Does treatment with proton pump inhibitors for gastroesophageal reflux disease (GERD) improve asthma symptoms in children with asthma and GERD? A systematic review.

OBJECTIVE: To evaluate pediatric studies of the effect on asthma symptoms of treatment with proton pump inhibitors (PPI) used to treat gastroesophageal reflux disease (GERD). METHODS: We entered the MeSH terms "gastroesophageal reflux AND asthma AND children" in the PubMed tool Clinical Queries, selecting "therapy" and "broad, sensitive search." The search ended on April 14, 2008. We included only clinical trials performed in pediatric patients. RESULTS: Four studies were considered to be relevant, although only 1 was a randomized, double-blind, placebo-controlled trial. The 3 nonrandomized trials showed that PPIs benefited patients with asthma. The randomized, double-blind, placebo-controlled trial found that omeprazole did not improve asthma symptoms. An improved (although not statistically significant) score was observed in the quality of life questionnaire in children with a reflux index greater than 10% and in those with more severe asthma treated with omeprazole compared with the placebo group. CONCLUSIONS: Scant data in these studies mean that we cannot make solid recommendations. However, in specific cases, we think that treatment of asthma symptoms with a PPI is valid as long as at least 2 conditions are satisfied: asthma must not respond to standard treatment, and 1 instrumental parameter of GERD severity must be satisfied, that is, a reflux index greater than or equal to 10 must be present.

Montelukast versus inhaled corticosteroids as monotherapy for prevention of asthma: which one is best?

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Clinical evaluation and treatment of acute asthma exacerbations in children.

This update on treatment of asthma exacerbations in children is the result of an Italian Pediatric Society Task-force, made up of a panel of experts working in 2007-2008. The aim is to give clear indications on the use of the drugs most employed in children, grading the quality of evidence and the strength of recommendations. Suggestions on their limits due to unlicensed and off-label use are reported. The level of evidence and the strength of recommendations for different therapeutic approaches demonstrate that frequently the use of drugs in children is extrapolated from the experience in adults and that more studies are required to endorse the correct use of different drugs in asthmatic children.

Efficacy and safety of the 200-300 mg sustained release formulation of diltiazem administered once daily in patients with stable angina.

The aim of this multicentre randomised double blind study was to compare the efficacy and safety of the 200-300 mg sustained release diltiazem formulation administered once daily (200-300 SR) with standard diltiazem (D) given three or four times daily to patients with stable angina. Patients aged 59 years, with a reproducible exercise test on placebo, were randomised to 4 weeks of treatment with 200-300 SR (n = 70) or D (n = 74). The initial dosage was 200 mg in the 200-300 SR group and 60 mg t.i.d. in the D group, increased to 300 mg once daily or 60 mg q.i.d., respectively, if ergometric parameters, which were always measured at the end of the dosing period, had not improved after two weeks. After 4 weeks of treatment, the antianginal efficacy at rest was comparable in the 200-300 SR and the D group; there was a prolongation of the total duration of exertion of 14% and 18% respectively (P < 0.01 vs placebo for both groups with no intergroup difference). A dose-effect relation was found with both formulations. The 200-300 SR formulation gave full 24 hour anti-ischaemic protection when administered once daily. Its efficacy and safety were comparable to those of standard diltiazem t.i.d. or q.i.d. in patients with stable angina. The once daily administration should improve treatment compliance.

Catheter ablation using radiofrequency or low-energy direct current in pediatric patients with the Wolff-Parkinson-White syndrome.

Percutaneous ablation of accessory pathways was performed in 22 consecutive children and adolescents (9 boys and 13 girls, age range 8 to 18 years). Low-energy direct current (DC) was used exclusively in the first 6 patients, whereas ablation was performed with radiofrequency energy in the following 16. Accessory pathways were located in the left free wall in 15 patients, were posteroseptal in 3, were in the right free wall in 3 and were anteroseptal in 1. A concealed accessory pathway was present in 7 patients (32%). There was no significant difference in clinical or electrophysiologic variables between both groups. Catheter ablation was successful in the initial 6 patients using low-energy DC, as compared with 13 of 16 patients using radiofrequency ablation. Low-energy DC was successful as a backup power source in all 3 patients who had unsuccessful radiofrequency ablation. There was no complication. The median procedural and fluoroscopic times for successful ablation were 2.5 hours and 49 minutes, respectively (p = NS between both power sources). Accessory pathway conduction recurred in 2 patients (33%) who had low-energy DC as compared with 1 (6%) who had radiofrequency ablation (p = NS). These 3 patients had successful reablation of their accessory pathways. In children and adolescents with accessory pathways, both new power sources compare favorably, with an overall success rate of ablation of 100% (22 of 22 patients). Radiofrequency ablation should be used initially because it does not require general anesthesia and is associated with a lower rate of recurrence of accessory pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of a comparative study of low energy direct current with radiofrequency ablation in patients with the Wolff-Parkinson-White syndrome.

