Bulletin Infovac-France COHEN, R; GUERIN, N; PINQUIER, D ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
05/2013, Letnik:
20, Številka:
5
Journal Article
Bulletin InfoVac-France ROMAIN, O; COHEN, R; GRIMPREL, E ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
04/2012, Letnik:
19, Številka:
4
Journal Article
The synthesis of a series of C-10 trifluoromethyl ethers of artemisinin has been achieved from key bromide 8, itself carried out in two steps from artemisinin. The substitution of 8 with methanol, ...ethanol, or succinic acid allowed the access of C-10 CF3 analogues of β-artemether, β-arteether, or artesunate, respectively, in good yields (up to 89%). The presence of the CF3 group at C-10 of artemisinin clearly increased the chemical stability under simulated stomach acid conditions. For example, the CF3 analogue of arteether was found to be around 45 times more stable than arteether itself. The influence of the CF3 moiety on biological activity was also highlighted. CF3 analogues of artemether and arteether exhibited a high in vivo antimalarial activity on mice infected with Plasmodium berghei NK173, with a complete clearance of the parasitemia during the entire observation period (25 days).
Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial ...of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: -3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.
A multicentre, open-label, randomized study was performed in 501 out-patients with acute otitis media, aged 6-36 months, to study the impact of treatment with either cefixime suspension 8 mg/kg/day ...bd or co-amoxiclav suspension 80 mg/kg/day tds for 10 days on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Of 426 patients with nasopharyngeal cultures at entry to the trial, end of treatment and at follow-up visit (35 days after inclusion), significant changes in carriage of S. pneumoniae were observed. The proportion of penicillin-resistant S. pneumoniae was higher in the samples taken at the end of treatment and follow-up than in those taken at inclusion, while the total number of children with this microorganism was lower. The difference at the end of treatment was greater with co-amoxiclav than with cefixime. For H. influenzae the resistance rate remained steady while the number of children with this microorganism decreased. At follow-up there was no significant difference between the two groups in terms of nasopharyngeal positive culture for S. pneumoniae or H. influenzae. Despite these differences, successful clinical responses were similar at the end of treatment and at follow-up.
Three hundred sixty children were tested for pertussis serology 0.5 to 1.58 months after complete whole-cell pertussis vaccination. An immunoblot assay was used to detect serum antibodies to ...pertussis toxin, filamentous hemagglutinin, adenylate cyclase-hemolysin, and pertactin, and agglutination was used for detection of anti-agglutinogen antibodies. Antibodies against pertussis toxin, pertactin, and agglutinogens decreased rapidly after vaccination but increased secondarily, suggesting exposure to infected persons. In contrast, anti-filamentous hemagglutinin antibodies persisted and anti-adenylate cyclase-hemolysin antibodies increased continuously, suggesting either cross-reaction with non-Bordetella antigens or exposure to Bordetella isolates expressing these two antigens, including Bordetella pertussis. These data suggest that unrecognized pertussis is common in France despite massive and sustained immunization in infants and that vaccinated children become susceptible to infection more than 6 years after their last vaccination.
Older children still contribute to the transmission of pertussis to infants in French regions with low booster coverage at 2 years of age. Booster vaccination seems crucial for protection against ...symptomatic pertussis in childhood.
Éloge de Géraud Lasfargues (1930–2018) Bégué, P.
Bulletin de l'Académie nationale de médecine,
November-December 2019, 2019-11-00, Letnik:
203, Številka:
8-9
Journal Article
The reactions of the ring-contracted aldehydes, derived from anhydrodihydroartemisinin, with gem-difluoroenoxysilanes in the presence of BF3·Et2O afforded the corresponding difluoromethylene ketol ...adducts in good yields. Similar Lewis acid catalyzed reactions of dihydroartemisinin acetate with the difluoroenoxysilanes provided the 10-substituted difluoromethylene ketones in good to moderate yields. Interestingly enough, the course and the stereochemistry of these reactions are highly dependent on the nature of the Lewis acids used; the addition reaction was accompanied by epimerization at C-9, and the stereochemistry at C-10 depends on the difluoroenoxysilane used. The best results were obtained using SnCl4 to give the 9α,10β-stereoisomer in high stereoselectivity. When 0.4 equiv of SnCl4 was used for the reaction with the α-(4-methoxyphenylenoxysilane)-β,β-difluoroenoxysilane, however, a rearrangement of the endoperoxide was observed.