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1.
Allergy ; 65(11): 1404-13, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20557300

RESUMO

BACKGROUND: Geographical variations in atopic sensitization in Canada have not been described previously. This study used the standardized protocol of the European Community Respiratory Health Survey-1 (ECRHS-1) to investigate the distribution and predictors of atopic sensitization in six sites across Canada and to compare the results with some ECRHS-1 centers. METHODS: Adults aged 20-44 years in six study sites across Canada underwent allergy skin testing using 14 allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae) cat, cockroach, grasses (Timothy grass, Kentucky grass), molds (Cladosporium herbarium, Alternaria alternata, Aspergillus fumigatus, Penicillium), trees (tree mix, birch, Olea europea), and common ragweed. RESULTS: The overall prevalence of atopy (skin test over 0 mm to any allergen) was 62.7%. There was significant geographical variation in the prevalence of atopy in the six study sites (lowest 55.6% [95% C.I.51.3-59.9] in Prince Edward Island, highest 66.0 [61.7-70.3] in Montreal) and of sensitization to each of the allergens tested even after adjustment for confounders. When the first eight of the nine allergens in the ECRHS were used to estimate the prevalence of atopic sensitization, the prevalence of atopy in Canada was 57% compared with 35.2% overall for centers in the ECRHS. The prevalence of atopy in Vancouver (57% [52.3-61.8]) was close to that of Portland, Oregon (52.1% [46.2-58.0]). CONCLUSION: There was a significant variation in atopic sensitization among different study sites across Canada. The prevalence of atopic sensitization is relatively high in Canada compared with sites in the ECRHS and this may, in part, account for the high prevalence of asthma and asthma symptoms in Canada.


Assuntos
Hipersensibilidade Imediata/epidemiologia , Adulto , Distribuição por Idade , Animais , Asma/epidemiologia , Canadá/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Testes Cutâneos , Inquéritos e Questionários , Adulto Jovem
2.
Can Respir J ; 17(1): 15-24, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20186367

RESUMO

BACKGROUND/OBJECTIVE: To integrate new evidence into the Canadian Asthma Management Continuum diagram, encompassing both pediatric and adult asthma. METHODS: The Canadian Thoracic Society Asthma Committee members, comprised of experts in pediatric and adult respirology, allergy and immunology, emergency medicine, general pediatrics, family medicine, pharmacoepidemiology and evidence-based medicine, updated the continuum diagram, based primarily on the 2008 Global Initiative for Asthma guidelines, and performed a focused review of literature pertaining to key aspects of asthma diagnosis and management in children six years of age and over, and adults. RESULTS: In patients six years of age and over, management of asthma begins with establishing an accurate diagnosis, typically by supplementing medical history with objective measures of lung function. All patients and caregivers should receive self-management education, including a written action plan. Inhaled corticosteroids (ICS) remain the first-line controller therapy for all ages. When asthma is not controlled with a low dose of ICS, the literature supports the addition of long-acting beta2-agonists in adults, while the preferred approach in children is to increase the dose of ICS. Leukotriene receptor antagonists are acceptable as second-line monotherapy and as an alternative add-on therapy in both age groups. Antiimmunoglobulin E therapy may be of benefit in adults, and in children 12 years of age and over with difficult to control allergic asthma, despite high-dose ICS and at least one other controller. CONCLUSIONS: The foundation of asthma management is establishing an accurate diagnosis based on objective measures (eg, spirometry) in individuals six years of age and over. Emphasis is placed on the similarities and differences between pediatric and adult asthma management approaches to achieve asthma control.


