Static and dynamic cultivation of bone marrow stromal cells on biphasic calcium phosphate scaffolds derived from an indirect rapid prototyping technique.

The adequate regeneration of large bone defects is still a major problem in orthopaedic surgery. Synthetic bone substitute materials have to be biocompatible, biodegradable, osteoconductive and processable into macroporous scaffolds tailored to the patient specific defect. Hydroxyapatite (HA) and tricalcium phosphate (TCP) as well as mixtures of both phases, biphasic calcium phosphate ceramics (BCP), meet all these requirements and are considered to be optimal synthetic bone substitute materials. Rapid prototyping (RP) can be applied to manufacture scaffolds, meeting the criteria required to ensure bone ingrowth such as high porosity and defined pore characteristics. Such scaffolds can be used for bone tissue engineering (BTE), a concept based on the cultivation of osteogenic cells on osteoconductive scaffolds. In this study, scaffolds with interconnecting macroporosity were manufactured from HA, TCP and BCP (60 wt% HA) using an indirect rapid prototyping technique involving wax ink-jet printing. ST-2 bone marrow stromal cells (BMSCs) were seeded onto the scaffolds and cultivated for 17 days under either static or dynamic culture conditions and osteogenic stimulation. While cell number within the scaffold pore system decreased in case of static conditions, dynamic cultivation allowed homogeneous cell growth even within deep pores of large (1,440 mm(3)) scaffolds. Osteogenic cell differentiation was most advanced on BCP scaffolds in both culture systems, while cells cultured under perfusion conditions were generally more differentiated after 17 days. Therefore, scaffolds manufactured from BCP ceramic and seeded with BMSCs using a dynamic culture system are the method of choice for bone tissue engineering.

Anterior frontal cortex and the effect of proactive interference in word pair learning--results of Brain-SPECT.

Technetium-99m-HMPAO-Brain-SPECT was performed twice in each of 12 right-handed students. The control condition was a standard word pair learning task. In the experimental condition, subjects had to overcome the detrimental effect that older memories exerted on the acquisition of new information (controlling proactive inhibition): they were presented with taxonomically similar words, which could easily be mixed up, and which reappeared in each list, but in different pairings. Results revealed an increase in right anterior frontal flow indices with the experimental condition. These results parallel the observed increase in negative event-related DC potential shifts. UHL et al. [J. cognit. Neurosci. 2, 373, 1990] recorded at frontopolar (Fp3, Fp4) scalp projections, although the extent of modulation was much higher for DC potentials (100%) than it was for SPECT (3%) thus suggesting different sensitivity.

Elaborative strategies in word pair learning--DC-potential correlates of differential frontal and temporal lobe involvement.

Cortical DC potentials were recorded while subjects were learning word pairs. The use of an elaborative mnemonic strategy resulted in a left frontal sustained negative shift. Its amplitude was independent of whether imagery mnemonics or semantic mnemonics were used. By contrast, posterior temporal potentials differed according to strategy: with imagery mnemonics, subjects had more symmetrical potentials over posterior temporal areas whereas with a semantic strategy, there was a left hemispheric preponderance of the DC potential. An interpretation within Stuss and Benson's theory on the frontal lobes is given.

Cortical slow potentials in verbal and spatial tasks--the effect of material, visual hemifield and performing hand.

Fifteen right-handed students voluntarily initiated the tachistoscopic presentation of visual stimuli containing either verbal (abstract words) or spatial (stereogeometric figures) material. Subjects had to reproduce stimulus material which had been presented either in their right or their left hemifield of vision by writing or drawing, either with their right or their left hand. Material-specific effects were found during the reproduction period: amplitudes of the performance-related negative potential shifts were larger in parietal and occipital recordings (P4, O1, and O2) when drawing as compared to writing. The opposite was true in frontal and left central leads (F3, F4, and C3) where writing was associated with larger negative amplitudes than drawing. Although subjects were informed about the nature of the forthcoming stimulus before voluntarily initiating the task, material-specific effects were missing in the preparation period. The performing hand had an influence on potentials in central leads, whereas hemifield of vision had no effect on preparation- and performance-related slow potential shifts.

Cortical DC potential shifts accompanying the central processing of visually presented analogue and digital time displays.

According to studies in brain-lesioned patients, the cortical substrate subserving the reading of digitally presented time displays seems to differ from that of reading analogue displays. While the right hemisphere has been assumed to be important for reading analogue displays, reading digital displays is attributed to the left hemisphere. This study attempts to localize the cortical substrate of reading analogue versus digital time displays in the intact human brain using scalp-recorded event-related slow negative DC potential shifts. In the arithmetic tasks, subjects had to judge whether or not the time conveyed by the last out of three tachistoscopically presented (analogue or digital) slides was the exact difference between the time conveyed by the first and the second slide. In the control condition, subjects only had to attend to (analogue or digital) time displays. With analogue slides, frontolateral recording sites revealed a right hemispheric preponderance of DC shifts measured in the interval between the second and third slide. Anterior temporal recording sites revealed a right hemispheric preponderance only when calculations were performed. By contrast, there was no hemispheric lateralization with digital slides. The arithmetic versus control manipulation modulated waveforms, but did not influence hemispheric laterality.

