[Efficacy and tolerability of paracetamol-sobrerol combination in patients with hyperpyrexia]. / Efficacia e tollerabilità dell'associazione paracetamolo-sobrerolo nel paziente iperpiretico.

The therapeutic efficacy and tolerability of the association paracetamol-sobrerol in comparison with paracetamol alone, was tested in a double-blind, randomized clinical trial, carried out on 287 out-patients, suffering from diseases of the respiratory tree with fever. The treatment was performed for up to five days. At the end of the treatment, both treatments lead to an important improvement of all considered clinical parameters; furthermore, the association paracetamol-sobrerol showed a statistically important difference versus paracetamol alone as to cough and difficulty to expectorate. As to body temperature, both paracetamol and paracetamol-sobrerol showed a good antipyretic activity; furthermore, the association compared to paracetamol alone obtained a statistically significant differences in times x treatments. These data fully confirm the results obtained from recent studies: the simultaneous administration of paracetamol and sobrerol obtains a better antipyretic action than paracetamol alone. This synergism allows to reduce paracetamol doses and, consequently, to eliminate the already low incidence of adverse reactions, without decreasing the antipyretic activity.

[Pharmacosurveillance of antipyretics. Evaluation of the risk-benefit ratio of a combination of paracetamol and sobrerol. Monitoring of 3501 ambulatory patients]. / Farmacosorveglianza degli antipiretici. Valutazione del rapporto rischio-beneficio della associazione paracetamolo-sobrerolo. Monitoraggio di 3501 pazienti ambulatoriali.

3501 outpatients with fever due to respiratory disorders or eruptive diseases or to other causes were included in a post-marketing surveillance study aimed at extending knowledge of antipyretics and particularly of the paracetamol-sobrerol combination. The antipyretic activity of the drug under test was comparable to that of the reference molecules. Paracetamol-sobrerol combination exerted an extremely valid therapeutic action on cough and difficult expectoration, parameters which usually are associated with the phlogosis and congestion typical for airway infections. As already observed in literature, patients receiving salicylates complained of side effects while patients treated with pyrazolics complained of side effects involving nervous system and cardiovascular apparatus. Side effect incidence in patients treated with the paracetamol-sobrerol combination (3.7%) was significantly lower than that observed in subjects treated with paracetamol (6.1% - P less than 0.01), salicylics (25.1% - P less than 0.001), pyrazolics (12.6% - P less than 0.001), propionics (20.3%, P less than 0.001) or other antipyretics (17.9% - P less than 0.001). These findings demonstrate that the paracetamol-sobrerol combination is a valid therapeutic tool and is particularly suitable in febrile airway pathology. In addition, the low incidence of side effects due to the lower doses of paracetamol, makes this product well tolerated also by at risk subjects such as children and old patients.

[Effectiveness and tolerance of a new molecule with secreto-dynamic activity: nesosteine]. / Efficacia e tollerabilità di una nuova molecola ad attività secretodinamica: la nesosteina.

232 patients with acute or chronic respiratory disorders characterized by increased secretion, were included in an open multicentre trial to evaluate the tolerability and the activity of a new molecule with secreto-dynamic action, nesosteine. The drug was administered orally at the dose of 900 mg/day for two consecutive weeks. The incidence of side effects (11.6%) was comparable to that observed in studies carried out on molecules with similar activity. Undesirable reactions were found mainly at the gastrointestinal level. Side effects were slight/moderate in most cases; only 3 patients abandoned treatment. Nesosteine therapeutic activity was highly valid; cough and expectorate were favourably affected by treatment. The drug, by restoring the natural characteristics of excreate viscoelasticity, favored a better mucociliary clearance and a more incisive cough expelling action. The activity/tolerability ratio was judged excellent/good by the investigator in 83% of the patients treated.

Activity of epomediol in the treatment of hepatopathies: a double-blind multi-centre study.

A multi-centre study with epomediol discoids (200 mg three times daily for 30 days) versus placebo was carried out in 519 patients either with symptoms attributable to hepatopathy and/or alterations in the hepatic function. Epomediol was given to 257 patients chosen at random and the remaining 262 were given placebo. In cases of hepatopathy in which there was no severe damage to the hepatic parenchyma the symptoms of the disease were reduced and the laboratory parameters were improved on treatment with epomediol, whereas the activity of the drug was low in patients with chronic hepatopathy. This confirms that the clinical use of epomediol is most useful in cases of hepatopathy in which the change in hepatic function is still reversible.

Clinical experience with two twice daily slow release theophylline preparations. Relation between serum theophylline concentrations, effectiveness, tolerability and compliance in elderly patients.

The relation between serum theophylline concentrations, effectiveness, tolerability and compliance were evaluated in 14 hospitalized elderly patients with broncho-obstructive pathology, using a new twice daily sustained release theophylline suspension compared to standard twice daily slow release tablets. The results showed that the mean theophylline serum concentration remains within the therapeutic range with both preparations. No significant difference exists between the two treatments with regard to effectiveness. Tolerability and compliance of the theophylline suspension, however, were higher.

