Pulse-synchronous rotational and vertical pendular eye movements in superior canal dehiscence syndrome.
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Eye Movements↗
Biomedical subjects
K Jahn
Publications and source records attributed to K Jahn.
Temporospatial coupling of networked synaptic activation of AMPA-type glutamate receptor channels and calcium transients in cultured motoneurons.
AMPA-type glutamate receptor (GluR) channels provide fast excitatory synaptic transmission in the CNS, but mediate also cytotoxic insults. It could be shown that AMPA-type GluR channel-mediated chronic excitotoxicity leads to an increased intracellular calcium concentration and plays an important role in neurodegenerative diseases like for example amyotrophic lateral sclerosis (ALS). As calcium is an important mediator of various processes in the cell and calcium signals have to be very precise in the temporospatial resolution, excessive intracellular calcium increases can seriously impair cell function. It is still unclear if AMPA-type receptors can directly interact with the intracellular calcium homeostasis or if other mechanisms are involved in this process. The objective of this study was therefore to investigate the calcium homeostasis in rat motoneurons under physiological stimulation of AMPA-type GluR channels using calcium imaging techniques and patch-clamp recordings simultaneously. It was found that spontaneous excitatory postsynaptic currents of cultured motoneurons did not elicit significant intracellular calcium transients. Large intracellular calcium transients occurred only when preceding fast sodium currents were observed. Pharmacological experiments showed that activation of AMPA-type GluR channels during synaptic transmission has a great functional impact on the calcium homeostasis in motoneurons as all kinds of activity was completely blocked by application of the selective kainate- and AMPA-type GluR channel blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore we suggest from our experiments that calcium transients of several hundred milliseconds' duration result from release of calcium from the endoplasmic reticulum via activation of ryanodine receptors (calcium-induced calcium release, CICR). Our results help to understand the regulatory function of AMPA-type GluR channels in the intracellular calcium homeostasis which is known to be disturbed in neurodegenerative diseases.
Amyotrophic Lateral Sclerosis↗
Detection of floccular hypometabolism in downbeat nystagmus by fMRI.
The authors evaluated floccular activity with fMRI during the performance of vertical smooth pursuit eye movements in four patients with downbeat nystagmus (DBN) due to cerebellar degeneration and in 16 healthy controls. Region of interest analysis revealed a significantly diminished activation of both floccular lobes during downward but not upward pursuit in DBN. These imaging data support the view that a functional deficiency of the flocculi in downward pursuit causes DBN.
Aged↗
[Polysomnographic as a therapeutic aid in of psychogenic-functioning paraplegia].
The case of a patient with complete sensory and motor paraplegia for more than 1 year is presented. Leg movements were documented during sleep by video and electromyographic recording because a psychogenic cause of the symptoms was suspected. We showed the video to the patient, which illustrated that leg movements were possible. This resulted in fast and complete resolution of the neurologic symptoms. The patient has now been free of them for more than 3 years. This example suggests that the achievement of consciousness of normal motor function is a therapeutic approach for long-standing improvement of psychogenic paralysis.
Adult↗
How the eyes move the body.
The increased postural sway of patients with disorders of the vestibular system improves with vision. The suppression of pathologic nystagmus also reduces sway. Because the latter effect cannot be attributed to retinal slip as a relevant feedback for postural control, the authors investigated how eye movements rather than retinal slip affect balance. They found that slow eye movements increase sway, possibly by an efference copy, which explains why spontaneous nystagmus causes postural imbalance.
Adult↗
[The effect of combined mitoxantrone and methylprednisolone therapy in primary and secondary progressive multiple sclerosis. An applied study in 65 patients].
Mitoxantrone (mitox) has been shown to be effective for secondary progressive (SP) and relapsing-remitting multiple sclerosis (MS). The aim of this open trial was to evaluate the effects of combined mitox and methylprednisolone (MP) therapy on patients with primary progressive (PP)-MS or with SP-MS. We present here the results of an interim analysis done after the study had lasted 5 years. Sixty-five patients (20 with PP-MS and 45 with SP-MS) have been included so far. The treatment involved ten cycles of combined mitox and MP. The intervals between the individual cycles were systematically prolonged from 3 months initially to 12 months, so the complete treatment took a total of 57 months. Conclusion This interim analysis indicates that mitox combined with MP beneficially reduces the progression of disability in patients with PP-MS and SP-MS. Therefore, this therapy regimen can also be considered a feasible option for PP-MS.
