PubMed Health⌕ Search

Biomedical subjects

A Bradbury

Publications and source records attributed to A Bradbury.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics and treatments of patients with peripheral arterial disease referred to UK vascular clinics: results of a prospective registry.

BACKGROUND: Peripheral arterial disease (PAD) is often associated with risk factors including cigarette smoking, hypertension and hypercholesterolaemia, and patients have a high risk of future vascular events. Good medical management results in improved outcomes and quality of life, but previous studies have documented sub-optimal treatment of risk factors. We assessed the management of cardiovascular risk factors in patients with PAD referred to specialist vascular clinics. METHODS: This was a prospective, protocol driven registry carried out in UK vascular clinics. Patients who were first-time referrals for evaluation of PAD were eligible if they had claudication plus ankle-brachial pressure index (ABPI) < or = 0.9. Statistical associations between key demographic and treatment variables were explored using a chi-squared test. RESULTS: We enrolled 473 patients from 23 sites. Mean age was 68 years (SD 10) and 66% were male. Mean estimated claudication distance was 100 m, and ABPI was 0.74. Mean systolic blood pressure (SBP) was 155 mmHg, and 42% had a SBP >160 mmHg. Forty percent were current smokers and half had tried to give up in the prior 6 months, but there was no evidence of a systematic method of smoking cessation. Mean total cholesterol was 5.4 (SD1.2) mmol/l and 30% had levels >6 mmol/l. Antiplatelet therapy had been given to 70% and statins to 44%. Prior CHD was present in 29% and these patients had significantly higher use of antiplatelet therapy, statins and ACE-inhibitors. CONCLUSIONS: In spite of attempts to raise awareness about PAD as an important marker of cardiovascular risk, patients are still poorly treated prior to referral to a vascular clinic. In particular, the use of evidence-based treatments is sub-optimal, while hypertension and cigarette smoking are poorly managed. More work needs to be done to educate health professionals about the detection and optimal medical management of PAD.

Adult↗
PubMed2006

Spontaneous pneumopericardium, pneumomediastinum and subcutaneous emphysema: unusual complications of asthma in a 2-year-old boy.

A 2-year-old boy presented to the emergency department with a history of sudden onset of cough, dyspnoea and a slight expiratory wheeze on the right lung base. He also had subcutaneous emphysema on the left side of the chest anteriorly. Chest x ray confirmed subcutaneous emphysema and also revealed pneumomediastinum and pneumopericardium. He had had no previous episode and was not known to have asthma. He was apyrexial but had a raised white cell count. The eosinophil count was within normal limits. He was successfully treated with nebulised salbutamol, steroids, antibiotics and high flow oxygen. He made a good recovery and was discharged after 7 days. This case highlights the need for a high index of suspicion of asthma in very young children presenting for the first time with such complications.

Albuterol↗
PubMed2005

Measuring the impact of venous leg ulcers on quality of life.

OBJECTIVE: To identify health-related quality-of-life (HRQoL) issues in patients with venous leg ulcers, with the aim of generating items for a treatment outcome measure. METHOD: Thirty-eight patients with venous leg ulcers were interviewed by a psychologist using a semi-structured guide; they also completed a HRQoL questionnaire (modified Skindex). Data from the questionnaire were examined to explore the impact of venous leg ulcers on patients' lives. Interview transcripts were analysed using qualitative methods to identify additional venous leg ulcer-specific HRQoL items. RESULTS: Skindex scores indicated that older patients had worse HRQoL (p<0.05), as did those with pain and non-healing ulcers. Ulcer duration and size did not correlate with HRQoL. Interviews revealed the following effects of ulceration: pain (80.5%); itching (69.4%); altered appearance (66.7%); loss of sleep (66.6%); functional limitation (58.3%); and disappointment with treatment (50%). Based on the interview transcripts, items were generated and discussed with an expert panel, with a view to including them in a venous leg ulcer-specific HRQoL questionnaire. CONCLUSION: Disease-specific HRQoL outcome measures should be considered when evaluating treatments for venous leg ulcers.

Activities of Daily Living↗
PubMed2004

Mass screening for coeliac disease using antihuman transglutaminase antibody assay.

