SEARCH · PubMed Health

Results for “CYSTIC FIBROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources

PubMed2003

Function and bulk of respiratory and limb muscles in patients with cystic fibrosis.

Inspiratory muscle weakness due to lung hyperinflation and muscle wasting may occur in cystic fibrosis. We therefore measured diaphragm function and bulk in 18 stable patients with cystic fibrosis and 15 matched control subjects; the abdominal and quadriceps muscles were studied for comparison. We assessed diaphragm mass, abdominal muscle thickness, twitch transdiaphragmatic and gastric pressures, quadriceps cross-section and isokinetic strength, and lean body mass. Lean body mass, quadriceps strength, and quadriceps cross-section were lower in patients with cystic fibrosis. Twitch transdiaphragmatic pressure was 23% lower and twitch gastric pressure was 22% greater in patients with cystic fibrosis than in control subjects, but diaphragm mass and abdominal muscle thickness were similar in the two groups. For any given lean body mass and quadriceps cross-section, patients with cystic fibrosis had greater diaphragm mass and abdominal muscle thickness. Diaphragm mass had greater intersubject variability in patients with cystic fibrosis than in control subjects. We conclude that diaphragm strength is decreased but abdominal muscle strength is increased in patients with cystic fibrosis. Diaphragm and abdominal muscle bulk are not affected by the general muscle wasting, which suggests that there may be a training effect of cystic fibrosis on respiratory muscles. However, the variability of diaphragm mass indicates that this beneficial response does not occur in all patients with cystic fibrosis.

Abdominal Muscles↗

PubMed2006

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.

Adolescent↗

PubMed2001

A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) normally functions as a phosphorylation-regulated chloride channel on the apical surface of epithelial cells, and lack of this function is the primary cause for the fatal disease cystic fibrosis (CF). Previous studies showed that purified, reconstituted CFTR can function as a chloride channel and, further, that its intrinsic ATPase activity is required to regulate opening and closing of the channel gate. However, these previous studies did not identify the quaternary structure required to mediate conduction and catalysis. Our present studies show that CFTR molecules may self-associate in CHO and Sf9 membranes, as complexes close to the predicted size of CFTR dimers can be captured by chemical cross-linking reagents and detected using nondissociative PAGE. However, CFTR function does not require a multimeric complex for function as we determined that purified, reconstituted CFTR monomers are sufficient to mediate regulated chloride conduction and ATPase activity.

Adenosine Triphosphatases↗

PubMed2002

An overview of the pathogenesis of cystic fibrosis lung disease.

The pathogenesis of cystic fibrosis (CF) lung disease is reviewed, focusing on an overview of the physiologic mechanisms that regulate mucus transport. A major emphasis is placed on the active transport systems that regulate the airway surface liquid (ASL) volume and, particularly, regulate the volume of the periciliary liquid (PCL) layer. A sequence is developed for CF whereby there is a depletion of the PCL that reflects the combined dysfunctions of accelerated Na(+)-dependent volume absorption and failure to secrete Cl(-). Both dysfunctions are a direct consequence of missing cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of airway epithelial cells. PCL depletion leads to failure of mucus transport, which is associated with persistent mucin secretion and formation of adherent mucus plaques and plugs. These plugs become the nidus for persistent bacterial airway infections that ultimately lead to a markedly anaerobic luminal environment.

Bacterial Infections↗

PubMed2002

Cystic fibrosis in North Indian children.

Cystic fibrosis is the most common life threatening, inherited disease of the Caucasians. Ever since the gene for this disease was delineated in 1989, there are about 900 mutations discovered so far. This disease is being reported with increasing frequency from North India now. We present our experience with the diagnosis and management of cystic fibrosis in children seen at Post-Graduate Institute of Medical Education and Research, Chandigarh.

Combined Modality Therapy↗

PubMed1999

[Cystic fibrosis lung disease and its management].

