RESUMEN
Cystic fibrosis care is expensive. In Belgium, its financial support is not provided by powerful charities but by the national health system, which also sponsors the Belgian Cystic Fibrosis Registry. Recent data allow to better evaluate the quality of care for patients with cystic fibrosis in our country. Overall, it is high but varies from one centre to another. Similarly, use of the main symptomatic treatments is heterogeneous. Access to lung transplantation is one of the fluidest in the world. However, Belgium was one of the last medicalised countries to implement a neonatal screening programme for cystic fibrosis. It also lags behind in regard of the reimbursement of modulators of the CTFR gene function. This is especially detrimental for the lack of reimbursement of a recent highly effective combination of three modulators. The cost of this triple therapy is opaque and far too high. However, its effectiveness is impressive and, in the long term, around 90 % of Belgian patients with cystic fibrosis are expected to greatly benefit from it.
La prise en charge de la mucoviscidose est coûteuse. En Belgique, elle n'est pas financée par de puissantes organisations caritatives, mais par le système de santé national, qui parraine également le Registre Belge de la Mucoviscidose. Des données récentes permettent de mieux situer la qualité des soins prodigués aux patients atteints de mucoviscidose dans notre pays. Globalement, elle est élevée, mais varie d'un centre à l'autre. De même, l'utilisation des principaux traitements symptomatiques est hétérogène. L'accès à la transplantation pulmonaire est l'un des plus fluides au monde. La Belgique a été l'un des derniers pays médicalisés à mettre en place un programme de dépistage néonatal de la mucoviscidose. Elle est également à la traîne en ce qui concerne le remboursement des modulateurs de la fonction du gène CTFR. Ceci est particulièrement préjudiciable pour le remboursement d'une récente combinaison de trois d'entre eux, hautement efficace. Le coût de cette trithérapie est opaque et beaucoup trop élevé, mais l'impact médical de ce traitement est impressionnant et, à terme, 90 % des patients belges devraient en bénéficier grandement.
Asunto(s)
Fibrosis Quística , Bélgica , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Humanos , Recién Nacido , Tamizaje Neonatal , Sistema de RegistrosRESUMEN
In cystic fibrosis, lung disease is early and insidious. It almost always conditions the prognosis. A pragmatic way of looking at prognostic factors is to distinguish those on which care management has little (environmental factors) or no grip (genetic factors) and those related to the quality of care, the latter being crucial. Recently, a triple-combination CFTR («Cystic Fibrosis Transmembrane conductance Regulator¼) modulator regimen has been shown a highly effective therapy. Ultimately, at least 90 % of Belgian patients with cystic fibrosis should benefit from this drug. However, its official price is extremely high (712 /day), lacks transparency and illustrates problematic aspects of current orphan legislations. For the majority of citizens in Western Europe, a social ideal still prevails that healthcare should be accessible to all in an equitable fashion. Somewhere between this price and the necessity for national health systems based on solidarity to keep the costs of orphan drugs at a sustainable level, patients are looking like hostages.
Précoce et sournoise, l'atteinte pulmonaire conditionne presque toujours le pronostic de la mucoviscidose. Il est pragmatique de considérer trois types de facteurs influençant ce pronostic. Les deux premiers (environnementaux et facteurs génétiques) offrent peu ou pas de prise à l'intervention médicale. Le troisième est déterminant et directement lié à la qualité de la prise en charge. Récemment, une combinaison de trois modulateurs de la protéine CFTR («Cystic Fibrosis Transmembrane conductance Regulator¼) est apparue très efficace. à terme, plus de 90 % des patients belges atteints de la mucoviscidose devraient en bénéficier. Cependant, le coût officiel actuel de cette médication est extrêmement élevé (712 /jour). Il est dépourvu de transparence et illustre une dérive du créneau des médications orphelines. Dans les pays d'Europe occidentale, un accès équitable aux soins représente une importante valeur sociétale. Un tel prix place les patients en position d'otages entre une firme forte d'un monopole et des décideurs qui doivent rester garants de la pérennité de systèmes de santé solidaires.
