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Persistent memory complaints following concussion often do not coincide with evidence of objective memory impairment. To the extent this clinical presentation represents Functional Cognitive Disorder (FCD), we would expect preservation or even enhancement of memory for instances of forgetting, based on two lines of prior evidence. First, emotional arousal enhances autobiographical memory. People who experience memory lapses as worrisome may better remember them. Second, individuals with FCD can paradoxically provide detailed accounts of memory lapses compared to patients with neurodegenerative disease, who tend to provide vague examples. The current study aimed to better characterize the recall of forgetting events in people with subjective memory problems following concussion.The study sample consisted of adults with chronic post-concussion symptoms (N = 37, M = 42.7 years old; 70.27% women; M = 24.9 months post-injury) and normal-range performance on conventional neuropsychological tests. Participants completed a measure of memory complaint severity and the Autobiographical Interview (AI). The AI was used to quantify the richness of narrative recollections of recent instances when they forgot something and (control) personal events that did not involve forgetting. Linear regression modeling assessed the relationship between memory complaint severity and AI variables, including narrative details, valence, arousal, and rehearsal of memories.There was no association between memory complaint severity and memory for forgetting vs. control events. We further found no association between memory complaint severity and AI performance overall (collapsing across forgetting and control events). Participants with greater memory complaints experienced past memory lapses as more negative than control memories, but did not consistently differ on other AI phenomenological variables.Autobiographical recall of memory lapses appears preserved but not selectively heightened in people who report experiencing severe memory problems long after concussion. This inconsistency supports conceptualization of persistent memory complaints after concussion as FCD.

Objective The etiology of persistent memory complaints after concussion is poorly understood. Memory perfectionism (highly valuing memory ability and intolerance of minor memory lapses) may help explain why some people report persistent subjective memory problems in the absence of corresponding objective memory impairment. This study investigated the relationship between memory perfectionism and persistent memory complaints after concussion. Methods Secondary analysis of baseline data from a randomized controlled trial. Adults (N = 77; 61% women) with persistent symptoms following concussion were recruited from outpatient specialty clinics. Participants completed the National Institutes of Health Toolbox Cognition Battery, Test of Memory Malingering-Trial 1, and questionnaires measuring memory perfectionism (Metamemory in Adulthood-Achievement subscale), forgetfulness and other postconcussion symptoms (Rivermead Postconcussion Symptoms Questionnaire; RPQ), and depression (Patient Health Questionnaire-2) at M = 17.8 weeks postinjury. Patients with versus without severe memory complaints (based on the RPQ) were compared. Results Memory perfectionism was associated cross-sectionally with severe memory complaint, after controlling for objective memory ability, overall cognitive ability, and depression (95% confidence interval for odds ratio = 1.11–1.40). Sensitivity analyses showed that this relationship did not depend on use of specific objective memory tests nor on inclusion of participants who failed performance validity testing. In a control comparison to test the specificity of identified relationships, memory perfectionism was not associated with severe fatigue (95% confidence interval for odds ratio = 0.91–1.07). Conclusions Memory perfectionism may be a risk factor for persistent memory symptoms after concussion, with potential relevance to the spectrum of functional cognitive disorders more broadly.

Introduction Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. Methods A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. Results Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. Conclusions In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.

Background Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD) unrelated to the disease or its treatment (Poullenot F et al. JCC 2022). The main aim of our study was to assess the risk of incident cancer according to the IBD treatment given in patients with prior breast cancer. Methods Consecutive IBD patients with prior breast cancer diagnosis were included in a multicenter retrospective cohort from 25 tertiary centres. Inclusion date corresponded to the diagnosis of index cancer. Follow up was calculated from the first administration of immunomodulator after cancer diagnosis (or cancer diagnosis date in absence of treatment) to the occurrence of incident cancer, corresponding to recurrence of breast cancer or de novo cancer, or to the last follow-up visit. Patients were categorized according to the use or not of immunomodulator after cancer diagnosis: thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab. Crude incidence rates were compared between patients receiving at least one immunomodulator and those without immunomodulator before and after matching on age, lymph node, and metastasis extension and tumor’s grade, using a propensity-score analysis with a 1:1 ratio. Results Among the 151 identified patients, 80 patients with full available data were analyzed: 76 (95%) women; mean age at index cancer diagnosis: 51.5 years [standard deviation (SD): 11.5 years]; 44 (55%) with Crohn’s disease, 35 (44 %) ulcerative colitis and 1 (1 %) indeterminate colitis; median IBD duration at inclusion was 13 years [interquartile range (IQR) 6-21]. After a median follow up of 84 months [IQR 49-154], 16 (20%) incident cancers were observed: 12 (15%) recurrences and 4 (5%) cancer de novo. Three (4%) patients died from cancer related cause during the follow up. 39 (49%) patients received no immunomodulator and, 11 (14%) were treated with thiopurines, 6 (7.5%) with methotrexate, 18 (22.5%) with anti-TNF, 5 (6%) with vedolizumab and one (1%) with ustekinumab. Those treatments were initiated with a median interval of 24 months [IQR 7-48] after cancer diagnosis. Crude incidence rate per 1000 person-years were 47.97 for patients not exposed to any immunomodulator and 12.61 for the others (p=0.0248). After matching, adjusted crude incidence rates per 1000 person-years were 50 and 27.27, respectively (p=0.3798). Rates of survival without incident cancer were not different between the two groups after matching on age, lymph node, metastasis extension, and tumor’s grade (p=0.17) (Figure 1). Conclusion In the present multicenter retrospective cohort, incident cancer risk among patient with IBD and prior breast cancer was not increased in patients subsequently exposed to immunomodulators.

