Ungewöhnlicher Verlauf einer α-Mannosidose mit Symptomen einer paranoid-halluzinatorischen Psychose

Zusammenfassung Wir berichten über eine 27-jährige Patientin, bei der nach 10-jährigem Krankheitsverlauf mit rezidivierenden paranoid-halluzinatorischen Episoden und Behandlung unter der Diagnose einer schizophrenen Psychose eine -Mannosidose als Ursache der psychiatrischen Symptome gesichert werden konnte. Die -Mannosidose ist eine seltene autosomal-rezessiv vererbte lysosomale Speichererkrankung mit verminderter Aktivität des Enzyms -Mannosidase. Im vorliegenden Fall wurde die Diagnose erst relativ spät nach therapierefraktärem Behandlungsverlauf und zusätzlichem Auftreten einer progredienten kognitiven Störung gestellt. Erst nach umfangreicher differenzialdiagnostischer Abklärung wurde über den Nachweis einer verminderten -Mannosidase-Aktivität in Serum und Leukozyten die Diagnose etabliert. Diese Kasuistik veranschaulicht, dass außergewöhnliche klinische Verläufe oder auffällige Symptomkonstellationen, insbesondere in Verbindung mit organischer Komorbidität, bei psychotischen Patienten zu differenzialdiagnostischen Überlegungen in Richtung hereditärer Stoffwechselerkrankungen Anlass geben sollten.     

Evaluation of the efficacy of a combined formulation (Grippostad-C) in the therapy of symptoms of common cold: a randomized,double-blind,multicenter trial

BACKGROUND: The aim of the present trial was to evaluate the efficacy of a combined product in the treatment of common cold and to examine the contribution of the separate components. In the published literature there is conflicting data on the efficacy of agents used in the treatment of common cold, especially when given in drug combinations. METHODS: A prospective, randomized, double-blind, multicenter, 4-arm, controlled trial was carried out in 1,167 patients with common cold treated with one of the following medications: Grippostad-C, a combination of acetaminophen, caffeine, chlorpheniramine and ascorbic acid (verum), ascorbic acid (control), chlorpheniramine and ascorbic acid (reference 1), as well as acetaminophen, caffeine, and ascorbic acid (reference 2). A score of common cold symptoms (headache, throat pain, extremities and joint pain, cough, blocked nose, and disturbances of sleep quality) was the primary outcome. The test drug was first compared with the control using a hierarchic test strategy, then with reference 1, followed by reference 2 with the aim of proving superiority. FINDINGS: A clinically relevant and statistically significant difference was demonstrated at each level of the hierarchy. Grippostad-C was significantly superior to all other treatment groups, the combination of acetaminophen, caffeine, and ascorbic acid was significantly superior to the control, and the combination of chlorpheniramine and ascorbic acid was not statistically different from the control. INTERPRETATION: The efficacy of Grippostad-C for the treatment of common cold was proven. The findings demonstrate that the combination is superior to each of its separate components and each of the components has its own distinctive contribution to the efficacy of the combination product.     

Physiological and technical limitations of functional magnetic resonance imaging (fMRI)--consequences for clinical use

Zusammenfassung Die funktionelle Magnetresonanztomographie (fMRT) ist eines der wichtigsten Verfahren der funktionellen Neuroanatomie. Aufbauend auf einer kurzen Darstellung des aktuellen Wissensstands bzgl. des Zusammenhangs zwischen lokaler neuronaler Aktivität und hämodynamischer Reaktion werden ausgewählte Möglichkeiten und Grenzen des Verfahrens für die klinische Anwendung diskutiert. Der Schwerpunkt liegt dabei auf der Darstellung der derzeitigen methodischen und technischen Einschränkungen hinsichtlich einer fMRT-basierten Detektion und Lokalisierung neuronaler Aktivität. Es werden die Hauptfehlerquellen und ihre Auswirkungen auf die Reliabilität und Validität des Verfahrens erläutert und aktuelle Lösungsansätze diskutiert. Abschließend erfolgt eine Bewertung der aktuellen klinischen Relevanz funktioneller MR-Diagnosemethoden.

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Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Dipeptidyl peptidase IV expression in cancer and stromal cells of human esophageal squamous cell carcinomas,adenocarcinomas and squamous cell carcinoma cell lines

Dipeptidyl peptidase IV (DPPIV) is a transmembrane serine protease which is involved in the process of tumor invasion and development of metastases in human cancers. The aim of this study was to investigate the expression of DPPIV in cancer and stromal cells of both esophageal adenocarcinoma and squamous cell carcinoma (SCC). Tissue material from 159 patients was analyzed using immunohistochemistry. Western blotting was performed on cell lines and fresh frozen tissue sections. Results were compared with clinicopathological features. Evaluation of the immunohistochemical findings revealed significant differences between DPPIV expression in carcinoma cells and stromal cells, depending on the histological tumor type. A significantly higher level of DPPIV was found in adenocarcinomas compared to SCCs while no DPPIV was detected in normal esophageal epithelium. Overexpression of DPPIV in patients with adenocarcinoma was additionally associated with distant metastases. Thus, differences of DPPIV level in esophageal carcinomas compared with normal epithelium showed that esophageal malignancies were associated with an increased amount of cell surface‐bound DPPIV. Radiotherapy in patients had no impact on DPPIV expression in analyzed tissue samples. There was no correlation between DPPIV expression in cancer or stromal cells and survival of the patients.