Toxic Shock-like Syndrome Associated with Necrotizing Streptococcus Pyogenes Infection

Two patients with toxic shock-like syndrome are presented. Both patients had necrotizing cellulitis due to Streptococcus pyogenes, and both patients required extensive surgical debridement. The association of Streptococcus pyogenes infection and toxic shock-like syndrome is discussed

Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial

International audienceObjectives: The primary objective was to compare a single, 6 ml, intra-articular injection of hylan G-F 20 with placebo in patients with symptomatic knee osteoarthritis. The safety of a repeat injection of hylan G-F 20 was also assessed. Methods: Patients with primary osteoarthritis knee pain were randomly assigned to arthrocentesis plus a 6 ml intra-articular injection of either hylan G-F 20 or placebo in a prospective, double-blind (one injector/one blinded observer) study. Results were evaluated at 4, 8, 12, 18 and 26 weeks post-injection. The primary outcome criterion was change from baseline over 26 weeks in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index A pain. Secondary outcome measures included WOMAC A1 and C, patient global assessment (PGA) and clinical observer global assessment (COGA) and Outcome Measures in Rheumatology, Osteoarthritis Research Society International responder rates. A 4-week, open, repeat treatment phase evaluated safety only. Results: A total of 253 patients (Kellgren-Lawrence grade II or III) was randomly assigned. Patients receiving hylan G-F 20 experienced statistically significantly greater improvements in WOMAC A pain scores (-0.15, SE 0.076, p=0.047), and several of the secondary outcome measures (WOMAC A1, PGA and COGA), than patients receiving placebo. There was no difference between the safety results of the two groups. No increased risk of local adverse events was observed in the open, repeat treatment phase. Conclusions: This placebo-controlled study demonstrated that, in patients with knee osteoarthritis, a single 6 ml intra-articular injection of hylan G-F 20 is safe and effective in providing statistically significant, clinically relevant pain relief over 26 weeks, with a modest difference versus placebo

Standardised cement augmentation of the PFNA using a perforated blade: A new technique and preliminary clinical results. A prospective multicentre trial

Producción CientíficaPertrochanteric fractures are a rising major health-care problem in the elderly and their operative stabilisation techniques are still under discussion. Furthermore, complications like cut-out are reported to be high and implant failure often is associated with poor bone quality. The PFNA1 with perforated blade offers a possibility for standardised cement augmentation using a polymethylmethacrylate (PMMA) cement which is injected through the perforated blade to enlarge the load-bearing surface and to diminish the stresses on the trabecular bone. The current prospective multicentre study was undertaken to evaluate the technical performance and the early clinical results of this new device. In nine European clinics, 59 patients (45 female, mean age 84.5 years) suffering from an osteoporotic pertrochanteric fracture (Arbeitsgemeinschaft fu¨ r Osteosynthesefragen, AO-31) were treated with the augmented PFNA1. Primary objectives were assessment of operative and postoperative complications, whereas activities of daily living, pain, mobility and radiologic parameters, such as cement distribution around the blade and the cortical thickness index, were secondary objectives. The mean follow-up time was 4 months where we observed callus healing in all cases. The surgical complication rate was 3.4% with no complication related to the cement augmentation. More than onehalf of the patients reached their prefracture mobility level within the study period. A mean volume of 4.2 ml of cement was injected. We did not find any cut-out, cut through, unexpected blade migration, implant loosening or implant breakage within the study period. Our findings lead us to conclude that the standardised cement augmentation using the perforated blade for pertrochanteric fracture fixation enhances the implant anchorage within the head–neck fragment and leads to good functional results

Structural Organization of the Presynaptic Density at Identified Synapses in the Locust Central Nervous System

In a synaptic active zone, vesicles aggregate around a densely staining structure called the presynaptic density. We focus on its three-dimensional architecture and a major molecular component in the locust. We used electron tomography to study the presynaptic density in synapses made in the brain by identified second-order neuron of the ocelli. Here, vesicles close to the active zone are organized in two rows on either side of the presynaptic density, a level of organization not previously reported in insect central synapses. The row of vesicles that is closest to the density's base includes vesicles docked with the presynaptic membrane and thus presumably ready for release, whereas the outer row of vesicles does not include any that are docked. We show that a locust ortholog of the Drosophila protein Bruchpilot is localized to the presynaptic density, both in the ocellar pathway and compound eye visual neurons. An antibody recognizing the C-terminus of the Bruchpilot ortholog selectively labels filamentous extensions of the presynaptic density that reach out toward vesicles. Previous studies on Bruchpilot have focused on its role in neuromuscular junctions in Drosophila, and our study shows it is also a major functional component of presynaptic densities in the central nervous system of an evolutionarily distant insect. Our study thus reveals Bruchpilot executes similar functions in synapses that can sustain transmission of small graded potentials as well as those relaying large, spike-evoked signals. J. Comp. Neurol. 520:384–400, 2012. © 2011 Wiley Periodicals, Inc

Smoking and response to rituximab in rheumatoid arthritis : results from an international European collaboration

Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (Delta DAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (Delta DAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). Conclusion: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.Peer reviewe

The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial [ISRCTN54513166]

BACKGROUND: Pharmacological treatment for osteoarthritis (OA) can be divided into two groups: symptom-modifying drugs and disease-modifying drugs. Symptom-modifying drugs are currently the prescription of choice for patients with OA, as disease-modifying drugs are not yet available in usual care. However, there has recently been a lot of debate about glucosamine sulphate (GS), a biological agent that is thought to have both symptom-modifying and disease-modifying properties. This assumption has yet to be proved. The objective of this article is to present the design of a blind randomised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA. This trial is ongoing and will finish in March 2006. METHODS/DESIGN: Patients with hip OA meeting the ACR-criteria are randomly allocated to either 1500 mg of oral GS or placebo for the duration of two years. The primary outcome measures, which are joint space narrowing (JSN), and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index (WOMAC), are determined at baseline and after two years of follow-up during the final assessment. Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures. Secondary outcome measures are changes in WOMAC stiffness score, quality of life, medical consumption, side effects and differences in biomarker CTX-II

Analysis of lysine recognition and specificity of the Bacillus subtilis L box riboswitch

The ever-changing environment of a bacterial cell requires sophisticated mechanisms to adjust gene expression in response to changes in nutrient availability. L box riboswitch RNAs regulate gene expression in response to cellular lysine (lys) concentrations in the absence of additional regulatory factors. In Bacillus subtilis, binding of lysine (lys) to the L box RNA causes premature transcription termination in the leader region upstream of the lysC coding sequence. To date, little is known about the specific RNA–lys interactions required for transcription termination. In this study, we characterize features of the B. subtilis lysC leader RNA responsible for lys specificity, and structural elements of the lys molecule required for recognition. The wild-type lysC leader RNA can recognize and discriminate between lys and lys analogs. We identified leader RNA variants with mutations in the lys-binding pocket that exhibit changes in the specificity of ligand recognition. These data demonstrate that lysC leader RNA specificity is the result of recognition of ligand features through a series of distinct interactions between lys and nucleotides that comprise the lys-binding pocket, and provide insight into the molecular mechanisms employed by L box riboswitch RNAs to bind and recognize lys