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Biomedical subjects

E Grossi

Publications and source records attributed to E Grossi.

15 recordsLinked to original sources

The effect of intravenous doxofylline or aminophylline on gastric secretion in duodenal ulcer patients.

The aim of this study was to compare the effects upon gastric secretion of therapeutic doses of aminophylline, with doxofylline, a new xanthine derivative proposed for the treatment of chronic asthma. Twelve patients with endoscopically-proven healed duodenal ulcer were studied twice under double-blind conditions in cross-over experiments. In a 1-hour infusion, six patients received either 240 mg aminophylline i.v. or 200 mg doxofylline i.v., and six received either 240 mg aminophylline i.v. or 400 mg doxofylline i.v. Compared with basal gastric secretion, for the hour after the infusion 240 mg aminophylline i.v. stimulated gastric acid output by a mean 213% (P less than 0.01) and mean pepsin output by 129% (P less than 0.01). Intravenous doxofylline did not stimulate a significant increase of either acid or pepsin output (200 mg: acid output +4%, pepsin output +10%; 400 mg: acid output +25%, pepsin output +27%). These findings suggest that doxofylline, unlike aminophylline, has a low secretagogue activity and it may be more suitable for asthmatic patients with peptic ulcer disease.

Adult

Treatment of reversible chronic airways obstruction with doxofylline compared with slow-release theophylline: a double-blind, randomized, multicentre trial.

A multicentre, double-blind, randomized trial was carried out in 11 Italian Pneumologic Clinics to investigate the therapeutic efficacy and tolerability of doxofylline compared with slow-release theophylline in 139 patients (86 males, 53 females) aged 17-77 years suffering from reversible chronic airways obstruction. The two groups of 69 patients on doxofylline and 70 patients on theophylline did not differ in their baseline clinical and functional parameters. After one week of wash-out, the two drugs were administered orally at a dose of 400 mg twice daily of doxofylline and 300 mg twice daily of theophylline. The treatment and follow-up lasted 28 days. Inhaled salbutamol on demand was allowed in the wash-out week and throughout the trial. The average serum levels at day 14 and 28 were: doxofylline 7.5 and 8.5 micrograms/ml; theophylline 10.4 and 7.95 micrograms/ml respectively. Both drugs significantly increased spirometric parameters (p less than 0.001 for all tests) and significantly reduced salbutamol consumption (p less than 0.001 for both drugs). Doxofylline was better tolerated than theophylline considering either the number of unwanted side-effects: (doxofylline 12; theophylline 37) or number of drop-outs due to side-effects (doxofylline 5; theophylline 10). From these results doxofylline seemed to be a good alternative to theophylline in the treatment of reversible chronic airway obstruction in view of its better safety profile.

Adolescent

Doxofylline, an adenosine-nonblocking xanthine, does not induce cardiostimulant effects.

Doxofylline (ANSIMAR) is a new adenosine-nonblocking anti-asthmatic drug with potent bronchodilator activity that does not display the typical extrapulmonary side effects of theophylline--a potent adenosine antagonist. The cardiac activity of doxofilline and theophylline was investigated in guinea pig right and left atrial preparations and in anestetized cat. In spontaneously beating right atria doxofylline slightly increased the atrial rate only at 0.3 mM, while theophylline induced a concentration-dependent positive chronotropic effect starting at 0.03 mM. The contractile force of electrically stimulated left atria was affected by doxofylline starting at 0.3 mM. Theophylline induced the same effect already at 0.03 mM. In the anesthetized cat, doxofylline (1-30 mg/kg.i.v.) did not affect the diastolic blood pressure, but the heart rate increased slightly at a dose of 30 mg/kg i.v. On the contrary, theophylline induced a marked dose-dependent hypotensive and positive chronotropic effect. Doxofylline was 10 times less potent that theophylline is its ability to antagonize the cardiodepressant activity induced by adenosine in isolated guinea pig atria. The pharmacodynamic differences between doxofylline and theophylline may bring new insights to the understanding of the mechanisms underlying the positive chronotropic effects of xanthines, and the functional importance of endogenous adenosine. Additionally, the lack of cardiostimulant effects makes doxofylline highly suitable for the treatment of chronic obstructive lung disease particularly in combination with beta 2-adrenergic agonists.

Adenosine

Evidence for a prostaglandin-mediated bone resorptive mechanism in subjects with fasting hypercalciuria.

