Polyploidization and centrosome hyperamplification in inflammatory bronchi

OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial cells of 32 patients were cultivated by standard cell culture procedures. METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7 and 8 versus the number of centrosomes. The resulting data were correlated with histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues and 40% of non- and low grade-inflammatory tissues. Additionally, we observed centrosome hyper-amplification and multipolar mitoses not only in the tumor but also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.     

C-arm-based mobile computed tomography: a comparison with established imaging on the basis of simulated treatments of talus neck fractures in a cadaveric study.

OBJECTIVE: To analyse the image quality and diagnostic effectiveness of a new C-arm-based 3D imaging method (C-arm-CT) for intraoperative evaluation of screw osteosyntheses adjacent to a peripheral joint. MATERIALS AND METHODS: Insertion of screws into four cadaveric specimens simulated the surgical treatment of talus neck fractures. Ten orthopedic surgeons and 10 radiologists evaluated X-ray, C-arm fluoroscopy, C-arm-CT and CT images. RESULTS: The best image quality was obtained with X-rays (p < 0.001), followed by C-arm fluoroscopy (2D) and CT, with the C-arm-CT (3D) being rated lowest (p < 0.001). The most correct diagnoses were obtained with CT and C-arm-CT (with no statistical difference between them), while C-arm-fluoroscopy was inferior (p < 0.001) and X-rays were the worst (p < 0.05). CONCLUSIONS: Even if the image quality of C-arm-CT is definitely inferior to that of CT, screw misplacements can be reliably detected using C-arm-CT. As compared to the current standard procedures (intraoperative fluoroscopy and postoperative radiography), C-arm-CT performed better. C-arm-CT is ideally suited to the intraoperative diagnosis of high-contrast inquiries like bone fragments and OS material, especially at the extremities. Coupling of the new 3D imaging to existing navigation systems is possible. C-arm-CT will support the further development and implementation of open and minimally invasive surgical procedures.     

Affinity profiles of BTM-1086 and BTM-1041 at muscarinic receptor subtypes and at H1- and alpha 1-receptors

The affinities of the (+) and (-) enantiomers of the antimuscarinic benzothiazepinone derivative, cis-2,3-dihydro-3-(4-methyl-1-piperazinylmethyl)-2-phenyl-1,5-benzoth iazepin-4 (5H)-one (BTM-1041 and BTM-1086), for muscarinic receptor subtypes, histamine H1-receptors and alpha 1-adrenoceptors were determined in vitro using isolated organs: field-stimulated rabbit vas deferens (M1-receptors), guinea-pig left atrium (M2-receptors), guinea-pig ileum (M3- and histamine H1-receptors) and rat vas deferens (alpha 1-adrenoceptors). We also assessed the binding profile of BTM-1041 and BTM-1086 at muscarinic receptor subtypes in guinea-pig cortex (M1), heart (M2) and salivary glands (M3) as well as at alpha 1-adrenoceptors in rat cerebral cortex. Functional and binding experiments showed that the (-) enantiomer (BTM-1086) had a high affinity (pA2 = 7.98-8.81; pKi = 8.31-9.15) for the three muscarinic receptor subtypes, whereas the (+) enantiomer (BTM-1041) showed a low antimuscarinic potency (pA2 = 4.87-5.31; pKi = 4.85-5.55). This results in an extremely high stereoselectivity for these optical isomers [-)/(+) ratios = 1023 to 6918). The affinity of the (-) enantiomer BTM-1086 was lower for both histamine H1- and alpha 1-receptors than for muscarinic receptors, whereas the reverse was true for the (+) enantiomer, BTM-1041. Thus, the stereochemical demands for the two optical isomers were most stringent at muscarinic receptors but were inverse and less pronounced at histamine H1- and alpha 1-receptors (stereoselectivity ratios = 0.16-0.22).     

Ossäre Echinokokkose

Zusammenfassung. Der Hundebandwurm, Echinococcus, kann in seinem Larvenstadium alle Teile des menschlichen K?rpers, zumeist die Leber, als Zwischenwirt befallen. Der prim?re Knochenbefall ist mit weniger als 2 % aller Echinococcusl?sionen sehr selten. Wir berichten über einen Fall eines ausgedehnten linksseitigen Becken- und Femurbefalls. Die Destruktion des Hüftgelenks, des Os pubis sowie der ausgedehnte Befall des Os ileum und des proximalen Femurs machten eine Hüftgelenk- und Beckenteilresektion sowie den prothetischen Ersatz notwendig. Ein Rezidiv im Bereich der linken Leiste nach 5 Jahren, ausgehend vom proximalen Femur, wurde mit erneuter Resektion und Hüftprothesenwechsel behandelt. Der prim?r eingebrachte Polyacetal-Beckenersatz mu?te dabei wegen Instabilit?t ebenfalls ausgetauscht werden. Ein sonderangefertigter CAD-Beckenersatz (CAD = „computer-aided designed“) wurde implantiert. Additiv wurde eine Chemotherapie mit Mebendazol durchgeführt. Die Radikalit?t der Resektion beim oss?ren Echinococcusbefall wird diskutiert.      

Effects of a new pteridine derivative on urinary sodium, potassium and magnesium excretion in conscious saline-loaded rats.

1. Two recently synthesized pteridine derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.     

Selective antagonists provide evidence that M1 muscarinic receptors may mediate carbachol-induced drinking in the rat

The present study served to investigate the ability of seven selective muscarinic antagonists to inhibit carbachol-induced drinking in the rat. The muscarinic antagonists were given by intracerebroventricular (i.c.v.) injection 1 min before the i.c.v. injection of carbachol (1 microgram/rat). The M2 antagonist, methoctramine, was inactive up to 80.3 nmol/rat. The M3 antagonist, p-fluoro-hexahydro-sila-difenidol, elicited a modest (42%) but statistically significant inhibition of drinking only at 80 nmol/rat. On the other hand, the selective M1 antagonists, (R)-trihexphenidyl, o-methoxy-sila-hexocyclium and pirenzepine, produced a marked and dose-dependent inhibition of carbachol-induced drinking, their ID50 values being 0.51, 7.36 and 9.31 nmol/rat. Also the M1/M3 antagonists, 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydro-sila-difenidol, were potent inhibitors of carbachol-induced drinking, their ID50 values (0.28 and 11.09 nmol/rat) being related to their pA2 values for M1 receptors in rabbit vas deferens. These data suggest that carbachol-induced drinking may be mediated by activation of muscarinic M1 receptors.