY RESULTS: Compound-17 and GW791343 were non-competitive inhibitors of human P2X(7) receptors. Receptor protection studies using decavanadate and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) showed that neither compound-17 nor GW791343 competitively interacted at the ATP binding site and so were probably negative allosteric modulators of the P2X(7) receptor. GW791343 prevented the slowly reversible blockade of the human P2X(7) receptor produced by compound-17 and inhibited [(3)H]-compound-17 binding to the P2X(7) receptor suggesting they may bind to similar or interacting sites. At rat P2X(7) receptors, compound-17 was a negative allosteric modulator but the predominant effect of GW791343 was to increase agonist responses. Antagonist interaction and radioligand binding studies revealed that GW791343 did not interact at the ATP binding site but did interact with the compound-17 binding site suggesting that GW791343 is a positive allosteric modulator of the rat P2X(7) receptor. CONCLUSIONS: Compound-17 was a negative allosteric modulator of human and rat P2X(7) receptors. GW791343 was a negative allosteric modulator of the human P2X(7) receptor but at the rat P2X(7) receptor its predominant effect was positive allosteric modulation. These compounds should provide valuable tools for mechanistic studies on P2X(7) receptors.


Assuntos
Glicina/análogos & derivados , Piperazinas/farmacologia , Quinolinas/farmacologia , Receptores Purinérgicos P2/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Regulação Alostérica , Animais , Sítios de Ligação , Linhagem Celular , Relação Dose-Resposta a Droga , Etídio/metabolismo , Glicina/metabolismo , Glicina/farmacologia , Humanos , Estrutura Molecular , Piperazinas/metabolismo , Conformação Proteica , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/metabolismo , Fosfato de Piridoxal/farmacologia , Quinolinas/metabolismo , Ensaio Radioligante , Ratos , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2X7 , Proteínas Recombinantes/metabolismo , Especificidade da Espécie , Fatores de Tempo , Transfecção , Vanadatos/metabolismo , Vanadatos/farmacologia
9.
Neuropharmacology ; 52(3): 985-94, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17157884

RESUMO

The preclinical pharmacology of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline, a novel smoking cessation agent is described. Varenicline binds with subnanomolar affinity only to alpha4beta2 nAChRs and in vitro functional patch clamp studies in HEK cells expressing nAChRs show that varenicline is a partial agonist with 45% of nicotine's maximal efficacy at alpha4beta2 nAChRs. In neurochemical models varenicline has significantly lower (40-60%) efficacy than nicotine in stimulating [(3)H]-dopamine release from rat brain slices in vitro and in increasing dopamine release from rat nucleus accumbens in vivo, while it is more potent than nicotine. In addition, when combined with nicotine, varenicline effectively attenuates the nicotine-induced dopamine release to the level of the effect of varenicline alone, consistent with partial agonism. Finally, varenicline reduces nicotine self-administration in rats and supports lower self-administration break points than nicotine. These data suggest that varenicline can reproduce to some extent the subjective effects of smoking by partially activating alpha4beta2 nAChRs, while preventing full activation of these receptors by nicotine. Based on these findings, varenicline was advanced into clinical development and recently shown to be an effective and safe aid for smoking cessation treatment.


Assuntos
Comportamento Animal/efeitos dos fármacos , Benzazepinas/farmacologia , Agonistas Nicotínicos/farmacologia , Quinoxalinas/farmacologia , Abandono do Hábito de Fumar/métodos , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Linhagem Celular Transformada , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Nicotina/administração & dosagem , Técnicas de Patch-Clamp/métodos , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Autoadministração , Transfecção , Vareniclina
10.
Br J Pharmacol ; 151(1): 103-14, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17339830

