Structural stability and thermoelectric performance of high quality synthetic and natural pyrites (FeS2).

Synthetic bulk and natural pyrite from the hydrothermal mine in Schönbrunn (Saxony, Germany) are confirmed to be stoichiometric FeS2 compounds and stable (for thermoelectric applications) up to ∼600 K by combined thermal, chemical, spectroscopic and X-ray diffraction analyses. Natural pyrite with a small amount (<0.6 wt%) of well-defined transition metal carbonates revealed characteristics of a nondegenerate semiconductor and is suitable as a model system for the investigation of thermoelectric performance. In the temperature range 50-600 K both natural and synthetic high quality bulk FeS2 samples show electrical resistivity and Seebeck coefficients varying within 220-5 × 10-3 Ω m and 4 - (-450) µV K-1, respectively. The large thermal conductivity (∼40 W m-1 K-1 at 300 K) is exclusively due to phononic contribution, showing a well pronounced maximum centered at ∼75 K for natural pyrite (grain size ≤5 mm). It becomes almost completely suppressed in the sintered bulk samples due to the increase of point defect concentration and additional scattering on the grain boundaries (grain size ≤100 µm). The thermoelectric performance of pure pyrite with ZT ∼ 10-6 at 600 K is indeed by a factor of ∼1000 worse than those reported earlier for some minerals and synthetic samples.

High frequency of partial SPAST deletions in autosomal dominant hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disease. The most frequent cause of autosomal dominant HSP is mutation of SPAST (SPG4 locus), but additional pedigrees remain mutation negative by conventional screening despite linkage to SPG4. OBJECTIVE: To determine the frequency of genomic copy number aberrations of SPAST in autosomal dominant HSP. METHODS: We developed and validated a multiplex ligation-dependent probe amplification assay targeting SPAST and SPG3A, another gene frequently involved in autosomal dominant HSP. In a multicenter study we subsequently investigated 65 index patients with autosomal dominant HSP, all of whom had previously been screened negative for SPAST mutations. Independent secondary samples, additional family members, and cDNA were analyzed to confirm positive findings. RESULTS: Aberrant MLPA profiles were identified in 12 cases (18%). They exclusively affect SPAST, represent deletions, segregate with the disease, and are largely pedigree specific. Internal SPAST deletions entail expression of correspondingly shortened transcripts, which vary in stability. Age at onset in SPAST deletion carriers does not differ from that associated with other SPAST mutations. CONCLUSIONS: Partial SPAST deletions, but not SPAST amplifications and SPG3A copy number aberrations, represent an underestimated cause of autosomal dominant hereditary spastic paraplegia. Partial SPAST deletions are likely to act via haploinsufficiency.

Unexpected pathogenic mechanism of a novel mutation in the coding sequence of SPG4 (spastin).

The authors report a nucleotide substitution (c.1216A>G) in SPG4 (spastin) causing hereditary spastic paraplegia. This apparent missense mutation in the ATPase domain confers aberrant, in-frame splicing and results in destabilization of mutated transcript. Mutated protein is deficient in microtubule-severing activity but, unlike neighboring mutations, shows regular subcellular localization. The authors' data point to haploinsufficiency rather than a dominant negative effect as the disease-causing mechanism for this mutation.

[Diplopia and cardiogenic shock]. / Doppelbilder und kardiogener Schock. Eine okuläre Myositis assoziiert mit einer Riesenzellmyokarditis.

Idiopathic giant cell myocarditis is a rare and frequently fatal inflammatory heart disease which leads to congestive heart failure or ventricular arrhythmias. It is often associated with other autoimmune disorders. We report a 39-year-old woman who first presented with diplopia and painful eye movements, the typical clinical picture of orbital myositis. Shortly afterwards, she developed rapidly progressive congestive heart failure due to giant cell myocarditis, which took a fatal course within some weeks. Autopsy confirmed both disorders. This case report underlines the importance of early and repeated monitoring of cardiac function, if orbital myositis is suspected, in order to consider cardiac transplantation, the only efficacious treatment of giant cell myocarditis, in time.

Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation.

