[Food protein-induced enterocolitis syndrome (FPIES) in 14 children]. / Syndrome d'entérocolite induite par les protéines alimentaires (SEIPA) : une série de 14 enfants.

INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) is a particular non-IgE-mediated food allergy, manifested by profuse and repetitive vomiting with hypotonia and lethargy in its acute form. METHODS: A retrospective descriptive single-center study was conducted. Subjects included in this study were children with acute FPIES who consulted the allergy outpatient clinic of the Nancy Regional University Hospital between November 2013 and June 2016. RESULTS: Among the 14 patients (eight boys and six girls), nine had a history of atopy: a family history for six (42.8%) and a personal history for five (35.7%). Three had chronic FPIES turning into acute FPIES. Cow milk was the most common triggering food (50%), followed by fish (21.4%), mussels (14.3%), wheat (7.1%), egg (7.1%), and poultry (7.1%). The average time from ingestion to symptom onset was 90minutes. The symptoms were typical and diarrhea was not systematic (42.8%). Six children were hospitalized, some of them several times, including once in intensive care for one patient. The treatments established were, in order of frequency: oral or intravenous rehydration, corticosteroids, antihistamines, and antiemetics. Diagnosis time was 7.6 months on average; it was significantly shorter for milk than for solid foods (1.4 vs. 12 months, P-value=0.02), on average after two episodes. Another diagnosis than FPIES was raised at first for five patients (acute gastroenteritis, gastroesophageal reflux, and bowel obstruction caused by bowel volvulus). Allergy tests were initially negative. Two chronic FPIES cases (one milk FPIES and one milk and wheat FPIES) developed an acute FPIES to another food (fish and mussels); one patient changed from an acute fish FPIES to an IgE-mediated phenotype over time. FPIES resolved for four patients: three milk FPIES, on average 15.7 months after the first reaction, and one wheat FPIES, 2.5 years after the first reaction. A child with a white fish FPIES was able to introduce salmon and tuna. CONCLUSION: FPIES is a pathology that has suffered from a lack of knowledge, delaying diagnosis for many months. The progression of chronic forms to acute forms and acute forms to an IgE-mediated allergy is not rare. Doctors need more detailed knowledge: profuse and repetitive vomiting accompanied by hypotonia and/or lethargy should suggest the diagnosis of acute FPIES. To improve the management of acute FPIES, a treatment protocol is proposed here.

Pallidum and lateral ventricle volume enlargement in autism spectrum disorder.

Studies on structural brain abnormalities in individuals with autism spectrum disorders (ASD) have been of limited size and many findings have not been replicated. In the largest ASD brain morphology study to date, we compared subcortical, total brain (TBV), and intracranial (ICV) volumes between 472 subjects with DSM-IV ASD diagnoses and 538 healthy volunteers (age range: 6-64 years), obtained from high-resolution structural brain scans provided by the Autism Brain Imaging Data Exchange (ABIDE). Compared to healthy volunteers, we found significantly larger pallidum (Cohen's d=0.15) and lateral ventricle volumes (Cohen's d=0.18) in ASD. These enlargements were independent of total brain volume and IQ, passed FDR correction for multiple comparisons, and were observed in overall, male-only, and medication-free subjects. In addition, intracranial, hippocampal, and caudate volumes were enlarged in ASD at a nominal statistical threshold of p<0.05. This study provides the first robust evidence for pallidum enlargement in ASD independent from TBV and encourages further study of the functional role of the pallidum in individuals with autism spectrum disorder.

Heritability of Hippocampal Formation Sub-region Volumes.

