A prospective study of anal symptoms and continence among obese patients before and after bariatric surgery.

BACKGROUND: The effects of bariatric surgery on anal continence are not known. Data about proctologic lesions are very rare and do not include clinical data. The aim of this prospective study was to evaluate anal continence and anal lesions before and after sleeve gastrectomy (SG). METHODS: We prospectively included all patients presenting for bariatric surgery consultation at Bichat-Claude Bernard University Hospital, Paris, France, between 20 April 2015 and 16 December 2017. The patients were evaluated with questionnaires, anorectal manometry and clinical examination before SG (at enrollment) and between 12 and 24 months after (SG). Anal incontinence was defined as a Vaizey score above 4. RESULTS: Of 118 enrolled patients, 98 had SG. The patients were mostly women (n = 99, 84.6%). Median patient age was 45 years (IQR 34-54 years). The median follow-up period after surgery among the 86 patients who completed follow-up was 15 months (IQR 12.5-17.3 months). There was no significant change in the prevalence of anal incontinence after SG (12.8% preoperatively vs 24.4% postoperatively, p = 0.06). The median Vaizey score was 4 (IQR 4-4) both before and after SG (p = 0.1). No patient had de novo anal incontinence but worsening of anal incontinence was noted in 10 patients. Manometry revealed significantly lower median resting pressure (29 mmHg [IQR 22-68 mmHg] vs 22 mmHg [IQR 15-30 mmHg], p = 0.0015) and maximal squeeze pressure (IQR 29-74 mmHg vs IQR 30-60 mmHg, p = 0.0008) after SG. Anismus was more frequent after SG and was associated with constipation and Bristol type 1-2 stool consistency. Quality of life was unchanged. Proctologic lesions were rare and were present in 11 patients (12%) at enrollment and in 2 (2.4%) at follow-up. CONCLUSIONS: SG affected clinical anal continence but not significantly, and manometric measurements for anal pressures were lower postoperatively. Proctologic lesions were rare in this study population.

Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-A(k) NOD mice.

NOD.H2(k) and NOD.H2(h4) mice carry the major histocompatibility complex (MHC) class II molecule I-A(k) associated with susceptibility to experimentally induced thyroiditis. Dietary iodine-enhanced spontaneous thyroid autoimmunity, well known in NOD.H2(h4) mice, has not been investigated in NOD.H2(k) mice. We compared NOD.H2(h4) and NOD.H2(k) strains for thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) without or with dietary sodium iodide (NaI) for up to 32 weeks. TgAb levels were significantly higher in NOD.H2(h4) compared with NOD.H2(k) mice on NaI, and TPOAb developed in NOD.H2(h4) mice but not in NOD.H2(k) mice. DNA exome analysis revealed, in addition to the differences in the chromosome (Chr) 17 MHC regions, that NOD.H2(k) mice, and particularly NOD.H2(h4) mice, have substantial non-MHC parental DNA. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis highlighted thyroid autoimmunity and immune-response genes on Chr 17 but not on Chr 7, and 15 parental B10.A4R DNA. Studies of parental strains provided no evidence for non-MHC gene contributions. The exon 10 Tg haplotype, associated with experimentally induced thyroiditis, is absent in NOD.H2(h4) and NOD.H2(k) mice and is not a marker for spontaneous murine thyroid autoimmunity. In conclusion, the absence of I-E is a likely explanation for the difference between NOD.H2(h4) and NOD.H2(k) mice in TgAb levels and, as in humans, autoantibody spreading to TPO.

Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice.

Immunoregulatory T cells have been identified as key modulators of peripheral tolerance and participate in preventing autoimmune diseases. CD4(-)CD8(-) (double negative, DN) T cells compose one of these immunoregulatory T-cell subsets, where the injection of DN T cells confers protection from autoimmune diabetes progression. Interestingly, genetic loci defining the function and number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) coincide with at least some autoimmune disease susceptibility loci. Herein, we investigate the impact of major insulin-dependent diabetes (Idd) loci in defining the number of DN T cells. We demonstrate that although Idd3, Idd5 and Idd9 loci do not regulate DN T-cell number, NOD mice congenic for diabetes resistance alleles at the Idd13 locus show a partial restoration in DN T-cell number. Moreover, competitive and non-competitive bone marrow chimera experiments reveal that DN T-cell number is defined by a bone marrow-intrinsic, but DN T-cell-extrinsic, factor. This suggests that non-autonomous candidate genes define DN T-cell number in secondary lymphoid organs. Together, our results show that the regulation of DN T-cell number in NOD mice is at least partially conferred by alleles at the Idd13 locus.

Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells.

OBJECTIVES: In obesity, while hyperleptinemia highly correlates with excess fat mass, the status of gastric leptin remains unknown. Here, we investigated the expression of leptin in stomach biopsies of obese humans and analyzed the temporal changes of gastric leptin expression in response to diet-induced obesity and its impact on 5-hydroxytryptamine (5HT)-producing cells. METHODS: Enterochromaffin (EC) cells and expression of leptin, PAX4 (critical factor for EC specification), tryptophane hydroxylase-1 (TPH1, the peripheral rate-limiting enzyme for 5HT) and 5HT were examined by immunofluorescence, quantitative real-time PCR, radioimmunoassay, respectively, in stomach and duodenum biopsies from 19 obese and 14 normo-weighed individuals, and in mucosa scrapings from C57Bl6/J diet-induced obese mice, leptin-deficient ob/ob mice and intestine-specific leptin receptor isoform B-deficient mice. RESULTS: Gastric mucosa of obese subjects displays an increased expression of leptin (LEP mRNA by fivefold and protein by twofold, P<0.01), TPH1 ((1.75-2.73, 95% confidence interval (CI)) vs (0.38-0.67, 95% CI); P<0.01) and PAX4 ((1.33-2.11, 95%CI) vs (0.62-0.81, 95% CI); P<0.01) as compared with normo-weighed individuals. In diet-induced obese mice, the overexpressions of gastric leptin, antral Pax4, Tph1 and increased EC cell number occurred before the onset of obesity and hyperleptinemia (reflect of adipocyte leptin production). In addition, leptin deficiency was associated with reduced Pax4 mRNA, whereas oral leptin treatment enhanced both Tph1 and Pax4 mRNA. Finally, mice with an intestine-specific deletion of leptin signaling exhibit significant decrease in duodenal mucosa 5HT content. CONCLUSIONS: These data demonstrate that gastric leptin is upregulated in obese individuals. RESULTS from high-fat diet mice showed that overexpression of gastric leptin that is linked to gut '5HT pathway' occurred before the onset of obesity and expansion of fat mass. This may be relevant in the pathophysiology of obesity.

Identification and characterization of a novel HIV-1 nucleotide-competing reverse transcriptase inhibitor series.

Several groups have recently reported on the identification of nucleotide-competing reverse transcriptase inhibitors (NcRTIs), a new class of RT inhibitors. NcRTIs reversibly inhibit binding of the incoming nucleotide to the RT active site but do not act as chain terminators, unlike the nucleos(t)ide reverse transcriptase inhibitor (NRTI) class. We identified a novel benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI chemical series. Structure-activity relationship evaluation of this series with both RT and viral replication assays led to the identification of compound A, a new NcRTI. Compound A inhibited HIV-1 RT in a primer extension assay (50% inhibitory concentration, 2.6 nM) but had no measurable activity against human DNA polymerase γ at 10 µM. It potently inhibited HIV-1 replication in vitro (50% effective concentration, 1.5 nM). The antiviral potency of compound A was unaffected by the presence of nonnucleotide RT inhibitor (NNRTI) mutations tested (L100I, K103N/Y181C, V106A, or Y188L). Notably, viruses encoding K65R were hypersusceptible to inhibition by compound A. Compound A also retained full activity against viruses encoding M184V. In vitro selection for resistant virus to compound A led to the selection of a single substitution within RT: W153L. A recombinant virus encoding the RT W153L was highly resistant to compound A (fold change, 160). W153 is a highly conserved residue in HIV RT and has not been previously associated with drug resistance. In summary, a novel NcRTI series with optimized antiviral activity, minimal cross-resistance to existing RT inhibitor classes, and a distinct resistance profile has been discovered. These results further establish NcRTIs as an emerging class of antiretroviral agents.