Asunto(s)
Fibrosis Quística , Quinolonas , Aminofenoles , Aminopiridinas , Benzodioxoles , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Europa (Continente) , Humanos , Mutación , PronósticoRESUMEN
INTRODUCTION: Small airways' involvement in cystic fibrosis (CF) pulmonary disease is a very early event, which can progress sub-clinically and insidiously since it is poorly reflected by commonly used lung function tests. STATE OF ART: Sensitive and discriminative tools are available to investigate small airways function. However their complexity and/or invasiveness has confined their use to research purposes and to some specialized research teams. By contrast, the multiple breath washout (MBW) test is more affordable and non-invasive. Lung clearance index (LCI), which is the most used derived parameter, is reproducible and much more sensitive than spirometry in detecting small airways disease. However, MBW is operator dependent. PERSPECTIVES: The recent commercialization of devices assessing LCI launches MBW as a potential tool in routine clinical care, although its use currently remains mostly dedicated to research purposes. However, important differences in LCI between various equipment settings raise a number of theoretical questions. Specific algorithms should be refined and more transparent. Standardization of MBW is still an ongoing process. Whether other MBW derived indices can prove superior over LCI deserves further study. CONCLUSIONS: In CF, LCI is now a well-established outcome in research settings to detect early lung function abnormalities and new treatment effects, especially in patients with mild lung disease. In these patients, LCI seems an attractive tool for clinicians too. Yet, further investigation is needed to define clinically significant changes in LCI and to which extent this index can be useful in guiding clinical decisions remains to be studied.
Asunto(s)
Fibrosis Quística/fisiopatología , Pulmón/fisiopatología , Fibrosis Quística/diagnóstico , Volumen Espiratorio Forzado , Indicadores de Salud , Humanos , Pruebas de Función Respiratoria , EspirometríaRESUMEN
BACKGROUND: The sweat test is the current gold standard for the diagnosis of cystic fibrosis (CF). CF is unlikely when sweat chloride (Clsw) is lower than 30mmol/L, Clsw>60 is suggestive of CF, with intermediate values between 30 and 60mmol/L. To correctly interpret a sweat chloride value, the biological variability of the sweat chloride has to be known. METHODS: Sweat tests performed in two centers using the classic Gibson and Cooke method were retrospectively reviewed (n=5904). Within test variability of Clsw was measured by comparing results from right and left arm collected on the same day. Between test variability was calculated from subjects with sweat tests performed on more than one occasion. RESULTS: Within test variability of Clsw calculated in 1022 subjects was low with differences between -3.2 (p5) and +3.6mmol/L (p95). Results from left and right arm were classified differently in only 3 subjects. Between test variability of Clsw in 197 subjects was larger, with differences between -18.2mmol/L (p5) and +14.1mmol/L (p95) between repeat tests. Changes in diagnostic conclusion were seen in 55/197 subjects, the most frequent being changing from indeterminate to 'CF unlikely' range (48/102). CONCLUSION: Variability of sweat chloride is substantial, with frequent changes in diagnostic conclusion, especially in the intermediate range.
Asunto(s)
Cloruros/análisis , Sudor/química , Distribución por Edad , Bélgica , Variación Biológica Poblacional , Niño , Fibrosis Quística/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/normas , Femenino , Humanos , Lactante , Masculino , Valores de Referencia , Estudios Retrospectivos , Adulto JovenRESUMEN
There is a need to find a cure for pulmonary disease in cystic fibrosis (CF), though full benefit of this approach will be restricted to those patients with well-preserved lungs. The most promising route is currently that of a pharmacological mutation-specific approach aiming at correcting the mechanism by which mutations lead to impairment of chloride conductance across respiratory epithelial cells. In the past 14years, 7 candidate drugs (CPX, 4PBA, gentamicin, PTC124, VX-770 or Ivacaftor, VX-809 or Lumacaftor, and Miglustat) have been investigated in CF patients. A postulate of 14 out of the 15 published studies has been that an effective agent had to improve total chloride secretion as assessed in vivo by nasal potential difference measurements. The present review casts a critical look at these studies. Apparent inconsistencies are discussed as well as possible limitations of nasal potential difference measurements as outcome parameters in these trials. Primarily targeting a mutation carried by less than 2% of French CF patients, the 2 Ivacaftor studies could well be a milestone on the long road toward a cure for CF. However, further data on safety and long-term efficacy are obviously needed and the current price of this medication in the US would make it unaffordable for European patients.