BACKGROUND: Hippocampal formation (HF) volume and episodic memory performance are substantially heritable, but HF subregion heritability estimates and their possible shared genetic variance with episodic memory performance remain to be determined. METHODS AND FINDINGS: This study provides heritability estimates for hippocampal subregions (e.g, Cornu Amonis, Subiculum, Parasubiculum, Molecular and Granule Cell Layers of the Dentate Gryus) and Total HF volumes obtained using FreeSurfer 6.0. In addition, this study assesses the heritability of object sequence and verbal episodic memory performance, and the amount of shared genetic variance between HF subregions and Total HF volume and episodic memory performance. HF volumes were obtained from high-resolution brain scans from a sample of 499 siblings (mean age±SD=30.0±3.1, 203 men), including 51 monozygotic and 46 dizygotic twin pairs and 305 non-twin siblings, collected by the Human Connectome Project (www.humanconnectome.org). Heritability estimates for HF subregions ranged from 0.42-0.87 and shared genetic variance of HF subregions with hippocampal volume was substantial (mean=0.79, range=0.50-0.98). HF subregion volumes residualized for Total HF and percent HF subregion volumes were also found to be substantially heritable (range=0.04-0.86 and 0.07-0.84, respectively). Verbal (h2=0.47) but not object sequence episodic memory was found to be significantly heritable; though the amount of shared genetic variance between HF subregions and verbal episodic memory was low (mean=0.10, range=0.01-0.20). CONCLUSIONS: These findings suggest that HF subregion volumes are heritable and can be used as quantitative phenotypes in genetic association studies. The low shared genetic variance between HF subregions and verbal episodic memory suggests that quantitative trait analyses may not benefit from including both HF volume and episodic memory as bivariate traits in healthy individuals. The extent to which HF subregion volumes share genetic variance with neuropsychiatric disorders, and as such add value to our ability to identify genetic risk loci for these disorders, remains to be determined.

Learn it now, sing it later? Field and laboratory studies on song repertoire acquisition and song use in nightingales.

In many bird species, song changes with age. The mechanisms that account for such changes are only partially understood. Common nightingales Luscinia megarhynchos change the size and composition of their repertoire between their first and second breeding season. To inquire into mechanisms involved in such changes, we compared the singing of 1-year-old and older free-living nightingales. Older males have more song types in common than have 1-year olds. Certain song types frequently sung by older birds did not (or only rarely) occur in the repertoire of yearlings ('mature' song types). We conducted learning experiments with hand-reared nightingales to address reasons for the lack of mature song types. The acquisition success of mature songs was as good as that of control songs (commonly sung by both age groups). However, the analysis of song type use revealed that all yearlings sang common song types more often than mature types. This indicates that the absence of certain song types in the repertoires of free-living yearlings cannot be accounted for by learning and/or motor constraints during song learning. Moreover, our results suggest that in communication networks, animals may restrict the actual use of their signal repertoire to a certain subset depending on the context.

(E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-indolinone blocks mast cell degranulation.

(E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-indolinone (indolinone) is an alkaloid that has been identified as a pharmacologically active compound in extracts of the traditional anti-inflammatory herb Isatis tinctoria. Indolinone has been shown to inhibit compound 48/80-induced mast cell degranulation in vitro. Application of indolinone to bone marrow derived mast cells showed that it was uniformly distributed in the cytoplasm and that cellular uptake was terminated within minutes. Pre-treatment of IgE-sensitized mast cells with 100nM indolinone rendered them insensitive against FcvarepsilonRI-receptor dependent degranulation. However, upstream signalling induced by antigen such as activation of PI3-K and MAPK remained unaffected. We conclude that indolinone blocks mast cell degranulation at the level of granule exocitosis with an IC(50) of 54nm.

Multidrug-resistant gram-positive infections in patients with ventricular assist devices: the role of daptomycin.