The function of the cystic fibrosis (CF) gene product, cystic fibrosis transmembrane conductance regulator (CFTR) is critical to normal lung defense. CFTR not only acts as a cAMP-dependent Cl-channel, but regulates other ion channels and several cellular functions. This article describes the current understanding of the clinical pathophysiology and the management of cystic fibrosis lung disease, particularly the CFTR-related bacterial colonization of the airways. Since chronic lung infection remains the major cause of early death, it is important to interrupt the cycle of infection and inflammation that leads to bronchiectasis and respiratory failure. Only a few cases have been reported in Japanese with no mutations including delta F508 identified. Those cases seem to be caused by unknown factors yet to be found.

Anti-Bacterial Agents↗

PubMedDate not supplied

[Cystic fibrosis: molecular update and clinical implications].

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic pneumopathy, pancreatic insufficiency, elevated sweat chloride levels and male infertility. It is caused by defects in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as a chloride channel. The identification of the CF-causing gene was a landmark in molecular medicine. Currently, over 1,300 disease-causing mutations have been reported to the Cystic fibrosis genetic analysis consortium. deltaF508 mutation is the most common CF allele, however a high heterogeneity of the CFTR mutations spectrum has been observed in populations, particularly in southern Europe and Latin America. Depending on the effect at the protein level, CFTR mutations can be divided in at least 5 classes. These mutations could cause totally (classes I-III) or partially (classes IV and V) loss of the protein function. The molecular defects resulting from different mutations in CFTR partially explain the clinical heterogeneity of the disease, suggesting the existence of modifier genes that are involved in modulating the phenotype and severity of the CF. In this review, we discuss the fundamental aspects and the recent progress that could give to the lector, the knowledge to understand the CFTR gene structure, the function of the CFTR protein, how CF mutations disrupt it, its phenotype consequences and finally, the strategies to design new therapies for the disease.

Cystic Fibrosis↗

PubMed2005

Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis.

BACKGROUND: Stunted children with cystic fibrosis (CF) have less net protein anabolism than do children without CF, and the result is retarded growth in the CF patients. It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body protein synthesis. OBJECTIVE: We studied the effects of 3 amounts of protein intake on whole-body protein synthesis and breakdown by using isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea in children with stable CF who required tube feeding. DESIGN: In 8 pediatric CF patients, we administered 3 randomly allocated isocaloric diets with normal (NP), intermediate (IP), and high (HP) amounts of protein (1.5, 3, and 5 g . kg(-1) . d(-1), respectively) by continuous drip feeding during a 4-d period at 6-wk intervals. Each patient acted as his or her own control. On the fourth day of feeding, whole-body protein synthesis and breakdown were measured. RESULTS: Protein synthesis was significantly higher in the HP group (x +/- SEM: 1.78 +/- 0.07 micromol . kg(-1) . min(-1)) than in the IP (1.57 +/- 0.08 micromol . kg(-1) . min(-1); P=0.001) and NP (1.37 +/- 0.07 micromol . kg(-1) . min(-1); P < 0.001) groups. There were no significant differences in protein breakdown. Net retention of nitrogen was significantly higher in the HP group (12.93 +/- 1.42 micromol . kg(-1) . min(-1)) than in the IP (7.61 +/- 1.40 micromol . kg(-1) . min(-1); P=0.01) and HP (2.48 +/- 0.20 micromol . kg(-1) . min(-1); P < 0.001) groups. CONCLUSION: In stunted children with CF requiring tube feeding, the highest stimulation of whole-body protein synthesis was achieved with a short-term dietary protein intake of 5 g . kg(-1) . d(-1).

Body Height↗

PubMed2004

Type III secretion phenotypes of Pseudomonas aeruginosa strains change during infection of individuals with cystic fibrosis.

