Management of chemotherapy-related anaemia with low-dose recombinant human erythropoietin in patients with small cell lung cancer.

We examined the efficacy of low-dose erythropoietin in the management of chemotherapy-related anaemia in patients with small cell lung cancer (SCLC). We gave recombinant human erythropoietin A (rHuEPO) to 63 SCLC patients, 30 with limited disease (LD) and 33 with extensive disease (ED) who underwent chemotherapy with carboplatin, etoposide and ifosfamide and had previously received blood transfusions for chemotherapy-related anaemia. rHuEPO was given at a dose of 2000 IU subcutaneously three times per week for 2 weeks after every chemotherapy cycle, starting 48 h after the end of chemotherapy. Before the use of rHuEPO, all patients in both groups had to be transfused after a mean of 5.5 CT cycles. In 64 CT cycles following administration of rHuEPO, only 5/30 LD patients (17%) had to be transfused in six cycles (9%). In 88 cycles following the use of rHuEPO, 7/33 ED patients (21%) had to be transfused in 11 cycles (12.5%). Haemoglobin values in patients with ED (but not those with LD) were significantly improved after rHuEPO administration on both day 14 and day 28 after chemotherapy. No adverse effects were recorded. rHuEPO considerably decreased the degree of anaemia and the need for blood transfusion at doses markedly lower (25-30 IU/kg body weight) than those reported in the literature so far (150 IU/kg body weight), without toxicity.

Interferon alpha-2a and combined chemotherapy as first line treatment in SCLC patients: a randomized trial.

BACKGROUND: Interferons (IFNs) are known to act synergistically with antineoplastic agents when applied to SCLC cell cultures. This study was conducted in order to detect the clinical benefits, if any, of the addition of IFN-alpha in the induction chemotherapy (CT) of SCLC patients. PATIENTS AND METHODS: Ninety previously untreated patients with SCLC were randomly assigned to receive either CT alone (arm A) or CT plus IFN alpha-2a in a dose of 3 MU/m2 twice weekly (arm B). CT for both arms consisted of carboplatin 420 mg/m2, etoposide 200 mg/m2 and ifosfamide 3.5 g/m2 or epirubicin 80 mg/m2 every 28 days for a total of eight cycles. Responding patients received primary site and prophylactic cranial irradiation and then had maintenance CT with cyclophosphamide 100 mg/m2/day for 20 days every month. Patients in arm B received IFN throughout these treatments. RESULTS: Eighty-one patients were evaluable for response, 39 in arm A and 42 in arm B. Both arms were comparable in terms of age, performance status and extent of disease. Overall response rates were not significantly different between the two arms (90% vs. 86%), although complete response rate was higher in arm B (38% vs. 28%). More importantly, Kaplan-Meier analysis disclosed a clear survival benefit in the arm receiving IFN-alpha (P < 0.05). For limited disease the difference was even more significant (P < 0.0067), while for extensive disease no significant difference was found (P < 0.35). Fever, fatigue and anorexia were more frequent in arm B (P < 0.001), as also leukopenia (P < 0.01). CONCLUSION: The addition of IFN-alpha to induction CT appears to confer a survival benefit to SCLC patients but optimal dosing schedule has yet to be defined.

A comparison of the clinical efficacy and patient acceptability of terbutaline Turbuhaler and salbutamol Rotahaler, in adult patients with asthma.

