Intestinal Conventional Ultrasonography, Contrast-Enhanced Ultrasonography and Magnetic Resonance Enterography in Assessment of Crohn's Disease Activity: A Comparison with Surgical Histopathology Analysis.

BACKGROUND AND AIMS: Contrast-enhanced ultrasonography (CEUS) is a potential interesting method for assessing accurately Crohn's disease (CD) activity. We compared the value of intestinal ultrasonography (US) coupled with contrast agent injection with that of magnetic resonance enterography (MRE) in the assessment of small bowel CD activity using surgical histopathology analysis as reference. METHODS: Seventeen clinically active CD patients (14 women, mean age 33 years) requiring an ileal or ileocolonic resection were prospectively enrolled. All performed a MRE and a US coupled with contrast agent injection (CEUS) less than 8 weeks prior to surgery. Various imaging qualitative and quantitative parameters were recorded and their respective performance to detect disease activity, disease extension and presence of complications was compared to surgical histopathological analysis. RESULTS: The median wall thickness measured by US differed significantly between patients with non-severely active CD (n = 5) and those with severely active CD (n = 12) [7.0 mm, IQR (6.5-9.5) vs 10.0 mm, IQR (8.0-12.0), respectively; p = 0.03]. A non-significant trend was found with MRE with a median wall thickness in severe active CD of 10.0 mm, IQR (8.0-13.7) compared with 8.0 mm, IQR (7.5-10.5) in non-severely active CD (p = 0.07). The area under the ROC curve (AUROC) of the wall thickness assessed by US and MRE to identify patients with or without severely active CD on surgical specimens were 0.85, 95% CI (0.64-1.04), p = 0.03 and 0.80, 95% CI (0.56-1.01), p = 0.07, respectively. Among the parameters derived from the time-intensity curve during CEUS, time to peak and rise time were the two most accurate markers [AUROC = 0.88, 95% CI (0.70-1.04), p = 0.02 and 0.86, 95% CI (0.68-1.04), p = 0.03] to detect patients with severely active CD assessed on surgical specimens. CONCLUSION: The accuracy of intestinal CEUS is close to that of conventional US to detect disease activity. A thickened bowel and shortened time to peak and rise time were the most accurate to identify CD patients with severe histological disease activity.

Clarithromycin stops lung function decline in airway-centered interstitial fibrosis.

Airway-centered interstitial fibrosis (ACIF) is a distinct type of lung interstitial fibrosis characterized by lesions centered on the airways. Several cases reported in the literature showed little to no effect of corticosteroids and a high mortality rate in the absence of lung transplantation. No other efficient approach is described for the treatment of this type of fibrosis. We report for the first time the case of a 44-year-old patient diagnosed with ACIF on surgical lung biopsy and stabilized with clarithromycin after failure of systemic corticosteroids. We need to confirm this benefit in other patients to ascertain the anti-inflammatory effect of macrolides, which are far less harmful compared to corticosteroids or immunosuppressant drugs.

Advanced nitrogen removal from anaerobically pre-treated potato wastewater via partial nitritation-anammox in a continuous fed SBR.

Partial nitritation-anammox was carried out successfully in a continuous fed Sequencing Batch Reactor (cf-SBR), composed of 3 compartments operated in continuous mode. The reactor was operated with floccular biomass (flocs) and biofilm to remove nitrogen from the anaerobic effluent from the potato industry at different nitrogen loading rates (0.16 g TN L-1 d-1 - 0.8 g TN L-1 d-1). At the maximum nitrogen loading rate (NLR) evaluated the nitrogen removal and ammonia oxidation achieved were 62% and 74% respectively. During the evaluation of the NLR, it was observed an improvement of the characteristics of the sludge, improving the Sludge Volumetric Index (SVI) from 228 to 63 mL g-1 MLSS. Moreover, molecular analysis (qPCR) confirmed the presence of anammox bacteria on the flocs and in the biofilm from the cf-SBR. The results showed the capability of the reactor to carry out the partial nitritation-anammox in the same reactor at pilot scale. The cf-SBR was presented as a suitable and feasible technology for advanced nitrogen removal under partial nitritation and anammox conditions.