The human perceptual system is responsive to numerical information within visual and auditory scenes. For example, when shown 2 displays of dots, observers can instantly, albeit approximately, identify the set that is more numerous. Theories in perceptual and cognitive psychology have focused on 2 mechanisms for how vision accomplishes such a feat: Under the domain-specific encoding theory, number is represented as a primary visual feature of perception, much like motion or color, while under the domain-general theory, the visual system represents number indirectly, through a complex combination of features such as the size of the dots, their total cluster, and so forth. Evidence for the latter theory often comes from "congruency effects:" the finding that participants frequently select the side where the dots on the screen are denser, larger, or brighter, rather than the side that is actually more numerous. However, such effects could also stem from response conflicts between otherwise independent dimensions. Here, we test these 2 competing accounts by embedding numerical displays within visual illusions that create large conflicts between number and other non-numeric dimensions-including contour length, convex hull, and density-and contrast participants' performance on a number discrimination task (i.e., "Which side has more dots?") against a number estimation task (i.e., "How many dots are there?"), which should eliminate response conflicts. Across 3 experiments, we find that while contour length illusions only affect number perception in discrimination tasks, the influences of convex hull and density on number perception persist in both discrimination and estimation tasks, supporting a more domain-general account of number encoding. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

OBJECTIVE Reporting of unexpected symptoms after concussion might, in some people, reflect a Functional Neurological Disorder (FND), Somatic Symptom Disorder (SSD), or exaggeration (feigning). This study aimed to determine whether reporting unexpected symptoms after concussion was associated with risk factors for FND/SSD, exaggeration, or both. METHOD Adults with persistent symptoms following concussion (N = 77; 61% women) rated the presence and severity of unexpected neurological symptoms (from the Screening for Somatoform Symptoms scale, e.g., paralysis) and somatic symptoms (from the Patient Health Questionnaire-15, e.g., stomach pain) that did not overlap with post-concussion symptom scale items. The independent variables were risk factors for exaggeration (neuropsychological performance validity test failure and personal injury litigation) and predisposing and perpetuating factors for developing FND and/or SSD (e.g., fear avoidance behavior). RESULTS When adjusting for all covariates, fear avoidance behavior was most strongly related to unexpected neurological symptoms (B = 0.11, 95% confidence interval = 0.05-0.18, p

Background Knowledge about the cancer risk when initiating a biologic in Inflammatory Bowel Disease (IBD) patients with prior malignancy remains scarce especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy according to the subsequent treatment given. Methods Consecutive cases of patients with IBD and a malignancy were retrospectively collected in, 33 centers in two countries. Patients with a biliary- or digestive tract cancer were excluded. Inclusion date corresponded to diagnosis of malignancy. Patients were categorized into different cohorts according to the first treatment they were exposed to after the malignancy diagnosis and before incident cancer. Follow-up time was calculated from the first administration of therapy to last follow-up visit. For patients receiving no therapy, follow-up started at diagnosis of cancer. Incident cancer during follow-up was defined as recurrence of the known cancer or occurrence of a new cancer. Crude cancer incidence rates were compared between the cohorts using chi-square test. Patients from the anti-TNF, vedolizumab, and no treatment cohorts were matched on age, lymph node and metastasis extension and malignancy recurrence risk according to the Penn classification using a propensity-score analysis with a, 1:1 ratio. Results Among the, 538 patients (58% female; mean [standard deviation (SD)] age inclusion:, 52 [15] years) analyzed, the most frequent malignancy was breast cancer (25%). First immunomodulator given after inclusion was a conventional immunosuppressant in, 27% of patients, anti-TNF in, 21% or vedolizumab in, 9%. With a median (inter-quartile range (IQR)) follow-up duration of, 55 (23–100) months, 100 incident cancers were observed. Crude cancer incidence rates per, 1000 person-years were, 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort and, 33.6 in the vedolizumab cohort (p=0.23). Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab (p=0.56). After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF or vedolizumab. On multivariate analysis, age ≥, 52 years at inclusion, follow-up after index cancer Conclusion In this large multicenter cohort study, we found no difference in terms of incident cancer rates in patients with IBD and a prior non-digestive malignancy treated by vedolizumab compared to those treated by other immunomodulatory therapies including anti-TNF.

