[Asthma mortality and utilization of antiasthmatic agents in Finland].
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Biomedical subjects
Publications and source records attributed to K Liippo.
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Dirithromycin, a new once-daily macrolide, was studied in a multicentre, randomised, double-blind trial in community-acquired bacterial pneumonia. A total of 591 patients received either a single daily dose of dirithromycin, 500 mg, or erythromycin, 250 mg, four times daily. Clinical response rates were similar in both treatment groups (127 dirithromycin-treated and 118 erythromycin-treated patients): at the time of the final consultation, the clinical and bacteriological response rates for dirithromycin-treated patients were 94.5% and 93.0%, while for erythromycin-treated patients, they were 92.1% and 90.3%, respectively. The nature and frequency of treatment-emergent events were comparable. We conclude that dirithromycin, 500 mg, once daily, is safe and effective in the treatment of community-acquired bacterial pneumonia. The once daily dose is likely to improve compliance, making it preferable to erythromycin.
Twenty-one adult asthmatic patients participated in a trial to compare the clinical equivalence of a single dose of salbutamol inhaled either from a novel multiple dose powder inhaler (MDPI), Easyhaler, or from a conventional metered dose inhaler (MDI). The trial was carried out as a randomized, double-blind, crossover study. The study involved 2 study days with a 6-hour follow-up period of spirometric indices. In addition, blood pressure and heart rate were measured immediately before each lung function test. Our data indicate that salbutamol treatment with the MDPI achieves values which are equivalent to those achieved with the conventional pressurized MDI as regards improving pulmonary function and tolerability. The mean maximum forced expiratory volume in 1 s (FEV1) after the powder dose was 2.44 +/- 0.96 liters and after the aerosol dose 2.45 +/- 0.93 liters. The mean area under the curve of absolute FEV1 values was 822 +/- 340 and 829 +/- 335, respectively. The mean percent change from the baseline in FEV1, forced vital capacity and peak expiratory flow following administration of the preparations was of equal magnitude in both cases. The treatments tested had no effect on blood pressure or heart rate and were well tolerated. A further important finding was that most patients found the MDPI easier or no more difficult to use than the conventional MDI and this probably facilitates the transition from pressurized MDIs to the novel MDPI.
The combination of carboplatin and etoposide was evaluated in 61 previously untreated patients with extensive small cell lung cancer. Treatment was given at four-week intervals with 450 mg/m2 of carboplatin intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1-3. The response was complete in 5 (9%) and partial in 28 (50%) of the 56 evaluable patients (overall response rate 59%). The median time to progression after response as well as the median survival time in all evaluable patients was 4.6 months. WHO grade 3 and 4 leukopenia and thrombocytopenia occurred in 8% and 11% of the courses respectively. Two treatment-related deaths were registered. The combination of carboplatin and etoposide used in the present study produced acceptable response rate and toxicity, but duration of response and median survival were shorter than expected from earlier studies.
A negative methacholine inhalation challenge (MIC) in a patient with suspected bronchial asthma is generally considered to make this diagnosis unlikely. Nevertheless, the patient may later develop asthma. To estimate the proportion that eventually becomes asthmatic, a 10 year follow-up study was carried out on 334 consecutive MIC-negative patients aged 14-80 years. The development of asthma among these patients was assessed on the basis of entitlement to preferential refund from the cost of antiasthmatic therapy granted for them under national health insurance. During the follow-up 30 patients (9%) were granted the refund. There was no significant difference between men and women in this respect. Patients who developed asthma were somewhat older than those who did not. A family history of allergy, allergic rhinitis, and positive reactions to skin prick tests were significantly more common in patients with future asthma. These patients also had a lower mean forced expiratory volume in 1 sec (FEV1) (% of predicted) and a higher mean increase in PEF after an inhaled sympathomimetic than those remaining free from asthma. In multivariate analyses with a logistic model, 3 risk indicators proved independent predictors of future asthma: age, positive family history of allergy, and FEV1 (% of predicted).
There are very few data as yet to quantify the effect of inhaled corticosteroids on bone metabolism, although the use of these drugs as a first-line treatment in bronchial asthma has widened. We determined the effect of three dose levels (200, 1000, 2000 micrograms/day, three weeks each) of inhaled beclomethasone on specific characteristics of bone metabolism in nine postmenopausal women with new asthma without any previous corticosteroid therapy. Significant decrease was noted in the mean serum morning osteocalcin concentration between the baseline and after nine weeks of beclomethasone (from 4.4 to 3.1 micrograms/l, p = 0.005). Significant increase in serum total and ionised calcium was found, although the parameters measuring bone resorption itself did not change. The results show that especially high-dose inhaled beclomethasone decreases serum osteocalcin in post-menopausal asthmatic women. Further studies are needed to assess the effects of inhaled beclomethasone, both on the ability of the osteoblasts to form bone matrix and on the density of bone during a longer treatment period on inhaled corticosteroids.
