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Biomedical subjects

A U Wells

Publications and source records attributed to A U Wells.

At least 37 records · Page 2Linked to original sources
PubMed2004

HRCT diagnosis of diffuse parenchymal lung disease: inter-observer variation.

BACKGROUND: This study was designed to measure inter-observer variation between thoracic radiologists in the diagnosis of diffuse parenchymal lung disease (DPLD) using high resolution computed tomography (HRCT) and to identify areas of difficulty where expertise, in the form of national panels, would be of particular value. METHODS: HRCT images of 131 patients with DPLD (from a tertiary referral hospital (n = 66) and regional teaching centres (n = 65)) were reviewed by 11 thoracic radiologists. Inter-observer variation for the first choice diagnosis was quantified using the unadjusted kappa coefficient of agreement. Observers stated differential diagnoses and assigned a percentage likelihood to each. A weighted kappa was calculated for the likelihood of each of the six most frequently diagnosed disease entities. RESULTS: Observer agreement on the first choice diagnosis was moderate for the entire cohort (kappa = 0.48) and was higher for cases from regional centres (kappa = 0.60) than for cases from the tertiary referral centre (kappa = 0.34). 62% of cases from regional teaching centres were diagnosed with high confidence and good observer agreement (kappa = 0.77). Non-specific interstitial pneumonia (NSIP) was in the differential diagnosis in most disagreements (55%). Weighted kappa values quantifying the likelihood of specific diseases were moderate to good (mean 0.57, range 0.49-0.70). CONCLUSION: There is good agreement between thoracic radiologists for the HRCT diagnosis of DPLD encountered in regional teaching centres. However, cases diagnosed with low confidence, particularly where NSIP is considered as a differential diagnosis, may benefit from the expertise of a reference panel.

Adult↗
PubMed2004

A retrospective study of the association between haematological and biochemical parameters and morphine intolerance in patients with cancer pain.

BACKGROUND: Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines of the World Health Organization (WHO). However, a minority of patients do not receive the desired analgesic effect or suffer intolerable side effects from morphine, and are switched to alternative opioids. METHODS: The aim of this retrospective study was to identify factors that might be associated with morphine intolerance. Data were analysed from 100 controls who tolerated morphine and 77 patients who were switched to an alternative opioid. We investigated whether currently logged data could fully explain the need to switch. Demographic details, cancer type (histological diagnosis) and markers related to organ function were included in an analysis of biochemical and haematological parameters. RESULTS: Patients over 78 years (P = 0.03), or with a high white cell (P = 0.002) or high platelet count (P = 0.003), were more likely to switch. Although our numbers were small, patients with severe organ impairment were more likely to switch. However, a model including white cell count, platelet count, age, serum albumin and alkaline phosphatase, accurately separated switchers and controls in only 68% of cases. There was no significant difference between the two groups in terms of the numbers of patients having cytotoxic drugs in the two weeks prior to the haematological and biochemical analysis. Similarly, there were no significant differences in histological diagnoses between groups. CONCLUSIONS: The white cell count was the strongest single effect observed and, as such, warrants further investigation. Further studies are needed in order to accurately define a model that will predict those patients likely to be intolerant of morphine.

Aged↗
PubMed2003

Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection.

OBJECTIVE: Pulmonary fibrosis is associated with an increased risk of lung cancer and outcome of surgical resection in this setting is unknown. METHODS: We studied 22 patients (24 operations) with pulmonary fibrosis and non-small cell lung cancer treated between 1991 and 2000 (study group) and compared outcome with 951 other patients (964 operations) treated for non-small cell lung cancer over the same period (control patients). RESULTS: The two groups did not differ significantly in age (68 vs 65 years), smoking history (86% vs 95% smokers), forced expiratory volume in 1 second (2.5 L/min vs 2.3 L/min) or forced vital capacity (3.2 L vs 3.7 L), but patients with pulmonary fibrosis were more likely to be male (72% vs 58%, P <.05). The operative mortality was higher in patients with pulmonary fibrosis than in control patients (17% vs 3.1%, P <.01) and there was a higher procedure-specific mortality in pulmonary fibrosis for pneumonectomy (33% vs 5.1%, P <.01) and lobectomy (12% vs 2.6%, P <.01). Patients with pulmonary fibrosis had a higher incidence of postoperative lung injury, (21% vs 3.7%, P <.01) and a longer mean hospital stay (17 vs 9 days, P <.05). In patients with pulmonary fibrosis, the actuarial 3-year survival was 54%. There were 11 deaths in the study group, 4 postoperatively (all acute respiratory distress syndrome) and 7 late deaths (metastatic disease, n = 2; progressive pulmonary fibrosis, n = 5). Median follow-up (to death or last review) was 13 months (range, 0-120 months). Five patients developed postoperative acute respiratory distress syndrome and in 4 of these patients this proved to be fatal. Postoperative acute respiratory distress syndrome was associated with lower preoperative total lung carbon monoxide diffusion capacity (median, 58% vs 70%, P =.03) and lower preoperative carbon monoxide diffusion capacity corrected for alveolar volume (median, 48% vs 58%, P =.05) and a higher preoperative composite physiological index (median, 44 vs 33, P =.008). None of the preoperative lung function parameters or operative finding were predictors of late death. CONCLUSION: Patients with pulmonary fibrosis undergoing pulmonary resection for non-small cell lung cancer have increased postoperative morbidity and mortality, but an important subgroup has a good long-term outcome. Postoperative acute respiratory distress syndrome is associated with low preoperative gas transfer and a high composite physiological index. Resection of non-small cell lung cancer is appropriate in pulmonary fibrosis, provided that the level of functional impairment is carefully factored into patient selection.

