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Biomedical subjects

U Cornelli

Publications and source records attributed to U Cornelli.

At least 19 recordsLinked to original sources

Pharmacokinetics of GM1 ganglioside following parenteral administration.

The pharmacokinetic parameters of monosialotetrahexosylganglioside (GM1) have been determined in healthy volunteers at 3 dose levels: 100, 200, 300 mg. Each dose was administered to separate groups of 12 volunteers. GM1 levels were determined in plasma, urine, and faeces by a method based on the property of the cholera toxin beta subunit to react specifically with GM1 ganglioside. A non-compartmental model was applied to determine standard pharmacokinetic parameters. The average AUC increased with dose (1002 +/- 121.2, 1306 +/- 146.1, 3155 +/- 121.6 micrograms mL-1 h after 100, 200, 300 mg, respectively). Plasma clearance was less than 3 mL min-1 and the distribution volume was close to the plasma volume (on average between 4.3 and 7.2 L). Mean residence time was about 43 h for all doses. GM1 was not detected in urine, while in faeces the amount of GM1 determined was similar to the baseline values obtained before dosing.

Adult

[A multicenter study of defibrotide in the prevention of deep venous thrombosis. Final results].

In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide and calcium heparin in the prophylaxis of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) an evaluation has been made on 4810 patients. 2810 patients received defibrotide (800 mg/die: 400 mg b.i.d. or 200 mg q.i.d. by IV route); 2000 patients received calcium heparin (500 IU b.i.d. or t.i.d. by SC route) till the 7th post-operative day. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routine criteria. The incidence of DVT has been 33/2810 (1.17%) in the defibrotide group and 47/2000 (2.35%) in the heparin group (chi 2 p = 0.002), while the cases of suspected or ascertained PE have been respectively 15/2810 (0.53%) and 23/2000 (1.15%) (p = 0.025). The post-operative course was totally normal in both groups; no significant adverse reactions were noticed. The obtained results suggest the effectiveness of defibrotide as an alternative to heparin in the prevention of post-operative DVT.

Adult

Antithrombotic drugs in pelvic surgery.

From the discussion, it is clear that several agents are available for the prophylactic antithrombotic management of pelvic surgery. Unlike other surgical procedures, the interventions are performed in women with many physiologic and pathologic predisposing factors. There is an increased risk of bleeding in these patients and the selection of an antithrombotic drug with a high safety to efficacy ratio is imperative. Although the introduction of newer drugs, such as defibrotide and low molecular weight heparins, provides certain advantages over the conventional drugs, large-scale prospective clinical trials are required to justify their use. Combination therapy will also be a useful and more effective approach in the management of pelvic surgical patients. However, optimization of dosage and an empiric determination of the safety and efficacy of different drugs used in combination will have to be made. Newer therapeutic agents will have a direct impact in this area in coming years. The practicing clinician should keep an open mind to provide better patient care.

Female

Lack of effect of a single-dose of sulglicotide on the bioavailability of diclofenac.

The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p less than 0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug.

Adult

Effect of methyldopa on prolactin serum concentration. Comparison between normal and sustained-release formulations.

In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.

Adult

[Defibrotide in the prevention of deep venous thrombosis in general surgery. Preliminary results of a multicenter study].

In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide in the prophylaxis of postsurgical deep vein thromboses (DVT) an ad interim evaluation has been made on 2626 patients thus far enrolled. 1323 had received defibrotide (200 mg q.i.d. by IV route from day -1 to day +7th postoperative), 941 calcium heparin (5000 IU b.i.d. or t.i.d. by SC route from day 0 to day +7 postoperative) and 362 other treatments (antiaggregating agents, placebo or no therapy). This group has not been included in the final evaluation, due to its limited size. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routinary criteria. The incidence of DTV has been 15/1323 (1.13%) in the defibrotide group and 21/941 (2.23%) in the heparin group (chi-square, p = 0.056) while the cases of suspected or ascertained PE have been respectively 3/1323 (0.22%) and 10/941 (1.06%) (p = 0.02). The incidence of adverse effects with defibrotide was less than 1%; occasional cases of increased serum transaminase levels were seen with heparin. These preliminary results supports the effectiveness of defibrotide in the prevention of post-surgery DVT, its effects being similar or more prominent than those of calcium heparin, currently regarded as the standard medication.

Adult

Lack of influence of sulglycotide on naproxen bioavailability in healthy volunteers.

We explored the bioavailability and kinetics of naproxen (N) in 12 healthy volunteers treated orally with single doses of 500 mg and retreated after a washout period with the same dose of N plus sulglycotide (S) 200 mg. Naproxen blood levels were measured by high-performance liquid chromatography (HPLC) in samples collected at 0.5, 1, 2, 4, 8, 12, and 24 h of dosing with N or with N + S. No statistically significant difference in terms of naproxen blood levels emerged as the product was administered alone or concurrently with sulglycotide. Peak plasma concentrations and AUC values were 71 +/- 3.16 micrograms/ml and 685 +/- 27 micrograms/ml/h, respectively for N alone, and 72.5 +/- 2.85 micrograms/ml and 651 +/- 28 micrograms/ml/h, respectively for N + S. The difference was not significant. Similarly, the kinetic behavior of naproxen was not modified by the simultaneous presence of sulglycotide, as shown by the t1/2 beta-values obtained with N alone (8.39 +/- 0.31 h) and with N + S (7.93 +/- 0.30 h), and likewise by the distribution volumes at equilibrium (7.63 +/- 0.42 and 7.9 +/- 0.38, respectively), Cmax (63.3 +/- 2.86 and 60.4 +/- 2.9 micrograms/ml, respectively) and tmax (0.95 +/- 0.06 and 1.10 +/- 0.10 h, respectively). From these findings it seems legitimate to claim that sulglycotide can be administered concurrently with naproxen to prevent possible gastric injury by the anti-inflammatory agent thanks to its wellknown antiulcer and cytoprotective activity on the gastric mucosa, without any undue interference with the absorption (hence effectiveness) of naproxen.

