Cystic Fibrosis

La fibrosis quística (FQ), con una incidencia de un caso cada 2.500 recién nacidos vivos, es la enfermedad hereditaria más frecuente en la raza caucásica. Se produce como consecuencia de la ausencia o la alteración de la función de una glucoproteína, llamada cystic fibrosis transmembrane conductance regulator (CFTR) 1 . La patogenia de la enfermedad no está aclarada, aunque parece ser que el círculo vicioso obstrucción-infeccióninflamación es el productor del daño pulmonar causante, a su vez, de las bronquiectasias quísticas y la fibro sis pulmonar propias de la enfermedad 2 . El diagnóstico de FQ se establece en el primer año de vida en el 70% de los casos, fundamentalmente por infecciones respiratorias agudas o persistentes o por malnutrición 3 .

Symptoms of anxiety and depression have important consequences for patients with chronic disease, including lower rates of adherence and increased morbidity. This review discusses the prevalence of anxiety and depression in patients with cystic fibrosis (CF) across the life span and highlights current understanding of how these symptoms affect adherence, health outcomes, and health-related quality of life (HRQOL). Anxiety and depression appear to be more common in patients with CF than in the general population. Recent studies also indicate that symptoms of anxiety occur more frequently than depression in this population. Both anxiety and depression have been shown to be associated with poorer disease outcomes, including HRQOL. Depression, specifically, leads to lower adherence to recommended therapies. Given the prevalence and impact of anxiety and depression in CF, it seems appropriate to recommend annual screening using a validated approach, with referral for either pharmacotherapy or cognitive behavioral therapy of those with apparent symptoms. A large-scale epidemiological study of anxiety and depression in CF is under way and should provide better prevalence estimates and more information on the effects of these psychological symptoms.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for ventilator-acquired pneumonia, acute lower respiratory tract infections in immunocompromised patients and chronic respiratory infections in cystic fibrosis patients. High incidence, infection severity and increasing resistance characterize P. aeruginosa infections, highlighting the need for new therapeutic options. One such option is to target the many pathogenic mechanisms conferred to P. aeruginosa by its large genome encoding many different virulence factors. This article reviews the pathogenic mechanisms and potential therapies targeting these mechanisms in P. aeruginosa respiratory infections.

The rapid spread of multidrug resistant bacterial strains limits the effectiveness of antibiotic treatments and induces intense research for alternatives. Today, the use of phage preparations as alternative approach is gaining attention, particularly for treating a wide variety of diseases which are difficult to control by chemotherapeutic agents. This article relates the phage therapy experience of the Eliava Institute of Bacteriophage, Microbiology and Virology.

La fibrosis quística es la enfermedad genética (autosómica recesiva) más frecuente como causa de muerte en la raza blanca, y afecta a 1:2.500 niños nacidos a término. Los avances en el conocimiento de la patogenia y en el tratamiento de la enfermedad han permitido incrementar las expectativas de vida de los pacientes, que se calcula en 40 años para los nacidos en la década de los años noventa. Esto ha causado un aumento de la población adulta entre los afectados de fibrosis quística, que en nuestro país representa el 34%. La presencia de infección bronquial crónica y de exacerbaciones de infección pulmonar, inicialmente por gérmenes como Staphylococcus aureus y Haemophilus influenzae nontypable, que suelen preceder a la infección bronquial por Pseudomonas aeruginosa, se acompaña de una respuesta inflamatoria intensa capaz de lesionar las vías aéreas y los mecanismos de defensa local, dando lugar al desarrollo progresivo de bronquiectasias e insuficiencia respiratoria, que son la causa principal de morbilidad y mortalidad en el 90% de los casos. Uno de los objetivos principales del tratamiento de los pacientes con fibrosis quística es la infección bronquial, tanto las exacerbaciones como la infección bronquial crónica. Los antibióticos nebulizados se utilizan en pacientes con fibrosis quística desde hace años, y recientemente también en pacientes con bronquiectasias no debidas a fibrosis quística. Su objetivo es conseguir concentraciones mayores del antibiótico en el lugar de la infección, a fin de evitar la necesidad de administrar dosis elevadas de éstos por vía oral o parenteral, y de reducir los riesgos de toxicidad sistémica. Sin embargo, existen algunas discrepancias o falta de evidencia científica en la bibliografía con relación a las indicaciones, el tipo de antibióticos, las dosis, la duración del tratamiento, los métodos de nebulización y la eficacia de esta forma de administrar los antibióticos. Dado que en nuestro país aproximadamente el 50% de los pacientes afectados de fibrosis quística reciben antibioticoterapia en aerosol de manera continua o intermitente, se ha hecho necesaria la elaboración de un documento de consenso. Este documento de consenso se ha elaborado con la participación de 18 unidades de fibrosis quística representativas de todo el territorio español, que en conjunto tratan a un total de 1.206 pacientes y de los que 415 (34%) son adultos. El documento intenta dar respuesta a las siguientes cuestio-nes sobre los antibióticos nebulizados en la fibrosis quística: indicaciones actuales; tipos de antibióticos, dosis, duración del tratamiento y métodos de nebulización más adecuados, e implicaciones microbiológicas.

