Severe hypokalemia secondary to abuse of ß-adrenergic agonists in a pediatric patient: Case report / Hipocalemia grave secundária a abuso de agonistas ß-adrenérgicos em paciente pediátrico: relato de caso

ABSTRACT This study reports a case of a 13-year-old male with a 3-year history of severe and intermittent hypokalemia episodes of unknown origin, requiring admission to the intensive care unit (ICU) for long QT syndrome (LQTS), finally diagnosed of redistributive hypokalemia secondary to the abuse of β-adrenergic agonists in the context of a probable factitious disorder.

RESUMO O presente estudo relata o caso de um jovem de 13 anos de idade com histórico, há três anos, de episódios de hipocalemia grave intermitente de origem desconhecida, internado em unidade de terapia intensiva (UTI) por síndrome do QT longo (SQTL). O paciente foi diagnosticado com hipocalemia por redistribuição secundária ao abuso de agonistas β-adrenérgicos, em contexto de provável transtorno factício.

Conduta terapêutica em pacientes com doença pulmonar obstrutiva crônica: monoterapia ou terapia cominada? / Therapy for chronic obstructive pulmonary disease patients: monotherapy or combination therapy?

Objetivo: Comparar a dupla terapia broncodilatadora com glicopirrônio mais indacaterol à monoterapia com glicopirrônio em pacientes portadores de doença pulmonar obstrutiva crônica. Métodos: Estudo clínico prospectivo, unicêntrico, controlado, cruzado, randomizado e duplo-cego realizado com 14 pacientes com diagnóstico de doença pulmonar obstrutiva crônica grau II. Os participantes receberam cada um dos tratamentos durante 30 dias. Antes de cada terapia, realizou-se período de wash-out por 7 dias, com broncodilador de curta ação. Antes e após cada intervenção, os pacientes passaram por exame de espirometria e responderam ao questionário COPD Assessment Test. Resultados: Observou-se melhora na função pulmonar medida por meio do volume expiratório forçado no primeiro segundo de 19mL (±36) para a monoterapia e 87mL (±33) para a terapia dupla. O ganho foi de 67mL (p=0,042) da associação dos medicamentos em relação ao glicopirrônio isolado. A melhora na qualidade de vida, medida a partir das pontuações do questionário, foi de 4,7 (±8,9) pontos para a monoterapia e 5,2 (±11) pontos para a dupla terapia (p=0,08). Conclusão: Ambos os tratamentos demonstram melhora na função pulmonar dos pacientes.

Objective: To compare dual bronchodilator therapy (Glycopyrronium with Indacaterol) versus Glycopyrronium monotherapy in patients with chronic obstructive pulmonary disease. Methods: This was a prospective, unicentric, controlled, crossover, randomized, and double-blind clinical trial with 14 patients diagnosed with grade II chronic obstructive pulmonary disease. The participants received each treatment during the period of 30 days. Before each therapy, a 7-day wash-out period with a short-acting bronchodilator was instituted. Before and after each intervention, the patients underwent spirometry and answered the COPD Assessment Test questionnaire. Results: An improvement in pulmonary function measured by forced expiratory volume during the first second of 19mL (±36) for monotherapy, and 87mL (±33) for dual therapy was observed. The gain was of 67mL (p=0.042) in the association of the drugs in relation to Glycopyrronium alone. The mean improvement in quality of life measured from the questionnaire scores was 4.7 (±8.9) points for monotherapy and 5.2 (± 11) points for dual therapy (p=0.08). Conclusion: Both treatments show improvement in the patients' pulmonary function.

Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis / Antagonistas muscarínicos de longa duração vs. β 2 -agonistas de longa duração em exacerbações da DPOC: revisão sistemática e meta-análise

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

RESUMO Objetivo: Determinar se long-acting muscarinic antagonists (LAMAs, antagonistas muscarínicos de longa duração) são superiores a long-acting β2 agonists (LABAs, β2-agonistas de longa duração) na prevenção de exacerbações da DPOC. Métodos: Revisão sistemática e meta-análise de ensaios clínicos controlados aleatórios com pacientes com DPOC estável, de moderada a grave, conforme os critérios da Global Initiative for Chronic Obstructive Lung Disease, tratados com LAMA (brometo de tiotrópio, aclidínio ou glicopirrônio), acompanhados durante pelo menos 12 semanas e comparados a controles que usaram LABA isoladamente ou com um corticosteroide. Resultados: Foram analisados 2.622 estudos para possível inclusão com base em seu título e resumo; 9 estudos (17.120 participantes) foram incluídos na análise. Em comparação com LABAs, LAMAs resultaram em maior diminuição da razão da taxa de exacerbações [risco relativo (RR) = 0,88; IC95%: 0,84-0,93]; menor proporção de pacientes que apresentaram pelo menos uma exacerbação (RR = 0,90; IC95%: 0,87-0,94; p < 0,00001); menor risco de hospitalizações em virtude de exacerbação da doença (RR = 0,78; IC95%: 0,69-0,87; p < 0,0001) e menor número de eventos adversos sérios (RR = 0,81; IC95%: 0,67-0,96; p = 0,0002). A qualidade geral das evidências foi moderada para todos os desfechos. Conclusões: O principal achado desta revisão sistemática e meta-análise foi que LAMAs reduziram significativamente a taxa de exacerbações (episódios de exacerbação/ano), os episódios de exacerbação, as hospitalizações e os eventos adversos sérios.

