No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial).

BACKGROUND: The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment. METHODS: We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes. RESULTS: Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged. CONCLUSION: Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed.

Focal cortical atrophy following transient meningeal enhancement in a progressive multiple sclerosis.

Recent studies identified chronic leptomeningeal enhancement (LME) in late-acquired FLAIR sequences in secondary progressive (SP) multiple sclerosis (MS). These LMEs correlate with focal cortical inflammation and demyelination observed by pathology, which are supposed to drive long-term cortical atrophy. We report a spontaneously remitting meningeal uptake in a patient suffering from SP MS. No cortical lesion was visible on FLAIR or DIR sequences, but the rate of cortical atrophy was higher in this area. This case suggests that conventional 3-T MRI, by contrary to white matter lesions, may be amnesic with regard to the potential burden of previous regressive meningeal lesions. Moreover, T1-enhanced sequences underscore the real inflammatory activity. LME could be more than passive markers of SP MS, but is also directly responsible for focal cortical atrophy and could be an early manifestation of cortical lesions.

Photoelectrocatalytic degradation of 17α-ethinylestradiol and estrone under UV and visible light using nanotubular oxide arrays grown on Ti-0.5wt%W.

Environmental concern with emerging contaminants has increased in recent years, especially with regard to endocrine-disrupting compounds (EDCs), among them hormones. Conventional water treatment processes have been shown to be ineffective in removing these compounds from water and sewage, while heterogeneous photocatalysis has been demonstrated to be a promising technique. However, the catalytic efficiency is strongly related to the choice of the photocatalyst material. In order to obtain a fast and efficient degradation of these endocrine disruptors, nanotubes grown on Ti-0.5wt%W alloy (NT/Ti-0.5W) were used in photocatalytic (PC) and photoelectrocatalytic (PEC) processes for the degradation of estrone (E1) and 17α-ethinylestradiol (EE2) under irradiation with ultraviolet (UV) and visible light. The NT/Ti-0.5W catalysts were synthesized by an anodization process, followed by thermal treatment at 450 °C. Raman, X-ray diffraction and diffuse reflectance spectroscopic analyses indicated that the tungsten doping process had modified the nanotubular TiO2. The doped samples exhibited superior photoactivity compared to un-doped samples and other semiconductors under UV and visible irradiation due to a reduction in the rate of recombination of photogenerated charges and the displacement of the flat-band potential to more negative values. Higher values of the degradation rate constant were found for both hormones in the PEC process using NT/Ti-0.5W under UV radiation; the percentage removals of EE2 and E1 were 66% and 53.4%, respectively, after only 2 min of treatment. With visible light, 1.8 min and 4.6 h were required for the removal of 50% of E1 and EE2, respectively. The degradation of E1 could be fit with a zero-order kinetic model, while a first-order kinetic model was required for EE2 degradation. Degradation routes were suggested for E1 and EE2. The results demonstrate that the combined use of NT/Ti-0.5W and the PEC process provides excellent performance for the degradation of emerging contaminants in wastewater when compared to a NT/TiO2 electrode.

Weston-Hurst syndrome with acute hemorrhagic cerebellitis.

Weston-Hurst syndrome is an exceptional variant of ADEM characterized by brain hemorrhages. Lesions are usually supratentorial and death is a usual outcome. We report a cerebellar Weston-Hurst syndrome early treated by craniectomy, steroids and plasma exchange. This is the first case of infratentorial Weston-Hurst syndrome associated with a favorable outcome.

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation.

OBJECTIVE: The low level of passively diffused IgG through the blood-brain barrier is sufficient to blur the estimation of intrathecal IgG synthesis (ITS). Therefore, this estimation requires a mathematical calculation derived from empirical laws, but the range of normal values in healthy controls is wide enough to prevent a precise calculation. This study investigated the precision of various methods of ITS estimations and their application to two clinical situations: plasma exchange and immune suppression targeting ITS. METHODS: Based on a mathematical model of ITS, we constructed a population of healthy controls and applied a tunable ITS. RESULTS: We demonstrate the following results: underestimation of ITS is common at individual level but true ITS is well fitted by cohorts; Q IgG increases after plasma exchange; IgG Loc calculation based on Qlim falsely increases when Q Alb decreases; the sample size required to demonstrate a decrease in ITS increases exponentially with larger Q Alb. INTERPRETATION: Studies evaluating changes in ITS level should be adjusted to Q Alb. Low amounts of ITS could be largely underestimated.

