Función pulmonar: función pulmonar en fibrosis quística / Lung function in cystic fibrosis

La fibrosis quística (FQ) es una enfermedad hereditaria autosómica recesiva, causada por la mutación del gen que codifica la proteína CFTR (cystic fibrosis transmembrane conductance regulator), afecta varios órganos, pero la enfermedad pulmonar es la primera causa de morbimortalidad. El diagnóstico a través del screening neonatal (SNN) y los nuevos tratamientos moduladores del CFTR han aumentado el interés por pesquisar y monitorizar la función pulmonar antes del inicio de los síntomas para lograr un tratamiento adecuado y oportuno con una mejor calidad de vida. Existen numerosas formas de medir la función pulmonar según la edad, colaboración y recursos disponibles. En este artículo se resumen las pruebas clásicas y las más novedosas, como técnicas de imágenes, en la búsqueda de marcadores precoces de daño pulmonar, herramientas con los que cada centro de fibrosis quística debiera contar en la era de tratamientos moduladores del CFTR, que están cambiando el pronóstico de los pacientes con esta enfermedad.

Cystic fibrosis (CF) is an autosomal recessive inherited disease, caused by mutation of the gene encoding the CFTR protein (cystic fibrosis transmembrane conductance regulator), affects several organs, but lung disease is the first cause of morbidity and mortality. Diagnosis through neonatal screening (NNS) and new CFTR modulating treatments have increased interest in screening and monitoring lung function before the onset of symptoms to achieve adequate and timely treatment with a better quality of life. There are numerous ways to measure lung function based on age, collaboration, and available resources. This article summarizes the classic and the most innovative tests, which have emerged from imaging techniques in the search for early markers of lung damage, tools that each cystic fibrosis center should have in the era of CFTR modulating treatments, which are changing the prognosis of patients with this disease.

Tracheal relaxation of five medicinal plants used in Mexico for the treatment of several diseases

OBJECTIVE@#To assess the relaxant effect of several organic extracts obtained from Agastache mexicana (A. mexicana), Cochlospermum vitifolium (C. vitifolium), Cordia morelosana (C. morelosana), Lepechinia caulescens (L. caulescens) and Talauma mexicana (T. mexicana) used in Mexican traditional medicine for the treatment of several diseases.@*METHODS@#Extracts were obtained by maceration at room temperature using hexane, dichloromethane and methanol for each plant material. The organic extracts were evaluated ex vivo to determine their relaxant activity on the contractions induced by carbachol (cholinergic receptor agonist, 1 μ mol/L) in isolated rat tracheal rings.@*RESULTS@#A total of 15 extracts were evaluated (three for each species). All test samples showed significant relaxant effect, in a concentration-dependent manner, on the contractions induced by 1 μ mol/L carbachol, with exception of extracts from C. morelosana. Active extracts were less potent than theophylline [phosphodiesterase inhibitor, EC50: (28.79±0.82) μg/mL] that was used as positive control. Concentration-response curves revealed that the extracts with more significant effects were dichloromethanic extracts of T. mexicana [Emax: (103.03±3.32)% and EC50: (159.39±3.72) μg/mL) and C. vitifolium [Emax: (106.58±2.42)% and EC50: (219.54±7.61) μg/mL]. Finally, hexanic and dichloromethanic extracts from A. mexicana were fully effective but less potent than T. mexicana and C. vitifolium.@*CONCLUSIONS@#Less polar extracts obtained from A. mexicana, T. mexicana and C. vitifolium exhibited greater relaxant effect on tracheal rat rings, which allows us to suggest them as sources for the isolation of bioactive molecules with potential therapeutic value in the treatment of asthma.

Eventos cardiorrespiratórios adversos após vacinação primária de recém-nascidos de muito baixo peso / Adverse cardiorespiratory events following primary vaccination of very low birth weight infants

