Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

OBJECTIVES: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Delineation of cellular stages and identification of key proteins for reduction and biotransformation of Se(IV) by Stenotrophomonas bentonitica BII-R7.

The widespread use of selenium (Se) in technological applications (e.g., solar cells and electronic devices) has led to an accumulation of this metalloid in the environment to toxic levels. The newly described bacterial strain Stenotrophomonas bentonitica BII-R7 has been demonstrated to reduce mobile Se(IV) to Se(0)-nanoparticles (Se(0)NPs) and volatile species. Amorphous Se-nanospheres are reported to aggregate to form crystalline nanostructures and trigonal selenium. We investigated the molecular mechanisms underlying the biotransformation of Se(IV) to less toxic forms using differential shotgun proteomics analysis of S. bentonitica BII-R7 grown with or without sodium selenite for three different time-points. Results showed an increase in the abundance of several proteins involved in Se(IV) reduction and stabilization of Se(0)NPs, such as glutathione reductase, in bacteria grown with Se(IV), in addition to many proteins with transport functions, including RND (resistance-nodulation-division) systems, possibly facilitating Se uptake. Notably proteins involved in oxidative stress defense (e.g., catalase/peroxidase HPI) were also induced by Se exposure. Electron microscopy analyses confirmed the biotransformation of amorphous nanospheres to trigonal Se. Overall, our results highlight the potential of S. bentonitica in reducing the bioavailability of Se, which provides a basis both for the development of bioremediation strategies and the eco-friendly synthesis of biotechnological nanomaterials.

INRS activities on risk assessment of glycol ethers.

The occupational exposure assessment uses data from published sources, from Industry (most often from the producers), and from dedicated occupational exposure data bases, as well as evaluations using the EASE model (Estimation and Assessment of Substance Exposure). Atmospheric concentrations and characteristics of skin contacts are evaluated in different scenarios (such as manufacturing, formulating, main and most polluting uses) and sub-scenarios (e.g. warm water dilution). Air concentrations of EGBE are low during production (most often <0.5 mg/m(3)), incidental excursions being <50 mg/m(3); the "worst-case" mean concentration is proposed as 9 mg/m(3). Skin contact, according to EASE, may be in the range of 0-0.1 mg/cm(2)(day), and should be mitigated by the use of suitable gloves. For formulations of products containing EGBE, air concentrations are evaluated as 10 mg/m(3) and skin contact as 0.19 mg/cm(2)(day). The "reasonable worst case" air concentrations (8-Hr TWA) are assessed at around 11 mg/m(3) (coating industry), from 5 to 20 mg/m(3) in printing activities (depending on the task), and in the 20-70 mg/m(3) range (upper limit 40 mg/m(3) in better controlled situations) for cleaning activities. Skin contact would be around twice the preceding level, i.e., 0.4 mg/cm(2)(day) for coating as well as cleaning activities. EGBE and its major metabolites, 2-butoxyacetaldehyde (2-BAL) and 2-butoxyacetic acid (2-BAA) have been subjected to tests for genetic toxicity tests both in vitro and in vivo. While some positive responses have been obtained, the balance of the evidence indicates that EGBE does not express significant genotoxic activity. There are no epidemiological data investigating a relationship between exposure to EGBE and human cancer. Two carcinogenicity inhalation bioassays have been conducted in rodents, one in rats and one in mice. Significant increases were found in forestomach tumours in female mice and haemangiosarcomas in male mice. No increases in tumour incidences were found in either male or female rats. Mechanistic studies have suggested the crucial involvement in the pathogenesis of haemangiosarcomas of a chain of events consisting of (1) haemolysis due to BAA, followed by (2) hepatic haemosiderin deposition and (3) the subsequent generation of reactive oxygen species within the endothelial cells from which haemangiosarcomas arise. Since human erythrocytes are particularly resistant to the haemolytic effects of BAA, it is extremely unlikely, according to this model, that the haemangiosarcomas observed in male mice will have human significance. Similarly, mechanistic studies on the female mouse forestomach tumours have suggested that these also are not important as an indication of human risk. In vivo, EGBE tested in a continuous breeding study and in repeated dose toxicity tests, did not produced specific effects on reproductive organs or fertility parameters. For developmental toxicity, rats, mice and rabbits were dosed via oral and/or inhalation routes. Foeto- and embryo-toxicity was observed in presence or maternal toxicity (haemolytic anaemia). The data available give plausible support to the hypothesis that this developmental toxicity is a direct consequence of maternal toxicity. There are no epidemiological data investigating a relationship between exposure to EGBE alone and human reproductive effects.

