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Biomedical subjects

R M Rudd

Publications and source records attributed to R M Rudd.

At least 55 records · Page 3Linked to original sources

Bronchoalveolar lavage and 99mTc-DTPA clearance as prognostic factors in asbestos workers with and without asbestosis.

The aims of this study are to investigate the change-over time of lung function and chest radiographic findings in patients with asbestosis (AS) and asbestos workers without asbestosis (AW). Secondly, to correlate these changes with broncho-alveolar lavage (BAL) profiles and with lung epithelial permeability, as detected by half-time lung-to-blood (t1/2 LB) clearance of an inhaled aerosol of diethylene triamine pentacetate labelled with technetium 99 (99mTc-DTPA) obtained a mean period of 4.2 yr (range 2.3-5.8) previously. Thirty-three patients with asbestosis and 24 asbestos workers with substantial asbestos exposure were followed-up. Nineteen healthy smokers (HS) with no asbestos exposure who were followed up for a mean period of 3.9 yr were taken as a control group for spirometric changes. Compared with AW, FEV1, FVC and TLCO were lower in AS (P < 0.0001 in each case). Smoker AS and AW had lower numbers (P < 0.03) and percentages (P < 0.004) of BAL lymphocytes and higher numbers (P < 0.04) and percentages (P < 0.02) of BAL neutrophils plus eosinophils than ex- and non-smokers. Annual declines of FEV1 (dFEV1 yr-1) and FVC (dFVC yr-1) in AS and AW were significantly greater than in HS and predicted annual declines (P < 0.002 in each case). Annual declines of TLCO (dTLCO yr-1) and KCO (dKCO yr-1) in AS and AW were significantly greater than predicted annual declines (P < 0.002 in each case). No significant differences were noted between AS and AW in annual declines in any lung function measurement. dTLCO yr-1, dKCO yr-1 were significantly greater in smokers than in ex- and non-smokers, (P < 0.05 and P < 0.04 respectively). Annual decline did not relate to base line values for any lung function measurement. Numbers and proportions of BAL lymphocyte were higher (P < 0.008 and P < 0.02, respectively) and numbers and proportions of BAL neutrophils and eosinophils were lower (P < 0.02 and P < 0.03, respectively) in patients in whom dTLCO yr-1 was less than 0.3 mmol min-1 kPa-1 than in patients in whom dTLCO yr-1 was more than 0.3 mmol min-1 kPa-1. dTLCO yr-1 inversely correlated with t1/2 LB; r = 0.51; (P < 0.008). Patients in whom the radiograph remained unchanged had higher numbers (P < 0.002) and percentages (P < 0.001) of BAL lymphocytes than patients in whom the radiograph deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnosis of asbestosis by a time expanded wave form analysis, auscultation and high resolution computed tomography: a comparative study.

BACKGROUND: Crackles are a prominent clinical feature of asbestosis and may be an early sign of the condition. Auscultation, however, is subjective and interexaminer disagreement is a problem. Computerised lung sound analysis can visualise, store, and analyse lung sounds and disagreement on the presence of crackles is minimal. High resolution computed tomography (HRCT) is superior to chest radiography in detecting early signs of asbestosis. The aim of this study was to compare clinical auscultation, time expanded wave form analysis (TEW), chest radiography, and HRCT in detecting signs of asbestosis in asbestos workers. METHODS: Fifty three asbestos workers (51 men and two women) were investigated. Chest radiography and HRCT were assessed by two independent readers for detection of interstitial opacities. HRCT was performed in the supine position with additional sections at the bases in the prone position. Auscultation for persistent fine inspiratory crackles was performed by two independent examiners unacquainted with the diagnosis. TEW analysis was obtained from a 33 second recording of lung sounds over the lung bases. TEW and auscultation were performed in a control group of 13 subjects who had a normal chest radiograph. There were 10 current smokers and three previous smokers. In asbestos workers the extent of pulmonary opacities on the chest radiograph was scored according to the International Labour Office (ILO) scale. Patients were divided into two groups: 21 patients in whom the chest radiograph was > 1/0 (group 1) and 32 patients in whom the chest radiograph was scored < or = 1/0 (group 2) on the ILO scale. RESULTS: In patients with an ILO score of < or = 1/0 repetitive mid to late inspiratory crackles were detected by auscultation in seven (22%) patients and by TEW in 14 (44%). HRCT detected definite interstitial opacities in 11 (34%) and gravity dependent subpleural lines in two (6%) patients. All but two patients with evidence of interstitial disease or gravity dependent subpleural lines on HRCT had crackles detected by TEW. In patients with an ILO score of > 1/0 auscultation and TEW revealed mid to late inspiratory crackles in all patients, whereas HRCT revealed gravity dependent subpleural lines in one patient and signs of definite interstitial fibrosis in the rest. In normal subjects crackles different from those detected in asbestosis were detected by TEW in three subjects but only in one subject by auscultation. These were early, fine inspiratory crackles. CONCLUSION: Mid to late inspiratory crackles in asbestos workers are detected by TEW more frequently than by auscultation. Signs of early asbestosis not apparent on the plain radiograph are detected by TEW and HRCT with similar frequency. off

