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Erdosteine is a new thiol compound with effects on bacterial adhesiveness as well as antioxidant and mucoactive properties. The EQUALIFE study, a fully randomized, double-blind, placebo-controlled, parallel-group, multicenter study, was designed to assets the effectiveness of long-term treatment with erdosteine in patients with moderate chronic obstructive pulmonary disease (COPD). One hundred and fifty-five patients received oral erdosteine, 300 mg b.i.d., or placebo for 8 months during the winter season to assess the effect of treatments on exacerbation rate, hospitalization, lung function and quality of life, assessed using the Short Form 36 and the St. George's Respiratory Questionnaire. A pharmacoeconomic analysis was also conducted to compare the two treatments. One hundred and twenty-four patients completed the study with erdosteine (n = 63) or placebo (n = 61). The group of COPD patients who received 8 months of continuous treatment with erdosteine had significantly fewer exacerbations and spent fewer days in the hospital than did the placebo group; furthermore, they had no loss of lung function. Patients in the erdosteine group also showed a significant improvement in health-related quality of life. The mean total COPD-related disease costs per patient were lower in the erdosteine group than in the placebo group over the study period. The results indicate that 8 months of treatment with erdosteine is effective in reducing exacerbation and hospitalization rates and in improving health status. The study suggests that erdosteine is likely to provide an important contribution to the therapy of patients with symptomatic COPD.

Transcription of eukaryotic tRNA genes relies on the TFIIIC-dependent recruitment of TFIIIB on a approximately 50 bp region upstream of the transcription start site (TSS). TFIIIC specifically interacts with highly conserved, intragenic promoter elements, while the contacts between TFIIIB and the upstream DNA have long been considered as largely non-specific. Through a computer search procedure designed to detect shared, yet degenerate sequence features, we have identified a conserved sequence pattern upstream of Saccharomyces cerevisiae tDNAs. This pattern consists of four regions in which particular sequences are over-represented. The most downstream of these regions surrounds the TSS, while the other three districts of sequence conservation (appearing as a centrally located TATA-like sequence flanked by T-rich elements on both sides) are located across the DNA region known to interact with TFIIIB. Upstream regions whose sequence conforms to this pattern were found to potentiate tRNA gene transcription, both in vitro and in vivo, by enhancing TFIIIB binding. A conserved pattern of DNA bendability was also revealed, with peaks of bending propensity centered on the TATA-like and the TSS regions. Sequence analysis of other eukaryotic genomes further revealed the widespread occurrence of conserved sequence patterns upstream of tDNAs, with striking lineage-specific differences in the number and sequence of conserved motifs. Our data strongly support the notion that tRNA gene transcription in eukaryotes is modulated by composite TFIIIB binding sites that may confer responsiveness to variation in TFIIIB activity and/or concentration.

We designed a prospective multicenter randomized controlled study in three long-term weaning units (LWU) to evaluate which protocol, inspiratory pressure support ventilation (PSV) or spontaneous breathing trials (SB), is more effective in weaning patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for more than 15 d. Fifty-two of 75 patients, failing an initial T-piece trial at admission, were randomly assigned to PSV or SB (26 in both groups). No significant difference was found in weaning success rate (73% versus 77% in the PSV and SB group, respectively), mortality rate (11.5% versus 7.6%), duration of ventilatory assistance (181 +/- 161 versus 130 +/- 106 h), LWU (33 +/- 12 versus 35 +/- 19 d), or total hospital stay. The results of these defined protocols were retrospectively compared with an "uncontrolled clinical practice" in weaning historical control patients. The overall 30-d weaning success rate was significantly greater (87% versus 70%) and the time spent under mechanical ventilation by survived and weaned patients was shorter in the patients in the study than in historical control patients (103 +/- 144 versus 170 +/- 127 h). The LWU and hospital stays were also significantly shorter (27 +/- 12 versus 38 +/- 18 and 38 +/- 17 versus 47 +/- 18 d). Spontaneous breathing trials and decreasing levels of PSV are equally effective in difficult-to-wean patients with COPD. The application of a well-defined protocol, independent of the mode used, may result in better outcomes than uncontrolled clinical practice.

