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 1,387 records · Page 77Linked to original sources

PubMed1996

[Epidemiologic study of the cystic fibrosis gene in the Champagne-Ardenne region].

Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder among Caucasians and is caused by abnormalities in the cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR gene encodes a chloride channel that regulates secretion in many exocrine tissues especially pancreatic and pulmonary tissues. The clinical presentation of cystic fibrosis is highly variable with isolated CAVD (congenital absence of vas deferens) and/or typical pancreatic and pulmonary manifestations. Over 500 mutations in the CFTR gene have been described and vary among different geographic locations. The severity of clinical manifestations and specially the pulmonary disease is poorly correlated with genotype. It is interesting to collect clinical and genetical data by analysing a larger cohort of CF patients. These results are likely to improve our understanding of the physiopathology of CF and the genetic counselling; particular biochemical defect could lead to more specific treatments in the future. From our 110 patients selected in Champagne-Ardenne country, we analysed the entire coding sequence of CFTR gene and detected 95% of CF mutations and in fact, 89.5% if we include the CAVD patients; 59.4% of CF mutations were detected for these patients. Three new mutations have been here reported. We found numerous CF mutations with a large distribution throughout the gene. Nevertheless, three exons are mainly involved: 10, 11 and 21. Relationships between the genotype and phenotype are difficult to assess.

Adolescent↗

PubMed1992

Dermatitis as a presenting sign of cystic fibrosis.

BACKGROUND: Three percent to 13% of patients with cystic fibrosis present with protein-energy malnutrition that is characterized by hypoproteinemia, edema, and anemia and is associated with high morbidity and mortality. Cutaneous manifestations of malnutrition are rare in patients with cystic fibrosis and have been attributed to deficiencies of protein, zinc, and essential fatty acids. OBSERVATIONS: We describe five patients who presented with failure to thrive, hypoproteinemia, edema, and a cutaneous eruption before the onset of pulmonary symptoms and before the diagnosis of cystic fibrosis was made. The rash had a predilection for the extremities (lower > upper), perineum, and periorificial surfaces. In most cases, erythematous, scaling papules developed by 4 months of age and progressed within 1 to 3 months to extensive, desquamating plaques. Alopecia was variable, and mucous membrane or nail involvement was not observed. The rash was associated with malnutrition and resolved in all survivors within 10 days of providing pancreatic enzyme and nutritional supplementation. The pathogenesis of the rash is unclear, but it appears to stem from deficiencies of zinc, protein, and essential fatty acids and may be mediated by alterations in prostaglandin metabolism. CONCLUSIONS: Cystic fibrosis should be included in the differential diagnosis of the red, scaly infant, particularly when failure to thrive, hypoproteinemia, and edema are also present. Recognition of rash as a sign of cystic fibrosis complicated by protein-energy malnutrition will allow earlier diagnosis and treatment of these patients and may improve their outcome.

Cystic Fibrosis↗

PubMed2003

Using disease registries for pharmacoepidemiological research: a case study of data from a cystic fibrosis registry.

BACKGROUND: The Epidemiologic Registry of Cystic Fibrosis (ERCF) was a multicentre, longitudinal follow-up project of cystic fibrosis patients enrolled at some 200 centres in nine European countries between 1994 and 1999. PURPOSE: We aimed to assess and improve the quality of a subset of data from the ERCF relating to seven English centres (1184 patients), prior to using the data for a long-term cost-effectiveness analysis of dornase alfa (Pulmozyme). Specifically we wanted to assess the completeness and accuracy of the data and the comparability of cases across centres. METHODS: We used a subset of ERCF data relating to seven UK cystic fibrosis (CF) centres. Following initial data editing, key variable data from a sample of patients from five centres were subjected to a detailed verification of ERCF data against original data sources available in the centres. Disagreements between ERCF reports and original data sources were identified and corrected in the study dataset. In addition, centre staff were questioned about relevant clinical and recording practices. RESULTS: Thanks to detailed routine data checking procedures on key variables operated by the ERCF, the rates of disagreement between ERCF data and original data as identified in our verification process on the assessed variables are generally low (0.4-3.7%). Some outcome variables (deaths, hospitalisations) seem to be under-reported by some centres. Episodes of pulmonary exacerbation are difficult to identify and also to verify. Twenty-four patients were registered twice (consecutively in two different centres). There were some differences between centres in their interpretation of recording rules. CONCLUSIONS: Researchers seeking to use disease registry data should consider detailed data quality review processes. Apart from data accuracy, reliable definitions of both critical events as well as their timing are important. The degree of under-reporting, particularly of outcome variables, should be estimated. Information on local clinical and reporting practices is necessary to interpret multi-centre data. Data protection issues may limit the possibilities for detailed data quality assessments of secondary data, as does the accessibility of original data for verification purposes. Our experiences and recommendations may be valuable for those intending to use disease registry data as well as those devising and operating such registries.

