Malignant mesothelioma.

INTRODUCTION: Mesothelioma is a malignant tumour of the pleura or peritoneum caused by asbestos. It is increasing in frequency and the prognosis remains grim, with average survival around 1 year. SOURCES OF DATA: Medical literature and personal experience. AREAS OF AGREEMENT: Amphibole fibres are far more potent than chrysotile in causing mesothelioma. AREAS OF CONTROVERSY: A minority view suggests that mesotheliomas in those exposed to chrysotile are caused only by tremolite (an amphibole) which contaminates chrysotile. There is a hypothesis, for which evidence is weakening, that Simian virus 40 may cause mesothelioma. GROWING POINTS: There is emerging evidence of genetic variation in susceptibility to fibre carcinogenesis. There are developments in treatment, particularly chemotherapy with pemetrexed and cisplatin which prolongs survival and helps symptoms. AREAS TIMELY FOR DEVELOPING RESEARCH: Targeted agents for treatment are under investigation and may improve the outlook. The role of radical and palliative surgery requires clarification.

Comparison of gemcitabine and carboplatin versus cisplatin and etoposide for patients with poor-prognosis small cell lung cancer.

BACKGROUND: The combination of cisplatin and etoposide (PE) has been a standard treatment for patients with poor-prognosis small cell lung cancer (SCLC). This non-inferiority design trial aimed to determine whether the combination of gemcitabine and carboplatin (GC) results in similar survival but is less toxic with better quality of life. METHODS: Previously untreated patients with SCLC with extensive disease or limited stage with poor prognostic factors were randomly assigned to six 3-weekly cycles of GC or PE. RESULTS: 241 patients (121 GC, 120 PE) were recruited, of which 216 (90%) had died. There was no difference in overall survival (HR 1.01, 95% CI 0.77 to 1.32). Median survival with GC and PE was 8.0 and 8.1 months, respectively. Median progression-free survival was 5.9 months with GC and 6.3 months with PE. Grade 3 or 4 myelosuppressions were more frequent with GC (anaemia: 14% GC vs 2% PE; leucopenia: 32% GC vs 13% PE; thrombocytopenia: 22% GC vs 4% PE), but these were not associated with increased hospital admissions, infections or fatalities. Grade 2-3 alopecia (68% PE vs 17% GC) and nausea (43% PE vs 26% GC) were more frequent with PE. Patients given GC received more chemotherapy as outpatients (89% GC vs 66% PE of treatment cycles). In QoL questionnaires, more patients receiving PE reported being upset by hair loss (p = 0.004) and impaired cognitive functioning (p = 0.04). CONCLUSIONS: GC is as effective as PE in terms of overall survival and progression-free survival and has a toxicity profile more acceptable to patients. TRIAL REGISTRATION NUMBER: ISRCTN 39679215.

Assessment of quality of life in the supportive care setting of the big lung trial in non-small-cell lung cancer.

PURPOSE: The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards. PATIENTS AND METHODS: EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks. RESULTS: A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks. CONCLUSION: There were no important adverse effects of chemotherapy on QoL.

Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.

PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.

Expression and prognostic significance of hypoxia-inducible factor 1alpha (HIF-1alpha) in malignant pleural mesothelioma (MPM).

Malignant pleural mesothelioma (MPM) is a highly chemoresistant cancer with a poor prognosis. Hypoxia is a specific property of solid tumours, contributes to low apoptotic potential, and can be selectively targeted by bioreductive drugs. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a subunit of a heterodimeric transcription complex that regulates several genes associated with tumour progression and anti-apoptosis. In this study, we measured for the first time the expression of HIF-1alpha in MPM. Our results show that HIF-1alpha is commonly expressed in MPM but not in normal mesothelium, consistent with the presence of hypoxia. HIF-1alpha does not appear to predict survival; however, this study suggests that bioreductive drugs should be investigated in clinical trials of MPM.

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.

Phase II study of vinorelbine in patients with malignant pleural mesothelioma.

