Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression.

The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [11C]ABP688 positron emission tomography (PET) scans on the same day-before and during intravenous ketamine administration-and a third scan 1 day later. At baseline, significantly lower [11C]ABP688 binding was detected in the MDD as compared with the control group. We observed a significant ketamine-induced reduction in mGluR5 availability (that is, [11C]ABP688 binding) in both MDD and control subjects (average of 14±9% and 19±22%, respectively; P<0.01 for both), which persisted 24 h later. There were no differences in ketamine-induced changes between MDD and control groups at either time point (P=0.8). A significant reduction in depressive symptoms was observed following ketamine administration in the MDD group (P<0.001), which was associated with the change in binding (P<0.04) immediately after ketamine. We hypothesize that glutamate released after ketamine administration moderates mGluR5 availability; this change appears to be related to antidepressant efficacy. The sustained decrease in binding may reflect prolonged mGluR5 internalization in response to the glutamate surge.

Learn how to interpret and use intracranial EEG findings.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.

[Rebound tonometry with sterilized probes]. / Rebound-Tonometrie mit sterilisierten Sonden.

BACKGROUND: Intraoperative measurement of intraocular pressure (IOP) opens up possibilities to investigate the influence of IOP on the stability of the eyeball during the performance of surgical maneuvers. Few techniques have been described, none of which are commercially available. This study investigated the use of sterilized probes for rebound tonometry, which could be used intraoperatively. MATERIAL AND METHODS: Tonometry was performed on 30 eyes using a noncontact tonometer and rebound tonometry with the iCare 100 and iCare 200 (iCare Finland Oy, Vantaa, Finland) in a sitting and in a supine position. When performing rebound tonometry probes from the package were used sequentially with sterilized probes. The comparability of sterilized and nonsterilized probes was investigated using different rebound tonometers and different settings. RESULTS: Measurements on a sitting subject were comparable with sterilized and nonsterilized probes. Statistically significant comparability was also found in a supine position. Measurements with identically sterilized probes on identically positioned subjects were comparable with iCare 100 und iCare 200 (T2 vs. T4, p = 0.003 und T3 vs. T5 p < 0.001). The comparison of measurements of the original probe with the sterilized probe in a sitting and in a supine position were possible with statistical significance (p < 0.005). Measuring with the iCare 200 in a sitting position showed a slightly lower IOP with the sterilized probe with the difference being statistically significant. DISCUSSION: Single autoclaving does not alter the probes' ability to measure IOP. CONCLUSION: The use of probes which have been sterilized according to the regulations for other surgical instruments opens up new possibilities for the intraoperative measurement of IOP. This facilitates the use in scientific studies on surgical techniques. In the postoperative period the use of sterilized probes can reduce the risk of infection.

Targeted density electrode placement achieves high concordance with traditional high-density EEG for electrical source imaging in epilepsy.

OBJECTIVE: High-density (HD) electroencephalography (EEG) is increasingly used in presurgical epilepsy evaluation, but it is demanding in time and resources. To overcome these issues, we compared EEG source imaging (ESI) solutions with a targeted density and HD-EEG montage. METHODS: HD-EEGs from patients undergoing presurgical evaluation were analyzed. A low-density recording was created by selecting the 25 electrodes of a standard montage from the 83 electrodes of the HD-EEG and adding 8-11 electrodes around the electrode with the highest amplitude interictal epileptiform discharges. The ESI solution from this "targeted" montage was compared to that from the HD-EEG using the distance between peak vertices, sublobar concordance and a qualitative similarity measure. RESULTS: Fifty-eight foci of forty-three patients were included. The median distance between the peak vertices of the two montages was 13.2 mm, irrespective of focus' location. Tangential generators (n = 5/58) showed a higher distance than radial generators (p = 0.04). We found sublobar concordance in 54/58 of the foci (93%). Map similarity, assessed by an epileptologist, had a median score of 4/5. CONCLUSIONS: ESI solutions obtained from a targeted density montage show high concordance with those calculated from HD-EEG. SIGNIFICANCE: Requiring significantly fewer electrodes, targeted density EEG allows obtaining similar ESI solutions as traditional HD-EEG montage.

Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.

Retained surfactant catheter and pneumothorax in a premature neonate.

