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Magnetic resonance imaging was used to monitor the one-dimensional space–time evolution of the gelation of a sodium alginate solution by the ingress of calcium ions. The data were compared with theoretical reaction–diffusion models of the gelation process. Good agreement was found for short-time behaviour but deviations appear at longer times, most probably owing to the onset of syneresis. Fitting the short-time behaviour showed that the mean number of calcium ions per alginate monomer in the gel is constant but that the gelation rate constant apparently decreases with diffusion time. The possible reasons for this are considered. Copyright © 2000 John Wiley & Sons, Ltd.

Mephedrone is a synthetic derivative of cathinone which is becoming more common on the recreational drug market. Several intoxications following mephedrone abuse have been reported though published papers have focused essentially on analytical approaches for biological fluids and only one has involved a hair sample. After the development and validation of a new method, the first series of positive results for mephedrone in hair specimens is reported here. After decontamination of the hair strand in methylene chloride, hair segments were cut into small pieces with scissors, weighed and incubated overnight in Soerensen buffer pH 7.0 in the presence of deuterated 3,4-methylenedioxymethamphetamine (MDMA) at 40°C. The incubation medium was extracted using ethyl acetate after alkalinisation with 1N sodium hydroxide (NaOH). Before injection, the dry extract was derivatized using a mixture of heptafluorobutyric anhydride/ethyl acetate (100:50, v/v), evaporated and dissolved in ethyl acetate (25μl). After introduction of 1μl of the extract onto a splitless injector, chromatographic separation was achieved on a HP 6890 gas chromatograph equipped with a 5-MS capillary column. Detection was achieved in single ion monitoring mode (m/z 254-119-210 for mephedrone, m/z 258-213 for MDMA-d5) using a 5973 MSD operating in electron impact mode. Sixty-seven hair specimens were tested for mephedrone. Thirteen of them were found positive for mephedrone with concentrations ranging from 0.2 to 313.2ng/mg with a mean concentration of 26.8ng/mg. It was difficult to compare our findings due to a lack of reference data, nevertheless mephedrone seems well incorporated into hair (concentrations in the ng/mg range) like other stimulant drugs such as amphetamines or cocaine. The aim of this work was to develop a specific and accurate method for mephedrone analysis in hair specimens and its application to a large number of samples (n=67). The developed analytical method appears sensitive enough to reveal occasional to regular use of mephedrone.

Frequency and dangerousness of falls in elderly people are a public health problem because of its prevalence and its consequences. Because of its high frequency a program designed to avoid the risk of fall and to restore the balance is of importance. Nowadays in Belgium, only the ones belonging to the F-pathology list are reimbursed for the walking functional reeducation. The troubles of walking and balance increasing the risk of falls, are evaluated by different tests like: Tinetti's test (POMA), Time-up-and-go tests. To screen the patient in its physical psychological and environmental sides is mandatory. The physiotherapist is the key to evaluate the patient globally. The main aim is to restore the patient's independence after a fall and to ensure an optimal quality of live. A functional reeducation including the relearning of walking, balance, standing up and proprioception is a must. A preventive way should be more adequate for the patient at risk and the society. A prevention program for fall involving a multidisciplinary team could be the solution of the public health's problem. A lost still remains to be done! In some countries such programs do exist. They inform the elderly about falls' risks and the sometimes tragic consequences. To prevent falls, GP's, ergotherapists, physiotherapists, nurses and social workers have to work together.