Pseudomonas aeruginosa is a frequent cause of respiratory exacerbations in individuals with cystic fibrosis. An important virulence determinant of this pathogen is its type III protein secretion system. In this study, the type III secretion properties of 435 P. aeruginosa respiratory isolates from 56 chronically infected individuals with cystic fibrosis were investigated. Although it had been previously reported that 75 to 90% of P. aeruginosa isolates from patients with hospital-acquired pneumonia secreted type III proteins, only 12% of isolates from cystic fibrosis patients did so, with nearly all of these isolates secreting ExoS and ExoT but not ExoU. Despite the low overall prevalence of type III protein-secreting isolates, at least one secreting isolate was cultured from one-third of cystic fibrosis patients. Interestingly, the fraction of cystic fibrosis patient isolates capable of secreting type III proteins decreased with duration of infection. Although 90% of isolates from the environment, the presumed reservoir for the majority of P. aeruginosa strains that infect patients with cystic fibrosis, secreted type III proteins, only 49% of isolates from newly infected children, 18% of isolates from chronically infected children, and 4% of isolates from chronically infected adults with cystic fibrosis secreted these proteins. Within individual patients, isolates of clonal origin differed in their secretion phenotypes, indicating that as strains persisted in cystic fibrosis patient airways, their type III protein secretion properties changed. Together, these findings indicate that following infection of cystic fibrosis patient airways, P. aeruginosa strains gradually change from a type III protein secretion-positive phenotype to a secretion-negative phenotype.

Adolescent↗

PubMed1991

Cystic fibrosis: current survival and population estimates to the year 2000.

BACKGROUND: Survival from cystic fibrosis is increasing rapidly. Estimates of the extent of this improvement should allow health care facilities to be planned to deal with the expanding population of patients with cystic fibrosis. Estimates of life expectancy are also essential if accurate information on current prognosis is to be given to parents of an affected child, or to prospective parents deciding whether to proceed with a pregnancy where the fetus may be affected. METHODS: Survival trends in the national data on cystic fibrosis have been analysed to produce estimates of the likely size of the cystic fibrosis population over the next decade and to predict the life expectancy of children born with cystic fibrosis in the years up to 1990. RESULTS: In England and Wales the estimated number of patients with cystic fibrosis is at present about 5200, of whom 3300 (63%) are aged under 16 years. By the year 2000 the total population will increase to 6000, with 3400 (57%) aged under 16. Thus the number of children with cystic fibrosis will remain fairly constant over the next 10 years, whereas adult numbers will increase by about 36% (from 1901 to 2577). The median life expectancy of children with cystic fibrosis born in 1990 is estimated to be 40 years, double that of 20 years ago. CONCLUSION: This study suggests that health service provision for children will not need to change substantially over the next 10 years whereas services for adults will need to increase by about a third. Parents can be counselled that the median life expectancy of a newborn child with cystic fibrosis is currently likely to be of the order of 40 years.

Age Factors↗

PubMedDate not supplied

Cystic fibrosis screening.

The integration of universal cystic fibrosis screening in women's health has considerably altered the way we care for obstetric patients and likely will be the foundation for incorporating other genetic tests into routine women's health care. Prior to this change in the standard of care, screening for genetic disease was primarily limited to those individuals who had a personal or family history of the genetic condition or who belonged to a particular ethnic or racial group characterized by a high frequency of carrier and affected individuals. However, technological advances have resulted in facile and economic methodologies for detecting an increasing number of genetic mutations and in the realization that screening for common and uncommon disorders will likely be a not-too-distant-future part of routine health care. Programs that permit clinicians to properly implement genetic protocols and allow patients to make informed decisions about genetic screening and diagnostic tests are needed. The implementation of universal cystic fibrosis screening allows clinicians to recognize the benefits and pitfalls of genetic testing of the general population and encourages the development of programs that will effectively communicate genetic information to professionals and laity.

Cystic Fibrosis↗

PubMed2000

The outcome of 72 pregnancies in 55 women with cystic fibrosis in the United Kingdom 1977-1996.