Many studies show consistently that repetitive transcranial magnetic stimulation (rTMS) with a frequency of 1 Hz and an intensity above the resting motor threshold (RMT) performed for several minutes over the primary motor cortex (M1) leads to a depression of cortical excitability. Furthermore, most studies concur on a facilitation of the non-stimulated contralateral M1. Little is known, however, about the physiological mechanisms underlying these effects. In 11 healthy volunteers, we stimulated the left M1 for 15 min with 1 Hz-rTMS of 115% RMT. Before, immediately after, and 30 min after the rTMS train, we examined short-interval intracortical inhibition (SICI; interstimulus interval (ISI) of 2 and 4 ms), intracortical facilitation (ICF; ISI 10 ms), and short-interval intracortical facilitation (SICF; ISI 1.5 ms) with established paired-pulse protocols. Mean unconditioned motor evoked potential (MEP) amplitudes and RMT were also measured. Two sessions were run at least 1 week apart, in one excitability of the stimulated M1 was tested, in the other one excitability of the non-stimulated M1. rTMS led to the expected reduction of MEP amplitude of the stimulated M1, which was significant only immediately after the rTMS train. rTMS increased MEP amplitude of the non-stimulated M1, which lasted for at least 30 min. RMT, SICI, ICF and SICF did not show any significant change in either M1, except for a long lasting increase of SICF in the non-stimulated M1. In conclusion, the MEP increase in the non-stimulated M1 lasted longer than the MEP decrease in the stimulated M1. Only the long-lasting MEP increase was associated with a specific change in intracortical excitability (increase in SICF). Modulation of motor cortical inhibition did not play a role in explaining the rTMS induced changes in MEP amplitude.

[Thrombotic thrombocytopenic purpura. Reduced activity of von Willebrand factor cleaving protease]. / Thrombotisch-thrombozytopenische Purpura. Verminderte Aktivität der von-Willebrand-Faktor-spaltenden Protease.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. Besides anemia and thrombocytopenia, neurological impairment is common in TTP. A 42-year-old woman was admitted to a department of obstetrics/gynecology because of severe vaginal bleeding due to thrombocytopenia. After platelet transfusion, the patient developed a reduced level of consciousness, confusion, headache, and fever. CT scan did not show pathological changes. Transcranial Doppler sonography revealed increased blood flow velocities of all basal cerebral arteries. Because encephalitis was suspected the patient was transferred to the neurological department. CSF and cerebral magnetic resonance imaging studies were normal. Finally, the detection of schistocytes in the peripheral blood smear and the strong elevation of LDH led to the diagnosis of TTP. After plasma exchange over 3 consecutive days the patient achieved complete remission. The diagnosis was confirmed by laboratory tests (activity of ADAMTS13 <5%, IgG antibodies against ADAMTS13). Platelet transfusion may adversely affect the outcome of patients with suspected TTP. Severely deficient activity of the von Willebrand factor cleaving protease (ADAMTS13) is specific for thrombotic thrombocytopenic purpura.

Click evoked myogenic potentials in the differential diagnosis of acute vertigo.

OBJECTIVE: In response to loud clicks, a vestibular evoked potential can be recorded from sternocleidomastoid muscles, called "click evoked myogenic potential" (CEMP). This paper reports on the usefulness of CEMP in the differential diagnosis of acute vertigo of presumed vestibular origin. METHODS: CEMP was examined in 40 patients with acute vertigo of vestibular origin (26 with acute peripheral vestibulopathy, five with Ménière's disease, three with benign paroxysmal positioning vertigo (BPPV), six with psychogenic vertigo) and the results compared with standard caloric reaction (CR). For CEMPs, clicks were delivered unilaterally via a pair of headphones. EMG activity was collected by surface electrodes placed on the sternocleidomastoid belly and averaged. RESULTS: In 29 patients, CR was unilaterally abnormal, pointing to a peripheral vestibular lesion. Seventeen of them had a corresponding loss of CEMPs; the other 12 patients had a normal CEMP. The remaining 11 patients had normal results in both tests. In comparison with CR, CEMP showed a sensitivity of 59% and a specificity of 100% for peripheral vestibular disorders. CONCLUSION: CR is a test of the horizontal canal whereas CEMP is thought to be a sacculus test. Different results of CR and CEMP may be due to this difference between target organs stimulated and may be of prognostic value.

Medicolegal risk in telemedicine: risk control in teleradiology.

Teleradiology, the largest single application of telemedicine in Australia, has the potential to improve healthcare access, delivery and standards, but also raise complex new legal and ethical issues. In the absence of any cases of alleged negligence in teleradiology before the courts, a hypothetical case reveals some of the medicolegal risks. These may be minimised by measures including adherence to the Royal Australian and New Zealand College of Radiologists' guidelines on teleradiology.