Aged↗
PubMed2003

Inhibitor kappa B-alpha (IkappaB-alpha) promoter polymorphisms in UK and Dutch sarcoidosis.

The aetiology of sarcoidosis is uncertain; current thinking implicates exposure of genetically susceptible hosts to environmental factors. The nuclear factor kappa B (NF-kappaB) family of transcription factors are critical regulators of immediate transcriptional responses in inflammatory situations and immune responses. Inhibitor kappa B-alpha (IkappaB-alpha) inhibits NF-kappaB and plays a major role in controlling its activity. We investigated IkappaB-alpha promoter polymorphisms using sequence-specific primer-polymerase chain reaction, at positions -881 (A/G), -826 (C/T), and -297 (C/T) in Caucasian sarcoidosis patients (UK and Dutch [NL]), each with their own controls. Disease severity at presentation was assigned using chest radiography and pulmonary function indices. In the combined populations, the -297T allele carriage was more prevalent in patients than in controls (P=0.008). Three common haplotypes were found, of which haplotype 2 (GTT) was significantly associated with sarcoidosis in comparison with control subjects (P=0.01). Subgroup analysis revealed that the -826T allelic carriage was most prevalent in stage II disease, and more prevalent in stage III than in stage IV (P=0.01). The -826T allelic carriage did not show any association with lung function. These results indicate that the NF-kappaB activation pathway might be associated with the inflammation of sarcoidosis.

Disease Progression↗
PubMed2003

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.

Bronchoalveolar Lavage↗
PubMed2002

Comparative appearances of non-tuberculous mycobacteria species: a CT study.

Our objective was to characterise the CT features of the various species of non-tuberculous mycobacteria (NTM) and to identify differences, if any, between Mycobacterium avium intracellulare( MAI) and other species. Fifty-five patients, who were culture positive on at least two occasions for a single NTM species, were evaluated. All patients had CT scans performed within 6 months of NTM identification. The CT scans were assessed for the presence and severity of bronchiectasis, nodules, cavities, tree-in-bud pattern, consolidation and for evidence of pre-existing lung disease. Bronchiectasis was identified in most patients (52 of 55, 95%) and nodules were present in approximately half (29 of 55, 53%). Patients with MAI ( n=16) were found to have significantly higher bronchiectasis scores and higher prevalence of nodules than the other species (both p<0.01). Patients with M.kansasii ( n=9) and M.xenopi ( n=9) had cavities, tree-in-bud pattern, and pre-existing emphysema as the dominant CT features. Patients with M.chelonae and M.fortuitum were younger than the other groups and also had a high incidence of pre-existing lung disease. Patients with MAI infection have more severe bronchiectasis and more nodules on CT than the other NTM species. Morphological differences between the other species were identified but were less distinct.

