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Neuroplasticity is the ability of the central nervous system to induce functional and microstructural changes in order to adapt to a new environment. However, so-called maladaptive neuroplasticity can also bring disadvantages, such as reduced inhibition of input signals, one of the suspected causes of chronic pain. With the method of repetitive transcranial magnetic stimulation (rTMS) a technique has been developed that makes it possible to study cortical excitability changes in the human brain non-invasively over a long time. Electrophysiological studies have shown that the application of rTMS over the primary motor cortex induces a facilitatory or inhibitory effect on the corticospinal and cortico-cortical excitability depending on the protocol used. The results of the clinical studies published suggest that rTMS can inhibit pain perception with regard to chronic pain and in experimentally induced pain conditions. An alternative method to induce neuroplastic changes is transcranial direct current stimulation (tDCS). tDCS acts primarily on the membrane potential, by hyper- or depolarizing it. The induced after-effects are NMDA receptor dependent. The effectiveness of tDCS is currently being explored in migraine research as well as experimentally induced and chronic pain conditions. In phase II trials its efficacy has been demonstrated. Ongoing studies are focusing on management of the placebo effect; however, it is easier to control this effect in tDCS compared to rTMS. Phase III trials are currently in preparation.

La 2 CuO 4 becomes superconducting at T c =44 K when subjected to an electrochemical oxydation in 1N NaOH at room temperature. Data on AC susceptibility of this compound as a function of temperature and DC fields from 0 to 85 Oe are presented and compared with those obtained on other known superconductors. Our studies indicate that the superconductivity in our sample is not confined to the surface as might be expected for a process dependent on small diffusion coefficients.

The X-ray absorption fine structure (XAFS) of single crystals of NbS2, Cu0.16NbS2, NbSe2 and Cu0.38NbSe2 is investigated at the Nb, Se and Cu edges. Measurements are made for different angles between the crystallographic c-axis and the X-ray beam. Nearest-neighbor and next-nearest-neighbor distances, as well as their variances, are extracted from the extended XAFS (EXAFS), indicating that intercalation of copper does not affect the average distances within the Nb-chalcogen layers while, at the same time, a structural disorder is introduced. The X-ray absorption near edge structure (XANES) of CuxNbSe2 is sensitive to the direction of empty electronic states and indicates that empty states with z-symmetry are separated from empty states with x- and y-symmetry by about 2.5 eV. It also shows that intercalation is accompanied by charge transfer from the Cu to the NbSe2 host lattice.

The semiconducting chromium spinel CuCr{sub 2}Se{sub 3}Br is shown to be accessible to reversible electrochemical and chemical reduction as well as to oxidation in Cu electrolytes by topotactic electron/ion transfer reactions leading to nonstoichiometric phases Cu{sub 1+y}Cr{sub 2}Se{sub 3}Br (O {le} y {le} 0.50) and Cy{sub 1{minus}y}CrSeBr (0 {le} y {le} 0.23). The oxidation proceeds under partial deintercalation of Cu and formation of valence band holes with a concurrent significant increase in the Curie temperatures {Tc}, which demonstrates the strong correlation between magnetic ordering and band holes with a concurrent significant increase in the Curie temperatures {Tc}, which demonstrates the strong correlation between magnetic ordering and band hole concentration. The final product obtained by cathodic reduction is the new metastable spinel Cu{sub 1.5}Cr{sub 2}Se{sub 3}Br. Neutron diffraction and electron spectroscopy studies reveal that copper intercalation leads to the formation of Cu{sub 3}{sup 2+} clusters with electron defect bonding. Changes in the electronic structure upon reduction and oxidation processes are discussed on grounds of band structure schemes.

Single crystal and powder electrodes of 2H−NbS 2 have been intercalated with hydrated Cs + ions forming Cs x (H 2 O) y [NbS 2 ]. Structural investigations have been performed in situ during the intercalation reaction on single crystals which were aligned on a powder diffractometer in a specially equipped electrochemical cell. Several intermediate phases were obtained, showing a complex X-ray pattern with sharp, broad, and diffuse reflection profiles simultaneously, which also do not fit to integral hkl values. They can be interpreted, however, assuming a statistical disordered layer sequence of fully occupied and empty interlayer gaps. The structural disorder is confirmed by simulation calculations of the X-ray patterns.

