PubMed Health⌕ Search

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 1,639 records · Page 91Linked to original sources
PubMed2005

The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era.

Cystic fibrosis (CF) is the most common inherited disorder of childhood. The diagnosis of CF has traditionally been based on clinical features with confirmatory evidence by sweat electrolyte analysis. Since 1989 it has been possible to also use gene mutation analysis to aid the diagnosis. Cloning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has advanced our understanding of CF, in particular the molecular basis of an expanded CF phenotype. However, because there are over 1000 mutations and 200 polymorphisms, many without recognised effects on CFTR, the molecular diagnosis can be troublesome. This has necessitated measurement of CFTR function with renewed interest in the sweat test. This review provides an overview of the clinical features of CF, the diagnosis and complex genetics. We provide a detailed discussion of the structure and function of CFTR and the classification of CFTR mutations. Sweat electrolyte analysis is discussed, from the physiology of sweating to the rigours of a properly performed sweat test and its interpretation. With this information it is possible to understand the relevance of the sweat test in the genomic era.

Journal Article↗
PubMed1999

Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease.

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.

Adolescent↗
PubMed2004

Pancreatitis in hispanic patients with cystic fibrosis carrying the R334W mutation.

BACKGROUND & AIMS: Cystic fibrosis (CF) results from abnormal production of sticky mucus, which obstructs many organs. In most cases, the pancreas is severely compromised, but 10%-15% of patients with CF have pancreas sufficiency (PS) and are subject to develop pancreatitis. The aim of this study is to determine which specific genotypes lead to the development of pancreatitis in patients with CF. METHODS: We used prospective data collected by the Cystic Fibrosis Foundation and performed a nested case-control study with all patients who reported at least 1 episode of pancreatitis constituting the cases. We used logistic regression to assess the association between pancreatitis and genotype and the Kaplan-Meier method to estimate the cumulative incidence of pancreatitis for selected genotypes. RESULTS: Three hundred sixty-four of 17,871 genotyped patients with CF (2.0%) reported at least 1 episode of pancreatitis. Only 0.9% of 12,997 patients with genotypes generally associated with pancreas insufficiency reported pancreatitis against 11.9% of 868 patients carrying at least 1 mild CF mutation generally associated with PS. The greatest rate of pancreatitis (19.0%) was observed for patients carrying an R334W mutation: 48% of these 79 patients were Hispanic and 13 patients were living in Puerto Rico. CONCLUSIONS: Of all patients with CF, those carrying an R334W mutation have the greatest risk for developing pancreatitis. This mutation is found mostly in Hispanic patients with CF living in Puerto Rico. There are no current data to determine whether asymptomatic carriers of the R334W mutation are at greater risk for developing pancreatitis or whether this mutation is frequent in Hispanics with idiopathic pancreatitis.

Adolescent↗
PubMed1982

Comparison of the polypeptide composition of cystic fibrosis plasma with normal plasma by high resolution electrophoresis.

Cystic fibrosis and normal plasma proteins were compared by the method of high resolution two-dimensional electrophoresis in polyacrylamide gels. For the first dimension, samples were treated with urea and dithiothreitol and then subjected to isoelectric focusing in pH gradients of 3.5-10.0 or 5.0-8.0. The second dimension involved sodium dodecyl sulfate electrophoresis into gels of 10-20% polyacrylamide gradients. In one "blind" experiment, an attempt to segregate 12 plasma samples into six cystic fibrosis and six normals based on the polypeptide patterns was unsuccessful. Experiments using known cystic fibrotic and normal plasma samples (three further samples of each), depleted of albumin prior to electrophoresis, also failed to confirm the presence of cystic fibrosis related proteins or peptides. We have not been able to substantiate, by electrophoretic means, changes of sialic acid content of any plasma glycoprotein which might be expected to occur, for example, as a result of the postulated altered sialyltransferase activity in cystic fibrosis liver.

Blood Proteins↗
PubMed1994

Osteopenia in adults with cystic fibrosis.