Asunto(s)
Cloruros/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/efectos de los fármacos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Mutación/efectos de los fármacos , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Células Epiteliales/efectos de los fármacos , Medicina Basada en la Evidencia , Humanos , Sudor/química , Resultado del TratamientoRESUMEN
INTRODUCTION: Chest physiotherapy is an essential part of the life-long therapeutic routine in patients with cystic fibrosis. STATE OF THE ART: Various manoeuvres are available but there is no consensus supporting one specific technique over others. These techniques can be classified as "manual" or "instrumental". Instrumental airway clearance techniques are based on physiological principles and consist in the application of vibrations or positive expiratory pressure during expiratory phase to enhance sputum clearance. Positive expiratory pressure can be delivered continuously or in an oscillating pattern. The effects of these devices have been investigated in many studies. PERSPECTIVES: Results suggest a potential place for these techniques in the management of cystic fibrosis, but they remain poorly used. CONCLUSION: A better knowledge of these approaches could enable them to integrate more widely into the physiotherapy management of patients with cystic fibrosis.
Asunto(s)
Oscilación de la Pared Torácica/métodos , Fibrosis Quística/terapia , Respiración con Presión Positiva/métodos , Terapia Respiratoria/métodos , Resistencia de las Vías Respiratorias , Humanos , Moco/metabolismo , VibraciónRESUMEN
Sildenafil and vardenafil, two selective inhibitors of phosphodiesterase type 5 (PDE5) are able, when applied by intraperitoneal injection, to activate chloride transport in cystic fibrosis (CF) mice homozygous for the F508del mutation. Oral treatment with the drugs may be associated with adverse haemodynamic effects. We hypothesised that inhaled PDE5 inhibitors are able to restore ion transport in F508del CF airway epithelium. We developed a restraint-free mouse chamber for inhalation studies. PDE5 inhibitors were nebulised for 15 min at concentrations adjusted from recommended therapeutic oral doses for male erectile dysfunction. We measured in vivo nasal transepithelial potential difference 1 h after a single inhalation of sildenafil, vardenafil or tadalafil in F508del CF and normal homozygous mice. After nebulisation with the drugs in F508del mice, chloride transport, evaluated by perfusing the nasal mucosa with chloride-free buffer containing amiloride followed by forskolin, was normalised; the forskolin response was increased, with the largest values being observed with tadalafil and intermediate values with vardenafil. No detectable effect was observed on sodium conductance. Our results confirm the role of PDE5 inhibitors in restoring chloride transport function of F508del CF transmembrane conductance regulator protein and highlight the potential of inhaled sildenafil, vardenafil and tadalafil as a therapy for CF.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Administración por Inhalación , Animales , Cloruros/metabolismo , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Homocigoto , Humanos , Imidazoles/administración & dosificación , Ratones , Ratones Transgénicos , Nebulizadores y Vaporizadores , Hidrolasas Diéster Fosfóricas/metabolismo , Piperazinas/administración & dosificación , Purinas/administración & dosificación , Citrato de Sildenafil , Sulfonas/administración & dosificación , Factores de Tiempo , Triazinas/administración & dosificación , Diclorhidrato de VardenafilRESUMEN
Nebulisers are a potential source of bacterial contamination in cystic fibrosis (CF) patients. The aims of the study were to survey patient practice regarding maintenance of home nebulisers and to assess the impact of standardised guidelines derived from a previous in-vitro study. In total, 42 CF patients were studied. During two consecutive home visits, a questionnaire regarding routine patient practice was completed by a nurse while sputum and equipment samples were taken for bacteriological analyses. The first visit took place at baseline, and the second followed the implementation of detailed instructions for cleaning and disinfecting the nebulisers using a 0.5% hypochlorite solution. The first visit identified a great diversity in routine patient practices. Commensal bacteria, environmental bacteria and potential CF pathogens contaminated 78.5%, 57.1% and 14.3% of nebulisers respectively. After hypochlorite disinfection, rate and degree of global contamination decreased significantly, but the number of CF pathogens was not affected. There was no concordance between CF pathogens isolated from patients' sputum and their equipment. We conclude that in this sample of patients, initial routine practices were varied. With regard to CF pathogens, the superiority of a hypochlorite solution over a mix of other disinfection methods was not demonstrated.
