Clinical signs in the diagnosis of deep vein thrombosis.

AIM: Deep vein thrombosis (DVT) is an insidious disease wherein more than 15 different clinical signs are described. The aim of this work was to focus on these clinical signs and to test them for their importance in making a diagnosis of DVT. METHODS: All patients treated with a tentative diagnosis of DVT in the emergency department were asked to take part in the study. Out of the 254 patients who were examined in order to exclude DVT, 204 patients agreed to participate in the study. The patients who agreed to take part were tested for fifteen clinical examination signs. The Wells score was then determined. RESULTS: Sixty-two were diagnosed with DVT. For 142 patients, DVT could be ruled out. The probability of DVT for 9 signs together is 88%, and for 3 signs is 78%. The negative predictive values are 91-95%. The combination of the clinical signs showed a specificity of 100%, independent if the patients were old, comorbid, and were diagnosed with the thrombosis in the lower limbs. The determination of the Wells score resulted in no convincing evidence for or against the diagnosis of DVT. CONCLUSION: We suggest a modified Wells score integrating missing clinical signs with more reliable predictive values. Even with the availability of ultrasound, clinical signs have not become superfluous. They are quick to carry out, safe, cheap and an important addition to the Wells score, particularly for multimorbid and elderly patients.

Interplay between subthreshold potentials and gamma oscillations in Mauthner cells' presynaptic inhibitory interneurons.

Oscillations are widely distributed throughout the nervous system. A number of models accounting for their generation and their contribution to the synchronization of the concerned neurons, have been proposed. Most of these schemes involve inhibitory interneurons. Here we studied, in vivo, the firing patterns of interneurons, identified as presynaptic to the goldfish Mauthner (M) cell, and called passive hyperpolarizing potential (PHP) cells. We found that a subset of these interneurons was characterized by the presence of subthreshold oscillations of their membrane potential. Such oscillations near the firing threshold generated action potentials that were phased-locked on the oscillations and consequently, the distributions of time intervals between these spikes were observed at integral multiple values of the oscillation cycles. Two superimposed oscillatory processes have been identified. The amplitude of the first one, "the carrier," was voltage dependent while that of the second, the "modulator," was not. The frequency of the carrier was distributed among four values (140, 100, 71 or 50 Hz), the frequency of the "modulator" was about 50 Hz in almost all the investigated neurons. The demonstration that the 50 Hz oscillations were shared by almost all PHP exhibiting neurons strongly supports the notion that these cells act synchronously. Finally, auditory stimulations activated "silent" interneurons whereas they inhibited "active" ones, confirming that the presence of oscillations endows the M-cell inhibitory network with dynamic properties which can effectively organize the timing of motor behavior. Our results demonstrate that multiple frequencies, all in the gamma range, can coexist in the same network and that oscillations are present in a well defined population of inhibitory cells that controls fast decision-making.

Interleukin-1beta induces hyperpolarization and modulates synaptic inhibition in preoptic and anterior hypothalamic neurons.

Most of the inflammatory effects of the cytokine interleukin 1beta (IL-1beta) are mediated by induction of cyclooxygenase (COX)2 and the subsequent synthesis and release of prostaglandin E2. This transcription-dependent process takes 45-60 min, but IL-1beta, a well-characterized endogenous pyrogen also exerts faster neuronal actions in the preoptic area/anterior hypothalamus. Here, we have studied the fast (1-3 min) signaling by IL-1beta using whole-cell patch clamp recordings in preoptic area/anterior hypothalamus neurons. Exposure to IL-1beta (0.1-1 nM) hyperpolarized a subset ( approximately 20%) of preoptic area/anterior hypothalamus neurons, decreased their input resistance and reduced their firing rate. These effects were associated with an increased frequency of bicuculline-sensitive spontaneous inhibitory postsynaptic currents and putative miniature inhibitory postsynaptic currents, strongly suggesting a presynaptic mechanism of action. These effects require the type 1 interleukin 1 receptor (IL-1R1), and the adapter protein myeloid differentiation primary response protein (MyD88), since they were not observed in cultures obtained from IL-1R1 (-/-) or from MyD88 (-/-) mice. Ceramide, a second messenger of the IL-1R1-dependent fast signaling cascade, is produced by IL-1R1-MyD88-mediated activation of the neutral sphingomyelinase. C2-ceramide, its cell penetrating analog, also increased the frequency of miniature inhibitory postsynaptic currents in a subset of cells. Both IL-1beta and ceramide reduced the delayed rectifier and the A-type K(+) currents in preoptic area/anterior hypothalamus neurons. The latter effect may account in part for the increased spontaneous inhibitory postsynaptic current frequency as suggested by experiments with the A-type K(+) channel blockers 4-aminopyridine. Taken together our data suggest that IL-1beta inhibits the activity of preoptic area/anterior hypothalamus neurons by increasing the presynaptic release of GABA.