Cerebral correlates of imagining colours, faces and a map--I. SPECT of regional cerebral blood flow.

The distribution of regional cerebral blood flow (rCBF) was assessed by single photon emission computerized tomography (SPECT) in subjects during a resting state and during imagining either colours or faces or a route on a map. Twelve out of 30 subjects reported the spontaneous occurrence of mental visual images during the resting state. In these subjects flow in both orbitofrontal regions was higher than in those subjects who had not experienced spontaneous imagery. Voluntary imagery led to an increase of regional flow indices in basal temporal regions of both hemispheres and to a rightwards shift of global hemispheric asymmetry. The local changes were distinctly more marked with faces than with any of the other two stimuli. Imagining faces was also the only condition that led to an increase of activity in the left inferior occipital region which has been suggested by previous studies as being a crucial area for visual imagery. It is concluded that the observed differences of rCBF patterns between imagery conditions are related to the amount of information conveyed by the mental image. In contrast to the results of a companion study on DC-shifts accompanying imagery there was no effect of the visual versus spatial character of the images.

Cerebral correlates of imagining colours, faces and a map--II. Negative cortical DC potentials.

Cortical activation patterns as measured by negative shifts of the scalp-recorded cortical steady potential ("DC shifts") were assessed in 28 normal subjects during imagining colours, faces, and a spatial map. Imaging resulted in sustained negative DC shifts at temporal, parietal and particularly at occipital sites. The topographic distributions of such DC shifts was modulated as a function of whether spatial or visual imagery was performed. During imaging the spatial map, a parietal maximum was observed, as opposed to a distribution in favour of temporal and occipital sites during imagining faces and colours. Results suggest a neuroanatomical dissociation between visual and spatial imagery. Since a similar visual-spatial dichotomy exists in perception, the finding is interpreted as further evidence of a shared cerebral substrate for images and percepts. The results are discussed in conjunction with the joint blood flow study.

Dynamic changes of plasma lipids and lipoproteins in patients after transient ischemic attack or minor stroke.

PURPOSE: Only few data are available concerning variations of lipids and lipoproteins in the acute stage after ischemic cerebrovascular events. It was the aim of this study to investigate whether the lipid and lipoprotein levels obtained in the first few days after a transient ischemic attack (TIA) or a minor stroke (MS) actually reflect "correct' values or "changed' (ie, false low) values, as in patients after acute myocardial infarction. PATIENTS AND METHODS: Total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglyceride (TG) levels of 37 unselected patients with TIA or MS were determined within 12-48 hours (Group A) or within 49-168 hours (Group B) after the acute event. After a mean observation period of 15.3 months, all patients were re-examined; the results were compared with those of the baseline evaluation. RESULTS: At the time of the baseline evaluation, TC and LDL-C levels of Group B patients were significantly lower than Group A levels. At the end of the observation period, however, Group A and Group B patients did not differ with regard to all four parameters. In comparison with the baseline examination, the values of Group A patients had not changed. In Group B patients, however, TC, HDL-C, LDL-C, and TG levels had significantly increased. CONCLUSION: Our results strongly suggest that lipid and lipoprotein levels of patients with TIA or MS should be assessed within a maximum of 48 hours after the acute event. If the examination cannot be performed within that period, the determination of reliable values is possible only after several weeks or months.

Unimanual motor learning impaired by frontomedial and insular lesions in man.

We correlated impaired unimanual motor learning with the lesion site in 53 patients with chronic lesions predominantly of the frontal lobe. The lesions were assessed using computed tomography (CT), then transferred to standard templates of nine slices parallel to the canthomeatal plane and digitized with a raster matrix of 3 mm by 3 mm width. The learning task was to track a moving target on a computer screen with a dot guided by the preferred hand, while the horizontal coupling between hand movement and screen was inverted. The mean tracking error was recorded over eight successive trials of 80s duration. If the mean error of the last three trials was not lower than that of the first three trials, impaired motor learning was assumed. We correlated performance and lesion with a contingency table analysis for each raster element. Impaired motor learning was associated with a lesion within the supplementary motor area and adjacent anterior cingulate, and within the anterior insular region. Our results indicate that these regions are critical for motor learning and functional plasticity in man. Our data support activation patterns obtained with positron emission tomography.