Asbestosis↗

Phase II study of Edatrexate in stage III and IV non-small-cell lung cancer.

A total of 49 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a new antifolate, Edatrexate (10-ethyl-10-deaza-aminopterin; 10-EdAM). Patients received 80 mg/m2 weekly for 12 weeks, and responders received a further 6 cycles at 2-week intervals. Dose reductions were carried out for haematological toxicity and mucositis. Response was assessed prior to each treatment according to WHO criteria. Among the 45 evaluable patients, 6 [13.3%; 95% confidence interval (CI), 6%-26%] achieved a partial response (PR) and 9 (20%; 95% CI, 11%-34%) showed a minor response (MR; 25%-50% reduction in the sum of 2 perpendicular tumour diameters). In those receiving four or more cycles of treatment, the PR and MR rates were 17.6% and 26.4%, respectively. The resultant toxicity mainly constituted skin rash, mucositis and myelosuppression. Edatrexate is active against NSCLC and produces toxicity profile similar to that of methotrexate.

Aged↗

Reduced pulmonary microvascular permeability in severe chronic left heart failure.

Pulmonary edema is a serious complication of heart failure, but often patients with chronic heart failure resist pulmonary edema despite elevated pulmonary venous pressures. This protection might be a result of decreased pulmonary microvascular permeability. Double-isotope scintigraphy with 113mindium-labeled transferrin and 99mtechnetium-labeled erythrocytes allows noninvasive estimation of pulmonary microvascular permeability; an index of transferrin accumulation is calculated that reflects microvascular permeability. Fourteen patients with severe chronic left ventricular dysfunction were compared with a control group of 15 patients with mild coronary artery disease. In the control group the transferrin accumulation index was 0.35 (range -0.3 to 1.0) x 10(-3)/min, and in patients with heart failure the index was 0.0 (range -1.0 to 0.7) x 10(-3)/min, which was significantly lower (p less than 0.01). The reduction in the transferrin accumulation index correlated weakly with the duration of heart failure (R = -0.5, p less than 0.02). These data indicate reduced protein efflux consistent with a decrease in pulmonary microvascular permeability in patients with severe chronic heart failure. Similar changes have been observed in severe mitral stenosis and may reflect a generalized adaptation to chronic pulmonary venous hypertension.

Aged↗

PCR-based RFLP analysis allows genotyping of the short arm of chromosome 3 in small biopsies from patients with lung cancer.

The tumors of patients with lung cancers often show loss of heterozygosity (LOH) at polymorphic loci on the short arm of chromosome 3. Most examples of small-cell lung carcinoma (SCLC) cannot be examined since they are infrequently resected. Small biopsies are, however, usually available from patients with this disease. We have used the polymerase chain reaction (PCR) to study lung tumor biopsies obtained by fiberoptic bronchoscopy and assign the genotype at 11 RFLPs in 7 well-established loci on 3p. We have demonstrated LOH in some and found that biopsy samples need to contain approximately 60% content of tumor cells if LOH is to be reliably detected. One SCLC tumor that we examined has an interstitial 3p deletion proximal to the locus D3F15S2 and thus provides information useful in mapping the position of the tumor suppressor gene on 3p.

Alleles↗

The histocompatibility antigen in asbestos related disease.

Thirty nine phenotypes of human leucocyte antigens (HLA)-A-B-DR and DQ were obtained from 99 asbestos workers (one woman and 98 men). Presence or absence of antinuclear antibodies and rheumatoid factor was determined in 91 of them. Workers were divided into five groups: asbestos workers with no apparent disease (AW; n = 17), diffuse benign pleural disease (PD; n = 31), asbestosis (AS; n = 24), asbestosis with lung cancer (AS-CA; n = 14), and mesothelioma (M; n = 13). Compared with AW, several trends of differences of HLA antigen prevalence were found in patients with asbestos related disease, but these did not achieve statistical significance when p was corrected (pcorr) by number of analyses undertaken. Analysis of the results obtained in previous studies together with the results of this study showed that compared with AW, AS patients had decreased prevalence of HLA-DR5 (pcorr < 0.02). Reasons for the differences in results of previous studies and statistical methods commonly used to compare prevalences of HLA antigen are discussed.

