Efficacy of trovafloxacin in treatment of experimental staphylococcal or streptococcal endocarditis.

The efficacy of trovafloxacin against Staphylococcus aureus and viridans group streptococci was investigated in vitro and in an experimental model of endocarditis. The MICs at which trovafloxacin and ciprofloxacin inhibited 90% of clinical isolates of such bacteria (MIC90s) were (i) 0.03 and 2 mg/liter, respectively, for 30 ciprofloxacin-susceptible S. aureus isolates, (ii) 32 and 128 mg/liter, respectively, for 20 ciprofloxacin-resistant S. aureus isolates, and (iii) 0.25 and 8 mg/liter, respectively, for 28 viridans group streptococci. Rats with aortic vegetations were infected with either of two ciprofloxacin-susceptible but methicillin-resistant S. aureus strains (strains COL and P8), one penicillin-susceptible Streptococcus sanguis strain, or one penicillin-resistant Streptococcus mitis strain. Rats were treated for 3 or 5 days with doses that resulted in kinetics that simulated those achieved in humans with trovafloxacin (200 mg orally once a day), ciprofloxacin (750 mg orally twice a day), vancomycin (1 g intravenously twice a day), or ceftriaxone (2 g intravenously once a day). Against the staphylococci, the activities of both trovafloxacin and ciprofloxacin were equivalent to that of vancomycin, and treatment of endocarditis with these drugs was successful (P < 0.05). However, ciprofloxacin selected for resistant derivatives in vitro and in vivo, whereas trovafloxacin was 10 to 100 times less prone than ciprofloxacin to select for resistance in vitro and did not select for resistance in vivo. Against the two streptococcal isolates, trovafloxacin significantly (P < 0.05) decreased bacterial counts in the vegetations but was less effective than the control drug, ceftriaxone. Thus, a simulated oral dose of trovafloxacin (200 mg per day) was effective against ciprofloxacin-susceptible staphylococci and was less likely than ciprofloxacin to select for resistance. The simulated oral dose of trovafloxacin also had some activity against streptococcal endocarditis, but optimal treatment of infections caused by such organisms might require higher doses of the drug.

L'hystérie : une entité historique, un trouble psychiatrique ou une maladie neurologique? [Hysteria : an historical entity, a psychiatric condition or a neurological disease?]

Il a été suggéré que l'hystérie avait disparu et n'était qu'un concept ancien, stigmatisant et péjoratif, voire erroné, reflétant l'incapacité de la communauté médicale à établir parfois un diagnostic. Actuellement ces troubles, appelés troubles dissociatifs ou de conversion, restent pourtant une réalité clinique fréquente et invalidante pour les patients. Plusieurs études et revues ont tenté de mieux décrire la présentation clinique, mais également de mieux comprendre les mécanismes neurobiologiques impliqués dans ces troubles grâce au développement de certaines techniques d'imagerie cérébrale. Si les corrélats neurobiologiques sont mieux compris, des traitements efficaces manquent encore et seule une prise en charge multidisciplinaire (généralistes, neurologues et psychiatres) et individualisée peut apporter un bénéfice au patient. It has been suggested that hysteria had waned and was an old-fashioned, stigmatizing and false concept, reflecting the incapacity of the medical community to establish a diagnosis in certain situations. Nowadays, however, those disturbances, now referred to as conversion or dissociative disorders, still remain a frequent and incapacitating condition that every clinician faces. These past decades, several studies have tried to better describe their clinical presentation and their neurobiological mechanisms, with the help of the development of new neuroimaging techniques. If the neurobiological correlates are now better understood, efficient treatments are still lacking and only a multidisciplinary (general practitioners, neurologists and psychiatrists) and individually-tailored therapy might be beneficial to the patients.

Robotic, fluoroscopic or EMG assisted pedicle screw insertion. A CT based comparative study

Introduction: In order to improve safety of pedicle screw placement several techniques have been developed. More recently robotically assisted pedicle insertion has been introduced aiming at increasing accuracy. The aim of this study was to compare this new technique with the two main pedicle insertion techniques in our unit namely fluoroscopically assisted vs EMG aided insertion. Material and methods: A total of 382 screws (78 thoracic,304 lumbar) were introduced in 64 patients (m/f = 1.37, equally distributed between insertion technique groups) by a single experienced spinal surgeon. From those, 64 (10 thoracic, 54 lumbar) were introduced in 11 patients using a miniature robotic device based on pre operative CT images under fluoroscopic control. 142 (4 thoracic, 138 lumbar) screws were introduced using lateral fluoroscopy in 27 patients while 176 (64 thoracic, 112 lumbar) screws in 26 patients were inserted using both fluoroscopy and EMG monitoring. There was no difference in the distribution of scoliotic spines between the 3 groups (n = 13). Screw position was assessed by an independent observer on CTs in axial, sagittal and coronal planes using the Rampersaud A to D classification. Data of lumbar and thoracic screws were processed separately as well as data obtained from axial, sagittal and coronal CT planes. Results: Intra- and interobserver reliability of the Rampersaud classification was moderate, (0.35 and 0.45 respectively) being the least good on axial plane. The total number of misplaced screws (C&D grades) was generally low (12 thoracic and 12 lumbar screws). Misplacement rates were same in straight and scoliotic spines. The only difference in misplacement rates was observed on axial and coronal images in the EMG assisted thoracic screw group with a higher proportion of C or D grades (p <0.05) in that group. Recorded compound muscle action potentials (CMAP) values of the inserted screws were 30.4 mA for the robot and 24.9mA for the freehand technique with a CI of 3.8 of the mean difference of 5.5 mA. Discussion: Robotic placement did improve the placement of thoracic screws but not that of lumbar screws possibly because our misplacement rates in general near that of published navigation series. Robotically assisted spine surgery might therefore enhance the safety of screw placement in particular in training settings were different users at various stages of their learning curve are involved in pedicle instrumentation.