OBJECTIVE: To compare two new power sources for catheter ablation in patients with the Wolff-Parkinson-White syndrome. DESIGN: 120 consecutive patients with accessory pathways had catheter ablation. Low energy direct current (DC) was used in the first 60 patients and radio-frequency current in the next 60 patients. SETTING: Electrophysiological laboratory of a large heart institute. PATIENTS: 72 men and 48 women (mean (SD) age 35 (14) years (range 9-75)). The accessory pathways were in the left free wall in 73 patients. They were posteroseptal in 35 patients, in the right free wall in five, and anteroseptal in seven. There was no significant difference in the clinical or electrophysiological variables between the two ablation groups. RESULTS: Catheter ablation with low energy direct current was successful in 55/60 patients (92%) and radiofrequency energy was successful in 52/60 patients (87%). Low energy direct current was also successful in four of the eight patients in whom radiofrequency ablation had failed. Radiofrequency ablation was successful in two of the five patients in whom low energy direct current ablation had failed. The mean (SD) procedure and fluoroscopy times for successful ablation were 3.2 (1.5) h and 61 (40) min respectively. These times were similar for both power sources. Accessory pathway conduction recurred in 17 patients (28%) who had low energy direct current and four patients (7%) who received radiofrequency energy (p < 0.004). All patients with recurrence of an accessory pathway had successful re-ablation. CONCLUSIONS: Both new power sources successfully ablated accessory pathways, (overall success rate 94% (113/120 patients)). Radiofrequency ablation, however, did not require general anaesthesia and was associated with a significantly lower rate of recurrence of accessory pathway conduction. Therefore radiofrequency should be used initially for ablation. Low energy direct current may be most useful as a back-up in patients in whom radiofrequency ablation fails.

Predictive factors for spontaneous closure of atrial septal defects diagnosed in the first 3 months of life.

OBJECTIVES: To establish the rate of spontaneous closure of atrial septal defects diagnosed before age 3 months, 101 infants (mean age 26 days) with an interatrial shunt confirmed by Doppler echocardiography were followed up for an average of 265 +/- 190 days. BACKGROUND: Even if interatrial shunts in the newborn are frequently encountered, little is known about their natural history. METHODS: Defect diameter on two-dimensional echocardiography and width of color flow jet were measured in the subcostal view. Right and left ventricular diameters and atrial septal curvature were also studied. Kaplan-Meier curves were obtained to predict age of spontaneous closure in relation to initial defect diameter. RESULTS: There was no significant correlation between the diameter of the atrial septal defect and right ventricular/left ventricular ratio or type of septal curvature (vertical or concave toward the left atrium). The classic predominance of girls over boys was observed only for defects > 5 mm. An overall rate of spontaneous closure of 87% was observed. Frequency and timing of closure were inversely correlated to atrial septal defect diameter: closure occurred in 100% (32 of 32) of defects in group 1 (diameter < 3 mm), 87% of defects (39 of 45) in group 2 (diameter 3 to 5 mm), 80% of defects (16 of 20) in group 3 (diameter 5 to 8 mm). Spontaneous closure did not occur in four patients of group 4 (defect > or = 8 mm) during an average follow-up interval of 417 days (range 294 to 597 days). CONCLUSIONS: These results suggest that infants with an atrial septal defect < 3 mm need not be followed up as 100% of these defects will be closed by age 18 months; those with a defect 3 to 5 or 5 to 8 mm should be evaluated by the end of the 12th and the 15th month, respectively, when > 80% of these defects will be closed. An atrial septal defect with a diameter > or = 8 mm may have little chance of closing spontaneously and the possibility of surgical correction should be considered. Defects < 3 mm probably do not constitute a cardiac malformation in light of their natural evolution and gender distribution.