To investigate the non-linear optical properties of nitrophenylhydrazones, a series of 4-nitro- and 2,4-dinitrophenylhydrazones of substituted aromatic aldehydes were synthesized. It was found that many of the dinitrophenythydrazone derivatives are liquid-crystalline and X-ray investigations show that the mesophase corresponds to a hexagonal columnar structure. To explain this unusual behaviour it is necessary to assume that a mesogenic structure is formed by intramolecular hydrogen bonding of the dinitrophenylhydrazones. Charge transfer induced antiparallel alignment of these moleculer dipoles leads to discoid structures, forming the columnar phases.

The expression of type VIII collagen was examined in the normal and diseased human brain. Focal immunoreactivity was seen in histologically abnormal vessels of all four angiomas and 40 of 52 brain tumours (gliomas, meningiomas and schwannomas). An extended staining pattern, as well as a punctate distribution, was frequently observed in affected vessels. Staining was not apparent in nine normal brains and in 15 pathologic brains showing various cerebrovascular abnormalities, including Alzheimer's, Leigh's and Wernicke's diseases. Immunoblotting of glioblastomas revealed two bands at 56 kD and 67 kD which were also present at low levels in normal frontal cortex. The extracellular distribution of type VIII collagen was different from that of the other collagen types which have been described in brain and resembles patterns of expression described for certain tissues during mammalian embryogenesis (Kapoor et al., 1988). Our results provide additional evidence for the participation of type VIII collagen in some types of angiogenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9

Oxygen-deficient YBa2Cu3O6+x samples were investigated by the muon spin rotation technique in zero external field. In an intermediate oxygen concentration region we find strongly relaxing μSR signals indicating the existence of internal magnetic fields. The strongly relaxing signals were observed only in samples with superconducting transition temperatures below 50 K. As an interpretation of the data we suggest that magnetic ordering and superconductivity coexist in these samples within regions of extensions of a few lattice constants, but not necessarily on the same sites.

We have previously reported the magnetic properties of the Er(Co,Mn)O3 solid solution, in which Mn atoms have been partially substituted by Co. Several magnetic entities coexist in this system (Er3+, Mn3+, Mn4+, Co2+, Co3+), resulting into a subtle interplay between different interactions and leading to unusual phenomena such as: a spin reversal due to antiferromagnetic exchange between erbium and transition-metal spins, a step-like transition due to reorientation of magnetic domains, a relaxation mechanism connected to the rotation energy of the domains, the intersection of the increasing and decreasing branches in the magnetization loops, etc. These results have been obtained in highly dense ceramic samples for compositions near ErCo0.50Mn0.50O3. In order to better understand the different mechanisms, we have started a program on crystal growth. High-quality single crystals of orthorhombic structure (S.G. Pbnm) of Er(Co,Mn)O3 manganite were grown in a floating-zone oven under oxygen atmosphere. Although the zero-field-cooled/field cooled (ZFC/FC) curves confirm the spin reversal observed in bulk samples, the remarkable effects seen on hysteresis loops for bulk samples were not present in single crystals, probably due to oxygenation conditions. On the other hand, a very large anisotropy was observed between two perpendicular orientations of the single crystal.

Single crystals of sodium oxocuprate(III) NaCuO2 with up to 5 mm length have been prepared from sodium hydroxide/peroxide melts. The structure has been refined by single crystal X-ray and neutron powder data. The Laue symmetry has been determined now unambiguously to be 2 m , resulting in a monoclinic Bravais lattice.

Semiquantitative histological evaluation of brain iron and ferritin in Parkinson's (PD) and Alzheimer's disease (DAT) have been performed in paraffin sections of brain regions which included frontal cortex, hippocampus, basal ganglia and brain stem. The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron. No such changes were observed in the same regions of DAT brains. The increase of iron is evident in astrocytes, macrophages, reactive microglia and non-pigmented neurons, and in damaged areas devoid of pigmented neurons. In substantia nigra of PD and PD/DAT, strong ferritin reactivity was also associated with proliferated microglia. A faint iron staining was seen occasionally in peripheral halo of Lewy bodies. By contrast, in DAT and PD/DAT, strong ferritin immunoreactivity was observed in and around senile plaques and neurofibrillary tangles. The interrelationship between selective increase of iron and ferritin in PD requires further investigation, because both changes could participate in the induction of oxidative stress and neuronal death, due to their ability to promote formation of oxygen radicals.