How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder.

Parkinsonism, as a gradually progressive disorder, has a prodromal interval during which neurodegeneration has begun but cardinal manifestations have not fully developed. A systematic direct assessment of this interval has never been performed. Since patients with idiopathic REM sleep behaviour disorder are at very high risk of parkinsonism, they provide a unique opportunity to observe directly the development of parkinsonism. Patients with idiopathic REM sleep behaviour disorder in an ongoing cohort study were evaluated annually with several quantitative motor measures, including the Unified Parkinson's Disease Rating Scale, Purdue Pegboard, alternate-tap test and timed up-and-go. Patients who developed parkinsonism were identified from this cohort and matched according to age to normal controls. Their results on motor testing from the preceding years were plotted, and then assessed with regression analysis, to determine when markers first deviated from normal values. Sensitivity and specificity of quantitative motor markers for diagnosing prodromal parkinsonism were assessed. Of 78 patients, 20 developed parkinsonism. On regression analysis, the Unified Parkinson's Disease Rating Scale first intersected normal values at an estimated 4.5 years before diagnosis. Voice and face akinesia intersected earliest (estimated prodromal interval = 9.8 years), followed by rigidity (4.4 years), gait abnormalities (4.4 years) and limb bradykinesia (4.2 years). Quantitative motor tests intersected normal values at longer prodromal intervals than subjective examination (Purdue Pegboard = 8.6 years, alternate-tap = 8.2, timed up-and-go = 6.3). Using Purdue Pegboard and the alternate-tap test, parkinsonism could be detected with 71-82% sensitivity and specificity 3 years before diagnosis, whereas a Unified Parkinson's Disease Rating Scale score >4 identified prodromal parkinsonism with 88% sensitivity and 94% specificity 2 years before diagnosis. Removal of action tremor scores improved sensitivity to 94% and specificity to 97% at 2 years before diagnosis (cut-off >3). Although distinction between conditions was often difficult, prodromal dementia with Lewy bodies appeared to have a slower progression than Parkinson's disease (prodromal interval = 6.0 versus 3.8 years). Using a cut-off of Unified Parkinson's Disease Rating Scale >3 (excluding action tremor), 25% of patients with 'still-idiopathic' REM sleep behaviour disorder demonstrated evidence of possible prodromal parkinsonism. Therefore, using direct assessment of motor examination before parkinsonism in a REM sleep behaviour disorder, we have estimated a prodromal interval of ∼4.5 years on the Unified Parkinson's Disease Rating Scale; other quantitative markers may detect parkinsonism earlier. Simple quantitative motor measures may be capable of reliably detecting parkinsonism, even before a clinical diagnosis can be made by experienced movement disorders neurologists.

Dermatoglyphic asymmetries and fronto-striatal dysfunction in young adults reporting non-clinical psychosis.

OBJECTIVE: Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is known about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. METHOD: A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). RESULTS: Participants reporting DAPS (n = 16; 7.2%) and no-DAPS (n = 205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. CONCLUSION: The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder.

Variations in incubator temperature and humidity management: a survey of current practice.

AIM: To describe and assess routine procedures and practices for incubator temperature and humidity management in France in 2009. METHODS: A questionnaire was sent to all the 186 neonatal care units in France. RESULTS: The questionnaire return rate was 86%. Seventy-five per cent of the units preferred skin servo-control to air temperature control in routine practice. Air temperature control was mainly used for infants with a gestational age of more than 28 weeks and aged over 7 days of life. In general, thermal management decisions did not depend on the infant's age but were based on a protocol applied specifically by each unit. All units humidified the incubator air, but there was a large difference between the lowest and highest reported humidity values (45% and 100% assumed to be a maximal value, respectively). More than 65% of the units used a fixed humidity value, rather than a variable, protocol-derived value. CONCLUSION: We observed large variations in incubator temperature and humidity management approaches from one neonatal care unit to another. There is a need for more evidence to better inform practice. A task force should be formed to guide clinical practice.

