Testing the validity of a set of diagnostic criteria for sensory neuronopathies: a francophone collaborative study.

There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria on a French multicenter study. 210 patients with sensory neuropathies from 15 francophone reference centers for neuromuscular diseases were included in the study with an expert diagnosis of non-SNN, SNN or suspected SNN according to the investigations performed in these centers. Diagnosis was obtained independently from the set of criteria to be tested. The expert diagnosis was taken as the reference against which the proposed SNN criteria were tested. The set relied on clinical and electrophysiological data easily obtainable with routine investigations. 9/61 (16.4 %) of non-SNN patients, 23/36 (63.9 %) of suspected SNN, and 102/113 (90.3 %) of SNN patients according to the expert diagnosis were classified as SNN by the criteria. The SNN criteria tested against the expert diagnosis in the SNN and non-SNN groups had 90.3 % (102/113) sensitivity, 85.2 % (52/61) specificity, 91.9 % (102/111) positive predictive value, and 82.5 % (52/63) negative predictive value. Discordance between the expert diagnosis and the SNN criteria occurred in 20 cases. After analysis of these cases, 11 could be reallocated to a correct diagnosis in accordance with the SNN criteria. The proposed criteria may be useful for the diagnosis of probable SNN in patients with sensory neuropathy. They can be reached with simple clinical and paraclinical investigations.

A framework for assessing the scale of influence of environmental factors on ecological patterns

The distribution of living organisms, habitats and ecosystems is primarily driven by abiotic environmental factors that are spatially structured. Assessing the spatial structure of environmental factors, e.g., through spatial autocorrelation analyses (SAC), can thus help us understand their scale of influence on the distribution of organisms, habitats, and ecosystems. Yet SAC analyses of environmental factors are still rarely performed in biogeographic studies. Here, we describe a novel framework that combines SAC and statistical clustering to identify scales of spatial patterning of environmental factors, which can then be interpreted as the scales at which those factors influence the geographic distribution of biological and ecological features. We illustrate this new framework with datasets at different spatial or thematic resolutions. This framework is conceptually and statistically robust, providing a valuable approach to tackle a wide range of issues in ecological and environmental research and particularly when building predictors for ecological models. The new framework can significantly promote fundamental research on all spatially-structured ecological patterns. It can also foster research and application in such fields as global change ecology, conservation planning, and landscape management.

Adaptive intelligent agent approach to guide the web navigation on the PLAN-G distance learning platform

Hypermedia systems based on the Web for open distance education are becoming increasinglypopular as tools for user-driven access learning information. Adaptive hypermedia is a new direction in research within the area of user-adaptive systems, to increase its functionality by making it personalized [Eklu 961. This paper sketches a general agents architecture to include navigationaladaptability and user-friendly processes which would guide and accompany the student during hislher learning on the PLAN-G hypermedia system (New Generation Telematics Platform to Support Open and Distance Learning), with the aid of computer networks and specifically WWW technology [Marz 98-1] [Marz 98-2]. The PLAN-G actual prototype is successfully used with some informatics courses (the current version has no agents yet). The propased multi-agent system, contains two different types of adaptive autonomous software agents: Personal Digital Agents {Interface), to interacl directly with the student when necessary; and Information Agents (Intermediaries), to filtrate and discover information to learn and to adapt navigation space to a specific student

Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer.

Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitative RT-PCR on a cohort of colorectal cancer patients. From a pool of more than 6000 genes identified unambiguously in the analysis, we found 2124 genes that were selectively expressed in colon cancer tissue and 147 genes that were differentially expressed to a significant degree between normal and cancer cells. Differential expression of many genes was confirmed by RT-PCR on a cohort of patients. Despite the fact that deregulated genes were involved in many different cellular pathways, we found that genes expressed in the extracellular space were significantly over-represented in colorectal cancer. Strikingly, we identified a transcript from a chromosome X-linked member of the human endogenous retrovirus (HERV) H family that was frequently and selectively expressed in colon cancer but not in normal tissues. Our data suggest that this sequence should be considered as a target of immunological interventions against colorectal cancer.