Sixty-seven tumor specimens of epithelial choroid plexus neoplasms obtained by 60 biopsies and 7 autopsies from 52 patients were investigated. Diagnoses of the first operations were choroid plexus papilloma (PP; 32 cases), choroid plexus papilloma with histological atypies (atypical PP; 6 cases), and choroid plexus carcinoma (PC; 14 cases). Carcinoembryonic antigen was expressed by 2 of the 3 biopsies autoptically recognized as metastatic carcinomas and by 2 autopsy cases of PC, while it was absent in all biopsies of true choroid plexus tumors. Tumor cells positive for transthyretin (TTR, prealbumin), S-100 protein (S100), and glial fibrillary acidic protein (GFAP) were detected in 39, 46 and 13, respectively, of the 49 cases of true choroid plexus tumors. Fourth ventricle tumors expressed more S100 (number of positive tumor cells) than lateral ventricle tumors, PP more S100 and TTR than atypical PP/PC. Tumors from patients 20 years of age and older expressed more GFAP and TTR than tumors from younger patients. Of the 30 patients with complete follow-up 19 were alive 2 to 11 years after surgery, including 7 recurrencies. Eleven died from the tumor 4 months to 7 years after surgery. The following histopathologic features (in order of decreasing significance) were correlated with poor prognosis (recurrency or fatal outcome): less than 50% of the tumor cells heavily positive for S100, presence of mitoses, absence of TTR-positive cells, brain invasion by cell nests, absence of marked stromal edema, and presence of necrotic areas. Our results indicate that some histologic features correlate significantly with poor prognosis and that immunohistochemical results correlate with tumor localization, age, and malignancy.

Fibroblast growth factor (FGF) is a potent angiogenic factor and a mitogen for a variety of mesoderm- and neuroectoderm-derived cell types (e.g., fibroblasts, endothelial cells, astrocytes, oligodendrocytes). After application of a monospecific polyclonal antiserum, we localized basic FGF on frozen sections of 73 human brain tumors using immunohistochemistry. FGF was present in a variable number of tumor cells (16/16 astrocytomas, 5/5 ependymomas, 0/3 benign and 4/7 anaplastic oligodendrogliomas, 11/12 glioblastomas, 11/11 meningiomas, 6/6 neurilemmomas, 0/3 pituitary adenomas, 2/2 choroid plexus papillomas, 0/1 neurocytoma, 2/2 benign fibrous histiocytomas, 2/5 metastatic carcinomas). FGF was detected in vascular cells of 59 tumors and in fibroblasts of connective tissue stroma from all papillomas and metastases. These results tend to indicate FGF involvement in the malignant progression of gliomas due to an autocrine or paracrine action. Histopathological aspects of malignant gliomas (e.g., pseudopalisading or pathological vessels) could be related to FGF activity.

A man, aged 58 years, suffered from progressive dementia, parkinsonism, and gaze paralysis for 30 months. Autopsy revealed severe degeneration of the substantia nigra, numerous swollen chromatolytic neurons within the cerebral cortex, scattered basal neurofibrillary tangles, and gliosis of the cerebral white matter and basal ganglia. Unusual globular inclusions positive for tau protein were detected within neurons of the upper cortical layers. Although the pathological findings were comparable with corticonigral degeneration with neuronal achromasia, several clinical and pathological features characteristic for progressive supranuclear palsy, progressive subcortical gliosis, and Pick's disease in this and the nine previously reported cases hampered the unequivocal nosological placement.

This article presents a survey of characteristic features of Williams–Beuren syndrome (WBS) as reported in the literature and the interdisciplinary treatment of a subject with WBS with special regard to morphological and functional disorders. Typical features of a patient with WBS and his dental development in a follow-up from 8 to 25 years of age are shown. Early orthodontic treatment approaches, later combined orthodontic–orthognathic surgical procedures, and the status 5 years after surgery are presented.