This open randomized, cross-over study compared the clinical efficacy and patient acceptability of the two bronchodilator delivery systems, terbutaline Turbuhaler (0.5 mg t.i.d.) and salbutamol Rotahaler (0.4 mg t.i.d.), each given for 3 weeks. Thirty-two adult asthmatics (21 males and 11 females with a mean age of 34 years) who demonstrated at least 15% reversibility in PEF or FEV1 in response to terbutaline, were enrolled for study. The median reversibility in FEV1 was 27.5% for the terbutaline-salbutamol group and 21% for the salbutamol-turbutaline group. Two patients discontinued during terbutaline treatment (one due to respiratory infection and one due to tachycardia, exhaustion and tremor) and five patients were lost to follow-up during salbutamol treatment, leaving data from 25 patients for an 'all patients treated' analysis. Mean morning PEF was 426 l min-1 during terbutaline and 410 l min-1 during salbutamol (difference 16 l min-1, 95% CI of difference 3-28 l min-1, P = 0.016), and mean evening PEF was 446 l min-1 during terbutaline and 428 l min-1 during salbutamol (difference 18 l min-1, 95% CI 5-30 l min-1, P = 0.0076). No significant differences were detected in diary symptom scores or in use of additional study drug during the day or night, and no serious adverse events were reported. When asked to state their treatment preferences on the basis of effects, side-effects and overall, more patients preferred Turbuhaler in each case, although no statistically significant differences were detected. In conclusion, terbutaline via Turbuhaler was significantly more effective than salbutamol via Rotahaler in controlling lung function (mean daily PEF) in adults with mild to moderate asthma, and it was the preferred treatment overall in 44% of patients, compared with 16% for Rotahaler (n.s.).

Pleural plaques in a rural population in central Macedonia, Greece.

The aim of this study was to investigate the prevalence and the causative factor of pleural plaques (PP) in 7 neighbouring villages (Monastiraki, Promachi, Megaplatanos, Orma, Polykarpi, Sarakini and Koryphi) located south-west of Aridea in Macedonia, Greece, where many cases of bilateral pleural calcifications were observed in the past. Full size chest radiographs were obtained from 1086 of the 3901 inhabitants over 5 years of age who agreed to participate in the study. The chest radiographs were scrutinized for PP according to International Labour Office criteria. From the total of 1737 inhabitants aged between 5 and 40 years, 268 were examined. None had a positive chest radiograph for PP. Therefore the prevalence of PP was evaluated for the subjects over 40 years of age. The highest prevalence of PP (41.7%) was observed in Monastiraki and none in Koryphi, with the prevalence of the other villages lying in between. Extremely high concentrations of chrysotile and tremolite fibres were found, using polarised light microscopy and X-ray diffraction, in the "white stones" which people use for white-washing their houses prior to 1935. The environmental study revealed 0.01 fibres/ml in a room purposely recently painted with the offending material, and 17.9 ff/ml after scraping. During the 28 months of our study five cases of malignant pleural mesothelioma were diagnosed.

Five cases of pleural mesothelioma with endemic pleural calcifications in a rural area in Greece.

The authors describe 5 cases of pleural mesothelioma in a rural population of Macedonia, Greece. This population had been covered by an X-ray study over a 3-year period to detect pleural calcifications compatible with asbestos exposure. The study revealed a 24.2% prevalence of pleural plaques among the inhabitants aged over 40 years of 7 rural villages. High contents of asbestos (chrysotile and tremolite)--up to 90% by volume--were found in the material that was used for whitewashing the houses up to 1935. Even now, environmental concentrations of 0.01 fibres/ml were recorded in the houses. The prevalence of pleural mesothelioma in this rural population is high compared to the general population. A possible explanation of the phenomenon may be a cumulative environmental exposure to asbestos which, even though presumably within the acceptable limits for occupational exposure, lasted over a much longer time period, in terms of both daily exposure and total duration.

Doppler echocardiographic evaluation of left ventricular diastolic function in patients with systemic sarcoidosis.