Objective: to evaluate the diagnosis of lung infection and colonization by Pseudomonas aeruginosa (Pa) through the detection of specific seric antibodies in fibrocystic patients. Data sources: the Medline database, was searched in the period 1986 to 2007, with the keywords cystic fibrosis and pseudomonas. Data synthesis: the epithelium cells disturb in ion transport cause a chronic airways obstruction, with secondary infections. The mucoid Pa is the main agent that increases morbidity and mortality in fibrocystic patients. The Endereço para correspondência:

Cystic fibrosis is the most common life-threatening recessively inherited disease in Caucasians. Due to early provision of care in specialized reference centers and more comprehensive care, survival has improved over time. Despite great advances in supportive care and in our understanding of its pathophysiology, there is still no cure for the disease. Therapeutic strategies aimed at rescuing the abnormal protein are either being sought after or under investigation. This review highlights salient insights into pathophysiology and candidate molecules suitable for CFTR pharmacotherapy. Clinical trials using Ataluren, VX-809 and ivacaftor have provided encouraging data. Preclinical data with inhibitors of phosphodiesterase type 5, such as sildenafil and analogs, have highlighted their potential for CFTR pharmacotherapy. Because sildenafil and analogs are in clinical use for other clinical applications, research on this class of drugs might speed up the development of new therapies for CF.

This study examined marital role strain in 33 couples caring for a child with cystic fibrosis (CF) and 33 couples with a healthy child. The relationship between role strain, marital satisfaction, and psychological distress was tested. Couples completed a structured interview, questionnaires, a card sort procedure, and 4 daily diaries assessing activities and mood. Couples in the CF versus comparison group reported greater role strain on measures of role conflict, child-care tasks, and exchanges of affection. They also spent less time in recreational activities, but no reliable group differences were found in marital satisfaction or depression. Regression analyses indicated that role strain was related to marital satisfaction and depression and that recreation time accounted for additional variance. Path analysis suggested that recreation mediated the negative relationship between role strain and distress. The importance of using a contextual, process-oriented approach is discussed.

Though the immune system is generally defined as a system of defense, it is increasingly recognized that the immune system also plays a crucial role in tissue repair and its potential dysregulations. In this review, we explore how distinct immune cell types are involved in tissue repair and how they interact in a process that is tightly regulated both spatially and temporally. We insist on the concept of immune cell plasticity which, in recent years, has proved fundamental for the success/understanding of the repair process. Overall, the perspective presented here suggests that the immune system plays a central role in the physiological robustness of the organism, and that cell plasticity contributes to the realization of this robustness.

