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Biomedical subjects

R M Rudd

Publications and source records attributed to R M Rudd.

At least 19 recordsLinked to original sources
PubMed1997

Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy.

BACKGROUND: Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with extensive disease. PURPOSE: The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy. METHODS: In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided. RESULTS: Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended. CONCLUSIONS: These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.

Administration, Oral↗
PubMed1997

British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society.

BACKGROUND: Mortality due to cryptogenic fibrosing alveolitis (CFA) is increasing, particularly in the elderly. Optimum management remains uncertain and previous studies of the disease have largely been from specialist centres. A national study was carried out of the presentation and initial management of CFA in the UK. METHODS: All respiratory physicians in England, Scotland and Wales were invited to enter patients with newly diagnosed CFA over a two year period. CFA was diagnosed on histological grounds or according to clinical criteria which included the absence of a defined connective tissue disorder or pneumoconiosis. Participating physicians (n = 150) completed a questionnaire at patient entry and at all subsequent follow up visits and death. RESULTS: A total of 588 patients (373 men, 63%) were studied of whom 441 (75%) were referrals from primary care. Their mean (SD) age was 67.4 (10.0) years and median duration of symptoms at presentation was 9.0 months. Clubbing was more common in men (203/373; 54%) than in women (86/ 215; 40%); 209 patients (36%) were graded as severely breathless at presentation. A history of dust exposure (organic or inorganic) was present in 274 patients (47%) of whom 87 had had some exposure to asbestos. Subjects exposed to dust were more likely to have smoked and had slightly higher mean lung volumes, but were otherwise indistinguishable from those not exposed in terms of clinical presentation, management, and outcome. Transbronchial biopsy specimens were taken in 164 patients (28%) and open lung biopsy specimens in 73 (12%), but 60% had no histological diagnostic procedure. Biopsy procedures were more likely to be performed in younger patients, those with better lung function, and those with a history of asbestos exposure. At presentation a decision not to initiate specific treatment was made in 284 cases (48%). The decision to initiate treatment was made predominantly on symptomatic grounds. Two years after the close of entry to the study 266 patients (45%) had died. CONCLUSIONS: CFA is predominantly a disease of elderly patients and has a poor prognosis. Physicians generally considered CFA to be a clinical diagnosis and did not initiate treatment in up to half of patients at presentation.

Age Factors↗
PubMed1996

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.

Adult↗
PubMed1996

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

BACKGROUND: Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. METHODS: A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. RESULTS: In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. CONCLUSIONS: In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Expandable metal stents for non-malignant bronchial obstruction.

An expandable metal stent was inserted to relieve bronchial obstruction following lobectomy for localised squamous carcinoma which had not been relieved by bronchoplasty with a Goretex flap. This resulted in substantial improvement in lung function and exercise tolerance for nine months, following which severe inflammation around the stents required residual pneumonectomy.

Airway Obstruction↗
PubMed1995

Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph?

This study was designed to test the hypothesis that the risk of lung cancer from asbestos exposure is confined to persons with radiographic evidence of pulmonary fibrosis. Occupational and smoking histories were obtained from 271 patients with a confirmed diagnosis of primary lung cancer and 678 referents (279 with other respiratory disease and 399 with cardiac disease). Histories were reviewed blind to assess the timing, duration, and probability of exposure to asbestos. To allow for a lag between asbestos exposure and the development of lung cancer, subjects were classified by the time they had spent in an occupation entailing definite or probable exposure more than 15 years before diagnosis. The presence and extent of fibrosis was assessed blindly from chest radiographs by three readers and scored for small opacities with the ILO 1989 International Classification of Radiographs of the Pneumoconioses. 93 (34.3%) cases had worked in an occupation with definite or probable asbestos exposure compared with 176 (25.8%) referents (crude odds ratio for lung cancer 1.49, 95% CI 1.09-2.04). After adjustment for age, sex, smoking history, and area of referral, the odds ratio (95% CI) was 2.03 (1.00-4.13) in the subgroup of 211 with a median ILO score for small parenchymal opacities of 1/0 or more, and 1.56 (1.02-2.39) in the 738 with a score of 0/1 or less (ie, those without radiological evidence of pulmonary fibrosis). These results suggest that asbestos is associated with lung cancer even in the absence of radiologically apparent pulmonary fibrosis.