Background: Treatment of biliary pancreatitis includes suppression of the biliary cause by cholecystectomy and common bile duct clearance. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy for eradication of biliary stones and laparoscopic cholecystectomy (L.C.) for residual gallbladder stones would be ideal but were once considered to be contraindicated by most surgeons. The timing of definitive biliary tract surgery and the role of ERCP have been the focus of discussion in recent years., Methods: During a two-year study period 51 patients with acute biliary pancreatitis were studied. Seven patients (14%) underwent emergency laparotomy, necrosectomy, cholecystectomy, exploration of the common bile duct and T-tube insertion, because unstable clinical conditions, with evidence of pancreatic and peripancreatic necrosis on CT-scan. Elective open cholecystectomy and CBD exploration were performed in 7 patients after the resolution of acute pancreatitis during the same hospital admission., Results: Early ERCP and L.C. were associated with favourable outcomes. 33 patients underwent ERCP preoperatively: 17 within 72 hours of admission and 16 after signs of clinical improvement. Laparoscopic cholecystectomy performed 3-25 days after admission was successful in 27 of 29 patients. Postsphincterectomy bleeding occurred in one patient and was treated successfully by endoscopic epinephrine injection. For median hospital stay and recurrence there were statistical differences between early and delayed ERCP., Conclusions: ERCP and sphincterectomy have a certain role in conjunction with laparoscopic cholecystectomy in the management of patients with acute biliary pancreatitis, particularly in institutions where there is easy access to expert interventional endoscopic techniques. This policy should reduce the risk of cholangitis and recurrent pancreatitis.

The effects of nedocromil sodium and of salbutamol on the generation of oxygen-derived free radicals in human polymorphonuclear leukocytes (PMNs) were compared in vitro by the luminol-amplified-chemiluminescence (LACL) assay induced by both particulate (Candida albicans) and soluble formyl-methionyl-leucyl-phenylalanine (fMLP) stimulants. Inhibitory dose-effect linear regressions were observed from 10(-3) to 10(-8) M for nedocromil and salbutamol after a 3' period of incubation with either C. albicans or fMLP. There was a linear regression with nedocromil sodium after 30' incubation, but desensitization was observed with salbutamol after this longer period of incubation. The generation of oxygen-derived free radicals was significantly greater for asthmatic patients than for normal subjects; therefore antiasthmatic drugs with this inhibitory activity could be an extra pharmacological benefit in the treatment of asthmatic patients.

Nocturnal hypoxemia occurs commonly in patients with chronic obstructive pulmonary disease (COPD). Because pulmonary hypertension and cardiac arrhythmias are associated with this phenomenon, the detection and treatment of nocturnal hypoxemia should be part of the management of COPD patients. The ability to predict nocturnal hypoxemia by evaluating an awake patient would be desirable economically and logistically because continuous nocturnal oximetry is not widely available and because it is costly and labor intensive. We sought to determine whether awake oximetry would be precise enough to be clinically useful in predicting the degree of nocturnal oxygen desaturation in patients with COPD. We studied 71 patients with COPD. During sleep, the arterial oxygen saturation (SaO2) decreased by an average of 9% with a maximum decrease of 21% (awake SaO2 93.0 +/- 0.4% vs nocturnal lowest SaO2 84.0 +/- 0.7%, p = 0.0001). The nocturnal oxygen desaturation in each patient, however, was poorly predicted from awake SaO2. The standard error of estimate was large with a value of 5.3%. These data suggest that awake SaO2 is not a good predictor of nocturnal oxygen desaturation in individual patients. The lack of a simple relationship between awake SaO2 and nocturnal SaO2 is due to a complex interplay of various physiologic and pathologic mechanisms involved in the control of breathing and oxygenation during sleep.