Aims In 2008, some synthetic cannabinoids named “Spice” were detected in herbal smoking mixtures and became popular owing to their strong cannabimimetic effects after smoking. Many other products have appeared since and are constantly changing in attempts by manufacturers to evade legislation. Hair samples, which generally contain the parent compounds, could be of interest to screen for these synthetic cannabinoids using a poor selective extraction method and a highly specific and sensitive analytical detection technique. A simple method was developed and validated for the quantitative detection of 18 synthetic cannabinoids, AM-694; AM- 2201;CP 47,497; HU-210; JWH-007; JWH-015; JWH-018 and its N-Pentanoic acid metabolite; JWH-019; JWH-020; JWH-073; JWH-081; JWH-122; JWH-200; JWH-203; JWH-210; JWH-250 and WIN 55, 212-2 in hair by HPLC-MS/MS and its application to authentic specimen. This work belong to a pilot study evaluating the prevalence of synthetic cannabinoids use in France and conducted with two other labs 2 , 3 . Methods After decontamination with methylene chloride, hair sections were cut into small pieces, weighed and incubated in methanol, overnight at 40 °C, in the presence of deuterated internal standards (JWH-018-d 9 , THC-d 3 , 11-OH-THC-d 3 , THC-COOH-d 3 ). Finally, the organic phase was evaporated to dryness and reconstituted in mobile phase. The HPLC-MS/MS system consisted of an UFLC (Shimadzu Prominence) coupled with a triple-quadrupole ABSciex 5500 QTRAP instrument. Chromatographic separation was achieved on a Kinetex™ XB-C18 (2.1×100mm, 2.6μm) column. Tandem mass spectrometry was employed using an electrospray interface in positive and negative ionisation mode and acquisition was performed in scheduled MRM mode. Results The method was linear from LQ to 500pg/mg with quantification limits ranging from 0.5 to 5 pg/mg for all the targeted synthetic cannabinoids. Intra and inter-day precisions were below 20% at 0.5; 10; 50; 75 and 250 pg/mg. Intra and inter-day accuracies were established to be between 80% and 120% for the same concentration levels. There was no carry over and the absence of significative ion suppression phenomena was controlled. Sixty-five authentic hair specimens obtained from our routine activity (French forensic cases) were screened for synthetic cannabinoids. None of the specimen was found positive for the 18 targeted compounds. These preliminary results are in favour with a current very low prevalence of synthetic cannabinoids use in France, and are in accordance with those obtained by the two other labs which investigated urine specimens for the same 18 compounds. Conclusion Regarding the rising scientific interest about the synthetic cannabinoids, it appears necessary to develop an accurate, sensitive, but also evolutive method for the detection and quantification of synthetic cannabinoids in hair. Liquid chromatographymass spectrometry was deemed the most suitable analytical technique for its accuracy and sensitivity, particularly after a simple and unique direct extraction step from hair using methanol. This first method version was developed and fully validated for the large screening of 18 synthetic cannabinoids in hair.

Between 1994 and early 1999, Mycobacterium xenopi was isolated in 11 HIV-negative patients seen at the Respiratory Disease Department of the Dijon University Hospital. Eight of these patients met the criteria of lung infection. Clinical and radiological features simulated pulmonary tuberculosis which delayed diagnosis until the germ was identified. Treatment is considered to be mandatory though it is difficult to manage and often disappointing. In spite of long-term medical care, sometimes associated with surgery, outcome is currently determined by the underlying disease rather than by Mycobacterium xenopi infection.

We described an in vitro 3-dimensional model to study the bactericidal activity of piperacillin (P), tazobactam (T) and amikacin (A) in combination against 5 strains of enterobacteria with different resistance patterns of beta-lactam antibiotics. A synergy was defined by calculation of sigma FBCP,T,A = BCp/MBCp + BCT/MBCT + BCA/MBCA and classic sigma FBCs for each double combination. The therapeutic value of each antibiotic was estimated by comparison of its bactericidal concentrations alone and in double or triple combination.

The uptake of ofloxacin by Escherichia coli NIHJ-JC2 was determined by a sensitive and convenient method using high-performance liquid chromatography (HPLC) with a fluorometric detection (sensitivity level: 1 ng/ml). Concentrations of ofloxacin were measured in bacteria after contact with 5 micrograms/ml of antibiotic for 1, 2, 3, 5, 10, 20 and 30 min. Ofloxacin uptake was rapid, 70% of broth concentration occurring within the first min and 96% after 5 min; then it reached a plateau which was 1.16 times as high as the broth concentration.