RESUMO

BACKGROUND AND PURPOSE: The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor. EXPERIMENTAL APPROACH: The P2X(7) receptor antagonist, N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17), was radiolabelled with tritium and binding studies were performed using membranes prepared from U-2 OS or HEK293 cells expressing human recombinant P2X(7) receptors. KEY RESULTS: Binding of [(3)H]-compound-17 was higher in membranes prepared from cells expressing P2X(7) receptors than from control cells and was inhibited by ATP suggesting labelled sites represented human P2X(7) receptors. Binding was reversible, saturable and modulated by P2X(7) receptor ligands (Brilliant Blue G, KN62, ATP, decavanadate). Furthermore, ATP potency was reduced in the presence of divalent cations or NaCl. Radioligand binding exhibited both positive and negative cooperativity. Positive cooperativity was evident from bell shaped Scatchard plots, reduction in radioligand dissociation rate by unlabelled compound-17 and enhancement of radioligand binding by KN62 and unlabelled compound-17. ATP and decavanadate inhibited binding in a negative cooperative manner as they enhanced radioligand dissociation. CONCLUSIONS: These data demonstrate that human P2X(7) receptors can be directly labelled and provide novel insights into receptor function. The positive cooperativity observed suggests that binding of compound-17 to one subunit in the P2X(7) receptor complex enhances subsequent binding to other P2X(7) subunits in the same complex. The negative cooperative effects of ATP suggest that ATP and compound-17 bind at separate, interacting, sites on the P2X(7) receptor.


Assuntos
Ensaio Radioligante/métodos , Receptores Purinérgicos P2/análise , Trifosfato de Adenosina/farmacologia , Sítios de Ligação , Células Cultivadas , Humanos , Iohexol/análogos & derivados , Iohexol/metabolismo , Cinética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2X7 , Trítio , Vanadatos/farmacologia
11.
Oncogene ; 36(17): 2366-2376, 2017 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27748757

RESUMO

Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease requiring treatment displayed resistance to these antibodies, whereas patients with stable disease were sensitive. Using enrichment strategies and transcriptomic analyses, we show that antibody-dependent tumour cell killing was FcγR-dependent and mediated by macrophages. Moreover, we show that resistance cannot be attributed to total numbers or established subtypes of monocytes/macrophages, or the efficiency with which they bind an immune complex. Rather, ADCC/ADP resistance was due to reduced signalling activity through the activating FcγRs resulting in the transfer of dominance to the inhibitory FcγRIIb within macrophages. Most significantly, we show that resistance is an actionable event that could be reversed using inhibitors of FcγRIIb signalling in primary cultures of CLL cells that were previously insensitive to obinutuzumab or CD62L-Ab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/imunologia , Selectina L/uso terapêutico , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Receptores de IgG/metabolismo , Anticorpos Monoclonais Humanizados/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Progressão da Doença , Humanos , Selectina L/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Monócitos/citologia , Monócitos/imunologia , Transdução de Sinais/imunologia
12.
Br J Pharmacol ; 149(1): 43-55, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16880767

RESUMO

BACKGROUND AND PURPOSE: Absorptive epithelia express apical receptors that allow nucleotides to inhibit Na(+) transport but ATP unexpectedly stimulated this process in an absorptive cell line derived from human bronchiolar epithelium (H441 cells) whilst UTP consistently caused inhibition. We have therefore examined the pharmacological basis of this anomalous effect of ATP. EXPERIMENTAL APPROACH: H441 cells were grown on membranes and the short circuit current (I(SC)) measured in Ussing chambers. In some experiments, [Ca(2+)](i) was measured fluorimetrically using Fura -2. mRNAs for adenosine receptors were determined by the polymerase chain reaction (PCR). KEY RESULTS: Cross desensitization experiments showed that the inhibitory response to UTP was abolished by prior exposure to ATP whilst the stimulatory response to ATP persisted in UTP-pre-stimulated cells. Apical adenosine evoked an increase in I(SC) and this response resembled the stimulatory component of the response to ATP, and could be mimicked by adenosine receptor agonists. Pre-stimulation with adenosine abolished the stimulatory component of the response to ATP. mRNA encoding A(1), A(2A) and A(2B) receptor subtypes, but not the A(3) subtype, was detected in H441 cells and adenosine receptor antagonists could abolish the ATP-evoked stimulation of Na(+) absorption. CONCLUSIONS AND IMPLICATIONS: The ATP-induced stimulation of Na(+) absorption seems to be mediated via A(2A/B) receptors activated by adenosine produced from the extracellular hydrolysis of ATP. The present data thus provide the first description of adenosine-evoked Na(+) transport in airway epithelial cells and reveal a previously undocumented aspect of the control of this physiologically important ion transport process.