PURPOSE: To examine the frequency and severity of osteopenia in adults with cystic fibrosis and the clinical variables associated with reduced bone mineral. PATIENTS AND METHODS: The bone mineral status of 22 white adults (14 women) with cystic fibrosis was compared with normative data from healthy white control subjects in a university medical center. Lumbar spine, femoral neck, and whole-body bone mineral was determined by dual energy x-ray absorptiometry and expressed as bone mineral content (g), bone mineral density (g/cm2), and bone mineral apparent density (g/cm3). Bone mass was related to age, body mass, gonadal function, pulmonary status, and glucocorticoid exposure to identify variables associated with reduced bone mineral in cystic fibrosis. RESULTS: Bone mineral in adults with cystic fibrosis was significantly below expected values for age and sex at all sites using all expressions of bone mass. The mean Z-score was -2.8 for the lumbar spine bone density, -2.5 for the femoral neck, and -2.0 for the whole body. Bone mineral apparent density (a term that minimizes the influence of bone dimensions) was also significantly reduced in patients at the lumbar spine (p < 0.0001) and femoral neck (p < 0.001 to p < 0.0001), indicating that the bone mineral deficit seen in adults with cystic fibrosis could not be attributed to differences in bone size. Age, weight, height, and body mass index were significantly correlated with bone mineral. Pulmonary status, glucocorticoid use, and gonadal function failed to predict bone mineral status. CONCLUSIONS: Osteopenia and osteoporosis occur commonly in young adults with cystic fibrosis. Age and body mass are predictive of bone mineral, although the pathogenesis of this bone mineral deficit is likely multifactorial.

Absorptiometry, Photon↗
PubMed1990

Preventing postoperative complications in the adult cystic fibrosis patient.

Herein we report on a 27-year-old cystic fibrosis (CF) patient who developed bronchospasm, secretory plugging of the trachea, and pneumothorax following general endotracheal anesthesia for intranasal polypectomy and bilateral Caldwell-Luc procedures at an adult facility. Intranasal polypectomy and paranasal sinus procedures are the most common surgical procedures performed on cystic fibrosis patients, making the otolaryngologist a frequent member of the cystic fibrosis team [8]. As survival improves, the pediatric otolaryngologist will find himself following CF patients into their 20's and 30's. Adult care facilities may not be as familiar with these patients as the surgeon would like. The otolaryngologist's familiarity with the unique perioperative requirements of the CF patient can prove invaluable in such a setting. Preoperative assessment should identify any acute pulmonary changes, assess nutritional status, assure good control of blood glucose levels, and rule out clotting abnormalities. Good perioperative hydration and meticulous attention to pulmonary toilet are of foremost importance in the surgical care of the cystic fibrosis patient. Chest physiotherapy and suctioning of the tracheobronchial tree should precede arousal from anesthesia and extubation. By insisting on appropriate anesthetic and perioperative care, the knowledgeable otolaryngologist may circumvent potential postoperative complications in the cystic fibrosis patient.

Adult↗
PubMed2006

Detection of F508del mutation in cystic fibrosis transmembrane conductance regulator gene mutation among Malays.

INTRODUCTION: Cystic fibrosis (CF) is one of the common genetic disorders in the western world. It has been reported to be very rare in Asian populations. According to the Cystic Fibrosis Genetic Analysis Consortium, more than 1,000 mutations of the CF gene have been identified. The CF gene, named the cystic fibrosis transmembrane conductance regulator (CFTR), is located on chromosome 7 and composed of 27 exons. This study aims to detect possible CFTR gene mutations in Malays. METHODS: We analysed 50 blood samples from healthy Malays with no symptoms of CF. DNA was extracted from blood using commercially available extraction kits (Eppendorf, Germany). Identification of CFTR gene mutation was performed using the CF OLA (Oligonucleotide Ligation Assay) kit (Applied Biosystems, USA). The PCR-ligation products were electrophoresed on eight percent sequagel using an ABI PRISM 377 genetic analyser (Applied Biosystems, USA). Electrophoresis data was analysed using the Genotyper software and a report of the CF genotype for all loci tested was created using the CF Genotyper Template software. Out of 50, one sample (two percent) was detected to have the F508del mutation (3bp deletion at exon 10), which is one of the most common CFTR gene mutations in Caucasians. RESULTS: The F508del mutation allele was detected in one subject. This indicates that she was a CF carrier. CONCLUSION: We report the finding of a carrier of the F508del mutation of the CFTR gene in the Malay population. Our finding revealed that CF could also affect the Malay population. Larger studies are necessary to determine the exact gene frequency of this population.

Asian People↗
PubMed2000

Reaching the diagnosis of cystic fibrosis--the limits of the spectrum.