Predictors of depression in multiple sclerosis patients.

Depression is one of the major problems associated with multiple sclerosis (MS). Several physical and psychological factors tend to interact and make it difficult to pinpoint the predictors of the depression. It seemed particularly important to examine how anxiety and illness evolution (characterized by the functional status) influence the appearance of depression symptoms. Thus, the aim of this article was to clarify the relationship between depression and the factors associated with it. One hundred and fifteen participants living at home recruited through various associations and MS clinics answered socio demographic, medical and psychological questions and questionnaires (depression, anxiety, coping, social support, locus of control, alexithymia, self-esteem). Results show that functional status (EDSS), trait anxiety, alexithymia and satisfaction with social support system are the predicting factors of depression. Trait anxiety and functional status are two predictors that independently and simultaneously lead to the appearance of depression symptoms, with trait anxiety playing a predominant role. Alexithymia and social support indirectly influence the appearance of these symptoms.

Characterization of a Multiple-Scan-Rate Voltammetric Waveform for Real-Time Detection of Met-Enkephalin.

Opioid peptides are critically involved in a variety of physiological functions necessary for adaptation and survival, and as such, understanding the precise actions of endogenous opioid peptides will aid in identification of potential therapeutic strategies to treat a variety of disorders. However, few analytical tools are currently available that offer both the sensitivity and spatial resolution required to monitor peptidergic concentration fluctuations in situ on a time scale commensurate with that of neuronal communication. Our group has developed a multiple-scan-rate waveform to enable real-time voltammetric detection of tyrosine containing neuropeptides. Herein, we have evaluated the waveform parameters to increase sensitivity to methionine-enkephalin (M-ENK), an endogenous opioid neuropeptide implicated in pain, stress, and reward circuits. M-ENK dynamics were monitored in adrenal gland tissue, as well as in the dorsal striatum of anesthetized and freely behaving animals. The data reveal cofluctuations of catecholamine and M-ENK in both locations and provide measurements of M-ENK dynamics in the brain with subsecond temporal resolution. Importantly, this work also demonstrates how voltammetric waveforms can be customized to enhance detection of specific target analytes, broadly speaking.

Radiology residents' skill level in chest x-ray reading.

RATIONALE AND OBJECTIVES: To evaluate the mean skill level of radiology residents in chest X-ray (CXR) reading, with regard to cognitive mechanisms involved in this task and to investigate for potential factors influencing residents' skill. MATERIALS AND METHODS: Eighty-one residents were evaluated through a test set including CXR expected to mobilize detection skills (n=10), CXR expected to mobilize interpretation skills (n=10) and normal CXR (n=4). For each radiograph, residents were asked to answer three questions: Does this radiograph show normal or abnormal findings? Does it require complementary computed tomography study? What is your diagnosis? Residents' answers were evaluated against an experts' consensus and analyzed according to year of residency, attendance at CXR training course during residency and the average number of CXR read per week. RESULTS: Residents' mean success rate was 90.4%, 76.6% and 52.7% for the three questions, respectively. Year of residency was associated with better diagnostic performances in the detection CXR category (P=0.025), while attendance at CXR training course was associated with better performances in the interpretation CXR category (P=0.031). There was no influence of the number of CXR read per week. CONCLUSION: These results may suggest promoting systematic CXR theoretical training course in the curriculum of radiology residents.

Radiofrequency ablation of stage IA non-small cell lung cancer in patients ineligible for surgery: results of a prospective multicenter phase II trial.