Perfil de resistência a antimicrobianos de Staphylococcus aureus isolados de queijo manteiga comercializado em feira pública da cidade de Macapá, AP / Antimicrobial resistance profile of Staphylococcus aureus isolated from butter cheese marketed at a public fair in the city of Macapa, AP

O comércio informal de leite e derivados possui relevante impacto na saúde pública, pelo risco de transmissão de doenças alimentares. O S. aureus configura-se um dos principais patógenos associados à contaminação de queijos. O objetivo do presente trabalho, portanto, foi estudar o perfil de resistência aos antimicrobianos de S. aureus isolados de amostras de queijo manteiga comercializadas nas feiras públicas de Macapá. Foram obtidas 20 amostras de queijo comercializados em feiras livres da cidade de Macapá, AP. O isolamento foi realizado em Agar Baird Parker e para confirmação das colônias típicas, foi realizada a coloração de Gram, identificação bioquímica, catalase, coagulase e DNase. Posteriormente, pela técnica de disco-difusão foram testados os seguintes antibióticos: Gentamicina 10 µg (GEN), clorafenicol 30 µg (CLO), tetraciclina 30 µg (TET), eritromicina 15 µg (ERI), norfloxacina 10 µg (NOR), nitrofurantoina 300 µg (NIT), sulfametoxazol/trimetoprim 1,25/23,75 µg (SUT), oxacilina 1 µg (OXA), vancomicina 30 µg (VAN). Das amostras avaliadas, 60% estavam fora do padrão para S. aureus, mas mostraram que os antibióticos NIT, SUT, TET, CLO e OXA foram eficazes frente a todas as cepas, por outro lado, das 12 estirpes avaliadas, cinco (41,67%%) apresentaram resistência total a ERI, 3 (25%) apresentaram resistência total a GEN e uma (8,33%) apresentou resistência intermediária a NOR. Estes resultados demonstram a importância de uma legislação mais rigorosa para o fortalecimento do Sistema de Vigilância Sanitária, com o intuito de fiscalizar alimentos oferecidos à população e seus lugares de comercialização, diminuindo os riscos à população que consome esses produtos.(AU)

The informal trade in milk and dairy products has a significant impact on public health because of the risk of transmission of foodborne diseases. S. aureus is one of the main pathogens associated with cheese contamination. The present work aimed to study the antimicrobial resistance profile of S. aureus isolated from samples of butter cheese commercialized in the public fairs of Macapá. twenty samples of cheese marketed in free markets of the city of Macapá. Isolation was performed in Baird Parker agar and for confirmation of typical colonies, Gram staining, biochemical identification, catalase, coagulase and DNase were performed. Subsequently, by the disc- -diffusion technique, the following antibiotics were tested: Gentamicin 10 µg (GEN), Chlorphenicol 30 µg (CLO), tetracycline 30 µg (TET), erythromycin 15 µg (ERI), norfloxacin 10 µg (NOR), nitrofurantoin 300 µg (NIT), sulfamethoxazole / trimethoprim 1,25 / 23, 75 µg (SUT), oxacillin 1 µg (OXA), vancomycin 30 µg (NPV). Of the samples evaluated, 60% were non-standard for S. aureus but showed that NIT, SUT, TET, CLO and OXA antibiotics were effective against all strains, on the other hand, of the 12 strains evaluated, 5 (41.67%) presented total ERI resistance, 3 (25%) presented total resistance to GEN, and 1 (8.33%) presented intermediate resistance to NOR. These results demonstrate the importance of stricter legislation for the strengthening of the Sanitary Surveillance System, with the purpose of inspecting food offered to the population and their places of sale, reducing the risks to the population that consumes these products.