Background Combination therapy with infliximab and anti-metabolites is a standard option for patients with Crohn’s disease (CD). The implications of long term use of combination therapy may lead patients and clinicians to contemplate treatment de-escalation once steroid-free remission has been achieved. The aim of our study was to assess the relapse rates and time spent in remission over 2 years, after withdrawal of infliximab or anti-metabolite compared to continuation of combination therapy. Methods CD patients treated with a combination therapy of infliximab (IFX) and anti-metabolite > 8 months and in sustained steroid-free remission > 6 months were recruited in 64 centers in France, United Kingdom, Belgium, Sweden, Australia, Germany and The Netherlands. Patients were randomized into 3 arms - continuing combination therapy (arm A); stopping IFX (arm B); or stopping anti-metabolite (arm C). In case of a relapse [defined by CDAI and an objective marker of inflammation (CRP or fecal calprotectin)], patients were retreated by resuming infliximab in arm B or the anti-metabolite in arm C, according to a pre-defined scheme, including optimization of IFX up to 10 mg/Kg if necessary in all arms. The two co-primary endpoints were the relapse rate and mean survival time spent in remission over 2 years. A major secondary endpoint was treatment failure (complications or not recapturing remission). Results 254 patients were screened, 211 randomized, 5 withdrew consent and 1 was lost to follow-up, leaving 205 patients for the analysis - 67 randomized to arm A, 71 to arm B and 67 to arm C. Demographic and clinical characteristics are shown in Table 1. The two-year relapse rates were 14% (IC95%: 4–23%) in arm A, 40% (IC95%: 28–51%) in arm B, and 10% (IC95%: 2–18%) in arm C (p=0.0003 arm B vs arm A and Conclusion Infliximab withdrawal, but not antimetabolite withdrawal, was associated with a significantly higher risk of relapse than continuation of combination therapy. Almost all patients who stopped IFX achieved rapid remission when resuming treatment. The time spent in remission over 2 years was similar across groups.

Introduction La maladie de Crohn, maladie inflammatoire chronique de l’intestin evoluant par poussees, provoque de vives douleurs abdominales et des diarrhees a l’origine d’une fatigue et d’un amaigrissement, alterant de facon importante la qualite de vie (QdV) des patients. La prise en charge de la maladie evolue selon son niveau de severite. En cas de forme moderee a severe, les anti-TNFα intraveineux (IV) ou sous-cutanes (SC), peuvent etre prescrits en complement ou relais des traitements conventionnels (corticosteroides, immunosuppresseurs). Alors que la resolution de la douleur abdominale et la normalisation du transit intestinal constituent des mesures rapportees par les patients (PROM) dont l’interet est de plus en plus reconnu comme cible therapeutique de la maladie, la QdV dans toutes ses dimensions ne l’est pas encore. Or, la connaissance des facteurs influencant chacune des dimensions de la QdV, tant lors de l’initiation d’un nouveau traitement qu’en periode d’entretien, peut concourir a l’optimisation de la prise en charge. L’objectif de l’etude COQC-PIT etait d’explorer l’evolution de la QdV des patients malades de Crohn dans les six mois suivant l’initiation d’un anti-TNFα (inclusion) et d’evaluer l’influence des caracteristiques individuelles, liees a la maladie et aux traitements sur chacune de ses dimensions. Methodes Le questionnaire de QdV specifique IBDQ-32 a ete administre a l’initiation du traitement anti-TNF puis tous les deux mois pendant six mois. Les caracteristiques individuelles et les donnees relatives a la maladie et aux traitements ont ete recueillies a la meme frequence. L’estimation du score global IBDQ-32 et de chacun des quatre scores dimensionnels (symptomes intestinaux, systemiques, fonction emotionnelle, sociale) a ete realisee par la methode des equations d’estimations generalisees (GEE). Resultats Les donnees longitudinales de 56 patients ont ete analysees. En moyenne, le score global de QdV augmentait significativement 2 mois apres l’initiation d’un anti-TNFα puis stagnait. A l’initiation, 39 % des patients avaient un score global superieur au seuil de remission clinique, 68 % a six mois. Alors que la voie d’administration n’influencait pas le score global, la fonction emotionnelle et les symptomes intestinaux semblaient s’ameliorer avec un anti-TNF SC (versus IV). La prise concomitante de corticosteroides et/ou d’immunosuppresseurs avaient un effet negatif sur la QdV, les premiers affectant plus particulierement la fonction emotionnelle. Le fait d’avoir des enfants ou de travailler alterait seulement la dimension relative aux symptomes intestinaux. L’echappement therapeutique et l’interruption du traitement anti-TNF reduisaient la QdV dans presque toutes ses dimensions. Conclusion Considerant le score global de l’IBDQ-32, la QdV des patients etait principalement influencee par les caracteristiques des traitements administres. L’effet negatif des caracteristiques individuelles (charge familiale et professionnelle) n’etait retrouve que dans la dimension « symptomes intestinaux ». L’alteration observee des dimensions emotionnelle et sociale de la QdV invite a ne pas considerer uniquement l’amelioration des symptomes rapportes par les patients comme cible therapeutique. Tenir compte des caracteristiques individuelles et considerer chacune des dimensions de la QdV des patients permettrait de leur proposer le traitement le plus adapte et de les orienter si necessaire vers d’autres professionnels de sante.