BACKGROUND: Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in Caucasians. Typically it is a multisystem disease diagnosed by increased chloride levels on sweat testing, with mortality due mainly to progressive respiratory disease. The clinical spectrum of CF has recently been much expanded. Genetic testing for mutant CF transmembrane regulator has revealed atypical cases where sweat test results are borderline or normal. In other patients, genetic mutations cannot be identified but abnormal CFTR function is shown using nasal potential difference measurement. OBJECTIVES: To highlight the diagnostic and therapeutic dilemmas in cases of atypical cystic fibrosis. METHODS: We reviewed patients with atypical CF and widely varying phenotype who are managed at Schneider Children's Medical Center of Israel. RESULTS: Two patients had severe lung disease but little expression in other organs. Accurate diagnosis was essential to enable aggressive therapy in a specialized center. Four other patients are in excellent general health but have symptoms limited to male infertility, heat exhaustion, pancreatitis or transient liver dysfunction, while lung disease is minimal. For these patients, careful counseling is needed to avoid unnecessary upheaval, inappropriately aggressive management, and the psychosocial implications of a CF diagnosis. These dilemmas have increased considerably in our center, as in others worldwide. CONCLUSION: It is our obligation as clinicians--at the level of both primary physician and referral center--to maintain an ever higher index of suspicion for CF, tempered by a rational program of counseling and management appropriate to the individual.

Adult↗
PubMed2000

Pitfalls in the immunohistochemical localization of the cystic fibrosis transmembrane conductance regulator in paraffin embedded sweat glands.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the hereditary disease cystic fibrosis. The most frequent mutant deltaF508 has been shown in vitro to be retained in the endoplasmic reticulum. Ex vivo studies using immunohistochemical labelling in cryofixed skin biopsies have confirmed the mislocalization of deltaF508 CFTR in sweat glands. The purpose of this study was to test CFTR antibodies in paraffin-embedded skin biopsies to take advantage of the superior tissue preservation as compared to cryofixation. A panel of 7 CFTR antibodies was applied to skin sections of healthy controls and of cystic fibrosis patients homozygous for the deltaF508 mutation. Sweat gland labelling consistent with CFTR localization and different between control and cystic fibrosis tissue was obtained with 2 antibodies. Conventional staining controls confirmed the labelling specificity. The antibodies were subsequently tested in a series of 237 sections of 16 biopsy specimens. However, the sweat gland labelling pattern proved not to be dependent on CFTR genotype. This finding was the sole indicator of non-specificity of the staining which was revealed only by the size of our random sample. Our results emphasize that CFTR immunolabelling following formalin fixation has to be interpreted with the utmost caution.

Antibodies, Monoclonal↗
PubMed1993

Molecular biology of cystic fibrosis.

The past decade of research in cystic fibrosis has produced a wealth of information about the underlying defect responsible for the disease. The initial finding that the physiological disturbance in CF is one of abnormal electrolyte transport across epithelial tissues led to the elucidation of a pathway in which epithelial chloride transport is normally elicited in response to beta-adrenergic stimuli and involves the second messenger cAMP to activate protein kinase A. While that pathway was being described, work on the genetic front was concurrently providing information about the genomic location of the gene causing CF, which ultimately led to the identification and cloning of the gene encoding the cystic fibrosis transmembrane conductance regulator. The cloned CFTR gene provided a powerful reagent to use in the next generation of cell physiology experiments, in which it was determined that CFTR is not only the substrate of PKA phosphorylation, a step previously determined to be in the activation pathway of the chloride channel, but is in fact a cAMP-dependent chloride conducting channel itself. Further analysis of the gene has shown that although there is a single mutation that accounts for most of CF, there are well over 200 other lesions within the gene that can cause disease as well. Identification of these mutations has provided information into the normal function of CFTR by studying these variants in heterologous expression systems. As a result, the molecular mechanism of CFTR function is beginning to unfold, as well as the mechanism by which particular mutations impair that function. From a clinical perspective, the research brings optimism from two directions. First, understanding how disease-causing mutations impair function may culminate in pharmacologic approaches that can restore function to some of these mutants. Second, treating the disease at the level of the gene appears to be a realistic goal: Gene transfer experiments in cultured CF cells have shown that the procedure will restore cAMP-dependent chloride conductance to the cells, laying the groundwork for somatic cell gene therapy as a feasible treatment for CF. Currently, work is rapidly progressing in developing delivery systems for this purpose. Finally, animal models that should not only aid in understanding the physiology of electrolyte transport in epithelia but should serve as indicators for tests of therapeutic approaches to treating CF are being developed, either by pharmacological means or by gene delivery protocols.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1998

Safety of paranasal sinus surgery in patients with cystic fibrosis.

