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A K Webb

Publications and source records attributed to A K Webb.

At least 37 records · Page 2Linked to original sources
PubMed2001

Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic.

We initiated a prospective surveillance study to investigate possible Pseudomonas aeruginosa cross-infection in our cystic fibrosis centre. We characterised isolates by pyocin typing and pulsed-field gel electrophoresis. 22 (14%) of 154 patients with chronic P aeruginosa had isolates with similar and new pyocin and pulsed-field gel electrophoresis types. The shared isolates showed unusual phenotypic features: they were non-pigmented, non-motile, and resistant to a number of antipseudomonal antibiotics. Cross-infection by a multiresistant P aeruginosa strain has therefore occurred in patients attending our cystic fibrosis centre. We recommend microbiological surveillance in other cystic fibrosis centres.

Adult↗
PubMed2001

Questionnaire survey of urinary incontinence in women with cystic fibrosis.

Cystic fibrosis is an inherited disease characterised by the production of infected secretions, and it requires lifelong daily treatment by airway clearance. We knew that some women attending our clinic for adults with cystic fibrosis leaked urine when performing airway clearance or spirometry, but they were dismissive during discussion and were rarely forthcoming about the problem. This study was designed to determine the prevalence of urinary incontinence in women with cystic fibrosis, to establish the importance of the problem as perceived by the patients, and to identify those women who wanted help.

Adolescent↗
PubMed2001

PCR-based detection and identification of Burkholderia cepacia complex pathogens in sputum from cystic fibrosis patients.

PCR amplification of the recA gene followed by restriction fragment length polymorphism (RFLP) analysis was investigated for the rapid detection and identification of Burkholderia cepacia complex genomovars directly from sputum. Successful amplification of the B. cepacia complex recA gene from cystic fibrosis (CF) patient sputum samples containing B. cepacia genomovar I, Burkholderia multivorans, B. cepacia genomovar III, Burkholderia stabilis, and Burkholderia vietnamiensis was demonstrated. In addition, the genomovar identifications determined directly from sputum were the same as those obtained after selective culturing. Sensitivity experiments revealed that recA-based PCR could reliably detect B. cepacia complex organisms to concentrations of 10(6) CFU g of sputum(-1). To fully assess the diagnostic value of the method, sputum samples from 100 CF patients were screened for B. cepacia complex infection by selective culturing and recA-based PCR. Selective culturing identified 19 samples with presumptive B. cepacia complex infection, which was corroborated by phenotypic analyses. Of the culture-positive sputum samples, 17 were also detected directly by recA-based PCR, while 2 samples were negative. The isolates cultured from both recA-negative sputum samples were subsequently identified as Burkholderia gladioli. RFLP analysis of the recA amplicons revealed 2 patients (12%) infected with B. multivorans, 11 patients (65%) infected with B. cepacia genomovar III-A, and 4 patients (23%) infected with B. cepacia genomovar III-B. These results demonstrate the potential of recA-based PCR-RFLP analysis for the rapid detection and identification of B. cepacia complex genomovars directly from sputum. Where the sensitivity of the assay proves a limitation, sputum samples can be analyzed by selective culturing followed by recA-based analysis of the isolate.

Adolescent↗
PubMed2001

Association of alpha(1)-antichymotrypsin deficiency with milder lung disease in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by an excess of free proteinases that destroy lung tissue. Despite this, previous studies have shown that patients with CF with a mild deficiency variant of the proteinase inhibitor alpha(1)-antitrypsin have less, rather than more, severe pulmonary disease. Alpha(1)-antichymotrypsin is another important serine proteinase inhibitor that protects the lung against proteolytic attack, and point mutations in the alpha(1)-antichymotrypsin gene that result in plasma deficiency are associated with chronic obstructive pulmonary disease. METHODS: The effect of alpha(1)-antichymotrypsin deficiency and the -15 alpha(1)-antichymotrypsin signal peptide genotype on lung function was assessed in patients with CF. RESULTS: One hundred and fifty seven patients with CF were screened and 10 were identified with a plasma deficiency of alpha(1)-antichymotrypsin (plasma concentration <0.2 g/l). In a multivariate analysis these individuals had significantly less severe lung disease than those who had normal or raised levels of alpha(1)-antichymotrypsin: forced expiratory volume in one second (FEV(1)) 69.9% predicted versus 53. 2% predicted (p=0.04) and chest radiographic score of 7.2 versus 9.7 (p=0.03) for those with and without alpha(1)-antichymotrypsin deficiency, respectively. The -15 signal peptide genotype did not affect plasma levels, but the -15 Ala/Ala signal peptide genotype was over-represented in individuals with CF compared with healthy blood donor controls. CONCLUSION: These data indicate that deficiency of alpha(1)-antichymotrypsin is associated with less severe pulmonary disease in patients with CF, and support our previous observations that mild genetic deficiency of a proteinase inhibitor is associated with an improved outcome.

Adult↗
PubMed2001

Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis.