OBJECTIVE: To identify pregnancies in women with cystic fibrosis and describe obstetric, infant and maternal medical outcomes in relation to the severity of maternal disease. DESIGN: Retrospective study, based on casenotes. SETTING: Eleven cystic fibrosis centres in the United Kingdom. POPULATION: Pregnant women with cystic fibrosis. METHODS: Single observer medical and obstetric casenote review categorising maternal cystic fibrosis (e.g. genotype, pancreatic, hepatic and diabetic status) and pre-pregnant severity (e.g. weight and lung function) and noting fetal outcome and maternal morbidity. MAIN OUTCOME MEASURES: Completed pregnancies and pregnancy losses, fetal outcome and complications, maternal morbidity, such as changes in weight, lung function, pulmonary infections during and after pregnancy. Relation of outcomes to severity of maternal cystic fibrosis. RESULTS: From 72 pregnancies identified, the outcomes were known for 69; there were 48 live births (70%) of which 22 were premature (46%); 14 therapeutic abortions (20%); and 7 miscarriages (10%). There were no stillbirths, neonatal or early maternal deaths. Three major fetal anomalies were seen, but no infant had cystic fibrosis. At the conclusion of our study three pregnancies were still continuing. Prematurity with increased fetal complications and maternal morbidity with infection, declining lung function and poor weight gain were associated with poor pre-partum lung function. CONCLUSION: Pregnancy occurs in women with cystic fibrosis of all degrees of severity. Outcomes for the infant are generally good but are variable for the mother. Predicting outcome on the basis of maternal severity is difficult but lung function appears to be the most significant determining factor. Pregnancy may be normal in women with normal lung function (forced expiratory volume > 80%). However, it may adversely affect mild and moderate lung disease due to cystic fibrosis and should be avoided in pulmonary hypertension, cor pulmonale and when forced expiratory volume < 50% predicted. Ideally, all pregnancies should be planned with prior counselling and monitored by dedicated cystic fibrosis teams, including obstetricians who are experienced in managing high risk pregnancies.

Abortion, Induced↗

PubMed1996

Partial purification of the pig kidney cystic fibrosis transmembrane regulator protein.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane protein that is expressed in several epithelia, including kidney tubules. Mutations in CFTR (a PKA-chloride channel and/or regulator of other epithelial channels) give rise to the clinical manifestation of cystic fibrosis, and result in the synthesis of mutated proteins responsible for altering ion transport across secretory epithelia. The low abundance of endogenous CFTR makes a difficult to purify enough of the native protein to prepare anti-CFTR antibodies. We have used differential centrifugation to prepare cortical brush border membrane vesicles from pig kidney, cBBMV, and developed a method for the partial purification of CFTR. This is the first step in the isolation of native CFTR. The results show that CFTR is present in cBBMV. The purified protein will provide a clearer picture of the biophysical and biochemical properties of native CFTR.

Animals↗

PubMed1996

Cystic fibrosis and the sinonasal tract.

Cystic fibrosis is considered to be one of the most common fatal inherited diseases. Sinonasal manifestations are not outstanding as compared with those in the lower respiratory tract. Panopacification of the paranasal sinuses is, however, almost universal on radiologic examination of patients, although many of these patients do not have sinonasal symptoms. Approximately 10% to 20% of cystic fibrosis patients will eventually require surgical treatment of their sinuses. All treatment, including surgery, is transiently effective; none is curative.

Adolescent↗

PubMed1991

Cl- channel activity in Xenopus oocytes expressing the cystic fibrosis gene.

The expression of the cystic fibrosis (CF) gene on its introduction into nonepithelial somatic cells has recently been shown to result in the appearance of distinctive low conductance chloride channels stimulated by cyclic AMP (Kartner, N., Hanrahan, J.W., Jensen, T.J., Naismith, A.L., Sun, S., Ackerley, C.A., Reyes, E.F., Tsui, L.-C., Rommens, J.M., Bear, C.E., and Riordan, J.R. (1991) Cell 64, 681-691; Anderson, M. P., Rich, D.P., Gregory, R.J., Smith, A.E., and Welsh, M.J. (1991) Science 251, 679-682). Since Xenopus oocytes provide a powerful system for ion channel characterization, we have examined whole cell and single channel currents in them after injection of cRNA to program the synthesis of the cystic fibrosis transmembrane conductance regulator (CFTR). This has enabled the direct demonstration that the cyclic AMP activation is mediated by protein kinase A and that CFTR is without effect on the endogenous calcium-activated chloride channels of the oocyte, which have been well characterized previously and widely used as reporters of the expression of G-protein-coupled receptors. These findings strengthen the argument that the CF gene codes for a novel regulated chloride channel rather than a regulatory protein which can modulate separate chloride channel molecules.

