[Eosinophilic esophagitis in children: Evaluation of practices through a multicenter study]. / L'œsophagite à éosinophiles chez l'enfant : évaluation des pratiques.

Eosinophilic esophagitis (EE) is a recent pathology defined by abnormal immune response of the esophageal mucosa to exogenous allergens, leading to chronic mucosa infiltration by 15 eosinophils per High-Power-Field (Eos/HPF). The present retrospective study was designed to assess the hospital care for children suffering from EE in several hospitals in western France in order to highlight discrepancies and improve future care. Twenty-eight children ranging from 1.5 months to 17 years old were included in the study. Episodes of food blockage were the most frequently reported symptoms (46 %). A ratio of 29 % of EE patients reported macroscopically normal endoscopy; diagnosis was then established upon histological anomalies found in biopsies. The mean eosinophil count was 72.4 Eos/HPF. Centralized immunohistochemical staining revealed the presence of IgG4-responding plasma cells in 76.5 % of patients, as well as IgG4 intraepithelial degranulation in 14 % of them. The evaluation of the treatment plan showed important inter-center discrepancies with only 43 % of patients receiving endoscopic reevaluation. This study objectively highlights heterogeneities in diagnosis and care provided to children suffering from EE. Therefore, improving the consistency of practices seems to be crucial to optimize the patients' outcome. The role of IgG4 as a new diagnosis marker remains to be clarified.

Effects of a chronic stress treatment on vaccinal response in lambs.

Farming systems can expose animals to chronic mild stress which is known to induce negative affective state. Affective state in animals, as in humans, can be assessed through behavioral cues. This study aimed to describe the effect of a chronic mild stress, known to induce a negative affective state, on sheep health through their response to vaccination. The study used 15 lambs subjected to a model of chronic mild stress for 15 weeks and 15 lambs reared under conventional farming as a control group. After 7 weeks of stressful treatment, the lambs were individually exposed to a judgment bias test to assess a putative stress-induced 'pessimism.' After 15 weeks of stressful treatment, antibody immune response was measured after an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment bias test, revealing a negative affective state. Stressed and control animals showed different immunological reactions to vaccine challenge: stressed sheep had lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase protein concentrations. Antibody response induced by the vaccine strain was not different between stressed and control sheep. Our results suggest that negative affective state induced by chronic stress treatment may induce a stronger inflammatory response to vaccine challenge in sheep. Improvement of animal health may be achieved through consideration of stressors that may affect the emotional and immunological state of sheep.

[Knowledge of adolescents with inflammatory bowel disease: Results of a multicenter cross-sectional survey]. / Connaissances des adolescents atteints de maladie inflammatoire chronique intestinale : résultats d'une enquête transversale multicentrique.

AIM: To assess knowledge acquired by adolescents about their inflammatory bowel disease (IBD). METHODS: An anonymous questionnaire was given during consultation to adolescents followed for IBD by pediatricians from 13 hospitals between 1 September 2012 and 1 July 2013. After parental consent, these physicians completed a form at the inclusion of each patient, in which the characteristics of IBD were detailed. The patients mailed back their questionnaire. RESULTS: A total of 124 patients from 12 to 19 years of age were included with a response rate of 82% (all anonymous); 23% of the patients thought that diet was a possible cause of IBD and 22% that one of the targets of their treatment was to cure their disease for good. Of the patients reported having Crohn disease, 46% knew the anoperineal location and 14% knew that Crohn disease can affect the entire digestive tract. Twenty-five percent of the patients were able to name one side effect of azathioprine (88% had already received this treatment), 24% were able to name one side effect of infliximab (54% had already received this treatment), 70% of the adolescents knew that smoking worsens Crohn disease, 68% declared they had learned about their IBD from their pediatrician, and 81% said they would like to receive more information. CONCLUSION: Adolescents with IBD have gaps in their general knowledge and the different treatments of their disease. Their main source of information is their pediatrician, warranting the implementation of customized patient education sessions.