Female↗
PubMed2002

Prostacyclin for pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Survival seldom exceeds five years. Pulmonary hypertension can be idiopathic or associated with other conditions. It is common in patients with diffuse scleroderma and the CREST syndrome where it is clinically, haemodynamically and prognostically indistinguishable from idiopathic primary pulmonary hypertension. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. Iloprost is a chemically stable derivative of prostacyclin with similar biologic properties and can be given orally, by infusion or nebulised. OBJECTIVES: To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension. SEARCH STRATEGY: A search was carried out using the Cochrane controlled clinical trial register. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving patients with primary pulmonary hypertension were selected by two reviewers. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes, using standard statistical techniques. MAIN RESULTS: Four RCTs were included, all of short duration (8-12 weeks). Three compared intravenous epoprostenol with conventional therapy, two were in PPH (n = 81 and n = 21) and one with pulmonary hypertension in scleroderma (n = 111). One compared intravenous Iloprost with placebo in 14 patients with scleroderma. Exercise capacity improved in patients treated with intravenous epoprostenol (Standardised Mean Difference) 0.69, 95% Confidence Intervals (CI) 0.40, 0.97. Several haemodynamic variables improved in the group treated with epoprostenol; e.g. mean pulmonary artery pressure fell: Weighted Mean Difference -6.3 mmHg (95% CI -3.9, -8.7). Mortality was improved Peto Odds Ratio 0.32 (95% CI 0.13, 0.77), although this effect was not significant when analysed using a more conservative random effects model: Odds Ratio 0.32 (95% CI 0.06, 1.58). Side effects and adverse events related to the indwelling catheter (sepsis and thrombosis) were common. REVIEWER'S CONCLUSIONS: Intravenous prostacyclin over 12 weeks improves exercise capacity, NYHA functional class and several cardiopulmonary haemodynamic variables. It may improve mortality.

Antihypertensive Agents↗
PubMed2002

Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis.

BACKGROUND: Previous studies suggest that bronchoscopy and a single induced sputum sample are equally effective for diagnosing pulmonary tuberculosis. METHODS: In a prospective study of subjects with possibly active pulmonary tuberculosis, the diagnostic yield of three induced sputum tests was compared with that of bronchoscopy. Subjects either produced no sputum or (acid fast) smear negative sputum. Bronchoscopy was only performed if at least two induced sputum samples were smear negative. RESULTS: Of 129 subjects who completed all tests, 27 (21%) had smear negative and culture positive specimens, 14 (52%) on bronchoscopy and 26 (96%) on induced sputum (p<0.005). One patient was culture positive on bronchoscopy alone compared with 13 on induced sputum alone; 13 were culture positive on both tests. Induced sputum positivity was strikingly more prevalent when chest radiographic appearances showed any features of active tuberculosis (20/63, 32%) than when appearances suggested inactivity (1/44, 2%; p<0.005). Induced sputum costs were about one third those of bronchoscopy, and the ratio of costs of the two tests per case of tuberculosis diagnosed could be as much as 1:6. CONCLUSIONS: In subjects investigated for possibly active or inactive tuberculosis who produce no sputum or have smear negative sputum, the most cost effective strategy is to perform three induced sputum tests without bronchoscopy. Induced sputum testing carries a high risk of nosocomial tuberculosis unless performed in respiratory isolation conditions. The cost benefits shown could be lost if risk management measures are not observed.

Adolescent↗
PubMed2002

Management of solitary pulmonary nodules: how do thoracic computed tomography and guided fine needle biopsy influence clinical decisions?

BACKGROUND: Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule < or = 3 cm in diameter on initial chest radiography. METHODS: Clinical, physiological, and outcome data on 114 patients with an SPN < or = 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later. RESULTS: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median kappa values 0.79-0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (kappa=0.33), rose with CT information (kappa=0.44), and increased further with the addition of the FNB data (kappa=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedman's test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31-70%). FNB data contributed most to the benefit (p<0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy. CONCLUSION: Both CT and FNB make cost effective contributions to the clinical management of SPN < or = 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.

Adult↗
PubMed2002

A comparison of serial computed tomography and functional change in bronchiectasis.

In bronchiectasis the morphological determinants of (marginal) fluctuations in pulmonary function tests are uncertain. The aim of the present study was to evaluate serial computed tomography (CT) changes in relation to pulmonary function trends in patients with bronchiectasis. The relationships between pulmonary function indices and CT scans in 48 adult patients with bronchiectasis were evaluated at baseline and at follow-up, at a median interval of 28 months (range 6-74 months). Two independent observers semiquantitatively scored CT features of bronchial and small airways disease. At initial assessment, the severity of airflow obstruction was linked primarily to the extent of mosaic attenuation. However, serial changes in pulmonary function indices were only associated with serial changes in mucous plugging scores. Alterations in mucous plugging on serial CT were associated with changes in the severity of bronchiectasis and bronchial wall thickness. Greater severity of all three morphological abnormalities at baseline CT were predictive of significant declines in forced expiratory volume in one second, with severe bronchial wall thickness being the most adverse prognostic determinant. Variations in mucous plugging on computed tomography correlate with minor fluctuations in pulmonary function tests in bronchiectasis. However, the severity of bronchial wall thickness is the primary determinant of subsequent major functional decline.