Asunto(s)
Bacterias/efectos de los fármacos , Infecciones Bacterianas/prevención & control , Fibrosis Quística/complicaciones , Desinfectantes/farmacología , Desinfección/métodos , Ácido Hipocloroso/farmacología , Nebulizadores y Vaporizadores/microbiología , Adolescente , Adulto , Bacterias/aislamiento & purificación , Niño , Humanos , Cooperación del Paciente/estadística & datos numéricos , Esputo/microbiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: In patients with symptoms suggestive of cystic fibrosis (CF) and intermediate sweat chloride values (30-60 mmol/l), extensive CFTR gene mutation analysis and nasal potential difference (NPD) measurement are used as additional diagnostic tests and a positive result in either test provides evidence of CFTR dysfunction. To define the phenotype of such patients and confirm the validity of grouping them, patients with intermediate sweat chloride values in whom either additional CF diagnostic test was abnormal were compared with subjects in whom this was not the case and patients with classic CF. METHODS: The phenotypic features of four groups were compared: 59 patients with CFTR dysfunction, 46 with an intermediate sweat chloride concentration but no evidence of CFTR dysfunction (CF unlikely), 103 patients with CF and pancreatic sufficiency (CF-PS) and 62 with CF and pancreatic insufficiency (CF-PI). RESULTS: The CFTR dysfunction group had more lower respiratory tract infections (p = 0.01), more isolation of CF pathogens (p<0.001) and clubbing (p = 0.001) than the CF unlikely group, but less frequent respiratory tract infections with CF pathogens than the CF-PS group (p = 0.05). Patients in the CF-PS group had a milder phenotype than those with PI. Many features showed stepwise changes through the patient groups. CONCLUSION: Patients with intermediate sweat chloride values and two CFTR mutations or an abnormal NPD measurement have a CF-like phenotype compatible with CFTR dysfunction and, as a group, differ phenotypically from patients with intermediate sweat chloride values in whom further CF diagnostic tests are normal as well as from CF-PS and CF-PI patients.
Asunto(s)
Algoritmos , Cloruros/análisis , Fibrosis Quística/genética , Sudor/química , Adolescente , Adulto , Niño , Fibrosis Quística/diagnóstico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/análisis , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Humanos , Masculino , Mutación , Fenotipo , Sodio , Adulto JovenRESUMEN
BACKGROUND: Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. METHODS: In this retrospective multicentric study, data from all CF children fulfilling the following criteria were collected: 1) Age 6-<18 at the end of 2003; 2) diagnosis before 8 y; 3) follow-up in an accredited CF Belgian centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred > or =2 years after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). RESULTS: Data from 217 children were collected (Group A: 67/217). Late referred patients had a lower FEV(1) (77.2%+/-22.4 vs 86.7% pred.+/-19.4, p=0.01) and a higher prevalence of Pseudomonas aeruginosa (38.6 vs 17.5%, p<0.05). CONCLUSION: In this population of CF children, a delay of 6.1 y (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13.