Adult↗

PubMed1989

Biliary stone disease in adults with cystic fibrosis.

A 27-year-old woman with cystic fibrosis had a 6-month history of fatty food intolerance and biliary colic. Ultrasonographic studies confirmed the presence of gallstones. A cholecystectomy and appendectomy were performed. An intraoperative cholangiogram showed anomalous drainage of the cystic duct into an accessory right hepatic duct. Patients with cystic fibrosis now commonly survive into adulthood and are at high risk for the development of cholelithiasis. The diagnosis may be obscured by other common gastrointestinal complications of cystic fibrosis. Optimal surgical management includes meticulous preoperative and postoperative pulmonary care. The surgeon must also have a thorough knowledge of the biliary tract anomalies that have been described in patients with cystic fibrosis.

Adult↗

PubMed1997

Dietary fibre and the occurrence of gut symptoms in cystic fibrosis.

OBJECTIVE: To evaluate the effect of currently recommended energy rich cystic fibrosis diets on fibre intake and to investigate the relationship between fibre intake and the occurrence of gut symptoms. METHOD: Prospective completion of non-weighed five day food diaries by 28 children with cystic fibrosis and comparison of mean daily fibre intake with age matched controls who did not have cystic fibrosis. Prospective completion of similar diaries to a total of 68 children with cystic fibrosis and comparison of fibre and lipase intake with the occurrence of gut symptoms. RESULTS: Mean daily fibre intake in children with cystic fibrosis was 7.00 g compared with 14.65 g in controls (p < 0.001). Mean daily fibre intake in eight patients troubled with moderate or severe abdominal pain was 0.144 g/kg. This was significantly lower (p < 0.01) than mean values for 22 patients with occasional but mild symptoms (0.249 g/kg) and 38 with no gut symptoms (0.312 g/kg). There was a trend towards higher pancreatic enzyme doses (lipase/kg/day) in children with abdominal pain. CONCLUSIONS: Currently recommended cystic fibrosis diets have a low fibre content. A low residue diet might be an important factor in the pathogenesis of gastrointestinal symptoms.

Abdominal Pain↗

PubMed1999

Hip fracture and bone histomorphometry in a young adult with cystic fibrosis.

A 25-yr-old male with cystic fibrosis sustained a fragility fracture of the left femoral neck, which required surgical correction. He had several risk factors for the development of low bone density and despite treatment with an oral bisphosphonate, his bone mineral density reduced further. The patient died 2 yrs after sustaining the fracture. Bone specimens obtained at post mortem demonstrated severe cortical and trabecular osteopenia, but the histological features were not typical of osteoporosis or osteomalacia. Osteoporosis is thought to be a common complication of cystic fibrosis. The novel histomorphometric appearances reported here suggest that the bone disease of cystic fibrosis may be more complex and possibly unique. Labelled bone biopsies are required to clarify the bone defect leading to low bone density in cystic fibrosis patients so that appropriate therapeutic strategies can be developed.

Adult↗

PubMed1999

Physiological basis of cystic fibrosis: a historical perspective.

