Student-Initiated Feedback Using Clinical Encounter Cards during Clinical Rotations in Veterinary Medicine: A Feasibility Study.

Despite its critical role for successful student learning, providing adequate teacher feedback is still a major issue during clinical education. In human medical education, the implementation of clinical encounter cards (CECs) has led to more frequent, timely, and structured teacher feedback. The present study aimed to introduce student-initiated CECs in a veterinary medical setting (clinical rotations). A total of 24 students were randomly assigned to a control group (standard rotations) and an intervention group where they had to ask for teacher feedback using CECs. The feasibility of implementing CECs was evaluated by examining the content of the completed CECs and by using anonymous student and teacher questionnaires. In addition, acceptance of the intervention and changes in feedback behavior were examined from both the teachers' and students' perspectives. Overall, it was shown that using CECs is not only feasible in a veterinary clinical setting but also conducive to more frequent and constructive teacher feedback. However, some teachers postponed completing the CECs due to time pressure, leading to less direct and timely feedback. Moreover, students felt more comfortable asking for feedback from less experienced, younger teachers, and teachers' quantitative ratings and open commentaries seemed to be affected by leniency bias. Finally, a focus group including teachers and students discussed these results in light of their practical experiences. This led to a streamlining of the implementation process and optimizations to facilitate future large-scale implementation. The study has implications for veterinary educators wishing to improve feedback in their institution.

Antimicrobial Formulations of Absorbable Bone Substitute Materials as Drug Carriers Based on Calcium Sulfate.

Substitution of bones is a well-established, necessary procedure to treat bone defects in trauma and orthopedic surgeries. For prevention or treatment of perioperative infection, the implantation of resorbable bone substitute materials carrying antibiotics is a necessary treatment. In this study, we investigated the newly formulated calcium-based resorbable bone substitute materials containing either gentamicin (CaSO4-G [Herafill-G]), vancomycin (CaSO4-V), or tobramycin (Osteoset). We characterized the released antibiotic concentration per unit. Bone substitute materials were implanted in bones of rabbits via a standardized surgical procedure. Clinical parameters and levels of the antibiotic-releasing materials in serum were determined. Local concentrations of antibiotics were measured using antimicrobial tests of bone tissue. Aminoglycoside release kinetics in vitro per square millimeter of bead surface showed the most prolonged release for gentamicin, followed by vancomycin and, with the fastest release, tobramycin. In vivo level in serum detected over 28 days was highest for gentamicin at 0.42 µg/ml, followed by vancomycin at 0.11 µg/ml and tobramycin at 0.04 µg/ml. The clinical parameters indicated high biocompatibility for materials used. None of the rabbits subjected to the procedure showed any adverse reaction. The highest availability of antibiotics at 14.8 µg/g on day 1 in the cortical tibia ex vivo was demonstrated for gentamicin, decreasing within 14 days. In the medulla, vancomycin showed a high level at 444 µg/g on day 1, decreasing continuously over 14 days, whereas gentamicin decreased faster within the initial 3 days. The compared antibiotic formulations varied significantly in release kinetics in serum as well as locally in medulla and cortex.

[Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials]. / Irreversibilitätsnachweis der klinischen Ausfallssymptome des Gehirns. Elektroenzephalographie und evozierte Potenziale.

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Optimising cell-based bioassays via integrated design of experiments (ixDoE) - A practical guide.

For process optimisation Design of Experiments (DoE) has long been established as a more powerful strategy than a One Factor at a Time approach. Nevertheless, DoE is not widely used especially in the field of cell-based bioassay development although it is known that complex interactions often exist. We believe that biopharmaceutical manufacturers are reluctant to move beyond standard practices due to the perceived costs, efforts, and complexity. We therefore introduce the integrated DoE (ixDoE) approach to target a smarter use of DoEs in the bioassay setting, specifically in optimising resources and time. Where in a standard practice 3 to 4 separate DoEs would be performed, our ixDoE approach includes the necessary statistical inference from only a single experimental set. Hence, we advocate for an innovative, ixDoE approach accompanied by a suitable statistical analysis strategy and present this as a practical guide for a typical bioassay development from basic research to biopharmaceutical industry.