Introduction La macrocheilite granulomateuse (MG) peut etre isolee ou associee a des granulomatoses systemiques comme la maladie de Crohn (MC). En cas d’echec des traitements conventionnels (corticoides, clofazimine, dapsone…), les anti-TNFα peuvent etre proposes. Le vedolizumab (VDZ), anticorps monoclonal dirige contre l’integrine α4 β7, est indique dans les maladies inflammatoires chroniques intestinales (MICI) refractaires. Son mode d’action etant specifique de la muqueuse intestinale, son utilisation dans les manifestations extra-intestinales (MEI) reste peu decrite. Nous rapportons l’efficacite du VDZ sur une MG refractaire a trois lignes d’anti-TNFα. Observations Une patiente de 28 ans avait une MC ileo-colique et ano-perineale traitee par infliximab (IFX) et azathioprine depuis 7 mois. Elle presentait une perte de reponse (immunisation anti-IFX) avec apparition d’une MG invalidante. L’IFX etait remplace par l’adalimumab (ADA), sans effet sur la MG qui necessitait des traitements iteratifs. Devant une immunisation contre l’ADA apres 27 mois, le golimumab etait instaure, en maintenant ces traitements iteratifs pour la MG recidivante (clofazimine, corticoides intralesionnels et per os). Apres 18 mois, le golimumab etait remplace par le VDZ (300 mg IV/4 semaines). Pendant les 5 premiers mois, la MG necessitait un traitement complementaire (doxycycline, corticoides intralesionnels), puis la maladie intestinale et la MG etaient progressivement controlees, avec un effet « fin de dose » necessitant un rapprochement des perfusions de VDZ. La MG et la MC etaient respectivement bien controlees a 11 et 15 mois, avec un recul total de 22 mois ( Fig. 1 et 2 ). Discussion Il s’agit de la premiere observation de l’utilisation du VDZ sur une MG associee a une MC. Le VDZ est dirige contre l’integrine α4 β7 exprimee par des lymphocytes T memoire a tropisme digestif, inhibant selectivement leur adhesion a la molecule MadCAM-1 (principalement exprimee dans les vaisseaux sanguins de la muqueuse intestinale et des tissus lymphoides associes a l’intestin). Bien que peu de donnees soient disponibles sur son utilisation sur les MEI des MICI, son efficacite a ete decrite sur les atteintes rhumatologiques et cutanees (erytheme noueux, pyoderma gangrenosum) des MICI. Cette action paradoxale serait liee au controle de l’inflammation intra-luminale et pourrait refleter un tropisme des lymphocytes exprimant l’integrine α4 β7 vers ces organes cibles. Dans notre cas, les remissions de la MG et de la MC, bien que retardees apres l’instauration du VDZ, etaient en faveur d’une efficacite du VDZ sur une maladie refractaire a trois lignes d’anti-TNFα. Conclusion Le VDZ, a l’action digestive specifique, peut toutefois constituer une alternative therapeutique des MEI, ici une macrocheilite granulomateuse, associees aux MICI refractaires aux anti-TNF alpha.

We investigated the effects of intrauterine mild hyperglycemia during late fetal life on glucose regulation and insulin secretion in adult rats. Unrestrained pregnant rats were continuously infused with glucose during the last week of pregnancy to induce mild hyperglycemia (6.5–8 mM). Control rats were infused with a glucose-free solution. The offspring were studied, as adults, from 1 to 20 mo by performing glucose tolerance and insulin secretion tests. Young-adult rats from hyperglycemie dams showed mild glucose intolerance and impairment of glucose-induced insulin secretion. This situation gradually evolved to basal hyperglycemia and severe impairment of glucose tolerance and insulin secretion. Insulin secretion was also studied in vitro in 20-mo-old rats with the isolated perfused-pancreas technique. Insulin release in response to glucose stimulation from pancreases of hyperglycemic dams was similar to that of controls, and the response to arginine was increased but not significantly. The possible involvement of enhanced sympathetic nervous system activity in the impairment of insulin secretion in adult rats from hyperglycemic mothers was then investigated by performing glucose tolerance and insulin secretion tests in the presence of the α2-blocker idazoxan in 8-mo-old rats. Under these conditions, rats from hyperglycemic dams recovered almost normal glucose tolerance, and glucose-induced insulin secretion was greatly improved. These data show that mild hyperglycemia induced in the fetus during late pregnancy leads to persistent impairment of glucose regulation and insulin secretion. They suggest that the impairment of insulin secretion in vivo results from a perturbation of the neuroregulation of insulin secretion rather than an intrinsic pancreatic β-cell defect.

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.

International audience; Over the tropics the atmospheric general circulation models usually fail in predicting horizontal wind divergence, which is closely related to atmospheric heating and to the vertical exchanges associated with convection. With the aim of forcing atmospheric models we present here a reconstruction of wind divergences based on the links between infrared brightness temperatures, convective activity, and large-scale divergence. In practice, wind divergences are reconstructed from brightness temperatures using correlations obtained from numerical simulations performed with a general circulation model. When building those correlations, a distinction must be made between the brightness temperatures of opaque clouds and those of semitransparent clouds, only the former being directly associated with convection. In order to filter out semitransparent clouds we use radiative thresholds in the water vapor channel in addition to the window channel. We apply our approach to Meteosat-5 data over the Indian Ocean. Comparison with wind divergences reconstructed independently from Meteosat water vapor winds partially validates our retrieval. Comparison with European Center for Medium-Range Weather Forecasts analyses indicates that much can be gained by adding information on the wind divergence in the tropics to force an atmospheric model.