We present a 31-year-old female patient with primary non-Hodgkin's lymphoma of the CNS after immunosuppressive therapy. Colitis ulcerosa had been diagnosed 2 years previously. Prophylactic therapy with azathioprine over 9 months was stopped after the development of listeria meningitis which was treated successfully with antibiotics. At this time native CCT was normal. Three months later the patient developed an epileptic seizure and multiple cerebral lesions were detected in CCT and MRI. Although antibiotic therapy was started, the cerebral lesions showed no regression. Stereotactic biopsy revealed immunochemical and histologic high-grade malignant B cell lymphoma. The risk of primary CNS lymphoma under azathioprine treatment for an autoimmune disease with a possible congenital immunodeficiency is presented and the literature is reviewed.

Brain stimulation with weak direct current has recently been reintroduced as a method to elicit and modulate neuroplasticity of the human cerebral cortex. Transcranial direct current stimulation (tD

Exaggerated caution or even deferment in the treatment of chronically ill mothers-to-be, for example, in the case of epilepsy, hypertension or bronchial asthma, may result in a dramatic worsening of the underlying disease and thus may threaten the further development of the fetus. On the other hand, an inadequate knowledge of the true risks of pharmacological treatment already applied in the early stages of pregnancy, leads to numerous abortions that are inappropriately indicated. As a basic rule, when planning pharmacological treatment in a pregnant woman, well tried and tested substances should be given preference over new drugs. If a pregnant woman has been exposed to an insufficiently tested substance as a result of ignorance of her pregnancy, recognized centers with appropriate data banks (www.reprotox.de) should be consulted.

The synthesis, via nuclear fusion reactions, of elements heavier than the actinides, allows one to probe the limits of the periodic table as a means of classifying the elements. In particular, deviations in the periodicity of chemical properties for the heaviest elements are predicted as a consequence of increasingly strong relativistic effects on the electronic shell structure1,2,3,4,5,6,7. The transactinide elements have now been extended up to element 112 (ref. 8), but the chemical properties have been investigated only for the first two of the transactinide elements, 104 and 105 (refs 9,10,11,12,13,14,15,16,17,18,19). Those studies showed that relativistic effect render these two elements chemically different from their lighter homologues in the same columns of the periodic table (Fig. 1). Here we report the chemical separation of element 106 (seaborgium, Sg) and investigations of its chemical behaviour in the gas phase and in aqueous solution. The methods that we use are able to probe the reactivity of individual atoms, and based on the detection of just seven atoms of seaborgium we find that it exhibits properties characteristic of the group 6 homologues molybdenum and tungsten. Thus seaborgium appears to restore the trends of the periodic table disrupted by relativistic effects in elements 104 and 105.

Patients with severe multiple sclerosis (MS) relapses which do not respond sufficiently to corticosteroids can undergo escalating immunotherapy with plasma exchange. We review the course of 14 apheresis cycles in 13 adult patients and three pediatric cases from our center between 2004 and 2005. Nine cases were due to optic neuritis, five had experienced clinically isolated syndromes, and two suffered from Devic's disease. Of the adult patients, 71% had good or very good outcome. The mean time point of improvement was after the third plasmapheresis session, and early initiation of plasma exchange therapy (within 1 month after begin of relapse) was associated with better outcome. In pediatric MS, two of three patients showed clear improvement. These data argue for a very good therapeutic effect of plasma exchange if performed early and with adequate indication.

The restless legs syndrome (RLS) is a clinical diagnosis based on the four essential criteria defined by the International Restless Legs Syndrome Study Group (IRLSSG). An idiopathic form can be separated from a symptomatic form. Neurophysiological studies have investigated the pathophysiology of the idiopathic RLS or have been used to exclude a symptomatic cause, in particular polyneuropathy. So far cortical excitability changes, corticomotor, somatosensory and auditory pathways, spinal cord excitability, B-wave rhythm and cycling alternating pattern, as well as reflex mechanisms have been investigated by electroencephalography, evoked potentials, Bereitschaftspotentials, nerve conduction and thermal threshold measurements, electromyography, transcranial Doppler sonography, measurements of the spinal flexor reflex as well as neuroimaging techniques. The etiology of the RLS cannot be revealed by these methods, neurophysiological studies in RLS are, however, useful for a better understanding of the pathophysiology and for exclusion of a polyneuropathy or other symptomatic causes. In addition to neurophysiological investigations, small fiber neuropathy, which seems to be a more common finding in RLS patients than expected to date, may need biopsy for confirmation. This review will focus on investigations of the different systems involved with diverse neurophysiological methods.

