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Biomedical subjects

A R Exley

Publications and source records attributed to A R Exley.

18 recordsLinked to original sources
PubMed2006

Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient characteristics.

The aim of the current study was to investigate the prevalence and clinical associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort of patients with adult-onset bronchiectasis. The sputum of all patients attending a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was examined for mycobacteria as part of an extensive diagnostic work-up. NTM-positive patients subsequently had further sputa examined. A modified bronchiectasis scoring system was applied to all high-resolution computed tomography (HRCT) scans from NTM-positive patients, and a matched cohort without NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first culture; of those, eight provided multiple positive cultures. Three patients were treated for NTM infection. A higher proportion of NTM-positive than -negative patients were subsequently diagnosed with cystic fibrosis (two out of nine versus two out of 75). On HRCT scoring, more patients in the NTM-positive group had peripheral mucus plugging than in the NTM-negative group. In the current prospective study of a large cohort of patients with bronchiectasis, 10% cultured positive for nontuberculous mycobacteria in a random clinic sputum sample. Few clinical parameters were helpful in discriminating between groups, except for a higher prevalence of previously undiagnosed cystic fibrosis and of peripheral mucus plugging on high-resolution computed tomography in the nontuberculous mycobacteria group.

Aged↗
PubMed2005

Chronic Burkholderia multivorans bronchial infection in a non-cystic fibrosis individual with mannose binding lectin deficiency.

The case history is presented of a woman with multiple respiratory infections and mannose binding lectin (MBL) deficiency but no evidence of bronchiectasis who developed a chronic Burkholderia multivorans infection. Careful microbiological assessment is needed in patients with recurrent respiratory infection and the presence of B multivorans should trigger further immunological investigation including assessment of MBL status.

Adult↗
PubMed2000

Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease?

BACKGROUND: Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mortality. This may result from arteriosclerosis following inflammatory damage to the vessel wall by vasculitis. Our hypothesis that vasculitis results in arteriosclerosis by causing vascular endothelial dysfunction was tested in patients with primary systemic necrotizing vasculitis (SNV). METHODS AND RESULTS: Endothelial function was assessed in cross-sectional and longitudinal studies of patients with primary SNV by measuring flow-mediated, endothelium-dependent brachial artery vasodilatation. These patients exhibited marked endothelial dysfunction compared with controls. Remission induction in patients with active primary SNV restored endothelial function. CONCLUSIONS: Endothelial function is significantly impaired in adults with primary SNV, supporting the hypothesis that premature arteriosclerosis in chronic inflammatory rheumatic disorders results from endothelial dysfunction secondary to vasculitis. Normalization of endothelial function after the treatment of primary SNV suggests that early suppression of disease activity in chronic inflammatory rheumatic disorders may reduce long-term vascular damage. The role of inflammation in atheroma formation is increasingly appreciated; this work raises questions regarding the potential for anti-inflammatory therapy in atherosclerosis itself.

Brachial Artery↗
PubMed2000

Percutaneous image-guided biopsy of lung nodules in the assessment of disease activity in Wegener's granulomatosis.

OBJECTIVE: In patients with known Wegener's granulomatosis (WG) and persistent chest radiographic abnormalities, assessment for disease activity is often difficult, prompting the need for histological diagnosis to determine appropriate treatment. Here we report the use of automated image-guided core needle biopsy of pulmonary lesions for the assessment of disease activity in WG, rather than for primary diagnosis. METHODS: Image-guided percutaneous core needle biopsy was performed on five occasions in four patients with thoracic WG and persistent radiographic abnormalities of the chest. Clinical features, indication for biopsy, radiographic abnormalities and pathological findings were recorded. RESULTS: Adequate pathological specimens were obtained, allowing exclusion of infection and tumour. Active chronic inflammation with or without vasculitis was demonstrated in each case, indicating the need for further immunosuppressive therapy. A small pneumothorax following biopsy in one case required no treatment. Follow-up chest imaging revealed a reduction in the extent of thoracic disease following therapy in all cases. CONCLUSIONS: The safety and diagnostic accuracy of image-guided core biopsy of thoracic lesions makes it a useful tool in the assessment of disease activity in WG patients with persistent chest radiographic lesions.

Adult↗
PubMed1999

Localized bowel vasculitis: postoperative cyclophosphamide or not?

We describe 2 patients with necrotizing vasculitis localized to the bowel, who were treated by excision of the involved tissue. Postoperatively, there was no evidence of active vasculitis, and both patients remain in remission on followup, without the use of immunosuppressive treatment. Evidence that an abnormal local microenvironment is necessary to sustain chronic inflammation may explain why surgical excision can be an important tool in the treatment of vasculitis.

Adult↗
PubMed1998

Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI).

