Synaptically evoked membrane potential oscillations induced by substance P in lamprey motor neurons.

Short-lasting application (10 min) of tachykinin neuropeptides evokes long-lasting (>24 h) modulation of N-methyl-D-aspartate (NMDA)-evoked locomotor network activity in the lamprey spinal cord. In this study, the net effects of the tachykinin substance P on the isolated spinal cord have been examined by recording from motor neurons in the absence of NMDA and ongoing network activity. Brief bath application of substance P (30 s to 2 min) induced irregular membrane potential oscillations in motor neurons. These oscillations consisted of depolarizing and hyperpolarizing phases and were associated with phasic ventral-root activity. The oscillations were blocked by the tachykinin antagonist spantide II. They were also blocked by tetrodotoxin (TTX), suggesting that they were not dependent on intrinsic membrane properties of the motor neurons but were synaptically mediated. Substance P could also have a direct effect, however, because a membrane potential depolarization persisted in the presence of TTX. Protein kinase agonists and antagonists were used to investigate the intracellular pathways through which substance P acted. The oscillations were blocked by the selective protein kinase C (PKC) antagonist chelerythrine. However, the TTX-resistant membrane potential depolarization was not significantly affected by blocking PKC. The protein kinase A and G antagonist H8 did not affect either the oscillations or the direct TTX-resistant membrane potential depolarization. The glutamate receptor antagonist kynurenic acid abolished the substance-P-evoked oscillations, suggesting that they were dependent on glutamate release. The oscillations were abolished or reduced by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione but were only reduced by the NMDA receptor antagonist D-AP5. The oscillations were thus mediated by glutamatergic inputs with a greater dependence on non-NMDA receptors. Blocking glycinergic inputs with strychnine resulted in large depolarizing plateaus and bursts of spikes. The glutamatergic and glycinergic inputs underlying the oscillations are apparently evoked through direct and indirect excitatory effects on inhibitory and excitatory premotor interneurons. Substance P thus has a distributed excitatory effect in the spinal cord. While it can activate premotor networks, this activation alone is not able to evoke a coordinated behaviorally relevant motor output.     

How Cluster Headache is Explained as an Intracavernous Inflammatory Process Lesioning Sympathetic Fibers

SYNOPSIS
A large body of evidence points to an inflammatory process in the cavernous sinus and tributary veins as being primarily responsible for cluster headaches. The inflammation obliterates the venous outflow from the cavernous sinus on one side and injures the through-running sympathetic fibers to the eye, upper eye lid, forehead skin, and the intracranial internal carotid artery and its branches. The active period ends when the inflammation is suppressed and the sympathetic fibers partially or fully recover. Evidence is presented that the symptoms suggestive of an enhanced parasympathetic activity during attacks may alternatively be explained as local pain fiber activation or a stasis in the outflow from the cavernous sinus. Vasodilator agents like nitroglycerin induce an attack by enhancing the venous load on the cavernous sinus. Constriction of the proximal intracranial internal carotid artery, spontaneously induced by tressful pain activation of the perivascular sympathetic nerves, or by exogenous administration of serotonin 1 D-like receptor agonists or oxygen, terminates the venous load and thus the pain and associated symptoms.     

A double-blind combination study of clonazepam with sertraline in obsessive-compulsive disorder.

This double blind, randomized, parallel, placebo-controlled study investigates whether clonazepam accelerates and/ or increases the overall response in patients with obsessive compulsive disorder (OCD) who are treated with sertraline. Thirty-seven patients were randomized with 20 in the sertraline and clonazepam group and 17 in the sertraline and placebo groups. Male and female outpatients, age 18-65 years, met criteria for a primary diagnosis of obsessive compulsive disorder according to DSM-IV, as determined by the structured clinical MINI interview. Appropriate safety and efficacy parameters were measured throughout the study. The determination of efficacy was based primarily on changes from baseline to the last observation taken through week 12. Analysis revealed no significant difference between groups at endpoint on the main scale.     

Homozygosity for the transthyretin-Met30-gene in seven individuals with familial amyloidosis with polyneuropathy detected by restriction enzyme analysis of amplified genomic DNA sequences

Familial amyloidotic polyneuropathy (FAP) with a mutation in position 30 of transthyretin (TTR) (previously called prealbumin) is an autosomal dominant inherited disorder characterized by varying degrees of peripheral neuropathy, nephropathy, gastrointestinal problems, and vitreous amyloid. We have earlier diagnosed homozygosity for the TTR-Met30-gene using Southern analysis in four Swedish individuals. We have found it possible to detect homozygosity for the Met-30 mutation by amplifying discrete regions of the TTR-gene using polymerase chain reaction (PCR), and the amplification products restricted with NsiI analysed by gel electrophoresis. Clinical data on seven homozygous individuals, including three new cases, are presented.     