Surfactant catheters are used to administer exogenous surfactant as a preventive and therapeutic measure for surfactant deficiency in premature neonates. We describe the case of a retained surfactant catheter in a 700 g premature neonate with associated pneumothorax.

A dynamical adaptive resonance architecture.

A set of nonlinear differential equations that describe the dynamics of the ART1 model are presented, along with the motivation for their use. These equations are extensions of those developed by Carpenter and Grossberg (1987). It is shown how these differential equations allow the ART1 model to be realized as a collective nonlinear dynamical system. Specifically, we present an ART1-based neural network model whose description requires no external control features. That is, the dynamics of the model are completely determined by the set of coupled differential equations that comprise the model. It is shown analytically how the parameters of this model can be selected so as to guarantee a behavior equivalent to that of ART1 in both fast and slow learning scenarios. Simulations are performed in which the trajectories of node and weight activities are determined using numerical approximation techniques.

[Helicobacter pylori gastric infections in children]. / Infections gastriques à Helicobacter pylori chez l'enfant.

OBJECTIVES: Numerous reports have established the association of Helicobacter pylori and recurrent abdominal pain in children. We investigated the clinical, bacteriological and therapeutic features of our patients seen over a 1 year period. METHODS: We investigated 121 children during 1992 in Hospital Saint Vincent-de-Paul, Paris. At endoscopy, biopsies were taken and sent for histology and bacteriology and urease testing. A decision regarding treatment by amoxicillin and metronidazol was made after positive results of bacteriology and/or histology. RESULTS: Heliobacter pylori was found in 47 antral biopsies after pathology examination with Giemsa staining alone 16 times, bacterial culture 9 times and both methods 22 times. Abdominal pain was the prominent symptom, occurring in 35.5% of Helicobacter pylori+patients. In 25 of the positive negative patients, a nodular gastritis was observed (53.1%) and in 27.6% of them a weight loss or a delay in weight gain. Few patients became after combined treatment with amoxicillin and metronidazol whereas eradication rates after triple therapy with amoxicillin-metronidazol and H2 antagonist or proton pump blocker were higher. CONCLUSION: Helicobacter pylori related gastritis is a common cause of abdominal complaints in children. The most common symptom is recurrent abdominal pain. Antral nodularity is a peculiar endoscopic finding in children. Two-drug therapy associating amoxicillin-metronidazol is often ineffective to eradicate the bacteria whereas eradication rates after triple therapy amoxicillin-metronidazol and H2 antagonist or proton pump blocker are higher.

Presystemic elimination of morphine in anesthetized rabbits. Contribution of the intestine, liver, and lungs.

To assess the role of the intestine and the lung in the first-pass uptake of morphine relative to that of the liver, five groups of 6-7 New Zealand rabbits were used. A control group of conscious rabbits received 2 mg/kg of morphine iv. The remaining groups included anesthetized rabbits who received morphine into the aortic cross (2 mg/kg), the jugular vein (2 mg/kg), the portal vein (14 mg/kg), or into the duodenum (20 mg/kg). Multiple blood samples were withdrawn for 3 hr from the abdominal aorta, and morphine and morphine-6-glucuronide were assayed by HPLC. Anesthesia and surgery decreased morphine presystemic clearance from 264 +/- 14 to 194 +/- 12 ml/min/kg (p < 0.05). When morphine was injected into the aortic cross, the area under morphine plasma concentration-time curve (AUCM 0-->infinity) normalized by the dose was 7.81 +/- 0.56 10(-3) kg min/ml, a value that decreased to 5.26 +/- 0.36 (p < 0.05), 2.50 +/- 0.35 (p < 0.05), and 0.87 +/- 0.10 (p < 0.05) 10(-3) kg min/ml when morphine was injected before the lung, liver, or intestine, respectively. The extraction ratio of morphine by the lung, liver, and intestine was 0.33, 0.52, and 0.65, respectively. Compared with the aortic route, the AUCM6G 0-->infinity normalized by the dose ratio tended to be greater (p > 0.05) when morphine was injected into the jugular and portal veins, suggesting that morphine-6-glucuronide is not the major product result of morphine first-pass uptake.(ABSTRACT TRUNCATED AT 250 WORDS)