Accuracy of computed tomographic colonography in a nationwide multicentre trial, and its relation to radiologist expertise.

OBJECTIVE: Reports on the accuracy of computed tomographic colonography (CTC) mainly involve series from expert institutions. The aims of this study were to assess CTC accuracy in a nationwide population and to relate it to radiologist performance in their initial training. DESIGN: Nationwide multicentre trial. SETTING: Twenty-eight radiologists, working in 26 mostly academic clinical units, were involved in the study after having attended a formal specialised 2-day training session on CTC. They worked through a training set of 52 cases with automatic feedback after an attempt at each case. PATIENTS: The study enrolled 845 patients with average and high risk of colorectal cancer, 737 of whom had both complete CTC and videocolonoscopy data, which constituted the dataset. INTERVENTIONS: Patients underwent same-day CTC followed by videocolonoscopy with segmental unblinding of CTC results. MAIN OUTCOME MEASURES: Sensitivity, specificity and positive and negative predictive values for detection of polyps ≥ 6 mm in per-patient and per-lesion analyses of CTC without computer-aided detection. RESULTS: Sensitivity, specificity and positive and negative predictive values for patients with polyps ≥ 6 mm were 69% (95% CI 61% to 77%), 91% (95% CI 89% to 94%), 67% (95% CI 59% to 74%) and 92% (95% CI 90% to 94%), respectively. Univariate analysis showed that the detection rate for polyps ≥ 6 mm was linked to neither radiologist case volume nor number of polyps, but was related to sensitivity achieved in the training set. Pooled sensitivity was 72% (95% CI 63% to 80%) versus 51% (95% CI 40% to 60%) for radiologists achieving above and below median sensitivity in the training set (61%), respectively. Multivariate analysis showed that sensitivity for polyps ≥ 6 mm in the training set was the only remaining significant predictive factor for subsequent performance. CONCLUSIONS: Radiologist sensitivity CTC for detection of polyps ≥ 6 mm in training was the sole independent predictor for subsequent sensitivity in detection of such polyps.

Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort.

BACKGROUND: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort. METHOD & RESULTS: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning. CONCLUSIONS: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

[Psychiatric symptoms of a paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis: A case report]. / Symptômes psychiatriques d'une encéphalite paranéoplasique à anticorps antirécepteurs NMDA : à propos d'un cas.

INTRODUCTION: We describe the case of a young woman affected by a benign ovarian teratoma with paraneoplastic encephalitis. Several cases have already been reported, but it is the first article that focuses on details of the psychiatric symptoms of this disorder. BACKGROUND: Paraneoplastic encephalitis usually begins with a prodromal phase, followed first by prominent psychiatric symptoms or, less frequently, short-term memory loss, seizure, catatonia-like symptoms, dyskynesias and, secondly, by autonomic instability and central hypoventilation requiring intensive care. In our case and to our knowledge, for the first time in the literature, the patient was hospitalized in a psychiatric unit for a suspected manic episode with psychotic features, in association with short-term memory impairment and anxiety. It has been shown that patients suffering from paraneoplastic encephalitis associated with ovarian teratoma display antibodies for anti-N-methyl-D-aspartate (NMDA) receptors in CSF or plasma (more specifically for the NR1 subunit of the NRl/NR2 heteromers required to form a functional NMDA receptor). The NR1/NR2B heteromers are preferentially expressed in the adult hippocampus/forebrain, which are brain regions involved in the pathogenesis of various psychiatric, psychotic in particular, symptoms. Furthermore, the glutamatergic NMDA receptors are the major mediator of excitotoxicity and their dysfunction had been associated with neurologic disorders, but also with schizophrenia and, more recently, with mood disorders. CASE REPORT: This case supports the idea that the dysfunction of NMDA receptors may play a major role in psychiatric disorders, especially in psychosis and affective disorders. This article will briefly summarize the different evidences and hypotheses reported in the literature on NMDA receptors implication and will report how these receptors may serve as therapeutic targets.

Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort.

BACKGROUND: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. METHODS: Based on a large national cohort, we included all BD women 16-50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. RESULTS: Of the 1018 included women 16-50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p<0.001), the date of French regulatory publication of restriction of valproate prescription. The multivariate analysis revealed that the inclusion period after May 2015 (OR=0.54, CI 95% 0.37-0.78, p=0.001), the age lower than 40 years (OR=0.65, CI 95% 0.43-0.98, p=0.040) and the number of lifetime mood episodes (OR=0.98, CI 95% 0.95-0.99, p=0.040) were the variables negatively associated with the use of valproate. LIMITATIONS: Study could be underpowered to determine a clinical profile associated with valproate prescription. CONCLUSIONS: The regulatory change in BD women of childbearing age had a significant impact on valproate prescription, even if the prescription rate remains high. Important efforts are needed to help clinicians and patients to improve quality of care in BD women of childbearing age.

Transfusions of whole blood prevent spontaneous diabetes mellitus in the BB/W rat.

Weekly transfusions of whole blood from a nondiabetic subline of BB/W rats reduced the incidence of diabetes in susceptible BB/W rats from 39 to 0 percent and the incidence of pancreatic insulitis from 64 to 6 percent. Responsiveness of lymphocytes to concanavalin A was found to be low in rats with diabetes or insulitis. Transfusion restored concanavalin A responsiveness to levels observed in control rats free of diabetes or insulitis. These data suggest that whole blood alters the course of autoimmune BB/W rat diabetes.

[The case of temporal lobes dysfunction in atypical psychiatric episodes]. / Dysfonctionnement des lobes temporaux et tableau psychiatrique atypique : à propos d'un cas.

CASE-REPORT: A thirty-seven-year-old man, with temporal epilepsy, had transient, atypical psychiatric states with periods of time without any symptom. These episodes included hypersexuality with qualitative changes of sex drive, obscene behavior, exhibitionism, masturbation and modified sexual orientation. Blunted affect, inability to recognize significant persons (visual agnosia) were also detected. Magnetic resonance imaging was normal and interictal single-photon emission computed tomography (SPECT) showed decreased cerebral perfusion in both temporal lobes. DISCUSSION: The principal hypothesis is a Klüver-Bucy syndrome (KBS). In animals and human beings, this syndrome can be produced by bilateral temporal lobectomy. It is characterised by hypersexuality, visual agnosia, strong oral tendency, dietary changes, hypermetamorphosis and blunted affect. A minimum of three KBS elements suggests bilateral temporal dysfunction and supports the diagnosis. The syndrome may occur in herpes encephalitis, head trauma, Pick disease and temporal epilepsy. A single case of a patient, without any evidence for structural lesion in temporal lobes, is presented with many KBS symptoms, behavioral changes being due to complex partial seizure. Bitemporal dysfunction for this patient was confirmed by SPECT scan. On the other hand, the detected behavioral changes cannot be explained by temporal epilepsy alone. Postictal hypersexuality in temporal epilepsy consists in sexual arousal but not sexual aberrations as found in KBS. CONCLUSION: KBS following complex partial status epilepticus is a rare phenomenum. The case described here shows how atypical psychiatric episodes can cover complex neurologic disorders.

Energy expenditure in acute pancreatitis evaluated by the Harris-Benedict equation compared with indirect calorimetry.

OBJECTIVES: Enteral nutrition (EN) is recommended for severe acute pancreatitis (AP) and for biliary AP if cholecystectomy is delayed. Energy expenditure (EE) is calculated using the Harris-Benedict equation (HBE), but indirect calorimetry (IC) can also be employed. We wished to compare EE evaluated by the HBE equation, modified HBE (mHBE) and IC at study inclusion and 1 month after AP resolution. METHODS: We undertook a single-center prospective study in Paris, France. RESULTS: Among 35 patients, 19 had biliary AP and 11 alcoholic-related AP. Eleven cases had severe AP. There was no significant difference between EE calculated by the HBE and that using IC at study inclusion. However, the EE calculated by the mHBE was significantly higher than that calculated using IC. For severe AP, the HBE underestimated EE whereas the mHBE overestimated it. No difference was found based on the cause of AP. There was no difference between methods for EE at 30 days. CONCLUSIONS: The HBE underestimated EE for severe AP, whereas the mHBE overestimated it. IC seems to be the best means of EE evaluation for AP.

