Acute therapy of ischemic cerebral infarct

The ischaemic cerebral attack is a disease prevailingly of older age. Its prognosis is distinguished by a mortality rate as high as ever. From 1975 to 1985, 520 patients with ischaemic cerebral attack have been treated in hospital, with specific acute therapy changing from the so-called vasodilator therapy via osmotherapy into haemodilution therapy with lowmolecular dextrane. Since during vasodilator therapy any early mobilisation nor continuous physiotherapy were carried out and the patients prevailingly died of bronchopneumonia, the significantly lower mortality rate under osmotherapy and haemodilution therapy cannot be attributed to the specific drug therapy. In all probability it is a result of the improvement of care and of the active early mobilisation of the patients.     

Rolle der Winkelstabilität bei der intramedullären Stabilisierung

Zusammenfassung Winkelstabile Plattenfixateur-interne-Systeme haben in den letzten 20 Jahren zunehmend an Bedeutung gewonnen. Die aus der Winkelstabilität resultierende flächenhafte Krafteinleitung und gleichmäßigere Kraftverteilung führen zu einer besseren Knochenbruchheilung insbesondere im metaphysischen Bereich und bei Osteoporose. Bei Marknagelsystemen ist die Winkelstabilität bislang nur partiell verwirklicht. Der vorgestellte winkelstabile Tibiamarknagel realisiert an jedem einzelnen Bolzen eine Winkelstabilität mit dem einliegenden intramedullären Kraftträger. Von Februar 2002–August 2004 wurden 21 Patienten mit ihm behandelt. In 13 Fällen wurden Frakturen stabilisiert, 6 Patienten hatten Fehlstellungen, 2 Patienten Pseudarthrosen. Zum Nachuntersuchungszeitpunkt waren alle Behandlungen abgeschlossen. Postoperative Komplikationen traten nicht auf. In allen Fällen wurde eine vollständige Durchbauung erreicht. In 6 Fällen fand sich radiologisch eine verzögerte Knochenbruchheilung. Die ersten klinischen Erfahrungen mit dem winkelstabilen Tibiamarknagel zeigen, dass dieser aufgrund der höheren Primärstabilität insbesondere im metaphysären Knochenbereich mit kurzen Fragmenten sowie bei Osteoporose Vorteile gegenüber anderen nichtwinkelstabilen oder nur partiell winkelstabilen Marknagelsystemen erbringt. Die verzögerten Knochenbruchheilungen bedürfen weiterer klinischer und biomechanischer Untersuchungen.     

Dependence and cross-dependence in the guinea-pig myenteric plexus

Summary Chronic activation of opioid receptors results in the development of tolerance and dependence. Tolerance may be confined to a single receptor type and thus has been termed selective tolerance. The present investigation reveals that prolonged activation of an inhibitory acting receptor type not only results in dependence associated with this receptor but also brings about cross-dependence. Cross-dependence involves both opioid receptors as well as non-opioid receptors, e. g. adrenoceptors. The experimental design employed did not permit conclusions to be drawn about whether those receptors exhibiting cross-dependence also developed tolerance. Regardless of the receptors and their specific subsequent transduction systems, all the receptors which showed dependence and cross-dependence proved sensitive to pertussis toxin, suggesting a critical function of GTP-binding proteins for the development of not only opioid dependence but also for drug dependence in general. Since multiple transmitter receptors may converge on the same ion channel, the concept of convergent dependences may be linked to GTP-binding proteins. However, no conclusions can be drawn with regard to the precise biochemical mechanisms underlying dependence. Send offprint requests to R. Schulz at the above address     

Rationale for clinical trials of opiate antagonists in treating patients with personality disorders and self-injurious behavior

