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Left cardiac myxoma and also consecutive embolization into the brain is well documented, whereas the association of myxomas with multiple fusiform cerebral aneurysms is rare. We analyze 33 previously reported patients and present a case of a 43-year-old woman with multiple cerebral infarctions 2 years after resection of a recurrent myxoma in the left atrium. Cerebral angiography displayed multiple fusiform aneurysms of several cerebral arteries, including a giant aneurysm of the basilar artery. Serum level of interleukin-6 (IL-6) was highly elevated. The clinical, radiological and pathological features of these aneurysms are summarized. The pathogenesis, including the role of IL-6 in the formation of myxomatous aneurysms, is discussed.

Die Atiologie und Pathogenese der amyotrophen Lateralsklerose (ALS) bleibt weitgehend ungeklart. In den zuruckliegenden Jahren sind bei den genetisch bedingten Varianten dieser Erkrankung wichtige Fortschritte bei der Identifizierung ihrer molekularbiologischen Grundlagen gemacht worden. Diese Fortschritte berechtigen zu der Hoffnung, das es in Zukunft gelingt, die Pathogenese der familiaren, aber auch der sporadischen Formen der Erkrankung zu erhellen und damit rationalen Therapieansatzen weiter den Weg zu bereiten. Im Rahmen dieser Ubersichtsarbeit soll sowohl auf die vorliegenden Befunde bei der familiaren Form der ALS (fALS) als auch auf die mogliche Bedeutung dieser Befunde fur pathogenetische Vorstellungen bei der sporadischen Form der ALS (sALS) eingegangen werden.

A qualitative immunohistochemical study was performed on calcineurin A- and calbindin-positive neurons in the spinal cord of transgenic mice, an animal model of amyotrophic lateral sclerosis, carrying the G93A mutation of the Cu/Zn-superoxide dismutase gene. The results show that calcineurin A-immunoreactive motoneurons are affected by the neurodegenerative process; in contrast, calbindin-positive cells are selectively spared. The findings suggest that calcineurin plays a role as an accessory factor responsible for selective vulnerability in the neurodegenerative process of amyotrophic lateral sclerosis.

The case of a 38-year-old patient with rapidly progressing motor neuron disease, complicated by major dysfunction of the extrapyramidal system and of vertical gaze is described. Neuropathological examination revealed a degenerative process that severely affected the lower motor neurons, as well as the neurons of the pars compacta of the substantia nigra, the nucleus of Darkschewitsch, the nucleus interstitialis of Cajal, the colliculi superiores, and the pallidum. The long tracts were unaffected at all levels of the brain stem and spinal cord. There was no convincing evidence for the presence of a multiple system atrophy or progressive supranuclear palsy; the results rather revealed a pattern of vulnerability characteristic of a variant of motor neuron disease.

At presently, the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are unknown. In recent years, the genetic background of hereditary motor neuron diseases has been partly defined. In particular, these advances represent an opportunity to improve our understanding of the pathogenesis of the familial and sporadic forms of ALS and thus provide a basis for rational therapeutic approaches. In this article, recent findings on the pathogenesis of the familial form of ALS and their implications for the sporadic form are discussed.

Summary Background Patients with sporadic amyotrophic lateral sclerosis (ALS) show disorganised collagen and elastin of the dermis. We looked for inflammatory alterations to cutaneous blood vessels. Patients and findings Seven patients with sporadic ALS were investigated; five were confined to bed, but none had bedsores. Light and electron microscopy of skin showed an oedematous dermis with collagen fibrils of irregular diameter. Small blood vessels were characterised by duplicated basement membranes and deposition of β-amyloid protein, the main component of the neuronal and non-neuronal amyloid deposits in Alzheimer's disease. These skin changes were seen in all degrees of disability, but none was found in age-matched and sex-matched controls. Interpretation The skin in ALS is characterised by a distinctive pattern of alterations of connective tissue and blood vessels. Examination of skin is an additional and easily accessible investigation which may help elucidate the pathogenesis of ALS.