Physiological Basis of Cystic Fibrosis: A Historical Perspective. Physiol. Rev. 79, Suppl.: S3-S22, 1999. - Cystic fibrosis made a relatively late entry into medical physiology, although references to conditions probably reflecting the disease can be traced back well into the Middle Ages. This review begins with the origins of recognition of the symptoms of this genetic disease and proceeds to briefly review the early period of basic research into its cause. It then presents the two apparently distinct faces of cystic fibrosis: 1) as that of a mucus abnormality and 2) as that of defects in electrolyte transport. It considers principal findings of the organ and cell pathophysiology as well as some of the apparent conflicts and enigmas still current in understanding the disease process. It is written from the perspective of the author, whose career spans back to much of the initial endeavors to explain this fatal mutation.

Cystic Fibrosis↗

PubMed1990

Frequency of the F508 deletion in the CFTR gene in Turkish cystic fibrosis patients.

The F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene was found in 8 out of 30 Turkish cystic fibrosis (CF) chromosomes (27%). Five Turkish delta F508 CF chromosomes were associated with the risk haplotype B in KM19 (2 allele)/XV2c (1 allele). In the Turkish population, cystic fibrosis is predominantly caused by mutations other than the F508 deletion.

Chromosome Deletion↗

PubMed2001

Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. I. Methods, safety, and clinical implications.

Cystic fibrosis (CF), an autosomal recessive disorder resulting from mutations in the cystic fibrosis trans-membrane conductance regulator (CFTR) gene, is the most common lethal genetic illness in the Caucasian population. Gene transfer to airway epithelium, using adenoviruses containing normal CFTR cDNA, leads to transient production of CFTR mRNA and, in some studies, to correction of the airway epithelial ion transport defect caused by dysfunctional CFTR. Inflammatory responses to the adenoviral vector have been reported, particularly at high viral titers. We evaluated the effects of adenovirus-mediated CFTR gene transfer to airway epithelium in 36 subjects with CF (34 individuals, 2 of whom received two separate doses of vector), 20 by lobar instillation and 16 by aerosol administration. Doses ranged from 8 x 10(6) to 2.5 x 10(10) infective units (IU), in 0.5-log increments. After lobar administration of low doses there were occasional reports of cough, low-grade temperature, and myalgias. At the highest lobar dose (2.5 x 10(9) IU) two of three patients had transient myalgias, fever, and increased sputum production with obvious infiltrates on CT scan. After aerosol administration there were no significant systemic symptoms until the 2.5 x 10(10) IU dose, when both patients experienced myalgias and fever that resolved within 24 hr. There were no infiltrates seen on chest CT scans in any of the patients in the aerosol administration group. There were no consistent changes in pulmonary function tests or any significant rise in serum IgG or neutralizing antibodies in patients from either group. Serum, sputum, and nasal cytokines, measured before and after vector administration, showed no correlation with adenoviral dose. Gene transfer to lung cells was inefficient and expression was transient. Cells infected with the vector included mononuclear inflammatory cells as well as cuboidal and columnar epithelial cells. In summary, we found no consistent immune response, no evidence of viral shedding, and no consistent change in pulmonary function in response to adenovirus-mediated CFTR gene transfer. At higher doses there was a mild, nonspecific inflammatory response, as evidenced by fevers and myalgias. Overall, vector administration was tolerated but transfer of CFTR cDNA was inefficient and transgene expression was transient for the doses and method of administration used here.

Adenoviridae↗

PubMed1992

Variation of sweat sodium and chloride with age in cystic fibrosis and normal populations: further investigations in equivocal cases.

Patients attending cystic fibrosis clinics had sweat sodium and chloride concentrations measured, were reassessed clinically and had DNA studies performed. Sweat test results were compared with a matched control population. In both populations sweat sodium increased with age up to 12 years, and did not change significantly thereafter. The age-related increase was significantly less in the cystic fibrosis group. Sweat chloride increased with age in normal, but not in cystic fibrosis children. After age 12 years there was no age-related change in the normal group, and a fall with age in the cystic fibrosis group. Sweat chloride provided the best discrimination between normal and cystic fibrosis populations and this was particularly important in older subjects. Combining sweat sodium and chloride results did not improve discrimination. Nine patients were identified with equivocal sweat chloride results. DNA studies showed six of these subjects were heterozygous for the delta F508 mutation in the cystic fibrosis gene. Clinical assessment did not always resolve cases with borderline sweat chloride results.