Short-term modulation of the ipsilateral primary sensory cortex by nociceptive interference revealed by SEPs.

We studied the modulation of the topographic arrangement of the human ipsilateral primary somatosensory cortex following interference of nociceptive stimuli by means of dipole source analysis. Multichannel somatosensory evoked potentials were obtained by electrical stimulation of digits 1 and 5 of the left hand before, during and after the application of pain to digits 2-4 of the right hand. The primary cortical response of the SEP (N20) was obtained for dipole localization of the representation of the primary sensory cortex receiving input from digits 1 to 5. The 3D-distance between these sides was calculated for further analysis. To account for possible attentional effects recordings were performed while simultaneously to this intervention subjects were asked to turn their attention to the right or left hand in a pseudorandom order. The application of pain induced an expansion of the 3D-distance between digits 1 and 5. Focusing attention to the stimulated limb or the site of the intervention did not yield to an additional effect. Our results provide further evidence for the presence of a quickly adapting interaction between primary somatosensory areas of both hemispheres following an interference of nociceptive stimulation in SEPs. This modifying process is probably mediated by interhemispheric and intercortical connections leading to hyperexcitability of the primary sensory cortex contralateral to that receiving nociceptive input. Spatial attention does not seem to have an impact on this kind of short-term intercortical plasticity.

Interference of tactile and pain stimuli on thalamocortical signal processing in humans revealed by median nerve SEPs.

OBJECTIVE: We investigated the interference of tactile and painful stimuli on human early somatosensory evoked potentials (SEPs) including high frequency oscillations (HFOs) to further study thalamocortical processing of somatosensory information. METHODS: Multi-channel median nerve SEPs were recorded during (1) no interference, (2) sensory interference by tactile stimulation to digits 2 and 3, and (3) application of pain to the same digits. Spatio-temporal source analysis separated brain stem (S1), thalamic (S2) and two cortical sources (S3, S4), which were evaluated for the low (20-450 Hz) and high (450-750 Hz) frequency portion of the signal. RESULTS: Low frequency SEPs showed a decrease of activity at cortical source S3 during both conditions, while thalamic source S2 was significantly increased during pain interference. HFOs showed an increase of cortical source S3 and in trend of thalamic source S2 and cortical source S4 during both kinds of interference. CONCLUSIONS: Although the painful stimulus might not be specific for the nociceptive afferents, the present data affirm that at this early stage of sensory information processing within the primary sensory cortex (area 3b, area 1) pain is handled similar to sensory interference. SIGNIFICANCE: HFOs might represent an intrinsic "somatosensory alerting" system which reacts to both interference stimuli in a similar way, therefore indicating an interference without a qualitative evaluation.

[Pseudoangiitis in bilateral ocular ischemia]. / Pseudoangiitis bei beidseitiger okulärer Ischämie.

BACKGROUND: The term 'frosted branch angiitis' was initially used to describe an idiopathic form of vasculitis in association with panuveitis. It has since also been used to describe the angiographic phenomenon of diffuse leakage along retinal vessels against the background of other ocular and systemic diseases. METHODS: We describe a 57-year-old male patient with acute bilateral reduction of visual acuity, headaches and absence of any pulse at the temporal arteries. Fluorescence angiography showed bilateral diffuse leakage along all the retinal vessels, which resembled frosted branches. Laboratory parameters and histology were not indicative of vasculitis. Imaging showed complete occlusion of both common carotid arteries and a hypoplastic vertebral artery on the left. CONCLUSIONS: Ocular ischemia may imitate primarily inflammatory conditions in its angiographic appearance.

Increased antibiotic release and equivalent biomechanics of a spacer cement without hard radio contrast agents.