This study was performed to assess whether treatment with prostaglandin synthesis inhibitors decreases calcium excretion in patients with idiopathic hypercalciuria. Nineteen hypercalciuric (12 with fasting hypercalciuria (FH), 7 with nonfasting hypercalciuria (NFH) and 8 control non-hypercalciuric stone formers were treated with sodium diclofenac, 50 mg t.i.d. for 2 weeks. After a washout phase, 7 FH patients received 200 mg/day of sulindac (a nonsteroidal antiinflammatory agent (NSAID) inactive on renal prostaglandin synthetase) for 14 more days. Diclofenac reduced urine calcium excretion in subjects with idiopathic hypercalciuria with either normal or elevated fasting urinary calcium (from 387 +/- 26 to 240 +/- 23 mg/day, P less than 0.001; and from 370 +/- 39 to 246 +/- 40 mg/day, P less than 0.05, respectively), whereas it was ineffective in normocalciuric stone formers. Similar antihypercalciuric effectiveness was exerted by sulindac in the seven FH patients. The antihypercalciuric action exerted by diclofenac in subjects with FH was associated with a significant increment in serum PTH (48 +/- 4 vs, 70 +/- 9 pmol/liter, P less than 0.05), whereas in NFH subjects, the antihypercalciuric effect of diclofenac on NFH was not associated with a change in parathyroid activity. Since the major effect of NSAIDs is to decrease prostaglandin synthesis, these data suggest that prostaglandins may play a pathogenetic role in idiopathic hypercalciuria. Furthermore, they suggest that PTH is suppressed in patients with FH, possibly due to stimulation of prostaglandin-mediated bone resorption process.

Adolescent

Use of carbamazepine in acute psychosis: a controlled study.

A randomized double-blind study was performed to compare the therapeutic effects of lithium and carbamazepine (CBZ) each administered in combination with chlorpromazine (CPZ) for 3 weeks in women with acute psychosis. Thirty patients were studied. The initial dose was 1200 mg/day for CBZ and 900 mg/day for lithium, and it was subsequently modified according to plasma levels and clinical indications. The dose of CPZ was free and depended on the severity of symptomatology. Both treatments produced a significant improvement in psychotic symptoms without significant differences between the treatment groups. Also, as regards tolerability no clinically relevant differences were found between the two groups. During the first week of treatment the CPZ dose required in the CBZ group was significantly lower than that administered to the lithium group, indicating that CBZ had a greater sedative action; however, this difference decreased as treatment continued. These results confirm that CBZ is a valid alternative to lithium in the treatment of acute psychosis.

Acute Disease

Strategy for treatment of acute evolving myocardial infarction with pulsatile left heart assist device. Can this modality increase survival and enhance myocardial salvage?

This article describes the technique of left heart bypass in the treatment of both experimental and clinical acute myocardial infarction. A new technique of closed-chest percutaneous left heart bypass that can be used in patients with acute evolving myocardial infarction and cardiogenic shock is also described.

Acute Disease

Pirenzepine in duodenal ulcer. A multicentre double-blind controlled clinical trial, First of two parts.

Eighty-four patients with endoscopically-proved active duodenal ulcer were admitted to a multicentre double-blind trial with either pirenzepine tablets (25 mg three times per day for 1 week followed by 25 mg two times per day for 3 weeks) or placebo. Seventy-nine patients completed the trial, 44 treated with pirenzepine and 35 with placebo. After 4 weeks, complete healing had been achieved in 52% of the pirenzepine-treated patients and in 34% of the placebo-treated ones. Symptomatic responses were signigicantly better in those receiving pirenzepine than in those receiving placebo. In addition, the supplementary antacid consumption was significantly lesser in the pirenzepine group than in the placebo group. No important side-effects were observed in the two groups.

Adult

Comparison of intravenously administered doxofylline and placebo for the treatment of severe acute airways obstruction.

This double-blind, randomized, placebo-controlled study investigated the therapeutic effects of a single dose of doxofylline, a methylxanthine derivative, in 10 patients aged 26-79 years. All patients had acute exacerbation of chronic obstructive airways disease partially reversible with salbutamol inhaler. Doxofylline was administered intravenously at a dose of 200 mg over 15 min on two different occasions separated by at least 24 h. Doxofylline increased forced expiratory volume in the first second of expiration compared with baseline as follows: +20% after 2 h (P less than 0.01); +31% after 4 h (P less than 0.01); and +13% after 6 h (NS). Changes produced by placebo at these times were -4.4%, -14% and -5% (all NS). The average differences between the groups were significant at all observation times. At the end of the observation period eight out of 10 patients given doxofylline and one out of 10 patients given placebo had improved clinically according to the patients' own opinion. Clinical tolerability of doxofylline proved to be good since no signs of local or general side-effects were observed in any of the patients treated.

Adult