Adolescent↗

PubMed1982

Lysosomal enzyme secretion by cystic fibrosis fibroblasts is normal.

Lysosomal enzyme secretion by skin fibroblasts derived from cystic fibrosis homozygotes and normal donors of the same range of age, sex and culture passage number were compared. No differences were detected between these groups in their rates of spontaneous lysosomal enzyme release. Incubation of either normal or cystic fibrosis fibroblasts with cystic fibrosis serum did not alter these secretion rates. The lysosomal enzyme secretion of both normal and cystic fibrosis fibroblasts responded similarly to incubation with NH4Cl, monensin, A23187, trifluoperazine or Cytochalasin B. It was concluded that lysosomal enzyme hypersecretion, which has previously been suggested to occur in cystic fibrosis, is unlikely to provide a reliable diagnostic test for the disease.

Acetylglucosaminidase↗

PubMed1982

Treatment and prognosis of rectal prolapse in cystic fibrosis.

Rectal prolapse occurred in 112 (18.5%) of 605 cystic fibrosis patients. In 48 patients prolapse preceded diagnosis of cystic fibrosis, but physicians (pediatricians, pediatric and general surgeons, and proctologists) rarely appreciated its importance as a symptom of this disease. Prolapses frequently cease with institution of pancreatic enzyme replacement therapy following diagnosis of cystic fibrosis. However, even when the disease remains undiagnosed, the symptom is often transient and frequently resolves at 3-5 yr of age. Prolapse occurring initially after cystic fibrosis is diagnosed rarely responds to manipulation of diet or enzyme doses. Many patients develop a method of reduction which involves voluntary abdominal, perineal, and gluteal muscles and does not require manual pressure on the prolapsed segment. Most patients do not need specific treatment for the prolapse. Surgery is rarely necessary. A sweat test should be obtained on any child who has had even a single episode of rectal prolapse.

Adolescent↗

PubMed1990

Cystic fibrosis patients' B-lymphocyte response is resistant to the in vitro enhancing effect of corticosteroids.

Cystic fibrosis is associated with an cAMP-regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B-cell dysfunction potentially related to this defect, we studied the in vitro IgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co-cultured with autologous monocytes and stimulated with Staphylococcus aureus Cowan or with Nocardia-delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10(-7) mol l-1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10(-6) mol l-1, whereas this agent induced a dose-related enhancement from 10(-8) to 10(-6) mol l-1 in cultures of normal cells. Co-culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti-CD3 antibody-induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 alpha- or beta-induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to bacterial bronchopulmonary infections.

Adolescent↗

PubMedDate not supplied

Ciprofloxacin pharmacokinetics in patients with cystic fibrosis.

The pharmacokinetics of ciprofloxacin were studied in cystic fibrosis patients and healthy volunteers following oral administration of 500 mg and 1000 mg. Serum kinetics as well as urinary recovery were monitored. As the body weights of cystic fibrosis patients and the healthy volunteers differed significantly, kinetic parameters were calculated on the basis of a constant relative dose in mg/kg body weight. Neither serum kinetics nor urinary recovery differed significantly between the two groups, as indicated by the serum concentration versus time curves ranging from 1.1 to 1.4 mg X h/l, the elimination half-life of 4.4 to 5.1 h and the 24 h urinary recovery which amounted to 35% to 41% of the dose administered. Serum concentrations were linearly proportional to the doses administered. Sputum concentrations were monitored in cystic fibrosis patients. Again, ciprofloxacin sputum levels were linearly proportional to the doses and were within the same range as serum concentrations. Thus, ciprofloxacin kinetics are not altered in cystic fibrosis patients as compared to healthy volunteers.

