Diagnostic and therapeutic iter in paediatric OSAS: personal experience.

Obstructive sleep apnoea syndrome in a child is characterized by prolonged episodes of obstructive hypopnoea and/or apnoea of upper airway leading to morbidity. The most common risk factor is adeno-tonsillar hypertrophy. Obstructive sleep apnoea syndrome diagnosis is based on clinical ENT evaluation and an instrumental approach, such as pulse oximetry or the gold standard overnight polysomnography. The aim is to establish, in a population of children with suspected obstructive sleep apnoea syndrome, the frequency of this disorder, the effect of adenotonsillectomy and the risk of post-operative complications. A total of 481 patients (297 male, 184 female) with suspected obstructive sleep apnoea syndrome (aged 2-14 years) were evaluated between March 2007 and April 2010 and divided into 3 morphological phenotypes: classic, adult and congenital. All patients underwent ENT assessment and a pulse oximetry with 4 channels cardiopulmonary monitoring. The examination following the Brouillette criteria was defined as negative, positive or inconclusive; when positive, adenotonsillectomy was the first therapeutic approach. At 6 months after surgery, all patients underwent check-up pulse oximetry. Of the overall sample, 96% of the patients had a classical phenotype, 3% an adult type and 1% a congenital type. The monitoring resulted pathological in 19% (17% of them were at increased post-operative risk), negative in 61% and inconclusive in 20%. All 5 patients with congenital phenotype were positive. Of the positive patients, 86% underwent adenotonsillectomy and a control pulse oximetry 6 months thereafter, 96% resulted negative. Pulse oximetry was efficient in order to avoid incorrect surgery indications, improving appropriateness and safety of adenotonsillectomy in children with obstructive sleep apnoea syndrome. Adenotonsillectomy showed a success rate of 96% and there were no episodes of post-surgery complications in particular in those patients at increased risk.

[The monitoring role of otoacoustic emission and oxidative stress markers in the protective effects of antioxidant administration in noise-exposed subjects: a pilot study]. / Il ruolo del monitoraggio delle emissioni otoacustiche e dei marcatori dello stress ossidativo negli effetti protettivi dello somministrazione di antiossidanti in soggetti esposti al rumore: uno studio pilota.

The aims of this study is to assess how DPOAEs can discriminate normal subjects with a risk of damage induced by noise, the effectiveness of OAEs in monitoring the effect of Q-Ter, and the role of blood tests to monitor therapy. In the placebo group, the amplitude of DPOAEs was reduced 1 hour and 16 hours after exposure, the group treated with Q-Ter showed normal DPOAEs. This pilot study confirms that DPOAEs represent a sensitive test for monitoring the effects of noise in preclinical conditions and pharmacological treatment.

Synthesis and structure-activity relations in the class of 2-(pyridyl)penems.

The isosteric CH----N substitution in the class of 2-arylpenems results in improved antibacterial activity, with retention of the favorable characteristic of stability towards renal dehydropeptidase. High therapeutic efficacy was demonstrated in experimental mice septicemias with the 2-(3-pyridyl) derivative 2b and its orally absorbed acetoxymethyl ester prodrug 4n.

Activity of FCE 22101 and other beta-lactam antibiotics against experimental genital infections in the rat and mouse.

The therapeutic activities of the parenterally administered penem FCE 22101, cefuroxime and ampicillin were compared in an experimental model of genital infections in progesterone-treated virgin rats and normal female mice. Treatment with FCE 22101 significantly inhibited the proliferation of Staphylococcus aureus ATCC 13709, Escherichia coli G and Enterobacter cloacae 1321 E, as compared with untreated controls. Against Staph. aureus ampicillin was slightly more active than cefuroxime, which showed equivalent activity to FCE 22101, while against Esch. coli and Ent. cloacae cefuroxime and ampicillin were less active than FCE 22101. The activity of the antibiotics against beta-lactamase-producing strains was also tested and here FCE 22101 exhibited the greatest inhibitory effect on bacterial growth.

Cephalosporins. VII. Synthesis and antibacterial activity of new cephalosporins bearing a 2-imino-3-hydroxythiazoline (2-aminothiazole N-oxide) in the C-7 acylamino side chain.

Introduction of a hydroxyl group into the thiazole ring nitrogen of cephalosporins belonging to the cefotiam and cefotaxime families gave rise to products, better described by the tautomeric N-oxide form, which proved particularly active against Gram-negative bacteria. Cephems bearing a (Z)-alkoxyimino functionality are of special interest for broadness of spectrum; among them, 7 beta-[(Z)-2-(2-amino-4-thiazolyl-N-oxide)-2 -methoxyiminoacetamido]-3-(tetrazolo-[1,5-b] pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (5c-7, FCE 20635), in other ways similar to cefotaxime, showed useful levels of activity against cephalosporinase-producing strains resistant to the reference drug. Preliminary in vivo studies demonstrated the therapeutic efficacy of the new compound in the treatment of experimental systemic, subcutaneous and urinary tract infections in mice.

Pharmacokinetic study of the new sulfamethopyrazine-trimethoprim combination (kelfiprim) in renal insufficiency.

The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant beta and the corresponding t1/2 beta, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cephalosporins. VI. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)acetamido]cephalosporins with a tetraxolopyridazine at the 3-position.

The synthesis and in vitro activity of 7 beta-[(Z)-2-alkoxyimino- 2-(2-aminothiazol-4-yl) acetamido]cephalosporins with a tetrazolo[1,5-b]pyridazine at the 3-position are described. These cephalosporins showed excellent activity against Gram-negative bacteria, including beta-lactamase producing strains. The most interesting compound of the series was 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetamido] -3-(8-carboxytetrazolo[1,5-b]pyridazin-6-yl)- thiomethyl-3-cephem-4-carboxylic acid (9, FCE 20485) because of its extraordinarily long half-life and marked in vivo activity.

Cephalosporins IV. Synthesis and structure-activity relationships of new 7 alpha-methoxy-7 beta-vinylenethioacetamido cephalosporins.

The synthesis and in vitro activity of 7 alpha-methoxy-7 beta-vinylenethioacetamido cephalosporins with various substituents at the 3-position are described. These cephalosporins showed good activity against beta-lactamase producing Gram-negative bacteria. 7 alpha-Methoxy-7-[(Z)-beta-cyano-vinylenethioacetamido]-3-[(1-methyl-1H-tetrazol -5-yl)thiomethyl]-3-cephem-4-carboxylic acid (3) was several times more active in vitro than cefoxitin and comparable to cefmetazole.

Cephalosporins. III. Synthesis and structure-activity relationships of 7-vinylenethioacetamid:o cephalosporins with a tetrazolo-pyridazine at the 3-position.

The synthesis and in vitro activity of 7-vinylenethioacetamido cephalosporins with a tetrazolo-pyridazine at the 3-position are described. These cephalosporins showed good activity against Gram-positive and Gram-negative bacteria. 7-[(Z)-beta-carboxyvinylenethio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8- amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid (K 13176, 21) was significantly more active in vitro and in vivo than cefazolin against Gram-negative bacteria.