We compared a novel calcium carbonate spacer cement (Copal® spacem) to well-established bone cements. Electron microscopic structure and elution properties of the antibiotics ofloxacin, vancomycin, clindamycin, and gentamicin were examined. A knee wear simulator model for articulating cement spacers was established. Mechanical tests for bending strength, flexural modulus, and compressive and fatigue strength were performed. The electron microscopic analysis showed a microporous structure of the spacer cement, and this promoted a significantly higher and longer antibiotic elution. All spacer cement specimens released the antibiotics for a period of up to 50days with the exception of the vancomycin loading. The spacer cement showed significantly less wear scars and fulfilled the ISO 5833 requirements. The newly developed spacer cement is a hydrophilic antibiotic carrier with an increased release. Cement without hard radio contrast agents can improve tribological behaviour of spacers, and this may reduce reactive wear particles and abrasive bone defects.

High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users.

Neurotoxic damage of central serotonergic systems has been demonstrated in numerous animal studies after exposure to methylenedioxyamphetamines (ecstasy). A high intensity dependence of auditory evoked potentials and, particularly, of the tangential N1/P2 source activity has been associated with low levels of serotonergic neurotransmission in humans. We performed an auditory evoked potentials study in 28 abstinent recreational ecstasy users and two equally sized groups of cannabis users and nonusers. The ecstasy users exhibited an increase of the amplitude of the tangential N1/P2 source activity with higher stimulus intensities; whereas, both control groups failed to exhibit this feature. These data are in line with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity. This feature of information processing is probably related to the well-recognized neurotoxic potential of ecstasy. Our data indicate that recreational ecstasy use may cause long-term alterations in the function (and possibly structure) of the human brain.

The timing of visual evoked potential activity in human area V4.

Studies of human occipital visual cortex have demonstrated functional specializations for colour and for motion, with a pivotal area for colour processing (area V4) being located in the fusiform gyrus. To study the timing of arrival of signals in area V4 we have recorded multi-channel visual evoked potentials (VEPS) to colour and grey 'Mondrian' stimuli, spatio-temporal dipole source analysis being computed on two independent group averages of five and six subjects respectively. Three active brain regions were identified, which we interpret to correspond to areas V1, V2 and V4; they showed sequential but overlapping activity in time with no difference in magnitude between colour and grey stimulated VEPs. Source analysis of the difference potentials, colour minus grey, isolated source activity resulting from colour stimulation and located it in the region of area V4. Activity in area V4 started at 100 ms and peaked at 135 ms after the onset of the visual stimulus.

Spatial attention modulates the cortical somatosensory representation of the digits in humans.

The topographic organization of the primary somatosensory cortex adapts to alterations of afferent input. Here, electric source imaging was used to show that spatial attention modifies cortical somatosensory representations in humans. The cortical representation of the electrically stimulated digit 2 (resp. digits 2 and 3) of the right hand was more medial along the somatosensory area 3b in subjects who focused attention on digit 4 of the right hand, while it was more lateral when subjects attended digit 4 of the contralateral hand. This effect was very fast since the direction of attention was changed every 6 min. The results indicate that cortical somatosensory representations not only depend on afferent input but vary when spatial attention is directed towards different parts of the body.

Fast visual evoked potential input into human area V5.

Studies of the human visual cortex have demonstrated that an area for motion processing (V5) is located in the lateral occipito-temporal cortex. To study the timing of arrival of signals in V5 we recorded multi-channel visual evoked potentials (VEPs) to checkerboard stimuli. We then applied dipole source analysis which was computed on a grand average of 10 subjects, and on five individual subjects, respectively. We demonstrate an early VEP component with onset before 30 ms and with a peak around 45 ms, located in the vicinity of V5. This early component was independent of a second activity, which started around 50 ms and peaked around 70 ms, and was located within the striate cortex (V1). These results provide further evidence for a very fast input to V5 before activation of V1.

Differential effects of pain and spatial attention on digit representation in the human primary somatosensory cortex.

Reorganization of primary somatosensory cortex subsequent to either reduced or enhanced peripheral input is well established. Recently, plastic changes following arm amputation in humans were shown to correlate with phantom limb pain. This raised the question whether spatial attention and pain may cause cortical reorganization in the absence of deafferentation. Using non-invasive neuroelectric imaging to study the digit representation in the human primary somatosensory cortex, we report a delayed shift of the representation of digits 2-3 due to pain on the digits 4-5, which outlasted the pain by several minutes. In contrast, reorganization during spatial attention was less pronounced, was seen almost immediately and only during the condition. These data indicate that spatial attention and pain without peripheral deafferentation cause cortical reorganization by different mechanisms. The differential time course of reorganizational effects observed at the cortex may be due to modulation of the lemniscal pathways by nociceptive input from the spinal cord dorsal horn.