Resume Nous rapportons un cas de carcinome pulmonaire a petites cellules se manifestant initialement par une pseudo-obstruction intestinale chronique et decouvert a l’occasion de l’exploration d’une achalasie du sphincter inferieur de l’œsophage. L’obtention d’une remission tumorale de plus de 21 mois apres radiochimiotherapie n’empechait pas le syndrome paraneoplasique de persister et le traitement medical restait sans effet sur la pseudo-obstruction et la dysphagie qui n’etait amelioree que par une dilatation œsophagienne.

In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease.The STORI trial patients (n=115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP).Median serum calprotectin was 8892 ng/mL (range: 410-125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8-3770 ng/mL) in controls (P0.0001). Serum calprotectin was significantly higher for active disease (median=19,584 ng/mL) than for inactive disease (median=8353 ng/mL) (P0.0001). Serum calprotectin correlated with hsCRP (r=0.4092, P0.0001) and CDAI (r=0.4442, P0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r=0.6458, 0.5515, 0.2577 with P0.0001, P0.0001, P=0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (5 mg/l) and fecal calprotectin (250 μg/g) to predict relapse after infliximab withdrawal (P=0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120).As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.

Early after lesion of the ventromedial hypothalamus nuclei (VMH), insulin-induced glucose utilization is increased in white adipose tissue (WAT), whereas oxidative and glycolytic muscles are, respectively, normoresponsive or resistant to insulin. Five weeks later, all of the muscles are resistant, whereas WAT returns to normal responsiveness. The aim of this study was to characterize the insulin receptor kinase activity in WAT and muscles 1 and 6 wk after lesion. The number and affinity of insulin receptors were not modified in any of the tissues studied. Autophosphorylation and phosphorylation of an exogenous substrate were similar in oxidative and glycolytic muscles of VMH and control rats both 1 and 6 wk after the lesion. Insulin receptors from WAT of 1-wk VMH rats exhibited a 2.5-fold increase in insulin-stimulated autophosphorylation and phosphorylation. Six weeks after the lesion, both autophosphorylation and phosphorylation returned to normal values. This suggests that insulin receptor tyrosine kinase activity does not play a significant role in the insulin resistance of skeletal muscles but has a crucial role in mediating the variations of insulin action on WAT observed during the development of VMH obesity.

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.

To explore the interplay between the mitotic activity of arterial smooth muscle cells and the variations of plasma glucose and insulin concentrations, we have studied over 14 days the response of thoracic aorta to injury with a balloon catheter in rats submitted to fasting and refeeding. Animals were fasted from the day before until the third day after injury. The proliferative reaction of intima-media was assessed 2, 3.5, 4, 6, 8, and 14 days after injury, comparing freely fed with fasted-refed rats. Fasting decreased plasma glucose and insulin concentrations and DNA synthesis by intima-media, whereas refeeding increased these three variables transiently. The DNA content of intima-media at any time during the response to injury and the intimal thickening on day 14 were not influenced by the sequence of fasting and refeeding, which suggests that the early decrease in DNA synthesis induced by fasting had been compensated for by the later increase in DNA synthesis induced by refeeding. In conclusion, besides hormonal influences (such as insulin), metabolic influences (such as the availability of energetic fuels) are likely to act on the proliferative response of arteries to injury.

Acute pandysautonomia is a rare acute autonomic neuropathy that mainly affects young women. We report a case of idiopathic acute pandysautonomia associated with an esophageal achalasia in a 30-year-old woman. The clinical features were inaugural dysphagia followed by signs of parasympathetic failure of the entire digestive tract, bladder and pupils. Twenty-four hours of electrocardiographic recording showed involvement of sympathetic adrenergic nerves. Esophageal achalasia was patent on esophageal manometry. Upper digestive tract motility was first involved and then extended to the entire digestive tract with intestinal obstruction, which required emergency ileostomy. Recovery of autonomic functions was slow. After 16 months, dysphagia and gut paresis improved and digestive continuity was restored. In case of subacute intestinal pseudo-obstruction associated with autonomic dysfunction, acute pandysautonomia should be suspected. In our report, the association with esophageal achalasia is uncommon.

We report a case of a small cell carcinoma of the lung revealed by chronic intestinal pseudo-obstruction associated with achalasia of the lower esophageal sphincter. Tumoral remission was achieved for more than 21 months after chemoradiotherapy but this did not prevent the paraneoplasic syndrome from persisting and medical treatment was not successful in treating the intestinal pseudo-obstruction or the dysphagia, which was not improved by esophageal dilation.