[Verner-Morrison syndrome revealing a ganglioneuroblastoma in an adult]. / Syndrome de Verner-Morrison révélant un ganglioneuroblastome chez un adulte.

Most vasoactive intestinal peptide (VIP)-producing tumours are from epithelial origin. Tumours derived from the sympathetic nervous system can produce VIP as well. We report here the case of a Verner-Morrison syndrome in a 40-year-old woman revealing a metastatic ganglioneuroblastoma. The diarrhea resolved after the resection of primary tumour and liver metastases. Neuroblastic tumours occur extremely rarely in adults. Thus, the management of these tumours is poorly defined in adults.

Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.

Signal transduction by the platelet integrin alpha IIb beta 3: induction of calcium oscillations required for protein-tyrosine phosphorylation and ligand-induced spreading of stably transfected cells.

We demonstrate an example of signal transduction by an integrin and have begun to define the pathway through which this signaling is achieved. We constructed a stably transfected derivative of 293 cells (ATCC 1573) that expresses the platelet integrin GPIIbIIIa (alpha IIb beta 3). This cell line, clone B, adheres to and spreads on fibrinogen, a ligand for alpha IIb beta 3, while the parent cell line does not. Stimulation of these cells either by adhesion to fibrinogen or with antiserum directed against alpha IIb beta 3 results in induction of calcium oscillations, followed by tyrosine phosphorylation of at least one protein of molecular weight approximately 125 kDa. We establish that this phosphorylation, as well as the morphological rearrangements, requires the mobilization of calcium.

Integrin alpha 6A beta 1 induces CD81-dependent cell motility without engaging the extracellular matrix migration substrate.

It is well established that integrins and extracellular matrix (ECM) play key roles in cell migration, but the underlying mechanisms are poorly defined. We describe a novel mechanism whereby the integrin alpha 6 beta 1, a laminin receptor, can affect cell motility and induce migration onto ECM substrates with which it is not engaged. By using DNA-mediated gene transfer, we expressed the human integrin subunit alpha 6A in murine embryonic stem (ES) cells. ES cells expressing alpha 6A (ES6A) at the surface dimerized with endogenous beta 1, extended numerous filopodia and lamellipodia, and were intensely migratory in haptotactic assays on laminin (LN)-1. Transfected alpha 6A was responsible for these effects, because cells transfected with control vector or alpha 6B, a cytoplasmic domain alpha 6 isoform, displayed compact morphology and no migration, like wild-type ES cells. The ES6A migratory phenotype persisted on fibronectin (Fn) and Ln-5. Adhesion inhibition assays indicated that alpha 6 beta 1 did not contribute detectably to adhesion to these substrates in ES cells. However, anti-alpha 6 antibodies completely blocked migration of ES6A cells on Fn or Ln-5. Control experiments with monensin and anti-ECM antibodies indicated that this inhibition could not be explained by deposition of an alpha 6 beta 1 ligand (e.g., Ln-1) by ES cells. Cross-linking with secondary antibody overcame the inhibitory effect of anti-alpha 6 antibodies, restoring migration or filopodia extension on Fn and Ln-5. Thus, to induce migration in ES cells, alpha 6A beta 1 did not have to engage with an ECM ligand but likely participated in molecular interactions sensitive to anti-alpha 6 beta 1 antibody and mimicked by cross-linking. Antibodies to the tetraspanin CD81 inhibited alpha 6A beta 1-induced migration but had no effect on ES cell adhesion. It is known that CD81 is physically associated with alpha 6 beta 1, therefore our results suggest a mechanism by which interactions between alpha 6A beta 1 and CD81 may up-regulate cell motility, affecting migration mediated by other integrins.