Human Chest Wall Function while Awake and during Halothane Anesthesia: I. Quiet Breathing

Background: Data concerning chest wall configuration and the activities of the major respiratory muscles that determine this configuration during anesthesia in humans are limited. The aim of this study was to determine the effects of halothane anesthesia on respiratory muscle activity and chest wall shape and motion during spontaneous breathing.

Methods: Six human subjects were studied while awake and during 1 MAC halothane anesthesia. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional fast computed tomography. Tidal changes in gas volume were measured by integrating respiratory gas flow, and the functional residual capacity was measured by a nitrogen dilution technique.

Results: While awake, ribcage expansion was responsible for 25 plus/minus 4% (mean plus/minus SE) of the total change in thoracic volume (Delta Vth) during inspiration. Phasic inspiratory activity was regularly present in the diaphragm and parasternal intercostal muscles. Halothane anesthesia (1 MAC) abolished activity in the parasternal intercostal muscles and increased phasic expiratory activity in the abdominal muscles and lateral ribcage muscles. However, halothane did not significantly change the ribcage contribution to Delta Vth (18 plus/minus 4%). Intrathoracic blood volume, measured by comparing changes in total thoracic volume and gas volume, increased significantly during inspiration both while awake and while anesthetized (by approximately 20% of Delta Vth, P < 0.05). Halothane anesthesia significantly reduced the functional residual capacity (by 258 plus/minus 78 ml), primarily via an inward motion of the end-expiratory position of the ribcage. Although the diaphragm consistently changed shape, with a cephalad displacement of posterior regions and a caudad displacement of anterior regions, the diaphragm did not consistently contribute to the reduction in the functional residual capacity. Halothane anesthesia consistently increased the curvature of the thoracic spine measured in the sagittal plane.     

Parvovirus B19 and parvovirus V9 are not associated with Henoch-Sch?nlein purpura in children.

BACKGROUND: Based on single case reports, parvovirus B19 (B19) has repeatedly been proposed as an etiologic agent in patients with Henoch-Sch?nlein purpura (HSP), perhaps causing vasculitis by direct invasion of vascular endothelial cells because of the tissue distribution of the cellular B19 receptor. A cohort of children with HSP and other vasculitic diseases was investigated and compared with healthy control children to assess the role of B19 as well as parvovirus V9 (a putative emerging B19-like virus). PATIENTS AND METHODS: Serum samples from 36 children with HSP (n = 29) or other vasculitic diseases (n = 7) were examined, and 38 healthy bone marrow donors were used as controls. The presence of specific B19 and V9 IgM and IgG antibodies was determined with a recently developed enzyme-linked immunosorbent assay, and viral DNA was detected by a novel nested PCR. RESULTS: Specific IgM was not present in any of the patient or control serum samples. B19 DNA was detected in one patient, a previously healthy 8-year-old boy diagnosed with HSP, whereas none of the controls was B19-positive. V9 was not detected in any of the clinical or control samples. It seems likely that B19 infection might have triggered the development of HSP in the B19-positive patient, because B19 viremia is otherwise uncommon. CONCLUSIONS: Although causality is difficult to construe in single cases, the data indicate that B19 is not a common contributing factor in the pathogenesis of vasculitis and that this pathogen is only rarely associated temporally with HSP or vasculitic diseases in children.     

The role of different imaging modalities: is MRI a conditio sine qua non for ETV?

Objective To describe the different imaging modalities used for the diagnosis and classification of hydrocephalus, their role in defining the optimal treatment of hydrocephalus and to define the optimal preoperative diagnostics for endoscopic third ventriculocisternostomy (ETV). Methods An overview on available imaging modalities for hydrocephalus will be given and their pros and cons discussed. In addition, different aspects of the treatment of hydrocephalus by shunts and by ETV will be highlighted. Discussion The role of the technical aspects of performing an ETV, the role of the surgeon’s philosophy, the role of the urgency of the procedure, and the role of informed consent on the requirements for the imaging of the hydrocephalus will be discussed. Conclusion The authors conclude that MRI is a conditio sine qua non for ETV in elective surgical cases.