AIMS: To determine coeliac disease prevalence by an anti-transglutaminase antibody assay in a large paediatric population; to evaluate acceptance of the screening programme, dietary compliance, and long term health effects. METHODS: Cross-sectional survey of 3188 schoolchildren (aged 6-12) and prospective follow up of diagnosed cases. Main outcome measures were: prevalence of coeliac disease defined by intestinal biopsy or positivity to both human tissue transglutaminase and anti-endomysium antibodies in HLA DQ2-8 positive subjects; percentage of children whose families accepted screening; dietary compliance as defined by negativity for anti-transglutaminase antibodies; and presence of clinical or laboratory abnormalities at 24 month follow up. RESULTS: The families of 3188/3665 children gave their consent (87%). Thirty biopsy proven coeliacs were identified (prevalence 1:106). Three other children testing positive for both coeliac related autoantibodies and HLA DQ2-8 but refusing biopsy were considered as having coeliac disease (prevalence 1:96). Of 33 cases, 12 had coeliac related symptoms. The 30 biopsy proven coeliacs followed a gluten-free diet. Of 28 subjects completing 18-24 months follow up, 20 (71.4%) were negative for anti-transglutaminase antibodies, while eight were slightly positive; symptoms resolved in all 12 symptomatic children. CONCLUSIONS: Prevalence of coeliac disease is high in Italian schoolchildren. Two thirds of cases were asymptomatic. Acceptance of the programme was good, as was dietary compliance. Given the high prevalence and possible complications of untreated coeliac disease, the availability of a valid screening method, and evidence of willingness to comply with dietary treatment population mass screening deserves careful consideration.

Antibodies↗
PubMed2004

Strategies to improve the effectiveness of abdominal aortic aneurysm screening programmes.

OBJECTIVE: Ruptured abdominal aortic aneurysms (rAAAs) occurring in patients with screen-detected aneurysms could be regarded as a failure of screening and reduce effectiveness of screening. To understand this issue, we studied the reasons why rAAAs occur in screened patients and estimated the cost-benefit ratio if these ruptures could be prevented. METHODS: All rAAAs occurring in the Huntingdon district in the UK during the study period (1991-2000) were traced via a combination of hospital admission, accident and emergency attendance, and intensive therapy unit admission records, operating theatre registers and post-mortem reports. Cross-referencing with the aneurysm-screening database identified those patients who had attended screening. Previously used cost-effectiveness models were used to estimate the cost benefits to screening. RESULTS: Ninety-three rAAAs occurred in men over the study period, of whom 23 (25%) had been invited for screening and 13 (14%) had accepted the invitation. All who had been screened (mean age 75 [65-82]) had abnormal aortic diameters (>30 mm) on their first scan. Of those invited, 10/23 (43%) did not attend their screening appointment, 4/23 (17%) were deemed not fit for open surgery, 4/23 (17%) ruptured whilst being assessed for aneurysm repair, 2/23 (9%) ruptured whilst under six-monthly surveillance, and 3/23 (13%) failed to attend scheduled six-monthly surveillance appointments. Reducing screened ruptures by one half could increase the cost-effectiveness of screening by 27%. CONCLUSION: There were no failures of the screening test. The benefits of aneurysm screening can be improved by increasing the uptake of screening, the compliance with surveillance, and by streamlining the work-up process before surgery.

Aged↗
PubMed2003

Treatment of urinary incontinence in cystic fibrosis.

BACKGROUND: Urinary incontinence (UI) is a newly recognised problem in cystic fibrosis. Whilst prevalence is well documented, there are no reports of assessment and treatment of the problem. METHODS: A previous study reports the prevalence of UI in women with CF to be 51/75 (68%). Nineteen women subsequently requested help for the problem and were referred to a physiotherapist specialising in women's health. A digital assessment was performed to measure pelvic floor muscle strength and endurance. An individualised programme of pelvic floor muscle exercises (PFME) was taught based on the assessment. A questionnaire addressed issues of assessment and treatment. RESULTS: 12 women were assessed. The median (range) age, FEV1% predicted and BMI were 20.9 (19.3-46.1) years, 45.9 (14.8-82.7) and 20.5 (16.1-26.0), respectively. The median strength of the pelvic floor muscle was moderate (Oxford Scale grade 3) with a hold time (endurance) of 5 s. At reassessment (median time 13.1 weeks), there was an improvement in endurance (P = 0.04), with no change in strength. This was supported by a subjective improvement in symptoms. Patients found the exercises were difficult to perform, difficult to fit into their treatment programme and adherence was poor. CONCLUSIONS: PFME are effective at improving endurance and reducing leakage over the short-term. Women are reluctant to be assessed and the CF team should provide support and encouragement with treatment. Long-term outcome and the mechanisms of UI in this group of patients need further evaluation.