[Stable tachycardia with wide QRS complex in pre-hospital emergency medicine]. / Stabile Tachykardie mit breitem QRS-Komplex in der prähospitalen Notfallmedizin -- Ergebnisse des NAVT-Trials (NotArzt und Ventrikuläre Tachykardie).

BACKGROUND: Sustained, stable wide QRS-complex tachycardia (WCT) remains a diagnostic challenge, because the treatment of supra-ventricular tachycardia (SVT) with aberrant conduction differs considerably from that of a ventricular tachycardia (VT). A usual recommendation for treating a case of a stable WCT is to manage it as if it were VT, in accordance with the consideration of "first do no harm". The aim of this study was to determine whether Board-certified emergency-physicians are able to differentiate VT from SVT with aberrant conduction in a high percentage of cases (> 90%), thus to assure more precise prehospital treatment." METHODS: Eight electrocardiograms with WCT (four with electrophysiologically proven VT or SVT, respectively) were evaluated in a blinded fashion by 64 Board-certified emergency-physicians (23 female, 41 male, mean age: 37,8 + 5,1 years). Initially, the diagnosis had to be made without any further information. Afterwards the same electrocardiograms were presented again, providing important additional information. RESULTS: 55% of the study population were able to establish the correct diagnosis merely by evaluating the electrocardiogram. Providing the above mentioned additional information, the number of correct diagnoses increased to 61%. These results were roughly similar in all subgroups, only the subgroup of cardiologists showed a trend to better results with correct diagnoses in 68% without and 73 % with additional information. None of the subgroups reached the pre-specified cut-off of > or = 90% correct diagnoses. Specialist status as well as experience in emergency medicine had no significant influence on the results, only the subgroup of emergency physicians with an experience of more than five years showed a trend towards a higher rate of correct diagnosis, compared with the subgroup with less than one year experience in emergency medicine. CONCLUSION: In cases of stable WCT the evaluation of the electrocardiogram without further information in prehospital emergency-medicine leads to unsatisfactory results. The correct diagnosis in WCT can be improved by using additional data but the diagnostic accuracy is still low. Therefore, the differential diagnosis of stable WCT in preclinical emergency-medicine cannot be recommended. Until proven otherwise, any stable WCT should be managed as if it were VT.

Electrophysiological properties and thermosensitivity of mouse preoptic and anterior hypothalamic neurons in culture.