OBJECTIVES: The rate of infection in patients who require ventricular assist devices (VADs) is estimated at more than 35%. Infections with multidrug-resistant (MDR) organisms in VAD recipients present a high mortality rate. Daptomycin (Cubicin, Novartis, Nuremberg, Germany), a new cyclic lipopeptide antibiotic, is useful for MDR gram-positive organisms. We report the successful use of daptomycin in patients presenting with MDR gram-positive infections after VAD implantation. METHODS: We retrospectively studied nine consecutive patients presenting with resistant gram-positive infections after VAD implantation treated with daptomycin. We analyzed type of VAD, type of infection, responsible microorganism, outcome, and adverse events. RESULTS: We studied nine patients (eight males, one female), of overall mean age of 51 +/- 8 years; 78% required a biventricular assist device or a left VAD (Berlin Heart, Berlin, Germany), 22% received other ventricular support. Sixty-six percent presented with catheter-related infections (CRIs). Therapy with daptomycin was empirically initiated in all cases. The initial dose was 6 mg/kg, continued at 4 mg/kg. The mean duration of therapy was 16 +/- 5 days. The reported pathogens were MRSA, 33%; E. faecium, 25%; methicillin-resistant staphylococcus epidermidis, 12.5%; methicillin-sensitive staphylococcus aureus, 12.5%; others, 17%. Successful outcomes were reported in seven subjects (78%), with two patients succumbing due to multiorgan failure related to their heart condition prior completing antibiotic therapy. No adverse events were reported. CONCLUSIONS: Among our VAD patients, daptomycin proved efficient as a therapy for CRI with bacteremia. However, controlled studies are necessary to evaluate this antibiotic in patients presenting with VAD and MDR bacteremia.

["Saar Stroke Teleservice--pilot study for stroke after care with a home care platform]. / "Schlaganfall-Teleservice Saar"-Pilotversuch zur Schlaganfallnachsorge mit einer Homecare-Plattform.

In the German region Saarland a pilot trial has been conducted for the post-clinical telecare and rehabilitation of stroke patients in there homes by a cooperative network of local healthcare providers. For that purpose an e-home care platform has been developed by a combine of Fraunhofer institutes under the leadership of the Fraunhofer Institute for Biomedical Engineering. A network formed by a clinic, 2 general practitioners and an advice centre cared for 18 patients using the so-called PHS Homecare Platform for telemonitoring and virtual visits by videophone. (PHS: Personal Health Service--A research initiative of the Fraunhofer Society in the years 1996-2001). In the underlying feasibility study the telecare of stroke patients in the context of the German healthcare system has been tested and the e-home care platform has been evaluated.

Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.

The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wild-type receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.

Microinjections of dopaminergic agents in the nucleus accumbens affect ethanol consumption but not palatability.

It was determined whether ethanol palatability in rats could be changed by manipulating the reinforcement experienced during limited access consumption. During the first 3 days of the experiment, initial taste reactivity (TR) testing to distilled water (1 day) and 10% alcohol (2 days) was performed. Following the establishment of baseline TR, separate groups of animals received bilateral microinjections (0.5 microl/side) into the nucleus accumbens of either the nonspecific dopamine agonist d-amphetamine sulfate (20 microg, n = 10), the D(2) antagonist raclopride (1.0 microg, n = 8), or physiological saline (n = 5). The injections occurred at the same time each day for 5 consecutive days. Five minutes after the microinjection, the fluid-deprived rats were given 30-min access to 10% ethanol. Over the 3 days following drug administration, TR to distilled water and 10% alcohol was repeated. After this, the rats were once again given 30 min of access to 10% ethanol for 5 consecutive days, but without drug microinjection prior to alcohol access. A final TR exposure (the same as the others) was performed over the final 3 days of the study. Both raclopride and d-amphetamine administration produced reductions in ethanol consumption (in comparison to saline treatment). However, treatment with d-amphetamine and raclopride during ethanol consumption did not cause significant, conditioned changes in palatability as measured by the taste reactivity procedure. These results suggest that dopamine plays a role in the motivation to consume ethanol but this neurotransmitter is not involved in evaluating its incentive value.

Taste reactivity in alcohol-preferring AA and alcohol-avoiding ANA rats.