Assuntos
Adenosina/farmacologia , Mucosa Respiratória/metabolismo , Sódio/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Transporte Biológico Ativo/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular , Interpretação Estatística de Dados , Corantes Fluorescentes , Fura-2 , Humanos , Antagonistas de Receptores Purinérgicos P1 , RNA/biossíntese , RNA/genética , Receptores Purinérgicos P2/efeitos dos fármacos , Receptores Purinérgicos P2Y2 , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
J Natl Cancer Inst ; 64(4): 701-13, 1980 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6928984

RESUMO

In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.


Assuntos
Café/efeitos adversos , Nitrosaminas/efeitos adversos , Doenças Profissionais/induzido quimicamente , Fumar/complicações , Neoplasias da Bexiga Urinária/etiologia , Fatores Etários , Idoso , Analgésicos/efeitos adversos , Exposição Ambiental , Feminino , Conservantes de Alimentos/efeitos adversos , Tinturas para Cabelo/efeitos adversos , Humanos , Masculino , Risco , Fatores Sexuais
14.
Arch Intern Med ; 151(12): 2445-8, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1747001

RESUMO

Blood donor screening for hepatitis B core antibody and elevation of serum alanine aminotransferase level, surrogate markers of hepatitis C/non-A, non-B (NANB) infection, was implemented in 1986. Reported cases of posttransfusion hepatitis (PTH) from 1985 to 1988 were reviewed to ascertain the effect of surrogate testing on the number and character of cases and to compare any changes with those in the incidence of hepatitis in the general population. The reports of all PTH, NANB PTH, and type B PTH decreased 61.5%, 75.4%, and 84.5%, respectively. The rates of reported cases of NANB hepatitis and hepatitis B in the general community also fell during the period of review. The decrease in PTH and background hepatitis was similar between 1985 and 1986. In 1987, the first complete year of surrogate testing, the incidence of PTH decreased at a greater rate, to levels 50% below what would have been projected on the basis of background changes alone for NANB PTH, and to 35% below projected for type B PTH. There appears to have been a substantial decrease in the risk of both type B PTH and NANB PTH in the northeastern United States between 1985 and 1988 due to a combined effect of donor surrogate testing and a decrease in the background rates of hepatitis in the donor population.


Assuntos
Alanina Transaminase/sangue , Doadores de Sangue , Anticorpos Anti-Hepatite/sangue , Hepatite B/transmissão , Hepatite C/transmissão , Programas de Rastreamento , Reação Transfusional , Hepatite B/epidemiologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite C/epidemiologia , Humanos , Incidência , Maine/epidemiologia , Massachusetts/epidemiologia , Prevalência
15.
J Med Chem ; 38(16): 3138-45, 1995 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-7636876

RESUMO

(1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (20, CP-101,606) has been identified as a potent and selective N-methyl-D-aspartate (NMDA) antagonist through a structure activity relation (SAR) program based on ifenprodil, a known antihypertensive agent with NMDA antagonist activity. Sites on the threo-ifenprodil skeleton explored in this report include the pendent methyl group (H, methyl, and ethyl nearly equipotent; propyl much weaker), the spacer group connecting the C-4 phenyl group to the piperidine ring (an alternating potency pattern with 0 and 2 carbon atoms yielding the greatest potency), and simple phenyl substitution (little effect). While potent NMDA antagonists were obtained with a two atom spacer, this arrangement also increased alpha 1 adrenergic affinity. Introduction of a hydroxyl group into the C-4 position on these piperidine ring resulted in substantial reduction in alpha 1 adrenergic affinity. The combination of these observations was instrumental in the discovery of 20. This compound potently protects cultured hippocampal neurons from glutamate toxicity (IC50 = 10 nM) while possessing little of the undesired alpha 1 adrenergic affinity (IC50 approximately 20 microM) of ifenprodil. Furthermore, 20 appears to lack the psychomotor stimulant effects of nonselective competitive and channel-blocking NMDA antagonists. Thus, 20 shows great promise as a neuroprotective agent and may lack the side effects of compounds currently in clinical trials.