Dextromethorphan, after administration, is rapidly and extensively transformed into dextrorphan. The aim of this study was to compare the cough-suppressing activity of 6, 12, 24, 48 mg/kg, i.p., of dextrorphan (dextro rotatory isomer of racemorphan) with that of dextromethorphan, using the model of citric acid-induced coughing in the unanaesthetized, unrestrained guinea pig. A significant dose-effect relationship of dextrorphan in reducing citric acid-induced cough was observed. This effect was comparable with that of dextromethorphan. However, at 48 mg/kg, i.p., dextromethorphan had a toxic effect while dextrorphan did not. Because dextrorphan is the major metabolite of dextromethorphan and has antitussive activity comparable to that of dextromethorphan, clinical use of dextrorphan is suggested.

There are changes in the rheological characteristics of mucus (viscoelasticity) in several pulmonary pathologies, and especially in chronic bronchitis. Seaprose, a proteolytic enzyme, is one of the pharmacological possibilities for affecting the rheology of bronchial mucus to correct mucostasis and improve its clearance. The action of this drug on the viscoelasticity of bronchial mucus was assessed in a double-blind vs placebo study with 20 randomly balanced chronic bronchitis patients using a new kind of portable rheometer with special features designed for routine bronchial mucus analysis in clinical practice at the patient's bedside. It was found that in the group of patients who were given the placebo, there were no particular changes in the rheological behaviour of mucus, while in those patients who were given seaprose there were significant changes in both viscosity and elasticity at the end of treatment. Eight days after the end of treatment with seaprose, there was still a significant beneficial effect on the viscoelasticity of mucus and a sort of "post-mucolytic effect" can be postulated. Seaprose also had antiinflammatory action, and since in chronic bronchitis there are variable degrees of inflammations, its beneficial long-lasting effect could also be ascribed to this concomitant action.

Seaprose is a semialkaline proteinase endowed with proteolytic effect and antiinflammatory activity tested in different clinical trials. There is clinical evidence that seaprose reduces sputum viscoelastic properties in chronic hypersecretory bronchitis. The present study evaluated (in a double-blind design vs. placebo) the activity of seaprose on bronchial inflammation, mucus glycoprotein secretion and bronchial humoral defence mechanism in chronic bronchitic patients clinically stable (10 per group). Markers of bronchial inflammation (albumin, albumin/total protein ratio) and bronchial infection (DNA), of mucus glycoproteins (fucose and N-acetylneuraminic acid) and of humoral defence mechanism (secretory-IgA) were tested in sputum. We found that ten-day treatment with seaprose (90 mg/day) reduced sputum albumin during the observation period, the difference being statistically significant at the 18th day. The sputum albumin/total protein ratio also decreased by 50% at the end of the study. In the same group, sputum DNA, secretory-IgA, fucose and N-acetylneuraminic acid remained unchanged after treatment. The placebo group did not show any significant changes in the sputum marker substances. This study provides experimental evidence for the antiinflammatory activity of seaprose on bronchial mucosa in chronic bronchitic patients studied in a stable phase of their disease. Furthermore the drug does not seem to affect mucus glycoprotein secretion or secretory-IgA production.

Therapeutic effectiveness of a new long-acting antiarrhythmic preparation was evaluated in 31 patients with sustained premature ventricular beats. After an observation period, a 24 hours Holter monitoring was performed. A group (21 patients) was treated with dihydrochinidine 250 mg twice a day; another group (11 patients) was treated with 500 mg twice a day. In the latter group was determined basal chinidinemia on the first and third day. A 24 hours Holter monitoring was repeated on the fourth day. In the first group we reached a 77.4% reduction of the arrhythmia: not enough, however, to agree with established statements. We reached a larger reduction (84.7%) with higher doses (1000 mg daily). This drug was well tolerated in both groups.

Epidermoid cysts of the central nervous system may show a wide variation of localization. It sometimes involves the diploe of the skull; in this case it may occasionally be detected by an X-ray as a small area of osteolysis. Surgical treatment is mandatory because of the tendency to grow. Incomplete excision is always followed by recurrence.