Adult↗

A new high resolution computed tomography scoring system for pulmonary fibrosis, pleural disease, and emphysema in patients with asbestos related disease.

The aim of this study was to describe a scoring system for high resolution computed tomographic (HRCT) scans analogous to the International Labour Office (ILO) scoring system for plain chest radiographs in patients with asbestos related disease. Interstitial fibrosis, pleural disease, and emphysema were scored, the reproducibility and the interobserver agreement using this scoring system were examined, and the extent of the various types of disease was correlated with measurements of lung function. Sixty asbestos workers (five women and 55 men) mean age 59 (range 34-78) were studied. The lungs were divided into upper, middle, and lower thirds. An HRCT score for the extent of pleural disease and pulmonary disease in each third was recorded in a way analogous to the International Labour Office (ILO) method of scoring pleural and parenchymal disease on chest radiographs. A CT score for the extent of emphysema was also recorded. Pleural disease and interstitial fibrosis on the plain chest radiographs were assessed according to the ILO scoring system. A chest radiographic score for emphysema analogous to that used for HRCT was also recorded. Two independent readers assigned HRCT scores that differed by two categories or less in 96%, 92%, and 85% compared with 90%, 78%, and 79% of cases for chest radiographs for fibrosis, emphysema, and pleural disease respectively. There was better intraobserver repeatability for the HRCT scores than for the chest radiograph scores for all disorders. Multiple regression analysis showed that scores for interstitial fibrosis, emphysema, and pleural disease on chest radiographs and HRCT correlated to a similar degree with impairment of lung function.

Adult↗

High resolution computed tomographic assessment of asbestosis and cryptogenic fibrosing alveolitis: a comparative study.

BACKGROUND: The aim of this study was to compare the distribution and configuration of lung opacities in patients with cryptogenic fibrosing alveolitis and asbestosis by high resolution computed tomography. METHODS: Eighteen patients with cryptogenic fibrosing alveolitis and 24 with asbestosis were studied. Two independent observers assessed the type and distributions of opacities in the upper, middle, and lower zones of the computed tomogram. RESULTS: Upper zone fibrosis occurred in 10 of the 18 patients with cryptogenic fibrosing alveolitis and in six of the 24 patients with asbestosis. A specific pattern in which fibrosis was distributed posteriorly in the lower zones, laterally in the middle zones, and anteriorly in the upper zones was seen in 11 patients with cryptogenic fibrosing alveolitis and in four with asbestosis. Band like intrapulmonary opacities, often merging with the pleura, were seen in 19 patients with asbestosis but in only two with cryptogenic fibrosing alveolitis. Areas with a reticular pattern and a confluent or ground glass pattern were the commonest features of cryptogenic fibrosing alveolitis (15 and 14 patients respectively) but were uncommon in asbestosis (four and three patients). Pleural thickening or plaques were seen in 21 patients with asbestosis and in none with cryptogenic fibrosing alveolitis. CONCLUSION: Apart from showing pleural disease high resolution computed tomography showed that confluent (ground glass) opacities are common in cryptogenic fibrosing alveolitis and rare in asbestosis whereas thick, band like opacities are common in asbestosis and rare in cryptogenic fibrosing alveolitis.

Adult↗

Assessment of asbestos-induced pleural disease by computed tomography--correlation with chest radiograph and lung function.

We compared computed tomography (CT) scanning with chest radiography in the assessment of asbestos-induced pleural disease (AIPD) in 20 patients (17 men and 3 women, mean age 55 years, range 43-74 years). Involved pleura was scored on plain chest radiographs according to the International Labour Office (ILO) method of evaluating AIPD. A CT score was calculated from the measurement, using a digital length probe, of the circumference of the chest wall involved by pleural disease in each slice. The maximum width of pleural disease was taken into account in a way analogous to the ILO method for the chest radiograph. The CT score correlated with the chest radiograph score (r = +0.82, P less than 0.0006). CT demonstrated discrete plaques in 95% of patients but these were identified only in 59% patients on the radiograph. Diffuse pleural thickening was evident on the CT scan in all patients and in 70% on the radiograph. There was more inter-reader agreement about the type of pleural disease on the CT scans than on the chest radiographs. CT and chest radiograph scores inversely correlated with all lung function measurements except KCO. We conclude that increasingly extensive pleural disease is associated with increasingly severe impairment of lung function. CT scanning demonstrates the type of AIPD better than plain chest radiography.