Non-allergic rhinitis (NAR) is a common disorder, which can be defined as chronic nasal inflammation, independent of systemic IgE-mediated mechanisms. Symptoms of NAR patients mimic those of allergic rhinitis (AR) patients. However, AR patients can easily be diagnosed with skin prick test or allergen-specific IgE measurements in the serum, whereas NAR patients form a heterogeneous group and are difficult to diagnose because of an extensive list of different phenotypes, all varying in severity, underlying etiology and type of inflammation. Characterization of those phenotypes, mechanisms and management of NAR represents one of the major unmet needs in the field of allergic and non-allergic diseases. This review aims at providing a comprehensive overview of the state of the art in classifying the NAR patients and focuses on the neuro-immune mechanisms involved in allergic and non-allergic rhinitis, including reflections on the pathophysiology and the currently available treatment opti...

Cystic fibrosis FEF Forced expiratory flow between 25% and 75% of vital capacity FEV 1 Forced expiratory volume in 1 second FVC Forced vital capacity MVV Maximal voluntary ventilation · VE Minute ventilation · VO 2max Maximal oxygen consumption W max Maximal working capacity

The Cystic Fibrosis Foundation established a process of systematic review of evidence to inform the development of clinical care guidelines and encourage evidence-based practice. The Subcommittee on Growth and Nutrition reviewed the evidence in two areas: energy intake and dosing for pancreatic enzyme replacement therapy. Evidence-based recommendations are presented here. Also, an ad hoc working group conducted a review of the literature and performed new analyses using the Cystic Fibrosis Foundation Patient Registry to update the recommendations for growth and weight-status monitoring. These Registry data-based recommendations are presented.

Traditionally, DNA used for PCR-based diagnostic analysis has originated from white cells fractionated from whole blood. Although this method yields substantial quantities of DNA, there are some drawbacks to the procedure, including the inconvenience of drawing blood, risk of exposure to bloodborne pathogens, liquid sample handling, and the somewhat involved extraction procedure. Alten13tively, DNA for genetic diagnosis has been derived from finger stick blood samples, hair roots, cheek scrapings, and urine samples. Oral saline rinses have also been used extensively as a means of collecting buccal epithelial cells as a DNA source. However, this method still requires liquid sample handling. Herein, we present our results involving the rapid extraction of DNA from buccal cells collected on cytology brushes and swabs for use in PCR reactions, specifically the multiplex amplification of 5 exons within the CFTR gene. The quality of DNA isolated from buccal cells, collected in this manner, has been sufficient to reproducibly support multiplex amplification. Cheek cell samples and the DNA prepared from them as described here are highly stable. The success rate of PCR amplification on DNA prepared from buccal cells is 99%. In a blind study comparing the analysis of 12 mutations responsible for cystic fibrosis in multiplex products amplified with DNA from both blood and buccal cell samples from 464 individuals, there was 100% correlation of results for blood and cheek cell DNA, validating the use of DNA extracted from cheek cells collected on cytology brushes for use in genetic testing.

Single strand conformation polymorphism (SSCP) is a reproducible, rapid and quite simple method for the detection of deletions/insertions/rearrangements in polymerase chain reaction amplified DNA. All the details for the use of PCR–SSCP are presented in the direction of genetic diseases (β-thalassaemia, cystic fibrosis), optimum gel conditions, sensitivity and the latest modifications of the method, which are applied in most laboratories. This non-radioactive PCR–SSCP method can be reliably used to identify mutations in patients (β-globin, CFTR), provided suitable controls are available. Moreover, it is widely used for mutation identification in carriers (β-thalassaemia, cystic fibrosis), making it particularly useful in population screening.

The current study sought to investigate differences in parenting capacity variables across four disease groups. Parents (N = 425), the majority of whom were mothers, of children with either cancer, asthma, Type 1 diabetes, or cystic fibrosis, completed measures of parental overprotection, perceived child vulnerability, and parenting stress. After controlling for significant demographic variables, parents of children with cystic fibrosis and asthma reported higher perceived child vulnerability than parents of children with either diabetes or cancer, while parents of children with asthma and diabetes reported higher parenting stress than parents of children with cancer or cystic fibrosis. No differences between disease groups were found for parental overprotection. The current study provides support for an illness-specific approach to understanding parenting capacity variables in the context of childhood chronic illnesses.