BACKGROUND: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis. The aim of this study was to assess the effect of intravenous pamidronate on BMD in these subjects. METHODS: Patients were invited to participate if they had a BMD Z score of -2 or less in the lumbar spine, proximal femur, or distal forearm. Patients were randomised to receive either 30 mg intravenous pamidronate every 3 months + 1 g calcium daily (pamidronate group) or 1 g calcium daily (control group). All pancreatic insufficient patients were prescribed oral vitamin D supplements. RESULTS: After 6 months of treatment the pamidronate group (n=13) showed a significant increase in absolute BMD compared with the control group (n=15) in the lumbar spine (mean difference 5.8% (CI 2.7% to 8.9%)) and total hip (mean difference 3.0% (CI 0.3% to 5.6%)). However, the pamidronate group showed a reduction in BMD compared with the control group in the distal forearm (mean difference -1.7% (CI -3.7% to 0.3%)). The use of pamidronate was associated with a high incidence of bone pain in non-corticosteroid treated individuals. CONCLUSION: Intravenous pamidronate increases axial BMD in adults with cystic fibrosis, but the high incidence of bone pain associated with this treatment might limit its use.

Adolescent↗
PubMed2001

Burkholderia cepacia: current clinical issues, environmental controversies and ethical dilemmas.

Burkholderia cepacia is a plant phytogen and is known as a hardy and versatile organism. Over the past two decades it has emerged as a pathogen in the cystic fibrosis (CF) community, with devastating effects. Pulmonary colonisation can lead to an accelerated decline in lung function. In some cases, it causes a rapid and progressive pneumonic illness termed "cepacia syndrome", which is untreatable and fatal. B. cepacia is inherently resistant to multiple antibiotics and highly transmissible and virulent strains have been identified. CF patients colonised with the organism have to be segregated from their peers to try to prevent cross-infection. However, the pathogenicity of B. cepacia is not limited to CF. Other groups, such as individuals with chronic granulomatous disease and immunocompromised patients are vulnerable and it has caused disease in healthy individuals. However, the agricultural and petrochemical industries are attempting to exploit properties of B. cepacia for use as a biopesticide and biodegradation agent. This article provides an up to date review of clinically based literature on the Burkholderia cepacia complex, highlighting clinical management issues for both cystic fibrosis and non-cystic fibrosis patients. The article also addresses the potential conflict between medicine and agriculture on plans to reintroduce strains of Burkholderia cepacia back into the environment.

Burkholderia Infections↗
PubMed2000

Pulmonary function, serum markers of inflammation, and IgG antibodies to core lipopolysaccharide of Burkholderia cepacia in adults with cystic fibrosis, following colonization with Burkholderia cepacia.

Eight patients with cystic fibrosis [CF] colonized with Pseudomonas aeruginosa (P. aeruginosa) had serial lung function, peripheral blood inflammatory markers, and serum IgG antibodies to Burkholderia cepacia (B. cepacia) lipopolysaccharide measured in the months preceding and following colonisation with B. cepacia. One patient experienced a fall in FEV(1) from 33% to 19% of predicted values, coinciding with the first sputum isolation of B. cepacia, and he died 12 weeks later. He had a rise in inflammatory markers preterminally, and this change was refractory to antibiotic therapy. There was no significant fall in FEV(1) % of predicted values in the remaining seven patients, and no significant changes in their serum markers of inflammation following colonization with B. cepacia over a median (range) period of 10.9 (7.3-12.0) months.

Adult↗
PubMed2000

Perceived body image and eating behavior in young adults with cystic fibrosis and their healthy peers.

Treatment aimed at achieving an ideal nutritional status is an integral part of the management of patients with cystic fibrosis (CF). Emphasis is continually placed upon dietary intake and weight. The effects of this on eating behavior and self-perceptions are unclear. This work compared male and female CF adults with a healthy male and female control population with regard to (a) clinical variables, (b) actual, perceived, and desired body shape/body mass index (BMI), and (c) body satisfaction, eating behaviors and attitudes, and self-esteem. Clinical data were recorded for 221 adults with CF and 148 healthy controls. All subjects completed BMI Charts (perception of body weight/BMI), the Eating Attitudes Test, and scales of body satisfaction and self-esteem. CF patients had poorer lung function and nutritional status than controls. Control males accurately perceived their body shape/BMI and were content with it, whereas CF males viewed their BMI as greater than it actually was and desired to be much heavier. Control females viewed their body shape/BMI as less than it actually was and desired to be even slimmer, in comparison with CF females, who perceived their BMI as less than it actually was but were happy with their perceived shape/weight. Control subjects, especially females, dieted to a greater extent and were more preoccupied with food (with binge eating and intended vomiting) than CF patients. Conversely, those with CF reported greater pressure from others to eat than did controls. More problems with food/eating behavior were associated with less body satisfaction and reduced self-esteem. In comparison with a healthy control population, the perceptions and behaviors of CF adults relating to eating, weight, and body image are not abnormal. Indeed, females with CF have fewer problems than their healthy peers.