Our study investigated whether a deterioration of glucose homeostasis and insulin secretion in adult female rats from hyperglycemic dams could be transmitted to the next generation independent of genetic interferences. Dams (F0) were rendered hyperglycemic by continuous glucose infusion during the last week of pregnancy. Females born of these rats (F1) exhibited glucose intolerance and impaired insulin secretion in vivo at adulthood. When they were 3 mo old, they were mated with males born of control dams. During pregnancy, their glucose tolerance remained impaired compared with that of controls. Consequently, F2 newborns of F1 hyperglycemic dams showed the main features of newborns from diabetic mothers: they were hyperglycemie, hyperinsulinemic, and macrosomic. As adults, they displayed basal hyperglycemia and defective glucose tolerance and insulin secretion. This indicates that the long-range deteriorating effects on glucose homeostasis of gestationai hyperglycemia in the F1generation are transmitted to the F2 generation and suggests that a perturbed fetal metabolic environment contributes to the inheritance of diabetes mellitus.

Small bowel dysmotility has previously been demonstrated in some patients with slow transit constipation (STC), suggesting a generalized intestinal disorder. However, no study has addressed whether the incidence of small intestinal dysfunction differs between subgroups of patients in this heterogeneous population. Using appropriate methodology, we aimed to determine prospectively the proportion of individuals with abnormal small bowel motility, and to assess whether heterogeneity in terms of pattern of colonic transit delay (based on (111)In diethylene-triamine-pentaacetic acid (DTPA) isotope scintigraphy), or mode of onset (based on clinical history) is of importance.Thirty-seven patients with STC underwent 24-h ambulatory jejunal manometry; data were compared with those obtained in 38 healthy controls. Automated quantitative analysis of seven variables of the nocturnal migrating motor complex was performed, to assess whether differences existed between groups, and whether individual patients had evidence of small intestinal dysmotility, defined as two or more measures of migrating motor complex variables outside the normal range. Four variables differed significantly between STC patients and controls: in phase III, propagation was slower, duration was longer, and contraction amplitude was higher; in phase II, contraction frequency was increased. Seven of 24 patients with a generalized pattern of colonic transit delay had abnormal small bowel motility compared with none of 13 with a left-sided delay (p0.04). These included four patients with chronic idiopathic symptoms and three with acquired symptoms. Approximately one third of patients with a generalized delay in colonic transit had evidence of jejunal enteric neuromuscular dysfunction. Individual patients with a left-sided colonic delay did not satisfy the criteria for nocturnal small bowel dysmotility, but as a group, some differences were noted from controls. In contrast to previous reports, evidence of generalized enteric dysmotility may be present irrespective of the mode of onset.

The aim of this prospective study was to determine whether anti-carcinoembryonic antigen (anti-CEA) scintigraphy is a useful additional technique in the diagnosis recurrence of colorectal cancer. Forty patients with suspected recurrence of colorectal cancer, underwent immunoscintigraphy (IS) and helical computed tomography (CT) in the 2 weeks before surgery. Surgical findings were used to evaluate the performance of the imaging techniques. Suspected areas on IS and CT were systematically explored. Helical CT was found to be superior to IS for the liver, the sensitivity and specificity of CT being 100% and 90%, respectively, vs 53% and 100% for IS. However, IS was better than CT for the detection of extra-hepatic abdominal recurrence: sensitivity and specificity of IS were 100 and 82% respectively vs 33 and 82% for CT. Seven cases of peritoneal carcinomatosis were overlooked by helical CT. Our results indicate that IS improves detection of extra-hepatic abdominal recurrence of colorectal cancer. Immunoscintigraphy is valuable as a guide to the treatment strategy and operative procedures.

The aim of this retrospective study was to determine the risk factors of early complications after progressive pneumatic dilation for achalasia.Five hundred four dilations were performed in 237 consecutive achalasic patients between 1980 and 1994 with the same technique: low-pressure pneumatic dilation every other day with balloons of increasing diameter until success criteria were obtained (depending on manometric examination and esophageal x-ray transit performed 24 h after each dilation). Clinical, radiographical, endoscopical, and manometrical data as technical procedure characteristics for patients with perforations or other early complications were compared with those without complications.We observed 15 complications (6% of patients): 7 perforations (3%), 3 asymptomatic esophageal mucosal tears, 4 esophageal hematomas, and 1 fever. Perforations occurred in 6 of 7 patients during the first dilation. The mean age was 68.5 yr in the group with complications versus 56.4 yr for the remainder (p0.05). Two deaths occurred in patients older than 90 yr. Instability of the balloon during dilations was noted in 8 of 15 cases of complications versus 57 of 222 patients (p0.05). No other data differed significantly.This study showed a low prevalence of early complications using this progressive technique. Patients with hiatal hernia, esophageal diverticulum, or vigorous achalasia may safely undergo progressive pneumatic dilation. Only patients older than 90 yr should be referred for progressive pneumatic dilation with caution. Most of perforations arose during the first dilation, but there was no predictive pretherapeutic factor of perforation.