Assuntos
Asma/diagnóstico , Asma/terapia , Canadá , Criança , Humanos , Adulto Jovem
3.
J Epidemiol Community Health ; 57(1): 68-73, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12490652

RESUMO

OBJECTIVE: To identify and describe advantages, challenges, and ethical considerations of web based behavioural data collection. METHODS: This discussion is based on the authors' experiences in survey development and study design, respondent recruitment, and internet research, and on the experiences of others as found in the literature. RESULTS: The advantages of using the world wide web to collect behavioural data include rapid access to numerous potential respondents and previously hidden populations, respondent openness and full participation, opportunities for student research, and reduced research costs. Challenges identified include issues related to sampling and sample representativeness, competition for the attention of respondents, and potential limitations resulting from the much cited "digital divide", literacy, and disability. Ethical considerations include anonymity and privacy, providing and substantiating informed consent, and potential risks of malfeasance. CONCLUSIONS: Computer mediated communications, including electronic mail, the world wide web, and interactive programs will play an ever increasing part in the future of behavioural science research. Justifiable concerns regarding the use of the world wide web in research exist, but as access to, and use of, the internet becomes more widely and representatively distributed globally, the world wide web will become more applicable. In fact, the world wide web may be the only research tool able to reach some previously hidden population subgroups. Furthermore, many of the criticisms of online data collection are common to other survey research methodologies.


Assuntos
Pesquisa Comportamental , Coleta de Dados/métodos , Internet/organização & administração , Coleta de Dados/ética , Coleta de Dados/normas , Humanos , Internet/ética , Internet/normas , Pesquisadores/ética , Pesquisadores/organização & administração
4.
Am J Respir Crit Care Med ; 163(6): 1415-9, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11371411

RESUMO

Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma. However, it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention. A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited; 98 completed the study. The first 45 patients were assigned to Group C (control; usual treatment). Thereafter, patients were randomized to either Group LE (limited education; teaching of the inhaler technique plus self- action plan given by the on call physician) or Group SE (same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations). At baseline, there was no difference between groups in asthma morbidity, medication needs, or pulmonary function. After 12 mo, only Group SE showed a significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. In the last 6 mo, the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE (p = 0.03). The number (%) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE (p = 0.02). We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment.


Assuntos
Asma/prevenção & controle , Nebulizadores e Vaporizadores , Planejamento de Assistência ao Paciente , Educação de Pacientes como Assunto/métodos , Participação do Paciente , Autocuidado/métodos , Ensino/métodos , Doença Aguda , Adulto , Análise de Variância , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/psicologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Morbidade , Pico do Fluxo Expiratório , Qualidade de Vida , Encaminhamento e Consulta , Autocuidado/psicologia , Resultado do Tratamento
5.
Can Respir J ; 8 Suppl A: 5A-27A, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11360044

RESUMO

The objective of the present document is to review the impact of new information on the recommendations made in the last (1999) Canadian Asthma Consensus Guidelines. It includes relevant published studies and observations or comments regarding what are considered to be the main issues in asthma management in children and adults in office, emergency department, hospital and clinical settings. Asthma is still insufficiently controlled in a large number of patients, and practice guidelines need to be integrated better with current care. This report re-emphasises the need for the following: objective measures of airflow obstruction to confirm the diagnosis of asthma suggested by the clinical evaluation; identification of contributing factors; and the establishment of a treatment plan to rapidly obtain and maintain optimal asthma control according to specific criteria. Recent publications support the essential role of asthma education and environmental control in asthma management. They further support the role of inhaled corticosteroids as the mainstay of anti-inflammatory therapy of asthma, and of both long acting beta2-agonists and leukotriene antagonists as effective means to improve asthma control when inhaled corticosteroids are insufficient. New developments, such as combination therapy, and recent major trials, such as the Children's Asthma Management Project (CAMP) study, are discussed.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/terapia , Glucocorticoides/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Adulto , Alérgenos , Animais , Asma/imunologia , Asma/prevenção & controle , Canadá , Serviços Médicos de Emergência , Humanos , Ácaros/imunologia , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Esteroides
6.
CMAJ ; 164(7): 995-1001, 2001 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-11314453