BACKGROUND: A prospective multicenter phase II trial to evaluate the survival outcomes of percutaneous radiofrequency ablation (RFA) for patients with stage IA non-small cell lung cancer (NSCLC), ineligible for surgery. METHODS: Patients with a biopsy-proven stage IA NSCLC, staging established by a positron emission tomography-computed tomography (PET-CT), were eligible. The primary objective was to evaluate the local control of RFA at 1-year. Secondary objectives were 1- and 3-year overall survival (OS), 3-year local control, lung function (prior to and 3 months after RFA) and quality of life (prior to and 1 month after RFA). RESULTS: Of the 42 patients (mean age 71.7 y) that were enrolled at six French cancer centers, 32 were eligible and assessable. Twenty-seven patients did not recur at 1 year corresponding to a local control rate of 84.38% (95% CI, [67.21-95.72]). The local control rate at 3 years was 81.25% (95% CI, [54.35-95.95]). The OS rate was 91.67% (95% CI, [77.53-98.25]) at 1 year and 58.33% (95% CI, [40.76-74.49]) at 3 years. The forced expiratory volume was stable in most patients apart from two, in whom we observed a 10% decrease. There was no significant change in the global health status or in the quality of life following RFA. CONCLUSION: RFA is an efficient treatment for medically inoperable stage IA NSCLC patients. RFA is well tolerated, does not adversely affect pulmonary function and the 3-year OS rate is comparable to that of stereotactic body radiotherapy, in similar patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01841060 registered in November 2008.

Lack of GSK3ß activation and modulation of synaptic plasticity by dopamine in 5-HT1A-receptor KO mice.

Psychiatric disorders are associated with excitation-inhibition (E-I) balance impairment in the prefrontal cortex. However, how the E-I balance is regulated is poorly known. The E-I balance of neuronal networks is linked to the action of numerous neuromodulators such as dopamine and 5-HT. We investigated the role of D2-receptors in tuning the E-I balance in a mouse model of anxiety, the 5-HT1A-receptor KO mice. We focused on synaptic plasticity of excitation and inhibition on layer 5 pyramidal neurons. We show that D2-receptor activation decreases the excitation and favors HFS-induced LTD of excitatory synapses via the activation of GSK3ß. This effect is absent in 5-HT1A-receptor KO mice. Our data show that the fine control of excitatory transmission by GSK3ß requires recruitment of D2-receptors and depends on the presence of 5-HT1A-receptors. In psychiatric disorders in which the number of 5-HT1A-receptors decreased, therapies should reconsider how serotonin and dopamine receptors interact and control neuronal network activity.

Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey.

BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period. RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients. CONCLUSION: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.

[Outpatient management of pulmonary embolism diagnosed in emergency services]. / Prise en charge ambulatoire de l'embolie pulmonaire diagnostiquée aux urgences.

In the emergency department, the management of patients with pulmonary embolism depends on the early mortality risk. Outpatient care is possible in low-risk patients. We present the existing scores and the strategy proposed by the North Alps Emergency Network, which uses the simplified PESI score (Pulmonary Embolism Severity Index) to select those low-risk patients, candidates for early discharge.

Signal transfer in passive dendrites with nonuniform membrane conductance.

In recent years it became clear that dendrites possess a host of ion channels that may be distributed nonuniformly over their membrane surface. In cortical pyramids, for example, it was demonstrated that the resting membrane conductance G(m)(x) is higher (the membrane is "leakier") at distal dendritic regions than at more proximal sites. How does this spatial nonuniformity in G(m)(x) affect the input-output function of the neuron? The present study aims at providing basic insights into this question. To this end, we have analytically studied the fundamental effects of membrane non-uniformity in passive cable structures. Keeping the total membrane conductance over a given modeled structure fixed (i.e., a constant number of passive ion channels), the classical case of cables with uniform membrane conductance is contrasted with various nonuniform cases with the following general conclusions. (1) For cylindrical cables with "sealed ends," monotonic increase in G(m)(x) improves voltage transfer from the input location to the soma. The steeper the G(m)(x), the larger the improvement. (2) This effect is further enhanced when the stimulation is distal and consists of a synaptic input rather than a current source. (3) Any nonuniformity in G(m)(x) decreases the electrotonic length, L, of the cylinder. (4) The system time constant tau(0) is larger in the nonuniform case than in the corresponding uniform case. (5) When voltage transients relax with tau(0), the dendritic tree is not isopotential in the nonuniform case, at variance with the uniform case. The effect of membrane nonuniformity on signal transfer in reconstructed dendritic trees and on the I/f relation of the neuron is also considered, and experimental methods for assessing membrane nonuniformity in dendrites are discussed.

[Interpreting carbon monoxide transfer coefficient: significance and difficulties]. / Intérêts et difficultés d'interprétation du coefficient de transfert du CO (TLCO/VA).