Aged↗
PubMed1995

Short-course chemotherapy for tuberculous pleural effusion and culture-negative pulmonary tuberculosis.

SETTING: Chest Clinics at Blackburn and Newham, UK. OBJECTIVE: To test the efficacy of a short-course regimen of 6 months rifampicin and isoniazid supplemented by 2 months initial pyrazinamide (2HRZ-4HR), in the treatment of smear and culture-negative pulmonary tuberculosis and tuberculous pleural effusion in routine clinical practice. DESIGN: The results of 152 patients with these forms of tuberculosis treated between 1981 and 1991 were analysed retrospectively. RESULTS: 127 patients, 65 with pleural effusion and 62 with culture-negative pulmonary tuberculosis, completed treatment as planned. 100 were followed up for a mean duration 20.5 months (range 4-72) for culture-negative disease and 14.6 months (range 3-46) for pleural effusion. There were no relapses, giving a relapse rate of 0% (95% confidence interval 0-3.62%). CONCLUSION: Unsupervised self-administered treatment with 2HRZ/4HR is a highly effective regimen for culture-negative pulmonary tuberculosis and tuberculous pleural effusion in service conditions.

Adolescent↗
PubMed1995

Assessment of 'quality of life' using a daily diary card in a randomised trial of chemotherapy in small-cell lung cancer.

BACKGROUND: Quality of life (QOL) was assessed using a daily diary-card within a multicentre randomised trial of treatment of small-cell lung cancer. The trial compared a weekly dose-intensive regimen with a 3-weekly conventional treatment in good prognosis patients, that is patients with limited disease or extensive disease with a good performance status (ECOG 0or 1) and alkaline phosphatase of less than one and a half times the upper limit of normal. The trial which has been previously reported detected no difference in response or survival. PATIENTS AND METHODS: Daily diary cards (DDCs) were collected for up to eight months from the first day of chemotherapy in a cohort of 75 patients at one centre. Percentages of scores over a specified level were calculated for each of the eight diary card questions and comparisons were made between treatment arms. RESULTS: During the period of chemotherapy compliance in completing DDCs was 72.5% in the weekly arm and 77.2% in the 3 weekly. Significantly worse scores were reported with weekly chemotherapy during this period for six of the eight parameters, namely: ;nausea, vomiting, happiness, appetite, general well-being and sleep. Recognised problems of QOL data collection, in particular, compliance, attrition and generalisability are highlighted by this study and are discussed in the paper. CONCLUSIONS: The QOL measurements indicate that 3 weekly chemotherapy is the preferred treatment. This study demonstrates that QOL measurements may be helpful in choosing between treatment alternatives where no difference in outcome is observed.

Adult↗
PubMed1994

Respiratory muscle function in patients with asbestos-related pleural disease.

The effect of asbestos-related pleural disease (ARPD) on the generation of maximum respiratory pressure was investigated in 11 male patients with ARPD mean age 57 years, range 45-74, and mean duration of asbestos exposure of 9.9 years, range 5-16. There were three smokers, seven ex-smokers and one non-smoker. Breathlessness ranged from grade 1-3 on the MRC score. The extent of pleural disease was calculated using a score based on the ILO score for pleural disease. Full respiratory function tests, global respiratory muscle strength and diaphragmatic strength were assessed. Respiratory muscle strength, including diaphragm strength, was normal. Recoil pressure was high or at the upper limit of normal in four patients and correlated with chest radiograph score for pleural disease (r = 0.65, P < 0.02). There was no difference in either global respiratory muscle or diaphragmatic strength between patients with and without involvement of one or both costophrenic angles or between patients with mild or severe breathlessness. We conclude that respiratory muscle strength is not importantly reduced in ARPD, and it is unlikely that weakness contributes to breathlessness in these patients. By contrast reduced chest wall compliance is likely to be an important factor in breathlessness in some cases.