Diagnostic et prise en charge de la thrombocytopénie immune primaire

La thrombocytopénie immune primaire (ITP) est une affection auto-immune acquise avec diminution de la survie des plaquettes et perturbation de la production plaquettaire. Il n'existe aucun test clinique simple permettant de prouver la nature auto-immune de l'affection. Pour cette raison, il s'agit presque toujours d'un diagnostic par exclusion d'autres causes. Bien que les plaquettes soient souvent inférieures à 10 x 109/l lors de la présentation initiale, la tendance hémorragique est étonnamment modérée chez la majorité des patients. Le traitement initial fait toujours appel aux corticostéroïdes, combinés à des immunoglobulines intraveineuses et à des transfusions de plaquettes dans les formes compliquées avec hémorragies significatives. Chez l'enfant, la maladie est souvent induite par des infections virales et son évolution est bénigne et spontanément régressive dans la majorité des cas. Chez l'adulte, la maladie est plus souvent persistante ou chroniquement récidivante, et le taux de plaquettes se situe souvent à un taux suffisant pour prévenir des hémorragies spontanées. Seule une faible proportion de patients souffre d'une thrombocytopénie sévère prolongée accompagnée de saignements réguliers avec risque d'hémorragies potentiellement fatales. C'est probablement ce groupe de patients restreint qui tirera surtout profit des nouvelles options thérapeutiques telles que les agonistes du récepteur de la thrombopoïétine. A la lumière de ces nouvelles possibilités, un groupe d'hématologues suisses s'est réuni pour élaborer des directives concernant la prise en charge de l'ITP conformément aux besoins et aux habitudes de notre pays.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury

BACKGROUND Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. METHODS Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). RESULTS 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. CONCLUSION This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. TRIAL REGISTRATION This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Acute coronary syndromes or myocarditis in young people: a difficult daily diagnostic challenge

Background: Chest pain (CP) represents about 5% of admissions to emergency departments (ED), even in young people. Acute coronary syndrome (ACS) and myocarditis are among the most important diagnoses to rule out. Clinical and ECG findings are not specific for either condition and separating both diagnoses is a challenge. Aim of the study: To evaluate the prevalence of ACS and myocarditis in young patients presenting with CP and elevated cardiac biomarkers to the ED and to determinate the differences in their clinical presentation. Methods: Retrospective study of all consecutive patients < 40 years old admitted to our ED from January 2009 to June 2011 for CP with elevated serum troponin concentration. All clinical, angiographic and cardiac magnetic resonance (CMR) data from the local database was reviewed. Clinical follow-up was obtained to assess all cause mortality, myocardial infarction and re-hospitalisation for CP. Results: 1588 patients < 40 years old were admitted to the ED with chest pain. 49 (3%) patients presenting with an elevated troponin I (> 0.09ug/l) were included in the study. 32.7% (16/49) were diagnosed with ACS (11 STEMI and 5 NSTEMI) and 59.2% (29/49) with myocarditis. Among the 29 patients with myocarditis, 17 presented with typical subepicardial late enhancement on CMR and 12 were diagnosed based on clinical presentation (6 had no complementary workup, 3 normal coronary angiogram and 3 inconclusive CMR). 8.1% (4/49) of patients had other diagnoses. Compared to patients with myocarditis, ACS patients were older (34.1±3.9 vs 26.9±6.4, p=0.0002) with significantly more cardiovascular risk factors (mean 2.06 vs 0.69, p<0.0001). Diabetes (18.8% vs 0%, p=0.004), dyslipidemia (56.3% vs 3.4%, p=0.0001) and family history of coronary artery disease (CAD) (37.5% vs 10.3%, p=0.050) were significantly associated with ACS. No significant association was found for smoking, hypertension and obesity. Fever (>38°C) or recent viral illness were present in 75.9% (22/29) of patients with myocarditis, and in 0% of ACS patients. During follow-up (mean 19.9 months ± 8.6), only 2 patients with myocarditis were re-admitted for chest pain. Conclusions: In this study, 32.7% of patients < 40 year old admitted to an ED with CP and elevated troponin had an ACS. Key clinical factors include diabetes, dyslipidemia, family history of CAD, fever or recent viral illness, and may help to differentiate ACS from myocarditis.

Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

BACKGROUND This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7) in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13) did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12). The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere) and the affectation (or not) of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. METHODS The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories), Digits span (WISC-R verbal scale) and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74) years from surgery in CE group and at 6.47 (SD = 2.77) in CE+ group. RESULTS The Medulloblastoma group showed severe executive deficit (</= 1.5 SD below normal mean) in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category) and moderate to slight deficit in Stroop (word and colour) tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables. CONCLUSION Results suggest a differential prefrontal-like deficit due to cerebellar lesions and/or cerebellar-frontal diaschisis, as indicate the results in astrocytoma group (without treatments), that also can be generated and/or increased by treatments in the medulloblastoma group. The need for differential rehabilitation strategies for specific clinical groups is remarked. The results are also discussed in the context of the Cerebellar Cognitive Affective Syndrome.