Alcohol-preferring rats (Alko alcohol or AA) were tested for taste reactivity to water, sucrose, quinine, and a range of alcohol concentrations (5-40%) both before and after a period of continuous alcohol access. The alcohol-avoiding line of rats (Alko nonalcohol or ANA) was also tested for comparison. It was found that AA rats displayed greater ingestive reactivity to alcohol compared to ANA rats both before and after a three-week period of continuous access to 10% alcohol (during which time AA rats drank significantly more alcohol than ANA rats). AA rats also made significantly more ingestive responses to a 0.3 M sucrose solution and a 0.0005 M quinine solution. Differences between AA rats and ANA rats in aversive reactivity appeared only after the alcohol consumption tests; AA rats made significantly fewer aversive responses to the 30% and 40% concentrations after continuous alcohol access. AA rats also made significantly more aversive responses to the quinine solution. The results suggest that line differences between AA rats and ANA rats in the reactivity response to alcohol solutions have been selected in association with the original selection phenotype of alcohol consumption.

Ethanol consumption in rats selectively bred for differential saccharin intake.

Rat lines selectively bred for high ethanol consumption consume more saccharin solution than do their low-ethanol-consuming counterparts. The present study utilized the technique of reciprocal selection to examine the reliability of the saccharin/ethanol relationship; specifically, consumption of 1-10% ethanol solution was measured in rats selectively bred for high vs. low saccharin consumption (Occidental HiS and LoS lines). HiS rats consumed more ethanol than did LoS rats. These results support the idea that individual differences in ethanol and saccharin consumption share some common mechanism(s).

Taste reactivity to alcohol and basic tastes in outbred mice.

The taste reactivity test was used to determine the response of outbred mice to orally infused taste solutions. For the initial measures, mice (n = 10) were tested with 3%, 6%, 9%, and 12% (v/v) alcohol and four taste solutions: sucrose, sodium chloride, hydrochloric acid, and quinine hydrochloride (a single concentration of each). A second group of naive mice (n = 16) was tested with 5%, 10%, 20%, 30%, and 40% alcohol. The final set of measures with naive mice (n = 26) was taken with a range of sucrose concentrations: 0.01 M, 0.05 M, 0.1 M, 0.5 M, and 1.0 M. In general, mice made similar reactivity responses to all solutions tested. A predominant component of the mouse response to all infused fluids was forelimb flailing; gaping was also a common response to all solutions. Despite the large number of aversive-type responses, mice rejected very little fluid via passive drip or fluid expulsion. The single, significant difference in responding to the four taste stimuli was that mice made fewer aversive responses to sucrose. Differential responding to the 5 to 40% alcohol concentrations and sucrose concentrations was observed. Mice increased ingestive responding as the concentration of alcohol and sucrose increased. Aversive responding decreased reliably only with increases in the sucrose concentration. Data provide the first reported taste reactivity responses of mice to orally infused taste solutions. These results can be compared with the extant data available in rats and can also be used as a basis for exploring taste factors in genetically defined mouse populations.

Naltrexone treatment increases the aversiveness of alcohol for outbred rats.

Acute naltrexone treatments (0.0, 0.5, 1., or 3.0 mg/kg body weight) were administered to separate groups of rats and alcohol taste reactivity and consumption were measured. Rats were given daily naltrexone injections and then tested for taste reactivity to 10% alcohol 30 and 60 min after injection. Each reactivity trial (total of 4) was 60 sec during which 1 ml of fluid was infused. The rats' orofacial and body movements were videotaped and scored later. In the final measure, rats were placed on a restricted fluid access schedule and given naltrexone treatments 10 min before being presented with the 10% alcohol solution in the home case (60-min drinking period). After 4 days of consumption tests under the drug condition, the rats were given 4 more daily tests without the drug. Results indicated that the two highest naltrexone doses significantly decreased ingestive responding and increased aversive responding, particularly at the 30-min test. Both the 1.0 and 3.0 mg/kg body weight doses also significantly decreased alcohol consumption as measured during the free access tests. Alcohol consumption returned to control levels immediately after the drug treatments were stopped. The data show that dosages of naltrexone 1.0 mg or higher significantly alter both alcohol taste reactivity (increased aversiveness and decreased palatability) and alcohol consumption (decreased intake) in outbred rats. These results are discussed in relation to naltrexone treatment as a means for decreasing alcohol use and abuse.

Taste reactivity in high-alcohol-sensitive and low-alcohol-sensitive rats.