Aged↗
PubMed1994

Lung crackle characteristics in patients with asbestosis, asbestos-related pleural disease and left ventricular failure using a time-expanded waveform analysis--a comparative study.

The aim of this study is to investigate lung crackle characteristics by time-expanded waveform (TEW) analysis in patients with asbestosis (AS), asbestos-related pleural disease (ARPD) and left ventricular failure (LVF). TEW was performed on a 33 s recording from each of 40 patients (12 AS, 17 ARPD and 11 LVF). They were 38 men and two women. Crackles on TEW were counted during inspiration and expiration, and the timing of clusters of crackles with respect to inspiration and expiration was noted. A total of 1117 crackles were identified. The initial deflection width (IDW) and the two cycle duration (2CD) were calculated for all crackles within one respiratory cycle for each patient (total of 298 crackles). Crackles were detected by TEW in all patients with AS, in seven patients with ARPD and in nine patients with LVF. Crackles in AS were mainly fine, mid- to late-inspiratory. Crackles in LVF took three patterns; in the first there were repetitive mid- to late inspiratory crackles similar to those seen in AS except that the crackles in LVF tended to be medium and coarse as well as fine (three patients); in the second crackles started early in inspiration followed by a crackle-free period then by another cluster of crackles lasting to the end of inspiration and to the early third of expiration (four patients) and in the third there were repetitive expiratory crackles with no or few inspiratory crackles (two patients). Crackles in ARPD generally took the configuration of fine crackles but another type of crackle preceded by a sharp deflection followed by an M-shape oscillation then by the largest oscillation was also found. IDW and 2CD for inspiratory crackles in ARPD were shorter than those in AS and LVF (for IDW P < 0.009 and P < 0.003 compared with AS and LVF respectively and for 2CD, P < 0.006 and P < 0.003 compared with AS and LVF respectively). IDW and 2CD in AS tended to be shorter than these for LVF but these results did not reach statistical significance. It is concluded that many differences exist between crackles in AS, LVF and ARPD. Differences in nature and timing of crackles may reflect differences in the pathophysiology and mechanism giving rise to lung crackles in these conditions. TEW provides informations of diagnostic value.

Adult↗
PubMed1994

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND: The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS: The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS: Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS: Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.

Adolescent↗
PubMed1994

Clinical evaluation of a serological assay using a monoclonal antibody (TB72) to the 38 kDa antigen of Mycobacterium tuberculosis.

We examined an enzyme-linked immunosorbent assay (ELISA) modification of a radioimmunoassay, using the TB72 monoclonal antibody, as a serological test for tuberculosis in a clinical setting. Sera were obtained from 238 patients with suspected pulmonary tuberculosis, 30 patients treated for tuberculosis, 28 contacts, and 480 random samples from inpatients. Antibody levels were measured as the dilution of serum causing 50% inhibition of binding of the TB72 monoclonal antibody, which binds to an epitope of the 38 kDa antigen specific to the Mycobacterium tuberculosis complex, a positive titre being > 3. Positive antibody titres were present in 21 out of 25 (84%) patients with smear-positive and 22 out of 27 (82%) patients with smear-negative, culture-positive tuberculosis, and 37 out of 41 (90%) patients successfully treated for tuberculosis but without bacteriological confirmation of disease. Three out of 82 (4%) patients with a firm alternative diagnosis to tuberculosis gave a positive result. Serological tests were negative within 2.5 yrs of successful treatment. Patients without a definite diagnosis one year after tuberculosis had been suspected, and those who had received inadequate treatment for tuberculosis, were frequently positive (21 out of 31 and 21 out of 32, respectively). Positive tests concurred with tuberculin reactivity in 8 out of 11 contacts given chemoprophylaxis. Screening of 480 random serum samples gave 22 positive titres, 16 of which were not associated with tuberculosis; none of these 16 had an antibody titre > 10. We conclude that the TB72 test provides additional information in the diagnosis and treatment of tuberculosis. Antibody titres > 10 suggests active tuberculosis; titres of 3-10 merit observation.

Adult↗
PubMed1994

Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.

Adult↗
PubMed1993

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↗