Responses of mouse preoptic and anterior hypothalamic neurons to variations of temperature are key elements in regulating the setpoint of homeotherms. The goal of the present work was to assess the relevance of culture preparations for investigating the cellular mechanisms underlying thermosensitivity in hypothalamic cells. Our working hypothesis was that some of the main properties of preoptic/anterior hypothalamic neurons in culture are similar to those reported by other authors in slice preparations. Indeed, cultured preoptic/anterior hypothalamic neurons share many of the physiological and morphological properties of neurons in hypothalamic slices. They display heterogenous dendritic arbors and somatic shapes. Most of them are GABAergic and their activity is synaptically driven by the activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors. Active membrane properties include a depolarizing "sag" in response to hyperpolarization, and a low threshold spike, which is present in a majority of cells and is generated by T-type Ca2+ channels. In a fraction of the cells, the low threshold spike repeats rhythmically, either spontaneously, or in response to depolarization. The background synaptic noise in cultured neurons is characterized by the presence of numerous postsynaptic potentials which can be easily distinguished from the baseline, thus providing an opportunity for assessing their possible roles in thermosensitivity. An unexpected finding was that GABA-A receptors can generate both hyper- and depolarizing postsynaptic potentials in the same neuron. About 20% of the spontaneously firing preoptic/anterior hypothalamic neurons are warm-sensitive. Warming (32-41 degrees C) depolarizes some cells, a phenomenon which is Na+-dependent and tetrodotoxin-insensitive. The increased firing rate of warm-sensitive cells in response to warming can be prepotential and/or synaptically driven. Overall, our data suggest that a warm-sensitive phenotype is already developed in cultured cells. Therefore, and despite obvious differences in their networks, cultured and slice preparations of hypothalamic neurons can complement each other for further studies of warm-sensitivity at the cellular and molecular level.

[Effects and cost-effectiveness analysis of inpatient treatment for somatoform disorders]. / Wirksamkeit und Kosten-Nutzen-Effekte der stationären Therapie somatoformer Störungen.

Patients with somatoform disorders represent an expensive problem group of the healthcare system characterized by inappropriately high medical costs. This paper describes a controlled inpatient treatment study using a cognitive-behavioral approach. The aim of this treatment program was to improve the patients' symptomatology and their psychosocial functioning, as well as reducing unnecessary medical costs. We treated 172 patients with somatoform disorders (DSM-IV) and compared them with 262 patients of a waiting control list. An additional control group consisted of 123 patients with other mental disorders. Direct and indirect illness-related costs for the two-year periods before and after treatment were re-calculated using objective data provided by the health insurance companies. The results show a marked improvement in the areas of bodily complaints, health anxieties, dysfunctional beliefs towards body and health, depression and psychosocial impairments. The medical costs in the post-treatment period decreased by 1,098 euro (-36.7 %) for inpatient and 382 euro (-24.5 %) for outpatient treatments. Indirect costs due to days lost from work were 6,702 euro (-35.3 %) lower than during the two-years before treatment. The treatment costs had amortized after 21.5 months. We identified a subgroup of high-utilizing somatoform patients for which per patient savings of 32,174 euro (-63.9 %) were found. These results confirm that the cognitive-behavioral approach is effective in improving complaints as well as reducing the health-economical burden of somatoform disorders.

Dynamical analysis reveals individuality of locomotion in goldfish.

Goldfish swimming was analysed quantitatively to determine if it exhibits distinctive individual spatio-temporal patterns. Due to the inherent variability in fish locomotion, this hypothesis was tested using five nonlinear measures, complemented by mean velocity. A library was constructed of 75 trajectories, each of 5 min duration, acquired from five fish swimming in a constant and relatively homogeneous environment. Three nonlinear measures, the 'characteristic fractal dimension' and 'Richardson dimension', both quantifying the degree to which a trajectory departs from a straight line, and 'relative dispersion', characterizing the variance as a function of the duration, have coefficients of variation less than 7%, in contrast to mean velocity (30%). A discriminant analysis, or classification system, based on all six measures revealed that trajectories are indeed highly individualistic, with the probability that any two trajectories generated from different fish are equivalent being less than 1%. That is, the combination of these measures allows a given trajectory to be assigned to its source with a high degree of confidence. The Richardson dimension and the 'Hurst exponent', which quantifies persistence, were the most effective measures.

Initial experience with the Endicor X-sizer thrombectomy device in patients with ST segment elevation myocardial infarction.

