Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

The present findings suggest that sleep deprivation produces hyperalgesic changes that cannot be explained by nonspecific alterations in somatosensory functions.

Nonlinear ionic interactions at the nerve cell membrane can account for oscillating membrane potentials and the generation of periodic neuronal impulse activity. In combination with noise, external modulation of the endogenous oscillations allows for continuous transitions between a variety of impulse patterns. Such "noisy oscillators" afford, thereby, an important mechanism of neuronal encoding as is demonstrated here with experimental data from peripheral cold receptors and corresponding computer simulations.

The aim of the present study was to characterize the EEG response pattern specific for tonic pain which is an experimental pain model resembling clinical pain more closely than phasic pain. Tonic experimental pain was produced by a series of heat pulses 1 degree C above pain threshold over 10 min. A series of heat pulses 0.3 degree C below pain threshold and a constant temperature of 37 degrees C served as non-painful heat control and as baseline condition, respectively. The level of attention was experimentally manipulated by instruction and by a distraction task. Twenty male, pain-free subjects had to rate the sensation intensity and sensation unpleasantness during thermal stimulation. Furthermore, a German version of the McGill Pain Questionnaire was to be filled out after tonic painful heat stimulation. The EEG was recorded via 10 leads according to 10/20 convention. Power density was calculated for the usual frequency bands. The ratings showed that tonic painful heat was experienced clearly distinct from tonic non-painful heat. An EEG response pattern emerged characterized by a rather generalized increased delta(2) activity, a left-biased fronto-temporally diminished theta activity, a fronto-temporal decrease in the alpha(1) activity and a left-sided temporal increase in the beta(1) activity. This observation agrees well with the findings of others. However, there was no evidence in our data that these EEG changes are specific to tonic heat pain as opposed to changes observed during tonic non-painful heat stimulation. Accordingly, the repeatedly reported EEG patterns are also likely to be produced by other forms of strong somatosensory stimuli and to be not specific for pain.

The German version of the FFI is a reliable and valid questionnaire for the self-assessment of pain and disability in German-speaking patients with foot complaints.

The short-term clinical and radiographic results after Mobility total ankle arthroplasty are encouraging and are at least comparable with those associated with other modern three-component implants. The minimum duration of follow-up of one year is short, and studies with longer follow-up are needed to confirm our findings.

Synchronization of electrosensitive cells of the paddlefish is studied by means of electrophysiological experiments. Different types of noisy phase locked regimes are observed. The experimental data are compared with computer simulations of a noise-mediated modified Hodgkin-Huxley neuron model and of a stochastic circle map. [S0031-9007(98) Since the historical work of Huygens [1], synchronization has attracted much attention. It occurs when a nonlinear oscillator, showing a stable limit cycle [2], is subjected to an external time-dependent force or is coupled with another oscillator. Synchronization has been observed in a wide variety of natural and man-made systems [3]. It is also important in various biological systems, including, most recently, the human heart-respiratory system, as well as certain brain functions revealed by magnetoencephalography [4].In this Letter we study experimentally the synchronization of electroreceptors of the paddlefish, Polydon spathula, which feeds on zooplankton, e.g., the water flea, Daphnia [5]. While adult fishes filter feed almost entirely on clouds of zooplankton, small paddlefish are particulate feeders, selecting and capturing zooplankton individually [6,7]. The paddlefish is named for its large rostrum, or "paddle," which is covered with an array of thousands of electrosensory organs (see Fig. 1). Recently it has been demonstrated that paddlefish are sensitive to weak electric fields, which they use for sensing prey electrically in the dark [8]. Both natural zooplankton and artificial electric dipoles were used to stimulate feeding [8].Each of the electrosensory organs on the rostrum ( Fig. 1) consists of a patch of ampullary-type cells, which synapse onto primary afferent (sensory) neurons sending long axons to the brain. The latter will be referred to as "electroreceptor cells" because their spike trains can be recorded, and are modulated by weak electric fields near the rostrum. We present here the first direct evidence that each cell contains a noise-mediated oscillator by showing that it can be synchronized with an external signal. In the absence of external stimuli, the cells generate noisy nearly periodic spike sequences. Noise mediated oscillators were previously studied in the electroreceptive cells of the dogfish (a kind of shark) and catfish [9] only indirectly by means of spike interval histograms. They have never been shown to exist in the primitive species of the order acipenseriformes (sturgeons and paddlefish).Extracellular recordings were obtained in vivo from single cells. In our experiments (for details see [8]) a cell was stimulated by a weak electric and/or magnetic field generated by a dipole or a small coil located near the rostrum. The electric field strengths (a few tens of mV ͞cm) were comparable in magnitude to those generated by the zooplankton. Recordings of the spike train from the cell and periodic signal from the dipole were digitized and analyzed by computer. An example recording is shown in Fig. 1. The synchronized 1:5 mode locking (5 s...

Two-thirds of the patients were active in sports after total ankle arthroplasty, and the majority of the patients met current health-enhancing physical activity recommendations. The clinical outcome as determined by AOFAS scores and the patient satisfaction were favorable. The present study found no association between sports participation, increased physical activity levels, and the appearance of periprosthetic radiolucencies 3.7 years after total ankle arthroplasty. However, these results have to be confirmed after longer follow-up, in particular of those patients regularly participating in sports with higher impact.