Assuntos
N-Metilaspartato/antagonistas & inibidores , Degeneração Neural/efeitos dos fármacos , Piperidinas/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Células Cultivadas , Genes fos/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , N-Metilaspartato/farmacologia , Piperidinas/síntese química , Piperidinas/química , Ratos , Relação Estrutura-Atividade
16.
Pediatrics ; 94(3): 341-6, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8065860

RESUMO

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has dramatically improved the survival of neonates with life-threatening respiratory and cardiac failure. However, ECMO requires numerous transfusions with significant risks. This study evaluated the effects of changing transfusion practices and blood component management on blood donor exposures in neonatal ECMO. DESIGN: A 3-year retrospective chart review of all neonatal ECMO patients from December 1989 through November 1992 was undertaken. During this 3-year period, transfusion practices and blood product preparation were altered twice to reduce blood donor exposures. The use of apheresis platelets and fresh frozen plasma (FFP), and preserving the expiration date on packed red blood cells (PRBCs) through the use of a sterile connecting device, allowed multiple transfusions from individual donor components. In addition, education of the ECMO physicians was focused on standardizing and reducing transfused volumes. Sixty-four surviving neonatal patients (91.4%) were evaluated. Five patients had excessive bleeding and were excluded from analysis. The remaining 59 patients were divided into three protocols based upon the transfusion practice at the time of their ECMO course. Protocol 1 received PRBCs less than 5 days of age, volume-reduced platelet concentrates, and standard FFP units up to 24 hours after thawing. Changes in transfusion practice for protocol 2 included extended outdate for PRBCs to 10 days, and using single donor apheresis platelet aliquots. The third protocol entailed the use single donor apheresis FFP aliquots in addition to the protocol 2 changes. RESULTS: Total PRBC transfusion volumes (721 +/- 406 ml for protocol 1, 637 +/- 172 ml for protocol 3) and associated blood donor exposures (5 +/- 2.1 for protocol 1, 3.9 +/- 0.9 for protocol 3) did not change substantially over the reviewed period. However, FFP transfusion volumes (478 +/- 170 ml for protocol 1, 274 +/- 63 ml for protocol 3), FFP-related donor exposures (4.5 +/- 1.6 for protocol 1, 1.2 +/- 0.4 for protocol 3) and platelet-related donor exposures (4.6 +/- 3.6 for protocol 1, 2.5 +/- 1.5 for protocol 3) were reduced progressively and significantly from protocol 1 to protocol 3 (P < .01, Tukey's B test adjusted for multiple comparisons). The total number of donor exposures per patient while on ECMO was decreased from 14.1 in protocol 1 to 10.0 in protocol 2 to 7.5 in protocol 3 (P < .01). CONCLUSIONS: We conclude that the changes in blood bank component selection and management as well as physician practice were effective in substantially reducing ECMO-related transfusion volumes and the resulting donor exposures.


Assuntos
Bancos de Sangue , Transfusão de Componentes Sanguíneos/métodos , Transfusão de Sangue/métodos , Oxigenação por Membrana Extracorpórea , Transfusão de Componentes Sanguíneos/efeitos adversos , Preservação de Sangue , Protocolos Clínicos , Humanos , Recém-Nascido , Avaliação de Processos e Resultados em Cuidados de Saúde , Plasma , Estudos Retrospectivos , Reação Transfusional
17.
Proc Biol Sci ; 268(1477): 1741-8, 2001 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-11506689

RESUMO

House mice (Mus domesticus) in the Victorian mallee region of southeastern Australia show irregular outbreaks. Changes in reproductive output that could potentially drive changes in mouse numbers were assessed from 1982 to 2000. Litter size in females is positively correlated with body size. When standardized to an average size female, litter size changes seasonally from highest in spring to lowest in autumn and winter. Litter size is depressed throughout breeding seasons that begin when the abundance of mice is high, but is similar in breeding seasons over which the abundance of mice increases rapidly or remains low. Breeding begins early and is extended on average by about five weeks during seasons when mouse abundance increases rapidly. The size at which females begin to reproduce is larger during breeding seasons that begin when mouse abundance is high. An extended breeding season that begins early in spring is necessary for the generation of a house mouse plague, but it is not in itself sufficient. Reproductive changes in outbreaks of house mice in Australia are similar but not identical to reproductive changes that accompany rodent population increases in the Northern Hemisphere. We conclude that food quality, particularly protein, is a probable mechanism driving these reproductive changes, but experimental evidence for field populations is conflicting.