Differential gating of slow postsynaptic and high-frequency spike-like components in human somatosensory evoked potentials under isometric motor interference.

Human cortical somatosensory evoked potentials (SEP) can be modified by concomitant motor tasks ('gating'), through peripheral occlusion and/or central mechanisms. The present study aimed (1) at refining earlier results concerning motor-gating of the primary cortical EPSP-related N20 response after electric median nerve stimulation, and (2) at providing first data on motor-gating of the 600 Hz SEP wavelet burst which occurs superimposed onto N20 and primarily reflects repetitive cerebral population spikes. In 12 healthy subjects median nerve SEP were elicited, using electrical stimuli with intensities below, at and above motor threshold, under either rest or an isometric fist clenching task. Amplitude and latency modifications were analysed for the peripheral compound action potential (CAP), low-frequency SEP components (N20, P25, N35 and P70) and the high-frequency burst. While the peripheral CAP remained unchanged, isometric motor innervation significantly attenuated N20, P25 and P70 amplitudes and shortened peak latencies progressively for all components after N20. In contrast, the high-frequency 600 Hz burst was modulated neither in amplitude nor in latency. Regular amplitude recruitment occurred for all components independent from the motor task, excluding channel saturation as an explanation for gating. We suggest that SEP gating under isometric motor innervation is a central process which selectively operates on specific SEP components and could partly reflect an "efference copy" mechanism.

The subcortical generated somatosensory evoked potentials in non-cephalic, cephalic, and anterior neck referenced recordings in a patient with a cervico-medullary lesion: a clue to the identification of the P14/N14 and N13 generators.

Median nerve somatosensory evoked potentials (SEPs) were studied in a patient before and after the development of a cervico-medullary lesion. The first examination demonstrated normal subcortical generated potentials N13 and N14. The second examination, following a subarachnoid haemorrhage at the cervico-medullary junction, displayed a delayed and reduced amplitude P14/N14 peak on both sides. P14/N14 showed the same latency in all montages, using non-cephalic, cephalic and anterior neck references. The N13 component was not significantly changed in latency compared with the first examination. The latencies of the N13 peak were variable in the different montages. They increased from the lower (C7) to the upper (C2) neck, whereas the latency of the N13 onset was identical in all montages. This alteration might be caused by a delayed near-field activity at C2 overlapping the N13 component. These results fit the hypothesis of two major generators responsible for subcortical SEPs; a near-field N13 component at the level of the lower neck and a far-field P14 component arising from the level of the cervico-medullary junction. An additional minor near-field activity generated by the cuneate nucleus is suspected.

Percutaneous transluminal angioplasty of the vertebral artery. A therapeutic alternative to operative reconstruction of proximal vertebral artery stenoses.

Percutaneous transluminal angioplasty (PTA) of the proximal vertebral artery was performed in 13 patients with stenosis of the proximal vertebral arteries. All of these patients had symptoms indicating vertebrobasilar insufficiency. PTA was performed only if an extreme reduction of the total diameter of both vertebral arteries was present. Only 13 patients have fulfilled the strict selection criteria in the last 3 years. All patients were monitored during the procedure by means of continuous-wave Doppler ultrasound and electrophysiological techniques. After PTA their neurological and vascular conditions were serially examined. Of the 13 patients, 8 showed marked improvement of both subjective and objective clinical symptoms. During an observation period of 2-25 months (average: 15 months) reocclusion of the angioplasty was observed in only 2 cases, without any additional neurological sequelae. Electrophysiological and Doppler sonographic monitoring during PTA helped to minimize the risk of angioplasty.

Stability of high-frequency (600 Hz) components in human somatosensory evoked potentials under variation of stimulus rate--evidence for a thalamic origin.