Cefpodoxime proxetil (RU 51 807) is the oral prodrug of cefpodoxime (RU 51 763), a third generation cephalosporin. The antibacterial activity of cefpodoxime was compared with the activities of amoxicillin in combination with clavulanic acid (AUG), cefaclor (CCl), cefuroxime (CXM) and cefotaxime (CTX), against species of Enterobacteriaceae showing a resistance pattern against ampicillin (AMP), ticarcillin (TIC), cefalothin (CFT) and cefotaxime (CTX) respectively. For strains AMP and TIC R, CFT and CTX S, MICs 90% of cefpodoxime were 1 mg/l (E. coli), 0.5 (K. pneumoniae), 0.06 (P. mirabilis), 0.5 (Shigella sp.) and 1 (Salmonella sp.); they were 4 to 16 times as high for AUG -CCL -CXM and 4 to 16 times as low for CTX. For K. pneumoniae AMP and TIC R, CFT I/R and CTX S, similar résults were obsereved for the 5 beta-lactam antibiotics, but with an activity 10 times as low. Among the species AMP R, TIC S, CFT R and CTX S, cefpodoxime was active against P. rettgeri, P. stuartii, C. diversus, E. aerogenes and Y. enterocolitica (MICs 90% ranging from 2 to 4 mg/l; from 0.12 to 1 mg/l for CTX) and less active or inactive against P. vulgaris, E. cloacae, S. marcescens, M. morganii and E. coli (MICs 90% ranged from 16 to 32 mg/l; from 1 to 4 mg/l for CTX).(ABSTRACT TRUNCATED AT 250 WORDS)

The ability of clavulanic acid and sulbactam to induce and inhibit cephalosporinases was evaluated in 16 clinical isolates of enterobacteria. Using the quantitative induction assay, the checkerboard method and the disc approximation test, clavulanic acid was shown to act as inducer for all species, whereas sulbactam only induced strains of Providencia stuartii. Antagonism was achieved using a combination of clavulanic acid and cefotaxime but a combination of sulbactam and cefotaxime was either synergistic or indifferent. This variation in effect was probably due to the fact that sulbactam, but not clavulanic acid could inhibit cephalosporinases. The data revealed a significant difference between sulbactam and clavulanic acid, which may have relevance to their relative usefulness in combination with beta-lactam antibiotics for the treatment of infections due to enterobacteria that produce inducible cephalosporinase.

Sixteen neonates developed staphylococcal septicemia (S. epidermidis in 10 cases and S. aureus in six). Two infections were due to maternofetal contamination and four to contaminated foreign material. Clinical symptoms included non-specific evidence of neonatal bacterial infection and, in S. aureus infections, suggestive skin or bone localizations. Fifteen patients recovered without sequelae and one died as a result of S. aureus septicopyemia. In view of the patterns of resistance to antimicrobial agents exhibited by S. aureus and S. epidermidis, the vancomycin-amikacin combination seems the most appropriate treatment in neonatal staphylococcal septicemias. However, the fosfomycin-cefotaxim combination can be proposed for the treatment of staphylococcal infections with osteoarticular or meningeal involvement.

The resistance of Gram positive cocci to oxacillin and cephalosporins do not appear to be in relation with the synthesis of a beta-lactamase, thus fosfomycin (FOS) could enhance the action of beta-lactam antibiotics by blocking another stage of the peptidoglycan synthesis. When FOS is combined with oxacillin (OXA) or cefotaxime (CTX) against fosfomycin sensitive strains (25 S. aureus 4-16 mg/l, 20 S. epidermidis 2-32 mg/l and 20 Enterococci 16-64 mg/l) one can see a dramatic synergistic effect of these two combinations. Respectively with S. aureus, S. epidermidis and Enterococci, FIC indices are 0.17-0.39 and 0.43 for FOS-OXA and 0.29-0.47 and 0.29 for FOS-CTX. If one considers the CSF concentrations of these three antibiotics, the combination of fosfomycin with oxacillin or cefotaxime may be used in the treatment of meningitis due to methicillin resistant Staphylococci.

Clinical and bacteriological effectiveness of the fosfomycin-cefotaxime combination is reported in four cases of serious staphylococcal infections in neonates (1 meningitis, 2 osteomyelitis, 1 superinfection of congenital varicella). Owing to the strong synergistic effect of this combination on methicillin-resistant staphylococcal strains, the authors suggest that the fosfomycin-cefotaxime combination should be considered for anti-staphylococcal therapy in neonates with deep tissue and/or methicillin-resistant infections.