Function and Dysfunction of Human Sinoatrial Node

Sinoatrial node (SAN) automaticity is jointly regulated by a voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release). Using optical mapping in Langendorff-perfused canine right atrium, we previously demonstrated that the beta-adrenergic stimulation pushes the leading pacemaker to the superior SAN, which has the fastest activation rate and the most robust late diastolic intracellular calcium (Cai) elevation. Dysfunction of the superior SAN is commonly observed in animal models of heart failure and atrial fibrillation (AF), which are known to be associated with abnormal SAN automaticity. Using the 3D electroanatomic mapping techniques, we demonstrated that superior SAN served as the earliest atrial activation site (EAS) during sympathetic stimulation in healthy humans. In contrast, unresponsiveness of superior SAN to sympathetic stimulation was a characteristic finding in patients with AF and SAN dysfunction, and the 3D electroanatomic mapping technique had better diagnostic sensitivity than corrected SAN recovery time testing. However, both tests have significant limitations in detecting patients with symptomatic sick sinus syndrome. Recently, we reported that the location of the EAS can be predicted by the amplitudes of P-wave in the inferior leads. The inferior P-wave amplitudes can also be used to assess the superior SAN responsiveness to sympathetic stimulation. Inverted or isoelectric P-waves at baseline that fail to normalize during isoproterenol infusion suggest SAN dysfunction. P-wave morphology analyses may be helpful in determining the SAN function in patients at risk of symptomatic sick sinus syndrome.

Cancer therapy using natural ligands that target estrogen receptor beta / 中国天然药物

Estrogen receptor beta (ERβ) is one of the two key receptors (ERα, ERβ) that facilitate biological actions of 17β-estradiol (E2). ERβ is widely expressed in many tissues, and its expression is reduced or lost during progression of many tumors. ERβ facilitates estrogen signaling by both genomic (classical and non-classical) and extra-nuclear signaling. Emerging evidence suggests that ERβ functions as a tissue-specific tumor suppressor with anti-proliferative actions. Recent studies have identified a number of naturally available selective ERβ agonists. Targeting ERβ using its naturally available ligands is an attractive approach for treating and preventing cancers. This review presents the beneficial actions of ERβ signaling and clinical utility of several natural ERβ ligands as potential cancer therapy.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or β-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or β- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress. .

Small Airways Dysfunction in Asthma: Evaluation and Management to Improve Asthma Control

The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored.

Clinical research of Salmeterol fluticasone propionate and Tiotropium bromide for improvement of pulmona-ry function in patients with chronic obstructive pulmonary disease and bronchial asthma / 中国基层医药

Objective To observe the improvement of Salmeterol fluticasone propionate and Tiotropium bromide for inhalation in the treatment of chronic obstructive pulmonary disease ( COPD ) with bronchial asthma patients.Methods 89 patients were randomly divided into the observation group with 46 cases and control group with 43 cases,both groups were given conventional therapy.The control group was given Salmeterol fluticasone propionate 50μg/500μg,twice a day;the observation group was given Tiotropium bromide 18μg, twice a day, based on the therapy of control group.The two groups were treated for 14 days,and then curative effect,score of SGRQ,pulmonary function and blood gas analysis index were evaluated, and adverse reactions were recorded.Results The total effective rate of treatment group was 86.1%,higher than that of the control group(68.6%) (Z=2.68,P<0.05);Compared with the control group after treatment,functional parameters[ FEV1 ( L) ,FEV1 (%) and FEV1/FVC(%) ] of the observation group increased significantly,and the observation group were all higher than that of the control group [(2.27 ±0.45) vs (1.92 ±0.36),(64.27 ±16.11) vs (53.64 ±15.55),(54.85 ±14.81) vs (45.33 ± 13.23)],the differences were all statistically significant(t=4.20,3.16,3.19,all P<0.05);PaO2 of the two groups patients were increased and PaCO2 were decreased,scores of SGRQ were decreased obviously,and the change of the observation group was obviously[(47.61 ±3.64) vs (49.34 ±4.23),(67.33 ±5.56) vs (63.66 ±5.21), (45.34 ±3.72) vs (50.65 ±4.16)],the difference was statistically significant(t =2.13,3.32,6.54,all P<0.05) .Conclusion Salmeterol fluticasone propionate and Tiotropium bromide for inhalation can improve lung func-tional parameters and respiratory conditions of the parents with COPD and bronchial asthma obviously, reduce the score of SGRQ,curative effect is distinct,worthy of clinical popularization and application.