The acoustic technique has been used for pharyngeal exploration but to date no such technique has been devised to assess esophageal motility. The aim of this study was to demonstrate that displacement through the esophagus can be quantified using this method in healthy subjects and in patients with gastroesophageal reflux. Concurrent manometric and acoustic recordings were also performed in the patients. Fifteen controls (38.5 +/- 13 years old) and 10 patients (34.9 +/- 6 years old) were included. All were recorded during wet and dry swallow sequences with microphones placed below the cricoid cartilage and on the xiphoid appendix. Standard manometry was performed for lower esophageal sphincter (LES) exploration. For the acoustic technique, the frequency of xiphoid signals (FX), esophageal transit time (ETT), duration of xiphoid sound (SD), and for the manometric study, the duration of LES relaxation (RD) were recorded and mean values were calculated (FXm), (ETTm), (SDm), (RDm). FXm for wet (94 vs 81.6%) and dry swallows (86 vs 66.6%) decreased in patients. ETTm was significantly higher (P0.01) for wet than for dry swallows (5.6 +/- 0.9 vs 5.2 +/- 1.2 sec) for controls but not for patients. ETTm was significantly higher for patients for wet (7.2 +/- 2.1 sec) and for dry swallows (6.5 +/- 2.3 sec) than for controls and SDm was lower. Xiphoid sound appeared in the second half of LES relaxation. Our noninvasive acoustic technique is simple and reproducible. It is well correlated with manometry, and it allows characterization of the displacement of the bolus through the esophagus and the LES. The technique could be used alone to determine appropriate pharmacological and surgical treatments for esophageal motility disorders.

We report the case of a 22-year-old-man having a familial adenomatous polyposis coli treated by total colectomy with ileo-rectal anastomosis. Two years after the operation, an asymptomatic mesenteric fibromatosis appeared which was nonresectable due to mesenteric vessels infiltration. Nine years later, sulindac therapy was started for residual polyps in the rectal stump. This treatment was taken intermittently, during periods of 1 to 8 months, for 6 years. After 4 years of treatment, the tumor was no longer palpable. Four years after sulindac discontinuation, the patient was operated on for suspicion of intestinal adhesion. The mesenteric fibromatosis had completely disappeared and mesenteric vessels were free. This complete macroscopic regression of a desmoid tumor after sulindac therapy emphasizes again the interest of this treatment for mesenteric fibromatosis.

We report the case of a 67-year-old-man presenting with pancreatic acinar cell carcinoma revealed by dermatological manifestations of cytosteatonecrosis and treated by hepatic artery ligation. The pancreatic etiology of these lesions was suspected due to hyperlipasemia, and was confirmed by abdominal computerized tomography showing a pancreatic tumor and multiple liver nodules, and by histological examination of one of these lesions. Because of symptomatic treatment failure, rapid impairment of patient's general condition, and by analogy with the treatment of hepatic metastases of neuroendocrine tumors, hepatic artery ligation was performed. Lipasemia decreased markedly and symptoms disappeared for 45 days. Hepatic artery obstruction may be used for emergency treatment of secreting liver metastases.

We report the case of a 61-year-old-man with an eosinophilic esophagitis with esophageal motor disorder associated with toxocariasis. He complained of non cardiac chest pain and had eosinophilia leading to the detection of Toxocara canis infection. Pain persisted despite treatment of toxocariasis. Basal manometry was normal but ambulatory 24-hour manometry-pHmetry showed diffuse esophageal spasm. Ultrasonography showed a thickening of the esophageal musculature in the two inferior thirds of the esophagus. After failure of treatment with sodium cromoglycate steroids and esophageal dilatation, calcium antagonists were partially effective. A long esophageal myotomy was performed permiting the disappearance of symptoms. The histological examination of a side myotomy biopsy showed an eosinophilic infiltration of the esophageal muscle layer. This observation leads to discuss the possible relation between toxocariasis, the esophageal motor disorder and the eosinophilic infiltration of the esophageal muscle layer.

PURPOSE A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise dose escalation in a weekly regimen, and pharmacokinetic monitoring, we defined a therapeutic range for 5-FU plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 to 8 hours [AUC0-8], 16 to 24 mg x h/L). The current study investigated 5-FU therapeutic intensification with individual dose adjustment in a multicentric phase II prospective trial. PATIENTS AND METHODS Weekly high-dose 5-FU was administered by 8-hour infusion with 400 mg/m2 leucovorin. The initial dose of 5-FU (1,300 mg/m2) was adapted weekly according to 5-FU plasma levels, to reach the therapeutic range previously determined. RESULTS A total of 152 patients entered the study from December 1991 to December 1994: 117 patients with measurable metastatic disease and 35 with assessable disease. Toxicity was mainly diarrhea (39%, with 5% grade 3) and hand-foot syndrome (30%, with 2% grade 3). Among 117 patients with measurable disease, 18 had a complete response (CR), 48 a partial response (PR), 35 a minor response (MR) and stable disease (SD), and 16 progressive disease (PD). Median overall survival time was 19 months. The 5-FU therapeutic plasma range was rapidly reached with a variable 5-FU dose in the patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 to 3,396). Thirteen patients were immediately in the toxic zone, whereas 51 required a > or = 50% dose increase. CONCLUSION Individual 5-FU dose adjustment with pharmacokinetic monitoring provided a high survival rate and percentage of responses, with good tolerance.

