Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium‐binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67‐GFP knock‐in mice) or PV+ neurons (PV‐Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67‐GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium‐sized (15–20 μm) GFP+ neurons. Most medium and large‐sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast‐firing and spontaneously active in vitro. They exhibited prominent hyperpolarization‐activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV‐Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep. J. Comp. Neurol., 521:1225–1250, 2013. © 2012 Wiley Periodicals, Inc.     

The effects of antithrombotic drugs in patients with left ventricular thrombi: assessment with indium-111 platelet imaging and two-dimensional echocardiography

Patients with left ventricular thrombi not caused by recent myocardial infarction were prospectively studied by indium-111 platelet imaging and two-dimensional echocardiography to determine the reproducibility of these techniques and the short-term effects of sulfinpyrazone (200 mg four times daily), aspirin (325 mg three times daily) plus dipyridamole (75 mg three times daily), and full-dose warfarin. At baseline, all patients underwent indium-111 platelet imaging and echocardiography, and the results were positive for thrombus. In six patients on no antithrombotic drug therapy, repeat platelet scans and echocardiographic studies at 6.0 +/- 3.3 weeks remained positive and were unchanged. In seven patients studied on sulfinpyrazone, three platelet scans became negative, two became equivocal, and two were unchanged; the presence and size of thrombus was constant by echocardiography in all seven patients. Of the six patients studied on aspirin plus dipyridamole, one platelet scan became negative, those of three became equivocal, and two were unchanged; all echocardiographic findings remained positive, but one patient had decreased thrombus size. Among four warfarin-treated patients, three had resolution of platelet deposition and one was unchanged; by echocardiography, thrombus resolved in one patient, was decreased in size in one, and was unchanged in two. We conclude that, in the absence of antithrombotic drug therapy, platelet imaging and echocardiographic findings are stable in patients with left ventricular thrombi not caused by recent myocardial infarction. Sulfinpyrazone, aspirin plus dipyridamole, and warfarin all interrupt platelet deposition in some patients with chronic left ventricular thrombi.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible Reversal of PTSD-Related DNA Methylation by Sympathetic Blockade

Studies have shown that brain-derived neurotrophic factor (BDNF) level increase is associated with post-traumatic stress disorder (PTSD) risk. BDNF may be a “missing-link” that mediates the interaction between genetics, environment, and the sympathetic system. Trauma has been shown to induce DNA methylation that in turn can increase BDNF concentration due to increased gene expression. Therapies that focus on the reduction of beta-NGF (BNGF) levels may impact PTSD symptoms. The focus of this paper is to discuss possible effect of stellate ganglion block (SGB) on epigenetic changes noted with PTSD mediated by BDNF and NGF. Stellate ganglion block has recently shown significant therapeutic efficacy for treatment of PTSD symptoms. Previously reported theoretical mechanisms of SGB impact on PTSD have focused on likely reduction of NGF, leading to eventual loss of extraneous sympathetic nerve growth, eventually leading to reduction of secondary norepinephrine level, which in turn is hypothesized to reduce PTSD symptoms. We used PUBMED to obtain available data following a search for the following: DNA, neurotrophic factors, post-traumatic stress disorder, and demethylation following local anesthetic application. A number of articles meeting criteria were found and reviewed. Based on the evidence summarized, trauma can lead to DNA methylation, as well as BNGF/NGF level increase, which in turn starts a cascade of sympathetic sprouting, leading to increased brain norepinephrine, and finally symptomatic PTSD. Cascade reversal may occur in part by demethylation of DNA caused by application of local anesthetic to the stellate ganglion.     

Digital chest imaging using a 57-cm image intensifier: A receiver-operating characteristic study of user performance

Chest radiography provides one of the great challenges to digital diagnostic imaging because of (1) the relatively large size of the chest field, (2) the contrast range required to resolve subtle pathological changes in soft tissue density, and (3) the high degree of spatial resolution required to discriminate pathological detail. The field size problem was resolved by using a 57-cm image intensifier whose video output of the chest could be digitized. The issue of contrast resolution was addressed in a recently completed receiver-operating characteristic study of the detectability of low-contrast densities in a humanoid chest phantom. The latter indicated that, despite the smaller size of the digital image, they were adequate for resolving clinically significant soft-tissue densities. The question of spatial resolution in digital diagnostic images is addressed in the study presented. A set of 41 clinical cases were selected to provide the typical range of diagnostic type experienced in routine diagnostic radiology. The images were each presented as conventional film, digital laser-printer, and digital video images. The results of an ROC analysis of five readers' performance in each of the viewing modes is presented.     