Administration, Oral↗

PubMed1993

Myocardial fibrosis--a rare complication in patients with cystic fibrosis.

We report a 10-month-old male infant who was admitted to our hospital with a history of failure to thrive and bulky stools. On examination, he was dystrophic and had a protruding abdomen, but he was well oxygenated and his lungs were clear on auscultation. A tachycardia of 145 beats per min and radiological evidence of cardiomegaly indicated involvement of the heart, but an ECG failed to show signs of myocarditis or cardiac hypertrophy. An elevated sweat chloride concentration of 141 mEq/l confirmed the diagnosis of cystic fibrosis (CF). Molecular analysis revealed heterozygosity for the common mutation delta F508. He died unexpectedly of a sudden cardiac arrest 2 days later. Autopsy revealed scattered myocardial necrosis and fibrosis. Some 50 documented cases of myocardial fibrosis in infants with CF have been reported. Suggested causes such as malnourishment and hypovitaminosis remain speculative as systematic studies have yet to be done.

Cardiomegaly↗

PubMed2002

Predictors of deterioration of lung function in cystic fibrosis.

The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.

Adolescent↗

PubMed1993

Pharmacokinetics of cyclosporine in heart and lung transplant candidates and recipients with cystic fibrosis and Eisenmenger's syndrome.

OBJECTIVE: To compare the pharmacokinetics of cyclosporine in patients with either cystic fibrosis or Eisenmenger's syndrome. METHODS: Patients in the study were heart and lung transplant candidates with either cystic fibrosis (n = 6) or Eisenmenger's syndrome (n = 5), as well as patients who received heart and lung transplantation for either cystic fibrosis (n = 13) or Eisenmenger's syndrome (n = 7). This was no experimental pharmacokinetic study in transplant candidates and an exploratory population pharmacokinetic study in transplant recipients. RESULTS: Patients with cystic fibrosis showed higher blood cyclosporine clearance, higher apparent oral clearance, shorter mean residence time, and more erratic absorption. The coefficient of variation of pharmacokinetic parameters was higher in patients with cystic fibrosis. There were no significant differences in metabolite indexes between the two groups of patients after either oral or intravenous administration. A significant negative correlation was found between cyclosporine clearance and hematocrit (r = 0.81 [95% confidence interval, -0.95 to -0.4.1]). Dose-normalized predose blood concentration measurements were lower in patients with cystic fibrosis after transplantation. There was a significant correlation between hematocrit and log dose-normalized cyclosporine concentration (r = 0.40 [95% confidence interval, 0.30 to 0.49]). The total daily dose per 100 ng/ml trough blood concentration required was estimated to be 2.36 times (95% confidence interval, 1.96 to 2.84) higher in patients with cystic fibrosis. CONCLUSIONS: Cyclosporine pharmacokinetics is more variable in patients with cystic fibrosis. The difference in cyclosporine clearance between the two groups is accounted for by differences in binding in blood rather than metabolism. The findings suggest that patients with cystic fibrosis could be conservatively given initial oral doses that are 1.5 times higher than those for patients who receive transplants because of Eisenmenger's syndrome.

Adult↗

PubMed1989

The effect of nicardipine, a calcium channel blocker, on the sweat test in adult patients with cystic fibrosis.

Impaired cell membrane chloride ion movement in cystic fibrosis results in reduced resorption of sodium and chloride from sweat gland ductules producing the high concentrations measured in the sweat as a diagnostic test. Normal chloride ion movement can be restored in vitro by blocking transepithelial calcium flux with lanthanum, suggesting a potential role for calcium channel blocking drugs in the management of cystic fibrosis. We studied the effect of nicardipine, a calcium channel blocker, on the sweat sodium in 17 adult patients with cystic fibrosis. Nicardipine was administered intravenously or topically using iontophoresis or occlusive dressing. No significant change in sweat sodium concentration was observed between pre- and post-drug administration. We conclude that nicardipine used in vivo does not exert the same effect as lanthanum demonstrates in vitro on transepithelial cell membrane chloride ion movement in cystic fibrosis.

Administration, Topical↗