Increased regional cerebral blood flow in inferior occipital cortex and cerebellum of early blind humans.

Cerebral flow indices were measured in 7 early blind and 13 sighted persons twice, during a task of passive and of active touch. In the blind, inferior occipital and cerebellar indices were higher. But they were not significantly modified by the kind of tactile task.

Slow potential shifts preceding human focal paroxysmal discharges, as represented by spikes of benign rolandic epilepsy of childhood.

We examined the slow potential shifts preceding interictal spikes in the scalp EEGs of the children with benign rolandic epilepsy of childhood (BREC). In contrast to our expectations and the observations reported by Stodieck and Wieser (1987), we were not able to detect focal negative slow shifts preceding interictal discharges. Possible reasons for this result are as follows. The cerebral event to which we triggered might have been too 'weak'. Another problem is that not every single spike generated in the deep reaches the surface. Thus, the moment, a spike occurs in the scalp-recordings does not necessarily represent the moment the brain changes from one state to another. The reference electrode might also play a role in obscuring any slow shift.

On the functionality of the visually deprived occipital cortex in early blind persons.

In early blind mammals, the deprived visual cortex undergoes anatomical and functional alterations. Its functional role was investigated in the early human blind by using patterns of cortical activation as measured by scalp-recorded event-related slow negative DC potential shifts. The blind showed higher occipital negativity than did sighted persons both during a tactile reading task and a non-reading tactile control task. Results point to a possible role for the blind's visual cortex in tactile processes.

Negative cortical potentials when classifying familiar and unfamiliar faces.

Event-related potential (ERPs) were recorded while subjects were classifying familiar faces of celebrities according to profession in one task, or unfamiliar faces according to gender in another task. Familiar faces given rise to an enhancement of the late negative ERP component confined to parieto-occipital sites. The finding is considered to reflect parietal and occipital lobe involvement in the activation of memories pertinent to familiar faces. Moreover, the late negative component was more prominent over the right than the left occipital lobe.

[Cocaine abuse--with special reference to cerebrovascular complications]. / Cocain-Missbrauch--unter besonderer Berücksichtigung zerebrovaskulärer Komplikationen.

The role of drug abuse as a risk factor for cerebrovascular events has been underestimated, particularly in patients with juvenile stroke. The drug most often associated with acute cerebrovascular events is cocaine. After cocaine hydrochloride abuse intracerebral hemorrhages or subarachnoid hemorrhages--predominantly caused by ruptured aneurysms or arteriovenous malformations--are by far the most frequently observed cerebrovascular complications, whereas on abuse with the alkaloidal form ("crack") intracranial hemorrhages and ischemic strokes are encountered with equal frequency. In most cases, the time interval between drug abuse and the cerebrovascular event is less than 3 hours. Several pathophysiological mechanisms are discussed as serving as triggers for the cerebrovascular event, either alone or in combination. No specific antidote to cocaine is known. Nevertheless drug screening (urine analysis) should be performed immediately to allow optimal management of patients with drug-associated acute cerebrovascular events, especially in cases with juvenile stroke.

[Mefloquine and sulfadoxine/pyrimethamine overdose in malaria tropica]. / Mefloquin- und Sulfadoxin/Pyrimethamin-Uberdosierung bei Malaria tropica.

A 39 year-old man with malaria due to Plasmodium falciparum received 3500 mg mefloquine over 3 days, in addition to 3250 mg chloroquine and 175/3500 mg sulfadoxine/pyrimethamine. He developed severe neuropsychiatric symptoms and had to be hospitalized. Treatment with diazepam, haloperidol and thioridazine achieved relief of the severe symptoms after 4 days. The patient was still suffering from discrete neuropsychiatric symptoms 8 months after treatment.

Ultrasound treatment for treating the carpal tunnel syndrome: randomised "sham" controlled trial.

OBJECTIVE: To assess the efficacy of ultrasound treatment for mild to moderate idiopathic carpal tunnel syndrome. DESIGN: Randomised, double blind, "sham" controlled trial with assessments at baseline, after 2 weeks' and 7 weeks' treatment, and at a follow up assessment 6 months later (8 months after baseline evaluation). SETTING: Outpatient clinic of a university department of physical medicine and rehabilitation in Vienna. SUBJECTS: 45 patients with mild to moderate bilateral carpal tunnel syndrome as verified by electroneurography. INTERVENTION: 20 sessions of ultrasound (active) treatment (1 MHz, 1.0 W/cm2, pulsed mode 1:4, 15 minutes per session) applied to the area over the carpal tunnel of one wrist, and indistinguishable sham ultrasound treatment applied to the other. The first 10 treatments were performed daily (5 sessions/week); 10 further treatments were twice weekly for 5 weeks. MAIN OUTCOME MEASURES: Score of subjective symptom ratings assessed by visual analogue scale; electroneurographic measures (for example, motor distal latency and sensory antidromic nerve conduction velocity). RESULTS: Improvement was significantly more pronounced in actively treated than in sham treated wrists for both subjective symptoms (P < 0.001, paired t test) and electroneurographic variables (motor distal latency P < 0.001, paired t test; sensory antidromic nerve conduction velocity P < 0.001, paired t test). Effects were sustained at 6 months' follow up. CONCLUSION: Results suggest there are satisfying short to medium term effects due to ultrasound treatment in patients with mild to moderate idiopathic carpal tunnel syndrome. Findings need to be confirmed, and ultrasound treatment will have to be compared with standard conservative and invasive treatment options.