Evoked isometric muscle contractions in myopathies: analysis of pathophysiological properties by different stimulus patterns.

Isometric twitches of the adductor pollicis muscle following ulnar nerve stimulation were investigated in healthy subjects (n = 35) and patients with different types of myopathies (myotonic dystrophy, n = 19; limb girdle muscular dystrophy, n = 10; metabolic myopathy, n = 6). The changes within the rising part (i.e. within the contraction time, CT) of the isometric twitches after single stimuli were similar in myotonic and limb girdle dystrophies: the first part of CT, which lasts until the maximal contraction rate is achieved, was shortened, whereas the following second part of CT, which lasts until the maximal twitch force is achieved, was normal. In metabolic myopathies the first part was normal, whereas the second part was prolonged. The relaxation was prolonged in all types of myopathies, particularly in metabolic myopathies. Using double stimuli with short interstimulus intervals (ISI), the absolute refractory period of the muscle contraction (healthy subjects: 1.35 +/- 0.16 ms) was shortened in patients with myotonic dystrophy (1.02 +/- 0.11 ms). In the other types of myopathies, the absolute refractory period was only shortened provided that the single twitch force was clearly reduced. A similar dependence on a reduced single twitch force was also found with regard to the maximal force development with two stimuli and the corresponding ISI: the force contributed by a second stimulus was pathologically enhanced if the single twitch force was clearly reduced. The ISI related to the maximal force with two stimuli was shifted towards very short values (healthy subjects: 10.5 ms, myotonic dystrophy: 4.6 ms, limb girdle dystrophies: 5.0 ms). Our results can be attributed to altered kinetics of calcium release and uptake by the sarcoplasmic reticulum in myopathies.

Antineuronal antibody-associated paraneoplastic neuropathy in Hodgkin's disease.

Paraneoplastic neurological syndromes in patients with Hodgkin's disease are rare findings. Subacute, paraneoplastic cerebellar degeneration or autonomic dysfunctions were described before. In some of these cases, autoantibodies against central or peripheral nervous system structures were found in serum and CSF. We present a 30-year-old white male who developed a progredient, clinical and electrophysiological distal sensomotoric neuropathy. Six months after the beginning of the neurological disturbances, Hodgkin's disease (Stadium III BE) was diagnosed. Other reasons for neuropathy, such as direct impairment of the peripheral nervous system by tumor masses or drug-induced neuropathy, were excluded. Cerebrospinal fluid (CSF) analysis showed a mild pleocytosis, elevated total protein (9.8 g/l) and identical oligoclonal bands in serum and CSF. Blood-CSF barrier damage was detected by Reiber formula. Indirect immunofluorescence and western blot analysis demonstrated an autoantibody against peripheral and central nervous system structures in serum and CSF. Although the autoantibody responded to a 38-40 kDa-protein in western blot and showed nuclear staining of myenteric plexus and Purkinje cell nuclei in the immunofluorescence test, this antibody was shown to be not identical to anti-Hu. An intrathecal synthesis of the antineuronal antibody was detected by antibody specificity index. Tumor therapy, plasmapheresis and treatment with intravenous immunoglobulins did not improve the neuropathy. According to our knowledge this is the first case of antineuronal antibody-associated sensomotoric neuropathy in Hodgkin's disease.

Hereditary motor and sensory neuropathy with spastic paraplegia and optic atrophy: report on a family.

We describe two siblings affected by a motor and sensory neuropathy starting in childhood. Already in infancy, a spastic gait disturbance had become obvious, leading later to multiple surgical interventions. In adolescence, progressive loss of vision developed. At the time of our examination, both siblings showed severe weakness and atrophy of the distal muscles of legs and arms. Tendon jerks were brisk in proximal muscles; in the lower extremities, muscle tone was increased. Visual acuity was severely decreased. Nerve conduction studies revealed an axonal degeneration. This finding was confirmed by evaluation of a sural biopsy specimen in one patient, showing only few remaining myelinated fibres without signs of demyelination. This combination of hereditary motor and sensory neuropathy with spastic paraplegia and optic atrophy shows features of both hereditary motor and sensory neuropathy V and VI according to the classification of Dyck, indicating that these subtypes may not represent distinct entities.

[Generalized myoclonus as the only symptom of neurosyphilis]. / Generalisierte Myoklonien als alleiniges Symptom einer Neurosyphilis.