OBJECTIVE: Document the safety of paranasal sinus surgery in cystic fibrosis patients and review the changing trends in paranasal sinus surgery in the cystic fibrosis population. STUDY DESIGN: Retrospective review. MATERIALS AND METHODS: Chart review of cystic fibrosis patients who underwent paranasal sinus surgery from 1955 to 1997. RESULTS: Indications for surgery included chronic sinusitis, nasal obstruction, purulent rhinorrhea, head pain, and pyocele. Average duration of anesthesia was 2.1 hours. The complication rate from general anesthesia was zero. Excessive bleeding and significant hypoxia did not occur. CONCLUSIONS: Paranasal sinus surgery and general anesthesia can be safely performed in cystic fibrosis patients. The indications for paranasal sinus surgery are changing from symptomatic nasal obstruction to pre-lung transplantation care. Today, treatment has evolved to include placement of sinus catheters for direct topical instillation of antibiotics and consideration of maxillary and frontal sinus obliteration.

Adolescent↗
PubMed1982

Overdiagnosis of cystic fibrosis.

In 7 patients seen over 3 years, cystic fibrosis had been wrongly diagnosed. The initial sweat test was misleadingly high in only 3 cases. In 1 case no sweat test had been done, and in 4 one or more normal sweat-test results were ignored. As a result of misdiagnosis 4 children were sent to schools for the physically handicapped and 1 man lost his job in the police. Despite warnings about the limitations of sweat tests and dangers of diagnosing cystic fibrosis without typical clinical features, cystic fibrosis is wrongly diagnosed in substantial numbers of children in England.

Adolescent↗
PubMed1982

Meconium peritonitis, intraperitoneal calcifications and cystic fibrosis.

Twelve cases of meconium peritonitis were retrospectively reviewed in this study. Five of these patients had cystic fibrosis. Of the patients with cystic fibrosis, intraperitoneal calcifications were present in three (60%) and two (40%) had none. All seven patients (100%) who had meconium peritonitis without cystic fibrosis had abdominal calcifications. These results indicate that the presence of intraperitoneal calcifications does not exclude the diagnosis of cystic fibrosis and that the absence of calcification favors cystic fibrosis. However, a review of the literature indicates the absence of calcification is merely of clue and not definitive as to the etiology of the meconium peritonitis.

Calcinosis↗
PubMed2000

Population screening for cystic fibrosis in Western Australia: community response.

We measured acceptance of carrier testing for cystic fibrosis in the community when offered in a primary care setting, determined variables influencing acceptance, and assessed knowledge of cystic fibrosis 3-6 months later. A total of 5,102 individuals age 18-50 years attending general practices or a family planning clinic in Western Australia completed questionnaires about knowledge of cystic fibrosis and the State Anxiety Inventory. Testing for the delta F508 gene was offered. After 3-6 months, carriers, a sample of consenting participants who were not tested, and a sample of test-negative participants were sent a further questionnaire; 43.5% of participants chose to be tested for cystic fibrosis carrier status. Women, younger people, people with higher education, people without children, and people planning to have children were more likely to be tested. After 3-6 months, carriers gave correct responses to questions about cystic fibrosis more frequently than those who tested negative or were not tested; 82.2% of carriers knew that they were definitely a carrier and 31.1% of test-negative individuals believed they were definitely not carriers. Thus, population carrier screening for cystic fibrosis offered in a community setting in Western Australia was acceptable to almost half of those offered testing, particularly younger people and those planning to have children, for whom knowledge of carrier status could be useful in making reproductive decisions. There was evidence that tested individuals recalled information in a way that minimised their risk of being a carrier.

Adolescent↗
PubMed1989

Clinical and genetic comparisons of patients with cystic fibrosis, with or without meconium ileus.