Adult↗
Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants.
Safety, reactogenicity and immunogenicity of GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix)hexa) was assessed when used for primary vaccination at 3, 4 and 5 months of age (N = 2163), compared to the separate administration of DTPa-IPV/Hib and HBV vaccines (N = 720). A similar safety and reactogenicity profile was demonstrated for both vaccine regimens, as well as a good immune response for all antigen components. By offering protection against six diseases in a series of single injections, the hexavalent DTPa-HBV-IPV/Hib vaccine was shown to be a safe, well tolerated and immunogenic alternative to primary immunization with licensed separately administered vaccines.
Bacterial Capsules↗
Vertical oscillopsia in bilateral superior canal dehiscence syndrome.
A patient sought treatment for vertical oscillopsia and impaired vision during locomotion, and unsteadiness of gait. Positive fistula tests and CT of the temporal bones confirmed a diagnosis of bilateral superior canal dehiscence. An impairment of the superior canal vestibulo-ocular reflex, documented by three-dimensional search coil eye movement recordings for oblique (single) and downward pitch head motion (bilateral canal testing), is proposed to induce vertical rather than torsional-vertical oscillopsia during locomotion.
Female↗
Treatment of alcohol withdrawal: chlormethiazole vs. carbamazepine and the effect on memory performance--a pilot study.
Although relatively little attention has been paid to the question how acute alcohol withdrawal might affect cognitive functions, this factor remains of particular interest because it influences psychotherapeutic treatment during detoxification. The clinical outcome and neuropsychological state of 37 inpatients with alcohol withdrawal was investigated in a randomized single-blind approach. Two different medical strategies [chlormethiazole (CMZ) vs. carbamazepine (CBZ)] in the treatment of inpatients with alcohol withdrawal syndrome were compared. Among comparable groups (related to gender, age, initial alcohol level, severity of abuses, severity of initial withdrawal symptoms such as tremor, perspiration, psychomotor agitation, hallucinations, orientation, intelligence, patient demographics), CBZ is just as potent as CMZ in therapy of withdrawal symptoms (circulatory function, vegetative function, psychomotor activity). Patients in both groups showed initial impairments in some neuropsychological tests (d2, Zahlen-Verbundings test, Beck Depression Inventory, Anxiety Sensitivity Index) with significant improvement during detoxification. Additionally, CBZ-treated patients showed significantly better verbal memory performance during the first days of treatment. Without any addictive potential, CBZ therapy could be very supportive in alcohol detoxification. In addition a higher verbal memory performance state could be favourable for a psychotherapeutic approach.
Adult↗
Treatment of downbeat nystagmus with 3,4-diaminopyridine: a placebo-controlled study.