Comparative study of nitric oxide production induced by selective estrogen receptors alpha and beta agonists in rats / Comparação da produção de óxido nítrico mediada por agonistas seletivos de receptores estrogênicos alfa e beta em ratos

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) is a potent vasodilator and estrogen-mediated vasodilation that increases NO production. The association of the vascular endothelium, gender and vasodilation induced by estrogen is due to the activation of two estrogen receptors, alpha (ERa) and beta (ERb). The aim of this study was to compare NO production stimulating receptors ERa and ERb with the use of selective agonists in thoracic aortas of rats. METHODS: Aortic rings were either treated with 17 ?-estradiol (17-BE2); acetylcholine (Ach); 4,4',4-[4-propil-(1H)-pirazol-1,3,5-triyl]tris-phenol (PPT), and 2,3-Bis(4-hydroxyphenyl)-propionitrile (DPN), or left untreated, and the concentration of NO was determined by spectrophotometry method. RESULTS: The females presented a higher basal concentration of nitrite than males. PPT determined increased production of nitrite in both females and males, compared to17-beta-estradiol (17-BE2). In males, the production of nitrite induced by DPN and PPT was higher than that induced by 17-BE2. The stimulation with 17-BE2 increased the production of nitrite in females compared to males. Regardless the gender, the stimulation of aortic rings by PPT caused a greater production of nitrite compared to that induced by 17-BE2. Interestingly, the stimulation of aortic rings from males with DPN provided an increase in the nitrite production compared to the levels induced by 17-BE2 incubation. CONCLUSION: The stimulation of estrogen receptor (ER) by PPT provides greater production of nitrite than 17-BE2 regardless of gender; in males, the stimulation of ER by DPN provides bigger production of nitrite than 17-BE2; the basal production of nitrite is higher in females compared to males.

JUSTIFICATIVA E OBJETIVOS: O óxido nítrico (NO) é um potente vasodilatador e o estrógeno promove vasodilatação aumentando a produção de NO. A associação entre endotélio vascular, gênero e vasodilatação induzida pelo estrógeno, é pela ativação de receptores estrogênicos, alfa (ERa) e (beta) ERb.O objetivo deste estudo foi comparar a produção de NO estimulando receptores estrogênicos, ERa e ERb, por agonistas seletivos em aorta torácica de ratos. MÉTODOS: Anéis aórticos foram tratados com 17 ?-estradiol (17-BE2), acetilcolina (Ach), 4,4',4-[4-propil-(1H)-pirazol-1,3,5-triyl]tris-fenol (PPT) e 2,3-Bis(4-hidroxifenil)-propionitrila (DPN) ou não tratados e a determinação de NO foi feita por método espectrofotométrico. RESULTADOS: As fêmeas apresentaram produção constitutiva basal de nitrito mais elevada do que os machos. O PPT causou elevação na produção de nitrito em ambos os sexos, em relação ao observado com 17-beta estradiol (17-BE2). Nos machos, PPT e DPN, aumentaram a produção de nitrito comparada àquela induzida por 17-BE2.A estimulação com 17-BE2 causou maior produção de nitrito em fêmeas que em machos. A incubação com PPT determinou maior produção de nitrito comparada àquela induzida por 17-BE2, independente do gênero. Interessantemente, em machos,a estimulação das artérias com DPN acarretou em elevação na produção de nitrito comparada ao efeito causado por 17-BE2.CONCLUSÃO: A estimulação de receptor estrogênico (ER) pelo PPT determina maior produção de nitrito do que 17-BE2 independente do gênero; a estimulação de ER pelo DPN determina maior produção de nitrito do que 17-BE2 em machos; a produção basal de nitrito é mais elevada em fêmeas comparada aos machos.

Há evidências favorecendo o uso de betabloqueadores e dobutamina na insuficiência cardíaca aguda? / Is there evidence favoring the use of beta-blockers and dobutamine in acute heart failure?