Symptomatic myoclonus syndromes can be caused by a broad range of etiological factors. We report the case of a 40-year-old woman who showed spontaneous and continuous myoclonus with predominance distally and in the arms as the only neurological symptom. CSF evaluation revealed acute neurosyphilis. Six months after antibiotic treatment, the movement disorder had disappeared.

Optomotor control of course and altitude in Drosophila melanogaster is correlated with distinct activities of at least three pairs of flight steering muscles.

Flight control in the fruitfly Drosophila melanogaster is achieved by minute sets of muscles on either side of the thorax. Control responses of wings and muscles were elicited during fixed flight by moving a striped pattern in front of the eyes. For example, pattern motion from the lower right to the upper left signals to the test fly a rotatory course deviation to the right and simultaneously a translatory altitude displacement downwards. The counteracting response to the displacement of the retinal image is an increase in thrust and lift on the right, accomplished mainly by increasing the wingbeat amplitude (WBA) on that side. A comparison of such responses with the simultaneously recorded action potentials in the prominent basalar muscles M.b1 and M.b2 and axillary muscles M.I1 and M.III1 on either side suggests that three of these muscles act on the WBA more or less independently and contribute to the optomotor control of course and altitude. During flight, M.b1 is almost continuously active with a frequency equal to or slightly below 1 spike per wingbeat cycle. The spikes occur within a narrow phase interval of this cycle, normally at the beginning of the transition from upstroke to downstroke. However, the visual stimulus described above causes a substantial phase lead in M.b1 on the right; the spikes occur shortly before the end of the upstroke. Such phase shifts are accompanied by comparatively smooth 'tonic' responses of the WBA. The activities of M.b2 and M.I1 are normally very low. However, the stimulus described above activates M.b2 on the right in a phase interval approximately two-thirds into the upstroke and M.I1 on the left in a phase interval at the beginning of the downstroke. The spikes tend to occur in bursts. These bursts are correlated with WBA-increasing 'hitches' (rapid changes in amplitude) on the right and WBA-decreasing hitches on the left. As fast 'phasic' responses, the burst-induced hitches are likely to account for the course-controlling 'body saccades' observed during free flight. For unknown reasons, M.I1 is activated by pattern motion but cannot conceivably assist the other muscles in altitude control. Unlike its homologues in larger flies (Musca domestica, Calliphora erythrocephala), M.III1 does not participate in optomotor flight control. Its activation seems to support the termination of flight and wing retraction at rest. The essential properties of the three pairs of muscles M.b1, M.b2 and M.I1 resemble those found in larger flies; the muscles are controlled by motion detectors with muscle-specific 'preferred directions' in the hexagonal array of retinal elements. Optomotor control of the three pairs of muscles in Drosophila melanogaster could explain most, but not all, of the WBA responses recorded so far.

Monosomy 1p is correlated with enhanced in vivo glucose metabolism in meningiomas.

The 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake of 25 human meningiomas was preoperatively evaluated in vivo by positron-emission tomography (PET). After surgery, meningioma biopsies were analyzed cytogenetically. Five meningiomas showed partial monosomy for chromosome 1p additional to other typical chromosome aberrations. This aberrant karyotype was correlated with increased FDG uptake. Three of five meningiomas with monosomy 1p were classified as grade II according to WHO, while only one of 20 tumors without monosomy 1p was classified as grade II. Thus, monosomy 1p and elevated FDG uptake in PET are to be regarded as cytogenetic and metabolic parameters for the aggressiveness of meningiomas.

[Intracranial manifestations of Langerhans-cell histiocytosis. Nuclear magnetic resonance findings]. / Intrakranielle Manifestationen der Langerhanszell-Histiozytose. Kernspintomographische Befunde.

We report on 3 patients with intracranial manifestations of Langerhans cell histiocytosis (LH). The results are correlated with histological, clinical and radiological reports on some 70 patients described in the literature as suffering from intracranial LH. Two different morphological pictures can be differentiated. First, typical infiltrates can be seen by microscopy; these can be located in every part of the brain, but are seen mainly in the region of the hypothalamus. These infiltrations are shown as space-occupying lesions with Gd-DTPA enhancement. The other manifestation is a demyelinized lesion with a sparse infiltration of Langerhans cells. These lesions, which are located mainly in the region of the nucleus dentatus of the cerebellum and the brain stem, show increased signal intensity in the T2 sequence and no Gd-DTPA enhancement on MRI.

