Abgeschlossene und derzeit laufende adjuvante Therapieprotokolle bei Patientinnen mit operablem Mammakarzinom (II)

Summary Background: Between 1984 and 1996 4336 patients with operated breast cancer were included in trials of the Austrian breast cancer study group. Methods: Based on prognostic factors patients were randomised with 2 different treatment groups. Results: The largest ever performed oncological trial (study VI) in postmenopausal breast cancer patients is already finished. 5 other trials are open for randomisation. Conclusions: It is the intention of the Austrian breast cancer study group to accrue patients for ongoing trials in whole Austria and to increase the number of randomised patients. K. Abbrederis, Ch. Armbruster, Gabriele Barbieri, Doris Bauer, Th. Bauernhofer, S. Beller, J. Berger, O. B?ckl, A. Brunhofer, F. Burger, Ursula Denison, Elke Derstvenscheg, Ch. Dittrich, Manuela Djavanmard, W. D?ller, Daniela Eckhoff, H. Eidtmann, R. Fegerl, J. Fellinger, F. Friedrich, Sabine Fuchs, Barbara Gebhart, Friederike Gieseking, Ch. Gr?ger, Karin Haider, D. Haidinger, E. Hanzal, E. Hell, C. Hinterbuchinger, W. Horvath, W. Jonat, Daniela Kandioler, Anna-Katrin Kasparek, M. Kern, R. Kocher, Veronika Kohlmayer, R. Kolb, Ch. Kopf, S. Kriwanek, Irene Kührer, Christine Kurz, Iris Kuss, W. Kwasny, Caroline Lackner, M. Lang, O. Langer, J. Lenz, S. Leodolter, A. Lepsinger, P. Lisborg, G. Lokker, H. Ludwig, G. Luschin-Ebengreuth, H. Maass, M. Markovic, P. Mayer, M. Medl, Elisabeth Melbinger, R. Menzel, Brigitte Mlineritsch, Elke Moosbrugger, E. Moritz, Renate Moser, W. Neunteufel, A. Obermair, J. Omann, P. Oppitz, M. Pecherstorfer, A. Pertl, Catharina Pietrzak, F. Ploner, M. Pober, R. P?hnl, R. Punzengruber, Friederike Püribauer, Ch. Rass, J. Ritschl, H. Rosen, Christine Sam, L. Schiller, W. Schippinger, J. Schüller, M. Seifert, M. Smola, P. Speiser, H. Spoula, G. Steger, Birgit Steiner, H. St?ger, G. Tatzer, Susanne Taucher, J. Tschmelitsch, P. Uher, A. Unger, M. Van Trotsenburg, N. Vavra, Sonja Vogl, B. Wenky, V. Wette, A. Wiegele, G. Winter, Monika Wirth, B. Zeh, G. Zimmermann.     

Bovine valved venous xenografts for RVOT reconstruction: results after 71 implantations.

BACKGROUND: Pediatric right ventricular outflow tract (RVOT) reconstruction with homo- or porcine xenografts is problematic because of limited availability, lack of material for reconstruction, early degeneration, and tissue ingrowth. Contegra, a bovine jugular vein graft, might be an interesting alternative to overcome these problems. PATIENTS AND METHODS: Within a Federal Drug Administration controlled study, we implanted 71 Contegra pulmonary valved conduits from May 1999 to September 2001 in 71 patients (male/female 33/38) in the age range 2 days-17.4 years, median 1.2 years. Twenty five were primary repairs, 22 had previous graft implantations, and 24 had other repairs/palliations. Preoperative diagnoses: truncus arteriosus communis (19 patients), tetralogy of Fallot (32), double outlet right ventricle (13), transposition of the great arteries (5), and two rare complex malformations. The size of implanted Contegra conduits ranged from 12 to 22 mm. Echocardiography was performed at 1 and 3 months, and then every 3 months postoperatively. Follow-up time was 27 months (maximal), 80 years in total. Results were compared with our 52 homograft- and 30 Tissuemed porcine xenograft recipients. RESULTS: Contegra enables the surgeon to perform all anastomoses without additional material. Its tissue is very apt for suturing and its insufficiencies are common, but without clinical significance or tendency to increase. We saw no sign of conduit or valve degeneration during the whole follow-up up to 27 months. There were no device related adverse events. Redos: five for peripheral pulmonary arteries, two residual ventricular septum defect (VSD) closures. There were six deaths (five early, one late). The maximal transvalvular gradients of 25-42 mmHg were measured in seven patients; these gradients did not increase further during the follow-up. Six patients with completely intact Contegra conduits developed pressure gradients of more than 70 mmHg immediately distal from the conduit. At 27 months, Contegra grafts were advantageous compared to homografts with respect to survival and freedom from explantation. Right ventricle to left ventricle (RV/LV) ratio development and freedom from explantation/redo were equal for Contegra conduits and homografts. Porcine Tissuemed xenografts were significantly inferior. CONCLUSION: The Contegra conduit offers unique tailoring and suturing options for primary and redo RVOT reconstruction. At 27 months, its durability seems at least equivalent to homografts and is superior to porcine Tissuemed xenografts.     

