Introduction of the use of a pediatric PICC line in a French University Hospital: review of the first 91 procedures.

PURPOSE: In order to assess the establishment of a pediatric PICC line service in a University Hospital after the first 91 consecutive procedures. MATERIALS/PATIENTS AND METHODS: Retrospective study over a period of 24months. The criteria analysed were success or failure of the procedure, indication, age when inserted, type of PICC line, mean length of use and development of complications such as accidental removal, venous thrombosis or infection. RESULTS: Ninety-one PICC lines were inserted in 74 patients between 4months and 25years old (sex-ratio: 1.1 girls/boys). The procedure was performed under general anaesthesia in four cases (4.4%) and under EMLA and MEOPA in 87 cases (95.6%). The insertion was ultrasound guided through the basilic (n=63, 70%), humeral (n=18, 20%) or cephalic (n=9, 10%) veins in the non-dominant arm (L in 62 cases, R in 28 cases). The insertion success rate was 99% (n=90). The main indications were starting antibiotic therapy (n=47, 52%), chemotherapy (n=34, 38%) and parenteral nutrition (n=5, 5%). The devices used were single lumen 3F (n=4, 4%), single lumen 4F (n=31, 34%), double lumen 4F (n=2, 2.2%), single lumen 5F (n=12, 13%), and double lumen 5F (n=41, 45%). The PICC line was used for an average period of 45days (14 to 300days). The complications found were accidental removal (n=2, 2.2%), catheter fracture (n=2; 2.2%), obstruction (n=5, 5.5%), suspected infection (n=1, 1.1%), and venous thrombosis and pulmonary embolism (n=3, 3.3%). The overall complication rate was 14.4% (n=13) including 4.4% serious complications (n=4). CONCLUSION: PICC lines are a future solution in pediatrics. This technique is reliable and has a similar complication rate to studies carried out in adults, most of which can be prevented by careful catheter maintenance and informing the care staff.

[The beta-2-agonists in asthma in infants and young children]. / Les beta 2-mimétiques dans l'asthme du nourrisson et du jeune enfant.

beta 2-agonists, by inducing a fast and long relaxation of the bronchial smooth muscle, are considered as the more potent bronchodilators. beta 2-receptors are present from the 16th gestational week, explaining a possible bronchial response in the youngest children. beta 2-agonists do not induce any bronchodilator response in healthy children. Short-acting beta 2-agonists (salbutamol or albuterol, terbutaline) are indicated for asthma attacks, as needed in chronic asthma, and for prevention of symptoms during effort. They are safe and secure. The more efficient route of administration in preschool children is pressurized metered-dose inhaler used with a spacer device. Therefore, whatever the route of inhalation chosen (inhalation, injection, or continuous nebulization in acute asthma attack), more specified indications and doses are needed in young children. Long-acting beta 2-agonists (formoterol, salmeterol) are not authorized in France in children under 4 to 5 years of age depending on the drug used. Because of new oral formulations and recent considerations about their use in asthma attack, instead of short-acting beta 2-agonists, their indication in preschool asthmatic children might be reconsidered.

[Role of leukotriene inhibitors in the treatment of childhood asthma]. / Place des antileucotriènes dans le traitement de l'asthme de l'enfant.

Leukotriene inhibitors are new pharmacological agents for the treatment of mild to moderate persistent asthma and exercise-induced asthma (EIA). Studies concerning their use in children remain scarce. Available data in the treatment of persistent asthma in children suggest that they could be an alternative to long-acting beta 2-agonists when asthma control cannot be obtained with inhaled steroids alone. Their main advantages are first that they are given orally once daily; second, that they do not induce tachyphylaxis to bronchoprotection against EIA, unlike long-acting beta 2-agonists. Studies specifically conducted in children are necessary to best describe their place in pediatric asthma treatment.

Biological and molecular analyses of structurally reduced analogues of endothelin-1.

Structurally reduced analogues of endothelin-1 (ET-1) were synthesized through linking with an aliphatic spacer [aminocaproic acid (Aca)], segment 3-11 of ET-1 to carboxyl-terminal fragments of various lengths (16-21, 17-21,...,21). The peptides were prepared in their linear or cyclic form, and a formyl group was or was not introduced on the Trp21 side chain. Pharmacological studies were carried out with the guinea pig lung parenchyma paradigm and the rat thoracic aorta bioassay. In the rat aorta, an ET(A) receptor preparation, all of the analogues were inactive. However, in the lung parenchyma, we observed that among the linear formylated derivatives, [Cys(Acm)3,11,Trp(For)21]-(3-11)-Aca-(17-21)ET was a partial agonist. In this series, the presence of His16, as in [Cys(Acm)3,11,Trp(For)21]-(3-11)-Aca-(16-21)ET, caused a decrease in contractile activity, suggesting that the imidazole group disfavors the proper interaction of the linear molecule with the ETB receptors of the lung parenchyma. The loss of biological activity of the deformylated linear analogues strongly suggested that the formyl group played a stabilizing role in the structure of the linear molecules. Interestingly, molecular modeling studies indicated the adoption of different conformations by the formylated and the nonformylated analogues. In contrast, the stabilizing effect of the formyl group was not observed with the cyclic compounds. Furthermore, the presence of His16 favored the contractile activity of the cyclic peptides. Finally, the results demonstrated that the carboxyl-terminal residues 18-21 are required for the activity in the guinea pig lung parenchyma ETB receptors.