The in vitro bactericidal activity of daptomycin and vancomycin alone or in combination was studied against enterococci in a microtiter checkerboard assay and by kill-kinetic experiments. Daptomycin was more active than vancomycin and was bactericidal. Better Fractional Bactericidal Concentration indices were observed with combinations of vancomycin with aminoglycosides, but in kill-kinetic studies, the combinations of 4 MICs of daptomycin with 4 mg/l of tobramycin or netilmicin produced the more lethal effect; these combinations were even more lethal than ampicillin and aminoglycosides in the same conditions. While vancomycin and ampicillin were antagonistic, synergistic FBC indices were observed with daptomycin and ampicillin in combination, but at 4 MICs of each antibiotic, the combination was less bactericidal than ampicillin alone. The bactericidal effect obtained with daptomycin in combination with aminoglycosides suggest that further evaluation of these combinations in enterococcal endocarditis could have a clinical interest if this bactericidal effect was confirmed by in vivo studies.

Resistance of ceftriaxone, cefotaxime and cefmenoxime to inactivation by the chromosomal constitutive cephalosporinases of Enterobacter cloacae P99, Morganella morganii GN 1510 and Serratia liquefaciens 132 was determined using high performance liquid chromatography. The inhibitory properties of ceftriaxone against the same cephalosporinases were studied by determining the residual amount of cephalothin used as the substrate. With a 1:50 cephalosporinase-cephalosporin ratio, ceftriaxone was less resistant to hydrolysis than cefotaxime of cefmenoxime but showed stronger inhibitory properties.

High performance liquid chromatography (HPLC) has shown that cefmenoxime and cefotaxime are stable to the cephalosporinase of Enterobacter cloacae P99 , Morganella morganii GN 1510 and Serratia liquefaciens 132. They are significantly resistant to hydrolysis by 100 cephalosporinase units (cephalosporinase production of 10(12) bacterial). Cefmenoxime and cefotaxime are also inhibitors of cephalosporinase at the concentration of 5.10-10 micrograms per 10-10 unit of enzyme.

Thirty-two patients were included in this trial: 22 with staphylococcal meningitis (including 5 methicillin-resistant) and 10 with enterobacterial meningitis. Mean duration of treatment was 14.5 and 15.9 days respectively. The combination was synergistic in vitro against 10 of the 12 strains of Staphylococcus and 5 of the 6 strains of Enterobacteriaceae studied. Bacteriological sterilization occurred in all cases which could be evaluated, and clinical recovery was obtained in 95.2% of patients with staphylococcal meningitis (4 unrelated deaths) and 100% of patients with enterobacterial meningitis (2 deaths). Bactericidal power of the cerebro-spinal fluid, often less than 1/8, was not correlated with effectiveness against Staphylococci. Mean CSF concentrations of cefotaxime, desacetylcefotaxime and fosfomycin on the 2nd and 15th days of treatment were 4, 3.5 and 39.8 mg/l and 2.2, 2.1 and 28.0 mg/l, respectively. Clinical and biological acceptability was satisfactory. There were three cases of superinfection or colonization, by Pseudomonas and Enterobacter.

We have studied strains of enterobacteria which are resistant to first generation cephalosporins, in relation to their cephalosporinase production. Therefore, this is not an epidemiological study. For these selected strains, if a difference in MIC greater than or equal to 2 base 2 logarithms is considered to be significant, Moxalactam appears as more potent than cefotaxim. An appropriate study shows that these findings are related to the production of cephalosporinase. If very little cephalosporinase is produced, cefotaxim is more potent, implying better accession to the lethal target of the bacteria. Conversely, when cephalosporinase production is higher, Moxalactam is more potent. Moxalactam can be shown to be more resistant to hydrolysis by cephalosporinases.

Quantitative bacteriologic monitoring of bronchial secretions obtained by protected distal catheterism was performed in 60 critically ill patients under mechanical ventilation. A number of factors which have significant bearing on bacterial growth in the respiratory tract were demonstrated. A statistical correlation was found between aspiration pneumonia and presence of Enterobacteriaceae, as well as between hospital-acquired pneumonia and recovery of opportunistic pathogens. S. aureus was especially prevalent in patients under corticosteroids. Aminoglycoside treatments increased the frequency of Acinetobacter infections, whereas prevalence of S. aureus and P. aeruginosa appeared unrelated to the use of any specific antibiotic. The value of bacteriology on protected distal catheter bronchoscopy specimens is to allow accurate diagnosis of lower respiratory tract infections and provide guidelines for the choice of appropriate antibiotics.

[This corrects the article DOI: 10.1371/journal.pone.0166126.].