[Aquagenic palmoplantar keratoderma in children with cystic fibrosis]. / Kératodermie palmoplantaire aquagénique chez l'enfant mucoviscidosique.

INTRODUCTION: Aquagenic palmoplantar keratoderma (APK) is a cutaneous phenomenon marked by the formation of edematous, translucent papules and plaques on the palms after water immersion. It can be observed in healthy subjects, but while this dermatosis is little known by practitioners treating these patients, most cases of APK have been described in patients with cystic fibrosis (CF). The primary objective of this study was to evaluate the frequency of APK in a population of children with CF. In addition, the relationship between APK and sex, genotype, pancreatic and pulmonary function, body mass index, and sweat chloride levels was analyzed. METHODS: This study was conducted in 60 children, 27 girls and 33 boys, aged 4 months to 18 years, followed at the CF care center at Angers (France) University Hospital, in whom CF had been confirmed by a positive sweat chloride level greater than 60 mmol. APK was determined by questioning searching for modifications of the palms noticed by the patient or his/her family after immersion in water and a clinical examination searching for the same signs before and after immersion of the right hand in a bucket of lukewarm water for 3 minutes (bucket sign). RESULTS: Forty-seven out of 60 children (78%) had a positive bucket sign. Thirty-eight upon these 47 children had already noticed modifications of the skin on their palms, appearing quickly during the bath and 6 had an edema and an increase in skin folds on the palms of the hands even before immersion of their hand in water. No genotype-phenotype correlations were detected in patients with APK, nor were there associations of APK with other phenotypic features of CF. CONCLUSION: APK is very frequent in patients with CF. It is most probably a consequence of the dysfunction of the CFTR protein. It should be systematically sought in all patients with CF. Its discovery in another context should suggest the diagnosis of CF or a carriage to the heterozygous state of a mutation involved in the disease.

A higher inherent trait for fearfulness is associated with increased anxiety-like behaviours and diazepam sensitivity in Japanese quail.

This study tested whether lines of Japanese quails divergently selected for a fear response, the tonic immobility, might constitute a reliable bird model for studying anxiety. Previous studies demonstrated that the selection modifies the general underlying emotionality of the birds rather than exerting its effect only on tonic immobility. The behavioural effects of intraperitoneal injections of diazepam, an anxiolytic drug, were assessed in two lines of quail selected either for their short (STI) or long (LTI) duration of tonic immobility. Effects of diazepam were examined in two tests used for measuring emotionality in birds, the open field and the tonic immobility tests. After being placed in the centre of the open field, birds with a high emotionality (LTI quails) stayed longer in the centre of the apparatus than STI quail. Diazepam had anxiolytic effect in LTI birds as it increased the time spent in the outer area. This effect of diazepam appears to be selective because the drug has no effect on other behaviours such as distress calls or escape attempts. The drug has also no effect on the tonic immobility response in any of the two lines. These findings reveal an "anxiogenic" trait of LTI birds in the open field test that can be modulated by the administration of an anxiolytic drug. Therefore quails selected for LTI and STI represent a valuable model to study the mechanisms underlying anxiety in birds.

[Adolescent with anorexia nervosa: consequences on bone mineralization]. / Anorexie mentale de l'adolescent : conséquences sur la minéralisation osseuse.

