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Biomedical subjects

S Kastner

Publications and source records attributed to S Kastner.

At least 19 recordsLinked to original sources

[Interventions for improvement of primary care in patients with low back pain: how effective are advice to primary care physicians on therapies and a multimodal therapy program arising out of cooperation of outpatient health care structures?].

BACKGROUND: Treatment for chronic low back pain in primary care has a poor-quality outcome. There is evidence that multimodal therapy is the most successful approach to its management. We tried to evaluate whether giving primary care physicians evidence-based recommendations on therapy of chronic back pain or directly implementing a multimodal program would improve the outcome of patients with low back pain treated in primary care. METHODS: In the first phase, physicians were asked to document the course of patients suffering from low back pain of at least 4 weeks' duration with no decrease in intensity, noting pain intensity before and after 6 months of conventional, nonsurgical treatments. In the present, second, phase of the study, recommendations issued by the Medicines Committee of the German Medical Profession and the U.S. Agency for Health Care Policy and Research for the management of back pain were presented to doctors in printed form and at conferences. In parallel with this, a multimodal program for the treatment of chronic low back pain (4 h/day for 20 days: medical training therapy, cognitive-behavioral therapy, physiotherapy, and patient education) was organized in a private health-oriented sports center in cooperation with three private physiotherapy practices, and a psychologist and a pain specialist from the outpatient pain clinic at the University Hospital in Erlangen. We examined how physicians changed the therapy and how effective it was, the latter as reflected in the mean sum value of the percent pre- to posttreatment changes in pain intensity, how much pain interfered with daily living, depressivity, and quality of life. Data after interventions were compared with baseline data from the first phase. RESULTS: Data relating to 36 patients following treatment by 14 primary care physicians who had been given information about therapy recommendations and to 51 patients who had participated in the multimodal therapy program were compared with baseline data recorded in 157 patients. Recommendations changed neither the therapy preferred by primary care physicians nor the quality of outcome of conventional treatment. In contrast, the multimodal program of therapy for chronic low back pain improved the outcome significantly more than conventional therapy (mean improvement in general outcome score 22 vs. 7%, respectively, compared with baseline data; P<0.001). CONCLUSIONS: Giving primary care physicians information on the therapy recommended for treatment of low back pain does not lead to any change in physicians' preferred therapy. Multimodal programs for treatment of chronic low back pain should be organized locally, with existing health care providers joining forces to improve the quality of outcome in chronic low back pain managed in primary care.

Adult↗

Neurons with large bilateral receptive fields in monkey prelunate gyrus.

In single-cell recordings from the dorsocaudal part of the prelunate gyrus of an alert monkey (Macaca fascicularis) we found neurons with unexpectedly large receptive fields (RFs) that spread bilaterally into the contra- and ipsilateral visual fields. These neurons (n=82) appeared to be clustered in the periphery of V4. They were surrounded by neurons with relatively small (3-10 degrees) and unilateral RFs in the contralateral field with properties similar to those previously described for neurons in area V4. Bilateral RFs extended over large parts of the lower visual field but always spared the fovea. Receptive fields typically revealed two foci of maximal responsiveness that were arranged symmetrically in the ipsi- and contralateral fields. Twenty-six cells did not respond to stimuli along the vertical meridian; these neurons had two distinct RFs. The preference for stimulus orientation, color, or motion was similar in all parts of these large RFs.

Animals↗

[Effects of recommendations and patient seminars on effectivity of outpatient treatment for headache].

BACKGROUND: Treatment of patients suffering from migraine and/or tension-type headache in primary care needs to be improved. To this purpose we tested two strategies for implementation of evidence-based recommendations for treatment of headaches: first, communication of recommendations to the primary care physicians and, second, standardized communication and discussion of these recommendations with patients in combination with exercising of progressive muscle relaxation during patient seminars. METHODS: Patients with at least 2 migraine attacks/month or 8 days of tension-type headache/month were included in the study. Evidence-based pharmacological and non-pharmacological recommendations of the Medicines Committee of the German Medical Profession for treatment of migraine and tension-type headache have been offered to primary care physicians by printed material and during conferences. Patient seminars at 10 days for 2 hours were organized by the outpatient pain facility of the neurological department of the university of Erlangen. During seminars the patients were informed about these recommendations and learned progressive muscle relaxation. Agreed therapy between physician and patient was documented by physicians and patients during a 6 months treatment interval and compared with the recommended therapy. Effectivity of treatment was assessed by pre-post changes of days of headache/month, attack frequency/month, headache intensity (visual analogue scale), pain related impairment (German version of the Brief Pain Inventory), and health related quality of life (German Version of the SF-36). 51 patients were documented by 24 primary care physicians after communication of recommendations and 46 patients completed the patient seminar. Data of both groups were compared with those of 80 patients from primary care physicians before interventions. RESULTS: Communication of recommendations for headache therapy to primary care physicians did not improve conformity of the agreed therapy with the recommended. Contrary conformity of the agreed therapy for pharmacological treatment of migraine attacks and interval therapy of migraine by progressive muscle relaxation with the recommended therapy improved significantly. However, interventions did not significantly improve the outcome quality of outpatient treatment as compared to the therapy of primary care physicians before interventions. CONCLUSION: Effectivity of headache treatment in primary health care could not be improved by communication of evidence-based recommended therapy to primary care physicians nor by direct information of patients about these recommendations in combination with provided availability to learn progressive muscle relaxation.