High, low, and control alcohol-sensitive (HAS, LAS, CAS, respectively) rats were tested for their perception of the taste of alcohol using the taste reactivity test. Reactivity tests with a single concentration of sucrose and quinine were also done. After initial taste reactivity, all rats were tested for alcohol consumption in a standard two-bottle test (water in the second bottle). Postconsumption taste reactivity tests completed the experiment. Results indicated that HAS, LAS, and CAS rats did not differ significantly in their taste reactivity response to a range of alcohol concentrations (5-40%), nor did they differ significantly in response to sucrose or quinine. Reactivity responses were similar for each group before and after the consumption tests. Despite the lack of line differences in taste reactivity, HAS and LAS rats consumed significantly less alcohol than the CAS rats during the two-bottle access tests. The present results are in contrast to research done with rats selectively bred for alcohol consumption (Alcohol Preferring and Nonpreferring rats, High Alcohol Drinking and Low Alcohol Drinking rats), which exhibit clear line differences in patterns of reactivity changes following alcohol access. The selection phenotype of alcohol sensitivity appears to be independent of rats' behavioral response to the taste of alcohol.

Continuous intraoral saccharin infusions in high vs. low saccharin-consuming rats.

Confirmed high saccharin (HiS)-consuming and low saccharin (LoS)-consuming rats were compared in their taste response to saccharin using a continuous intraoral infusion procedure. On 2 separate days, rats were infused with 0.1% saccharin (rate = 1 ml/min) until they rejected fluid via passive drip or forceful fluid expulsion (at which time infusion was stopped for 30 s), and then again rejected fluid within 30 s after infusion was reinitiated. Two dependent measures were collected during infusion procedures: latency to first fluid rejection and total infusion time. On the first infusion day, HiS and LoS rats produced similar latencies to first rejection and total infusion times. However, HiS rats displayed significantly longer latencies to first rejection than LoS rats on the second infusion day. The results indicate that continuous infusion procedures exposed differences between HiS and LoS lines, but only after an initial experience with saccharin, albeit a relatively short exposure. The absence of immediate line differences with infusion procedures suggests that preference differences for saccharin between HiS and LoS lines are not mediated by brainstem taste reflexes, but rather are guided by associative processes accomplished above the brainstem.

Temporary vessel occlusion during intracranial aneurysm repair.

Any method that decreases the risk of intraoperative rupture should improve outcome if complications associated with its use do not negate positive effect. If application time is limited and a form of cerebral protection and appropriate monitoring of cerebral function are used, temporary clip application may meet these requirements. The efficacy of temporary occlusion as an adjunct to aneurysm clipping may be limited by technical considerations with respect to regional anatomy, aneurysm size, and aneurysm consistency. In areas of limited access, positioning proximal clips may not be feasible. The use of endovascular techniques of balloon occlusion may provide proximal control in these situations (9, 106). The decision to use total circulatory arrest and profound hypothermia, as opposed to temporary clip application, remains largely a matter of the surgeon's judgment. The role of proximal parent vessel ligation must also be considered in the decision-making process regarding the treatment of giant or technically difficult aneurysms (114). Further refinements in cerebral monitoring that can accurately reflect intracellular processes in all territories affected by the application of temporary clips or balloon occlusion and development of more effective forms of cerebral protection may permit safer use of this technique. An adequately controlled clinical trial of temporary occlusion with or without putative "cerebral protection" is needed to confirm the efficacy of this technique.

