[Abscess-forming and necrotizing aspergillus myocarditis in a surgical intensive care patient--a rare occurrence]. / Abszedierende und nekrotisierende Aspergillusmyokarditis bei einem chirurgischen Intensivpatienten--ein seltenes Ereignis.

The case of an 89 year old patient is reported, in whom an aspergillus myocarditis was unexpectedly found at autopsy. Preoperatively, the patient showed no risk factors for an invasive mycosis. 5 days after uncomplicated surgery he developed septic shock due to peritonitis. After surgery and intensive care therapy the patient recovered initially. 23 days after the first operation the patient suddenly developed catecholamin-resistant myocardial failure and died. Ten days before, aspergillus spec. was found in a specimen of bronchial secretion. This finding was interpreted as colonisation and not treated.

Action mechanism of retinoid-synergistic dibenzodiazepines.

4-[5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-methyldibenzo[b,e][1,4 ]diazepin-11-yl]benzoic acid (HX600), as well as its oxa- (HX620) and thia- (HX630) analogs, enhanced the activity of retinoic acid and a receptor alpha (RAR alpha)-selective agonist Am80 in HL-60 cell differentiation assays. HX600 synergizes with Am80 by binding to, and transactivating through, the RXR subunit of the RXR-RAR heterodimer. HX600 exhibited RXR pan-agonist activity in transient transfections with a DR1-based reporter gene and synergized with RA-bound RAR alpha and RAR beta in inducing transcription from a DR5-based reporter. In addition, all three compounds at high concentrations acted as RAR pan-antagonists in stably transfected RAR "reporter cells." These efficient synergists bind only weakly with RXRs in vitro, suggesting that they are RXR-RAR heterodimer-selective activators. These HX retinoids exhibited dual functionality, since they affected signalling through both retinoid receptor families (RARs and RXRs).

Regulation of retinoidal actions by diazepinylbenzoic acids. Retinoid synergists which activate the RXR-RAR heterodimers.

In human HL-60 promyelocytic leukemia cells, diazepinylbenzoic acid derivatives can exhibit either antagonistic or synergistic effects on the differentiation-inducing activities of natural or synthetic retinoids, the activity depending largely on the nature of the substituents on the diazepine ring. Thus, a benzolog of the retinoid antagonist LE135 (6), 4-(13H-10,11,12,13-tetrahydro-10, 10,13,13,15-pentamethyldinaphtho[2,3-b][1,2-e]diazepin-7-yl) benzoic acid (LE540, 17), exhibits a 1 order of magnitude higher antagonistic potential than the parental LE135 (6). In contrast, 4-[5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyldibenzo[b,e] [1,4]diazepin-11-yl]-benzoic acid (HX600, 7), a structural isomer of the antagonistic LE135 (6), enhanced HL-60 cell differentiation induced by RAR agonists, such as Am80 (2). This synergistic effect was further increased for a thiazepine, HX630 (29), and an azepine derivative, HX640 (30); both synergized with Am80 (2) more potently than HX600 (7). Notably, the negative and positive effects of the azepine derivatives on retinoidal actions can be related to their RAR-antagonistic and RXR-agonistic properties, respectively, in the context of the RAR-RXR heterodimer.

[Hydrophobic modification of polyelectrolytes as solubility enhancers in preparations for parenteral administration]. / Hydrophob modifizierte Polyelektrolyte als Solubilisationshilfsstoffe in Zubereitungen zur intravasalen Anwendung.

Up to now there is no excipient for the solubilization of poorly watersoluble drugs that can be used without limitations in pharmaceutical preparations for intravasal application. The available surfactants show considerable hemolytic activity, cause anaphylactic reactions are chemically instable or have no sufficient solubilizing capacity. By polymerisation of non-ionic surfactants amphiphilic side-chain-polymers are obtained which show in vitro the same solubilization capacity as the monomers but exhibit practically no hemolytic activity. The objective of this work was to investigate, if this findings are also true for ionic oligomers. For this purpose, polyacrylic acids were substituted with long-chain alkyl amines. The solubilization capacity of these oligomers exceeds that of non-ionic amphiphilic side-chain-polymers and that of other surfactants. The hemolytic activity of the oligomers was below that of common ionic surfactants. The solubilization capacity as well as the hemolytic activity depends on the oligomers degree of substitution. Considering their high solubilization capacity and their low hemolytic activity, these oligomers may be excipients in preparations for parenteral application.

[Treatment and results in severe craniocerebral trauma]. / Behandlung und Ergebnisse beim schweren Schädelhirntrauma.

Treatment of severe craniocerebral traumas in medium and major hospitals not provided with special neurosurgical equipment requires particularly close interdisciplinary cooperation between surgeons, neurologists and anaesthesiologists. CT facilities are an essential prerequisite for best possible patient care. Patient safety during the posttraumatic and postoperative phases is improved by measuring the intracranial pressure. Whereas corticosteroid treatment may be arguable, barbiturate treatment should presently not be a routine procedure because of its side effects and high rate of complications.