INTRODUCTION: Anorexia nervosa is responsible for abnormalities in bone mineralization, which are well known and described in adults, but less well documented in adolescents. The aim of this research was to evaluate the frequency and severity and to determine predictive factors for these abnormalities in a population of adolescents with diagnosed anorexia nervosa. PATIENTS AND METHODS: This retrospective study involved 39 female adolescents with anorexia nervosa having undergone dual energy X-ray absorptiometry prior to the age of 18 years. Clinical (age, Tanner puberty stages, weight, body mass index [BMI] at different times during the anorexia phase and amenorrhea features), radiological (bone mineral density [BMD] in Z-score units and in absolute values), and biological (calcemia and vitamin D) parameters were collected. RESULTS: In total, 20 patients (51%) presented osteopenia (Z-score <-1 DS and >-2.5 DS) and 2 (5%) had osteoporosis (Z-score <-2.5 DS). Five (13%) exhibited a Z-score less than -2 DS. BMD expressed in Z-scores correlated with none of the parameters assessed. At univariate analysis, BMD in absolute values correlated with the age at disease onset, BMI, weight loss at the lowest weight achieved and BMI at the time of densitometry (P<0.01). At multivariate analyses, only the correlation with the age at disease onset persisted (P<0.05). CONCLUSION: Bone loss in anorexia nervosa is a complication that may be present as early as adolescence. It must be systematically searched for in all adolescents with severe malnutrition because, even if BMD correlated with nutritional parameters, no clinical predictor for osteoporosis or osteopenia could be identified in this study.

[Body composition analysis in patients with cystic fibrosis. Comparison of 3 methods: dual energy x-ray absorptiometry, bioelectrical impedance analysis, and skinfold measurements]. / Composition corporelle des patients mucoviscidosiques - comparaison de 3 techniques de mesure : anthropométrie, absorptiométrie biphotonique et impédancemétrie.

Nutritional status must be closely monitored in cystic fibrosis (CF) patients. This study compared three methods of measuring body composition in CF patients and then examined the relationships between two simple anthropometric markers of nutritional status - tricipital skinfold thickness (TSK) and arm muscular circumference (AMC) - and the results given by each method. Fifty-five patients with CF, 27 females and 28 males, participated in this study. The mean age at the time of the study was 14 ± 5 years, ranging from 4 to 29 years. The four skinfolds (SK) and arm circumference were measured in all patients and fat mass (FM) and AMC were calculated. Fifty patients underwent dual energy x-ray absorptiometry (DEXA) and 38 underwent bioelectrical impedance analysis (BIA). The values for FM as calculated by the three methods were highly correlated, as were the values for lean body mass (LM) (p<0.001). The LM assessed by anthropometry was overestimated by 8 ± 4% compared with DEXA and by 6 ± 7% compared with BIA. BIA overestimated LM by 4 ± 6% compared with DEXA (p<0.001). The LM values measured by SK, DEXA, and BIA were highly correlated with AMC (p<0.001) and FM calculated using these three techniques were highly correlated with TSK (p<0.001). The measurement of TSK and AMC are simple and rapid ways to evaluate body composition. The excellent correlation between the three methods used to measure body composition suggests that they are valid for use in patients with CF, but the results were not identical. The measurement from each technique must be interpreted according to its own norms and comparisons can only be made if the same technique is used in the same patient.

Afferent and efferent connections of the cortical and medial nuclei of the amygdala in sheep.

The cortical (CoA) and the medial (MeA) nuclei of the amygdala are involved in the processing of olfactory information relevant to social recognition in the ewe. To better understand the neural pathways responsible for these effects, the connections of both CoA and MeA with the telencephalic and diencephalic regions were studied by injecting an anterograde (Biotin-Dextran-Amine, BDA) or a retrograde (Fluorogold, FG) neuronal tracer into either the CoA or the MeA. Concerning the primary olfactory structures, the CoA receives inputs from both the main olfactory bulb and the accessory olfactory bulb (AOB), while the MeA is innervated by cells only from the AOB. Among the other olfactory structures, only the entorhinal cortex and the tenia tecta are connected with both the CoA and the MeA. With respect to the other secondary olfactory structures, the connections with the CoA and the MeA show segregating neuronal routes. The CoA is connected with the accessory olfactory nucleus, the piriform, the endopiriform and the orbitofrontal cortices while the MeA exhibited connections with the nucleus of the lateral olfactory tract, the perirhinal and the insular cortices. Concerning the diencephalic structures, only the MeA receives projections from the PVN and the MBH. On the other hand, we showed that the BNST is the major site of connection with both the CoA and the MeA. Reciprocal projections were observed between the CoA and the MeA and between both nuclei and the basal or the lateral nuclei of the amygdala with the exception of the CoA which does not send inputs to the lateral nucleus. These data are discussed in relation with olfactory learning in the context of sexual and maternal behavior in sheep.