RESUMO

BACKGROUND: Reported prevalence rates of asthma vary within and between countries around the world. These differences suggest environmental factors in addition to genetic factors in the cause of the disease and may provide clues for preventive strategies. We examined the variability of asthma-related symptoms and medication use among adults in 6 sites across Canada (Vancouver, Winnipeg, Hamilton, Montreal, Halifax and Prince Edward Island) and compared our findings with those from sites that had participated in a recent European survey. METHODS: We used the same sampling strategy and standardized questionnaire as those used in the European Community Respiratory Health Survey (ECRHS). The 6 Canadian sites were selected to represent different environments with respect to climate, air pollution and occupational exposure. Community-based samples of 3000 to 4000 people aged 20-44 years were randomly selected in each site. Subjects were asked to complete the questionnaire by mail between March 1993 and November 1994. Prevalence rates (and 95% confidence intervals [CIs]) of asthma symptoms, self-reported asthma attacks and use of asthma medication were compared across the Canadian sites and with sites that had participated in the ECRHS. RESULTS: The overall response rate of those selected to receive the questionnaire was 86.5% (range 74.5%-92.8%). The prevalence rates of most asthma symptoms varied significantly among the Canadian sites. For instance, 21.9% (Montreal) to 30.4% (Halifax) of the men and 24.0% (Vancouver) to 35.2% (Halifax) of the women reported wheezing in the year before the survey. Depending on the site, 4.4% to 6.3% of the men and 5.2% to 9.5% of the women reported an asthma attack in the last year, and 4.0% to 6.1% of the men and 4.9% to 9.7% of the women were currently using asthma medication. Prevalence rates of symptoms, asthma attacks and medication use did not change with age, but they were higher among women than among men. Compared with the results from the ECRHS sites, those from the Canadian sites were among the highest. INTERPRETATION: Significant variation in the prevalence of asthma symptoms, asthma attacks and use of asthma medication between Canadian sites and international sites suggests environmental influences. Different combinations of factors in different sites may be responsible for the high prevalence rates and should be the subject of further research to guide clinical management and public health intervention.


Assuntos
Asma/epidemiologia , Adulto , Asma/tratamento farmacológico , Asma/patologia , Broncodilatadores/uso terapêutico , Canadá/epidemiologia , Estudos Epidemiológicos , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Prevalência , Índice de Gravidade de Doença , Fatores Sexuais
7.
Anaesth Intensive Care ; 29(6): 591-4, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11771600

RESUMO

Hypotension associated with the rapid infusion of human serum albumin products was first recognised in Australasia in the early 1970s. An association with the angiotensin converting enzyme inhibitor class of drugs (ACE-I) followed, leading to a proposed mechanism involving bradykinin generation through pre-kallikrein activator (PKA) presence in the infused fluid. The newer generation albumin products (Albumex) contain very low concentrations of PKA and are generally thought safe to use in most patient populations. Anecdotal reports of paradoxical hypotension with rapid infusion of 4% albumin in our department led to an audit of practice over three months. Four out of 36 patients (11%) who received 4% albumin intravenously experienced paradoxical hypotension. Three of these patients were taking ACE-I preoperatively (P=0.04). There was no observed hypotension associated with intravenous infusion of crystalloid fluid. We believe 4% albumin should be used with caution, particularly in those patients receiving ACE-I preoperatively.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Hipotensão/induzido quimicamente , Albumina Sérica/efeitos adversos , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bradicinina/metabolismo , Interações Medicamentosas , Feminino , Hidratação/efeitos adversos , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Pré-Calicreína/metabolismo , Estudos Prospectivos , Albumina Sérica/administração & dosagem , Cirurgia Torácica
8.
Am J Respir Crit Care Med ; 162(6): 2058-62, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11112114