Investigation of the degradation mechanism of 5-aminosalicylic acid in aqueous solution.

The solution degradation of the antiinflammatory agent 5-aminosalicylic acid (5-ASA) was investigated in order to elucidate a mechanism for degradation. Two degradation pathways were considered: decarboxylation by analogy to 4-aminosalicylic acid (4-ASA) decomposition and oxidation from consideration of 5-ASA's aromatic ring substitution pattern (i.e., relation to p-aminophenol). The oxidation of 5-ASA was investigated using cyclic voltammetry and flow electrolysis. These studies showed that 5-ASA is more easily oxidized than is 4-ASA and that 5-ASA undergoes a two-electron, two-proton oxidation consistent with formation of 5-ASA-quinoneimine (5-ASA-QI). This oxidation is followed by subsequent complex chemistry. The decomposition of 5-ASA in solution was examined under a variety of conditions. 5-ASA decomposes most rapidly under conditions promoting oxidation and is most stable under conditions tending to inhibit oxidation. Decarboxylation was not found to be a significant degradation pathway.

The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide.

Rac-ML-1035 (MDL 201,035: 4-amino-5-chloro-2-[2-(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide hydrochloride) is a racemic gastroprokinetic with serotonergic (5-hydroxytryptamine, 5-HT) activity and a novel chiral sulfoxide substituent. Chromatographic and chemical methods have been developed to resolve the enantiomers of rac-ML-1035, and the absolute configuration of the (R)-enantiomer has been determined. We also report pharmacological characterization of rac-ML-1035 and its respective isomers. Radioligand binding to rat cortical membranes revealed that (R)-ML-1035 (MDL 201,226) and (S)-ML-1035 (MDL 201,227) had equivalent activity at the 5-HT3 receptor. However, in isolated tissue studies including field-stimulated guinea pig ileum, field-stimulated rat fundic strip, and nonstimulated guinea pig ileum, (S)-ML-1035 was equally potent yet had greater maximal activity than (R)-ML-1035 in eliciting or facilitating cholinergic contractions. Thus, enantiomers of rac-ML-1035 can be resolved, and the relative configuration of these isomers influences their pharmacological activity.

Determination of aniline and metabolites produced in vitro by liquid chromatography/electrochemistry.

A method utilizing reverse-phase liquid chromatography/electrochemistry (LC/EC) was developed for the simultaneous determination of aniline and its hydroxylated derivatives, p-aminophenol, o-aminophenol, m-aminophenol, and N-phenylhydroxylamine. To achieve separation of these compounds, a mobile phase of 3.0% dimethylformamide and 97.0% 0.05 M piperazine acetate, pH 5.4, containing 0.05 M KNO3 was developed. A procedure is also presented for the determination of p-nitrophenol, nitrobenzene, and nitrosobenzene, possible aniline metabolites in higher N-oxidation states, using reductive amperometric detection. The hydroxylated compounds, including the hydroxylamine, and nitrosobenzene are easily detected as metabolites of aniline in mouse liver slice or microsomal preparations. No prior extraction, preconcentration, or derivatization steps are needed for the determinations, which can be accomplished by a direct injection of the incubation mixture. The Km value for the hepatic aniline 4-hydroxylase activity in male Cox-Swiss mice microsomal preparations has been determined to be 0.52 mM; the Vmax value is 2.90 +/- 0.64 nmol min-1 mg microsomal protein-1. Detection limits for all compounds of interest are in the picomole range.

Determination of hydroxylated aromatic compounds produced via superoxide-dependent formation of hydroxyl radicals by liquid chromatography/electrochemistry.

Hydroxyl radicals may be formed in a xanthine oxidase/hypoxanthine system, where the superoxide anion radical O-.2 and H2O2 are produced. The superoxide-dependent production of the OH. radicals may be monitored by determining the amount of hydroxylated aromatic compounds formed in such a system. Liquid chromatography/electrochemistry is a powerful tool for the determination of hydroxylated aromatic compounds. A technique is presented in which aniline and phenol are hydroxylated in xanthine oxidase/hypoxanthine incubations. No sample derivatization is needed for the determinations which can be accomplished by direct injection of the incubation mixture. Detection limits for 1,2- and 1,4-hydroxylated compounds are in the picomole range.