Pulsatile cerebrospinal fluid and plasma ghrelin in relation to growth hormone secretion and food intake in the sheep.

As in other species, exogenous administration of ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptors can stimulates feeding behaviour and GH secretion in the sheep. However, the importance of endogenous ghrelin for these two functions as well as its central or peripheral origin remained to be established. In the present study, cerebrospinal fluid (CSF) ghrelin concentrations were measured in five anoestrous ewes and found to be more than 1000-fold lower than circulating plasma levels, in keeping with the even lower concentration in hypothalamic compared to abomasum tissue extracts. Cluster analysis indicated that CSF ghrelin levels were markedly pulsatile, with a greater number of peaks than plasma ghrelin. Pulsatility parameters were closer for GH and CSF ghrelin than between GH and plasma ghrelin. Plasma ghrelin and GH levels were significantly correlated in three out of five ewes but CSF ghrelin and GH in one ewe only. Half of the CSF ghrelin episodes were preceded by a ghrelin peak in plasma with a 22-min delay. Cross-correlations between plasma GH and plasma or CSF ghrelin did not reach significance but a trend towards cross-correlation was observed from 20 to 0 min between plasma and CSF ghrelin. At 09.00 h, when food was returned to ewes, voluntary food intake did not elicit a consistent change in plasma or CSF ghrelin levels. By contrast, a peripheral ghrelin injection (1 mg, i.v.) immediately stimulated feeding behaviour and GH secretion. These effects were concomitant with a more than ten-fold increase in plasma ghrelin levels, whereas CSF ghrelin values only doubled 40-50 min after the injection. This suggests that peripherally-injected ghrelin crosses the blood-brain barrier, but only in low amount and with relatively slow kinetics compared to its effects on GH release and food intake. Taken together, the results obtained in the present study support the notion that, in the ovariectomised-oestradiol implanted sheep model, peripheral ghrelin injection rapidly induces GH secretion, and feeding behaviour, probably by acting on growth hormone secretagogue receptor subtype 1 located in brain regions in which the blood-brain barrier is not complete (e.g. the arcuate nucleus).

Nutrition and hypothalamic neuropeptides in sheep: histochemical studies.

The identification and role of neuropeptides in the control of food intake and energy balance have been extensively studied in rodents, and for more than ten years, similar studies have been performed in sheep. As a photoperiodic ruminant, sheep are an interesting alternative animal model to rodents. In this review, we summarize the results obtained in sheep concerning the distribution of peptide-containing neurones in the hypothalamus and their central role in the control of food intake and energy balance, and compared them with relevant data from rodents. Even if the general organization and the role of hypothalamic neuropeptides are similar in sheep and rodents, numerous differences have been observed between these two species. In sheep, the magnocellular neurones of the paraventricular and supraoptic nuclei are characterized by the low density and the lack of galanin- and neuropeptide-Y-containing neurones, respectively. The sheep pituitary stalk presents neurones containing neuropeptides such as neuropeptide-Y or beta-endorphin, which are also found in the deep part of the infundibular nucleus. In this structure, several neuronal populations, including galanin, agouti-gene related peptide, somatostatin, are sensitive to energy balance variations, undernutrition or overfeeding, which may specifically modify neuropeptide levels in discrete neuronal subgroups. This feature is well illustrated by the number of neuropeptide-Y labelled neurones, that increases in the lateral part of the infundibular nucleus of undernourished ewes and decreases in the ventral part of overfed ewes. Conversely, after 24 hours of food deprivation, the number of neuropeptide-Y-immunolabelled neurones is unchanged in the sheep infundibular nucleus, whereas increased levels of this neuropeptide are described, in rats, by radioimmuno-assay. In conclusion, our review shows that peptide-containing neurone systems, involved in the regulation of food intake and energy balance in sheep, are generally similar to those observed in other species, but they present specific differences according to the physiological characteristics of the animal model.