RESUMO

We examined the prevalence, population attributable risk (PAR), and clinical characteristics of occupational asthma (OA) in a randomly selected population in six communities in Canada. Our study followed the European Community Respiratory Health Survey protocol. A randomly selected population of 18,701 (87% response rate) persons from the study communities, ranging in age from 20 to 44 yr, completed an initial questionnaire, of whom 2,974 (39% response rate) attended the laboratory and completed supplementary questionnaires. Of these latter individuals, 383 had asthma. Asthma was defined as physician-diagnosed asthma, and adult-onset asthma was defined as a first attack at age 15 yr or older. We used several methods for estimating OA as follows: (1) reporting of a high-risk job (occupation and industry) for OA at the time of asthma onset (Probable OA); (2) reporting of exposure to a substance that may cause OA (Possible OA) while not in a high-risk job at the time of asthma onset; and (3) combination of the PAR for high-risk jobs and exposures. The prevalence (95% confidence interval [CI]) of Probable OA and Possible OA combined was 36.1% (31.3 to 41.0%) among subjects with adult-onset asthma. The occupations most commonly reported in association with OA were nursing in the Probable OA group and clerical and food preparation in the Possible OA group. The clinical characteristics and exposures reported by both groups were similar. The PAR for adult-onset asthma in high-risk jobs and exposures was 18.2%. The assessment of occupation and industry alone, rather than of exposures, may underestimate the contribution of occupational exposures to asthma prevalence.


Assuntos
Asma/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , Análise de Variância , Asma/diagnóstico , Canadá/epidemiologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Doenças Profissionais/diagnóstico , Prevalência , Distribuição Aleatória , Risco , Inquéritos e Questionários
10.
Am J Respir Crit Care Med ; 161(5): 1479-84, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10806142

RESUMO

It has been suggested that high-level training could contribute to the development of airway hyperresponsiveness (AHR), but the comparative effects of different sports on airway function remains to be determined. We evaluated 150 nonsmoking volunteers 18 to 55 yr of age; 100 athletes divided into four subgroups of 25 subjects each according to the predominant estimated hydrocaloric characteristic of ambient air inhaled during training: dry air (DA), cold air (CA), humid air (HA) and a mixture of dry and humid air (MA), and 50 sedentary subjects. Each subject had a respiratory questionnaire, a methacholine challenge, allergy skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. The athletes had a 49% prevalence of AHR (PC(20) < 16 mg/ml), with a mean PC(20) of 16.9 mg/ml, compared with 28% (PC(20): 35.4) in sedentary subjects (p = 0.009). The prevalence (%) of AHR and mean PC(20) (mg/ml) varied as followed in the four subgroups of athletes: DA: 32% and 30.9; CA: 52% and 15.8; HA: 76% and 7.3; and MA: 32% and 21.5 (p = 0.002). The estimated parasympathetic tone was higher in athletes (p < 0.001), but this parameter showed only a weak correlation with PC(20) (r = -0.17, p = 0.04). This study has shown a significantly higher prevalence of AHR in athletes than in the control group because of the higher prevalence in the CA and HA groups. Parasympathetic activity may act as modulator of airway responsiveness, but the increased prevalence of AHR in our athlete population may be related to the type and possibly the content of inhaled air during training.


Assuntos
Hiper-Reatividade Brônquica , Esportes/fisiologia , Adolescente , Adulto , Testes de Provocação Brônquica , Temperatura Baixa , Tosse/etiologia , Exercício Físico , Feminino , Volume Expiratório Forçado , Humanos , Umidade , Hipersensibilidade Imediata/diagnóstico , Masculino , Cloreto de Metacolina , Pessoa de Meia-Idade , Sons Respiratórios/etiologia , Testes Cutâneos , Capacidade Vital
11.
Thromb Haemost ; 83(3): 416-20, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10744147

RESUMO

We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was <2.0, moderate of the score was 2.0 to 6.0 and high if the score was over 6.0. Pulmonary embolism unlikely was assigned to patients with scores < or =4.0 and PE likely if the score was >4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Modelos Biológicos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Algoritmos , Estudos de Coortes , Humanos , Probabilidade , Estudos Prospectivos , Análise de Regressão
12.
J Neurosci ; 20(1): 89-102, 2000 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-10627585