Adult↗

The neural basis of biased competition in human visual cortex.

A typical scene contains many different objects that compete for neural representation due to the limited processing capacity of the visual system. At the neural level, competition among multiple stimuli is evidenced by the mutual suppression of their visually evoked responses and occurs most strongly at the level of the receptive field. The competition among multiple objects can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that biasing signals due to selective attention can modulate neural activity in visual cortex not only in the presence, but also in the absence of visual stimulation. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals likely derives from a distributed network of areas in frontal and parietal cortex. Attention-related activity in frontal and parietal areas does not reflect attentional modulation of visually evoked responses, but rather the attentional operations themselves.

Evoked Potentials, Visual↗

Modulation of sensory suppression: implications for receptive field sizes in the human visual cortex.

Neurophysiological studies in monkeys show that when multiple visual stimuli appear simultaneously in the visual field, they are not processed independently, but rather interact in a mutually suppressive way. This suggests that multiple stimuli compete for neural representation. Consistent with this notion, we have previously found in humans that functional magnetic resonance imaging (fMRI) signals in V1 and ventral extrastriate areas V2, V4, and TEO are smaller for simultaneously presented (i.e., competing) stimuli than for the same stimuli presented sequentially (i.e., not competing). Here we report that suppressive interactions between stimuli are also present in dorsal extrastriate areas V3A and MT, and we compare these interactions to those in areas V1 through TEO. To exclude the possibility that the differences in responses to simultaneously and sequentially presented stimuli were due to differences in the number of transient onsets, we tested for suppressive interactions in area V4, in an experiment that held constant the number of transient onsets. We found that the fMRI response to a stimulus in the upper visual field was suppressed by the presence of nearby stimuli in the lower visual field. Further, we excluded the possibility that the greater fMRI responses to sequential compared with simultaneous presentations were due to exogeneous attentional cueing by having our subjects count T's or L's at fixation, an attentionally demanding task. Behavioral testing demonstrated that neither condition interfered with performance of the T/L task. Our previous findings suggested that suppressive interactions among nearby stimuli in areas V1 through TEO were scaled to the receptive field (RF) sizes of neurons in those areas. Here we tested this idea by parametrically varying the spatial separation among stimuli in the display. Display sizes ranged from 2 x 2 degrees to 7 x 7 degrees and were centered at 5.5 degrees eccentricity. Based on the effects of display size on the magnitude of suppressive interactions, we estimated that RF sizes at an eccentricity of 5.5 degrees were <2 degrees in V1, 2-4 degrees in V2, 4-6 degrees in V4, larger than 7 degrees (but still confined to a quadrant) in TEO, and larger than 6 degrees (confined to a quadrant) in V3A. These estimates of RF sizes in human visual cortex are strikingly similar to those measured in physiological mapping studies in the homologous visual areas in monkeys.

Adult↗

Mechanisms of visual attention in the human cortex.

A typical scene contains many different objects that, because of the limited processing capacity of the visual system, compete for neural representation. The competition among multiple objects in visual cortex can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that, both in the absence and in the presence of visual stimulation, biasing signals due to selective attention can modulate neural activity in visual cortex in several ways. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals derives from a network of areas in frontal and parietal cortex.

Animals↗

Texture segregation in the human visual cortex: A functional MRI study.

The segregation of visual scenes based on contour information is a fundamental process of early vision. Contours can be defined by simple cues, such as luminance, as well as by more complex cues, such as texture. Single-cell recording studies in monkeys suggest that the neural processing of complex contours starts as early as primary visual cortex. Additionally, lesion studies in monkeys indicate an important contribution of higher order areas to these processes. Using functional MRI, we have investigated the level at which neural correlates of texture segregation can be found in the human visual cortex. Activity evoked by line textures, with and without texture-defined boundaries, was compared in five healthy subjects. Areas V1, V2/VP, V4, TEO, and V3A were activated by both kinds of line textures as compared with blank presentations. Textures with boundaries forming a checkerboard pattern, relative to uniform textures, evoked significantly more activity in areas V4, TEO, less reliably in V3A, but not in V1 or V2/VP. These results provide evidence that higher order areas with large receptive fields play an important role in the segregation of visual scenes based on texture-defined boundaries.

