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In this article, we report in vivo 1H MRS performed in 1.8‐μL voxels in a mouse model of Down syndrome (DS). To characterise the excitation–inhibition imbalance observed in DS, metabolite concentrations in the hippocampi of adult Ts65Dn mice, which recapitulate features of DS, were compared with those of their euploid littermates at a voxel 42‐fold smaller than in a previously published study. Quantification of the metabolites was performed using a linear combination model. We detected 16 metabolites in the right and left hippocampi. Principal component analysis revealed that the absolute concentrations of the 16 detected metabolites could differentiate between Ts65Dn and euploid hippocampi. Although measurements in the left and right hippocampi were highly correlated, the concentration of individual metabolites was sometimes significantly different in the left and right structures. Thus, bilateral values from Ts65Dn and euploid mice were further compared with Hotelling's test. The level of glutamine was found to be significantly lower, whereas myo‐inositol was significantly higher, in the hippocampi of Ts65Dn relative to euploid mice. However, γ‐aminobutyric acid (GABA) and glutamate levels remained similar between the groups. Thus, the excitation–inhibition imbalance described in DS does not appear to be related to a radical change in the levels of either GABA or glutamate in the hippocampus. In conclusion, microliter MRS appears to be a valuable tool to detect changes associated with DS, which may be useful in investigating whether differences can be rescued after pharmacological treatments or supplementation with glutamine. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   
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STUDY OBJECTIVE: To assess the accuracy of chest ultrasonography in predicting pleural effusions > 500 mL in patients receiving mechanical ventilation. DESIGN: Prospective study. SETTING: Surgical and medical ICU in a teaching hospital. PATIENTS: Forty-four patients receiving mechanical ventilation with indications of chest drainage of a nonloculated pleural effusion. INTERVENTIONS: Diagnosis of pleural effusion was based on clinical examination and chest radiography. Chest drainage was indicated when considered as potentially useful for the patient (hypoxemia and/or weaning failure). Sonograms were performed before drainage at the bedside, in the supine position, and measurements were performed at the end of expiration. Effusions were classified as > 500 mL or < or = 500 mL according to the drained volume. MEASUREMENTS AND RESULTS: The drained volume ranged from 100 to 1,800 mL (mean, 730 +/- 440 mL [+/- SD]). The distance between the lung and posterior chest wall at the lung base (PLDbase) and the distance between the lung and posterior chest wall at the fifth intercostal space (PLD5) were significantly correlated with the drained volume (PLDbase, r = 0.68, p < 0.001; PLD5, r = 0.56, p < 0.001). A PLDbase > 5 cm predicted a drained volume > 500 mL with a sensitivity of 83%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 82%. Interobserver and intraobserver percentages of error were, respectively, 7 +/- 6% and 9 +/- 6% for PLDbase, and 6 +/- 5% and 8 +/- 5% for PLD5. The PaO2/fraction of inspired oxygen ratio significantly increased after chest drainage in patients with collected volumes > 500 mL (p < 0.01). CONCLUSIONS: Bedside pleural ultrasonography accurately predicted a nonloculated pleural effusion > 500 mL in patients receiving mechanical ventilation using simple and reproducible measurements.  相似文献   
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Rationale:Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy.Patient concerns:A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia.Diagnoses:A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis.Interventions:The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area.Outcomes:Disease progression finally led to the patient''s death 3 years after diagnosis.Lessons:This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.  相似文献   
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Background and aims

Lynch syndrome (LS) is associated with an increased risk of small bowel tumors but routine screening is not recommended in international guidelines. The aim of our study was to determinate the prevalence of duodenal tumors in a French cohort of LS patients.

Methods

Patients carrying a germline pathogenic variant in a MMR gene, supported by our local network, in which at least one upper endoscopy had been performed, were included. We registered the occurrence of duodenal lesions in those patients.

Results

154 LS patients were identified including respectively 85 MSH2 and 41 MLH1 mutated patients respectively. Seven out of 154 (4.5%) had at least one duodenal lesion. Median age at diagnosis was 58 years (range: 49–73). The twelve lesions locations were: descending duodenum (n?=?7), genu inferius (n?=?2), duodenal bulb (n?=?1), ampulla (n?=?1), fourth duodenum (n?=?1). Three lesions were invasive adenocarcinomas. The incidence rate of duodenal lesions in patients with MSH2 or MLH1 pathogenic variants was respectively 7.1% (6 out of 85) and 2.4% (1 out of 41) emphasizing a trend toward increased risk of developing duodenal lesion in MSH2 mutated patients: OR: 5.17, IC95% (0.8–60.07), p?=?0.1307.

Conclusion

Regarding this high prevalence rate, especially in MSH2 patients, regular duodenal screening during upper endoscopy should be considered in routine in LS patients.  相似文献   
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Summary Several calcium antagonists are useful in the treatment of ischemic heart disease. This open randomized study was designed to determine the effects of bepridil, a new long-acting calcium antagonist with antiarrhythmic properties, on the course of acute myocardial infarction (AMI). Two hundred patients with AMI of less than 48 hours duration (average 10.9 hours) were randomly assigned to two treatment groups: The first one was treated with bepridil (BEP, n=100), and the second one was considered as a control group, using isosorbide dinitrate at a low dosage (ISDN, n=100). BEP was administered intravenously for 48 hours at a dosage of 4 mg/kg/day; at the same time, an oral dose of 200 mg t.i.d. was started and continued for 21 days. In the control group, ISDN was given orally at the low dosage of 5 mg every 4 hours for 21 days. An uneventful course was seen in 28 BEP patients versus 15 in the control group (p<0.05). Mortality and recurrence of angina were lower in the BEP group than in the control group, but the difference is not significant. On the other hand, moderate and severe hemodynamic complications did not occur in 80 BEP patients versus 65 in the control group (p<0.05). Ventricular arrhythmias occurred in 36 BEP patients versus 50 in the control group (p<0.05). Antiarrhythmic therapy was required in 14 BEP patients versus 61 in the control group (p<0.001). These results show that bepridil seems capable of improving the hemodynamics and arrhythmologic course of AMI.  相似文献   
40.
Exposure to allergens could be either a risk factor of sensitization and nonspecific hyperresponsiveness in genetically predisposed patients or a risk of onset of asthma attack in certain allergic asthma. During the past 20 years, in western countries the houses have become higher and the number of furred pets have increased and have been more kept inside the house which makes probable that exposure to indoor aeroallergen has increased. The development of new methods of allergen measurements allows a more precise identification of allergen source and reservoirs, an assessment of allergen exposure and a monitoring of allergen eviction methods. Concerning mite allergens, controlled studies which showed a clinical efficacy are those with a global mite eviction and at least a 6 months follow-up for cat and dog allergens, high efficiency-filters air cleaners or vacuum-cleaners are able to reduce airborne cat or dog allergen levels. According to the increasing number of papers about allergen eviction, it seems logical to propose allergen eviction as "first line treatment" of allergic asthma. In the future, it would be interesting to develop biological markers to identify more accurately patients who have a clinical improvement after allergen eviction.  相似文献   
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