Adolescent↗
PubMed2002

Mapping the C terminal epitope of the Alzheimer's disease specific antibody MN423.

The mapping of monoclonal antibody epitopes is now predominantly carried out using molecular diversity techniques, phage display in particular. However, until very recently, phage display methods have been inappropriate for the analysis of epitopes that require a free carboxy terminus. Here we describe the use of two different techniques to analyze the known C terminal epitope specificity of MN423, a monoclonal antibody specifically staining truncated tau in Alzheimer's brain. Using a lambda phage based C-terminal random peptide library, and an intracellular expression library based on truncated tau, we show that this antibody has an absolute requirement for a glycine at position -3 with respect to the C terminus. Both methods give similar results, and identify other important residues in the binding site. However, affinity analysis of synthetic peptides revealed that the affinity of the antibody for identified tripeptides was far lower than the pentapeptide sequence in the native target, and that this in turn was considerably below the affinity for the native target itself. This suggests that molecular diversity methods may define minimum, but not necessarily complete epitopes. The methods described here have a general application to the analysis of antibody epitopes suspected to be found at the C terminus.

Aged↗
PubMed2002

A reliable screening procedure for coeliac disease in clinical practice.

BACKGROUND: The main autoantigen recognized by the sera of patients with coeliac disease (CD) is tissue transglutaminase (tTG). A human-recombinant form of tTG was used to develop an ELISA to measure anti-tTG serum antibodies for the diagnosis of CD. Preliminary retrospective reports suggest that the human tTG-based ELISA could identify coeliac patients missed by the IgA-anti-endomysium antibody test (AEA). Whether the human recombinant tTG ELISA is sufficiently accurate to become the main diagnostic CD tool in everyday clinical practice is unknown. The objective was to determine, in a prospective study, the sensitivity and specificity of an ELISA test based on the use of human tTG compared with AEA, to analyse the discordant cases for HLA DQ2-8 and for clinical and intestinal biopsy characteristics. METHODS: 1106 patients referred to a gastrointestinal outpatient clinic for symptoms attributable to CD, 52 first-degree relatives of CD patients and 200 healthy controls were tested for both anti-human tTG and AEA antibodies. RESULTS: Out of 1158 subjects, 146 were tested positive for anti-tTG antibodies and 140 were biopsy-proven coeliacs. The AEA test identified 126/1158 coeliacs who also tested positive for anti-tTG antibodies. The 14 patients missed by the AEA test carried the typical HLA-DQ for CD; they had normal levels of total serum IgA and had milder pathology than those with both anti-tTG and AEA positivity (P < 0001). CONCLUSIONS: These results prove that human tTG-based ELISA is an excellent diagnostic tool for CD, for mass screening by both the specialist and the general clinic.

Adolescent↗
PubMed2001

Using an in vivo phagemid system to identify non-compatible loxP sequences.

The site-specific recombination system of bacteriophage P1 is composed of the Cre recombinase that recognizes a 34-bp loxP site. The Cre/loxP system has been extensively used to manipulate eukaryotic genomes for functional genomic investigations. The creation of additional heterologous loxP sequences potentially expands the utility of this system, but only if these loxP sequences do not recombine with one another. We have developed a stringent in vivo assay to examine the degree of recombination between all combinations of each previously published heterologous loxP sequence. As expected, homologous loxP sequences efficiently underwent Cre-mediated recombination. However, many of the heterologous loxP pairs were able to support recombination with rates varying from 5 to 100%. Some of these loxP sequences have previously been reported to be non-compatible with one another. Our study also confirmed other heterologous loxP pairs that had previously been shown to be non-compatible, as well as defined additional combinations that could be used in designing new recombination vectors.

Attachment Sites, Microbiological↗
PubMed2001

Antibodies in haystacks: how selection strategy influences the outcome of selection from molecular diversity libraries.