INTRODUCTION: Interpreting measurements of carbon monoxide can be problematic. STATE OF THE ART: The transfer factor (TLCO) is usually calculated by multiplying the decrease in alveolar CO concentration between the beginning and the end of a 10 second breath hold (KCO) by the alveolar volume (VA). Thus a reduced TLCO may occur due to either a low KCO, a reduced VA, or a combination of both. PERSPECTIVES: A careful examination of KCO and VA will usually suggest a specific explanation for a reduction in TLCO. In restrictive lung diseases from extrapulmonary origin, TLCO is low but TLCO/VA [[/INF 120% of the reference values. In interstitial lung disease, the value of TLCO/VA depends on whether the loss of lung units is diffuse or not, and probably also on the status of the microcirculation. In airflow obstruction, a low VA is caused by uneven distribution of inspired He/CO mixture within the breath-hold time. CONCLUSIONS: The transfer factor for carbon monoxide is best interpreted in terms of its components, alveolar volume and carbon monoxide transfer coefficient.

Regulation of glucose transporters in cultured rat adipocytes: synergistic effect of insulin and dexamethasone on GLUT4 gene expression through promoter activation.

A triggering effect of insulin on GLUT4 expression in adipocytes is consistently observed in vivo, whereas GLUT1 is roughly unaffected. However, in cultured rat adipocytes, insulin increases GLUT1 but fails to increase GLUT4, suggesting that additional factors are involved in vivo. This prompted us to evaluate the potential role of glucocorticoids as coregulators with insulin of glucose transporter expression using 3T3-F442A adipose cells and primary cultured rat adipocytes. In both systems, insulin increased and dexamethasone decreased GLUT1 messenger RNA (mRNA) and protein, an effect inhibited by the glucocorticoid antagonist RU 38486. When the two hormones were added together, the effect of dexamethasone was dominant in 3T3-F442A cells, but was totally antagonized in rat adipocytes. Moreover, in rat adipocytes, the GLUT1 gene transcription rate (run-on) was identical in the absence or presence of the two hormones. With regard to GLUT4 expression, neither insulin nor dexamethasone alone had any significant effect after 2 days of treatment. In contrast, the combined hormones markedly increased GLUT4 mRNA (+550% in rat adipocytes; +130% in 3T3-F442A cells) and protein (+164% in rat adipocytes; +79% in 3T3-F442A cells) with a 24- to 48-h delay after mRNA induction. Studies of the molecular mechanism(s) showed that exposure of rat adipocytes to dexamethasone plus insulin did not affect GLUT4 mRNA stability, but increased the GLUT4 gene transcription rate 3-fold. Transient transfections of rat adipocytes with the 5'-flanking 2.2-kilobase sequence of the rat GLUT4 gene fused to luciferase demonstrated that promoter activity was unchanged by insulin, increased 50% by dexamethasone, and increased 3-fold in the presence of both. These data show that insulin elicits an increase in GLUT4 gene expression provided glucocorticoids are present. Our results indicate that the synergism between insulin and glucocorticoids on GLUT4 gene transcription is mediated through GLUT4 promoter activation.

Dynamics of host-parasite interactions: the example of population biology of the liver fluke (Fasciola hepatica).

Knowledge of the population dynamics of parasites and their hosts is essential to build veterinary and health programs. The example chosen is that of Fasciola hepatica, a food-borne trematode responsible for severe human and animal infections on the five continents. In this paper, we review the relationships between the liver fluke and its intermediate (mollusc) and definitive (vertebrate) hosts.

Immunohistochemistry of tryptophan hydroxylase in the rat brain.