Diversos estudos relataram os benefícios dos betabloqueadores (BB) para pacientes com insuficiência cardíaca sistólica. No entanto, muitos pacientes hospitalizados em decorrência de insuficiência cardíaca aguda já estão usando os BB e requerem dobutaminas para hipotensão arterial e baixo débito cardíaco. Portanto, deve-se tomar uma decisão a respeito de se o BB deve ser mantido ou até mesmo iniciado nesses casos. O objetivo deste estudo foi determinar se há provas que sustentem a segurança e a eficácia dos BB junto com a dobutamina para pacientes com insuficiência cardíaca aguda descompensada (ICAD). Foi realizada uma pesquisa na literatura de língua inglesa nas bases de dados MEDLINE, ISI Web of Science, Biblioteca Virtual em Saúde, Cochrane Library e o Portal de Revistas Científicas do Capes para identificar estudos relacionados. Literatura adicional foi obtida mediante a análise das respectivas referências encontradas nos artigos identificados. Os resultados esperados incluíram informações sobre o prognóstico (intra-hospitalar e na mortalidade no acompanhamento, número de dias de internação e reinternação), eficácia e segurança (agravamento dos sintomas, choque, intolerância) do uso concomitante desses medicamentos em pacientes hospitalizados com ICAD e baixo débito cardíaco. Esta análise incluiu nove estudos. No entanto, não foram encontrados ensaios clínicos randomizados sobre o assunto. A maioria dos estudos inclui baixo número de pacientes, e não foram encontrados estudos que abordem a segurança do uso concomitante desses medicamentos. Os dados resultantes sugerem que uma cuidadosa revisão da literatura não forneceu evidências para o uso sistemático de BB em pacientes com síndrome de baixo débito cardíaco que necessitam de suporte inotrópico com dobutamina.

Several studies have reported the benefits of beta-blockers (BB) for patients presenting with systolic heart failure. however, many patients hospitalized as a result of acute heart failure are already using BB and require dobutamine for arterial hypotension and low cardiac output. Therefore, a decision must be made regarding whether BB should be maintained or even started in such cases. The aim of this study was to establish whether there is evidence supporting the safety andyeffectiveness of BB together with dobutamine for patients presenting with acute decompensated heart failure (ADHF). We conducted a search of the English-language literature in the databases MEDLINE, ISI Web of Science, Virtual Health Library, Cochrane Library and the CAPES Portal of Scientific Journals to identify related studies. Additional literature was obtained through the review of relevant references in the identified articles. The expected outcomes included information on the prognosis (in-hospital and on follow-up mortality, number of days of hospitalization and readmission),yeffectiveness and safety (worsening of symptoms, shock, intolerance) of the concomitant use of these drugs in hospitalized patients with ADHF and low cardiac output. This review included nine studies. however, no randomized clinical trials on this subject were found. Most studies include a low number of patients, and no studies addressing the safety of the concomitant use of these drugs were found. The resulting data suggest that a careful literature review did not supply evidence for the systematic use of BB in patients with low cardiac output syndrome who require dobutamine for inotropic support.

Combination therapy with single inhaler of long-acting β2-adrenoceptor agonists/inlaled corticosteroids compared with higher dose of inhaled corticosteroids in asthmatic patients / 中国基层医药

Objective To provide a quantitative summary estimate on the efficacy and safety measures of the combination therapy.Methods We searched databases(Medline and Embase)from January 1997 to December 2009 using‘ Fluticasone and salmerterol' or‘ Seretide' or‘ Advair' or‘ budesonide/formoterol' or‘ Symbicort Turbuhaler' in combination with ‘ Randomised controlled trial'.The databases of GlaxoSmithKline Clinical Trial Register and Cochrane Controlled Trials Register,or relevant original studies and review articles were approached for additional studies or details of all relevant studies.Results Morning peak expiratory flow(PEF),evening PEF and clinic FEV1 were 17.59L/min,14.95L/min and 0.08L/min higher with combination therpy than with increasing ICSs by two fold or more at endpoint,respectively.The risk of asthmatic exacerbation was reduced in the combination therpy group compared with the increased doses of ICS groups,with OR being 0.61(95 ％ CI 0.53 ～ 0.70,P ＜ 0.01).Significantly increases in the percent of symptom-free days 6.30(95％ CI 3.52 ～9.10),asthma-control days 9.49(95％ CI 4.74 ～14.25)and relieve-free days 6.59(95％ CI 6.10 ～ 7.08)were observed in patients treated with ICS/LABA compared with increased doses of ICSs at endpoint.Reduction in reliever medication use(inhalations/day)0.22(95 ％ CI 0.11 ～0.33)with significant difference was also observed at endpoint.Conclusion Combination products of ICS/LABA were more effective than a high dose of ICSs in improving lung function,reducing asthmatic exacerbation and use of reliever medication and improving control of asthma.