Subtotal aplasia of myelinated nerve fibers in the sural nerve.

Thus far, only very few cases with neuronal maldevelopment in the peripheral nervous system have been reported (Table 1). The present sporadic case manifested itself with peripheral sensorimotor polyneuropathy in early infancy. Clinical findings included pareses and hypaesthesia of distal extremities and severely reduced nerve conduction velocities. During adolescence, cerebellar ataxia developed. Sural nerve biopsy taken at the age of 14.5 years showed severe fascicular hypoplasia, aplasia of large myelinated nerve fibers, and subtotal deficiency of small myelinated nerve fibers without numerical reduction of unmyelinated axons. There was no structural evidence of a progression of myelinated fiber breakdown although some collagen pockets and empty Schwann cell processes among preserved unmyelinated axons indicated some loss of unmyelinated fibers. These findings are interpreted as representing maldevelopment of the myelinated fibers in the peripheral nervous system. Appropriate classification of this unique disease among the known developmental disorders of peripheral nerves is discussed.

Renaut bodies contain elastic fiber components.

Renaut bodies (RB) are fusiform endoneurial structures preferentially found at sites of nerve entrapment, often occupying more than 30% of the cross-sectional area of a nerve fascicle. Their composition and significance, however, are still incompletely understood. In this study, further evidence for the link between the appearance of RB and nerve entrapment is presented. Reanaut bodies were already found at the age of 1 year in the median nerve at the level of the wrist, i.e. in the carpal tunnel, a possible site of entrapment. Here, their number increased with age. Renaut bodies were absent, however, in fetal nerves at this site. Many of the cells in RB resembled perineurial cells or pericytes. They were stained with antibodies against vimentin and epithelial membrane antigen and were partially covered by a basal lamina reactive with antibodies against collagen IV, laminin, and s-laminin. Focally accumulated filaments and bundles of 30-40 nm collagen fibrils were major extracellular components of RB. The diameter of the filaments (8-12 nm) corresponded to the size of the microfibril, i.e. the oxytalan component of elastic fibers. Renaut bodies were intensely stained with antibodies against these microfibrils and several types of collagen glycoproteins. On the basis of these results, we conclude that RB are composed of cells that show perineurial differentiation. These cells produce an extracellular matrix highly enriched in elastic fiber components.

Recruitment of dorsal column fibers in spinal cord stimulation: influence of collateral branching.

An electrical network model of myelinated dorsal column nerve fibers is presented. The effect of electrical stimulation was investigated using both a homogeneous volume conductor and a more realistic model of the spinal cord. An important feature of dorsal column nerve fibers is the presence of myelinated collaterals perpendicular to the rostro-caudal fibers. It was found that transmembrane potentials, due to external monopolar stimulation, at the node at which a collateral is attached, is significantly influenced by the presence of the collateral. It is concluded that both excitation threshold and blocking threshold of dorsal column fibers are decreased up to 50% compared to unbranched fibers.

Immunocytochemical analysis of cellular responses to BCG.

The study reported here was performed to find out whether changes in the number of mycobacteria in various organs of BCG-infected mice can be related to changes in the phenotype of monocytes, macrophages and lymphocytes in the blood, various tissues, and peritoneal cavity and to the formation of granulomas in the spleen, liver and lungs. The relative amounts of various antigens on the leukocytes were assessed semi-quantitatively after immunocytochemical detection of the binding of monoclonal antibodies. Granuloma formation was determined after immunocytochemical staining of cells in sections of liver and lung tissue with a monoclonal antibody against the common leukocyte antigen and in sections of the spleen with a monoclonal antibody against the Mac-2 antigen. The results showed that during the first week of infection the number of BCG in spleen, liver and lungs declined considerably. Multiplication of mycobacteria during the second week of infection was associated with decreased expression of antigen F4/80 and increased expression of Ia antigen and Mac-2 antigen by blood monocytes and macrophages. Reduction of the numbers of BCG in the spleen and liver during the third week after i.v. injection of BCG and in lungs during the fourth week of the infection was found to be correlated with the degree of granuloma formation in these organs. After intravenous injection of killed BCG no changes were observed in the phenotype of monocytes and the macrophages in spleen, liver, lungs and peritoneal cavity. These mice showed considerably less granuloma formation than BCG-infected mice. The present results indicate that live but not killed mycobacteria induce macrophage activation.