The mode of action of antimycobacterial benzylamines

The antimycobacterial effects of benzylamines are not related to an inhibition of aminoacyl-tRNA synthetases.     

Age-Dependent Differences in Survival of Striatal Somatostatin–NPY–NADPH–Diaphorase-Containing Interneurons versus Striatal Projection Neurons after Intrastriatal Injection of Quinolinic Acid in Rats

Some authors have reported greater sparing of neurons containing somatostatin (SS)–neuropeptide Y (NPY)–NADPH-diaphorase (NADPHd) than projection neurons after intrastriatal injection of quinolinic acid (QA), an excitotoxin acting at NMDA receptors. Such findings have been used to support the NMDA receptor excitotoxin hypothesis of Huntington's disease (HD) and to claim that intrastriatal QA produces an animal model of HD. Other studies have, however, reported that SS/NPY/NADPHd interneurons are highly vulnerable to QA. We examined the influence of animal age (young versus mature), QA concentration (225 mMversus 50 mM), and injection speed (3 min versus 15 min) on the relative SS/NPY/NADPHd neuron survival in eight groups of rats that varied along these parameters to determine the basis of such prior discrepancies. Two weeks after QA injection, we analyzed the relative survival of neurons labeled by NADPHd histochemistry, SS/NPY immunohistochemistry, or cresyl violet staining (which stains all striatal neurons, the majority of which are projection neurons) in the so-called lesion transition zone (i.e., the zone of 40–60% neuronal survival). We found that age, and to a lesser extent injection speed, had a significant effect on relative SS/NPY/NADPHd interneuron survival. The NADPHd- and SS/NPY-labeled neurons typically survived better than projection neurons in young rats and more poorly in mature rats. This trend was greatly accentuated with fast QA injection. Age-related differences may be attributable to declines in projection neuron sensitivity to QA with age. Since rapid QA injections result in excitotoxin efflux, we interpret the effect of injection speed to suggest that brief exposure to a large dose of QA (with fast injection) may better accentuate the differential vulnerabilities of NADPHd/SS/NPY interneurons and projection neurons than does exposure to the same total amount of QA delivered more gradually (slow injection). These findings reconcile the discordant results found by previous authors and suggest that QA injected into rat striatum does reproduce the neurochemical traits of HD under some circumstances. These findings are consistent with a role of excitotoxicity in HD pathogenesis, and they also have implications for the basis of the more pernicious nature of striatal neuron loss in juvenile onset HD.     

Immunohistochemical study of the telencephalon of the spiny dogfish, Squalus acanthias

The paucity of experimental data and the differences in telencephalic organization between sharks and other jawed vertebrates have complicated telencephalic comparisons. The distribution of neuropeptides has been extremely useful in recognizing and comparing major subdivisions of the telencephalon among vertebrates. Immunohistochemical techniques were therefore used to study the distribution of substance P (SP), leucin-enkephalin (LENK), and serotonin (5HT), as well as tyrosine hydroxylase (TH), an indicator of catecholamines, in the telencephalon of the spiny dogfish. The distribution of SP and LENK provides a clear distinction between pallial and subpallial portions of the telencephalon. Two regions of the ventrolateral telencephalon, area superficialis basalis and area periventricularis ventrolateralis, exhibit histochemical similarities to the pallidal and striatal subdivisions, respectively, of the basal ganglia in amniotes. Lower densities of LENK+ and SP+ perikarya and fibers occur in the medial pallium and the pars centralis of the dorsal pallium. Similar histochemical traits characterize the sensory thalamorecipient telencephalic structures in amniotes. The lateral pallium in dogfishes is distinguished by the presence of large numbers of TH+ neurons with radially oriented processes. The presence of these distinctive cells also in the medial wall of the rostral telencephalon suggests that the lateral pallium has a medial extension that is situated ventral to the medial pallium. Neurons containing TH were widely distributed in the telencephalon of spiny dogfish and were particularly abundant in the dorsal pallium, olfactory pallium, and area superficialis basalis. It is currently unclear whether these TH+ telencephalic neurons are, in fact, catecholaminergic or merely contain a TH-like substance unrelated to catecholamine synthesis.     

Hydatid disease of the pelvis and the femur: A case report

We report a case of left-sided extended pelvic infestation of hydatid disease. The destruction of the hip joint, os pubis, larger parts of os ileum and the femoral head made pelvic resection and prosthetic replacement necessary. Recurrence of a hydatid cyst 5 years later in the left groin originating in the femur was treated with a second femoral resection and total hip replacement. Because of instability, the pelvic replacement also had to be changed to a custom-made CAD replacement. This surgical procedure was combined with chemotherapy by mebendazole. The need for radical resection in osseal hydatid disease is discussed.     