The generators of spike-like high-frequency (600 Hz) wavelets superimposed on the primary cortical response (N20) in human median nerve somatosensory evoked potentials (SEP) have been localized anatomically both close to the primary somatosensory hand cortex and in deep axon segments of thalamo-cortical projection neurons. Here, N20 and 600 Hz burst components were functionally dissociated by varying the stimulus rate (1.5, 3, 6, 9 Hz). The N20 source amplitudes were significantly reduced at the higher stimulus rates. In contrast, the source amplitudes of the 600 Hz oscillations remained stable across all stimulus rates. This reflects different source origins, confirming a postsynaptic intracortical generation of the N20 component and provides further evidence for a presynaptic origin of the 600 Hz activity like repetitive neuronal population spikes conducted in deep and superficial segments of thalamo-cortical projection fibers.

Different origins of low- and high-frequency components (600 Hz) of human somatosensory evoked potentials.

OBJECTIVE: Human median nerve somatosensory evoked potentials (SEPs) contain a low-amplitude (<500 nV) high-frequency (approximately 600 Hz) burst of repetitive wavelets (HFOs) which are superimposed onto the primary cortical response 'N20.' This study aimed to further clarify the cortical and subcortical structures involved in the generation of the HFOs. METHODS: 128-Channel recordings were obtained to right median nerve stimulation of 10 right-handed healthy human subjects and in 7 of them additional to right ulnar nerve. Data were evaluated by applying principal component analysis and dipole source analysis. RESULTS: Different source evaluation strategies provided converging evidence for a cortical HFO origin, with two different almost orthogonally oriented generators being active in parallel, but with a phase shift of a quarter of their oscillatory period, while the low-frequency 'N20' is adequately modeled by one tangential dipole source. Median and ulnar derived low-frequency and HFO cortical sources show a somatotopic order. Additionally, generation of the HFOs was localized in subcortical, near-thalamic and subthalamic source sites. The near-thalamic dipole was located at significantly different sites in HFO and low-frequency data. CONCLUSIONS: The cortical HFO source constellation points to a 'precortical' source in terminals of thalamocortical fibers and a second intracortical HFO origin. Furthermore, HFOs are also generated at subcortical and even subthalamic sites. Near-thalamic, the HFO and low-frequency signals are generated or modulated by different neuron populations involved in the thalamocortical outflow.

N30 and the effect of explorative finger movements: a model of the contribution of the motor cortex to early somatosensory potentials.

OBJECTIVES: The source of the N30 potential in the median nerve somatosensory evoked potentials (SEP) has been previously attributed to a pre-central origin (motor cortex or the supplementary motor area, SMA) or a post-central located generator (somatosensory cortex). This attribution was made from results of lesion studies, the behavior of the potential under pathological conditions, and dipole source localization within spherical volume conductor models. METHODS: The present study applied dipole source localization and current density reconstruction within individual realistically shaped head models to median nerve SEPs obtained during explorative finger movements. RESULTS: The SEPs associated with movement of the stimulated hand showed a minor reduction of the N20 amplitude and a markedly reduced amplitude for the frontal N30 and parietal P27, exhibiting a residual frontal negativity around 25 ms. The brain-stem P14 remained unchanged. Mapping of the different SEPs (movement of the non-stimulated hand minus movement of the stimulated hand) showed a bipolar field pattern with a maximum around 30 ms post-stimulus. In eight out of ten normal subjects, both the N30 and the gN30 (subtraction data) sources resided within the pre-central gyrus, more medially than the post-centrally located N20. Two subjects, in contrast, showed rather post-centrally localized sources in this time range. A model of the cortical SEP sources is introduced, explaining the data with respect to previously described findings of dipole localization, and from lesion studies and the alterations seen in motor diseases. CONCLUSIONS: The results provide evidence for a pre-central N30 generator, predominantly tangentially oriented, located within the motor cortex, while no sources were detected elsewhere. It is suggested that the mechanisms underlying the 'gating' effect during explorative finger movements in the 30 ms time range predominantly arise in the motor cortex.