Assessment of disease severity in systemic vasculitis encompasses mortality, which is now uncommon, and morbidity, which is increasing in significance. Morbidity includes permanent scars or damage, an evolving concept offering a novel perspective which may be particularly valuable in chronic disease. We have developed a method for assessing damage in systemic vasculitis, but the relationship between damage and disease severity was unknown. Therefore, we examined whether the number of items of damage or the pattern of damage varied with the severity of systemic vasculitis. We established the characteristics of severe disease by examining fatal vasculitis as an example of the most severe disease possible. We then showed that more damage occurred in fatal vasculitis, more systems were damaged, and critical damage akin to organ failure was more common in fatal than non-fatal vasculitis. These observations were reproduced in specific diagnostic groups, namely classical Wegener's granulomatosis and systemic rheumatoid vasculitis. Thus, severe disease was characterized by many items of damage, multisystem damage and critical damage. This pattern of damage was also seen in a subgroup of patients with non-fatal vasculitis, who also have severe disease.

Adult↗
PubMed1997

Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides.

OBJECTIVE: To develop and validate the Vasculitis Damage Index (VDI) for the standardized clinical assessment of damage in the systemic vasculitides. METHODS: Using a nominal group consensus approach, the Birmingham Vasculitis Group generated guiding principles for assessment of damage in all systemic vasculitides. Damage was defined as irreversible change resulting from scars. Consensus principles were developed into the VDI, including guidelines for use, a list of items of damage, and a glossary. RESULTS: For 100 surviving patients with systemic vasculitis, the median VDI score at last observation was 3 (range 0-8). Within the Wegener's granulomatosis subgroup, the median VDI score for 12 non-survivors was higher than for 47 survivors (non-survivors median score 7, interquartile range 5-8 versus survivors median score 4, interquartile range 2-5; P = 0.003). VDI scores for 100 patients with systemic vasculitis increased from initial presentation to last observation by a median score of 3 (range 1-4; P < 0.001). The VDI assesses more items and is more sensitive to change than other indices of damage (P < 0.001). Using the VDI, trained observers can produce moderately consistent damage scores. CONCLUSION: The VDI is a sensitive, reproducible, comprehensive, and credible clinical tool for quantifying damage. The data presented herein should enable further validation and testing of the VDI in specific vasculitic syndromes, and should facilitate the comparison of different therapies.

Humans↗
PubMed1997

Disease assessment and management of the vasculitides.

The improvement in survival with chemotherapy has resulted in a change of the natural history of the systemic vasculitic syndromes. The vasculitides are now viewed as chronic disease rather than fatal conditions. Their course is frequently characterized by relapse as well as the scars of irreversible organ damage from disease and drug toxicity. Assessment tools are available which can serve as outcome measures in clinical trials as well as a guide to better management of individual patients. Improvements in therapy in future are dependent on a better understanding of the pathogenesis of these conditions and the ability to assess disease accurately.

Animals↗
PubMed1997

Damage occurs early in systemic vasculitis and is an index of outcome.

Because death after acute systemic vasculitis is now uncommon, alternative measures of outcome are required. A significant component of patient morbidity is disease-related damage, which can be quantified by the Vasculitis Damage Index (64 items in 11 organ-based systems). We investigated serially the time-course of damage in 120 patients with systemic vasculitis, to determine the earliest indicators of outcome. High damage scores at 2 years after presentation were characteristic of fatal disease (OR 8.1-12.4). Significant damage occurred within 6 months of presentation, and was a feature of fatal disease. More damage occurred after presentation than after relapse. Lung and multi-system damage were early indicators of poor outcome in severe non-fatal disease. Damage occurs early in systemic vasculitis, and is an indicator of poor outcome. This novel observation, together with evidence of persistent subclinical disease activity and the high frequency of relapse, suggests a need for new treatment strategies. Analogy with the management of acute leukaemia suggests a strategy of early diagnosis and intensive induction of remission, with early escalation of treatment for resistant disease.

Acute Disease↗
PubMed1996

Clinical disease activity in systemic vasculitis.

Long-term follow-up data indicate that the systemic vasculitides are chronic relapsing diseases with high morbidity. It is therefore of paramount importance to distinguish activity, which requires cytotoxic or immunosuppressive therapy, from damage requiring rehabilitation. Damage due to underlying disease or treatment highlights the need for more effective, less toxic treatment regimens. An integrated package for clinically based assessment of disease activity in systemic vasculitis, the Vasculitis Integrated Assessment Log, has been accepted for further evaluation and implementation by the European Community Study Group for use in therapeutic trials. The added value of serologic tests and inflammatory markers in clinical assessment is becoming more clear, and unsuspected disease activity has been revealed by biopsy and imaging of standard sites or affected areas. Integration of these data should enable characterization of high- and low-risk patient subgroups to determine specific therapies.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Tumour necrosis factor-alpha and other cytokines in Guillain-Barré syndrome.

The efficacy of plasma exchange implicates myelinotoxic humoral factors in the pathogenesis of Guillain-Barré syndrome. Candidate factors include autoantibodies to peripheral nerve myelin, which are not unique to Guillain-Barré syndrome; and cytokines such as tumour necrosis factor-alpha (TNF-alpha) which are T cell/macrophage products. Plasma cytokine concentrations were determined in 26 patients with Guillain-Barré syndrome undergoing plasma exchange, 25 with other acute neurological diseases, and 40 healthy controls. Raised TNF-alpha concentrations (> 25 pg/ml) were found in seven of 26 patients with Guillain-Barré syndrome v none of 23 disease controls (p = 0.001). The peak grade of clinical deficit correlated with TNF-alpha concentrations (r = 0.6, p < 0.01). There was no significant difference between interleukin-1 beta or interferon-gamma concentrations in patients and disease controls. The data suggest that TNF-alpha may be a critical factor in the pathogenesis of Guillain-Barré syndrome.