Retroperitoneal fibrosis in association with urothelial tumor

One of the less common associations of retroperitoneal fibrosis is malignancy. Although there have been many reports on tumors associated with retroperitoneal fibrosis urothelial tumors are rare. We report a case of retroperitoneal fibrosis and urothelial malignancy of the renal pelvis.     

Mechanism of inhibition in vitro of mammalian acetylcholinesterase and cholinesterase in solutions of 0,0-dimethyl 2,2,2-trichloro-1-hydroxyethyl phosphonate (Trichlorphon).

The rate of decomposition of trichlorphon into DDVP was measured polarographically at pH 7.4. The first order rate constants of decomposition at 25° are 7.27 × 10^?4 and 6.05 × 10^?4 min^?1 for trichlorphon concentrations of 0.150 and 15.0 mM respectively; at 37° the corresponding rate constants are 53.1 × 10^?4 and 37.1 × 10^?4 min^?1. The rate of decomposition of trichlorphon was also calculated from the kinetics of inhibition of acetylcholinesterase (EC 3.1.1.7) and cholinesterase (EC 3.1.1.8) in trichlorphon solutions at 25° and 37° (pH 7.4). The following enzyme sources were used: bovine erythrocytes and rat brain acetylcholinesterase, and human, horse and rat plasma cholinesterase. The rate of decomposition of trichlorphon was calculated by assuming that only DDVP formed from trichlorphon is the enzyme inhibitor, while trichlorphon itself does not act as an inhibitor. The calculated rate constants for the decomposition of trichlorphon are lower or just within the range of the rate constants obtained by the polarographic method. This agreement was taken as kinetic evidence that trichlorphon is not an inhibitor of mammalian cholinesterases. The effect of pH on enzyme inhibition supports this conclusion. The rate of inhibition of bovine erythrocyte acetylcholinesterase by DDVP is the same at pH 7.4 and pH 6.0 (37°). However, the rate of enzyme inhibition in trichlorphon solutions is 30 times faster at pH 7.4 than at pH 6.0, and this agrees with the greater stability of trichlorphon at the lower pH value. The rate of spontaneous reactivation of the enzyme was measured (37°, pH 7.4) after inhibition in trichlorphon solutions of acetylcholinesterase (human and bovine erythrocytes) and cholinesterase (human plasma). For all three enzyme preparations, the rate of spontaneous reactivation was the same as that obtained after inhibition by DDVP. All results point to the conclusion that trichlorphon in vitro is not an inhibitor of mammalian cholinesterases.     

Ultrastructural single- and double-label immunohistochemical studies of substance P-containing terminals and dopaminergic neurons in the substantia nigra in pigeons.

The vast majority of striatonigral projection neurons in pigeons contain substance P (SP), and the vast majority of SP-containing fibers terminating in the substantia nigra arise from neurons in the striatum. To help clarify the role of striatonigral projection neurons, we conducted electron microscopic single- and double-label immunohistochemical studies of SP+ terminals and/or dopaminergic neurons (labeled with either anti-dopamine, DA, or anti-tyrosine hydroxylase, TH) in pigeons to determine: (1) the synaptic organization of SP+ terminals, (2) the synaptic organization of TH+ perikarya and/or dendrites, and (3) the synaptic relationship between SP+ terminals and TH+ neurons in the substantia nigra. Tissue single-labeled for SP revealed numerous SP+ terminals contacting thin unlabeled dendrites in the substantia nigra, but few SP+ terminals were observed contacting perikarya or large-diameter dendrites. SP+ terminals contained round, densely packed, clear vesicles, and often contained one or more dense-core vesicles. Synaptic junctions between SP+ terminals and their targets were more often symmetric (86%) than asymmetric. In tissue single-labeled for DA, we observed few terminals contacting DA+ perikarya, whereas terminals contacting DA+ dendrites were more abundant. Terminals contacting DA+ structures comprised at least four different morphologically distinct types based on the morphology of the clear synaptic vesicles and the type of synaptic junction. One type of terminal contained round clear vesicles and made symmetric synapses, and thus resembled the predominant type of SP+ terminal. The second type contained round clear vesicles and made asymmetric synapses, the third type contained medium-size pleomorphic clear vesicles and made symmetric synapses, and the fourth type contained small pleomorphic clear vesicles and made symmetric synapses. The presence of contacts between SP+ terminals and dopaminergic dendrites in the substantia nigra was directly demonstrated in tissue double-labeled for SP (by the peroxidase-antiperoxidase procedure, or PAP, with diaminobenzidine) and TH (by either the silver-intensified immunogold procedure or the PAP procedure with benzidine dihydrochloride). SP+ terminals commonly contacted thin TH+ dendrites in the substantia nigra, but few SP+ terminals contacted large-diameter TH+ dendrites or perikarya. Synapses between SP+ terminals and TH+ neurons were always symmetric. TH+ dendrites also were contacted by terminals not labeled for SP, which were more abundant than were SP+ terminals. Non-TH+ neurons were also contacted by both SP+ terminals and non-SP+ terminals.(ABSTRACT TRUNCATED AT 400 WORDS)