Antibodies against most antigens can be isolated from high quality phage antibody libraries. However, not all antibodies binding a particular antigen are necessarily found when standard selections are performed. Here we investigate the effect of two different selection strategies on the isolation of antibodies against a number of different antigens, and find that these different strategies tend to select different antibodies, with little overlap between them. This indicates that the full diversity of these libraries is not tapped by a single selection strategy and that each selection strategy imposes different selective criteria in addition to that of antigen binding. To fully exploit such libraries, therefore, many different selection strategies should probably be employed for each antigen. The use of alternative strategies should be considered when selection apparently fails, or when the number of different antibodies recognizing an antigen needs to be maximised. Furthermore, the microtitre selection strategy developed is likely to prove useful in the application of phage antibody libraries to the human genome project, allowing the high throughput selection of antibodies against multiple antigens simultaneously.

Antibodies↗
PubMed2001

Using an in vivo phagemid system to identify non-compatible loxP sequences.

The site-specific recombination system of bacteriophage P1 is composed of the Cre recombinase that recognizes a 34-bp loxP site. The Cre/loxP system has been extensively used to manipulate eukaryotic genomes for functional genomic investigations. The creation of additional heterologous loxP sequences potentially expands the utility of this system, but only if these loxP sequences do not recombine with one another. We have developed a stringent in vivo assay to examine the degree of recombination between all combinations of each previously published heterologous loxP sequence. As expected, homologous loxP sequences efficiently underwent Cre-mediated recombination. However, many of the heterologous loxP pairs were able to support recombination with rates varying from 5 to 100%. Some of these loxP sequences have previously been reported to be non-compatible with one another. Our study also confirmed other heterologous loxP pairs that had previously been shown to be non-compatible, as well as defined additional combinations that could be used in designing new recombination vectors.

Attachment Sites, Microbiological↗
PubMed2001

Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease.

Celiac disease (CD) is an intestinal malabsorption characterized by intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and tissue transglutaminase, an autoantigen located in the endomysium. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. The role of gliadins in eliciting the immune response in CD and how transglutaminase is linked to the primary reaction are still unclear. In this work, we report the production and analysis of six phage Ab libraries from the peripheral and intestinal lymphocytes of three CD patients. We were able to isolate Abs to transglutaminase from all intestinal lymphocytes libraries but not from those obtained from peripheral lymphocytes. This is in contrast to Abs against gliadin, which could be obtained from all libraries, indicating that the humoral response against transglutaminase occurs at the local level, whereas that against gliadin occurs both peripherally and centrally. Abs from all three patients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family. The possible role of these anti-transglutaminase Abs in the onset of CD and associated autoimmune pathologies is discussed.

Adult↗
PubMed2001

In vivo recombination as a tool to generate molecular diversity in phage antibody libraries.

The creation of diversity in populations of polypeptides has become an important tool in the derivation of polypeptides with useful characteristics. This requires efficient methods to create diversity coupled with methods to select polypeptides with desired properties. In this review we describe the use of in vivo recombination as a powerful way to generate diversity. The novel principles for the recombination process and several applications of this process for the creation of phage antibody libraries are described. The advantage and disadvantages are discussed and possible future exploitation presented.

Animals↗
PubMed2000

Early expression of GABA(A) receptor delta subunit in the neonatal rat hippocampus.

The cDNA library screening strategy was used to identify the genes encoding for GABA(A) receptor subunits in the rat hippocampus during development. With this technique, genes encoding eleven GABA(A) receptor subunits were identified. The alpha5 subunit was by far the most highly expressed, followed by the gamma2, alpha2 and alpha4 subunits respectively. The expression of the beta2, alpha1, gamma1, beta1 and beta3 subunits was moderate, although that of the alpha3 and delta subunits was weak. In situ hybridization experiments, using digoxigenin-labeled cRNA probes, confirmed that the delta subunit was expressed in the neonatal as well as in the adult hippocampus, and is likely to form functional receptors in association with other subunits of the GABA(A) receptor. When the more sensitive RT-PCR approach was used, the gamma3 subunit was also detected, suggesting that this subunit is present in the hippocampus during development but at low levels of expression. The insertion of the delta subunit into functional GABA(A) receptors may enhance the efficacy of GABA in the immediate postnatal period when this amino acid is still exerting a depolarizing and excitatory action.

Animals↗