Functional MR evaluation of temporal and frontal language dominance compared with the Wada test.

OBJECTIVE: To evaluate the reliability of temporal and frontal functional MRI (fMRI) activation for the assessment of language dominance, as compared with the Wada test. PATIENTS AND METHODS: Ten patients with temporal lobe epilepsy were studied using blood oxygen level dependent fMRI and echoplanar imaging (1.5-T). Three tasks were used: semantic verbal fluency, covert sentence repetition, and story listening. Data were analyzed using pixel by pixel autocorrelation and cross-correlation. fMRI laterality indices were defined for several regions of interest as the ratio (L - R)/(L + R), L being the number of activated voxels in the left hemisphere and R in the right hemisphere. Wada laterality indices were defined as the difference in the percentages of errors in language tests between left and right carotid injections. RESULTS: Semantic verbal fluency: The asymmetry of frontal activation was correlated with Wada laterality indices. The strongest correlation was observed in the precentral/middle frontal gyrus/inferior frontal sulcus area. Story listening: The asymmetry of frontal, but not temporal, activation was correlated with Wada laterality indices. Covert sentence repetition: No correlation was observed. CONCLUSIONS: There was a good congruence between hemispheric dominance for language as assessed with the Wada test and fMRI laterality indices in the frontal but not in the temporal lobes. The story listening and the covert sentence repetition tasks increased the sensitivity of detection of posterior language sites that may be useful for brain lesion surgery.

Is the underlying cause of epilepsy a major prognostic factor for recurrence?

BACKGROUND: We investigated the prognostic value of the type of epilepsies and epileptic syndromes for seizure recurrence. In patients with partial epilepsy, we focused on the prognostic value of any structural brain abnormality and of the location of the epileptogenic region. METHODS: A total of 2,200 adult outpatients were included in a hospital-based observational survey, with a follow-up of 1 to 7 years. Twenty-two percent of the patients exhibited generalized epilepsy, 62% partial epilepsy, and 16% undetermined epilepsy. RESULTS: Seizure control (>1 year without seizure) was achieved in 82% of patients who had idiopathic generalized epilepsy, 35% of those with symptomatic partial epilepsy, 45% of those with cryptogenic partial epilepsy, and 11% of those with partial epilepsy associated with hippocampal sclerosis (HS). Temporal lobe epilepsy (TLE) was the most refractory partial epilepsy, with only 20% of such patients remaining seizure free, compared with 36% of extra-TLE patients. In partial epilepsy, HS, cerebral dysgenesis, and dual pathology (HS and another lesion) were associated with a low rate of seizure-free patients (11%, 24%, and 3%, respectively). No significant difference in seizure control was found between patients with extra-TLE and those with TLE and no HS. CONCLUSIONS: In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.

A homogeneous caspase-3 activity assay using HTRF technology.

Caspases are cysteine proteases presenting a conserved active site that cleaves protein substrates at a highly specific position. They are involved in different aspects of the active cell death pathway. Most of them act through proteolytic degradations of cellular components. This paper describes the assay development, assay validation, and screening for inhibitors of this enzyme, which could be potential drug candidates. The assay uses homogeneous time-resolved fluorescence based on energy transfer from europium cryptate as donor to cross-linked allophycocyanin as acceptor (XL665). A double-tagged substrate, biotinyl-epsilon-aminocaproyl-L-aspartyl-L-glutamyl-L-valyl-Laspartyl-L-alanyl-L-propyl-N(epsilon)-(2,4-dinitrophenyl)-L-lysine-amide (biotin-X-DEVDAPK(dnp)-NH(2)), is conjugated with streptavidin cryptate and anti-dnp-XL665 monoclonal antibody. The close proximity between donor and acceptor induces a specific time-resolved fluorescence signal. In the presence of enzyme activity, the substrate cleavage induces an unlinking of the two fluorescent probes and, subsequently, the disappearance of the specific signal as a result of loss of proximity. Experiments to optimize the reagent concentration, incubation times, precision, reproducibility, and robustness are discussed in comparison with a fluorometric method.