PURPOSE: To evaluate the response rate and impact on quality of life of vinorelbine given as cycles of 30 mg/m(2) weekly for 6 weeks to patients with malignant pleural mesothelioma. PATIENTS AND METHODS: Twenty-nine patients with histologically proven malignant pleural mesothelioma were enrolled (26 male patients and three female patients; median age, 58 years [range, 29 to 77 years]). Seventeen patients had epithelioid tumors, two had sarcomatoid tumors, and 10 had biphasic tumors. The International Mesothelioma Interest Group staging system was used: one patient had stage Ib disease, 10 had stage II disease, eight had stage III disease, and 10 had stage IV disease. Patients were treated with weekly injections of vinorelbine 30 mg/m(2). A cycle consisted of six weekly injections. The new guidelines to evaluate the response to treatment in solid tumors were used. Responses were measured by spiral computed tomography scan. RESULTS: All twenty-nine patients had measurable disease and were assessed for response. There were seven partial responses (24% [95% confidence interval, 10% to 44%]), 16 patients had stable disease (55%), and six patients had disease progression on therapy (21%). The median number of vinorelbine injections was 12 (range, 2 to 30). Quality-of-life analyses showed a benefit for vinorelbine therapy. CONCLUSION: Vinorelbine shows promise in the palliation of patients with malignant pleural mesothelioma. The relatively low toxicity of the drug suggests that trials of vinorelbine in combination with other agents should be feasible.

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.

Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.

PURPOSE: Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease. PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses. RESULTS: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01). CONCLUSION: MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.

Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes.

PURPOSE: Gemcitabine-platinum combination activity has been clearly established in a number of phase II studies. It has also been compared against other combinations in many phase III trials. It is generally believed that all such regimens have an equivalent impact on survival. This meta-analysis aims to quantify the treatment effect of gemcitabine plus a platinum agent in the treatment of advanced NSCLC and compare the combination to other regimens used globally. DESIGN: Data from a total of 4556 patients from 13 randomized trials investigating gemcitabine in combination with a platinum agent versus any other platinum-containing regimen were included in a meta-analysis of time-to-event outcomes. RESULTS: A significant reduction in overall mortality in favor of gemcitabine-platinum regimens was observed, hazard ratio (HR) 0.90 (95% CI: 0.84-0.96) with an absolute benefit at 1 year of 3.9%. Median survival was 9.0 months for the gemcitabine-platinum regimens and 8.2 months for the comparator regimens. Sub-group analysis of the first- and second-generation platinum-based comparator regimens also indicated a significant benefit for gemcitabine-platinum regimens, HR 0.84 (CI: 0.71-0.9985). Analysis of third-generation agent plus platinum regimens showed a non-significant trend favoring gemcitabine-platinum regimens, HR 0.93 (CI: 0.86-1.01). There was a significant decrease in the risk of disease progression in favor of gemcitabine-platinum regimens, HR 0.88 (CI: 0.82-0.93). An absolute benefit of 4.2% at 1 year was estimated. Median progression-free survival was 5.1 months for gemcitabine-platinum regimens compared with 4.4 months for the comparator regimens. Sub-group analysis indicated a statistically significant progression-free survival benefit for patients assigned to gemcitabine-platinum treatment compared to first- and second-generation platinum regimens, HR 0.85 (CI: 0.77-0.94), and third-generation agent plus platinum regimens, HR 0.89 (CI: 0.82-0.96).

De novo cardiac beta adrenoceptor synthesis in adult rats under normoxic and hypoxic conditions.

Bromoacetylalprenololmenthane (BAAM), an alkylating irreversible beta adrenoceptor antagonist, was used to study in vivo beta adrenoceptor synthesis in adult rat left ventricle under normoxic and hypoxic conditions. In normoxic conditions cardiac beta adrenoceptor density decreased by 50% 15 h after treatment and recovered to control values after about 250 h. A similar decrease in receptor density and pattern of recovery was found in environmental hypoxia. Neither hypoxia nor treatment with BAAM had a significant effect on the dissociation constant of the radioligand. These results show that cardiac beta adrenoceptor synthesis occurs rather slowly and suggest that alteration of the rate of receptor synthesis in hypoxic states is not a major determinant of reported changes in density.

Membranous nephropathy resolving with treatment of bronchial carcinoid tumor.

The nephrotic syndrome and membranous nephropathy is well recognized in association with solid tumors, although less is understood of the process that links them. We report a 27-year-old man presenting with the nephrotic syndrome and stage I membranous glomerulonephritis on biopsy. A bilar mass with regional lymphadenopathy was found simultaneously, the histology of which was shown to be an infiltrative atypical bronchial carcinoid tumor. The neoplasm was successfully treated with combined chemotherapy and radiotherapy, and over this period his nephrotic-range proteinuria resolved. As has been described with other malignancies, membranous nephropathy associated with a bronchial carcinoid tumor may resolve with treatment of the underlying condition.