Recruitment experience in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Several approaches for recruitment of African American adults with renal insufficiency due to hypertension (glomerular filtration rate between 25 and 70 ml/min/1.73 m2) were explored in the Pilot Study for the African American Study of Kidney Disease and Hypertension (AASK). Over a period of 42 weeks, prescreening information was obtained on 2880 individuals, of whom 498 (17%) were evaluated at a screening visit. Two hundred and twenty-five (8%) had an 125I-iothalamate assessment of glomerular filtration rate. Ninety-four of 97 participants who met all the study eligibility criteria were enrolled in the trial. The most common reasons for ineligibility during screening were absence of renal insufficiency or hypertension, presence of diabetes mellitus, and a body mass index above the acceptable level. Overall, an average of 31 prescreen contacts and 8 screening visits were conducted for every randomization (3.3% yield from prescreening to randomization). Screening in clinical practice was the most efficient method for recruitment (12.6% yield from prescreen contact to randomization compared to 1.1% from mass mailing campaigns, 1.3% from mass media campaigns, and 1.7% from referrals by patients with end-stage renal disease). Randomization yields increased with progressively higher age ranges (2.4%, 3.3%, and 6.0% prescreen to randomization yields for those aged < or = 50, 51-60, and 61-70, respectively). A slight majority (51%) of the prescreen contacts were women, but 75% of the randomized participants were men. Our results suggest that clinic-based screening is an effective approach for recruitment of African Americans with hypertension and renal insufficiency into clinical trials. They also suggest that enrollment of African American women in such studies is a special challenge.

Harvey Cushing and Claude Beck: a surgical legacy.

Harvey cushing's contribution to neurosurgery and other surgical specialties has been profound. The accomplishments of his many pupils have further immortalized Cushing's role as a pioneering advocate of surgical science. Claude S. Beck, the first professor of cardiovascular surgery in the United States, was one such student. Beck's career and successes are illustrative of Cushing's guidance and enduring support for his surgical heirs. Beck's first encounter with Cushing evoked a spirit of fraternity and fashioned a respect and loyalty to Cushing that lasted for the duration of Beck's career. Cushing's personality and the methods by which he perpetuated a rich surgical tradition are illuminated by details of Beck's stay at the Peter Bent Brigham Hospital as a Cabot Fellow in Cushing's laboratory, by diary accounts of his later 6-week visit in 1927, and by the numerous telling correspondences between the two men. This article traces Beck's association with Cushing and provides unique insights into Cushing, his Cleveland connections, and his neurosurgical service at the Brigham.

Taste reactivity in rats selectively bred for high vs. low saccharin consumption.

Rats selectively bred for high (HiS) vs. low (LoS) saccharin consumption were compared on taste reactivity responses to 0.1% saccharin before and after continuous access to 0.1% saccharin. The rats were also tested with other saccharin concentrations (0.01-0.3%) before and after the consumption test. Finally, all rats were tested for reactivity to 0.1 M sucrose, 0.0001 M quinine hydrochloride, and a sucrose + quinine mixture. HiS rats ingested more saccharin than did LoS rats, but the groups did not differ in total ingestive or total aversive reactivity on any of the taste tests. When aversive reactivity was analyzed further to distinguish passive drip from other, more active responses, HiS rats made more active responses than LoS rats; the latter showed a consistent tendency to passive drip more than HiS rats. Overall, aversive responding decreased and ingestive responding increased as saccharin concentration rose and from the first to the second concentration series. Because the brain stem-mediated hedonic evaluation of tastes by HiS and LoS rats appears to be similar, the difference in saccharin consumption must be mediated by psychological processes whose neural substrates lie above the brain stem.

Structure of the Ras-binding domain of c-Raf-1 as determined by NMR spectroscopy and identification of the region that interacts with Ras.

The structure of the Ras-binding domain of human c-Raf-1 (residues 55 to 132) as determined in solution by NMR spectroscopy is presented. It consists of a five-stranded beta-sheet, a twelve residue alpha-helix, and an additional one-turn helix. The fold belongs to a known family whose members include ubiquitin and protein G. The surface of Raf55-132 that interacts with Ras has been identified by resonance perturbation mapping. The binding site is a spatially contiguous patch comprised of the two-N-terminal beta-strands, the loop between them, and the C-terminal end of the alpha-helix. A model of the Raf-Ras complex is presented, which was derived by analogy to the complex between protein G and a Fab fragment of IgG. In the model, edge beta-strands of each protein align in an antiparallel orientation, forming a unified beta-sheet, and side chains from both proteins are able to participate in ionic and hydrophobic interactions at the interface.