Assuntos
Camundongos/fisiologia , Reprodução/fisiologia , Animais , Austrália , Cruzamento , Feminino , Tamanho da Ninhada de Vivíparos , Masculino , Camundongos/genética , Densidade Demográfica , Estações do Ano
18.
Int J Parasitol ; 26(4): 383-98, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8773526

RESUMO

A 12-month manipulative field study of the effect of a liver parasite, Capillaria hepatica, on mouse populations (Mus domesticus) was conducted in the Mallee wheatlands of northwestern Victoria. There were 2 untreated and 4 treated sites each consisting of a 16 km2 sampling zone. The parasite was released in September (spring) 1993 into an increasing mouse population which had a medium density (100-250 mice per ha). A third untreated site was monitored from January 1994. A simple but effective baiting method was developed and with the assistance of local farmers about 40,000 mice were dosed on the 4 sites; an estimated 5-7% of the population. During a second release, a month later, a further 20,000 mice were infected, boosting the level of infection to around 10%. Two months after the release approximately 30% of the population was infected. Thereafter, although there was effective transmission of the parasite, this was associated with a significant reduction in prevalence with time. The parasite reduced host survival by 5-10%, although this difference was not statistically significant, and had a minimal effect on the breeding and the rate of growth of mouse populations. Densities of 500-800 mice per ha were attained at each site in autumn 1994. Thus a spring release of the parasite into a rapidly increasing mouse population in the Victorian Mallee wheatlands did not prevent the population from increasing. The occurrence of very dry conditions following its release and the low but sustained transmission of the parasite indicate that we need to know more about factors that influence the survival and transmission of the parasite under field conditions.


Assuntos
Capillaria/patogenicidade , Infecções por Enoplida/veterinária , Camundongos/parasitologia , Doenças dos Roedores , Animais , Animais Selvagens , Infecções por Enoplida/epidemiologia , Infecções por Enoplida/transmissão , Feminino , Interações Hospedeiro-Parasita , Lactação , Fígado/parasitologia , Masculino , Densidade Demográfica , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/veterinária , Prevalência , Estações do Ano , Vitória
19.
Ann Epidemiol ; 8(6): 402-9, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9708876

RESUMO

PURPOSE: To describe the prevalence of disabilities and the medical conditions and risk factors associated with mobility and agility disabilities among seniors. METHODS: In the 1986 and 1991 Canadian Census, every fifth person answered a screening question about activity limitation and disabilities. A probability sample of both those reporting and not reporting disability was selected to complete the Health and Activity Limitations Surveys (HALS) in 1986 and 1991. These two cross-sectional surveys conducted five years apart collected detailed activity limitation information about persons over 15 years of age. The current analysis was based on only respondents aged 65 years and older. The sample size for 65 years and older was 38518 in 1986 and 5106 in 1991. A computer link with the Census data provided household income and additional socio-demographic data for all respondents. RESULTS: Over 40% of Canadian seniors reported at least one disability, and approximately a quarter of disabled seniors were classified as severely disabled. Mobility and agility disabilities accounted for over 80% of all disabilities reported by seniors, and senior women were more likely than men to report having a mobility or agility disability. Arthritis/rheumatism was reported as the cause of over 30% of all mobility and agility disabilities. CONCLUSIONS: The continued monitoring of disabilities through surveys such as HALS will help determine the prevalence as well as aid in the identification of the causes of disabilities. Such information may be used to guide the implementation of appropriate public health interventions that will meet the changing health care needs of seniors.


Assuntos
Atividades Cotidianas , Avaliação da Deficiência , Pessoas com Deficiência/estatística & dados numéricos , Inquéritos Epidemiológicos , Fatores Etários , Idoso , Artrite/epidemiologia , Canadá/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Doenças Reumáticas/epidemiologia , Fatores de Risco , Tamanho da Amostra , Inquéritos e Questionários
20.
J Clin Epidemiol ; 41(8): 793-802, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3138391

RESUMO

While measurement of the actions of providers (process) are a vital part of assessing the quality of care in long-term care settings, instruments that are appropriate to such measurement in program evaluation, auditing staff performance, and evaluation of continuing education programs are often unavailable. Long-term care providers are therefore faced with the challenge of either selecting an instrument from the few available or constructing a new one. This article describes several scientifically acceptable measurement properties for instruments measuring the actions of long-term care providers and their application to instruments reported in the long-term care literature. Only five of the 23 instruments reviewed met four or more of the seven measurement properties.


Assuntos
Assistência de Longa Duração/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Projetos de Pesquisa , Estudos de Avaliação como Assunto , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde , Padrões de Referência
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