Asunto(s)
Fibrosis Quística/terapia , Derivación y Consulta , Adolescente , Bélgica , Niño , Fibrosis Quística/diagnóstico , Fibrosis Quística/microbiología , Progresión de la Enfermedad , Humanos , Evaluación de Resultado en la Atención de Salud , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Capacidad VitalRESUMEN
OBJECTIVES: To document the relevance of sweat potassium concentration in a reported case of a white Caucasian 27-month-old boy who presented with non-specific respiratory symptoms and several abnormal sweat test results compatible with cystic fibrosis (CF). DESIGN AND METHODS: Repeated sweat tests using the Gibson-Cooke technique in the presence and absence of the mother. RESULTS: The high within- and between-test variability, the very low sweat potassium concentrations, several aspects of the family's history and a negative exhaustive genetic analysis to identify any CFTR mutation, raised suspicion for pediatric condition falsification. Two additional sweat tests performed in the absence of the mother were normal. CONCLUSION: CF diagnosis was then discarded and a Munchausen syndrome by proxy diagnosis was proposed.
Asunto(s)
Cloruros/análisis , Síndrome de Munchausen Causado por Tercero/diagnóstico , Potasio/análisis , Sudor/química , Preescolar , Fibrosis Quística/diagnóstico , Humanos , MasculinoRESUMEN
Soy isoflavones (IFs) have shown a bone-sparing effect through epidemiological studies in the Asian population. However, there is no evidence as to whether such protection would result from a lifelong exposure. We investigated the impact of an early exposure to IFs on bone status. Sixty female Wistar rats were fed either a standard diet (n=30) or the same food enriched with IFs (0.87 mg/g of diet) (n=30). After 1 month, they were allowed to mate, and were kept on the same regimen during the whole gestation and lactation periods. At weaning, female pups were each assigned to one of four nutritional groups; within each experimental group, animals were split into two groups, fed either the standard or the IF-rich diet. At 2, 3, 6, 12, 18, and 24 months after birth, 10 animals in each group were sacrificed. Femurs were collected for mechanical testing and bone mineral density (BMD) measurement. The rats perinatally or lifelong exposed to the IF-rich diet exhibited higher body weight and fat mass at 24 months of age. Peak bone mass was achieved between 6 and 12 months and did not differ between groups. In animals perinatally exposed to IF, BMD continued to increase. Thus, at 24 months, femoral total BMD (P<0.05), metaphyseal BMD (P<0.01), and failure load (P<0.05) were higher in the offspring born from mothers provided IF during pregnancy. Postnatal exposure alone did not improve bone parameters. This experiment provides evidence that perinatal exposure to phytoestrogens leads to a higher BMD later in life. It is suggested that these changes may have occurred as a consequence of programming effects, as has been shown for the endocrine and immune systems.
Asunto(s)
Envejecimiento/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Glycine max/química , Isoflavonas/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Biomarcadores/orina , Peso Corporal/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Femenino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Útero/efectos de los fármacosRESUMEN
The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/prevención & control , Remodelación Ósea/efectos de los fármacos , Hesperidina/farmacología , Hipolipemiantes/farmacología , Osteoporosis/prevención & control , Ovariectomía/efectos adversos , Factores de Edad , Aminoácidos/orina , Animales , Fenómenos Biomecánicos , Composición Corporal , Conservadores de la Densidad Ósea/sangre , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/fisiopatología , Resorción Ósea/prevención & control , Colesterol/sangre , Modelos Animales de Enfermedad , Femenino , Fémur/efectos de los fármacos , Fémur/fisiopatología , Hesperidina/sangre , Hesperidina/uso terapéutico , Hipolipemiantes/sangre , Hipolipemiantes/uso terapéutico , Osteocalcina/sangre , Osteoporosis/etiología , Osteoporosis/metabolismo , Osteoporosis/fisiopatología , Ratas , Ratas Wistar , Triglicéridos/sangre , Útero/efectos de los fármacos , Útero/patologíaRESUMEN
In the elderly, nutritional deficiencies, such as low energy and protein intake, are suggested to increase the risk of osteoporotic fractures. Modulation of the amount and quality of protein intake under energy deficient conditions represents an interesting strategy to prevent aged-related bone loss. We investigated the effect of a 5-month dietary restriction on bone status in 16-month-old male rats. Rats were randomised into six groups (n 10 per group). Control animals were fed a normal diet containing either casein (N-C) or whey protein (N-WP). The other groups received a 40 % protein and energy-restricted diet with casein or whey protein (PER-C and PER-WP) or a normal protein and energy-restricted diet (ER-C and ER-WP). Both restrictions (PER and ER) induced a decrease in femoral bone mineral density (BMD), consistent with impaired biomechanical properties and a reduced cortical area at the diaphysis. Plasma osteocalcin and urinary deoxypyridinoline levels suggested a decrease in bone turnover in the PER and ER groups. Interestingly, circulating insulin-like growth factor 1 (IGF-1) levels were also lowered. Overall, normal protein intake did not elicit any bone sparing effect in energy-deficient rats. Regarding protein quality, neither casein nor WP appeared to significantly prevent the BMD decrease. This study confirms that nutritional deficiencies may contribute to osteopenia through decreased IGF-1 levels. Moreover, it seems that impaired bone status could not be significantly prevented by modulating the amount and quality of dietary proteins.