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A polymerase chain reaction (PCR) assay for the rapid detection of mycobacterial DNA is described. Oligonucleotide primers, derived from the sequence of a gene coding for the 32-kDa antigen of Mycobacterium tuberculosis, amplified DNA from all 28 species of mycobacteria tested. All nonmycobacterial species tested were negative. An oligonucleotide probe hybridized to the PCR products of the strains belonging to the M. tuberculosis complex. This method could detect as little as 50 fg, as tested with purified M. tuberculosis DNA. By this amplification method, 127 sputum specimens were tested, with 7.9% of the specimens proving to be inhibitory in PCR. The sensitivity of detection by PCR compared with that by culture was 55.9%; when the inhibitory specimens were excluded, the sensitivity was 70.4%. The specificity of PCR combined with hybridization was 100%.
A 44-year-old man with nasal and respiratory symptoms combined with positive serum antibodies to neutrophil cytoplasmic antigens (ANCA) suggestive of Wegener's granulomatosis was treated with antibacterial agents. Complete clinical response was achieved with co-trimoxazole, and the titer of ANCA declined. After a 12-month treatment period, the patient contracted fever and respiratory symptoms and fatigue again, and he had proteinuria and hematuria. After the institution of conventional treatment with oral prednisolone and cyclophosphamide, a favorable response was achieved. Wegener's-like granulomatosis is difficult to diagnose at its early stage, but the presence of ANCA may be helpful. We suggest that co-trimoxazole should be considered as a first-line treatment, under careful supervision, for young patients whose disease is limited to the respiratory organ.
An analysis of 33 patients with histologically confirmed intrathoracic tuberculous lymphadenopathy was made. Tuberculosis could have been diagnosed without mediastinoscopy only in 3 patients: 2 had positive bronchial cultures and 1 simultaneous cervical lymph node tuberculosis. Bacteriological confirmation is conclusive, but seldom possible. Mediastinoscopy provides the best method to obtain tissue samples, and consequently, it is still necessary in the diagnosis of intrathoracic tuberculous lymphadenitis.
We report a male patient who developed an unusual periodic breathing. At presentation, the differential diagnosis at bedside between Cheyne-Stokes and primary hyperventilation syndrome was laborious, and the final verification was based on the result of capnography.
Sixty-eight patients with limited small cell lung cancer were treated between April 1988 and October 1990 with combination carboplatin 450 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1-3 (CarE) for two courses, followed by thoracic radiotherapy (TRT) 50 Gy, and then vincristine 1 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 750 mg/m2 on day one (VAC) for four courses. Prophylactic cranial irradiation (30 Gy) was given to patients with CR after completion of chemotherapy. Sixty patients (89%) achieved an objective response (40% complete responses). The median time to progression was 8.5 months and median survival time 12.1 months. Predicted one- and two-year survival was 50% and 12% respectively. Myelosuppression was the main toxicity, with WHO grade 3 and 4 leukopenia occurring in 32% of VAC courses. There were 5 (7%) treatment-related deaths, all of them during VAC. We conclude that the present combination is active in terms of response rate, but it did not demonstrate any superiority in survival. The frequency of haematological toxicity was substantial during VAC courses.
Procaterol is a new, potent, long-acting beta-2-adrenergic bronchodilator. The magnitude and duration of the immediate bronchodilatation produced by inhaled procaterol aerosol have been compared with those produced by inhaled salbutamol aerosol in 20 asthmatic patients. Patients inhaled two puffs of procaterol (20 micrograms) or two puffs of salbutamol (200 micrograms) and PEF, FVC and FEV1 were measured after 5, 15, 30, 60, 120 and 180 min. The changes in mean PEF, FEV1 and FVC values were greater after procaterol than salbutamol, but the difference in bronchodilatation was not significant. The response to rimiterol after 180 min was greater in the salbutamol group. The increases in heart rate and systolic blood pressure were slightly higher after procaterol. Eleven patients reported adverse effects; 5 after procaterol, 3 after salbutamol, and 3 after both drugs. Thus, procaterol was a potent bronchodilator when inhaled as a single dose of 20 micrograms, but it did not appear to be an ultra long-acting preparation.
The cases of two patients with ulcerative colitis are described who developed pulmonary infiltrates during the early months of treatment with sulphasalazine. The first patient had a hypersensitivity pneumonitis, which was confirmed by challenge. Recovery was complete. The second patient developed a fibrosing alveolitis type reaction, with fatal outcome.