A contribution of hepatic enzymes responsible for detoxification and toxification of xenobiotics and endogenous compounds has been suspected to contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). We studied 12 potentially relevant enzymes in 150 ALS patients and 373 controls on the genetic level and could not detect any significant difference between both groups. These results strongly support a view that—in contrast with earlier observations—hepatic foreign compound metabolism does not contribute to the pathogenesis of ALS. Genetic studies of familial ALS have yielded at least six chromosomal loci and two disease genes (“alsin” and superoxide dismutase 1).1–3 Mutations on the superoxide dismutase 1 initially suggested a role for free radicals in the disease process but recent results clearly argue for a gain of function mechanism. The mechanisms through which the mutant enzyme exerts …

Melts of diverse fractions of linear polyethylene have been investigated by longitudinal and transverse proton relaxation. A three-component model of molecular fluctuations allows to describe the longitudinal relaxation times in the frequency range of our experiments (10 4 to 10 8 Hz). The components are ‘anisotropic segment reorientation’, ‘reptation’ and the ‘conformational fluctuation of the surrounding tube’. The molecular weight dependences of the corresponding time parameters are τ s ∼ M 0 , τ l ∼ M 1 and τ r ∼ M 3 , respectively. These quantities also permit us to explain the molecular weight dependence of the transverse relaxation curves which have been described by the aid of the Anderson-Weiss theory. It is shown that the influence of the molecular weight distribution is not negligible. Rather it is the reason for non-exponential relaxation decays. The free induction decays have been found to decrease essentially faster than the relaxation decays even if the inhomogeneity of the magnet was negligible. As an explanation, internal inhomogeneities caused by microscopic voids have been assumed. An estimate of this effect is given. In addition to the pure fractions we have also studied a mixture of short chains in a matrix of long deuterated chains. It turns out that the fluctuation of the local network depends on both molecular weights and the ratio of mixture.

The magnetic-field dependence of the E.S.R. linewidth in amorphous silicon has been measured in order to investigate the influence of the exchange interaction on the E.S.R. linewidth. A different field dependence was obtained for amorphous silicon prepared by the glow-discharge technique and by electron-beam evaporation. The experimental results are discussed in terms of exchange-coupled spins which are distributed either homogeneously or inhomogeneously. It is concluded that exchange interaction is necessary to account for a variety of experimental results obtained in these materials.

Self-difusion in polyethylene and polystyrene melts has been investigated using a modified n.m.r. field-gradient technique. In both polymer examples, self-diffusion coefficients were found to be proportional to M−2.0±0.1w above and below the critical molecular weight Mc. The observation of undeuterated chains in deuterated matrices of varying chain length indicates only relatively weak matrix effects. The influence of internal field gradients, which have previously been reported for polyethylene melts, is demonstrated and discussed. Certain peculiarities have been observed in the temperature dependences of the diffusion coefficients.

To determine if blood lactate (LA) is the stimulus responsible for ‘breakaway’ ventilation (VE), the lactate (LT) and ventilation (VT) thresholds were monitored during one-legged cycling exercise. Ten healthy volunteer male subjects (Mean 2-legged \(\dot V_{O_{2\max } } \) =4.27 l·min−1) performed prior exercise (PE) to reduce muscle glycogen stores by cycling at 75–85% of maximal heart rate (HR max) for 60–75 min, followed by a 30 h low carbohydrate diet. Pre- and post- LT and VT tests were performed on a cycle ergometer employing a continuous protocol with increments of 16 W every 3 min. Muscle biopsies were taken from the vastus lateralis muscle before the PE ride, prior to the threshold test 24 h later, and before testing the non-exercised (NE) leg. An I.V. catheter placed in the antecubital vein was used for serial blood samples taken at rest, and during the final 30 s of each progressive load. Gas analysis was calculated every 30 s (Beckman Metabolic Measurement Cart). Biopsies (N=3) showed that the exercise and diet regimen elicited glycogen reduction which significantly (p

The signal intensity and contrast of NMR images depend both on measurement parameters and on tissue parameters. The most essential measurement parameters are the repetition time TR and the spin echo time TE. The effect of the echo time on the image contrast is demonstrated by the multi echo images shown in Fig. 3.1. The significant change in image contrast with increasing echo time is clearly demonstrated. The tissue specific parameters are the relaxation times T1 and T2, the proton density P and the diffusion coefficient D. Furthermore, the signal intensity in vessels is also fundamentally influenced by the flow velocity of the blood (see below). By applying chemical shift imaging methods, it is also possible to generate separate images of fat, water and magnetic susceptibility.

A method for chemical shift imaging is disclosed. A first radio frequency pulse at the resonance frequency of hydrogen and second radio frequency pulse at the resonance frequency of atoms to be examined are applied. Spatial resolution is obtained by phase encoding gradients. The repetition time is shorter than the spin-lattice relaxation time. The first radio frequency pulse at the resonance frequency of hydrogen causes a Nuclear Overhauser Effect enhancement of the resonance line of the atoms to be examined.