RESUMO

Modulation of postsynaptic AMPA receptors in the brain by phosphorylation may play a role in the expression of synaptic plasticity at central excitatory synapses. It is known from biochemical studies that GluR1 AMPA receptor subunits can be phosphorylated within their C terminal by cAMP-dependent protein kinase A (PKA), which is colocalized with the phosphatase calcineurin (i.e., phosphatase 2B). We have examined the effect of PKA and calcineurin on the time course, peak open probability (P(O, PEAK)), and single-channel properties of glutamateevoked responses for neuronal AMPA receptors and homomeric GluR1(flip) receptors recorded in outside-out patches. Inclusion of purified catalytic subunit Calpha-PKA in the pipette solution increased neuronal AMPA receptor P(O,PEAK) (0.92) compared with recordings made with calcineurin included in the pipette (P(O,PEAK) 0.39). Similarly, Calpha-PKA increased P(O,PEAK) for recombinant GluR1 receptors (0. 78) compared with patches excised from cells cotransfected with a cDNA encoding the PKA peptide inhibitor PKI (P(O,PEAK) 0.50) or patches with calcineurin included in the pipette (P(O,PEAK) 0.42). Neither PKA nor calcineurin altered the amplitude of single-channel subconductance levels, weighted mean unitary current, mean channel open period, burst length, or macroscopic response waveform for recombinant GluR1 receptors. Substitution of an amino acid at the PKA phosphorylation site (S845A) on GluR1 eliminated the PKA-induced increase in P(O,PEAK), whereas the mutation of a Ca(2+), calmodulin-dependent kinase II and PKC phosphorylation site (S831A) was without effect. These results suggest that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Receptores de AMPA/metabolismo , Sinapses/enzimologia , Animais , Calcineurina/farmacologia , Células Cultivadas , Ácido Glutâmico/farmacocinética , Hipocampo/citologia , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Rim/citologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Mutagênese Sítio-Dirigida/fisiologia , Técnicas de Patch-Clamp , Células Piramidais/química , Células Piramidais/citologia , Células Piramidais/enzimologia , Ratos , Receptores de AMPA/genética , Proteínas Recombinantes/metabolismo , Transfecção
14.
Ann Intern Med ; 129(12): 997-1005, 1998 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9867786

RESUMO

BACKGROUND: The low specificity of ventilation-perfusion lung scanning complicates the management of patients with suspected pulmonary embolism. OBJECTIVE: To determine the safety of a clinical model for patients with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Five tertiary care hospitals. PATIENTS: 1239 inpatients and outpatients with suspected pulmonary embolism. INTERVENTIONS: A clinical model categorized pretest probability of pulmonary embolism as low, moderate, or high, and ventilation-perfusion scanning and bilateral deep venous ultrasonography were done. Testing by serial ultrasonography, venography, or angiography depended on pretest probability and lung scans. MEASUREMENTS: Patients were considered positive for pulmonary embolism if they had an abnormal pulmonary angiogram, abnormal ultrasonogram or venogram, high-probability ventilation-perfusion scan plus moderate or high pretest probability, or venous thromboembolic event during the 3-month follow-up. All other patients were considered negative for pulmonary embolism. Rates of pulmonary embolism during follow-up in patients who had a normal lung scan and those with a non-high-probability scan and normal serial ultrasonogram were compared. RESULTS: Pretest probability was low in 734 patients (3.4% with pulmonary embolism), moderate in 403 (27.8% with pulmonary embolism), and high in 102 (78.4% with pulmonary embolism). Three of the 665 patients (0.5% [95% CI, 0.1% to 1.3%]) with low or moderate pretest probability and a non-high-probability scan who were considered negative for pulmonary embolism had pulmonary embolism or deep venous thrombosis during 90-day follow-up; this rate did not differ from that in patients with a normal scan (0.6% [CI, 0.1% to 1.8%]; P > 0.2). CONCLUSION: Management of patients with suspected pulmonary embolism on the basis of pretest probability and results of ventilation-perfusion scanning is safe.


