Effect of intragastric volume and osmolality on mechanisms of gastroesophageal reflux in children with gastroesophageal reflux disease.

OBJECTIVE: Both transient lower esophageal sphincter (LES) relaxations (TLESRs) and periods of low/absent LES pressure (LESP) are the main mechanisms of gastroesophageal reflux. These events are believed to be triggered by stimuli from different areas of the upper GI tract. We aimed at investigating the relationship between LESP profile and gastric emptying and distension after meals of different composition in 30 children with gastroesophageal reflux disease (median age 7.0 yr, range 12 months-12 yr). METHODS: Recordings of LESP and intraesophageal pH for 1 h fasting and for 2 postprandial h were performed with a perfused sleeve catheter and flexible electrode, respectively; gastric emptying and distension of antral area were simultaneously recorded with real-time ultrasonography. Ten patients had a standard meal (group A), 10 had a high-volume meal (group B), and 10 had a high-volume and osmolality meal (group C). RESULTS: Postprandial esophageal acid exposure was significantly higher in patients of groups B and C than in patients of group A (p < 0.01); it was also more prolonged in patients of group C than in subjects of group B (p < 0.05). A higher postfeeding rate of reflux episodes caused by TLESRs was detected in patients of groups B and C as compared with patients of group A (p < 0.01). This increase did not statistically differ in patients of groups B and C. Patients of group C exhibited a higher postprandial rate of reflux episodes associated with low/absent tone of the LES as well as a more prolonged gastric emptying time and a higher postfeeding gastric distension as compared with patients of groups A and B (p < 0.01). Finally, a significant correlation was only found between the postprandial rate of reflux events resulting from low/absent LESP and the degree of antral distension in patients of group C (p < 0.01). CONCLUSION: Gastroesophageal reflux is worsened by increasing the volume and osmolality of meals through significant changes of LESP. Meals of high volume and meals with high volume and osmolality cause a comparable increase of reflux episodes as a result of TLESRs. However, meals with high volume and osmolality cause the higher degrees of esophageal acid exposure than meals with high volume resulting from a higher rate of reflux episodes associated with low/absent LESP. This finding correlates with a high postfeeding antral distension.

Role of drug therapy in the treatment of gastro-oesophageal reflux disorder in children.

Gastro-oesophageal reflux (GOR) is the effortless passage of gastric contents into the distal oesophagus. It can be classified as functional (or symptomatic), in which the infant remains free from disease, or a pathological (GOR disease, GORD), in which gastrointestinal, respiratory or neurobehavioural signs occur with intraoesophageal acidification and the development of oesophagitis. Functional or symptomatic GOR is successfully treated by conservative measures and does not require investigative diagnostic tools; however, both drug administration and an investigative approach are mandatory in patients with GORD. There is currently a great range of proven therapeutic options for GORD that are directed at counteracting the pathogenetic components of the disorder. In this report we discuss the role of different drug classes for treating GORD in children. The choice of therapy for GORD depends upon the severity of signs and the degree of oesophagitis. The presence of oesophagitis, as documented by endoscopy, suggests the use of antisecretory drugs; H2 receptor antagonists are the first-line agents. Nevertheless, individuals with refractory disease or those patients requiring potent inhibition of acid secretion (for example, GORD with respiratory involvement) can be given proton pump inhibitors. Other groups of patients who need potent inhibition of acid secretion are children with neurological dysfunction and those with Barrett's oesophagus. It is still unclear whether patients with frequent relapses are candidates for long term administration of antisecretory drugs or for surgical fundoplication.

Lansoprazole in the treatment of gastro-oesophageal reflux disease in childhood.

BACKGROUND: Acid suppressive therapy is the mainstay of pharmacologic treatment of gastro-oesophageal reflux disease. Use of proton pump inhibitors in children is still limited and has only included omeprazole in a few controlled studies. AIM: To determine efficacy of lansoprazole, a relatively new proton pump inhibitor, on symptoms and oesophagitis in a group of children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists. The required dose of the drug for inhibiting gastric acidity was also determined. PATIENTS AND METHODS: A series of 35 children (median age: 7.6 years, range: 3-15) with oesophagitis refractory to H2 receptor antagonists received a 12-week therapeutic course with lansoprazole. Prior to the study children underwent symptomatic and endoscopic assessment, oesophageal manometry and 24-hour intragastric and intra-oesophageal pH test. The latter was repeated after one week of therapy while patients were on treatment in order to monitor the degree of acid suppression and adjust the dose of the drug. Symptomatic assessment and endoscopy were repeated at the end of the trial RESULTS AND CONCLUSIONS: In 12 patients (group A), the initial dose of the drug was efficacious (1.3 to 1.5 mg/kg/day), whereas in 23 [group B) the initial dose (0.8 to 1.0 mg/kg/day) was increased by half because of insufficient inhibition of intragastric acidity (i.e., when the intra-gastric pH remained below 4.0 for more than 50% of the recording time). Nine patients in group A (75%) and 8 in group B (53.5%) healed (chi2: 3.6, p<0.05); 1 patient in group A [8.3%) and 7 in group B (30.5%) remained unchanged (chi2: 6.9, p<0.01); 2 patients in group A and 8 in group B improved and underwent a further month of therapy. The two groups did not differ as far as concerns baseline pH, endoscopic and clinical variables. In both groups, those patients failing to respond at the end of the trial showed a more impaired oesophageal motility than improved or healed patients. The drug was well tolerated and no significant laboratory abnormalities occurred. In children with gastro-oesophageal reflux disease refractory to H2 receptor antagonists, a 12-week course of lansoprazole is effective both in healing oesophagitis and improving symptoms. An initial dose of 1.5 mg/kg/day of the drug is suggested. However, if during treatment, patients remain symptomatic the dose should be increased and a prolonged intra-gastric and intra-oesophageal pH test performed to evaluate the acid suppression efficacy of the adjusted dose. A short course of lansoprazole appears to be safe and well tolerated in paediatric age.