Aceptación del uso de aerocámaras / Acceptance of the use of holding chambers

Objetivo: Obtener una aproximación objetiva de la aceptabilidad de los aerosoles de salbutamol por las madres de los pacientes con sibilancias o asma. Metodología: Estudio descriptivo, observacional, realizado con encuestas aplicadas a madres de pacientes que están usando o han usado salbutamol como tratamiento broncodilatador. La encuesta se realizó desde el 1 de julio al 31 de agosto de 2010 a pacientes que acudieron al consultorio. Se analizaron los datos con el programa EPI- Info 2002. Resultados: Respondieron a la encuesta 102 madres de pacientes, el rango de edad de los niños fue: 0 a 11 años y la media de 3 años. Usó salbutamol en aerosol: 79,4% de los pacientes, jarabe: 65,7 % y nebulizaciones: 72,5%. Cuál le parece mejor: 72% salbutamol en aerosol en aerocámara; 19% en jarabe y el 9% en las nebulizaciones. Alguien le dijo que el aerosol produce adicción: 40,6% y le dijo un vecino en el 50%, un familiar 12,5%, una enfermera 10,4%, un pediatra 8,3% y un médico general 15,7%. Cree que produce adicción: Sí 12,9%. Recomendaría el uso de aerocámaras el 76,8% de las encuestadas. Conclusión: Hay un porcentaje mayor de encuestadas que acepta la utilización del aerosol como mejor forma de usar el salbutamol, sin embargo hay un 28 % que no acepta los aerosoles. Un respetable número de pacientes (34,4%) refieren ser desaconsejadas en el uso de la aerosolterapia por profesionales sanitarios. El jarabe goza de una cierta aceptación, argumentando mayor aprobación por el niño y mayor efectividad. Pesa mucho la creencia popular en la forma de administrar el salbutamol, lo cual resalta la disrelación entre la evidencia científica y la aceptación del paciente o de su madre y del profesional sanitario que aplica el tratamiento broncodilatador con salbutamol.

Introduction: The latest recommendations of scientific publications, the Global Initiative for Asthma (GINA), and European consensus all agree that the best way to administer salbutamol is as an aerosol due to its effectiveness, more direct action, greater convenience, and reduced side effects. However, not all patients, including some health professionals, accept their use due to cultural reasons, beliefs, or due to being out of date or reluctant to try innovations. What is recommended by science is not always accepted and incorporated into daily practice by patients or healthcare professionals. Objective: To obtain an objective estimate of the acceptability of aerosol salbutamol by the mothers of patients with wheezing or asthma. Methodology: A descriptive observational study carried out by surveying mothers of patients who are using or who have used salbutamol as a bronchodilator. The survey was carried out between July 1 and August 31, 2010 on patients attending the clinic. Results: The survey was completed by 102 mothers of patients, with children ranging from age 0 to 11 years with a mean age of 3 years. Salbutamol was used as aerosol by 79.4% of patients, as syrup by 65.7%, and in a mist by 72.5%. Asked which seems better, 72% cited salbutamol aerosol with a holding chamber, 19% syrup, and 9% the mists. Asked if someone had told them the aerosol causes addiction, 40.6% said someone had, with 50% citing a neighbor, 12.5% a relative, 10.4% a nurse, 8.3% a pediatrician, and 15.7% a general practitioner. Asked if they believe it causes addiction, 12.9% said they did, and 76.8% said they would recommend the use of holding chambers. Conclusion: A majority of respondents accepts the use of aerosol as the best way to administer salbutamol, while 28% do not accept aerosols. A notable number of mothers (34.4%) reported being discouraged from the use of aerosol by health professionals...

Predictors of Pulmonary Function Response to Treatment with Salmeterol/fluticasone in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV1, FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV1 change after 3 months of treatment included wheezing history, pre-bronchodilator FEV1, post-bronchodilator FEV1 change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD.

Tratamiento farmacológico para el control del asma en el niño

El presente artículo presenta las recomendaciones de un grupo de expertos venezolanos reunidos en Caracas en Octubre de 2009 por la Sociedad Venezolana de Puericultura y Pediatría en relación al tratamiento farmacológico del asma infantil. Se presentan los objetivos del tratamiento, los medicamentos recomendados, la terapia inicial y de mantenimiento y el tipo de dispositivo para la administración de drogas por vía inhalatoria, de acuerdo a la edad del paciente.