éducateurs pour mener les séances éducatives. Ces conducteurs précisent l'âge des enfants concernés par l'objectif, la durée de la séance, le matériel nécessaire, ce que doivent faire les soignants, le patient, la technique d'apprentissage, les critères et outils d'évaluation. À titre d'exemple, dans le conducteur « Repérer les signes d'alerte d'une exacerbation pulmonaire » que l'on propose à des enfants de plus de 7 ans, le soignant peut poser à l'enfant cette question d'appel : « Qu'est-ce qui peut te faire penser que tu respires moins bien ? ». L'enfant écrit les signes puis essaie de les classer en « modérés » ou « sérieux » en les entourant de couleurs différentes… À la fi n de la séance, l'évaluation est réalisée à l'aide d'un jeu qui comporte une situation et des propositions de réponses sur des cartes. Au dos de chaque carte, la conséquence de la proposition est inscrite. L'enfant choisit les cartes qui constituent d'après lui la ou les bonnes propositions. Les travaux du groupe peuvent être consultés sur le site du Réseau MucoOuest et sur le site de la fédération française des CRCM [4]. Ils s'appuient sur le guide méthodologique édité en 2007 par la Haute Autorité de Santé [5].

Cystic fibrosis (CF) is a common and lethal genetic disorder with a carrier frequency of 1 in 29 Caucasians. Chronic respiratory infections with Pseudomonas aeruginosa are the leading cause of morbidity and mortality in individuals with CF. Aminoglycoside antibiotics, including gentamicin, are highly effective against P. aeruginosa, but severe toxicity limits their use. One potential strategy for avoiding this problem is to encapsulate aminoglycosides in liposomes. In this study, we compared the bactericidal capacity of liposome-encapsulated gentamicin with that of free antibiotic against clinical isolates of P. aeruginosa. Liposome size, encapsulation efficiency and minimal inhibitory concentrations (MICs) of the free and liposomal gentamicin against gentamicin-sensitive and -resistant strains of P. aeruginosa were determined. In vitro time-kill studies were performed using free and liposomal gentamicin at 1, 2 or 4 times the MICs. The average liposomal size was 426.25 ± 13.56 nm, with a gentamicin encapsulation efficiency of 4.51 ± 0.54%. The MICs for liposomal gentamicin were significantly lower than those of corresponding free gentamicin. In addition, the time-kill values for liposomal gentamicin were either equivalent to or better than those of the free antibiotic. In conclusion, our liposomal gentamicin formulation is a more potent antipseudomonal drug with an improved killing time and prolonged antimicrobial activity.

La fibrosis quística es la enfermedad genética (autosómica recesiva) más frecuente como causa de muerte en la raza blanca, y afecta a 1:2.500 niños nacidos a término. Los avances en el conocimiento de la patogenia y en el tratamiento de la enfermedad han permitido incrementar las expectativas de vida de los pacientes, que se calcula en 40 años para los nacidos en la década de los años noventa. Esto ha causado un aumento de la población adulta entre los afectados de fibrosis quística, que en nuestro país representa el 34%. La presencia de infección bronquial crónica y de exacerbaciones de infección pulmonar, inicialmente por gérmenes como Staphylococcus aureus y Haemophilus influenzae nontypable, que suelen preceder a la infección bronquial por Pseudomonas aeruginosa, se acompaña de una respuesta inflamatoria intensa capaz de lesionar las vías aéreas y los mecanismos de defensa local, dando lugar al desarrollo progresivo de bronquiectasias e insuficiencia respiratoria, que son la causa principal de morbilidad y mortalidad en el 90% de los casos. Uno de los objetivos principales del tratamiento de los pacientes con fibrosis quística es la infección bronquial, tanto las exacerbaciones como la infección bronquial crónica. Los antibióticos nebulizados se utilizan en pacientes con fibrosis quística desde hace años, y recientemente también en pacientes con bronquiectasias no debidas a fibrosis quística. Su objetivo es conseguir concentraciones mayores del antibiótico en el lugar de la infección, a fin de evitar la necesidad de administrar dosis elevadas de éstos por vía oral o parenteral, y de reducir los riesgos de toxicidad sistémica. Sin embargo, existen algunas discrepancias o falta de evidencia científica en la bibliografía con relación a las indicaciones, el tipo de antibióticos, las dosis, la duración del tratamiento, los métodos de nebulización y la eficacia de esta forma de administrar los antibióticos. Dado que en nuestro país aproximadamente el 50% de los pacientes afectados de fibrosis quística reciben antibioticoterapia en aerosol de manera continua o intermitente, se ha hecho necesaria la elaboración de un documento de consenso. Este documento de consenso se ha elaborado con la participación de 18 unidades de fibrosis quística representativas de todo el territorio español, que en conjunto tratan a un total de 1.206 pacientes y de los que 415 (34%) son adultos. El documento intenta dar respuesta a las siguientes cuestio-nes sobre los antibióticos nebulizados en la fibrosis quística: indicaciones actuales; tipos de antibióticos, dosis, duración del tratamiento y métodos de nebulización más adecuados, e implicaciones microbiológicas.