The major aims in tissue characterization are the differentiation between normal, benign and malignant (primary, metastatic) tissues, the determination of prognostic information (e.g. tumor growth rate) and the detection of early stages or precursors of tumors. At the present time, mainly the anatomical information of standard SE images as well as the MR parameters T1, T2, and spin density are used for the clinical diagnosis In many cases, however, the measurement accuracy and selectivity of these parameters do not suffice for a detailed analysis. In addition to Bo generate images of the magnetic susceptibility and the diffusion coefficient as well as images of fat and water separately In spite of the large number of parameters the problem of tissue characterization is quite difficult. The open questions are: Which of these parameters contain the relevant information ? How could the relevant information be extracted ? Is it necessary to calculate images of each of these parameters or are special combinations of these parameters required ?

The major aims in tissue characterization are the differentiation between normal, benign and malignant (primary/metastasic) tissues. Usually the information of standard spin echo images as well as the MR parameters T1, T2 and spin density are used for clinical diagnosis. Pattern recognition methods are applied to improve the specificity of MRI. The variety of all these parameters requires the selection of the parameters containing the relevant diagnostic information. Therefore images with optimum contrast to a given diagnostic task are generated.

Von entscheidender Bedeutung fuer die klinische Anwendung der KST ist die Trennbarkeit von normalen, gutartigen und boesartigen Geweben. Ueblicherweise werden die anatomische Information von Spinechobildern, sowie die daraus ableitbaren physikalischen Parameter T1, T2 und die Prontonendichte zur klinischen Diagnosestellung verwendet. Um zu objektivierbaren Aussagen bezueglich der Gewebsdifferenzierung zu gelangen werden Methoden der Mustererkennung angewandt.

Kidney diseases, healthy kidney tissue and adjacent organs like liver, musculature and fatty tissue were evaluated in respect to their T1-, T2-relaxation times and proton density values. In addition the results of an evaluation of T2-short, T2-long, Rho-short, Rho-long, which were calculated from the T2-relaxation times, are reported. The T2-times are very sensitive in demonstrating differences between the tissues, as significantly different values for healthy kidney tissue and hypernephromas could be found. Different values could be seen dependent on the calculation mode, whereby the calculations had been made from double echo and multiple echo sequences. The T1-relaxation times were less sensitive, differences could be also found between the calculations from the IR and SE mode. The values of T2-long and T2-short and the proton density values differed very much for the same organ in the examined groups of patients, therefore these additionally calculated values unlikely will help in the differential diagnosis of unknown kidney diseases.

Magnetic Resonance Imaging (MRI) has the ability to visualize blood flow noninvasively and without contrast agents, since the MR signal depends not only on the spin-density and the relaxation times T1 and T2, but also on the velocity of the moving spins itself. Besides the magnitude image a phase image, which is highly sensitive to motion, can be calculated from the complex signal after the Fourier transform. With the magnitude as well as the phase information conclusions about the flow characteristics and the velocity profile can be made, which is particularly important for instance for the diagnosis of aneurysms and stenoses [1].

Galanthamine proved effective in symptomatic treatment of senile dementia of Alzheimer's type. The aim of this study was to elucidate the metabolism of galanthamine. Two novel metabolites of galanthamine have been isolated from the urine of eight young men after single doses of 10-15 mg. Some 19.8% of the doses were excreted as O-demethylgalanthamine glucuronide, 5% as N-demethylgalanthamine, 25.1% as galanthamine, and 0.8% as epigalanthamine. After coadministration of quinidine hydrogen sulfate, which inhibits cytochrome P450 2D6 (CYP2D6) selectively, O-demethylgalanthamine glucuronide was highly diminished in urine. In vitro, human liver microsomes metabolized galanthamine to O-demethylgalanthamine with Vmax 5.2 nmol/mg protein/h and Km 187 microM. Ki of quinidine to inhibit O-demethylation was 28 nM. To inhibit cholinesterases, O-demethylgalanthamine was 10-fold more selective for acetylcholinesterase (AChE) versus butyrylcholinesterase (BuChE) than galanthamine. After glucuronidation, O-demethylgalanthamine failed to inhibit AChE and BuChE. N-Demethylgalanthamine inhibited cholinesterases less potently than galanthamine.