In order to estimate left ventricular diastolic function in systemic sarcoidosis, Doppler echocardiography was utilized in 10 normal female subjects (aged 45 +/- 13 years) and in 10 female patients (aged 48 +/- 14 years), with biopsy proven sarcoidosis and without any clinical evidence of other cardiac disease or hypertension. Left ventricular systolic function assessed by two-dimensional echocardiography was normal in both groups (ejection fraction greater than 60%). The following Doppler echocardiographic parameters were measured: peak early diastolic flow velocity (E), peak late atrial diastolic flow velocity (A), the ratio (E/A) and deceleration of the flow velocity in early diastole (E-F slope). The results showed that 5 patients had two or more abnormal Doppler diastolic indexes, indicating impaired left ventricular relaxation, while the remaining 5 patients had values within or just outside normal limits. The mean values for the patients as a whole showed increased A velocity (0.77 +/- 0.11 m/s versus 0.61 +/- 0.10 m/s; P + 0.05), decreased E/A ratio (1.05 +/- 0.32 versus 1.4 +/- 0.30; P + 0.01), normal E velocity and normal E-F slope, compared with the mean values of the normal group. We concluded that a large percentage (50%) of patients with systemic sarcoidosis, had reduced diastolic performance of the left ventricle, at a stage of the disease when systolic dysfunction is not yet evident.

Acoustic quantification: new diastolic indices of left ventricular function in hypertension correlation with Doppler echocardiography.

A study of left ventricular diastolic function in early hypertension was performed by the new method of acoustic quantification and Doppler echocardiography. A total of 23 untreated patients, five males and 18 females (mean age 53.52 +/- 9.10 years) with mild or moderate hypertension (160 +/- 13/98 +/- 10 mmHg) and 12 normal, age- and heart-rate-matched, control subjects were studied. All subjects showed normal left ventricular systolic function and wall thickness on two-dimensional echocardiography. The following indices were obtained. (1) Acoustic quantification (AQ): the time rate of area change in early diastole (dA/dt)E, in late diastole (dA/dt)A and their ratio (dA/dt)E/(dA/dt)A. (2) Doppler echocardiography: the early peak E, the late peak A flow velocities, their ratio E/A and deceleration E-F slope in early diastole. Measurements of left ventricular diastolic function by acoustic quantification showed, in the patient group, that the time rate of area change in early diastole (dA/dt)E was significantly lower (64.7 +/- 11.0 cm2/second versus 74.3 +/- 5.9 cm2/second; P < 0.01), the rate of area change in late diastole (dA/dt)A was not significantly higher (43.3 +/- 9.2 cm2/second versus 38.4 +/- 6.0 cm2/second; P > 0.05), and the ratio between the above indices (dA/dt)E/(dA/dt)A was significantly lower (1.55 +/- 0.42 versus 1.95 +/- 0.20; P < 0.01), compared with normal values. Doppler diastolic indices were all significantly abnormal in patients, in comparison with the values of the control group. Reduced left ventricular diastolic function was found in nine of 23 patients (39.1%) by the AQ method and eleven of 23 patients (47.8%) by Doppler echocardiography. Acoustic quantification was in agreement with Doppler echocardiography in identifying left ventricular diastolic dsyfunction in nine of 11 hypertensive patients with reduced Doppler diastolic values (82% sensitivity, 100% specificity). The correlation between the two methods showed that the time rate of area change in early diastole (dA/dt)E correlated well with the early peak E flow velocity (r = 0.59), the ratio between the time rates in early and late diastole (dA/dt)E/(dA/dt)A also correlated well with the Doppler E/A ratio (r = 0.89), while a poor correlation was found between the time rate of area change in late diastole (dA/dt)A and peak A flow velocity (r = 0.26). Thus abnormal diastolic filling of the left ventricle can be seen in the early stages of hypertension, even in the presence of normal systolic function and wall thickness, while acoustic quantification could be considered as a useful noninvasive modality for the early identification of left ventricular diastolic abnormalities.

Influence of pindolol on asthmatics and effect of bronchodilators.