Background: Little is currently known about the co-morbidity of depression and cystic fibrosis (CF) and there is currently no empirical research on the effects of depressive symptoms on adherence in children and adolescents with CF. The primary aim of this study was to evaluate the extent of depressive symptoms in children and adolescents with CF and their parents, and determine whether depressive symptoms in the child and/or parent was associated with adherence to airway clearance. We also evaluated whether children's perceptions of relational security with a parent were associated with adherence to airway clearance. Methods: Participants included 39 children with CF ages 7-17 years and their primary caregivers. Depressive symptoms were measured with the Children's Depression Inventory (CDI) and the Center for Epidemiological Studies-Depression Scale (CES-D). The Relatedness Questionnaire assessed the quality of parent-child relational security. Adherence to airway clearance was measured using the daily phone diary (DPD), an empirically validated adherence measure for youth with CF. Results: Rates of depressive symptoms were elevated in children with CF and their parents (29% for children; 35% for mothers; 23% for fathers). Child depressive symptoms were significantly associated with lower rates of adherence to airway clearance, after controlling for demographic variables (r ¼ À0.34, P ¼ 0.02). Child depressive symptoms were associated with worse perceptions of parental relationships (t(35) ¼ 3.2; P ¼ 0.002) and the quality of this relationship was also related to worse adherence (r ¼ 0.42, P ¼ 0.005). Conclusions: A large percentage of youth with CF and their parents reported elevated symptoms of depression. Children scoring in the depressed range on a standardized screening measure and those with less secure parent-child relationships were at greatest risk for poor adherence. Thus, depressive symptoms and family relationships are appropriate targets for adherence promotion interventions, which may ultimately improve health outcomes.

Weserin Reserve Univ., Cleveland, OH. Genome-wide screens using polymorphic markers in segregating multiplex families are now routine for localizing disease genes. In principle, susceptibility loci may even be mapped in simplex families by searching for allelic associations between genetic markers and disease phenotype. This exercise is most efficient in isolated populations where large genomic segments will be shared by affected individuals on the basis of common ancestry. We demonstrate the identification of multiple genomic regions that harbor putative susceptibility loci for Hirschsprung disease (HSCR) in a large, inbred Mennonite kindred by using genome-wide association mapping. We previously demonstrated the segregation of a missense mutation (W276C) in the endothelin-B receptor gene (EDNRB) on chromosome 13q22 in this kindred. This mutation demonstrated a sex and dosage dependent penetrance consistent with the complex pattern of inheritance of HSCR in the Mennonites. We analyzed the genotypes of 527 autosomal and X-linked microsatellite markers in 33 simplex HSCR cases and their parents. For each locus, associations between allele frequencies on the transmitted (T) and untransmitted (U) chromosomes were evaluated by chi-square statistics and multipoint association lod scores across each chromosome.