Adult↗

Increased activity in human visual cortex during directed attention in the absence of visual stimulation.

When subjects direct attention to a particular location in a visual scene, responses in the visual cortex to stimuli presented at that location are enhanced, and the suppressive influences of nearby distractors are reduced. What is the top-down signal that modulates the response to an attended versus an unattended stimulus? Here, we demonstrate increased activity related to attention in the absence of visual stimulation in extrastriate cortex when subjects covertly directed attention to a peripheral location expecting the onset of visual stimuli. Frontal and parietal areas showed a stronger signal increase during this expectation than did visual areas. The increased activity in visual cortex in the absence of visual stimulation may reflect a top-down bias of neural signals in favor of the attended location, which derives from a fronto-parietal network.

Attention↗

High-frequency repetitive transcranial magnetic stimulation delays rapid eye movement sleep.

Repetitive transcranial magnetic stimulation (rTMS) is a promising new treatment for patients with major depression. However, the mechanisms underlying the antidepressive action of rTMS are widely unclear. Rapid eye movement (REM) sleep has been shown to play an important role in the pathophysiology of depression. In the present study we demonstrate that rTMS delays the first REM sleep epoch on average by 17 min (102.6 +/-22.5 min vs 85.7+/-18.8 min; p < 0.02) and prolongs the nonREM-REM cycle length (109.1+/-11.4 min vs 101.8+/-13.2min, p< 0.012). These rTMS-induced changes in REM sleep variables correspond to findings observed after pharmacological and electroconvulsive treatment of depression. Therefore, it is likely that the capability of rTMS to affect circadian and ultradian biological rhythms contributes to its antidepressive action.

Adult↗

Mechanisms of directed attention in the human extrastriate cortex as revealed by functional MRI.

A typical scene contains many different objects, but the capacity of the visual system to process multiple stimuli at a given time is limited. Thus, attentional mechanisms are required to select relevant objects from among the many objects competing for visual processing. Evidence from functional magnetic resonance imaging (MRI) in humans showed that when multiple stimuli are present simultaneously in the visual field, their cortical representations within the object recognition pathway interact in a competitive, suppressive fashion. Directing attention to one of the stimuli counteracts the suppressive influence of nearby stimuli. This mechanism may serve to filter out irrelevant information in cluttered visual scenes.

Adult↗

Transient visual field defects induced by transcranial magnetic stimulation over human occipital pole.

Transient visual field defects (VFDs) and phosphenes were induced in normal volunteers by means of transcranial magnetic stimulation (TMS) using a circular magnetic coil of 12.5 cm diameter placed with its lower rim 2-4 cm above the inion in the midline. Subjects had to detect small, bright dots presented randomly for 14 ms in one of 60 locations on a computer screen resulting in a plot of the central 9 degrees of the visual field. In 8 of 17 subjects, transient VFDs were inducible at peak magnetic field strenghts of 1.1-1.4 T. In the central 1-3 degrees, detection of targets was impaired in both the upper and lower visual field, whereas at 4-9 degrees large parts of only the lower visual field were affected with a sharp cut-off along the horizontal meridian. Targets at 1 degree in the lower field were affected with lower TMS intensities than corresponding locations in the upper or peripheral locations in the lower field. Detection of central targets was affected at more caudal stimulation sites than detection of peripheral targets. Phosphenes were elicitable in 14 of 17 subjects at clearly lower field strengths of 0.6-1.0 T. Many subjects perceived chromatophosphenes. From a discussion of the literature on patients with VFDs and the known topography of the human visual system, it is concluded that the transient VFDs at 1-3 degrees are probably due to stimulation of both striate cortex (V1) and extrastriate areas (V2/V3), while VFDs in the lower visual field at eccentricities 4-9 degrees are due to stimulation of V2/V3 but not V1.

Adult↗

A reversible system for chronic recordings in macaque monkeys.

We propose a system for head fixation and neuronal recording that minimizes surgery for implantation. Fixation is obtained by posts which are attached to the opposite sides of the skull and are connected by a rigid frame around the animal's head. As forces are counterbalanced and distributed around the head, the system does not need to be implanted into the skull, and thus allows for continuous adjustment to the growing skull in young animals. Except for small incisions for the posts, the skin over the skull is left intact. Recording is achieved through small bone holes which are easily reached by means of conical guide tubes. The system provides perfect stability of recording, allows flexible access to various areas of the brain and can be easily removed during longer pauses in experiments. The use of this system may also decrease the number of laboratory animals needed.

Animals↗

Evidence for asynchronous development of sleep in cortical areas.