Sensitivity of galanin- and melanin-concentrating hormone-containing neurones to nutritional status: an immunohistochemical study in the ovariectomized ewe.

The sensitivities of galanin and melanin-concentrating hormone (MCH) neuronal systems to nutrition are poorly understood in sheep compared to rodents. The aim of this study was to describe the changes in the numbers of galanin and MCH neurones in ovariectomized ewes submitted to different nutritional levels. In the first experiment, ewes were fed ad libitum or food deprived for 24 h. In the second experiment, two groups of ewes were fed at maintenance level (group 100) or undernourished (group 40) for 167 days, after which one-half of each group was killed or refed ad libitum (group 100R and 40R) for 4 days. The MCH neuronal population located in the lateral hypothalamic area was not affected by these nutritional changes. Long-term undernutrition enhanced the number of galanin neurones located in the infundibular nucleus and the dorsal hypothalamic area (DHA), refeeding resulted in an increase of neurones in the DHA and preoptic area, but short-term starvation had no effect on any galanin subpopulations. Our data suggest that the sensitivity of MCH neuronal populations to nutrition in sheep differs from that of rodents. Various populations of galanin-containing neurones differ in sensitivity in ewes subjected to long undernutrition and refeeding but not to short starvation.

Long-term undernutrition followed by short-term refeeding effects on the corticotropin-releasing hormone containing neurones in the paraventricular nucleus: an immunohistochemical study in sheep.

The effect of nutritional level on the immunoreactivity of corticotropin-releasing hormone (CRH) in neurones of the hypothalamic paraventricular nucleus was described in sheep, a ruminant, whose feeding strategy differs from that of monogastric species. Two groups of ewes were underfed (40%), or fed at maintenance (100%) for 167 days, after which one-half of each group was killed or ad libitum refed (at least 150% of maintenance) for 4 days before killing. The presence of CRH in the paraventricular nucleus was examined by immunohistochemistry. The number of CRH immunoreactive neurones was increased in underfed ewes, but without modification of the plasma concentration of cortisol, indicating that the rise of CRH was not released in the portal blood nor linked to the pituitary-adrenal axis. Refeeding did not modify significantly the number of CRH immunoreactive neurones in the nucleus although these neurones were increased, only in refed ewes that were previously underfed. These data differ from those for rats and mice where CRH expression is decreased or not modified by underfeeding which could reflect different effects of undernutrition on CRH immunoreactive neurones in monogastric compared to ruminants species.

Effect of feeding on Fos protein expression in sheep hypothalamus with special reference to the supraoptic and paraventricular nuclei: an immunohistochemical study.

The hypothalamus plays an important role in the control of food intake in different species, but there is little relevant information for ruminants like sheep. In order to study the putative role of several hypothalamic nuclei in food intake in sheep, Fos expression, a marker of cellular activity, was compared by immunohistochemistry between fed and unfed ewes. The expression of Fos protein was stimulated in the supraoptic nucleus of fed ewes, whereas it was increased in the paraventricular nucleus of unfed animals. In the latter nucleus, Fos immunoreactivity was mainly localized close to the third ventricle, an area corresponding to the parvocellular system of the nucleus, but never in the magnocellular system. In the paraventricular nucleus, the number of corticotrophin releasing factor-immunoreactive neurons and the number of Fos/corticotrophin releasing factor double-labelled neurons were not affected by feeding or lack of feeding. The number of Fos-immunoreactive neurons was higher in the lateral septum, the infundibular, the ventromedial and in the dorsomedial nuclei of unfed ewes than in those of fed ewes. Our results show for the first time that the dorsomedial and ventromedial nuclei are involved in the control of feeding in sheep as in rodents. The supraoptic nucleus of sheep is activated by the same conditions as in rodents but, conversely, the paraventricular nucleus is activated in unfed sheep, whereas in rodents and primates, this nucleus is activated by satiety as well as by fasting. In sheep, unlike in rodents, corticotrophin releasing factor did not appear to be involved in short-term regulation of food intake.