We set out to determine if the clinical course or genetic profiles of patients with cystic fibrosis who had meconium ileus differed from those of other patients with cystic fibrosis. Since 1950 we have followed 158 patients with meconium ileus among 1175 patients with cystic fibrosis (13.4%). Patients with meconium ileus had lower birth weight (3026 +/- 610 gm) than patients with no meconium ileus (3169 +/- 534 gm; p less than 0.008); the deficit was especially evident in female patients. Survival in the first year of life increased from 55% in those born between 1958 and 1972 to 96% in those born between 1973 and 1987. Since 1973 the median survival of male and female patients with meconium ileus was similar to that in female patients with no meconium ileus (21 years), whereas 78% of males with no meconium ileus survived to this age (p less than 0.0001). Patients with meconium ileus born before 1972 had lower weight and height percentiles at age 13 years compared with patients with no meconium ileus, but this difference was not as apparent in patients born after 1973. There were no differences between the two groups in forced vital capacity, forced expiratory volume in 1 second, or forced expiratory flow in the middle half of forced vital capacity. Patients with meconium ileus acquired Pseudomonas aeruginosa at a younger age than did patients with no meconium ileus (4.20 +/- 4.67 vs 7.18 +/- 5.19 years), but there was no difference in age of acquisition of P. cepacia. In families in which the first child had meconium ileus, 29% of subsequent siblings with cystic fibrosis had meconium ileus, compared with 6% of siblings born to families in which the first child did not have meconium ileus. Allelic frequencies and haplotypic variants for cystic fibrosis chromosomes with respect to DNA markers closely linked to the cystic fibrosis locus were similar in families with cystic fibrosis with meconium ileus and those with no meconium ileus. These findings suggest that patients with cystic fibrosis and those without meconium ileus do not have major intrinsic differences and that the previously poor outlook in patients with meconium ileus has improved greatly.

Adolescent↗
PubMed1996

Prevalence of cystic fibrosis mutations in pregnancies with fetal echogenic bowel.

OBJECTIVE: To determine the prevalence of the most common cystic fibrosis mutations in pregnancies complicated by fetal echogenic bowel by using DNA testing. METHODS: Forty-five pregnancies with fetal echogenic bowel were studied prospectively for cystic fibrosis mutations. Using polymerase chain reaction, DNA from fetal amniocytes (n = 21), fetal blood (n = 5), or parental blood (n = 19) was amplified and tested for delta F508, G551D, G542X, and 621 + 1G-->T cystic fibrosis mutations, which account for about 85% of the mutations in the British population. In selected cases, further mutations were tested according to the parental ethnic background. RESULTS: Only one of the 26 fetuses screened was heterozygous for cystic fibrosis mutations. Among 38 parental samples screened from the remaining 19 pregnancies, cystic fibrosis mutations were detected in two cases, only one of the parents being a carrier in each case. The prevalence of cystic fibrosis carrier status in fetal and parental samples (1:26 and 1:19, respectively) is within the expected prevalence in the British population (1:25). No fetuses were affected by cystic fibrosis in this series, but five were found to have growth restriction, two trisomy 21, two congenital infection, and two bowel obstruction. CONCLUSION: Our results suggest that ultrasonographic detection of fetal echogenic bowel is not associated with an increased prevalence of cystic fibrosis mutations in pregnancies at low risk for this disease.

Adolescent↗
PubMed1976

Electrophoretic studies of the cystic fibrosis ciliary inhibitor and its interaction with immunoglobulin G.

The cystic fibrosis ciliary inhibitor (CFCI) has been partially purified from serum and plasma of cystic fibrosis (CF) homozygotes and heterozygotes, and from media of cultured fibroblasts derived from cystic fibrosis genotypes. Characterization and comparison of fractions containing the CFCI were carried out by polyacrylamide gel electrophoresis. Gel electrophoresis confirmed previous molecular weight estimations of 4,500 to 11,000 for the CFCI and provided an estimate of the number of proteins present in the fractions. Low molecular weight proteins from serum and media were combined with IgG preparations. No specific binding to IgG by the media fraction containing the CFCI could be demonstrated by the techniques employed. There was decreased binding of the low molecular weight serum fraction containing CFCI to native IgG molecules from cystic fibrosis patients as compared to IgG from normal individuals. However, IgG from CF individuals demonstrated increased binding of the cfci-containing low molecular weight serum fraction after gel filtration in the presence of guanidinium chloride. This suggests: 1) that very low concentrations of CFCI are present in media fractions; and 2) that native CF IgG cannot bind the low molecular weight CFCI fractions to the same degree as native IgG from normals or CF IgG that has been dissociated from non-covalently bound components.

Blood Proteins↗