We have recorded from extrastriate area V4 in monkeys performing a visual search task. When animals became tired or drowsy, responses to visual stimulation were often reduced or even completely blocked, and background activity changed to the burst-pause pattern typically seen in sleep. In spite of such neuronal sleep observed in V4, animals continued to perform the visual task, indicating that at least the primary visual cortex was still working. This observation shows that sleep does not develop simultaneously in all cortical areas but may affect some areas earlier than others. In particular conditions, local sleep of certain areas may be a stable and long-lasting phenomenon.

Animals↗

Modulation of transferrin receptor expression by dexrazoxane (ICRF-187) via activation of iron regulatory protein.

Dexrazoxane (ICRF-187) has recently been demonstrated to reduce cardiac toxicity induced by chemotherapy with anthracyclines, although the reason for this phenomenon has remained obscure thus far. In order to investigate whether ICRF-187 might exert its effects by modulating iron metabolism, we studied the drug's potential to influence the maintenance of iron homeostasis in two human cell lines. We demonstrate that ICRF-187 enhanced the binding affinity of iron regulatory protein (IRP), the central regulatory factor for posttranscriptional iron regulation, to RNA stem loop structures, called iron responsive elements (IRE), in THP-1 myelomonocytic as well as K562 erythroleukemic cells. Increased IRE/IRP interaction was paralleled by an elevation of transferrin receptor (trf-rec) mRNA levels which, according to the well-established mechanism of posttranscriptional iron regulation, was likely due to stabilisation of trf-rec mRNA by IRP. Subsequently, ICRF-187 treatment of cells increased trf-rec surface expression and enhanced cellular iron uptake. All these events, i.e. IRP activation, stabilisation of trf-rec mRNA and increased surface expression of the protein in response to ICRF-187, follow a dose-response relationship. Increased cellular uptake and sequestration of iron in response to ICRF-187 may contribute to the protective activity of ICRF-187 by reducing the iron-anthracycline complex and iron-catalysed generation of hydroxyl radicals via the Haber-Weiss reaction.

Antineoplastic Agents↗

Regulation of cellular iron metabolism by erythropoietin: activation of iron-regulatory protein and upregulation of transferrin receptor expression in erythroid cells.

Erythropoietin (Epo) is the central regulator of red blood cell production and acts primarily by inducing proliferation and differentiation of erythroid progenitor cells. Because a sufficient supply of iron is a prerequisite for erythroid proliferation and hemoglobin synthesis, we have investigated whether Epo can regulate cellular iron metabolism. We present here a novel biologic function of Epo, namely as a potential modulator of cellular iron homeostasis. We show that, in human (K562) and murine erythroleukemic cells (MEL), Epo enhances the binding affinity of iron-regulatory protein (IRP)-1, the central regulator of cellular iron metabolism, to specific RNA stem-loop structures, known as iron-responsive elements (IREs). Activation of IRP-1 by Epo is associated with a marked increase in transferrin receptor (trf-rec) mRNA levels in K562 and MEL, enhanced cell surface expression of trf-recs, and increased uptake of iron into cells. These findings are in agreement with the well-established mechanism whereby high-affinity binding of IRPs to IREs stabilizes trf-rec mRNA by protecting it from degradation by a specific RNase. The effects of Epo on IRE-binding of IRPs were not observed in human myelomonocytic cells (THP-1), which indicates that this response to Epo is not a general mechanism observed in all cells but is likely to be erythroid-specific. Our results provide evidence for a direct functional connection between Epo biology and iron metabolism by which Epo increases iron uptake into erythroid progenitor cells via posttranscriptional induction of trf-rec expression. Our data suggest that sequential administration of Epo and iron might improve the response to Epo therapy in some anemias.

Animals↗

Neuronal correlates of pop-out in cat striate cortex.

Neuronal responses to static and moving texture patterns were investigated in the striate cortex of anaesthetized and paralysed adults cats. Texture patterns were composed of a central light bar presented in the excitatory receptive field of a cell and an array of many similar elements in the surround. For the static condition, elements in the surround were either parallel or orthogonal to the centre line (orientation test). For the moving condition, centre and surround elements (all at same orientation) moved either in the same or in the opposite directions (motion test). Thirty-six percent (31/86) of the neurons tested for motion and 24% (24/99) of the neurons tested for orientation responded more strongly to the patterns displaying feature contrast than to the uniform patterns. These neurons may form a neural basis for visual pop-out of orientation and motion.

Animals↗

Adolescents with mental retardation: perceptions of sexual abuse.

Reactions of nonretarded female undergraduates to sexually coercive situations in which neither, one, or both protagonists had mental retardation were examined. Results indicated that retardation affected perceptions of both responsibility and harm. Implications for the education of mental health professionals about the emotional needs of individuals with retardation are discussed.

Adolescent↗