Distribution of galanin immunoreactivity in the sheep diencephalon.

Although the physiological role of galanin has been demonstrated in several endocrine regulations in sheep, the anatomical characteristics of this neuronal system has never been studied. The distribution of galanin-containing neurones was described by immunohistochemistry using galanin antiserum in the diencephalon of adult ewes, both ovariectomized or treated with colchicine. Galanin-immunoreactivity was found throughout the diencephalon. In the ovariectomized ewes, galanin-immunoreactive neurones were mainly observed in the medial preoptic area and the infundibular nucleus. The highest density of immunoreactive fibres was found in the external layer of the median eminence. Numerous galanin-immunoreactive fibres were also observed in the preoptic area, the mediobasal hypothalamus, the periphery of the supraoptic and the paraventricular nuclei. With colchicine treatment, the number of labelled neurones increased, and additional galanin-immunoreactive perikarya were observed in the bed nucleus of the stria terminalis, the lateral septum, the supraoptic, the paraventricular and the periventricular nuclei and the paraventricular nucleus of the thalamus. In the caudal part of the diencephalon, the density of labelled neurones was lower in both groups of animals than in other species studied. Regardless of treatment, labelling was not seen in the suprachiasmatic nucleus and only rarely in the ventromedial nucleus. These results describe, for the first time, the distribution of galanin-immunoreactive neurones in the sheep diencephalon. Compared to other species studied, distribution in the sheep diencephalon has several distinct differences. In ovariectomized animals, the medial preoptic area presents more labelled neurones in sheep than in monkeys, whereas in the supraoptic nucleus the density of labelled neurones is lower in sheep than in humans or opossums. After colchicine treatment only very few differences were observed between sheep and rats, but in contrast to other species, the suprachiasmatic nucleus of the sheep does not contain labelled neurones.

Presence of galanin in dopaminergic neurons of the sheep infundibular nucleus: a double staining immunohistochemical study.

The distribution of tyrosine hydroxylase (TH) and of galanin immunoreactive (IR) neurons were examined in the sheep infundibular nucleus. Antisera raised against TH and galanin were used on adjacent sections and for double immunohistochemical staining of the same sections. There was considerable overlap in the distribution of TH and galanin-IR neurons in the medial part of the nucleus. Most of the galanin-IR neurons were also TH-IR, but less than 50% of the TH-IR neurons also expressed galanin immunoreactivity. Neurons immunoreactive to TH alone were observed close to the third ventricle and in the rostral part of the infundibular nucleus. In the median eminence, TH and galanin-IR fibres overlapped mainly in the lateral and dorsal parts of the external layer, but the colocalisation of both antigens could not be assessed on the available material. Thus, in sheep, the population of catecholaminergic neurons of the infundibular nucleus may be subdivided into different subpopulations according to their peptide content, but does not appear segregated as in rat and human.

[The weaning of alcoholic patients in a general medicine hospital department. The value of tiapride]. / Le sevrage des malades alcooliques dans un service hospitalier de médecine générale. Intérêt du tiapride.

Every practitioner knows that, following alcohol withdrawal, the alcoholic patient may experience severe disorders. These are preventable by various measures such as a high fluid intake and therapy with sedatives and/or neuroleptics. Tiapride was given to 25 patients, with satisfactory results in 19. The authors believe that, in this indication, tiapride is effective, well tolerated and reduces the duration of the hospital stay.