We investigated 16 patients with ST segment elevation myocardial infarction who had an occluded coronary artery (TIMI 0) at initial angiogram. Instead of balloon angioplasty and stenting, patients were subjected to thrombectomy (Endicor X-sizer) and stenting. In 15/16 patients the occlusion could be crossed by the thrombectomy device resulting in TIMI flow 3 in all of them. Thereafter, stenting was performed. At final angiogram all 15 patients continued to show TIMI flow grade 3. Twelve-lead ECG was performed prior to and post-intervention. ST elevation was measured as the sum of eight leads for anterior infarction and of five leads for inferior infarction. In 13/15 patients, ECG analysis was possible (2 developed bundle branch block post-intervention). In all 13 patients, a > 50% ST decrease of the initial amount of ST elevation was observed reaching a > 70% reduction in 11 patients. Procedural complications were low (one coronary dissection after thrombectomy) and 30 days follow-up was uneventful. Thrombectomy using the Endicor X-Sizer device may become an attractive mechanical reperfusion strategy for patients with acute myocardial infarction.

Further evidence for a reversed crossing of foveal projections in schizophrenic vulnerability.

Further evidence in support of the thesis developed in a previous article published in Medical Hypotheses (Sept. 2000) proposing that schizophrenic vulnerability might consist of the temporal instead of the nasal foveal projections crossing over in the chiasma opticum has been provided by an experiment in which pinholes are used to isolate foveally stimulated from peripherally stimulated vergence. By shifting the pinholes inwards or outwards a dilemma is created regarding the fusion of the edges of the two pinholes or of a single diode light seen at the inner or outer edges of the pinholes. It was revealed that schizophrenic patients never solved the dilemma in favour of what was represented on the temporal foveal halves while this was always the case in the control group. At best, the patients fusioned neither the diode light nor the pinhole edges but saw both double. An explanation is given as to how this disturbance might be based on the interchange of nasal and temporal foveal projections and might lead to the dissociation of the visual goals of the two eyes, as shown in a previous test. The cause of markers of schizophrenic vulnerability mentioned in literature, in particular saccaded SPEM, P50 response and hyperdopaminergia, is related to such an interchange and suggestions are made for further experiments. Finally, the difficulty of schizophrenic patients to distinguish between reality and illusion is attributed to a disconnection of spatial and object perception.

Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA.

1. Two ligand binding alpha subunits, alpha1 and alpha2, of the human (H) glycine receptor (GlyR) are involved at inhibitory synapses in the adult and neonatal spinal cord, respectively. The ability of homomeric alphaH1 and alphaH2 GlyRs to be activated by glycine, taurine and GABA was studied in Xenopus oocytes or in the human embryonic kidney HEK-293 cell line. 2. In outside-out patches from HEK cells, glycine, taurine and GABA activated both GlyRs with the same main unitary conductance, i.e. 85 +/- 3 pS (n = 6) for alphaH1, and 95 +/- 5 pS (n = 4) for alphaH2. 3. The sensitivity of both alphaH1 and alphaH2 GlyRs to glycine was highly variable. In Xenopus oocytes the EC50 for glycine (EC50gly) was between 25 and 280 microM for alphaH1 (n = 44) and between 46 and 541 microM for alphaH2 (n = 52). For both receptors, the highest EC50gly values were found on cells with low maximal glycine responses. 4. The actions of taurine and GABA were dependent on the EC50gly: (i) their EC50 values were linearly correlated to EC50gly, with EC50tau approximately 10 EC50gly and EC50GABA approximately 500-800 EC50gly; (ii) they could act either as full or weak agonists depending on the EC50gly. 5. The Hill coefficient (n(H)) of glycine remained stable regardless of the EC50gly whereas n(H) for taurine decreased with increasing EC50tau. 6. The degree of desensitization, evaluated by fast application of saturating concentrations of agonist on outside-out patches from Xenopus oocytes, was similar for glycine and taurine on both GlyRs and did not exceed 50 %. 7. Our data concerning the variations of EC50gly and the subsequent behaviour of taurine and GABA could be qualitatively described by the simple del Castillo-Katz scheme, assuming that the agonist gating constant varies whereas the binding constants are stable. However, the stability of the Hill coefficient for glycine was not explained by this model, suggesting that other mechanisms are involved in the modulation of EC50.