Fast solid support detection of human papillomavirus in in vitro amplified DNA using a DNP-anti DNP monoclonal antibody couple.

In some anogenital lesions the detection of certain types of human papilloma virus, especially oncogenic types, is of interest. In a first step during a prospective study, we compared two methods for the detection of human papillomavirus (HPV) DNA in clinical samples: Southern blotting followed by hybridization with a cloned radioactive genomic probe and a classical polymerase chain reaction (PCR) followed by hybridization with a 32P-labelled oligonucleotide probe. 118 biopsies and swabs were examined for HPV 6/11, 16, 18 and 33, 67 positive reactions were found by both methods, 5 positives only by PCR and 2 positives only by Southern blot for unidentified HPV. Patients with anogenital condylomas, dysplasias and carcinomas or asymptomatic patients were studied. Most high grade (II and III) dysplasias were associated with HPV 16 and HPV 18. Condylomata lesions and low grade dysplasia (grade I) were associated mostly with HPV 6/11, mixed type of HPV, less frequently with HPV 16 or HPV 18. As a second step a nested PCR coupled to solid support detection method was used as described by Sauvaigo et al. (1990) Nucleic Acids Res. 18, 3175-3183) to study a panel of 30 previously qualified different HPV DNA extracts. In this procedure the second round of PCR amplification involves biotinylated and dinitrophenylated labelled primers allowing the capture of PCR amplified HPV DNA sequences on streptavidin coated tubes and its revelation. We describe an improvement of HPV DNA detection by means of single-step immunoenzymatic revelation involving anti-DNP monoclonal antibodies conjugated to horseradish peroxidase enzyme. A perfect correlation with the previous results was obtained. This solid support method allows a faster and easier HPV typing compared to methods using membrane transfer.

Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias.

Specificity of memory deficits after right or left temporal lobectomy.

An impairment of verbal memory has consistently been associated with resection of the left dominant temporal lobe, whereas non-verbal memory deficits have been less reliably observed following resection of the right temporal lobe. Such a dissociation may be due to material-specific differences of processing between verbal and non-verbal information. Alternatively, the influence of the left and right limbic structures may vary according to the stage of memory processing. The aim of the study was to test these hypotheses by comparing verbal and spatial learning in patients with left or right temporal lobe resection for intractable epilepsy, using verbal and visuospatial memory tasks with the same design: control of encoding, multiple trial learning, free and cued recall, short and long delays. The results showed: (1) a similar pattern of learning and recall in the two groups; (2) a higher performance in spatial learning for patients with left temporal lobe resection and in verbal learning for patients with right temporal lobe resection; (3) material-specific effects characterized by a higher sensitivity to cues in the verbal domain and a better retention of information during delays in the spatial domain. These results suggest parallel processing of the two temporal lobes at the various memory stages, rather than an interaction between memory stage and side of the lesion similar to that already proposed for the frontal lobes. They also confirm a double dissociation between verbal/spatial information processing and side of temporal lobe resection.

Europium cryptate labeled deoxyuridine-triphosphate analog: synthesis and enzymatic incorporation.

The synthesis of an europium tris-bipyridine cryptate labeled 2'-deoxyuridine-5 '-triphosphate analog (K-11-dUTP) is described. This labeled triphosphate was incorporated into DNA through enzymatic reactions with terminal transferase and DNA polymerases. The enzymatic reactions were monitored by TRACE (Time Resolved Amplification of Cryptate Emission), a homogeneous method using Fluorescence Resonance Energy Transfer (FRET) from an europium cryptate as donor to a modified allophycocyanine as acceptor.

[Lansoprazole versus ranitidine in the prevention of early recurrences of digestive hemorrhages from gastroduodenal ulcers. Randomized double-blind multicenter study]. / Lansoprazole versus ranitidine dans la prévention des récidives précoces des hémorragies digestives ulcéreuses gastro-duodénales. Etude multicentrique randomisée en double aveugle.