Adult

Serum theophylline and ventilatory function in chronic obstructive lung disease. Comparison between two slow-release formulations of theophylline.

Pharmacokinetics and ventilatory response to Theodur (Th) was compared to that of Aminomal R (AR) in a randomized within-patient double-blind study, carried out in patients with chronic obstructive lung disease. Both slow-release preparations of theophylline were given every 12 hours for 14 days each at the end of a placebo wash-out period. Th and AR did not differ significantly in their bronchodilating effect at 3 and 12 hours after intake. Salbutamol consumption was not dissimilar in the 2 preparations. Mean serum theophylline levels remained within the therapeutic range at 2, 3 and 12 hours after sustained administration of both Th and AR, but were slightly lower and less fluctuating after Th. Gastrointestinal side effects such as epigastric discomfort, nausea, abdominal pain and diarrhea were more common after AR, a result likely due to its higher content of anhydrous theophylline per tablet (474 mg vs 300 mg in Th). In conclusion, we failed to detect differences between Th and AR in their bronchodilating effect after sustained treatment in patients with chronic obstructive lung disease. Th, however, although containing less theophylline per tablet, resulted in comparable theophylline levels with similar ventilatory response, in presence of a better gastrointestinal tolerability. These results suggest a better bioavailability of Th, likely accounted for by a more advanced pharmaceutical technology.

Albuterol

[In-hospital and long-term prognosis in acute myocardial infarction. Comparative longitudinal study of 2 patient groups].

The in-hospital mortality, the causes of death, the actuarial survival curves were compared in two subsequent groups of patients admitted to our CCU for acute myocardial infarction: the first (group A) includes 791 pts, admitted from september '67 to december '72, the second (group B) includes 542 pts admitted from january '78 to june '80. The in-hospital mortality was significantly reduced in group B (A: 186/791, 23.5%; B: 72/542, 13,3%, p less than 0.01). This could be due to a reduction of the number of deaths for cardiogenic shock (A: 71/791, 9%; B: 30/542, 5.6%; p less than 0.01) and to reduction in the mortality rate for pulmonary oedema (from 6% to 1.5%, p less than 0.01), although the frequency of pulmonary oedema was the same during the two periods (A: 205 pts, 26%; B/156 pts 29%). We did not observe any significant difference in the long-term prognosis (54 months: A 79.3%, B 71.5%). The actuarial survival curves overlapped after the 1st semester after discharge. The most frequent cause of death during follow-up was a new myocardial infarction. None in the group A and only 3% in the group B were referred to the surgeon for coronary artery bypass grafting. We conclude that, in spite of a significant reduction of the in-hospital mortality, possibly related to the evolution in diagnosis and management of the disease, the long-term survival was not improved in a non-surgically treated population with myocardial infarction.

Adult

Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis.

Fifteen grass pollen--sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens (except Bermuda grass), no previous IT, and residence and occupation in an area monitored by serial pollen counts. They underwent a double-blind trial of specific IT with a mixture of three grass pollen--aqueous extracts (velvet, sweet vernal, and timothy) or placebo. After 10 mo, the mean maintenance dose of pollen extract (assayed by RAST inhibition) in eight actively treated patients was 6000 RAST units (range 3000 to 8000) and the mean total dose was 18,700 RAST units (range 10,200 to 30,000). Results were assessment done by the following clinical and immunological data: (1) during the pollen season, daily symptom scores; (2) PD 20% FEV1, IgE antibody to timothy by RAST in serum and in nasal secretions, serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay, and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season. Symptom scores of both treated patients and controls correlated with pollen counts (R = 0.88, p less than 0.05 and R = 0.71, p less than 0.05, respectively). There was a significant difference between the mean symptom score values of treated patients versus controls (Kruskal-Wallis test, p less than 0.001). No significant differences or changes either in the PD 20% FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A screening method for substances potentially active on learning and memory.

A series of substances from different pharmacological classes was examined by two different tests for their activity on learning and memory. A concomitant evaluation was performed by use of a one-trial passive avoidance immediately followed by electroshock in mice and the pole-climbing test in rats. Only doses not producing changes in gross behavior (Irwin's test) were used. A facilitating action on all the considered parameters was observed for d-amphetamine, caffeine, L-glutamine, Mg pemoline, phosphorylserine, piracetam, strychnine, and tricyanoaminopropene. A worsening action was found for atropine, cycloheximide, diazepam, and morphine. Chlorpheniramine, diphenylhydantoin, GABA, imipramine, meclizine, mescaline, metrazol, and testosterone showed no or doubtful activity. Our results suggest that the parallel use of these relatively simple tests supplies information that is satisfactory for screening purposes and that has a high degree of predictability as substantiated by literature data.

Animals

Sodium cromoglycate and provocation tests in chronic urticaria.

Twenty patients with chronic urticaria exacerbated by aspirin or tartrazine were challenged with the offending substance after pre-treatment with either oral sodium cromoglycate or placebo in a double-blind, crossover study. The sequential vascular response test (SVR) described by Fisherman and Cohen 1-4 was used to assess response to challenge. Eighteen patients were protected by oral sodium cromoglycate and one by placebo, taking as a positive response an increase in the bleeding time of 100% or more over control values.

Adult