Antagonistic effects of guanabenz, carteolol, and muzolimine on hypertensive responses in the anesthetized dog.

In dogs, treatment with guanabenz, carteolol, and muzolimine for 7 days, reduced the blood pressure responses to bilateral occlusion of the carotid arteries, electric stimulation of central vagus nerve, acetylcholine after atropinization, nicotine, l-noradrenaline, angiotensin II, l-adrenaline, KC1 and asphyxia.

Cardiovascular and respiratory effects of spermidine and spermine: an experimental study.

Spermidine (SPD) and spermine (SPM) produced in anaesthetized dogs significant cardiovascular changes at higher doses than other transmitters, i.e. l-noradrenaline, l-adrenaline, histamine, acetylcholine, which produce cardiovascular effects at doses of 0.01-0.05 micrograms/kg given intravenously. SPD was shown to be more active than SPM. The hypotensive response observed after i.v. injection is due to histamine release. The hypotensive and bradycardic effects observed after microinjection of SPD into III cerebral ventricle or into the vertebral artery and of SPM into the vertebral artery are due to an increase in parasympathetic output. Spermidine increased and spermine decreased the baroreceptor reactivity. SPD and SPM did not change the vascular beta- and alpha-adrenergic, cholinergic and histaminergic receptor reactivity.

On the hypolipemic properties of bendaline.

Bendaline, like tiadenol, clofibrate and clofibric acid generally inhibits: a) some hyperlipemias and lipoidoses induced by either an increased exogenous supply of lipids or the stimulation of cholesterol synthesis or mobilization of lipids; b) platelet aggregation in vitro.

Derivatives of 1,3,3-trimethyl-6-azabicyclo[3.2.1]octane with hypotensive activity. I.

The synthesis of three series of glycinamides (IV), amides (V) and diamines (VI) starting from 1,3,3-trimethyl-6-azabicyclo[3.2.1]octane is described. Some of compounds (IV), (V) and (VI) showed a moderate hypotensive activity in rats. Effects on heart rate in rats, infiltration anesthesia and antiarrhythmic activity in mice, as well as antiacetylcholine activity in vitro, are also reported.

Derivatives of 5,7,7-trimethyl-6-oxa-3-azatricyclo[3.2.2.0(2.4)]nonane with antiarrhythmic, local anesthetic and hypotensive activities.

The synthesis of ureas (IV) and amides (V) derived from the tricyclic terpenoid amine 5,7,7-trimethyl-6-oxa-3-azatricyclo[3.2.2.0(2.4)]nonane (III) is described. A number of these compounds showed hypotensive and bradycardic activity in rats, as well as infiltration anesthesia and antiarrhythmic activity in mice. In particular, the n-butylurea (IV b) was superior to lidocaine concerning the anesthetic effect, and the benzamide (V f) showed the same degree of local anesthetic and antiarrhythmic activity as lidocaine. Antiacetylcholine activity in vitro and antitumor activity against P388 lymphocytic leukemia in mice are also reported.

[Phosphocreatine and skeletal musculature: in vivo research]. / Fosfocreatina e muscolatura scheletrica. Ricerche in vivo.

Phosphocreatine has been shown having significant effects on striated skeletal musculature. In fact, it was shown, by experimental researches, that phosphocreatine interfered with the state of fatigue induced in the Mus musculus and in rats, by the swimming test.

Cardiovascular effects of 15(S) 15 methyl-PGF2 alpha.

The effects of 15(S) 15-methyl-PGF2 alpha were studied on the cardiovascular system of dogs. Intravenous and intravertebral artery administration of 15(S)-methyl-PGF 2 alpha induced arterial hypertensive and respiratory effects more intense and longer lasting than those observed for PGF2 alpha. Intravenous administration of 15(S) 15-methyl-PGF2 alpha induced a decrease of vascular reactivity to 1-norepinephrine and 1-epinephrine and to carotidal occlusion. Infiltration of the carotid sinus walls with 15(S) 15-methyl-PGF2 alpha decreased the baroreceptor reactivity.

[Analysis of the hypolipemic, hypocholesteremic and platelet anti-aggregating effects of tibric acid]. / Analisi degli effetti ipolipidemizzanti, ipocolesterolemizzanti ed antiaggreganti piastrinici dell'actibrico

Tibric acid shows interesting hypocholesteremic and hypolipemic activity greater than that of clofibrate. In addition high concentrations of tibric acid affect platelet aggregation. Tibric acid does not show choleretic activity and does not affect liver function.

[Experimental analysis of the interactions between heparin and a duodenal heparinoid]. / Analisi sperimentale delle interazioni tra l'eparina e un eparinoide duodenale

It is shown that positive synergism exists between the clarifying, hypocholesterolaemising, hypolipidaemising and fibrinolytic effects of heparin sodium and a duodenal heparinoid. The results of pharmacokinetic and chemicophysical investigations are also presented.