Adult↗
PubMed2001

Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity.

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.

Adult↗
PubMed2001

Reproducibility of the WHO/IASLC grading system for pre-invasive squamous lesions of the bronchus: a study of inter-observer and intra-observer variation.

AIMS: Although many workers have graded pre-invasive squamous lesions arising in the bronchus, there has been no consensus classification system until the latest edition of the WHO/IASLC histological classification of pulmonary and pleural tumours. Because the value of any such system is dependent on its reproducibility, we have circulated a series of such lesions to a panel of histopathologists to assess interobserver and intra-observer variation when the WHO/IASLC classification was applied. METHODS AND RESULTS: Colour transparencies of 28 pre-invasive squamous lesions were assessed by six histopathologists (two with a special interest in pulmonary pathology, two generalists and two trainees) on three separate occasions over a period of 3 months, using the criteria of the WHO/IASLC (mild, moderate and severe dysplasia, and in-situ carcinoma). An additional category of metaplasia was added for those cases that showed no dysplasia. Weighted kappa coefficents of agreement (K(w)) were used to evaluate paired observations with a standard quadratic weighting being employed, such that kappa coefficients corresponded to intra-class correlation coefficients. Wilcoxon's sign-ranked test was used to measure the statistical significance of group trends, when comparing kappa values for the three grading systems. Various 3-point systems were also assessed, through combination of the above groups. Intra-observer agreement was substantially better than interobserver variation (mean: 0.71 vs. 0.55). Between the various pathologist groups, inter-observer variation was relatively minor, although intra-observer variation was higher within the trainee pathologist group. Using weighted kappa values, there was no significant difference in either inter-observer or intra-observer agreement between the five point grading system and a 3-point system of metaplasia/mild, moderate and severe/in-situ grades. However, there was a significant increase in variation when a 3-point system of metaplasia/mild, moderate/severe and in-situ carcinoma was used. CONCLUSION: This study shows levels of interobserver and intra-observer variation similar to those found in other grading systems in histopathology, with no significant decrease in variability found by abridging the system. The WHO/IASLC system is therefore recommended for future use in both clinical and research fields.

Bronchial Neoplasms↗
PubMed2001

Spirometric lung volumes in the adult Pacific Islander population: comparison with predicted values in a European population.

OBJECTIVE: Prediction equations for spirometric lung volumes have been developed mainly in Europe and North America and may not be relevant to Pacific Islanders. This study was undertaken to determine whether currently available prediction equations adequately describe spirometric lung volumes in the asymptomatic adult Pacific Islander population. METHODOLOGY: Healthy asymptomatic Pacific Island adults aged 15-70 years were recruited. Pulmonary function was measured in the laboratory at Green Lane Hospital, Auckland, New Zealand, in accordance with American Thoracic Society standards. Measured results were compared with predicted values derived from four sets of prediction equations relevant to, or currently used in, New Zealand. RESULTS: A total of 101 volunteers took part in the study; mean age 28 years (range 18-66 years), 39% male, body mass index = 32 (range 22-54). For forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), when measured values were compared with reference values, the slopes of the regression lines were not significantly different from 1 and the intercepts were not significantly different from zero. Prediction equations derived for African-Americans did not provide a better fit than the prediction equations for Caucasians. Predictions were improved when ideal rather than actual bodyweight was used. CONCLUSION: Respiratory parameters (FEV1 and FVC) in healthy asymptomatic adult Pacific Islanders in New Zealand are adequately described by currently available prediction equations and no adjustment for ethnicity is required.

Adolescent↗
PubMed2001

Pneumonitis complicating methotrexate therapy for pustular psoriasis.

We report a patient with pustular psoriasis who developed interstitial pneumonitis after receiving weekly methotrexate (MTX) therapy at an average dose of 20 mg for 26 years. The patient responded dramatically to withdrawal of the drug and administration of corticosteroids. Pulmonary toxicity is a rare adverse effect of MTX therapy and is particularly uncommon in psoriatics. As interstitial pneumonitis is a potentially fatal but reversible complication, early respiratory symptoms even in patients on low-dose MTX treatment should be appropriately investigated.

Female↗