Role of the neutral endopeptidase 24.11 in the conversion of big endothelins in guinea-pig lung parenchyma.

1. We have studied the conversion of big endothelin-1 (big ET-1), big endothelin-2 (big ET-2) and big endothelin-3 (big ET-3) and characterized the enzyme involved in the conversion of the three peptides in guinea-pig lung parenchyma (GPLP). 2. Endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3) (10 nM to 100 nM) caused similar concentration-dependent contractions of strips of GPLP. 3. Big ET-1 and big ET-2 also elicited concentration-dependent contractions of GPLP strips. In contrast, big ET-3, up to a concentration of 100 nM, failed to induce a contraction of the GPLP. 4. Incubation of strips of GPLP with the dual endothelin converting enzyme (ECE) and neutral endopeptidase (NEP) inhibitor, phosphoramidon (10 microM), as well as two other NEP inhibitors thiorphan (10 microM) or SQ 28,603 (10 microM) decreased by 43% (P < 0.05), 42% (P < 0.05) and 40% (P < 0.05) the contractions induced by 30 nM of big ET-1 respectively. Captopril (10 microM), an angiotensin-converting enzyme inhibitor, had no effect on the contractions induced by big ET-1. 5. The incubation of strips of GPLP with phosphoramidon (10 microM), thiorphan (10 microM) or SQ 28,603 (10 microM) also decreased by 74% (P < 0.05), 34% and 50% (P < 0.05) the contractions induced by 30 nM big ET-2 respectively. As for the contractions induced by big ET-1, captopril (10 microM) had no effect on the concentration-dependent contractions induced by big ET-2. 6. Phosphoramidon (10 microM), thiorphan (10 microM) and SQ 28,603 (10 microM) significantly potentiated the contractions of strips of GPLP induced by both ET-1 (30 nM) and ET-3 (30 nM). However, the enzymatic inhibitors did not significantly affect the contractions induced by ET-2 (30 nM) in this tissue. 7. These results suggest that the effects of big ET-1 and big ET-2 result from the conversion to ET-1 and ET-2 by at least one enzyme sensitive to phosphoramidon, thiorphan and SQ 28,603. This enzyme corresponds possibly to EC 3.4.24.11 (NEP 24.11) and could also be responsible for the degradation of ETs in the GPLP.

Structure-activity studies of the C-terminal segment of structurally reduced analogues of ET-1.

Structurally reduced analogues of endothelin-1 (ET-1) were synthesized by linking via aminocaproic acid (Aca) the segment 3-11 of ET-1 to C-terminal fragments of various lengths [16-21, 17-21,...,21]. Analogues were studied in their linear or cyclic form in the absence or presence of a formyl group on the Trp21 side-chain, and their biologic activities were tested using guinea pig lung parenchymal strips. The absence of the first disulfide bridge and the presence of the Aca spacer caused a slight decrease in activity. The presence of His16 is essential for the contractile activity of the monocyclic peptides. Formylation of these monocyclic analogues did not modify this behavior. Similarly, linear analogues carrying S-acetamidomethyl (Acm) functions and an Aca linker were still active. However, most formylated linear derivatives were partial agonists, whereas the addition of His16 caused a decrease in contractile activity. In these latter analogues, molecular modeling studies suggested that formylation produces different conformations.

Characterization of the endothelin-converting enzyme in guinea pig upper bronchus.

We studied the pharmacologic effects of big endothelin-1 (big ET-1), big endothelin-2 (big ET-2), and big endothelin-3 (big ET-3), and characterized the enzyme involved in the conversion of the three peptides in guinea pig upper bronchus (GPUB). ET-1, ET-2 and ET-3 (0.1-300 nM) elicited similar concentration-dependent contractions of GPUB. Big ET-1 and big ET-2, but not big ET-3, also elicited potent concentration-dependent contractions of GPUB. The conversion of big ET-1 to ET-1 in the GPUB is sensitive to phosphoramidon but not to thiorphan or captopril. Phosphoramidon inhibited the conversion of big ET-2 to ET-2, thiorphan had minimal effect, and captopril was without effect. These results suggest that the putative endothelin-converting enzyme (ECE) is involved in the conversion of big ET-1 to ET-1 in GPUB and the conversion of big ET-2 to ET-2 by a nonselective enzymatic process.