OBJETIVO: Examinar a relação entre vacinação primária de recém-nascidos pré-termo e razões de prevalência de fatores associados a eventos cardiorrespiratórios indesejados, seguindo recomendações do Comitê Consultivo de Práticas de Imunização do Centers for Disease Control and Prevention para imunização de recém-nascidos pré-termo aos 2 meses de idade cronológica. MÉTODOS: Estudo retrospectivo de 2 anos de recém-nascidos de muito baixo peso que receberam vacinação primária. Foram registrados eventos cardiorrespiratórios maiores, como apneia, bradicardia, dessaturação de SpO2, e eventos menores, como instabilidade de temperatura, comportamento inapropriado e reações locais. Foi calculada a razão de prevalência com intervalo de confiança de 95% para fatores associados entre recém-nascidos com e sem eventos cardiorrespiratórios. RESULTADOS: Foram estudados 80 recém-nascidos (mediana de peso ao nascer [:intervalo]: de 970 g [:428-1.490]:), idade gestacional de 27,4 semanas (23,3-33). Ocorreram reações adversas em 35 (44%): eventos menores em 19 (24%) pacientes, eventos maiores em 28 (35%). Recém-nascidos com eventos maiores tiveram idade gestacional significativamente menor (p = 0,008) e incidência mais alta de displasia broncopulmonar (71% versus 48%; p < 0,05). Em recém-nascidos de muito baixo peso com eventos maiores, o número de casos de dessaturação de O2 antes da vacinação foi 3,40 (1,41-8,23) vezes maior, e o tratamento com metilxantina para síndrome de apneia e bradicardia foi 8,05 (2,50-25,89) vezes maior em comparação com recém-nascidos sem eventos maiores. CONCLUSÃO: Eventos cardiorrespiratórios maiores ocorreram em mais de 1/3 de todos os recém-nascidos de muito baixo peso após a vacinação. Os fatores associados foram baixa idade gestacional, displasia broncopulmonar, tratamento com metilxantina e dessaturação de O2 persistente antes da vacinação. A vacinação primária de recém-nascidos de muito baixo peso deve ser realizada sob monitoramento contínuo de parâmetros vitais.

OBJECTIVE: To examine the relationship between primary vaccination of preterm infants and prevalence ratios of associated factors for unwanted cardiorespiratory events, following the recommendation of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for immunization of preterm infants at 2 months of chronological age. METHODS: Two-year retrospective study of very low birth weight infants receiving their primary vaccination. Major cardiorespiratory events, such as apnea, bradycardia, SpO2 desaturation, and minor adverse events, such as temperature instability, poor handling and local reactions, were recorded. Prevalence ratio with 95% confidence interval for associated factors between infants with and without cardiorespiratory events was calculated. RESULTS: Eighty neonates were studied (median [:range]: birth weight 970 g [:428-1,490]:), gestational age of 27.4 weeks (23.3-33). Adverse reactions occurred in 35 (44%): minor events in 19 (24%) patients, major events in 28 (35%). Infants with major events had significantly lower gestational age (p = 0.008) and a higher incidence of bronchopulmonary dysplasia (71% vs. 48%; p < 0.05). In very low birth weight infants with major events, O2 desaturations before vaccination were 3.40 (1.41-8.23) times higher and treatment with methylxanthines for apnea and bradycardia syndrome was 8.05 (2.50-25.89) times higher compared to infants without major events. CONCLUSION: Major cardiorespiratory events occurred in over 1/3 of all very low birth weight infants after vaccination. Associated factors were low gestational age, bronchopulmonary dysplasia, methylxanthine treatment, and persisting O2 desaturations before vaccination. Primary vaccination of very low birth weight infants should be performed under continuous monitoring of vital parameters.

Effect of doxapram on the respiratory rhythmical discharge activity in the brainstem slice of neonatal rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of doxapram on the respiratory rhythmical discharge activity (RRDA) in the brainstem slices of neonatal rats.</p><p><b>METHODS</b>Thirty neonatal SD rats (of either sex, 0-3 days old) were randomly divided into 6 equal groups (groups I-VI), and the brainstem slices which contained the medial region of the nucleus retrofacialis (mNRF) were prepared. All the slices were perfused with modified Kreb's solution (MKS), and in group I (control group), the slices were perfused with MKS only; in groups II to IV, the slices were perfused with doxapram in MKS continuously at the concentrations of 2, 5, and 10 micromol/L, respectively; in groups V and VI, the slices were perfused with 20 micromol/L propofol and 20 micromol/L propofol plus 5 micromol/L doxapram, respectively. The RRDA in the hypoglossal nerve was recorded by suction electrode. The discharge time course of the inspiratory (TI), expiratory (TE), respiratory cycle (RC) and integral amplitude of the inspiratory discharge (IA) were recorded at 1, 3, 5, 10, 15, and 30 min after the application of the drugs.</p><p><b>RESULTS</b>The hypoglossal nerve in groups I, II and VI showed no significant changes of RRDA in the entire course of the experiment (P>0.05). In groups III and IV, the TI, IA increased and TE decreased significantly 5 min after doxapram application (P<0.05), and the RC was shortened only at 10 min. In group V, the TI and IA decreased and the RC and TE increased significantly after the drug application (P<0.05).</p><p><b>CONCLUSION</b>Doxapram (>5 micromol/L ) can directly stimulate the RRDA and prevent propofol-induced inhibitory effects in the brainstem slice of neonatal rats, and the effects are mediated by its actions upon the inspiratory neurons in the mNRF.</p>

Ventilatory strategies and adjunctive therapy in ARDS.