Assuntos
Técnicas de Apoio para a Decisão , Embolia Pulmonar/diagnóstico , Algoritmos , Angiografia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Probabilidade , Estudos Prospectivos , Embolia Pulmonar/fisiopatologia , Cintilografia , Reprodutibilidade dos Testes , Fatores de Risco , Ultrassonografia , Relação Ventilação-Perfusão
15.
J Neurosci ; 18(20): 8175-85, 1998 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-9763464

RESUMO

The mechanisms by which polyamines block AMPA and kainate receptors are not well understood, but it has been generally assumed that they act as open-channel blockers. Consistent with this, voltage-jump relaxation analysis of GluR6 equilibrium responses to domoate could be well fit, assuming that spermine, spermidine, and philanthotoxin are weakly permeable open-channel blockers. Analysis of rate constants for binding and dissociation of polyamines indicated that the voltage dependence of block arose primarily from changes in koff rather than kon. Experiments with changes in Na concentration further indicate that the voltage dependence of polyamine block was governed by ion flux via open channels. However, responses to 1 msec applications of L-Glu revealed slow voltage-dependent rise-times, suggesting that polyamines additionally bind to closed states. A kinetic model, which included closed-channel block, reproduced these observations but required that polyamines accelerate channel closure either through an allosteric mechanism or by emptying the pore of permeant ions. Simulations with this model reveal that polyamine block confers novel activity-dependent regulation on calcium-permeable AMPA and kainate receptor responses.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Poliaminas/farmacologia , Receptores de AMPA/fisiologia , Receptores de Ácido Caínico/fisiologia , Células Cultivadas , Condutividade Elétrica , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/farmacologia , Humanos , Íons , Ácido Caínico/farmacologia , Rim/citologia , Cinética , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Fenóis/farmacologia , Espermidina/farmacologia , Espermina/farmacologia , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia
16.
Postgrad Med J ; 74(875): 545-6, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10211330

RESUMO

A case of deliberate overdose of barium sulphide in a psychiatric setting is presented, with resulting flaccid paralysis, malignant arrhythmia, respiratory arrest and severe hypokalaemia, but ultimately with complete recovery. The degree of paralysis appears to be related directly to serum barium levels. The value of early haemodialysis, particularly with respiratory paralysis and hypokalaemia, is emphasised.


Assuntos
Bário/intoxicação , Transtorno Bipolar/psicologia , Paralisia/induzido quimicamente , Adulto , Cerâmica , Feminino , Humanos , Hipotonia Muscular/induzido quimicamente , Intoxicação/terapia , Diálise Renal , Tentativa de Suicídio
17.
J Physiol ; 502 ( Pt 3): 575-89, 1997 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-9279810