Is there chaos in the brain? I. Concepts of nonlinear dynamics and methods of investigation.

In the light of results obtained during the last two decades in a number of laboratories, it appears that some of the tools of nonlinear dynamics, first developed and improved for the physical sciences and engineering, are well-suited for studies of biological phenomena. In particular it has become clear that the different regimes of activities undergone by nerve cells, neural assemblies and behavioural patterns, the linkage between them, and their modifications over time, cannot be fully understood in the context of even integrative physiology, without using these new techniques. This report, which is the first of two related papers, is aimed at introducing the non expert to the fundamental aspects of nonlinear dynamics, the most spectacular aspect of which is chaos theory. After a general history and definition of chaos the principles of analysis of time series in phase space and the general properties of chaotic trajectories will be described as will be the classical measures which allow a process to be classified as chaotic in ideal systems and models. We will then proceed to show how these methods need to be adapted for handling experimental time series; the dangers and pitfalls faced when dealing with non stationary and often noisy data will be stressed, and specific criteria for suspecting determinism in neuronal cells and/or assemblies will be described. We will finally address two fundamental questions, namely i) whether and how can one distinguish, deterministic patterns from stochastic ones, and, ii) what is the advantage of chaos over randomness: we will explain why and how the former can be controlled whereas, notoriously, the latter cannot be tamed. In the second paper of the series, results obtained at the level of single cells and their membrane conductances in real neuronal networks and in the study of higher brain functions, will be critically reviewed. It will be shown that the tools of nonlinear dynamics can be irreplaceable for revealing hidden mechanisms subserving, for example, neuronal synchronization and periodic oscillations. The benefits for the brain of adopting chaotic regimes with their wide range of potential behaviours and their aptitude to quickly react to changing conditions will also be considered.

Isolation and characterization of an alpha 2-type zebrafish glycine receptor subunit.

The complementary DNA for a novel alpha subunit of the glycine receptor, alphaZ2, was isolated from a zebrafish adult brain library. The molecular characteristics, phylogenetic relationships and messenger RNA length of this alphaZ2 subunit show it to be an alpha2-type glycine receptor subunit isoform. The leader peptide however, diverges from those of known glycine receptor alpha isoforms. Recombinantly expressed in Xenopus oocytes, alphaZ2 formed functional glycine receptor channels. These homomeric channels were activated by glycine and taurine, with apparent affinities similar to those reported for zebrafish alphaZ1 glycine receptor, and were also effectively antagonized by nanomolar concentrations of strychnine. However, during prolonged applications of agonists, ionic currents of alphaZ2 receptor channels declined to a much lower steady-state level than those of alphaZ1, indicating different desensitization properties. Analysis of messenger RNA revealed that alphaZ2 is specifically expressed in adult brain tissue and present in both adult and embryonic zebrafish. This report contributes to the characterization of the diversity of glycine receptor isoforms in vertebrates.

Regional distribution of glycine receptor messenger RNA in the central nervous system of zebrafish.