The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome.

STUDY OBJECTIVE: To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder (ASD) and fragile X syndrome (FXS). METHODS: A 4-week, randomized, double blind, placebo-controlled, crossover design was conducted following a 1-week baseline period. Either melatonin, 3 mg, or placebo was given to participants for 2 weeks and then alternated for another 2 weeks. Sleep variables, including sleep duration, sleep-onset time, sleep-onset latency time, and the number of night awakenings, were recorded using an Actiwatch and from sleep diaries completed by parents. All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS. RESULTS: Data were successfully obtained from the 12 of 18 subjects who completed the study (11 males, age range 2 to 15.25 years, mean 5.47, SD 3.6). Five participants met diagnostic criteria for ASD, 3 for FXS alone, 3 for FXS and ASD, and 1 for fragile X premutation. Eight out of 12 had melatonin first. The conclusions from a nonparametric repeated-measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes (p = .02), mean sleep-onset latency was shorter by 28 minutes (p = .0001), and mean sleep-onset time was earlier by 42 minutes (p = .02). CONCLUSION: The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS.

Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors.

The purpose of this study was to assess the long-term outcomes of patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) without Five-Factor Score (FFS)-defined poor-prognosis factors (FFS=0) and enrolled in a prospective clinical trial. Patients were followed (2005-2012) under routine clinical care in an extended study and data were recorded prospectively. Long-term survival, disease-free survival (DFS), relapses, therapeutic responses and sequelae were analyzed. Mean±SD follow-up was 98.2±41.9months. After having initially received glucocorticoids (GC) alone, according to the study protocol, 82% (97/118) patients achieved remission but 18% (21/118) required ≥1 immunosuppressant(s) (IS) before 19/21 achieved remission. Two patients died before entering remission. After remission, 53% (61/116) patients relapsed 25.6±27.9months after starting treatment. The 5- and 8-year overall survival rates were 93% and 86%, respectively, with no difference between PAN and MPA, and between relapsers and nonrelapsers. DFS was shorter for MPA than PAN patients (P=0.02). Throughout follow-up, 47% of patients required ≥1 IS. At the last follow-up visit, 44% were still taking GC and 15% IS. The mean vasculitis damage index score was 1.9±1.9; the most frequent sequelae were peripheral neuropathy, hypertension and osteoporosis. For PAN or MPA patients without poor-prognosis factors at diagnosis and treated initially with GC alone, long-term survival was excellent. However, relapses remained frequent, requiring IS introduction for nearly half of the patients. To lower the frequencies of relapses and sequelae remains a challenge for FFS=0 PAN and MPA patients.

Clinical follow-up of women infected with human papillomavirus-16, either alone or with other human papillomavirus types: identification of different risk groups.

OBJECTIVES: Evaluation of the clinical impact of multiple infections of the cervix by human papillomavirus, including human papillomavirus-16, compared with single human papillomavirus-16 infection. STUDY DESIGN: One hundred sixty-nine women were classified in 3 categories depending on their human papillomavirus profile: human papillomavirus-16 only, human papillomavirus-16 and low-risk type(s), and human papillomavirus-16 and other high-risk type(s). Cervical brush samples were analyzed for human papillomavirus DNA by polymerase chain reaction and reverse line blot hybridization. All women were evaluated with colposcopy during 24 months or more. Management was according to the Bethesda recommendations. RESULTS: Women infected with human papillomavirus-16 and other high-risk human papillomavirus type(s) presented more progression or no change in the grade of dysplasia, compared with women of the other groups (relative risk [RR], 1.39; 95% confidence interval [CI], 1.07-1.82; P = .02 at 6 months; RR, 2.10; 95% CI, 1.46-3.02; P < .001 at 12 months; RR, 1.82; 95% CI, 1.21-2.72; P = .004 at 24 months). CONCLUSION: Coinfection of women with human papillomavirus-16 and other high-risk human papillomavirus type(s) increases the risk of unfavorable evolution.

Differential species-specific ectoparasitic mite intensities in two intimately coexisting sibling bat species: resource-mediated host attractiveness or parasite specialization?

1. The mechanisms underlying host choice strategies by parasites remain poorly understood. We address two main questions: (i) do parasites prefer vulnerable or well-fed hosts, and (ii) to what extent is a parasite species specialized towards a given host species? 2. To answer these questions, we investigated, both in the field and in the lab, a host-parasite system comprising one ectoparasitic mite (Spinturnix myoti) and its major hosts, two sibling species of bats (Myotis myotis and M blythii), which coexist intimately in colonial nursery roosts. We exploited the close physical associations between host species in colonial roosts as well as naturally occurring annual variation in food abundance to investigate the relationships between parasite intensities and (i) host species and (ii) individual nutritional status. 3. Although horizontal transmission of parasites was facilitated by the intimate aggregation of bats within their colonial clusters, we found significant interspecific differences in degree of infestation throughout the 6 years of the study, with M. myotis always more heavily parasitized than M. blythii. This pattern was replicated in a laboratory experiment in which any species-specific resistance induced by exploitation of different trophic niches in nature was removed. 4. Within both host species, S. myoti showed a clear preference for individuals with higher nutritional status. In years with high resource abundance, both bat hosts harboured more parasites than in low-resource years, although the relative difference in parasite burden across species was maintained. This pattern of host choice was also replicated in the laboratory. When offered a choice, parasites always colonized better-fed individuals. 5. These results show first that host specialization in our study system occurred. Second, immediate parasite choice clearly operated towards the selection of hosts in good nutritional state.