This article presents the recommendations made by a group of Venezuelan experts during a consensus meeting held in Caracas in October, 2009, under the auspices of the Venezuelan Society of Pediatrics, on the pharmacological treatment of childhood asthma. Goals of treatment, recommended medications, initial and maintenance therapy, and devices utilized for delivery of inhaled drugs according to patient’s age are presented.

Ractopamina em dietas para suínos machos imunocastrados, castrados e fêmeas / Ractopamine in diets for immunocastrated, barrows and females

O objetivo do trabalho foi avaliar o desempenho e as características quantitativas de carcaça de suínos machos imunocastrados, castrados e fêmeas, na fase de terminação, alimentados com dietas contendo 10ppm de ractopamina. Foram utilizados 120 animais, com peso inicial de 99,1±5,3kg, distribuídos em delineamento de blocos ao acaso, em esquema fatorial 2 x 3 (dois níveis de ractopamina, 0 e 10ppm e três sexos), cinco repetições com quatro animais cada. A inclusão de 10ppm de ractopamina na dieta melhorou (P<0,05) a conversão alimentar dos suínos, independentemente do sexo. A inclusão de ractopamina prejudicou (P<0,05) o ganho de peso dos machos imunocastrados e aumentou (P<0,05) o ganho de peso dos machos castrados e das fêmeas, sem, no entanto, afetar (P>0,05) as características quantitativas de carcaça dos suínos. O sexo foi determinante para o desempenho e as características quantitativas de carcaça; as fêmeas apresentaram rendimento de carcaça quente superior (P<0,05) aos machos imunocastrados, que apresentaram rendimento superior (P<0,05) aos machos castrados. Os machos imunocastrados e as fêmeas apresentaram maior (P<0,05) percentual de carne magra em relação aos machos castrados. Os resultados desta pesquisa evidenciam a necessidade de estudos visando à adequação dos níveis nutricionais das dietas contendo ractopamina para suínos imunocastrados.

The objective of this study was to evaluate the performance and the quantitative characteristics of carcass of immunocastrated, barrows and females in the finishing phase fed with diets containing 10ppm of ractopamine. One hundred and twenty animals were used, with initial weight of 99.1±5.3kg, distributed in a randomized blocks factorial design in 2 x 3 (two ractopamine levels, 0 and 10ppm and three sex), five replicates of four animals each. The inclusion of 10ppm of ractopamine in the diet improved (P<0.05) feed conversion in pigs, independent of sex. The inclusion of ractopamine damaged (P<0.05) the weight gain of the immunocastrated and increased (P<0.05) the weight gain of the barrows and the females, without, however, affect (P>0.05) quantitative carcass characteristics of pigs. The sex was determining factor in performance and carcass quantitative traits and the females had higher (P<0.05) hot carcass yield for immunocastrated male and they have yield above (P<0.05) the barrows. Immunocastrated males and females had higher (P<0.05) percentage of lean meat for barrows. The results of this study highlight the need for studies to adjust the nutrient levels of diets containing ractopamine to immunocastrated pigs.

Terapia de resgate com amiodarona em crianças com grave disfunção ventricular esquerda causada por veneno de escorpião / Antiadrenergic rescue therapy with amiodarone in children with severe left ventricular dysfunction secondary to scorpion envenomation / Terapia de rescate con amiodarona en niños con severa disfunción ventricular izquierda ocasionada por veneno de escorpión

Fundamentos: As crianças picadas por escorpião, pressintam ativação maciça do sistema nervoso simpática com vários graus de disfunção sistólica ventricular esquerda. Oobjetivo: Testar um protocolo de resgate em crianças com grave disfunção ventricular esquerda causada por picada de escorpião. Métodos: Quatro crianças após serem picadas por escorpião foram submetidas a: Encubação endotraqueal e suporte respiratório, eletrocardiograma, radiografia de tórax, ecocardiograma e determinação sérica da norepinefrina e troponina I. As análises foram repetidas após 12, 24 e 48 horas. As seguintes medicações intravenosas foram administradas: dobutamina 4-6 μg/kg/min; amiodarona 3 mg/kg durante duas horas, com dose de manutenção de 5 mg/kg/dia; e furosemida 0,5 mg/kg. Amiodarona, dobutamina e furosemida foram administradas durante as primeiras 48 horas. Bloqueadores beta-adrenérgicos e inibidores da enzima conversora da angiotensina foram administrados até 48 após a internação, uma vez que o estado clínico havia melhorado e a fração de ejeção ventricular esquerda encontrava-se acima de 0,35 por cento. Resultados: Na admissão, a dosagem da norepinefrina foi 1.727,50± 794,96 pg/ml, a de troponina I 24,53 ± 14,09 ng/ml e a fração de ejeção do ventrículo esquerdo foi 0,20 ± 0,056. Após 12 horas, os níveis séricos de norepinefrina e de troponina I diminuíram para a metade dos valores iniciais e a fração de ejeção aumentou para 0,32 ± 0,059. Durante as 24 e 48 horas subseqüentes, a fração de ejeção elevou-se para 0,46 ± 0,045 (p<0,01) e a norepinefrina e de troponina I diminuíram para 526,75 ± 273,73 (p< 0,02) e 2,20 ± 2,36 (p<0,02) respectivamente. Conclusão: É bem provável que a amiodarona, ao agir como neuromodulador, seja responsável pela redução rápida e progressiva dos níveis séricos de norepinefrina.