Interventional radiology in the airway in children

Interventional procedures in the airway can be performed in interventional radiology suites or the operating room, by radiologists or other specialists. The most common therapeutic interventions carried out by radiologists are balloon dilatation, stenting, and the treatment of certain airway fistulas. These operations can be very challenging for anesthetists in terms of planning, airway management, the identification and treatment of procedural complications and postoperative care. In particular, a multidisciplinary approach to decision‐making and planning is important to obtain the best results.     

A comparison of the efficacy and safety of olanzapine and risperidone in the treatment of elderly patients with schizophrenia: an open study of six months duration

BACKGROUND: Following an earlier study in which elderly patients with schizophrenia had their typical antipsychotic medication changed to olanzapine or risperidone, the 61 patients were followed for up to a further six months to see if either treatment was superior in terms of efficacy or side effects. AIMS: To determine whether either olanzapine or risperidone was superior in terms of efficacy or side effects when treating schizophrenia in late life. METHODS: Psychiatric symptoms, side effects and quality of life were rated every six weeks for 24 weeks of open label comparative treatment using standard measures. Group differences were examined using analysis of covariance and within-group changes over time were assessed using paired t-tests. RESULTS: There were 34 olanzapine and 32 risperidone patients who entered the study, but intention to treat data was only available for 61 of the 66 patients. There were no clinical or demographic differences between the groups. Parkinsonism, positive and negative symptoms of schizophrenia improved in both groups both from baseline switch to olanzapine or risperidone and during the six month follow-up after completion of crossover. No significant differences were seen between groups on most measures. However, patients treated with olanzapine showed a significantly greater improvement in quality of life from baseline compared to risperidone patients. CONCLUSIONS: Both drugs were well tolerated and their use was associated with fewer symptoms of schizophrenia and less adverse effects than were seen when the patients were taking a typical antipsychotic at baseline. Olanzapine appears to have particular benefit with regard to quality of life.     

Characterization of GABAergic neurons in rapid-eye-movement sleep controlling regions of the brainstem reticular formation in GAD67-green fluorescent protein knock-in mice

Recent experiments suggest that brainstem GABAergic neurons may control rapid-eye-movement (REM) sleep. However, understanding their pharmacology/physiology has been hindered by difficulty in identification. Here we report that mice expressing green fluorescent protein (GFP) under the control of the GAD67 promoter (GAD67-GFP knock-in mice) exhibit numerous GFP-positive neurons in the central gray and reticular formation, allowing on-line identification in vitro . Small (10–15 µm) or medium-sized (15–25 µm) GFP-positive perikarya surrounded larger serotonergic, noradrenergic, cholinergic and reticular neurons, and > 96% of neurons were double-labeled for GFP and GABA, confirming that GFP-positive neurons are GABAergic. Whole-cell recordings in brainstem regions important for promoting REM sleep [subcoeruleus (SubC) or pontine nucleus oralis (PnO) regions] revealed that GFP-positive neurons were spontaneously active at 3–12 Hz, fired tonically, and possessed a medium-sized depolarizing sag during hyperpolarizing steps. Many neurons also exhibited a small, low-threshold calcium spike. GFP-positive neurons were tested with pharmacological agents known to promote (carbachol) or inhibit (orexin A) REM sleep. SubC GFP-positive neurons were excited by the cholinergic agonist carbachol, whereas those in the PnO were either inhibited or excited. GFP-positive neurons in both areas were excited by orexins/hypocretins. These data are congruent with the hypothesis that carbachol-inhibited GABAergic PnO neurons project to, and inhibit, REM-on SubC reticular neurons during waking, whereas carbachol-excited SubC and PnO GABAergic neurons are involved in silencing locus coeruleus and dorsal raphe aminergic neurons during REM sleep. Orexinergic suppression of REM during waking is probably mediated in part via excitation of acetylcholine-inhibited GABAergic neurons.