Effect of long-term treatment with sobrerol on the exacerbations of chronic bronchitis.

706 chronic bronchitic patients were admitted to a double-blind controlled multicenter study to evaluate the effect of the prolonged administration of sobrerol on exacerbations, clinical signs and respiratory function indexes. Patients were treated at random with sobrerol 300 mg b.i.d. or placebo b.i.d. for 3 consecutive months during the winter of 1983/1984. At the beginning of the study, sex, body surface, smoking habits, environment, anti-influenzal vaccination, concomitant pathologies and therapies, respiratory anamnesis, clinical condition and spirometric indexes were equivalent in the two groups. Among the patients admitted to the study, 76% of the sobrerol group did not complain of any exacerbations compared to 58% of the placebo group (p less than 0.001), moreover the risk of exacerbation was about twice higher than with the drug. The use of antibiotics was equivalent in the two groups, whilst the consumption of bronchodilators/theophyllines was markedly lower in the sobrerol group. The response of the clinical signs (dyspnea and auscultatory semeiotics) and of the spirometric indexes (RV, VC and FEV1) to therapy, was significantly higher in the patients treated with sobrerol compared to the placebo group. The opinion expressed by the experimenter and by the patient at the end of each month of treatment was again in favor of sobrerol. Side effects, which were minor and no different from those claimed by the patients treated with placebo, and the hematological and hematochemical assessments, carried out before and after treatment, support the good tolerance of sobrerol. These results let us hope for a more appropriate use of the mucus-regulating agents, particularly in the chronic bronchopulmonary pathologies for which these drugs seem to represent the most rational care.

[Ulterior observations on the use of C3 in acute myocardial infarction: 105 patients were treated within the 1st 6 hours after the symptoms started]. / Observaciones ulteriores sobre el uso del C3 en el infarto miocárdico agudo: 105 pacientes tratados a las seis horas del comienzo de los sintomas

Two homogeneous groups of patients with acute myocardial infarction were observed within the first six hours from the coronary attack. On admittance and for ten days, 105 patients were treated with C3: the mortality rate resulted in 13.3%. The control group of 108 patients showed a mortality of 18.5%. Strict criteria of randomization were followed in allocating patients to the two groups. Although the difference is not statistically significant it is however interesting since it confirms a previous research. Statistically significant differences between the two groups were observed in all surviving patients in the injury signs regression time and in the cardiac volume in favour of the group treated with C3.

[Prognostic value of serial determination of CPK in acute myocardial infarction (author's transl)]. / Valore prognostico della determinazione seriata della CPK nell'infarto miocardico acuto

Serial determinations of CPK enzyme were performed every 4 hours during a 72 hour period in 40 patients with acute myocardial infarction (AMI) admitted to the Coronary Care Unit in the first 6 hours (average 2.6) from the appearance of symptoms. The peak ratio of activity of CPK was 708 mU/ml +/- 48 E.S. as medium value in the whole group was reached in a medium period of 21,1 +/- 0,74 E.S. hours from the attack. Half value of the peak ratio activity was reached after a medium time of 19,1 +/- 1,0 E.S. hours. A significant statistical correlation between the CPK peak ratio and the prognostic index of Selvini et al. was found. The peak ratio resulted in 571 +/- 41 E.S. in patients with uncomplicated AMI, whereas in those with complications such as arrhythmias and heart failure the average value was 901 +/- 136 E.S. No significant correlation between CPK values and ST wave evolution of the ECG peak ratio of 1638 mU/ml was found; however, one patient who died of cardiac rupture showed a low level of 395 mU/ml. The diagnostic and prognostic value of the serial determination of CPK during the first 48 hours of a coronary attack is emphasized.

A multicenter double blind clinical trial on 3.4.5-trimethoxybenzoiyl-epsilon-aminocaproic acid (C-3) in acute myocardial infarction.

186 out of 391 patients with acute myocardial infarction were treated with C-3 and 205 with placebo in a multicenter, double-blind clinical trial. Ensuing complications were treated in the same way in both groups. C-3 was injected i.v. slowly at the dose of 2 g statim plus 6 g by continuous drip infusion over 24 hrs for 5 days. During treatment, clinical progress was influenced only in regard to cardiac failure since in the C-3 group the improvement was more significant than in the placebo one (P less than 0.0025). Mortality rates were 8.1% and 11.2% for the C-3 and placebo groups, respectively. The difference in mortality was significant (P less than 0.05) for patients treated with C-3 for more than 24 hours. Mortality in male patients treated with C-3 for more than 12 hours was significantly lower (P less than 0.025). In patients less than 60 years old mortality rate was significantly lower (P less than 0.05) and was more so in patients receiving C-3 for more than 12 hours (P less than 0.025). Mortality due to complications was lower in the C-3 group, with arrhythmias (9.8% vs 14.2%), cardiogenic shock (69.2% vs 75%), and cardiac failure (9% vs 19.4%). Results agree with the hypothesis that C-3 may be effective in acute myocardial infarction by improving the action of traditional antiarrhythmic drugs, and augmenting myocardial contraction energy.