Background: Children with scorpion envenomation have massive sympathetic activation and variable degrees of left ventricular systolic dysfunction. Objective: To evaluate a rescue protocol for children with severe left ventricular dysfunction secondary to scorpion envenomation. Methods: Four children, after scorpion envenomation, were subjected to a rescue protocol for acute left ventricular dysfunction: Endotracheal intubation and respiratory assistance, electrocardiograms, chest x-Ray, echocardiograms and blood samples for norepinephrine and troponin I serum levels. Samples and echocardiograms were repeated at 12, 24 and 48 hours. Intravenous medications: Dobutamine: 4-6 μg/kg/min. Amiodarone: 3 mg/kg during a 2 hour period. Maintenance: 5 mg/kg/day. Furosemide: 0.5 mg/kg/dose. Diuretics were given when the systemic blood pressure was above percentile fifty. Amiodarone, Dobutamine and Furosemide were administered during the first 48 hours. Beta-adrenergic blockers and angiotensin converting enzyme were given, at 48 hours after admission, once the left ventricular Ejection fraction > 0.35 and the clinical status had improved. Results: On admission, norepinephrine was 1,727.50 ±794.96 pg/ml, troponin I 24.53 ± 14.09 ng/ml and left ventricular ejection fraction 0.20 ± 0.056. At twelve hours, norepinephrine and troponin I serum levels were down to half of the initial values and the ejection fraction increased to 0.32 ± 0.059. During the next 24 and 48 hours, the ejection fraction rose to 0.46 ± 0.045, (p<0.01) and norepinephrine and troponin diminished to 526.75 ± 273.73 (p < 0.02) and 2.20 ± 2.36 (p<0.02) respectively. Conclusion: Amiodarone, by acting as a neuromodulator, is very likely responsible for the early and progressive decrease of serum norepinephrine.

Fundamento: Los niños con picaduras de escorpión sufren activación masiva del sistema nervioso simpático con varios grados de disfunción sistólica ventricular izquierda. Objetivo: Probar un protocolo de rescate en niños con disfunción ventricular severa izquierda ocasionada por picadura de escorpión. Métodos: Cuatro niños tras un escorpión picarlas se sometieron a: incubación endotraqueal y soporte respiratorio, electrocardiograma, radiografía de tórax, ecocardiograma y determinación sérica de la norepinefrina y troponina I. Los análisis se repitieron tras 12, 24 y 48 horas. Las siguientes medicaciones intravenosas se administraron: dobutamina 4-6 mcg/kg/min; amiodarona 3 mg/kg durante dos horas, con dosis de mantenimiento de 5 mg/kg/día; y furosemida 0.5 mg/kg. Amiodarona, dobutamina y furosemida se administraron durante las primeras 48 horas. Bloqueante betaadrenergicos e inhibidores de la enzima convertidora de la angiotensina se administraron hasta 48 tras la internación, una vez que el estado clínico había mejorado y la fracción de eyección ventricular izquierda se hallaba superior a un 0,35 por ciento. Resultados: Al ingreso, la dosificación de la norepinefrina fue 1727,50± 794,96 pg/ml, la de troponina I 24,53 ± 14,09 ng/ml y la fracción de eyección del ventrículo izquierdo fue 0,20 ± 0,056. Tras 12 horas, los niveles séricos de norepinefrina y de troponina I disminuyeron para la mitad de los valores iniciales y la fracción de eyección aumentó para 0,32 ± 0,059. Durante las 24 y 48 horas subsiguientes, la fracción de eyección se elevó para 0,46 ± 0,045 (p<0,01) y la norepinefrina y de troponina I se redujeron para 526,75 ± 273,73 (p< 0,02) y 2,20 ± 2,36 (p<0,02) respectivamente. Conclusión: Es bien probable que la amiodarona, al actuar como neuromodulador, sea responsable de la reducción rápida y progresiva de los niveles séricos de norepinefrina.

Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder

In the present review article, we present an overview of beta-adrenoceptor (beta-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the beta3-AR, the in vivo effect of beta3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of beta3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of beta3-AR mRNA in human bladder, constituting 97% of total beta-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the beta3-ARs. Moreover, the presence of beta1-, beta2-, and beta3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial beta-ARs results in the release of nitric oxide and an unknown substance inhibiting detrusor contractions from the urothelium. Intravenous application of CL316,243, a selective beta3-AR agonist, in rats selectively inhibits mechano-sensitive Adelta-fiber activity of the primary bladder afferents. A number of selective beta3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the beta3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The beta3-AR agonists act to facilitate bladder storage function probably through at least two mechanisms: first, direct inhibition of the detrusor, and second, inhibition of bladder afferent neurotransduction.

Successful pharmacotherapy for asthma exacerbation in an asthmatic patient with long QT syndrome / 대한내과학회지

beta -Blockers can cause bronchospasm in asthma. beta 2-agonists prolong the QT interval and alter the clinical course of long QT syndrome (LQTS). We report a case of asthma exacerbation treated cautiously with beta 2-agonists in a patient with LQTS, while LQTS was controlled with low-dose beta 1-antagonists. A 31-year-old woman with LQTS visited the emergency room for asthma exacerbation. FEV1 was 0.5 L (18%) and QTc interval was 520 ms. Low doses of salbutamol or salmeterol were used and gradually increased, while monitoring the QT interval. Simultaneously, a low dose of atenolol was maintained. FEV1 was increased to 2.2 L (83%) without further QT prolongation or cardiac events. The case suggests that lower doses of beta 1-antagonists can be tried for cardiac diseases, even in the presence of asthma exacerbations. beta 2-Agonists may be initiated at lower doses and, if tolerated, the dose can be increased in asthmatic patients with a risk for QT prolongation.

Effect observation of 115 children with asthma treated with salmeterol/flutieasone propionate inhalation / 中国基层医药

Objective To observe the effect of salmeterol/flutieasone propionate on children with asthma. Methods Salmeterol/flutieasone propionate inhalation of different dosages were given according to different illness condition of asthma. Investigate the effects of 180 days inhalation of SM/FP among children. Results After 180 days' treatment, the PEFam and PEFpm of those children of asthma were significantly increased. The lung function has a perceptible improvement. In addition, the daytime and noctural symptom scores and asthma symptom were improved. Moreover, the shore-acting β2 agonist was used with decreasing frequency. The effects of SM/FP inhalation were marvelous after 1 week of treatment and should make a long persisting time alter six months of treatment. Conclusion SM/FP is an effective medicine for children with asthma and should be make more widespread.

Salmeterol/fluticasone combined with N-acetylcysteine in treatment of airway inflammation of stable chronic obstructive pulmonary disease / 中华全科医师杂志

Objective To evaluate salmeterol/fluficasone combined with N-acetylcysteine in treatment of stable chronic obstructive pulmonary disease (COPD). Methods Sixty patients with stable COPD were randomized into treatment group(n = 30) and control group(n = 30). Patients in control group were given salmeterol/fluticasone twice per day ; while patients in treatment group in addition to salmeterol/ fluticasone, also took N-acetylcysteine 0.6 g three times per day. The course of treatment lasted for four weeks. Pulmonary function was measured in all patients; interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), superoxide dismntase (SOD) and malondialdehyde (MDA) in blood serum and induced sputum were determined. The white cell count and classification in sputum smear was examined and the quality of life (QOL) of patients was evaluated. Results FEV1, FEV1 %, QOL evaluation, IL-8, TNF-α, white cell count and the percentage of neutrophil granulocytes in induced sputum after treatment were significantly improved compared with those before treatment in control group (P <0.05 or P <0.01). FEV1, FEV1%, QOL evaluation, SOD and MDA in blood serum, IL-8, TNF-α, SOD and MDA, total white cell count, the percentage of neutrophil granulocytes and macrophage in induced sputum after treatment were significantly improved in treatment group (P <0. 05 or P <0.01). The differences in SOD and MDA in blood serum and the percentage of neutrophil granulocytes in induced sputum smear between treatment group and control group were staffsticaUy significant (93 ± 8) × 10-6 U/L, (4. 0 ± 1.0) × 10-3 mmol/L and 0. 5 ± 0. 3 vs (85 ± 10) ×10-6U/L,(4.2±1.1) ×10-3mmol/Land0.6±0.2; allP<0.05. Conclusion Combination of salmeterol/fluticasone and N-acetylcysteine has better therapeutic results in treatment of airway inflammation of stable COPD.