A new rating scale to evaluate the potential benefit of therapeutic drug monitoring

Aims: Therapeutic Drug Monitoring (TDM) is an established tool to optimize thepharmacotherapy with immunosupressants, antibiotics, antiretroviral agents, anticonvulsantsand psychotropic drugs. The TDM expert group of the Association ofNeuropsychopharmacolgy and Pharmacopsychiatry recommended clinical guidelinesfor TDM of psychotropic drugs in 2004 and in 2011. They allocate 4 levelsof recommendation based on studies reporting plasma concentrations and clinicaloutcomes. To evaluate the additional benefit for drugs without direct evidence forTDM and to verify the recommendation levels of the expert group the authorsbuilt a new rating scale. Methods: This rating scale included 28 items and wasdivided in 5 categories: Efficacy, toxicity, pharmacokinetics, patient characteristicsand cost effectiveness. A literature search was performed for 10 antidepressants,10 antipsychotics, 8 drugs used in the treatment of substance related disordersand lithium, thereafter, a comparison with the assessment of the TDMexpert group was carried out. Results: The antidepressants as well as the antipsychoticsshowed a high and significant correlation with the recommendations inthe consensus guidelines. However, meanderings could be detected for the drugsused in the therapy of substance related disorders, for which TDM is mostly notestablished yet. The result of the antidepressants and antipsychotics permits aclassification of the reachable points; upper 13 - TDM strongly recommended10 to 13 - TDM recommended, 8 to 10 - TDM useful and below 8 - TDMpotentially useful. Conclusion: These results suggest this rating scale is sensitiveto detect the appropriateness of TDM for drug treatment. For those drugs TDM isnot established a more objective estimation is possible, thus the scoring helps tofocus on the most likely drugs to require TDM.

Altered adaptive but not veridical decision-making in substance dependent individuals.

Drug addiction is associated with impaired judgment in unstructured situations in which success depends on self-regulation of behavior according to internal goals (adaptive decision-making). However most executive measures are aimed at assessing decision-making in structured scenarios, in which success is determined by external criteria inherent to the situation (veridical decision-making). The aim of this study was to examine the performance of Substance Abusers (SA, n = 97) and Healthy Comparison participants (HC, n = 81) in two behavioral tasks that mimic the uncertainty inherent in real-life decision-making: the Cognitive Bias Task (CB) and the Iowa Gambling Task (IGT) (administered only to SA). A related goal was to study the interdependence between performances on both tasks. We conducted univariate analyses of variance (ANOVAs) to contrast the decision-making performance of both groups; and used correlation analyses to study the relationship between both tasks. SA showed a marked context-independent decision-making strategy on the CB's adaptive condition, but no differences were found on the veridical conditions in a subsample of SA (n = 34) and HC (n = 22). A high percentage of SA (75%) also showed impaired performance on the IGT. Both tasks were only correlated when no impaired participants were selected. Results indicate that SA show abnormal decision-making performance in unstructured situations, but not in veridical situations.

Chlamydia: signes d'appel, diagnostic et traitement [Chlamydia: diagnostic and treatment].

Chlamydia are obligate intracellular bacteria. Three species are considered human pathogens. Chlamydophila pneumoniae is one of the most common agents of atypical community-acquired pneumonia. Chlamydophila psittaci causes psittacosis, a severe zoonotic pneumonia transmitted by birds. Finally, Chlamydia trachomatis is the etiologic agent of trachoma and urogenital infections. The latter are commonly asymptomatic or paucisymptomatic. Thus, they may remain undiagnosed for years, leading to serious late complications such as salpingitis, ectopic pregnancy and infertility. Currently, the diagnosis of chlamydial infections is essentially based on molecular methods. Treatment should use an antibiotic with good intracellular bioavailability such as tetracycline, macrolides and new generation fluoroquinolones.

Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses.

The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1&#946; production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1&#946; processing. Moreover, the SEA component binds to the Dectin-2/FcR&#947; (Fc receptor &#947; chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1&#946; has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1&#946; levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1&#946; production and unravel a crucial role of Nlrp3 during S. mansoni infection.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-&#945;), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-&#945; and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.