In order to compare the medium term antihypertensive effectiveness and tolerability of atenolol with those of bopindolol (LT 31-200), a new non-selective beta-blocker with slight PAA (partial agonist activity), a randomized double-blind study was performed. Thirty-one outpatients with mild-to-moderate essential hypertension (WHO stage I-II) were enrolled and after a placebo run-in randomly allocated to bopindolol (1 to 4 mg/day) or atenolol (50 to 200 mg/day). The dose was titrated according to the individual pressor responses, and thereafter it was kept constant until the end of the treatment (12 weeks). Both drugs induced statistically significant decreases in SBP, DBP and HR, both in resting conditions and during an ergometric test. Accordingly, most patients achieved the main goal of the therapy, i.e., supDBP less than or equal to 90 mmHg, 11/15 (74%) with bopindolol versus 8/13 (62%) with atenolol. There were no significant differences between the effects of the two compounds. Resting airway resistance (expressed as Peak Expiratory Flow) was not influenced by the treatments. The antihypertensive efficacy was still evident after 12 months in 8 patients who were evaluated for non-comparative long-term effectiveness of bopindolol monotherapy, and improvements in plasma lipid profiles were also observed. Side effects were relatively mild and transient, with two patients in the atenolol group discontinuing therapy (one for inefficacy and one because of undesirable reactions) and one dropped out in the bopindolol group (late evidence of not fulfilling inclusion criteria).(ABSTRACT TRUNCATED AT 250 WORDS)

The results of a breast tumour prevention campaign conducted in 1977-78 by the Varese/3 Southern Outer Health Consortium are described. All women aged 30-65 yr were asked to come for a clinical examination of the breast by suitably trained midwives. Periodic self-examination was explained on this occasion and a card was prepared with historical data for evaluation of the risk factors. 4708 of the 8226 women approached came for examination (57%). Of those subjected to further diagnostic tests, 170 are still under out-patient control, while 34 have been hospitalised with a neoplastic incidence of the order of 1.28%, coupled with a pathological picture with various probabilities of degeneration. On the whole, it is felt that the most useful feature of the venture was its contribution towards the health education of the female population, and its bringing out of risk factors. A favourable judgement is passed on the campaign and its continuation is suggested.

The rheological properties of bronchial mucus samples, collected from randomly selected patients with chronic bronchitis by protected expectoration, under steady-state conditions without any exacerbation, were investigated in a double-blind multicentre study before and after five days of treatment with 4.5 g/day carbocysteine or with glucose as a placebo. Viscous and elastic properties of the mucus were measured with a rheometer fitted with coaxial cylinders set up in an oscillating instead of a rotating mode. The shapes of the ellipses obtained characterized the rheological properties of each bronchial mucus sample before and after treatment. Two different rheological patterns were observed. In the group of patients with initial viscosity greater than or equal to 10,000 mPa.s-1, carbocysteine treatment reduced viscosity and elasticity more than those of the placebo-treated patients. In the group of patients with viscosity lower than 10,000 mPa.s-1, the rheological modifications were the same for both groups. These results are discussed in terms of both the efficacy of carbocysteine and the necessity of rheological characterization of the patients before treatment into different groups, according to the rheological properties of their secretions, for better and targetted therapy with mucus modifying drugs.

The effectiveness and safety of dihydroergotoxine mesylate (DHT) and clonidine (CLO) as acute antihypertensive treatments were studied in a single-blind randomized controlled study of 28 patients hospitalized after abrupt increases in mean blood pressure (MAP) to more than 150 mmHg, with concomitant symptoms related to hypertensive status (16 patients). Intravenous infusion of 1.5 mg DHT significantly reduced both systolic (SBP) and diastolic (DBP) blood pressure from 227 +/- 2/128 +/- 2 mmHg to 160 +/- 4/94 +/- 2 mmHg by 1 hour after the onset of infusion (p less than 0.01). In patients given CLO, BP values fell from 221 +/- 3/123 +/- 3 mmHg to 166 +/- 5/95 +/- 3 mmHg after 150 minutes. After that BP values did not change significantly up to 6 hours after both treatments. One hour after the onset of infusion, mean heart-rate (HR) had decreased by 15 beats/min in the DHT group and by 10 beats/min in the CLO-group. Twenty-one per cent of the patients given DHT and 78% of the patients given CLO complained of mild or moderate side-effects. The results of this study showed that DHT is an effective and well tolerated agent for the treatment of hypertensive emergencies and can be used safely even when continuous monitoring of blood pressure cannot be carried out.