RESUMO

1. Polyamine block of rat GluR6(Q) glutamate receptor channels was studied in outside-out patches from transiently transfected HEK 293 cells. With symmetrical 150 mM Na+ and 30 microM internal spermine there was biphasic voltage dependence with 95% block at +40 mV but only 20% block at +140 mV. Dose-inhibition analysis for external spermine also revealed biphasic block; the Kd at +40 mV (54 microM) was lower than at +80 (167 microM) and -80 mV (78 microM). 2. For internal polyamines relief from block was most pronounced for spermine, weaker for N-(4-hydroxyphenylpropanoyl)-spermine (PPS), and virtually absent for philanthotoxin 343 (PhTX 343), suggesting that permeation of polyamines varies with cross-sectional width (spermine, 0.44 nm; PPS, 0.70 nm; PhTX 343, 0.75 nm). 3. With putrescine, spermidine, or spermine as sole external cations, inward currents at -120 mV confirmed permeation of polyamines. For bi-ionic conditions with 90 mM polyamine and 150 mM Na+i, reversal potentials were -12.4 mV for putrescine (permeability ratio relative to Na+, PPut/PNa = 0.42) and -32.7 mV for spermidine (PSpd/PNa = 0.07). Currents carried by spermine were too small to analyse accurately in the majority of patches. 4. Increasing [Na+]i from 44 to 330 mM had no effect on the potential for 50% block (V1/2) by 30 microM internal spermine; however, relief from block at positive membrane potentials increased with [Na+]i. In contrast, raising [Na+]o from 44 to 330 mM resulted in a depolarizing shift in V1/2, indicating a strong interaction between internal polyamines and external permeant ions. 5. The Woodhull infinite barrier model of ion channel block adequately described the action of spermine at membrane potentials insufficient to produce relief from block. For 30 microM internal spermine such analysis gave Kd(O) = 2.5 microM, z theta = 1.97; block by 30 microM external spermine was weaker and less voltage dependent (Kd(O) = 37.8 microM and z delta = 0.55); delta and theta are electrical distances measured from the outside and inside, respectively. 6. Fits of the Woodhull equation for a permeable blocker adequately described both onset and relief from block by spermine over a wide range of membrane potentials. However, the rate constants and z delta values estimated for block by internal spermine predicted much stronger external block than was measured experimentally, and vice versa. 7. An Eyring rate theory model with two energy wells and three barriers explained qualitatively many characteristic features of the action of polyamines on GluRs, including biphasic I-V relationships, weaker block by external than internal spermine and low permeability.


Assuntos
Ativação do Canal Iônico/fisiologia , Receptores de Ácido Caínico/antagonistas & inibidores , Receptores de Ácido Caínico/fisiologia , Espermina/farmacologia , Animais , Linhagem Celular , Condutividade Elétrica , Eletrofisiologia , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Rim/citologia , Peso Molecular , Ratos , Receptores de Ácido Caínico/química , Sódio/química , Sódio/farmacologia , Espermina/química , Transfecção , Receptor de GluK2 Cainato
18.
Chest ; 110(3): 595-603, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8797398

RESUMO

BACKGROUND: It has been suggested that overuse of fenoterol metered-dose inhalers (MDIs) may increase the risk of death from asthma due to cardiac arrhythmias. Our primary objective was to compare the cardiovascular safety of fenoterol and albuterol MDIs when administered in maximal bronchodilating or maximal tolerated doses to an absolute maximum of 16 puffs, for the emergency department (ED) treatment of acute severe asthma. METHODS: Asthmatic patients presenting to the ED with acute severe asthma (FEV1 less than 50% of predicted) were enrolled in a multicenter, randomized, double-blind, parallel-group study. Following baseline measurements, (medical history, physical examination, determination of serum potassium and serum theophylline levels, oximetry, 12-lead ECG, and spirometry), each patient received 4 puffs of either fenoterol, 200 micrograms per puff, or albuterol, 100 micrograms per puff, 1 puff every 30 s via an MDI attached to a holding chamber. Additional doses of inhaled beta 2-agonist were administered by dose titration, 2 puffs every 10 min to a maximal cumulative dose of 16 puffs of albuterol or fenoterol, side effects were intolerable to the patient, or an FEV1 plateau (i.e., < 10% improvement for 2 consecutive doses) occurred. ECG was recorded continuously via Holter monitor, and respiratory rate, BP, dyspnea (Borg scale), and FEV1 were assessed after each dose. RESULTS: 128 patients were randomized to receive fenoterol and 129 to receive albuterol. Overall, fenoterol increased FEV1 160 mL more than albuterol. The mean (SEM) FEV1 increase from baseline was 0.75 +/- 0.06 L in the fenoterol group and 0.59 +/- 0.06 L in the albuterol group (p < 0.03). Both beta 2-agonists caused a decrease in serum potassium level that was significantly greater in the fenoterol (0.23 +/- 0.04 mmol/L) than in the salbutamol (0.06 +/- 0.03 mmol/L) group (p = 0.0002). There was also a greater increase in the Q-Tc interval in the fenoterol group, 0.011 +/- 0.003 s compared with 0.003 +/- 0.003 s in the albuterol group (p < 0.05). Differences in hypokalemia and Q-Tc prolongation associated with fenoterol and albuterol were significantly different only after 8 puffs of fenoterol had been given. 32 patients exhibited ventricular premature beats, 14 in the fenoterol group and 18 in the albuterol group. There were 34 patients with episodes of supraventricular premature beats, 17 in each group. No episodes of sustained ventricular tachycardia were detected in either group. CONCLUSIONS: In adequately oxygenated patients, using dose titration of fenoterol, in a formulation of 200 micrograms per puff by MDI valved holding chamber and mask, to a total dose of 3,200 micrograms and salbutamol (100 micrograms per puff) to a total dose of 1,600 micrograms over 90 min, showed cardiovascular safety in acute severe asthma. This was evidenced by absence of cardiovascular mortality or clinically significant arrhythmias in either group. The 100% greater dose of fenoterol improved FEV1 significantly more than salbutamol and was associated with a relatively small but significantly greater prolongation of the Q-Tc interval and decrease in serum potassium level. This study does not exclude the possibility that adverse cardiac events could occur with severe hypoxemia.


Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Albuterol/administração & dosagem , Asma/tratamento farmacológico , Fenoterol/administração & dosagem , Doença Aguda , Administração por Inalação , Adolescente , Adulto , Asma/fisiopatologia , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Clin Nephrol ; 45(6): 383-5, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8793230

RESUMO

The previous methods to biopsy renal allografts at our institution involved the use of the Franklin-Silverman or Tru-Cut needles. Unfortunately they had a significant rate of post biopsy bleeding secondary to deep penetration when excess force was used to penetrate a tough transplant capsule. Although spring loaded biopsy devices have been widely used for native kidney biopsies over the past three years, the complication rate for renal allograft biopsies has not been sufficiently evaluated. We describe our experience using a disposable spring loaded biopsy device on transplanted renal grafts. Fifty-four biopsies were performed with the device, all under ultrasound guidance. The ASAP automatic biopsy system by Medi-tech was used comprising of a spring loaded gun with a 15 cm long 15 GA needle echogenic tip and 17 mm specimen notch. All patients were ultrasounded immediately post biopsy to look for hematomas. Compared to 55 previous biopsies performed using Tru-Cut needles, we conclude that the ASAP automated biopsy system proved equally effective in obtaining adequate tissue for diagnosis with fewer post-biopsy hematomas compared to traditional biopsy methods.


Assuntos
Biópsia por Agulha/métodos , Transplante de Rim , Rim/patologia , Complicações Pós-Operatórias , Biópsia , Biópsia por Agulha/efeitos adversos , Biópsia por Agulha/instrumentação , Hematoma/etiologia , Humanos , Estudos Retrospectivos , Transplante Homólogo
20.
Eur Respir J ; 8(12): 2191-3, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8666118

RESUMO

A 41 year old male with psoriatic arthritis developed progressive dyspnoea and airflow obstruction following 4 months of intramuscular gold therapy. Open lung biopsy revealed bronchiolitis obliterans of the constrictive type. This case suggests a possible aetiological role for gold in the pathogenesis of constrictive bronchiolitis obliterans, or alternatively an association between psoriatic arthritis and this inflammatory airway condition.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Bronquiolite Obliterante/induzido quimicamente , Adulto , Antirreumáticos/uso terapêutico , Biópsia , Bronquiolite Obliterante/complicações , Bronquiolite Obliterante/patologia , Humanos , Pulmão/patologia , Masculino , Compostos Organoáuricos
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