Burkholderia cepacia complex (BCC) is an important group of pathogens affecting patients with cystic fibrosis and chronic granulomatous disease as well as immunocompromised and hospitalised patients. Therapeutic options are limited owing to high levels of resistance of the organism, either intrinsic or acquired, to many antimicrobial agents. Co-trimoxazole (trimethoprim/sulfamethoxazole) has been a drug of choice. However, in some cases it cannot be administered because of allergic or hypersensitivity reactions, intolerance or resistance. We systematically searched for relevant publications including clinical data in PubMed and Scopus. The search identified 48 relevant case reports (57 cases) and 8 cohort studies or trials. Nineteen (33.3%) of 57 patients included in the case reports received ceftazidime-based regimens, 14 (73.7%) of whom were cured. Meropenem was administered in seven patients (12.3%), one (14.3%) of whom improved and five (71.4%) were cured. Seven (12.3%) of 57 cases were treated with penicillins, four of which were piperacillin (all had a favourable outcome). Based on the data reported in the eight relevant cohort studies or trials identified, favourable outcomes were observed in 68.4% (26/38) to 100% (16/16) of cases treated with ceftazidime and 66.7% (6/9) of cases treated with meropenem. Also, 9/12 (75%) of patients receiving penicillins improved. Thus, Ceftazidime, meropenem and penicillins, mainly piperacillin, either alone or in combination with other antimicrobial agents, may be considered as alternative options for BCC infections, according to the in vitro antimicrobial susceptibility patterns and clinical results. However, the available clinical data are not sufficient and further clinical experience is required to clarify the appropriateness of these antibiotics for BCC infections.

This paper reports on a research trial designed to evaluate the benefits of a health mentoring programme supported with a web and mobile phone based self-monitoring application for enhancing self-efficacy for self-management skills and quality of life for people with CF. This randomised, single-blind controlled trial evaluated two strategies designed to improve self-management behaviour and quality of life. Task-specific self-efficacy was fostered through mentorship and self-monitoring via a mobile phone application. Trial participants were randomised into one of three groups: Control, Mentor-only and Mentor plus mobile phone. Analysis and discussion focus on the experiences of participants through a methodology utilising descriptive statistics and semi-structured interviews. The results highlight the challenges of stimulating self-management behaviours particularly in adolescents and in the evaluation of the role of mobile applications in supporting them.

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are characterized by airway obstruction and an inflammatory process. Reaching early diagnosis and discrimination of subtypes of these respiratory diseases are quite a challenging task than other chronic illnesses. Metabolomics is the study of metabolic pathways and the measurement of unique biochemical molecules generated in a living system. In the last decade, metabolomics has already proved to be useful for the characterization of several pathological conditions and offers promises as a clinical tool. In this article, we review the current state of the metabolomics of COPD, asthma and CF with a focus on the different methods and instrumentation being used for the discovery of biomarkers in research and translation into clinic as diagnostic aids for the choice of patient-specific therapies.

Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa
(P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication
with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and
dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication
systemknown as quorumsensing (QS) involving the virulence factor (pyocyanin), thus representing an
attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently
developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as
mucus and bacterial biofilms, which limits its biomedical application.
Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing:
1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance
of the anti-virulence activity of the QSI.
In this context, various pharmaceutical lipidswere used to prepare ultra-small solid lipid nanoparticles (us-SLNs)
by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties,
drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newlydeveloped
confocalmicroscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization
efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence
efficacy was investigated by pyocyanin formation in P. aeruginosa cultures.
Ultra-small SLNs (b100nmdiameter) provided high encapsulation efficiency (68–95%) according to SLN composition,
high burst in phosphate buffer saline compared to prolonged release of the payload over N8 h in simulated
lung fluidwith minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of
Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model.
SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall,
nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most
interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to
anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate
significance in the area of nano-based delivery of novel anti-infectives.

Objective: to evaluate the diagnosis of lung infection and colonization by Pseudomonas aeruginosa (Pa) through the detection of specific seric antibodies in fibrocystic patients. Data sources: the Medline database, was searched in the period 1986 to 2007, with the keywords cystic fibrosis and pseudomonas. Data synthesis: the epithelium cells disturb in ion transport cause a chronic airways obstruction, with secondary infections. The mucoid Pa is the main agent that increases morbidity and mortality in fibrocystic patients. The Endereço para correspondência:

Nanotechnology provides new materials in the nanometer range with many potential applications in clinical medicine and research. Due to their unique size-dependent properties nanomaterial such as nanoparticles offer the possibility to develop both new therapeutic and diagnostic tools. Thus, applied nanotechnology to medical problemsnanomedicinecan offer new concepts that are reviewed.