We report the cloning of the zebrafish beta subunit of the glycine receptor and compare the anatomical distribution of three glycine receptor subunit constituents in adult zebrafish brain (alphaZ1, alphaZ2 and betaZ) to the expression pattern of homologous receptor subunits (alpha1, alpha2 and beta) in the mammalian adult CNS. Non-radioactive hybridization was used to map the distribution of the alphaZ1, alphaZ2 and betaZ glycine receptor subunit messenger RNAs in the adult zebrafish brain. The anterior-posterior expression gradient found in adult zebrafish brain was similar to that reported in mammalian CNS. However, the glycine receptor transcripts, notably the alphaZ1 subunit, were more widely distributed in the anterior regions of the zebrafish than in the adult mammalian brain. The isoform-specific distribution pattern was less regionalized in zebrafish than in the rat mammalian CNS. Nevertheless, there was some regionalization of alphaZ1, alphaZ2 and betaZ transcripts in the diencephalic and mesencephalic nuclei where different sensory and motor centers express either alphaZ1/betaZ or alphaZ2 subunits. In contrast to the widespread distribution of the beta subunit in adult mammalian brain, alphaZ2 messenger RNA presented the widest expression territory of all three glycine receptor subunits tested. alphaZ2 messenger RNA was expressed in the absence of alphaZ1 and betaZ messenger RNA in the outer nuclear layer of the retina, the inferior olive and the raphe of the medulla oblongata, as well as in the nucleus of Cajal of the medulla spinalis. In contrast, an identified central neuron of the reticular formation, the Mauthner cell, expresses all three glycine receptor subunits (alphaZ1, alphaZ2 and betaZ). This report extends the already described glycine receptor expression in the vertebrate CNS and confirms the importance of glycine-mediated inhibition in spinal cord and brainstem.

Slow inhibitory potentials in the teleost Mauthner cell.

In vivo recordings from Mauthner cells in adult zebrafish (Danio rerio) and goldfish (Carassius auratus) preparations with potassium chloride filled electrodes revealed a new class of long-lasting synaptic events in these cells. Their decay time constant ranged from 20 to 80ms, which is about 20 times longer than that of previously identified fast glycinergic inhibitory postsynaptic potentials in this neuron. The average time to peak of these slow events ranged from 1 to 6ms. We demonstrated that they are also inhibitory since (i) they were resistant to antagonists of the excitatory glutamatergic receptors; (ii) their amplitude was increased following chloride loading of the Mauthner cell; (iii) their reversal potential was the same as that of fast, glycinergic inhibitory postsynaptic potentials; and (iv) they produced an inhibitory shunt of the cell's membrane resistance. Furthermore, as with the fast inhibitory postsynaptic potentials, the decay time of the slow events is voltage dependent, increasing when the Mauthner cell is depolarized. However, these inhibitory postsynaptic potentials had a different pharmacological profile to the fast glycinergic ones. That is, they persisted in the presence of strychnine at doses that abolished the fast ones and they were more sensitive to bicuculline. These data are compatible with the notion that these inhibitory postsynaptic potentials are mediated by activation of a different inhibitory receptor type, and may be GABAergic. In addition, the decay time constant of the fast inhibitory postsynaptic current was shorter than the first of the two components that contribute to the bi-exponential decay reported previously for miniature inhibitory postsynaptic currents in Mauthner cells of larval zebrafish. This suggests developmental modifications and/or a switch in the assembly of glycine receptor subtypes. While amplitude distributions of the fast miniature inhibitory postsynaptic potentials recorded in the presence of tetrodotoxin generally could fit with a single Gaussian function, the amplitude histograms of slow miniature events were skewed, often with multiple nearly equally spaced peaks, consistent with the synchronous release of several quantal units. These previously undescribed slow unitary inhibitory postsynaptic potentials contribute to inhibitory synaptic noise recorded in the Mauthner cells. Specifically, autocorrelation analysis revealed gamma-like rhythms (30-80Hz) in each of two phases, characterized as "noisy" and "quiet", and dominated by the fast and slow inhibitory postsynaptic potentials, respectively. The major frequencies of these two states were significantly different (i.e. around 90 and 40Hz, respectively), suggesting that the fast and slow inhibitory postsynaptic potentials are derived from different inhibitory networks. Chloride-filled Mauthner cells gradually hyperpolarized in the presence of tetrodotoxin, reflecting the effect of ongoing activity in the interneurons that produce the slow events. We conclude that this new class of inhibitory postsynaptic potentials contributes to the tonic inhibition which controls the Mauthner cell's excitability. In physiological conditions, this regulatory influence is expressed as a continuous shunt of this neuron's input resistance and responsiveness to sensory inputs.