Adolescent↗
PubMed2000

Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis.

The major cause of mortality in patients with cystic fibrosis (CF) is lung disease. Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in the airways is a potential treatment. Clinical studies in which the CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in modest, transient gene expression. It seems likely that repeated administration of the gene transfer vector will be required for long-term gene expression. We have undertaken a double-blinded study in which multiple doses of a DNA/liposome formulation were delivered to the nasal epithelium of CF patients. Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes, whilst two subjects received placebo. Each subject received three doses, administered 4 weeks apart. There was no evidence of inflammation, toxicity or an immune response towards the DNA/liposomes or the expressed CFTR. Nasal epithelial cells were collected 4 days after each dose for a series of efficacy assays including quantitation of vector-specific DNA and mRNA, immunohistochemistry of CFTR protein, bacterial adherence, and detection of halide efflux ex vivo. Airway ion transport was also assessed in vivo by repeated nasal potential difference (PD) measurements. On average, six of the treated subjects were positive for CFTR gene transfer after each dose. All subjects positive for CFTR function were also positive for plasmid DNA, plasmid-derived mRNA and CFTR protein. The efficacy measures suggest that unlike high doses of recombinant adenoviral vectors, DNA/liposomes can be successfully re-administered without apparent loss of efficacy.

Adolescent↗
PubMed2000

Antibody response to Burkholderia cepacia in patients with cystic fibrosis colonized with Burkholderia cepacia and Pseudomonas aeruginosa.

INTRODUCTION: This study was designed to determine the relationship between formation of serum antibodies to lipopolysaccharide (LPS) core antigen of Burkholderia cepacia and pulmonary colonization with B. cepacia and Pseudomonas aeruginosa in patients with cystic fibrosis (CF), and to define if an enhanced host humoral immune response to B. cepacia was related to a poor clinical outcome. METHODS: Serum IgG to B. cepacia LPS core antigen was measured in adult cystic fibrosis patients colonized with B. cepacia and P. aeruginosa, and serial titres were measured in 13 B. cepacia and 41 P. aeruginosa colonized patients followed prospectively over 18 months. RESULTS: The median B. cepacia antibody titre was significantly greater in the patients colonized with B. cepacia compared to those colonized with P. aeruginosa, a group which grew B. cepacia intermittently from their sputum. and nine healthy controls. The median antibody titre at recruitment into the study was significantly greater in patients who later went into exacerbations compared with those who remained clinically stable. but there was no difference between B. cepacia antibody titres in patients who died and those who survived the study duration. DISCUSSION: The degree of overlap of serum IgG levels to B. cepacia LPS core antigen in cystic fibrosis patients colonized with B. cepacia and P. aeruginosa does not allow this antibody to be used in a clinical context to define infection status. The magnitude of the humoral response to B. cepacia may influence occurrence of pulmonary exacerbations, but a more exuberant humoral immune response to B. cepacia core LPS is not the mechanism by which pulmonary deterioration occurs.

Adolescent↗
PubMed2000

Development of a disease specific health related quality of life measure for adults and adolescents with cystic fibrosis.

BACKGROUND: Health related quality of life (HRQoL) measurement is important in determining the impact of disease on daily functioning and subsequently informing interventions. In cystic fibrosis (CF) generic HRQoL measures have been employed but these may not be sufficiently specific. The aim of the current work was to develop and validate a disease specific HRQoL measure for adults and adolescents with cystic fibrosis. METHODS: Areas of concern to adults and adolescents with CF were identified by unstructured interviews, self-administered questionnaires, consultation with multidisciplinary specialist staff, a review of the relevant literature, and examination of other HRQoL measures. Items for the questionnaire were generated on the basis of this process. Continued evaluation and development of the Cystic Fibrosis Quality of Life (CFQoL) questionnaire was undertaken by a process of statistical analysis and continued feedback from patients. The full testing and validation of the CFQoL questionnaire took place over four phases: (1) initial item generation and testing of a preliminary questionnaire, (2) testing and validation of the second version of the questionnaire, (3) test-retest reliability of a third and final version of the questionnaire, and (4) sensitivity testing of the final version of the questionnaire. RESULTS: Nine domains of functioning were identified using principal components analysis with varimax rotation. Internal reliability of the identified domains was demonstrated using Cronbach alpha coefficients (range 0.72-0.92) and item to total domain score correlations. Concurrent validity (range r = 0.64-0.74), discriminatory ability between different levels of disease severity, sensitivity across transient changes in health (effect size range, moderate d = 0.56 to large d = 1.95), and test-retest reliability (r = 0.74-0.96) were also found to be robust. CONCLUSIONS: The CFQoL questionnaire is a fully validated disease specific measure consisting of 52 items across nine domains of functioning which have been identified by, and are of importance to, adolescents and adults with cystic fibrosis. This measure will be useful in clinical trials and longitudinal studies.

Adolescent↗