Asunto(s)
Huesos/fisiopatología , Restricción Calórica , Caseínas/administración & dosificación , Proteínas de la Leche/administración & dosificación , Osteoporosis/metabolismo , Aminoácidos/orina , Animales , Biomarcadores/sangre , Biomarcadores/orina , Densidad Ósea , Resorción Ósea , Calcio/orina , Suplementos Dietéticos , Fémur , Factor I del Crecimiento Similar a la Insulina/análisis , Leptina/sangre , Masculino , Modelos Animales , Osteocalcina/sangre , Osteoporosis/fisiopatología , Distribución Aleatoria , Ratas , Ratas Wistar , Proteína de Suero de LecheRESUMEN
The source of acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF) patients remains unknown. Patient-to-patient transmission has been well documented but the role of the environment as a source of initial infection is as yet unclear. In the present study, the origin of the first P. aeruginosa isolate in CF patients was investigated by comparing the P. aeruginosa genotype(s) from newly infected patients with genotypes of P. aeruginosa isolates from the home environment and from other patients from the same CF centre. A total of 50 newly infected patients were studied. P. aeruginosa could be cultured from 5.9% of the environmental samples, corresponding to 18 patients. For nine of these, the genotype of the environmental P. aeruginosa isolate was identical to the patient's isolate. In total, 72% of the environmental P. aeruginosa isolates were encountered in the bathroom. Patient-to-patient transmission within the CF centre could not be ruled out for three patients. In summary, a low prevalence of Pseudomonas aeruginosa was found in the home environment of the newly infected cystic fibrosis patients. The bathroom should be targeted in any preventive cleaning procedures. An environmental source of the new infection could not be ruled out in nine patients.
Asunto(s)
Fibrosis Quística/microbiología , Monitoreo del Ambiente , Vivienda , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosa/aislamiento & purificación , Adolescente , Adulto , Niño , Preescolar , Femenino , Genotipo , Humanos , Lactante , Masculino , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidad , Esputo/microbiologíaRESUMEN
In children under 5 years, most lower respiratory tract infections are caused by viruses and do not require antibiotics. This is true for almost all episodes of bronchitis and bronchiolitis but also for the majority of pneumonias. Atypical pneumonias due to Mycoplasma pneumoniae or Chlamydia pneumoniae predominate in older children while Streptococcus pneumoniae remains by far the most common cause of bacterial pneumonia. Diagnosis of pneumonia itself can be difficult and relies on a combination of clinical judgement and radiological and laboratory investigations. In real-life situations, etiologic agents are rarely identified, an issue further complicated by the possibility of mixed infections particularly in hospitalised children. Since viruses are often the sole cause of pneumonia in childhood, it is appropriate not to treat every child with antibiotics. However, when a bacterial origin can not be excluded, antibiotics efficient on Streptococcus pneumoniae are to be prescribed. Amoxicillin is the first choice empirical antibiotic treatment, having a higher efficacy on poorly sensitive pneumococcus than cephalosporins. Macrolides are indicated for the treatment of atypical pneumonia. Current immunisation strategies have decreased the number of bacterial pneumonias. However, there is some evidence that among hospitalised children the rate of complicated pneumonias is increasing with an emerging role of Streptococcus pneumoniae serotype 1, which is not covered in the 7-valent vaccine.