A subgroup of patients with personality disorders from the DSM-III-R (American Psychiatric Association 1987) "flamboyant" cluster is characterized by repetitive self-injurious behavior (SIB) apparently not motivated by suicidal intent. After describing the clinical and demographic characteristics of these patients, the clinical and preclinical evidence suggesting the involvement of endogenous opiate systems in this behavior is reviewed. Patients with personality disorders and SIB have been found to have elevated levels of plasma beta-endorphin. However, the available evidence is not sufficient to show whether this is a cause of or a consequence of SIB. Behavioral stereotypies resulting in self-injury in animals and SIB in mentally retarded patients have been shown to be abolished by opiate antagonist administration in a significant proportion of both groups. The available evidence suggests that clinical trials of oral opiate antagonist drugs should be undertaken because of the promise such drugs have in the treatment of this sometimes life-threatening disorder.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

IL-18 induces the differentiation of Th1 or Th2 cells depending upon cytokine milieu and genetic background

The functional division of CD4(+) T cells into Th1 and Th2 subsets is generally accepted but the mechanisms leading to their preferential induction remain elusive. Cytokines are considered the main determining factors in the initial differentiation of precursor T cells into these distinct subsets. Thus, IL-12 drives Th1 cells whereas IL-4 drives Th2 cells. Recently IL-18, originally designated as IFN-gamma-inducing factor, has been reported to synergize with IL-12 in the induction of Th1 cells. We report here that IL-18 can also induce T cells to differentiate into Th2 cells, in the presence of TCR activation, either alone or together with IL-4. This effect of IL-18 is mediated primarily on CD4(+) T cells compared with CD8(+) T cells and is inhibited in the presence of IL-12. IL-18, however, has no effect on functionally committed Th2 cells.( )Moreover, the effect of IL-18 on Th2 cell development is differentially manifest in different mouse strains, suggesting profound underlying genetic influences. BALB/c mice infected with Leishmania major and treated with recombinant IL-18 developed exacerbated disease and enhanced Th2 response compared with untreated controls. These data therefore provide a novel mechanism for Th2 cell development. Thus, IL-18, a cytokine constitutively expressed by cells of the innate response, is capable of inducing Th2 cell differentiation in the absence of IL-4.     

Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice

We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals.     

Serotoninbestimmungen an Thrombocyten und an Fraktionen von Thrombocyten

Zusammenfassung Aus Suspensionen zerstörter Thrombocyten des Menschen wurden reine Fraktionen von Hyalomer und Granulomer hergestellt. Von den Fraktionen wurde jeweils ein Teil für die elektronenmikroskopische Untersuchung, ein anderer Teil für die Bestimmung des Serotonins verwandt. Durch die elektronenmikroskopische Untersuchung jeder einzelnen Fraktion wurde die Reinheit der Fraktionen überprüft. Die Bestimmung des Serotoningehaltes erfolgte am isolierten Rattenmagen. In Kontrollversuchen wurde ferner der Serotoningehalt intakter Thrombocyten bestimmt.Intakte Thrombocyten besitzen im Mittel einen Serotonin-Gehalt von 52 ng/10⁸ Thrombocyten. In den Fraktionierungsversuchen fanden wir 95% des Serotonins in den Hyalomer-Fraktionen und nur 5% des Serotonins in den Granulomer-Fraktionen. In vivo findet sich also der hohe Serotoningehalt fast ausschließlich im Hyalomer der Thrombocyten.

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Summary Pure fractions of hyalomer and granulomer were prepared from suspensions of destroyed human thrombocytes. One portion of the fractions was used for the electron microscopic studies, and the other part for the determination of serotonin (5-hydroxytryptamine). The electron microscopic investigation allowed to check the purity of each single fraction. On the isolated rat stomach the determination of the concentration of serotonin was performed. In control preparations we studied the serotonin concentration of intact thrombocytes. These thrombocytes have a mean serotonin concentration of 52 ng/10⁸ platelets. In fractioning experiments we found 95% of the serotonin in the hyalomer fractions and only 5% of the serotonin in the granulomer fractions. In vivo therefore, the high concentration of the serotonin is found almost exclusively in the hyalomer of the thrombocytes.

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Die Ergebniss wurden vor der Medizinischen Gesellschaft Düsseldorf am 23. 1. 1963 mitgeteilt. Herrn Prof. Dr.Meessen danken wir für die Anregung und Förderung der Arbeit, Herrn Prof. Dr.Greeff für die Hilfe bei den Serotoninbestimmungen.