Acute chemotherapy-induced diarrhoea may require reducing or even stopping subsequent therapy. Antidiarrhoeal drug efficiency has not been extensively studied and the effects of the new antisecretory compound acetorphan--a potent enkephalinase inhibitor active in acute diarrhoea--are unknown. The aim of this study was to investigate the possible effects of acetorphan on 5 FU-induced diarrhoea in man.Fifteen patients reporting acute diarrhoea following chemotherapy were included in this study. They presented with metastatic colo-rectal cancer (n = 14) or pancreatic carcinoma (n = 1) and were treated, once weekly, by an 8-hour IV infusion of folinic acid 200 mg/m2 and 5 FU 1,800 to 3,000 mg/m2. In each patient, number and consistency of stools were assessed every day during the week following chemotherapy, once without (control period) and once with acetorphan p.o. 300 mg/d/7d.During the control period, 3 out of 15 patients did not have significant diarrhoea, but 2 out of 3 patients had abdominal pain which was relieved by acetorphan without appearance of constipation. Twelve out of 15 patients presented with diarrhoea (3 stools/day for2 days: WHO grades 2 and 3); with acetorphan, the number of stools per day was reduced in all cases from 6.3 (range: 3-10.6) to 4.9 (range: 2.6-8.9) (P0.002), and the number of days with liquid stools dropped from 4.7 (range: 2-7) to 2.4 (range: 0-7) (P0.02). In addition, during treatment with acetorphan, there was a close positive linear relationship between the percent reduction in the number of stools and the number of stools during control period up to a 8 stools/day level (8 patients) above which efficiency decreased (4 patients).These results suggest the efficacy of acetorphan on chemotherapy-induced diarrhoea and urgent need for a randomized controlled trial.

A magnetostrictive fiber optic interferometric sensor that detects low-intensity magnetic fields has been realized. The sensor is fabricated with 850-nm, single-mode fiber optic cable and couplers configured in a Mach-Zehnder interferometric arrangements. Four sensing arm configurations were fabricated where the magnetostrictive material was geometrically coupled to the fiber optic cable as a: ribbon, cylinder, sandwich, and sputter-coated sheath. The four classes of sensing arms were evaluated using MetglasTM, nickel, and a combination of MetglasTM and nickel. Optimization techniques were applied to maximize the sensor's sensitivity. These techniques included: annealing the magnetostrictive material, operating the magnetic field over a range of frequencies, applying a DC bias current to the Helmholtz coil's AC current component, and fabricating sensing arms with polarization maintaining fiber optic cable. The measurements employing the various sensor arm classes revealed that the lowest detectable magnetic flux density was 0.3 mG. This result was achieved using a MetglasTM ribbon-fiber optic cable configuration where the ribbon's magnetization direction was aligned perpendicularly with the applied 52 kHz AC magnetic field that had a 5- volt DC bias. When operating this configuration with a 10 Hz AC magnetic field that had a 5- volt DC bias, the lowest magnetic flux density that could be detected was 8.9 mG.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Using an electronic barostat in the human terminal ileum, we studied ileal tone in response to various stimuli in 10 healthy volunteers. Phasic activity was also measured by manometry. Graded orad (ileal) and caudad (cecal) balloon distensions did not produce any significant changes in ileal tone at all levels tested, even when a sensation of discomfort was felt. A linear relationship between pressure and volume was observed during in situ isobaric ileal distensions. Meal induced a biphasic tonic response with a brief (20 min) and immediate decrease in intrabag volume (64 +/- 7% of preprandial value, P < 0.05), followed by a prolonged increase in intrabag volume (158 +/- 10% of preprandial value, P < 0.05). A significant correlation was found between volume variations and phasic activities during the first phase (r = 0.88, P < 0.05), whereas no correlation was found during the second phase (r = 0.55, NS). The administration of glucagon induced a significant increase in intrabag volume from 45 +/- 5 to 70 +/- 8 ml (P < 0.05). We conclude that 1) regional distensions do not influence ileal tone and phasic motility, 2) the ileum does not show accommodation to distensions, and 3) meal produces an immediate increase in phasic and tonic activity followed by a prolonged relaxation.

Assessment of total and segmental colonic transit times (CTT) in man using a single type of radiopaque marker and one abdominal X-ray has been validated but not extensively studied. The aims of our prospective study were to establish normal values of this method as a function of age, gender and fiber intake in healthy subjects. Eighty-two healthy volunteers (51 men, 31 women, mean age 38 yr, range 21-61) with normal stool frequency (between 3/day and 3/week) and no history of gastrointestinal disease or medication were enrolled and ingested 10 small (3 mm edge) radiopaque markers every morning for 6 consecutive days. On the 7th day, an abdominal X-ray was performed to calculate total and segmental (right, left, rectosigmoid) CTT according to Arhan's method (CCT = 2.4 N; N = number of markers in the considered zone). During the study the number of stools was recorded and fiber intake estimated on a questionnaire. Stool frequency, total and segmental CTT were evaluated for differences due to age, gender and/or fiber intake. In volunteers, total, left and rectosigmoid CTT were closely related to stool frequency (P = 0.0001) being longer in women than in men (P0.02). In contrast, right CTT was independent of gender or stool frequency. Finally, in this group CTT were independent of age and fiber intake. This study confirms the influence of gender on CTT and demonstrate the ability of this simple and non-invasive method (0.08 mrad surface exposure) to assess CTT. Its use as a diagnostic tool in self-defined constipated patients would be of interest in clinical practice.