Acute respiratory distress syndrome, a diagnosis based on physiologic and radiological criteria, occurs commonly in critical care setting. A major challenge in evaluating therapies that may improve survival in ARDS is that it is not a single disease entity but, rather, numerous different diseases that result in endothelial injury, where the most obvious manifestation is within the lung resulting in pulmonary oedema. It has been shown that poor ventilatory technique that is injurious to the lungs can propagate systemic inflammatory response and adversely affect the mortality. The current data suggest that high tidal volumes with high plateau pressures are deleterious and a strategy of ventilation with lower tidal volumes and lower plateau pressure is associated with lower mortality. There may be a role for recruitment manoeuvres as well. Other forms of respiratory support still require further research. The present understanding of optimal ventilatory management and other adjunctive therapies are reviewed.

Clinically reported drug interactions with Erythromycin-an update

Erythromycin, the prototypical macrolide, has been widely used since 1950s in the management of infections. It is often combined with other drug therapies, thus creating a potential for pharmacokinetic interactions. It can both inhibit drug metabolism in the liver by complex formation and inactivation of microsomal drug oxidizing enzymes, and also by interfering with microorganisms of the enteric flora through its antibiotic effects. Methodology: Using MEDLINE search [1975-April 2002] all available clinical studies, review articles, and case reports were reviewed to provide an unbiased account of drug interactions with erythromycin. A number of reports and controlled studies have incriminated erythromycin as a potential source of clinically severe drug interactions. For example torsades de pointes associated with QT prolongation occurred with terfenadine, astemizole, and cisapride. Cases of rhabdomyolysis have been reported on concomitant use of statins. Symptomatic hypotension occurred with calcium channel blockers or sildenafil. Excessive sedation occurred from concurrent use of benzodiazepines, buspirone and zopiclone. Ataxia occurred with carbamazepine and valproate, and ergotism with ergotamine. Serotonin syndrome was reported with the use of sertraline and psychosis with bromocriptine. Interactions with cyclosporine, tacrolimus, theophylline, and warfarin are also clinically important. These interactions are due to decreased clearance of these drugs. Increase in digoxin concentration was mainly due to increase in bioavailability. Erythromycin should, therefore, be not administered with some of these drugs or their dosage schedule readjusted. Conclusions: In most cases, the extent of drug interaction varies widely among individuals; this is likely dependent on interindividual differences in CYP3A4 tissue content, preexisting medical conditions and possibly, age. Interactions may occur under single dose conditions or only at steady state. The pharmacodynamic consequences may or may not closely follow pharmacokinetic changes. Drug interactions may be most important when patients are stabilized on the affected drug and erythromycin is then administered

Perfil das intoxicaçöes por medicamentos utilizados no tratamento das rinites na cidade de Säo Paulo / Intoxication by medicines for treatment of rhinitis in Säo Paulo

0s autores fazem revisäo da literatura sobre a farmacologia dos medicamentos usados no tratamento das rinites e analisam os casos de intoxicaçöes pelos mesmos (antialérgicos, descongestionantes, vasoconstritores nasais, antígenos respiratórios) notificados ao Centro de Controle de Intoxicaçöes (CCI-Jabaquara) do Hospital Municipal Dr. Arthur Ribeiro de Saboya e ao Centro de Assistência Toxicológica (CEATOX) na cidade de Säo Paulo durante o segundo semestre de 1996. Foram encontrados 177 casos de intoxicaçöes por esses fármacos, correspondendo a 2,66 por cento do total de intoxicaçöes notificadas aos dois serviços naquele período. Análise da distribuiçäo dos casos segundo sexo e idade mostrou predomínio de intoxicaçöes na populaçäo pediátrica (94 por cento das intoxicaçöes por antígenos respiratórios) e no sexo feminino (75 por cento das intoxicaçöes por antialérgiocos). Estudo das circunstâncias das intoxicaçöes revelou prevalência da ingestäo acidental para todos os grupos de medicamentos. Säo propostas medidas para prevenir as intoxicaçöes na utilizaçäo de medicamentos para o tratamento das rinites