An antiserum raised against tryptophan tetrahydropterine oxygen oxidoreductase was used to examine in rat brain the immunohistochemical localization of this rate-limiting enzyme catalysing the biosynthesis of serotonin. Tryptophan tetrahydropterine oxygen oxidoreductase was detected in numerous nerve cell bodies, proximal dendrites and axon varicosities or terminals corresponding to those of serotonin neurons as judged by their anatomical distribution and concomitant immunoreactivity to an antiserum against serotonin. In hypothalamus, a serotonin-containing nerve cell group previously visualized in the pars ventralis of the nucleus dorsomedialis by radioautography after serotonin uptake, and by serotonin immunohistochemistry after tryptamine loading, remained tryptophan tetrahydropterine oxygen oxidoreductase-unreactive even in rats treated with colchicine. On the other hand, a small group of tryptophan tetrahydropterine oxygen oxidoreductase-positive cells was identified in the rostrolateral portion of nucleus dorsomedialis, which could play a part in the intrinsic serotonin innervation of hypothalamus. There was no overlap between tryptophan tetrahydropterine oxygen oxidoreductase immunostaining and the cellular distribution of N-acetyl serotonin as reported in earlier studies. It is therefore likely that the synthesis of N-acetyl serotonin from tryptophan does not take place in N-acetyl serotonin-containing neurons.

Acrania: a manifestation of the Adams-Oliver syndrome.

A 10-year-old male with acrania, distal limb anomalies, and abnormal arterial and venous cranial blood vessels is reported. Parental films and examination are normal. This case supports the hypothesis that acrania is a severe form of aplasia cutis congenita and is within the spectrum of Adams-Oliver syndrome. It is proposed that the diagnosis of acrania requires assessment of both parents and proband to assess other manifestations of vascular disruption in order to provide accurate genetic counselling.

Robin sequence with facial and digital anomalies in two half-brothers by the same mother.

Two half-brothers by the same mother presented with the Robin sequence and facial and digital anomalies. The mother has a normal face and mild hyperopia without abnormality on radiographs of the hands, feet, and pelvis. The older son is 4 years and the younger is 6 months old. Both have normal psychomotor development. To the best of our knowledge this familial association has not been reported before and probably represents a previously unrecognized heritable malformation syndrome. The occurrence of the syndrome in 2 half-brothers by the same unaffected mother suggests X-linked recessive inheritance.

Mucolipidosis type IV: clinical manifestations and natural history.

The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV.

Adenylosuccinate lyase (ADSL) and infantile autism: absence of previously reported point mutation.

Autism is a heterogeneous neuropsychiatric syndrome of unknown etiology. There is evidence that a deficiency in the enzyme adenylosuccinate lyase (ADSL), essential for de novo purine biosynthesis, could be involved in the pathogenesis of certain cases. A point mutation in the ADSL gene, resulting in a predicted serine-to-proline substitution and conferring structural instability to the mutant enzyme, has been reported previously in 3 affected siblings. In order to determine the prevalence of the mutation, we PCR-amplified the exon spanning the site of this mutation from the genomic DNA of patients fulfilling DSM-III-R criteria for autistic disorder. None of the 119 patients tested were found to have this mutation. Furthermore, on preliminary screening using singlestrand conformation polymorphism (SSCP), no novel mutations were detected in the coding sequence of four ADSL exons, spanning approximately 50% of the cDNA. In light of these findings, it appears that mutations in the ADSL gene represent a distinctly uncommon cause of autism.

Presence of vasopressin, oxytocin and neurophysin in the retina of mammals, effect of light and darkness, comparison with the neuropeptide content of the neurohypophysis and the pineal gland.

Arginine vasopressin (AVP) and oxytocin (OT) as well as their CNS carrier neurophysins (Np) have been found in the pineal gland. In view of the analogy between the pineal gland and the retina, the contents of these neuropeptides in rat, human and bovine retinae were determined. AVP, OT and Np were detected by specific radioimmunoassay (RIA) and their presence confirmed by RIA measurements (1) in rat and human retinae on HPLC fractions and (2) by the detection of the C-terminal portion of the precursor to AVP and its associated Np = propressophysin (CPP). The AVP and OT content in the retina of the rat was modified by light: AVP and OT content was smaller at 2 a.m. than at 2 p.m., but was increased by a 7 day constant exposure to darkness. In contrast, pituitary content was decreased after 7 days of constant darkness. If one optic nerve was cut we observed a decrease in retinal AVP content compared to the contralateral side and a decrease in pituitary AVP content. Our data clearly demonstrated the presence of AVP, OT and Np in the retina and their variation induced by light. It is probable that these peptides are of central origin.