Reator anaeróbio tipo UASB conjugado com processo Fenton para remoção de cor e demanda química de oxigênio de água residuária sintética de indústria têxtil / Anaerobic reactor type UASB conjunction with process Fenton to remove color and chemical oxygen demand textile industry of synthetic wastewater

RESUMO A contaminação por despejos de efluentes industriais têxteis tem sido uma preocupação emergente de pesquisadores e ambientalistas, pois esses apresentam composição extremamente heterogênea e grande quantidade de material tóxico e recalcitrante, o que dificulta seu tratamento. Durante o processamento têxtil, uma ampla gama de corantes é liberada e alguns desses, como os azo corantes, que se caracterizam pela função azo (-N=N-) ligada a grupos aromáticos e podem ser tóxicos, carcinogênicos e/ou mutagênicos. Em vista disso, esta pesquisa teve como principal objetivo avaliar os benefícios da utilização de um reator anaeróbio tipo reator anaeróbico de fluxo ascendente com manta de lodo (UABS), seguido de processo oxidativo avançado (POA) do tipo Fenton na degradação de cor e demanda química de oxigênio (DQO) de efluente sintético de indústria têxtil. Com os resultados, foram verificadas remoções de DQO em torno de 82,0% para o reator UASB e de 95,6% para o conjunto. A cor alcançou 96,1% de remoção no reator UASB e 100,0% ao final do processo.

ABSTRACT Contamination by textile industrial wastewater discharges has been an emerging concern of researchers and environmentalists, as they have extremely heterogeneous composition and loads of toxic and recalcitrant material, which complicates treatment. In the textile processing, a wide range of dye is released and some of these, such as dyes, azo, characterized by the feature azo (-N=N-) attached to aromatic groups and may be toxic, carcinogenic and/or mutagenic. In view of this, this research aimed to evaluate the benefits of using an anaerobic reactor type anaerobic reactor upflow sludge blanket (UABS), followed by advanced oxidation process (AOP) type Fenton in color degradation and chemical oxygen demand (COD) of synthetic textile industry effluent. From the results of COD removal was observed at around 82.0% for the UASB reactor and 95.6% for the group. The color reached 96.1% removal in UASB reactor and 100.0% at the end of the process.

No evidence of disease activity (NEDA) in MS should include CSF biology - Towards a 'Disease-Free Status Score'.

The concept of NEDA (no evidence of disease activity) was forged to describe relapse-free patients under treatment with recent drugs, but this goal is reached by less than half of all patients and not sustained over time. However a complete remission of disease is expected to be associated with the normalization of CSF biomarkers. On pathophysiological grounds, we propose to add the criterion of no evidence of biological activity in CSF to design a future 'disease-free status score'. This composite criterion, which should concern neurodegenerative and immune activation biomarkers, would be better suited for assessing the persistence of biological processes long before CNS atrophy occurs and should help in predicting long-term remission/progression of MS.

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection - a model of chronic CNS inflammation?

HIV infects the central nervous system (CNS) during primary infection and persists in resident macrophages. CNS infection initiates a strong local immune response that fails to control the virus but is responsible for by-stander lesions involved in neurocognitive disorders. Although highly active anti-retroviral therapy now offers an almost complete control of CNS viral proliferation, low-grade CNS inflammation persists. This review focuses on HIV-induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early occurs in more than three-quarters of patients in response to viral infection of the CNS and persists throughout the course of the disease. Viral antigens are targeted but this specific response accounts for <5% of the whole intrathecal synthesis. Although the nature and mechanisms leading to non-specific synthesis are unknown, this prominent proportion is comparable to that observed in various CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells account for a minority of the whole synthesis, which mainly takes place in perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and lineage across the blood-brain-barrier have not yet been described. We review common technical pitfalls and update the pending questions in the field. Moreover, since HIV infection is associated with an intrathecal chronic oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade axonal lesions, this could be an interesting model of the chronic intrathecal synthesis occurring during multiple sclerosis.

Natalizumab is effective in controlling the inflammatory rebound after its discontinuation and failure of an alternative treatment.

Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NAT) is used in the treatment of relapsing multiple sclerosis (MS). JC virus serologic status is a currently established risk factor for PML. When seroconversion occurs, NAT discontinuation should be based on a solid rationale to avoid an MS inflammatory resurgence. The JC virus index value may also provide further useful information to help practitioners and patients in their decision process.

Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials.