Animals↗

PubMed2003

GFP-tagged CFTR transgene is functional in the G551D cystic fibrosis mouse colon.

Trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) is central to its function, with the most common mutation, deltaF508, resulting in abnormal processing and trafficking. Therefore, there is a significant need to develop tools, which enable the trafficking of CFTR to be studied in vitro and in vivo. In previous studies it has been demonstrated that fusion of the green fluorescent protein (GFP) to the N-terminus of CFTR does lead to functional expression of CFTR chloride channels in epithelial cell lines. The aim of the present study was to examine whether it is possible to express GFP-tagged CFTR as a transgene in colonic and airway epithelial cells of cystic fibrosis (CF) mice and to correct the CF defect. Using the epithelial-specific human cytokeratin promoter K18, we generated bitransgenic mice cftr(G551D/G551) K18-GFP-CFTR(+/-), designated GFP mice. Transcripts for GFP-CFTR could be detected in bitransgenic mice by use of RT-PCR techniques. Expression of GFP-CFTR protein was detected specifically in the colonic epithelium by both direct GFP fluorescence and the use of an anti-GFP antibody. Ussing chamber studies showed that the ion transport defect in colon and airways observed in cftr(G551D/G551D) mice was partially corrected in the bitransgenic animals. Thus, K18-GFP-CFTR is functionally expressed in transgenic mice, which will be a valuable tool in studies on CFTR synthesis, processing and ion transport in native epithelial tissues.

Animals↗

PubMed2001

'CFTR-opathies': disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations.

Cystic fibrosis is a genetic disease that is associated with abnormal sweat electrolytes, sino-pulmonary disease, exocrine pancreatic insufficiency, and male infertility. Insights into genotype/phenotype relations have recently been gained in this disorder. The strongest relationship exists between 'severe' mutations in the gene that encodes the cystic fibrosis transmembrane regulator (CFTR) and pancreatic insufficiency. The relationship between 'mild' mutations, associated with residual CFTR function, and expression of disease is less precise. Atypical 'mild' mutations in the CFTR gene have been linked to late-onset pulmonary disease, congenital bilateral absence of the vas deferens, and idiopathic pancreatitis. Less commonly, sinusitis, allergic bronchopulmonary aspergillosis, and possibly even asthma may also be associated with mutations in the CFTR gene, but those syndromes predominantly reflect non-CFTR gene modifiers and environmental influences.

Aspergillosis, Allergic Bronchopulmonary↗

PubMed2001

Gastric IgA in cystic fibrosis in relation to the migrating motor complex.

BACKGROUND: Gastrointestinal symptoms in cystic fibrosis are frequent, but little is known about the underlying pathophysiology. Mucosal secretion of IgA is important for the immunologic function in the human gastrointestinal tract but has not been studied in cystic fibrosis. The aim of this study was to quantify the release of IgA by the gastric mucosa in relation to interdigestive motor activity in patients with cystic fibrosis with different genotypes. METHODS: The study included 7 healthy adult volunteers and 10 adult patients with cystic fibrosis, all Helicobacter pylori-negative. All patients had pathological sweat tests and clinical symptoms and signs of cystic fibrosis. All but one were colonized with Pseudomonas aeruginosa. Three patients were pancreatic sufficient. The investigation was performed using intragastric perfusion and gastroduodenal manometry. RESULTS: During the investigation, 8 of 10 patients with cystic fibrosis showed the characteristic pattern of interdigestive motility. The patients had significantly lower levels of gastric IgA compared to healthy subjects during phases II and III of migrating motor complex, median (range) 120 (67-442) and 36 (6-299) microg/5 min. 382 (40-1176) and 56 (4-398) (P = 0.03 and P = 0.04), respectively. Only one patient with genotype R668C/unknown showed IgA levels within the normal range. There was no correlation to gastric presence of duodenogastric reflux markers. CONCLUSION: The interdigestive motility pattern was normal in most patients with cystic fibrosis. The low levels of IgA released from the gastric mucosa in the patients might indicate a defective gastric transmucosal IgA transport in cystic fibrosis.

Adult↗