Cytokines↗
PubMed1993

Treatment of septic shock with antibodies to tumour necrosis factor.

The high mortality associated with septic shock has prompted intensive study of the pathophysiological basis of this syndrome in an effort to better understand the processes that lead to tissue injury. One important outcome of this work has been the recognition that the cytokine tumour necrosis factor (TNF) is an important mediator of endotoxin-induced lethality. Accordingly, studies were done which showed that antibodies to TNF could protect animals from death in a variety of model systems, and based on these findings, clinical studies were initiated. This paper reviews the present status of clinical trials of anti-TNF in sepsis. These antibodies appear to be safe, and preliminary experience suggests that they may be effective in some patients with the sepsis syndrome. A final assessment of efficacy must await the large, placebo-controlled trials that are now in progress.

Adult↗
PubMed1993

Attention deficit hyperactivity disorder, creativity, and the effects of methylphenidate.

Given that children with attention deficit hyperactivity disorder (ADHD) are more impulsive than peers, this study explored whether they are correspondingly more creative, and whether creativity declines when impulsivity is decreased through methylphenidate (Ritalin) therapy. A repeated-measures quasi-experimental design was used to compare the performance of 19 boys with previously diagnosed ADHD and 21 comparison boys aged 8 through 11 on two administrations of alternate forms of the Torrance Tests of Creative Thinking-Figural (nonverbal). Boys with ADHD received prescribed methylphenidate only for the first session. Overall, mean Torrance summary scores for comparison boys (mean = 115.1, SD = 16.1) were higher than for boys with ADHD (mean = 107.6, SD = 12.7). However, the difference between means was small (7%) and did not meet the 25% criterion for a clinically significant difference. No changes in performance over time (comparison group) or medication state (ADHD group) were observed. These data suggest that, when measured nonverbally, the creative thinking performance of boys with ADHD is not superior to that of peers who do not have ADHD. Regarding the effects of methylphenidate, prescribed therapy did not influence performance on this measure of creative thinking.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis.

Endotoxaemia and circulating tumour necrosis factor are important prognostic factors in severe sepsis and are implicated in the pathogenesis of septic shock. Because clinical and pathological features in acute pancreatitis are similar to septic shock this study sought to determine whether endotoxin and tumour necrosis factor were prognostic factors in 38 patients with prognostically severe acute pancreatitis. Endotoxaemia, present in 19/37 (51%) patients on day 1, was more common in nonsurvivors than survivors (10/11, 91% v 9/26, 35%, p = 0.003). Day 1 serum endotoxin concentrations were higher in patients with a severe outcome (median (interquartile range) 314 (173-563) pg/ml v 0 (0-185) pg/ml, p<0.01) and in non-survivors (266 (173-586) pg/ml v 0 (0-165) pg/ml, p<0.01). Serum tumour necrosis factor was detectable in 47 of 109 samples (43%) from 38 patients (median 35 pg/ml, range 5-943 pg/ml). Day 1 serum tumour necrosis factor correlated with a worse prognostic score and a severe outcome in all patients (n = 38, r = 0.36, p = 0.027; r = 0.33, p<0.05) and with mortality in patients with gall stones (n = 23, r = 0.50, p = 0.02). Our data suggest that endotoxin and tumour necrosis factor could be prognostic factors in severe acute pancreatitis.

Acute Disease↗
PubMed1990

Optimal collection of blood samples for the measurement of tumor necrosis factor alpha.

We have examined how delayed separation of plasma from cells affects the recovery of recombinant human tumor necrosis factor alpha (rhTNF alpha) from whole blood. Storage of heparinized whole blood samples at room temperature for 1 hr results in a significant (p = 0.036) fall in recovery of plasma TNF alpha from 788 +/- 119 pg/mL to 472 +/- 77 pg/mL, measured by specific enzyme-linked immunosorbent assay (ELISA). Storage of whole blood samples at 4 degrees C for 1 hr reduces but does not prevent the fall in recovery of plasma TNF alpha: 725 +/- 82 pg/mL at time 0, 472 +/- 81 pg/mL after 1 hr, p = 0.038. Recovery of bioactive TNF alpha (cytotoxocity for L929 cells) after 1 hr at room temperature is also significantly reduced from 576 +/- 139 pg/mL to 450 +/- 154 pg/mL, p = 0.036. Studies with 125I-rhTNF alpha confirmed the fall in plasma activity and revealed a rapid commensurate increase in 125I-rhTNF alpha activity in the cell fractions. We recommend that clinical samples for the measurement of cytokines should be kept at 4 degrees C and separated rapidly (within half an hour) before storing the plasma at -70 degrees C.

Animals↗