A case of acute coma & respiratory arrest in Wernicke's encephalopathy caused by malnutrition / 대한내과학회지

We shoud give attention to Wernicke's encephalopathy as a cause of sudden coma & respiratory arrest in patients, who are not usually suspected to develop the disorder and empirical treatment with thiamine in cases of coma of unknown cause is recommended. Respiratory stimulants, doxapram & aminophylline have an effect in assisting ventilatory weaning in patient with central hypoventilation as a complication of acute Wernicke's encephalopathy No previous reports where doxapram had been used to assist weaning from mechanical ventilation in adults were noted. Nor has newly developed central hypoventilation been identified as an impediment to weaning in literature to date in Korea. We reported a rare case of Wernicke's encephalopathy caused by poor oral intake & inadequate nutritional suppliment after car accident, showing acute coma & respiratory arrest and treated adequately by thiamine replacement & mechanical ventilation with respiratory stimulant.

Utilizaçäo de medicamentos por crianças atendidas em creches / Use of medicines by children attending nursery schools

Para identificar o padräo de utilizaçäo de medicamentos em crianças, foram acompanhadas 1.382 crianças matriculadas em 15 creches municipais de Säo Paulo, SP (Brasil), durante 2 meses; 512 crianças (37 por cento) utilizaram 1.409 medicamentos (média de 50,9 medicamentos/100 crianças/mês). Mais de 80 por cento das crianças menores de dois anos utilizaram um ou mais medicamentos, enquanto nas outras idades esse consumo foi sempre inferior a 45 por cento. Os fármacos mais utilizados foram os antiinfecciosos, medicamentos com açäo no aparelho respiratório, e analgésicos/antitérmicos utilizados, respectivamente, por 20 por cento, 19 por cento e 14 por cento das crianças estudadas. A maioria dos fármacos foi prescrita por médicos (93 por cento), porém, mais de 65 por cento dos antibióticos utilizados foram considerados inadequados; houve grande consumo de medicamentos de açäo questionável e de fármacos näo aprovados para utilizaçäo em crianças

Manejo de las infecciones respiratorias agudas a nivel del hogar : Informe Final / Treatment of acute respiratory infections: Finnal report

Documento que recoge una investigación cualitativa para estudiar la semántica, las percepciones populares y los comportamientos de salud respecto a las IRAs en dos aldeas del Departamento de Madriz, Nicaragua, situado en noroeste del país. Estas percepciones y comportamientos de las familias tienen un impacto significativo en el manejo doméstico de las IRAs y en la prevención, así como los tratamientos caseros y la búsqueda de atención con proveedores de saluds. Presenta también la situación actual de las IRA en Nicaragua, la metodología utilizada en la investigación y los resultados encontrados.

Comparative study of the analeptic-respirogenic agents doxapram HCl and nikethamide: I - the acute toxicity and analeptic activity in mice

LD50 determinations showed that both Doxapram HCl and Nikethamide fall in the category of moderate toxicity; but Doxapram HCl was the less toxic. Assessment of the arousal capacity of Doxapram HCl against sleeping doses of pentobarbitone sodium in mice demonstrated that the drug has a high therapeutic index. Assessment of the restorative activity of Doxapram HCl and of Nikethamide against toxic doses of pentobarbitone sodium as percentage survival in mice, demonstrated the higher potency of Doxapram HCl

Comparative study of the analeptic-respirogenic agents doxapram HCl and nikethamide: II - respirogenic and cardiovascular pharmacodynamic activites in dogs

Experiments in pentobarbitone-sodium anesthetized dogs revealed that Doxapram HCl was a more potent respirogenic agent than Nikethamide; but at higher doses tachyphylaxis develops. Further assessments of its respirogenic activity in halothane-anesthetized dogs, by calculation of the minutevolume demonstrated a significant increase in ventilatic. These respirogenic effects were accompanied by transientrise in blood pressure at lower doses, and by bradycardia at higher doses. Nikethamide lowered the blood pressure at all dose levels, while it produced no ECG changes. Both drugs produced a dose-related direct myocardial depression of the isolated heart. The site of the respirogenic and cardiovascular effects of Doxapram HCl, was investigated after vagotomy, by intravertebral injection and in the spinal dog. The results demonstrated that the drug acts by central and peripheral mechnisms; and that its action may be partly through sympathetic influence