[Rescue thrombectomy after stent implantation in a degenerating aortocoronary bypass]. / Rescue-Thrombektomie nach Stentimplantation in einem degenerierten aortokoronaren Venenbypass.

BACKGROUND: Distal showering of atherosclerotic debris or thrombus is a feared event during percutaneous angioplasty of degenerated vein grafts. CASE REPORT: We report on a 66-year-old male patient with a history of coronary artery disease who was admitted into hospital with an acute coronary syndrome. He had had coronary artery bypass graft surgery in 1995. His chest pain resolved under treatment with aspirin, heparin, betablocker, and nitrate. A diagnostic angiogram demonstrated two critical stenoses of the left anterior descending graft. After a continuous infusion of tirofiban administered for 24 h prior to elective angioplasty, a JR 4SH 6 F guiding catheter (Cordis) was positioned. The lesions were crossed with a 0.014" Galeo F wire (Biotronik). A 4 mm x 16 mm stent graft (Jostent, Jomed) was deployed in the distal stenosis and a 4.5 mm x 32 mm self-expandable stent (Magic Wallstent, Boston Scientific) in the proximal stenosis. Thereafter, the patient suffered from chest pain, and the ECG showed ST elevation from V1 to V5. Angiography revealed total occlusion of the left anterior descending artery. An X-Sizer catheter (EndiCOR Medical, Inc.) was introduced and advanced through the vein graft with slow back-and-forth movements. After several aspirations, blood flow was significantly improved. A modest CK elevation (127 U/l) indicated a rather small loss of myocardial tissue. CONCLUSION: Percutaneous revascularization of narrowed aortocoronary saphenous vein grafts is associated with increased risk of distal embolization and "no reflow". The X-Sizer catheter system is compatible with commercially available guiding catheters, and capable of retrieving thrombotic debris after macroembolization from degenerated saphenous vein grafts including the native coronary artery.

Synaptic efficacy and the transmission of complex firing patterns between neurons.

In central neurons, the summation of inputs from presynaptic cells combined with the unreliability of synaptic transmission produces incessant variations of the membrane potential termed synaptic noise (SN). These fluctuations, which depend on both the unpredictable timing of afferent activities and quantal variations of postsynaptic potentials, have defied conventional analysis. We show here that, when applied to SN recorded from the Mauthner (M) cell of teleosts, a simple method of nonlinear analysis reveals previously undetected features of this signal including hidden periodic components. The phase relationship between these components is compatible with the notion that the temporal organization of events comprising this noise is deterministic rather than random and that it is generated by presynaptic interneurons behaving as coupled periodic oscillators. Furthermore a model of the presynaptic network shows how SN is shaped both by activities in incoming inputs and by the distribution of their synaptic weights expressed as mean quantal contents of the activated synapses. In confirmation we found experimentally that long-term tetanic potentiation (LTP), which selectively increases some of these synaptic weights, permits oscillating temporal patterns to be transmitted more effectively to the postsynaptic cell. Thus the probabilistic nature of transmitter release, which governs the strength of synapses, may be critical for the transfer of complex timing information within neuronal assemblies.

Schizophrenic vulnerability: a deficiency of the correlation between foveal perception and oculomotor proprioception?

In a previous paper published in Medical Hypotheses, the author proved by a simple mirror test a dissociation between the goals of selective attention and bifoveal fixation in a schizophrenic patient. In the present article, she enters into the details of the patient's results in ophthalmological tests which revealed an opposite deviation of accommodation and vergence, compensated in a way incompatible with Hering's law. She expounds that Hering's law is based on the correlation of retinal data with proprioceptive information of the exterior eye-muscles, and that schizophrenic vulnerability might consist of a disturbance of this correlation favouring fusion of patterns in the remote and external space over fusion in the near and central space. Some phenomena found in schizophrenic patients and their carrier parents are explained in the light of this hypothesis. Finally, the author gives detailed advice on how to overcome difficulties in the correction of the ophthalmological deviations that induce the vulnerability to take effect. ¿