La Fibrosis Quística es una enfermedad genética que altera la función de las glándulas exocrinas determinando la formación de secreciones poco hidratadas y espesas. El resultado final a nivel pulmonar es un déficit en la función de limpieza y evacuación mucociliar, con la consecuente acumulación de moco en las vías aéreas y desarrollo de complicaciones, principal causa de morbimortalidad en estos pacientes. El tratamiento actual comprende sólo medidas de sostén y la inhalación de solución salina hipertónica se presenta como opción terapéutica para mejorar el clearance mucociliar. Para analizar sus propiedades y eficacia se revisaron artículos, obtenidos en la base de datos MEDLINE y revistas, y textos de medicina y patología. Las diferentes publicaciones revisadas documentan que la depleción del líquido superficial de la vía aérea es la clave patogénica en la enfermedad pulmonar por Fibrosis Quística. Las soluciones hiperosmolares actuarían restaurando su hidratación y volumen con el consiguiente incremento en el clearance mucociliar y mejora en la función pulmonar. En conclusión, las inhalaciones con solución salina hipertónica, precedidas de un broncodilatador, han demostrado ser eficaces, seguras y económicas y podría ser una terapia adicional para su uso a corto y largo plazo en pacientes con enfermedad pulmonar por Fibrosis Quística.

Since the first description of Cystic fibrosis (CF) more than 75 y ago, significant advances have been made in understanding its pathogenesis and in developing specific therapies. The pace of these developments was further accelerated after the discovery of CF gene in 1989 and since then, CF has been transformed from being a pediatric illness into a chronic life-limiting genetic disorder with survival up to the fourth decade. The development of mutation-specific therapies in the first decade of the 21st century has the potential to change the natural history of CF and has now ushered in the era of 'Precision Medicine'. The ability to revert the basic defect in CF by using Personalized Medicine approach based on each individual's genetic profile will serve as a model for other chronic disorders as well. This review highlights the recent advances in the field of CF research that have led to a paradigm shift in its management and outcomes.

Cystic fibrosis is the most frequent autosomal recessive genetic disease in North European population. This pathology seems to not be rare in Tunisia. On another hand, development of molecular biology techniques has largely contributed to implement the study of the different mutations in the CFTR gene where over 1,300 mutations were reported. Herein, we describe the strategy used to detect molecular defects responsible of cystic fibrosis on 390 children (383 families) in Tunisian population. Several techniques were performed for genotype diagnosis: DNA extraction was from peripheral blood. Polymerase chain reaction (PCR) and polyacylamide gel electrophoresis, and reverse dot blot procedures were used to detect known point mutations. Denaturant gradient gel electrophoresis (DGGE) were used in a next step searching for the unknown point mutations that are later identified by automated sequencing on ABIprism 310. This strategy allowed us to detect 17 different mutations located on the ...

The presence of obsessive-compulsive disorder (OCD) has been linked to decreased quality of life (QoL) among adults, yet little is known about the impact of OCD on QoL in pediatric patients. Sixty-two youth with OCD and their parent(s) were administered the Children's Yale-Brown Obsessive Compulsive Scale following a clinical interview. Children completed the Pediatric Quality of Life Inventory and parents completed the Pediatric Quality of Life Parent Proxy Inventory and Child Behavior Checklist. QoL scores for OCD patients were significantly lower than for healthy controls, but similar to QoL in a general psychiatric sample on the majority of domains. Parent-child agreement on QoL was moderate to strong across age groups. Results indicate that, in youth with OCD, QoL is reduced relative to healthy controls, related to OCD symptom severity per parent-report, and are strongly predicted by the presence of comorbid externalizing and internalizing symptoms.