The relative risk of mesothelioma associated with different levels of exposure to asbestos was evaluated. The exposure was assessed from work histories of 51 mesothelioma cases and 51 sarcoidosis referents. The lung fiber concentration of the mesothelioma patients was compared with that of two reference groups (13 random autopsy cases and 43 male lung cancer patients). When the categories definite and probable were used as an estimated probability of occupational exposure, an odds ratio of 17.7 [90% confidence interval (90% CI) 3.4-253] and 3.0 (90% CI 0.9-10.6), respectively, was obtained. A lung fiber concentration of greater than 1 million fibers/g of dry tissue as an indicator of accumulated exposure gave an odds ratio of 14.4 (90% CI 2.5-178) for the men in comparison with the autopsy cases and 3.1 (90% CI, 1.3-7.5) in comparison with the lung cancer patients. Elevated risk of mesothelioma was shown to be associated with a lung fiber concentration of greater than 1 million fibers/g of dry tissue.
Lactate dehydrogenase (LD; EC 1.1.1.27) and creatine kinase (CK; EC 2.7.3.2) are widely distributed cytoplasmic enzymes. LD has five and CK has three isoenzymes distributed in different proportions in various tissues. The amounts of LD and CK and the distribution of isoenzymes in different body fluids are not thoroughly characterized. We have measured the total LD and CK concentrations and their isoenzyme distribution in pleural aspirates and in serum from 22 patients with benign conditions and from 14 patients with malignant effusions. In malignant pleural fluid, the mean total LD was 662 U/L; in benign conditions, it was nearly 5840 U/L with large variations (91-43 400 U/L) according to clinical diagnosis, the highest values being reached in inflammatory lesions. The mean total CK concentration in pleural fluid was close to the serum value in both groups of patients, as was the pleural CK isoenzyme distribution. The LD isoenzyme distribution in pleural effusions differed from that in serum in both groups, with LD-4 and -5 being the main isoenzymes in their pleural fluid specimens (greater than 42% of total LD). The total LD concentration correlated somewhat (r = 0.57) with the total pleural protein content. In conclusion, the pleural LD isoenzyme distribution, both in benign and malignant conditions, differs from that in serum, having shifted towards more anaerobic and embryonic isoenzymes (LD-4 and -5). Moreover, the greater the concentration of pleural total LD, the greater the proportion of LD-4 and -5. These data suggest that visceral or parietal pleural cells are rich in LD isoenzymes 4 and 5.
This phase I study was carried out to determine the maximal tolerated dose of carboplatin (Car) together with a fixed dose of etoposide (E) and to recommend the optimal dose for a phase II study. The dose of E was 100 mg/m2 given i.v. on days 1-3, and the starting dose of Car was 200 mg/m2 given i.v. on day 1. The dose was escalated until WHO grade 4 toxicity developed after two treatment cycles in more than one-third of the patients. A total of 33 patients with advanced lung cancer entered the trial. The maximal tolerated toxicity of the combination was reached at a dose of 500 mg/m2 Car. Myelosuppression was moderate, and hematological toxicity of WHO grade 4 was encountered in one of five patients at 475 mg/m2 and in two out of five patients at 500 mg/m2. The main toxic effects were leucopenia and thrombocytopenia. The frequency of treatment-related infections was low and no deaths were caused by treatment. There was a significant overall correlation between the platelet nadir and creatinine clearance. One complete response and three partial responses were achieved after two treatment cycles. Based on the results of the present study, the dose of carboplatin (combined with 100 mg/m2 eposide given on days 1-3) recommended for phase II studies is 450 mg/m2.
A total of 80 patients with limited disease of small cell lung cancer were randomized to receive either vincristine 1 mg/m2 (max. 2 mg), doxorubicin 50 mg/m2 and cyclophosphamide 750 mg/m2 (VAC) i.v. on day 1, or the same drugs and etoposide 80 mg/m2 i.v. daily for 3 days (VACE) every 3 weeks for nine courses. Chest irradiation was given in both regimens after the second course. The response rate was 84% for VAC (41% complete responses) and 75% for VACE (46% complete responses). The median survival time was 10 months with VAC regimen, and 14 months with VACE (difference statistically not significant). The median duration of remission was 8 months with VAC and 14 months with VACE (p = 0.03), and the median survival for complete or partial responders was 12 months and 20 months respectively (p = 0.006). Myelosuppression was significantly greater in the VACE group, and there was one treatment related death in the group receiving VACE. In this study the addition of etoposide to VAC improved the duration of response, but did not lead to longer survival of patients with limited disease of small cell lung cancer.