Bronchospasm is a known side effect of the administration of beta-blockers to asthmatics. The purpose of this study was to investigate the frequency of bronchospasm caused by the administration of relatively low doses (2.5-7.5 mg) of pindolol, a beta-blocker with intrinsic sympathetic activity (ISA) to asthmatics, the severity of the bronchospasm and its reversibility and the probable correlations of bronchial asthma (BA) characteristics (severity, duration, allergy and airway hyperreactivity) with existing or nonexisting bronchospasm. Seventeen asthmatic patients: 10 men and 7 women, with a mean age of 44 +/- 10 years, participated in this study. The duration and severity of BA, the presence of allergy determined by skin tests and the bronchial hyperreactivity to methacholine inhalation challenge were observed on the first day of study. On the following days, the respiratory function parameters forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), and the pulse rate were measured before and 30, 60 and 90 min after the administration of placebo and pindolol. Then salbutamol was administered by a dosimetric aerosol (DA) at the usual dosage (200 micrograms) and the change in FEV1 was observed at 60 min; thereafter 40 micrograms of ipratropium bromide (IB) were administered by DA and FEV1 was measured after 60 min. Pindolol was administered gradually by mouth (2.5 mg every 30 min), the maximal total dose being 7.5 mg. Administration of pindolol caused a significant fall of FEV1 of 12 +/- 11% compared to placebo. A significant total decrease of FEV1 (greater than or equal to 20% of baseline) was observed in 9 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of left ventricular diastolic dysfunction in hypertensive patients 1 month after ACE inhibition therapy: evaluation by ultrasonic automated boundary detection.

The purpose of this study was to detect any improvement in left ventricular diastolic dysfunction in hypertensive patients 1 month after cilazapril therapy. Twenty-three patients, 5 men and 18 women (mean age, 53.52 +/- 9.10 years), with mild or moderate hypertension (160 +/- 13/98 +/- 10 mm Hg), and free of other cardiac or systemic diseases, were studied using ultrasonic automated boundary detection (ABD) and pulsed Doppler echocardiography, before and 1 month after a daily dose of 2.5 mg of cilazapril. The following new ABD diastolic indices were determined: the time rate of area change in early diastole (dA/dt)E, that in late diastole (dA/dt)A, and their ratio (dA/dt)E/(dA/dt)A, while Doppler transmitral flow measurements of left ventricular diastolic filling were also simultaneously recorded. The ABD results showed left ventricular diastolic dysfunction (LVDD) in 9 of 23 patients (39%) compared with the ABD values of 12 normal volunteers. Neither method revealed any significant difference before and after treatment in the patient group as a whole. However, in the group of 9 patients with diastolic dysfunction, the ABD ratio (dA/dt)E/(dA/dt)A was significantly improved after cilazapril therapy (1.20 +/- 0.21 versus 1.41 +/- 0.17; P < 0.05). We concluded that a large percentage (39%) of patients with mild or moderate hypertension had reduced diastolic performance of the left ventricle at a stage of the disease when systolic dysfunction and/or hypertrophy were not evident. Significant improvement of diastolic dysfunction in hypertensive patients could be detected by the proposed ABD new diastolic indices 1 month after cilazapril therapy. In conclusion, automatic boundary detection should be a useful non-invasive modality for the early diagnosis of left ventricular diastolic dysfunction, as well as early recognition of its improvement.

Effect of ipratropium bromide on repeated methacholine challenges.

The purpose of this study was to trace the protective effect of ipratropium bromide (IB) during methacholine inhalation challenge (MIC) at the first and fourth hour after its administration. IB-inhaler contains 0.02 mg IB in each puff and it was used in the usual dosage of two puffs (0.04 mg). In 20 asthmatic patients, the dose of methacholine caused a drop in FEV1 of 20% (PD20-FEV1). It was concluded that IB protected patients significantly one hour after its administration and showed a significant bronchodilating effect in comparison to placebo. IB protected 19 of the 20 patients one hour after administration during MIC while placebo protected none. IB protected 13 of the 20 patients, after the second PD20-FEV1 with methacholine, four hours after its administration.