Adult↗

Short course chemotherapy for pulmonary tuberculosis.

A retrospective survey of the treatment of culture positive pulmonary tuberculosis with a standard 6-month course of unsupervised therapy, comprising rifampicin and isoniazid daily for 6 months with pyrazinamide for the first 8 weeks is reported. Of the 164 patients who commenced this regimen, 110 completed therapy as planned. There were five relapses, three of whom admitted significant non-compliance, giving a relapse rate of 4.59% (95% confidence interval, 1.49-10.7). The regimen gives satisfactory results in routine unsupervised treatment.

Adolescent↗

Portable oxygen therapy: assessment and usage.

Fifty portable oxygen assessments, based on 6-min walking tests, were reviewed to produce guidelines for assessment and prescription of portable oxygen, and to evaluate factors predicting benefit. Patients with a portable cylinder were questioned about benefits/difficulties and usage of portable oxygen. A significant improvement on the oxygen compared to the air walk was found (median 9.7%) which correlated with the oxygen desaturation on the baseline walk (r = 0.51, P less than 0.05). A placebo effect was demonstrated using an air cylinder (median improvement 6.1%). There was no correlation between improvement in walking distance and decrease in visual analogue scale (VAS) score of breathlessness. We recommend standard portable oxygen assessments based on a series of 6-min walks. Improvements of 10% in walking distance or VAS score from the oxygen to the air walk would lead to the patient being offered a portable oxygen cylinder.

Adult↗

A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

In a study of chemotherapy as palliative treatment, 300 patients with untreated limited and extensive stage small cell lung cancer (SCLC), who did not have progressive disease after the first cycle of chemotherapy, were randomised to receive either regular 'planned' chemotherapy or chemotherapy given 'as required' (AR). All patients received the same chemotherapy: cyclophosphamide 1 gm m-2 i.v., vincristine 2 mg i.v., and etoposide 120 mg m-2 i.v. on day 1, and etoposide 100 mg b.d. orally on days 2 and 3. Planned chemotherapy was given regularly every 3 weeks. AR chemotherapy was given for tumour-related symptoms, or for radiological progression of disease. Both groups of patients were assessed every 3 weeks and a maximum of eight cycles of chemotherapy was given. A detailed quality of life assessment was made using daily diary cards. The median survival (MS) of patients given AR chemotherapy was not significantly worse than those receiving planned treatment [MS: Planned = 36 weeks (95% C.I. 32-40 weeks), AR = 32 weeks (95% C.I. 28-37 weeks) P = 0.960]. In the AR patients the median interval between treatments was 42 days. On average AR patients received half as much chemotherapy as planned patients. AR patients with a treatment-free interval (TFI) of more than 8 weeks between the first and second cycles of chemotherapy survived longer than those in whom this interval was less than 4 weeks; [MS: TFI greater than 8 = 47 weeks (95% C.I. 32-53 weeks); TFI less than 4 = 24 weeks (95% C.I. 17-34 weeks) P = 0.013]. Contrary to expectation, in the quality of life assessment the AR patients scored themselves as having more severe symptoms than patients receiving planned treatment. AR chemotherapy is a novel method of attempting to use cytotoxic drugs palliatively, which resulted in less drug treatment for approximately equivalent survival. However the palliative effect seen with as required treatment was less satisfactory than with planned chemotherapy.

Aged↗

Pulmonary microvascular permeability in patients with severe mitral stenosis.

Patients with rheumatic mitral stenosis often have no pulmonary oedema despite considerably increased pulmonary venous pressure. Pulmonary microvascular permeability was measured non-invasively by a previously validated method of double isotope scintigraphy with indium-113m and technetium-99m. This permits calculation of an index reflecting transferrin efflux and thus, indirectly, the microvascular permeability. Fifteen patients with severe mitral stenosis (defined as valve area less than 1.0 cm2) were compared with a control group of 11 patients with mild coronary artery disease. The permeability index was significantly lower in patients with mitral stenosis than in the control group. Furthermore, the extent of reduction of the permeability index correlated with the severity of mitral stenosis as reflected by the Gorlin valve area. This finding may account for the relative resistance of these patients to pulmonary oedema despite chronic pulmonary venous hypertension.

Adult↗