Progressive multifocal leucoencephalopathy (PML) is an opportunistic infection caused by human polyomaviruses such as the JC virus. It usually occurs as a severe complication of immunosuppression in patients with primary disorders of the immune system or secondary impairment of immune function, for example, after iatrogenic states of immunosuppression. PML usually takes a rapidly progressive course and advances to death within 1 to 18 months. Today, PML is mainly seen in AIDS, while previously it was typically found in patients with granulomatous, neoplastic, or infectious diseases. In granulomatous diseases particularly, PML is thought to occur as a result of iatrogenic states of immunosuppression, but it is also seen in patients aggressively treated with immunosuppressive agents for systemic lupus erythematosus (SLE).1,2 PML progresses to death in most of these patients even after withdrawing immunosuppressive therapy.2 Therefore additional therapy, aimed at supporting a more rapid restoration of immune function his warranted. We report a 40 year old woman diagnosed with SLE at the age of 20 years, based on four American College of Rheumatology criteria (erythema, arthritis, elevated antinuclear antibodies, and anti-dsDNA antibodies). Owing to neuropsychiatric lupus (the patient had experienced several psychotic episodes) with suspected vasculitic changes on cerebral magnetic resonance imaging (MRI), the patient had undergone 12 cycles of cyclophosphamide pulse …

To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression.Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM.Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p0.001). Upregulation of TNFalpha, IL-1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFalpha gene expression. In patients with AS there was a strong inverse relation between circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014), between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p = 0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = -0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFalpha gene expression than were patients with well compensated DCM (p = 0.011).TNFalpha gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFalpha gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.

Dermatomyositis/polymyositis (DM/PM) and Lambert-Eaton myasthenic syndrome (LEMS) are two autoimmune disorders that have very rarely been reported to occur together in the same patient. We report on two patients with DM who were later diagnosed with concomitant LEMS, and point out diagnostic challenges in identifying LEMS in patients with DM/PM. As specific treatment for LEMS is available, it is important to identify those DM/PM patients who suffer from concomitant LEMS.

Choroid plexus carcinomas (CPC) have been shown to carry mutations in the hSNF5/INI1 gene on chromosomal arm 22q11.2. A recent study on choroid plexus papillomas (CPP) and CPC revealed frequent losses of chromosomal portions on the long arm of chromosome 22 (-22q). The region harbouring hSNF5/INI1 was affected in 47% of the CPP and 73% of the CPC, respectively. -22q occurred more frequently in adult than in infantile CPP suggesting different pathogenetic pathways for these tumours. These findings may indicate a potential tumour suppressor gene function of hSNF5/INI1 in a subset of choroid plexus tumours. In order to examine its potential role in the pathogenesis of choroid plexus tumours, we analysed exons 1-9 of hSNF5/INI1 by SSCP analysis in a series of 21 formalin-fixed and paraffin-embedded CPP. No alterations in migratory patterns were detected. These data indicate that somatic point mutations of hSNF5/INI1 do not play a role in the pathogenesis of CPP and that CPP and CPC may arise by two different molecular pathways.

Pharmacotherapy in pregnancy is often problematic, since both the mother-to-be and her doctor are often concerned about possible risks for the unborn child. On the other hand, we now have sufficient knowledge of a whole range of medications, to enable the recommendation of safe drug treatment in almost any clinical situation. The family doctor, too, is often consulted by pregnant women requiring treatment for internistic problems. These include such pregnancy-unrelated problems as essential hypertension or bronchial asthma, as well as pregnancy-related disorders such as urinary tract infection or gastrointestinal problems.