3D-Cultivation of bone marrow stromal cells on hydroxyapatite scaffolds fabricated by dispense-plotting and negative mould technique.

The main principle of a bone tissue engineering (BTE) strategy is to cultivate osteogenic cells in an osteoconductive porous scaffold. Ceramic implants for osteogenesis are based mainly on hydroxyapatite (HA), since this is the inorganic component of bone. Rapid Prototyping (RP) is a new technology in research for producing ceramic scaffolds. This technology is particularly suitable for the fabrication of individually and specially tailored single implants. For tissue engineering these scaffolds are seeded with osteoblast or osteoblast precursor cells. To supply the cultured osteoblastic cells efficiently with nutrition in these 3D-geometries a bioreactor system can be used. The aim of this study was to analyse the influence of differently fabricated HA-scaffolds on bone marrow stromal cells. For this, two RP-techniques, dispense-plotting and a negative mould method, were used to produce porous ceramics. The manufactured HA-scaffolds were then cultivated in a dynamic system (bioreactor) with an osteoblastic precursor cell line. In our study, the applied RP-techniques give the opportunity to design and process HA-scaffolds with defined porosity, interconnectivity and 3D pore distribution. A higher differentiation of bone marrow stromal cells could be detected on the negative mould fabricated scaffolds, while cell proliferation was higher on the dispense-plotted scaffolds. Nevertheless, both scaffold types can be used in tissue engineering applications.

Tactile mental imagery in sighted persons and in patients suffering from peripheral blindness early in life.

Patterns of cortical activity as measured by scalp-recorded event-related slow negative DC potential shifts were recorded in 9 early blind and 23 sighted normals while they imagined the feel of textures with the fingertips of one hand. All sighted subjects reported to have concomitant visual imagery as well. Hence, it was not surprising to observe occipital negative shifts, previously described as a sign of occipital visual cortex involvement in visual mental imagery. Though having never had visual perception, the blind, too, had occipital negativities. Their absolute amplitudes were smaller than in the sighted, not only occipitally but also and more pronounced at other areas, particularly frontally where amplitudes were even positive. On the hypothesis that the smaller overall amplitudes in the blind could obscure topographical differences between groups, the relative distribution of negativity across the scalp was assessed, using normalized data. Such normalized parameters significantly differed between groups, indicating that the occipital potentials of the blind were relatively more negative as related to the other scalp areas, than were the occipital potentials of the sighted as related to the other scalp areas. This occipital finding might indicate a participation of the blind's visually deprived occipital cortex in tactile imagery. Second, parietal DC potentials were maximal over the hemisphere contralateral to the imaging hand, possibly indicating involvement of the contralateral parietal association cortex in tactile imagery. Reasons why this was true only for the sighted, are discussed.

[Hyperhomocyst(e)inemia--an independent risk factor of stroke]. / Hyperhomocyst(e)inämie--ein unabhängiger Risikofaktor des Schlaganfalls.

The total of free and protein-bound homocysteine including its derivatives is usually summarised as "homocyst(e)ine [H(e)]". Several congenital enzyme deficiencies may cause markedly elevated H(e) plasma levels, leading to the well-known clinical syndromes of homocystinuria. Recently, mild hyperhomocyst(e)inemia has been recognised as an independent risk factor for ischaemic cerebrovascular disease, coronary heart disease, and peripheral artery disease. H(e) levels are also related to the extent of atherosclerotic vessel wall alterations. The role of mild hyperhomocyst(e)inemia in venous thromboembolic disease, however, is not yet clear. A considerable proportion of patients with mild hyperhomocyst(e)inemia suffers from a deficiency of folate, vitamin B12, and/or vitamin B6. Supplementation of these agents--alone or combined with betain--leads to a decrease or even to a normalisation of elevated H(e) levels in the majority of such patients. Hitherto, no prospective randomised studies dealing with the clinical efficacy of such a--probably innocuous--supplementation have been performed. In the meantime, adequate alimentary intake of folate should be ensured.