Asbestosis. Bronchoalveolar lavage fluid proteins and their relationship to pulmonary epithelial permeability.

We measured levels of albumin and immunoglobulins in serum and bronchoalveolar lavage (BAL) fluid in 28 men with asbestosis and 11 control subjects. The half-time clearance of inhaled diethylene triamine pentacetate labelled with technetium-99m (99mTc-DTPA) from the lungs (t1/2LB) was measured in 26 patients with asbestosis and in 31 normal nonsmoking controls. In those individuals in whom immunoglobulins were detected in BAL fluid, the mean IgG:albumin ratio in BAL fluid was 0.30 (range, 0.11 to 0.97), significantly less than the ratio of 0.43 (0.28 to 0.66) in control subjects (p less than 0.05). There was no significant difference in IgA:albumin ratios between patients and control subjects. The mean BAL:serum albumin ratio in patients with asbestosis was 2.3 X 10(-3) (range, 0.2 to 9.5 X 10(-3), significantly greater than the ratio of 1.2 X 10(-3) (0.5 to 2.0 X 10(-3] in control subjects (p less than 0.02). The t1/2LB was significantly shorter in both smokers and nonsmokers with asbestosis, compared with 31 normal nonsmoking controls, but there were no relationships between t1/2LB and BAL:serum albumin ratio or any other BAL protein levels in either smokers or nonsmokers with asbestosis.

A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma.

A total of 29 previously untreated patients with histologically proven malignant pleural mesothelioma, with an ECOG score of < or = 2 and UICC stage I-II disease, were enrolled between May 1994 and October 1996. On days 1 and 2, 18 x 10(6) IU/day of rIL-2 was administered by continuous intravenous infusion, and 6 x 10(6) IU/day of rIL-2 by subcutaneous injection on days 5--20 inclusive of a 42-day cycle. Further treatment was administered if no radiological disease progression was demonstrated. A total of 29 patients were assessable for toxicity and 25 for response, and 49 cycles of IL-2 were administered with a median of one per patient (range, < 1-4). Toxicity included mild fever, nausea and vomiting, and skin rashes, < grade II. Three patients failed to complete one cycle of treatment because of toxicity and one died of disease before response evaluation. Two patients achieved a partial response (8%, 95% CI 1-26%) surviving 18.1 and 18.7 months from diagnosis. A total of 11 patients (44%, 95% CI 24-65%) with stable disease had a median survival of 13.6 months (range 6.5-33.8). The median survival was 8.6 months (range 3.7-34.5) for the 12 patients with progressive disease (48%, 95% CI 28-69%). This regimen of rIL-2 is well tolerated and shows limited activity in mesothelioma.

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.

Six months' chemotherapy for lymph node tuberculosis.

A retrospective report of the experience using the policy of six-month short-course chemotherapy as standard treatment for lymph node tuberculosis is presented. Forty-one patients completed 6 months' treatment as planned. All made a complete recovery, except one who had a 1 cm residual node at the completion of treatment, and one who relapsed four months after treatment, was re-treated and recovered. Nine other patients had changes in treatment because of side-effects (5), drug-resistant organisms (3) and pregnancy (1). Treatment was prolonged in another seven patients, four in error and three because of previous drug treatment. The results suggest that 6 months' treatment of lymph node tuberculosis may be as satisfactory as 9 months', and support the need for a control comparison of these regimens.

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)

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.

Asbestos-related pericardial thickening detected by magnetic resonance imaging.

Magnetic resonance imaging was performed in four male asbestos workers in whom the chest radiograph revealed pleural but not pulmonary or pericardial disease. Patients underwent thoracic multislice spin echo imaging, with measurement of left and right ventricular volumes at end-diastole and end-systole, and a study of the flow in the superior vena cava as an indirect measure to the filling of the right ventricle. Patients also underwent respiratory function tests and high-resolution computed tomography (HRCT). Magnetic resonance, but not HRCT, showed pericardial thickening in two patients. Magnetic resonance demonstrated reduced diastolic flow in the superior vena cava in one patient, reflecting impaired right ventricular filling. All other magnetic resonance measurements of cardiac function were normal. HRCT demonstrated mild asbestosis in three patients in which neither the chest radiograph nor magnetic resonance showed signs of parenchymal disease, and pericardiac calcification without thickening in one patient. It is concluded that magnetic resonance is superior to HRCT in identifying pericardial thickening, but that HRCT is superior to magnetic resonance in identifying asbestos-related pleural and pulmonary disease.

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.