Asunto(s)
Infecciones Comunitarias Adquiridas/terapia , Neumonía/terapia , Niño , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/etiología , Humanos , Neumonía/diagnóstico , Neumonía/etiologíaRESUMEN
Cystic fibrosis and Pseudomonas aeruginosa current and future strategies Pseudomonas aeruginosa is long recognized as the main pathogen in cystic fibrosis and avoiding or postponing chronic colonization of the lungs by this germ is considered as the most important challenge for the clinicians dedicated to the care of CF patient. The need for early intervention is widely accepted but its optimal modalities are still debated and the failure rate of this approach is estimated around 20%. This underlines the potential of other strategies including attempts to develop an effective vaccine against PA and anti-PA prophylaxis. Surprisingly enough, the latter approach which could involve early use of inhaled antibiotics has never been studied prospectively. In chronically colonized patients, inhaled antibiotics and oral azythromycin are of value, slowing the FEV1 decline and reducing the number of exacerbations. Whether intravenous antibiotics are to be used electively (during exacerbations) or more systematically (every 3 months for example) remains controversial.
Asunto(s)
Fibrosis Quística/complicaciones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/etiología , Fibrosis Quística/microbiología , Humanos , Infecciones por Pseudomonas/microbiologíaRESUMEN
INTRODUCTION: Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor. METHODS: A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 microg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 mug/g body weight/d, simultaneously with short-chain FOS (Actilight, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX. RESULTS: Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant. CONCLUSION: In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.
Asunto(s)
Densidad Ósea/fisiología , Glycine max/química , Isoflavonas/farmacología , Osteoporosis/prevención & control , Fitoestrógenos/farmacología , Animales , Biomarcadores/análisis , Peso Corporal/fisiología , Resorción Ósea/fisiopatología , Modelos Animales de Enfermedad , Equol , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Genisteína/sangre , Genisteína/farmacología , Isoflavonas/sangre , Tamaño de los Órganos , Osteocalcina/sangre , Osteoporosis/metabolismo , Ovariectomía , Fitoestrógenos/sangre , Ratas , Ratas Wistar , Útero/patologíaRESUMEN
Pseudomonas aeruginosa is a major cause of nosocomial infections. This organism shows a remarkable capacity to resist antibiotics, either intrinsically (because of constitutive expression of beta-lactamases and efflux pumps, combined with low permeability of the outer-membrane) or following acquisition of resistance genes (e.g., genes for beta-lactamases, or enzymes inactivating aminoglycosides or modifying their target), over-expression of efflux pumps, decreased expression of porins, or mutations in quinolone targets. Worryingly, these mechanisms are often present simultaneously, thereby conferring multiresistant phenotypes. Susceptibility testing is therefore crucial in clinical practice. Empirical treatment usually involves combination therapy, selected on the basis of known local epidemiology (usually a beta-lactam plus an aminoglycoside or a fluoroquinolone). However, therapy should be simplified as soon as possible, based on susceptibility data and the patient's clinical evolution. Alternative drugs (e.g., colistin) have proven useful against multiresistant strains, but innovative therapeutic options for the future remain scarce, while attempts to develop vaccines have been unsuccessful to date. Among broad-spectrum antibiotics in development, ceftobiprole, sitafloxacin and doripenem show interesting in-vitro activity, although the first two molecules have been evaluated in clinics only against Gram-positive organisms. Doripenem has received a fast track designation from the US Food and Drug Administration for the treatment of nosocomial pneumonia. Pump inhibitors are undergoing phase I trials in cystic fibrosis patients. Therefore, selecting appropriate antibiotics and optimising their use on the basis of pharmacodynamic concepts currently remains the best way of coping with pseudomonal infections.