Synthesis and alpha-adrenolytic activities of 2-(1,4-benzodioxan-2-yl- methyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives

The synthesis of the title compounds starting from 2-Chlormethylbenzdioxan and Tetrahydroisochinolines is presented. Their actions on the platelet aggregation and the inhibition of alpha-adrenoceptors at the isolated rabbit aorta and the vas deferens of the guinea pig were investigated.     

Circular stereotactic callosotomy: A preliminary report

Summary The authors propose a new method for performing Stereotactic callosotomy, which they have named circular callosotomy. The operating device is the original Riechert-Mundinger's string electrode, which can be protruded through a side window and by rotating the probe it is possible to cut the commisural pathways to the extent required. The anatomical results of the operation can be checked using MRI scanning.     

Ein neuer Score für die tägliche Schweregradklassifizierung auf herzchirurgischen Intensivstationen

Zusammenfassung Einleitung: Das Ziel dieser Studie war die Entwicklung eines spezifischen Schweregradklassifizierungssystems für die Beurteilung und Vorhersage von Organfunktionsstörungen und Überleben bei herzchirurgischen Intensivpatienten. Methoden: Hierzu wurden konsekutiv alle erwachsenen Patienten nach einem herzchirurgischen Eingriff unter Einsatz der Herzlungenmaschine über einen Zeitraum von 3 Jahren in die Studie aufgenommen. Im Konstruktionsset erfolgte die Auswahl der Variablen mit Hilfe der Patienten, die mindestens 24 Stunden auf der Intensivstation verbrachten. Die Ergebnisse wurden dann in zwei Validierungssets mit allen Intensivpatienten überprüft. Die Qualität des Scores wurde mit dem Hosmer-Lemeshow-Test (HL) sowie der ROC-Analyse beurteilt, und mit dem APACHE-II- und dem MODS-Score verglichen. Ergebnisse: Insgesamt wurden 3230 Patienten über einen Zeitraum von 3 Jahren auf unserer Intensivstation aufgenommen. Die HL-Werte für den neuen Score waren 5,8 (APACHE-II: 11,3; MODS: 9,7) für das Konstruktionsset, 7,2 (APACHE-II: 8,0; MODS: 4,5) für das Validierungsset I und 5,9 für das Validierungsset II. Die Fläche unter der ROC-Kurve war 0,91 (APACHE-II: 0,86; MODS: 0,84) für den neuen Score im Konstruktionsset, 0,88 (APACHE-II: 0,84; MODS: 0,84) in dem Validierungsset I, und 0,92 in dem Validierungsset II. Schlussfolgerung: Der neue CASUS (Cardiac Surgery Score) zeigt für herzchirurgische Intensivpatienten eine exzellente Kalibrierung und Diskriminierung bezüglich der 30-Tage-Letalität. Die Variablen des CASUS sind einfach, reproduzierbar und werden routinemäßig in herzchirurgischen Intensivstationen erfasst. Der CASUS könnte als Expertensystem für das Diagnostizieren von Organfunktionsstörungen, der Entscheidungsfindung, der Ressourcenauswertung und Vorhersage der Letalität für herzchirurgische Intensivpatienten dienen.     

New players in old amyloid precursor protein-processing pathways

The amyloid precursor protein (APP) gives rise to beta-amyloid peptides, which are the main constituents of senile plaques in brains of Alzheimer's disease (AD) patients. The generation of beta-amyloid peptides requires the enzymatic activity of the beta-site APP-cleaving enzyme 1 (BACE1). BACE1 is primarily expressed by neurons and increased BACE1 protein concentrations and enzymatic activities have been reported in the brains of AD patients. However, there is accumulating evidence that, in addition to neurons, reactive astrocytes are capable of expressing BACE1 and, therefore, may contribute to beta-amyloid plaque formation. This suggests that conditions accompanied by chronic astrocyte activation may contribute to developing AD. Non-amyloidogenic processing of the APP can be stimulated by phorbol esters (PEs) and by intracellular diacylglycerol (DAG) generation. This led to the hypothesis that classical and novel protein kinase Cs (PKCs), which are activated by DAG/PEs, regulate APP processing. However, in addition to PKCs, there are other DAG/PE receptors present in neurons which may participate in the modulation of APP processing. Munc13-1, a presynaptic protein with an essential role in synaptic vesicle priming, represents such an alternative target of the DAG second messenger pathway. Using Munc13-1 knock-out mice and human neuroblastoma cells transfected with wild-type and mutant Munc13-1 constructs it was demonstrated that Munc13-1 acts independently of and in parallel with PKC to modulate APP metabolism. Therefore, agonists specific for the Munc13-1 C1-domain or small molecules mimicking the function of the endogenous Munc13-1 activator RIM1 may prove useful to shift APP processing towards the non-amyloidogenic pathway.     

A Neuromagnetic Study of the Functional Organization of the Sensorimotor Cortex

Movement-related neuromagnetic fields from eight healthy human subjects were investigated in a Bereitschaftspotential paradigm. The three conditions studied were right-sided mouth, index finger and foot movement. The neuromagnetic field patterns corresponding to the motor field and the movement-evoked field I were analysed using a moving dipole model. For both components a somatotopic organization was found: the estimated dipole locations for the mouth were more lateral and those for the foot more medial than the estimated dipole positions for the index finger movement. With regard to possible clinical applications, e.g. non-invasive mapping of the sensorimotor cortex and studies of plasticity of the motor function, the present results suggest that the investigation of movement-evoked field I for the index finger condition is most likely to yield further results.     

Eminectomy for the treatment of chronic subluxation and recurrent dislocation of the temporomandibular joint and a new method of patient evaluation.

We have performed this technique bilaterally on 39 patients with chronic subluxation and 13 patients with recurrent dislocation since 1985 and have had good results with patient satisfaction. These patients had significantly higher articular eminences than normal control individuals. Also, we have used echography as a new application of an old technique, to evaluate the patients objectively in the preoperative and postoperative periods.     

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.