Strong inhibition of acid secretion could be able to decrease gastric and duodenal ulcer early rebleeding. OBJECTIVE--The aim of this double blind randomized trial was to compare early rebleeding rates of 2 groups of patients treated with ranitidine (600 mg/day) or lansoprazole (60 mg/day) per os for 6 consecutive days. METHODS--Seventy five patients with a high risk of rebleeding (clinical and endoscopical criteria) were included in this trial. These ulcers were Ia (n = 10), Ib (n = 20), IIa (n = 13), IIb (n = 32) in Forrest classification. RESULTS--Nineteen out of 75 patients rebled (25.3%): 11 out of 37 (30%) and 8 out of 38 (21%) in the ranitidine and lansoprazole groups respectively. Rates of rebleeding were 10%, 12.5%, 36% and 29% respectively in the ulcers grade Ia (previously treated with endoscopic sclerosis), Ib, IIa and IIb in the Forest classification. CONCLUSION--The rates of rebleeding were not statistically different in the 2 groups of treatment. The high rebleeding rates observed with Forrest IIa and IIb and duodenal ulcers support the need of haemostatic endoscopic therapy associated to antisecretory treatment in such patients.

[Experience in mass screening of breast cancer with mammography in France]. / Les expériences de dépistage de masse du cancer du sein par mammographie en France. Un protocole commun d'évaluation.

In the framework of the National Fund for Prevention, Health Education and Information, the setting-up in France, on an experimental basis, of mass breast cancer screening programs by mammography in ten departments leads to suggest a common protocol for the evaluation of these programs, before an eventual generalization to the whole country. These programs are based on common principles: local screening based on existing medical facilities, single view mammography with double reading. However, the screening organisation is different in each department according to the target population, the screening interval, the mode of invitation, the methods for arranging double reading, etc. The purpose of this article is to report on the work of the evaluation group of the ten programs, and to propose a methodology for comparing the screening experiences in order to measure the role of the organisation methods. It gives definitions and modes of calculations for the evaluation criteria in four fields: impact, quality, efficacy and cost (with details about the feasibility of data collection) and proposes a reflection on analysis techniques in order to develop an optimum mass screening strategy.

[Study of hemispheric lateralization of language regions by functional MRI. Validation with the Wada test]. / Etude de latéralisation hémisphérique des aires du langage en IRM fonctionnelle. Validation par le test de Wada.

Language hemispheric dominance can be assessed by the Wada test before temporal lobectomy, in patients with refractory epilepsy of the mesial temporal lobe. Functional MR is a less invasive technique which recently demonstrated the ability to localize some language areas. The aim of this study was to determine if functional MR can be substituted to the Wada test in the determination of language dominance. Seven patients with a refractory epilepsy of the mesial temporal lobe were included. The MR protocol was carried out using a 1.5 T system including 12 axial gradient echo BOLD EPI images. A semantic fluency task, interspersed with rest periods, was used as activation paradigm. An activation of middle and inferior frontal region was found in all patients. It predominated in the left hemisphere in 6 cases and in the right hemisphere in 1 case. The hemispheric and frontal lobe lateralization of the functional MR activation was correlated with the hemispheric language dominance as assessed by the Wada test. In conclusion, functional MR is a promising technique in the determination of language dominance.

[Mass screening programs for breast cancer in France. Comparative evaluation]. / Les programmes de dépistage de masse du cancer du sein en France. Evaluation comparative.

OBJECTIVE: The purpose of this work was to comparatively assess the results of mass screening programs for breast cancer implemented in six French departments in 1986, within the scope of the National Fund for Health Prevention, Education and Information of the National Health Insurance Office of Salaried Workers. MATERIAL AND METHODS: The data collected by the screening centres were analyzed by ten assessment teams that were independent from the program promotion staff, all using the same evaluation form. A complementary population study performed in eight French districts then, allowed assessing the frequency of self-referred screening (mammography performed out of program). RESULTS: The rate of participation in screening programs, in relation to the invited population, ranged from 21 to 48%, according to the district (36% in average). This low participation was probably related to the extent of self-referred screening. In fact, 19 to 40% of women, according to the district, had previously had a screening mammographic coverage: rate was around 68% in women aged 50 to 69 years. Positive findings with mammography ranged from 4.5 to 15.8% (10.1% in average), while intervention rates ranged from 0.7 to 1.6% and detection rates from 3.8 to 6.2%. The ratio between benign tumors and cancers ranged from 0.7 to 2.1 according to the district. In order to enlighten the judgement on French results, we propose a comparison with the international standards in force. CONCLUSION: The various experiences with breast cancer screening in France show that this screening is technically feasible on the basis of existing medical structures. However, some criteria are still below the expected values, especially if compared with international standards. This result is probably accounted for by the high rate self-referred screening before age 40 in France. In these conditions, the question is whether extending breast cancer screening programs in France is an appropriate course of action.

