Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

Protein kinase C agonist and antagonist effects in normal human epidermal keratinocytes

Abstract Several lines of evidence implicate protein kinase C (PKC) in the development of basal cell and squamous cell carcinomas, tumors which originate from epidermal keratinocytes. To examine PKC in a model relevant to human skin, we exposed normal human epidermal keratinocytes (NHEK) in serum-free media to a variety of PKC agonists and antagonists. NHEK PKC activity increased up to 10-fold within the 1st hour of exposure to tetradecanoyl phorbol acetate (TPA), and gradually returned to control values within 72 h. TPA-induced PKC activity was enhanced by pretreatment of cultures with protein and RNA synthesis inhibitors. TPA-induced growth arrest and differentiation was antagonized by staurosporine. Down-regulation by bryostatin pretreatment blocked TPA-stimulated differentiation. Our overall conclusion is that activation of PKC in cultured human keratinocytes is required for differentiation. These results are crucial to the analysis of compounds suspected of promoting or inhibiting epidermal tumors.     

Mycotic aneurysm of the aorta: MRI and MRA features

Mycotic aneurysms of the abdominal aorta are potentially fatal but uncommon. We report the MRI and MRA features of an abdominal aortic mycotic aneurysm in a patient who presented with nonspecific low back pain. By delineating the saccular nature of the aneurysm and identifying the coexistence of vertebral enhancement, MRI was crucial for the final diagnosis. A potential pitfall of contrast-enhanced MRA is also demonstrated.     

Substance P augments the rate of vasodilation induced by calcitonin gene-related peptide in porcine ophthalmic artery in vitro.

Peptides may function as neurotransmitters liberated antidromically by sensory nerve fibres, provoking vascular responses having potential importance in some neurological disorders. Dose-response relaxation curves induced by substance P (SP) and calcitonin gene related peptide (CGRP) have been studied in porcine ophthalmic arteries in vitro. Both peptides induced vasodilation when tested separately (CGRP much greater than SP). Because of the putative interactions between such peptides in this vascular territory, a computerised system was also used for analysing over time the response to a single addition of either 10(-8) M CGRP, 10(-8) M SP or a combination of 10(-8) M SP + 10(-8) M CGRP. SP did not augment the maximum relaxation induced by CGRP alone, but increased significantly the rate of relaxation during the initial phase of the response. The effect induced by the SP+CGRP combination was stronger than the sum of the individual SP and CGRP-induced relaxations during the first 4 min of the response, which suggests a SP-CGRP synergism in this artery.     

Cluster headache: phospholipid metabolism in polymorphonuclear cells

Our group has previously reported significant changes in the incorporation of precursors into glycerophospholipids, particularly phosphatidylserine, in polymorphonuclear cells obtained from the peripheral blood of cluster headache patients, when compared with controls. The potential of these results led to further work using both the previous methodology and a modified isolation technique to obtain polymorphonuclear cells in as pure a state as possible. Neither the new results obtained using the original technique, nor the results with high purity polymorphonuclear cells from controls and cluster headache patients, confirm the marked changes in precursor uptake into glycerophospholipids originally reported.     

Theory and practice of sampling studies: exemplified by the MONICA survey

Résumé Parallèlement à l'enregistrement systématique des cas d'infarctus, le projet MONICA prévoit de mesurer à trois reprises le niveau des facteurs de risque cardio-vasculaires auprès d'un échantillon aléatoire. L'article présente le plan d'échantillonnage de ce premier «examen de santé» MONICA réalisé dans les cantons de Vaud, de Fribourg et du Tessin. Il s'agit d'un plan à deux niveaux, avec tirage stratifié des communes en fonction de leur taille, puis tirage des individus dans les fichiers communaux. Les conditions d'un plan d'échantillonnage efficace dans le cadre plus général de l'inférence statistique sont abordées dans une première partie théorique. Les raisons pratiques (contraintes budgétaires, problèmes de logistique, disponibilité des fichiers administratifs) qui ont motivé le choix de ce plan sont exposées ensuite. Une troisième partie décrit toutes les étapes de sa réalisation, avec les difficultés méthodologiques et concrètes rencontrées. La discussion porte sur une évaluation critique de toute la procédure qui, dans le cadre du projet MONICA, a produit des échantillons dont le degré d'adéquation avec la population est assez élevé.

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Theoretical and practical aspects of sampling: the MONICA-Project.

Summary In parallel with the systematic registration of myocardial infarction, the MONICA-Project attempts to investigate at three different times the prevalence of risk factors for cardiovascular disease in the population. This article presents the sampling plan of the first MONICA survey in the cantons of Vaud, Fribourg and Tessin. The sampling procedure was at two levels: first, a sample of communes stratified according to community size was chosen, and secondly, within these communities, individuals were selected from the population registries. The prerequisites for an efficient sampling plan are discussed on a theoretical level. In addition, the practical constraints (budget, organizational problems, population registry files) are presented. Finally, all steps of the sampling procedure are described including the difficulties encountered. The discussion attempts a critical evaluation of the whole MONICA sampling procedure whose results are largely satisfactory.

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Theorie und Praxis der Stichprobenbildung: das Beispiel des MONICA-Projektes

Zusammenfassung Neben einer systematischen Erfassung der Infarktfälle sieht das MONICA-Projekt eine dreimalige Erfassung der Risikofaktorenprävalenz vermittels einer Zufallsauswahl vor. Der vorliegende Artikel schildert den Stichprobenplan der ersten in den Kantonen Waadt, Freiburg und Tessin durchgeführten Untersuchung. Es handelt sich um einen zweistufigen Stichprobenplan: zuerst wurde eine Ziehung der Gemeinden — stratifiziert nach Gemeindegrösse — vorgenommen, danach wurden die Individuen auf Grund der Einwohnerregister gezogen. Die Grundbedingungen für einen effizienten Stichprobenplan werden in einem ersten theoretischen Abschnitt diskutiert. Im weiteren werden die konkreten Bedingungen der MONICA-Stichprobenziehung dargestellt (Budget-Limiten, organisatorische Probleme, Aufbau der Einwohnerregister). Ein dritter Teil beschreibt sämtliche Schritte der eigentlichen Stichprobenbildung einschliesslich der aufgetretenen Schwierigkeiten. Die Diskussion nimmt eine Gesamtbeurteilung der Stichprobenziehung im MONICA-Projekt vor, deren Ergebnis recht befriedigend ausfällt.