Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT)

In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin. We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC₅₀) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights in cord vs. adult plasma. Markedly lower concentrations (IC₅₀) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic therapy.     

Bioactive isocoumarins isolated from the endophytic fungus Microdochium bolleyi

Three new isocoumarin derivatives ( 2- 4) were isolated together with monocerin ( 1) from Microdochium bolleyi, an endophytic fungus from Fagonia cretica, a herbaceous plant of the semiarid coastal regions of Gomera. Compounds 2 and 3 are both 12-oxo epimers of 1, and 4 is a ring-opened derivative of 1. The structures were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations were determined by a modified Mosher's method. Compounds 1, 3, and 4 showed good antifungal, antibacterial, and antialgal activities against Microbotryum violaceum, Escherichia coli, Bacillus megaterium, and Chlorella fusca. Compound 2 was moderately antifungal and antialgal.     

Tierexperimentelle Beobachtungen über das intracerebrale Wachstum menschlicher Tumoren

Zusammenfassung Das Wachstumsverhalten zweier in das Gehirn von Goldhamstern implantierter menschlicher Tumoren (H. Ad. Nr. 1 und H. S. Nr. 1) wurde untersucht. Bei allen Tieren konnte ein Tumorwachstum histologisch nachgewiesen werden. Cortisonvorbehandlung der Wirtstiere begünstigte bei H. Ad. Nr. 1 die Tumorausbreitung und führte frühzeitiger zum Tode. Das intracerebrale Tumorwachstum führte jedoch auch unabhängig von der Wirtsvorbehandlung bei allen Tieren zum Tode innerhalb von 4 Wochen nach der Transplantation. Beide Geschwulst-typen wuchsen am besten in den liquorhaltigen Räumen, weniger in der Hirnsubstanz. Die Bevorzugung der Meningen durch beide Tumortypen entspricht der allgemeinen Erfahrung über die cerebrale Metastasierung entdifferenzierte Sarkome und Adenocarcinome.

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Summary The growth behavior of two human tumors (H. Ad. No. 1 and H. S. No. 1) transplanted to the hamster brain has been studied. Tumor growth could be histologically verified in all animals inoculated. Cortisone-conditioning of the host increased tumor expansion and resulted in an earlier and more rapid death rate in the H. Ad. No. 1 group. Regardless of tumor or host-conditioning employed, all animals succumbed to intracerebral tumor growth by the end of the fourth week post transplantation. Both tumor types grew better in the ventricles and subarachnoid space than in the brain tissue itself. The predilection of these two tumor types for the meninges confirms our clinical knowledge on the pattern of cerebral metastasis of dedifferentiated sarcomas and adenocarcinomas.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Bacteriologische Studien über den Gonococcus

Ohne Zusammenfassung Im Auszug vorgetragen von Dr. R. Kraus am IX. internat. Congresse für Hygiene und Demographie (Madrid April 1898).     

Feasibility of navigated resection of liver tumors using multiplanar visualization of intraoperative 3-dimensional ultrasound data

BACKGROUND: Intraoperative ultrasound is widely used in liver surgery, but primarily for diagnostic purposes. We have developed and evaluated a system for navigated liver resections using on intraoperatively acquired 3-dimensional (3D) ultrasound data. METHODS: Navigation technique based on 3D ultrasound and an optical tracking system. Accuracy of the system was validated experimentally in a tumor model. Subsequently, clinical application was evaluated in 54 patients for resection of central liver tumors. Clinical feasibility and accuracy of the navigation technique were assessed with respect to practicability, adequacy of visualization, and precision of navigated resection (free margin). RESULTS: Evaluation of the system in the tumor model showed a significant increase of the accuracy of navigated resections compared with conventional resection (P < 0.05). Clinical application of 3D ultrasound-based navigation was feasible in 52 of 54 patients. Sufficient visualization was obtained with 2 orthogonal section planes. This navigation strategy provided complete anatomic orientation and accurate position control of surgical instruments. Mean histologic resection margin was 9 mm with a maximum deviation of 8 mm from the planned virtual resection margins. CONCLUSIONS: Optoelectronic navigation with section mode visualization in 2 orthogonal planes does sufficiently display intraoperative 3D data and enables accurate ultrasound-based navigation of liver resections.     

Golimumab improves socio economic and health economic parameters in patients with rheumatoid arthritis,psoriatic arthritis,and ankylosing spondylitis

Abstract

Background

Golimumab (GLM) has shown its efficacy and safety in various clinical trials. We aimed to assess the effect of GLM on socio economic and health economic parameters in daily clinical practice.     

Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.     

Relationship between body fat mass,carbohydrate tolerance and iri response during glucose infusion in subjects with early diabetes

Summary We have studied the interrelationship of total body fat mass, carbohydrate tolerance and IRI response in 17 non-obese and obese subjects, who were suspected of having early diabetes. We carried out an i.v. glucose infusion test consisting of a priming injection of 0.33 g/kg followed by constant glucose infusion of 12 mg/kg/min in all persons. Total body fat mass was estimated by the tritium dilution method. There was a positive correlation of body fat mass, fasting glucose concentration and blood glucose concentration at 150 min as well as a strong correlation between body fat mass and BG area 60–120 min as parameters of carbohydrate tolerance in all subjects, i.e. the degree of carbohydrate intolerance was directly related to the quantity of total body fat mass. A similar correlation was found when the non-obese and obese groups were analyzed separately. In neither group did total body fat mass correlate with parameters of IRI response. In obese subjects with pathological carbohydrate tolerance, however, a positive correlation of basal IRI concentration and total body fat mass was found. Furthermore, a close relation between basal IRI level and parameters of carbohydrate tolerance could be demonstrated in obese subjects. The present study failed to demonstrate any correlation of parameters of carbohydrate tolerance and glucose-induced IRI response in either group. Thus, the significant relationship between body fat mass and degree of carbohydrate intolerance indicates that total body fat mass plays an important role in the disturbance of blood glucose homeostasis in early diabetes with and without obesity. Investigation performed within the medical research project ‘Diabetes mellitus and disturbances of lipid metabolism’, Ministry of Health, GDR.