BACKGROUND: Several drugs that primarily act on gamma-aminobutyrate or muscarinic receptors have been used to treat downbeat nystagmus (DBN) syndrome despite their having only moderate success and causing several side effects that limit their effectiveness. These drugs were tested under the assumption that DBN was caused by a disinhibition of a physiologic inhibitory cerebellar input on vestibular nuclei. OBJECTIVE: To evaluate the effects of a single dose of the potassium channel blocker 3,4-diaminopyridine (3,4-DAP), which is known to increase the excitability of Purkinje cells, on DBN in a prospective, placebo-controlled, double-blind study with a crossover design. METHODS: Seventeen patients with DBN due to cerebellar atrophy (5), infarction (3), Arnold-Chiari malformation (1), or unknown etiology (8) were included in the study (1 of 18 patients had to be excluded). Mean peak slow-phase velocity (PSPV) was measured before and 30 minutes after randomized ingestion of 20 mg of 3,4-DAP or placebo orally; at least 1 week later, the treatments were switched. RESULTS: 3,4-DAP reduced mean PSPV of DBN from 7.2 +/- 4.2 degrees /s (mean +/- SD) before treatment to 3.1 +/- 2.5 degrees/s 30 minutes after ingestion of the 3,4-DAP (p < 0.001, two-way analysis of variance). Placebo had no measurable effect. In 10 of 17 subjects, the mean PSPV decreased by >50% and in 12 of 17 by >40%. In parallel, the subjects had less oscillopsia and felt more stable while standing and walking. Nine of the subjects continued to take the drug with success. Except for transient minor perioral or digital paresthesia reported by three subjects and nausea and headache reported by one, no other side effects were observed. CONCLUSIONS: In this study, the authors demonstrated that a single dose of 3,4-DAP significantly improved DBN. In view of animal studies reporting that micromolar concentrations of 4-aminopyridine increased the excitability of Purkinje cells, it is suggested that the efficacy of 3,4-DAP may be due to an increase of the physiologic inhibitory influence of the vestibulocerebellum on the vestibular nuclei.
4-Aminopyridine↗
IgG from patients with Guillain-Barré syndrome interact with nicotinic acetylcholine receptor channels.
In Guillain-Barré syndrome (GBS), immunoglobulin G (IgG) antibodies block neuromuscular transmission pre- and postsynaptically and thus are of potential pathogenic relevance. We investigated whether IgG from GBS patients has a direct interaction with nicotinic acetylcholine receptor (nAChR) channels. Purified IgG fractions from six GBS patients that blocked neuromuscular transmission in a previous study were analyzed by the patch-clamp technique in combination with an ultrafast system for solution exchange. Sera from three patients with other inflammatory neurological disorders were used as controls. Mouse myotubes expressing native embryonic-type nAChR channels and human embryonic kidney (HEK) 293 cells transiently transfected with recombinant adult-type nAChR channels were used. Repeated 20-ms pulses of acetylcholine (ACh) were applied to outside-out patches in the presence of GBS-IgG. IgG of the patients had a significant reversible blocking action on embryonic- and adult-type nAChR channels with some variability in the magnitude of the block. Activation and desensitization kinetics were not affected when GBS-IgG was applied. None of the control sera blocked the AChR channels. The observed postsynaptic block effect fulfills the criteria of a channel-blocking IgG antibody similar to those seen in autoimmune myasthenia and may contribute to muscle weakness during the acute phase of GBS.
Animals↗
Another adverse effect of aspirin: bilateral vestibulopathy.
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Anti-Inflammatory Agents, Non-Steroidal↗
Anterior canal failure: ocular torsion without perceptual tilt due to preserved otolith function.
A patient with anterior semicircular canal dehiscence syndrome underwent surgical patching that caused an isolated dysfunction of the left anterior semicircular canal postoperatively. He exhibited significant ocular torsion toward the side of the affected labyrinth (17 degrees excyclotropia of the ipsilateral eye), but no displacement of the subjective visual vertical. This dissociation suggests that an isolated ocular torsion may occur after an anterior semicircular canal lesion. A combined ocular torsion and subjective visual vertical tilt, which is usually seen with vestibular lesions, requires an associated otolith dysfunction.
Eye Diseases↗
Analysis of a slow desensitized state of recombinant adult-type nicotinic acetylcholine receptor channels.
A characteristic feature of the kinetics of nicotinic acetylcholine receptor (nAChR) channels is fast and nearly complete desensitization with a time course between 10 and 100 ms and recovery from desensitization in the range of some hundred ms. In the present study we used a piezo-driven system for ultra-fast solution exchange, analysed the recovery from the fast desensitized state of mouse recombinant adult-type nAChR channels and found no difference to that of embryonic-type channels. By double pulse experiments with application of pulses with a saturating concentration of 1 mm acetylcholine (ACh) with increasing duration of the first pulse and a constant interval between pulses we detected a second slow desensitized state which was entered with a time constant of 2835 ms. Recovery from the slow desensitized state proceeded with a single exponential with a time constant of 16134 ms. The experimental data were interpreted by the addition of a transition from the desensitized state with two bound ACh molecules to a slow desensitized state to the well known circular kinetic scheme of activation and desensitization of nAChR channels. This slow desensitized state might play a role in muscle fatigue or in pathological states like myasthenic syndromes.