Rituximab has demonstrated a major effect in B-cell lymphoma and in a wide range of autoimmune disorders. Unfortunately, the blood-brain-barrier excludes the disorders restricted to the central nervous system (CNS) from the action of rituximab. The progressive phase of multiple sclerosis (MS) is a prototypical CNS autoimmune disorder characterized by an intrathecal compartmentalization of inflammation resisting all the available immunosuppressive treatments. As a consequence, intrathecal therapeutics are promising new approach in progressive MS. We first review data gathered from animal models and human off-label intrathecal rituximab use in CNS lymphomas, then summarize the recent evidence supporting the need for trials based on the intrathecal use of rituximab in multiple sclerosis. The experience obtained in these settings offers valuable preliminary data for future studies in CNS autoimmunity.

Middle cerebral artery dissection: diagnostic and prognostic value of transcranial color-coded sonography.

We report 2 patients with ischemic stroke related to an initial severe focal narrowed middle cerebral artery caused by a dissection mechanism, a presentation that has received little attention to date. Diagnostic modalities and follow-up using transcranial color-coded sonography are reported and discussed. Results with transcranial color-coded sonography were correlated with computed tomographic angiography, showing the great value of this radiation-free arterial monitoring process in this setting, especially in young adults.

Postpartum four-vessel cervical artery dissection.

A postpartum four-vessel cervical artery dissection with no stroke is reported. This transient vasculopathy took place in the autoimmune context of the HELLP syndrome combined with the reversible posterior leucoencephalopathy syndrome. Correlations between the clinical, radiological and biological entities are discussed.

Cerebral abscesses in hereditary haemorrhagic telangiectasia: a clinical and microbiological evaluation.

OBJECTIVES: Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder that can lead to neurological manifestations including strokes and cerebral abscesses. Our objectives were to describe clinical, radiological, bacteriological, and outcome characteristics of patients with cerebral abscess and HHT, and to concurrently compare this group with a control group with cerebral abscess, but without HHT. PATIENTS AND METHODS: Patients with HHT and cerebral abscess in 5 French medical centers were included. Their clinical, radiological, biological data and prognosis were compared to the data of unselected patients with cerebral abscesses but without HHT included during the same period of time. RESULTS: Twenty-six patients (13 men and 13 women; 44.7±17.2; range 12-79 years), with HHT and cerebral abscess were included. A pulmonary arteriovenous malformation (AVM) was present in all cases. Cerebral abscesses were solitary, supratentorial, and mostly lobar. In all cases, pathogens were anaerobic or facultative anaerobic germs (particularly streptococcus). No death was observed, but various sequels were present in up to two-thirds of the patients. We observed a recurrence of the cerebral abscess in 4 patients with a mean delay of 81 months. In comparison with the control group, cerebral abscesses were generally of later recurrence and significantly more often unique and less often due to staphylococcus. CONCLUSION: HHT cerebral abscesses are particularly linked to pulmonary arteriovenous malformations and anaerobic germs. Their clinical, radiological and bacteriological characteristics are quite different than in a control group with more solitary brain localizations, no staphylococcus infection and a significantly longer interval to recurrence.

Stroke thrombolysis in the emergency department as an alternative service for community hospitals lacking a stroke unit.

OBJECTIVE: A significant advancement in the management of acute ischemic stroke has been the use of the recombinant tissue plasminogen activator (rtPA). French guidelines recommend that stroke patients should be treated in stroke units (SU); however, community hospitals experience practical difficulties in treating their patients because SUs are not sufficient in number. Only one SU is available in the Aquitaine area (southwest of France) and it is located in Bordeaux. To improve quality of care and to provide modern stroke therapy, we decided to assess whether thrombolysis was feasible in our community hospital located in Pau, 200 km from Bordeaux. METHODS: Selected patients were treated with rtPA and observed for 24 h in the emergency department. According to French legislation, rtPA therapy was defined as 'off-label use'. National Institutes of Health stroke scale (NIHSS) was obtained on admission, immediately after treatment and 24 h after treatment. RESULTS: Results from the first 40 patients are reported in this study. They were treated between September 2004 and June 2006. In total, 1169 patients were admitted for stroke during this period. Outcomes and mortality rates were consistent with experience elsewhere. CONCLUSIONS: According to the local infrastructural criteria and prerequisites described in this study, thrombolysis is a viable and feasible treatment option for stroke patients in emergency departments of French community hospitals. In the absence of an SU, this type of emergency treatment can be used as an alternative until SUs become more numerous throughout the country.