[Acute necrotizing enterocolitis during a prolonged treatment with neuroleptics]. / Entérocolite aiguë nécrosante au cours d'un traitement prolongé par neuroleptiques.

A 32-year old man treated for several years with phenothiazine for chronic psychosis developed acute necrotizing colitis. The causal relationship with neuroleptics was reinforced by the absence of any other treatment and by histological findings including extensive mucosal necrosis without stenotic lesion and without mesenteric vessels alteration. The patient required emergency total colectomy and was discharged after 7 weeks of hospitalisation in the intensive care unit.

[Irritation and allergy to acrylates and methacrylates. - Part I: Common monoacrylates and monomethacrylates (author's transl)]. / Irritation et allergie aux acrylates et méthacrylates. Première partie. Monoacrylates et monométhacrylates simples.

Acrylates and methacrylates are industrial chemicals with insufficiently known irritating and allergenic effects. In this paper, the simple monoacrylates and monomethacrylates are considered. Methyl acrylate is an irritant, giving a reaction in 10 out of 30 patients, when tested at 20 p. 100 in olive oil. It is also an allergen (2 out of 22 cases). Because of its irritating properties, the concentration of 2 p. 100 is proposed for allergeric investigations. Methyl methacrylate, at 20 p. 100 in olive oil, is not an irritant for humans, although we have observed a sensitization rate of about 15 p. 100 with an undiluted product. In animal studies (technic of Kligman and Magnusson), 10 p. 100 of the subjects reacted to a working concentration of 1 p. 100 in petrolatum (allergenicity degree II). A risk of sensitization due to test repetition exists, about 9 p. 100 and 15 p. 100 for methyl acrylate (20 p. 100) and undiluted methyl methacrylate, respectively. For the latter, sensitization appears around the 16 th-18th day and may be preceeded by an irritation (1 out of 3 cases). Allyl acrylate and allyl methacrylate are irritants which should be studied at a concentration of about 0,1 p. 100. A 5 p. 100 concentration in olive oil seems appropriate for studying allergies to the following monoacrylates and monomethacrylates: acrylamide and acrylonitrile, n-butyl, cyclohexyl, ethyl, ethyl-2-hexyl, ethoxy-2-ethyl, phenyl acrylates, cyclohexyl dodecyl, ethyl-2-hexyl, ethoxy-2-ethyl, methyl methacrylates.

[Irritation and allergy to acrylates and methacrylates. - Part II: Polyfunctional acrylic monomers (author's transl)]. / Irritation et allergie aux acrylates et mèthacrylates. Deuxième partie. Monomères acryliques polyfonctionnels.

Acrylates and methacrylates are industrial chemicals with insufficiently known irritating and allergic effects. After considering simples monoacrylates and monomethacrylates, this paper deals with the n-ethyleneglycol acrylates and methacrylates and some polyol polyacrylates and polymethacrylates. All of the diacrylates tested are irritants for humans at 3 p. 100 in olive oil but there is no irritation at 0,1 p. 100. Monomethacrylate and dimethacrylate are not irritants at 3 p. 100 in olive oil. Studies with animals confirm that diacrylates are more irritating than dimethacrylates and the Magnusson and Kligman method shows that the substances induce delayed hypersensitivity. Cross reactions were observed in homogeneous series (diacrylates or dimethacrylates) but not between series. These results are in good agreement with clinical observations. The irritating power of 5 polyacrylates and polymethacrylates of other polyols were tested in animals. For some of them, clinical observations indicate an allergic potential.