Acetylcholine↗
Deactivation and desensitization of mouse embryonic- and adult-type nicotinic receptor channel currents.
Recombinant nicotinic acetylcholine receptor (nAChR) channels transiently expressed in HEK293 cells were investigated using the patch-clamp technique in the cell-attached and outside-out modes for single-channel analysis and ultra-fast agonist application to multiple channels. Deactivation (current decay after removal of agonist) and desensitization (current decay in the presence of agonist) were analyzed at embryonic- (gamma) and adult-type (epsilon) nAChR channels. Time constants of desensitization were similar for both receptor types (epsilon: 53.1+/-16.9 ms; gamma: 49.2+/-15.7 ms) and corresponded to the mean duration of clusters of single channel openings activated by pulses of 1 mM ACh. Deactivation showed distinct characteristics. Time constants were 1.76+/-0.16 ms for epsilon- and 3.19+/-0.18 ms for gamma-nAChR channels, corresponding to mean burst duration analyzed from single channels in the same preparation (epsilon: 1.85+/-1.2 ms, gamma: 3.85+/-2.1 ms). It is assumed that differences in deactivation are of functional relevance at the muscle endplate.
Acetylcholine↗
Quantification of mycophenolate mofetil in human skin extracts using high-performance liquid chromatography-electrospray mass spectrometry.
A sensitive and selective method for the quantification of mycophenolate mofetil and its active metabolite mycophenolic acid in different human skin layers after dermal administration is presented. The skin layers were separated after in vitro penetration experiments and a methanolic extraction was performed. Positive ion electrospray HPLC-MS in selected ion monitoring mode was used to quantify the substances after isocratic separation by a C18 analytical column. The minimum detectable concentrations were 850 pg/ml for MMF and 1 ng/ml for MPA. The peak areas depended linearly on the concentration of both drugs over the range of 25-1,000 ng/ml (r2 > or = 0.996) with accuracy < or =9.8% and precision < or = 13.2%. Total imprecision at quantification limits was 15.2% at 10 ng/ml and 16.3% at 1,500 ng/ml for MMF and 15.1% at 21.0 ng/ml and 17.5% at 1,300 ng/ml for MPA. This HPLC-MS method will be applicable to the profiling of MMF amounts in skin and its conversion to MPA after application of different formulations.
Chromatography, High Pressure Liquid↗
Intracranial hypotension syndrome due to duropleural fistula after thoracic diskectomy.
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Adult↗
Visually induced gait deviations during different locomotion speeds.
Optic flow is essential for the perception of self motion and the control of path integration during locomotion. Inverting prisms oriented 15 degrees off vertical in the roll plane were used to experimentally distort optic flow during locomotion. Depending on the direction in which the prisms were rotated, optic flow was diagonally upward to the right or upward to the left. A reproducible deviation of gait toward the direction of perceived optic flow was found in ten healthy subjects. This deviation is explained to be a gait deviation that compensates for misleading perceived self motion induced by optic flow. The amount of deviation was dependent on locomotion speed. When walking slowly (about 1 m/s), mean deviation was 0.22+/-0.08 m/s to the right and -0.18+/-0.08 m/s to the left for right and left, respectively, diagonal prism orientation. Deviation was significantly less when running (about 3 m/s) with mean deviations of 0.05+/-0.03 m/s and -0.06+/-0.03 m/s, respectively (ANOVA, P<0.01). It is assumed that path integration during running is largely achieved by highly automated spinal programs operating independently of sensory control. In contrast, walking is more dependent on afferent and reafferent visual control. Thus, the experiments show that visual control of locomotion is direction specific and dependent on optic-flow-induced vection. It becomes less influential with increasing speed of locomotion, e.g., when walking in contrast to running.
Adult↗