Bei Rhinoplastiken erfordert die Korrektur der Nasenspitze die größte Erfahrung. Sie entscheidet in vielen Fällen erst über das Gelingen einer Nasenkorrektur. Es ist sinnvoll, einen gewissen Algorithmus bei der Korrektur der Nasenspitze zu befolgen: ausgehend vom anatomischen Befund über das Operationsziel bis hin zu den Operationstechniken, den operativen Zugängen und letztendlich den Inzisionen. Neben In- und Exzisionstechniken und der Anwendung von Knorpeltransplantaten haben sich in den letzten Jahren vor allem Nahttechniken etabliert, die eine weitgehende strukturerhaltende Rhinoplastik ermöglichen. Während bei geringfügigen und mittelgradigen Nasenspitzendeformierungen Nahttechniken zu bevorzugen sind, bleiben die beiden anderen Techniken hauptsächlich den ausgeprägten Varianten unproportionierter Nasenspitzen vorbehalten. Man kann für alle Techniken sowohl den geschlossenen als auch den offenen Zugang wählen; mit der „offenen Rhinoplastik“ sind aber alle Techniken übersichtlicher und präziser durchzuführen. Zuletzt ist es auch eine Frage der persönlichen Erfahrung, die entsprechenden Techniken, Zugänge und Inzisionen auszuwählen.

Much experience is needed for the correction of nasal tip deformities; in many cases, a good rhinoplasty result depends on the successful modification of the tip. It is advisable to follow a specific algorithm, starting with exploration of the nasal anatomy and the operative goal, followed by the choke of technique, approach, and incisions. In addition to excision and incision techniques on the tip cartilage and the use of tip grafts, within the last decade suture techniques that allow so-called nondestructive tip modifications became popular. These suture techniques are preferred in minor and moderate deformities, whereas in major deformities the other techniques should be the first choice. Each of these techniques can be used alone or can be combined with each other. For all techniques, dosed as well as open approaches can be used; however, with the open approach, all techniques can be performed with more precision under direct vision. The surgeon's personal experience is also important in realizing the most convenient and effective techniques, approaches, and incisions.

The first experiments with a penetrator with enhanced lateral efficiency (PELE) were carried out in 1996. The unusual behaviour of the penetrator as it perforates a target can generally be described in three main stages. In the first stage the different kinetic energies of the jacket and the filling lead to the enclosure of the filling material. This induces a pressure rise in the filling, which dilates the surrounding jacket in the second stage. During the last stage the high-density jacket breaks into pieces. When a thin target, as in our case, is perforated, a fourth stage must be added to the other three. This new stage describes the interaction between the filling and the plug, which is produced during the impact. For the lateral efficiency of the PELE, the second stage is the important one. The behaviour in this stage (pressure build-up and radial expansion of the jacket) is dominated by only a few physical parameters. For weak shock waves, these parameters are determined by theoretical consideration. A number of experiments were carried out in the velocity range between 900 and 3000m/s in order to obtain an experimental database. In the last section a comparison between the physical model and experimental data gives a short outline of the complex impact behaviour of the PELE projectile. The physical model and the experimental data are in good agreement for impact velocities under 1400m/s. For higher velocities causing stronger shock waves, the theory has to be modified; but the set of physical parameters influencing the terminal ballistic behaviour of PELE remains valid.

Sildenafil citrate, marketed as Viagra®, for the treatment of erectile dysfunction, has a proven record of safety in humans as predicted by the results of extensive pharmacological and toxicological testing in animals and in vitro, and confirmed by pharmacokinetic exposure data. The aim of this paper is to review succinctly the main findings resulting from these experiments. Daily doses of sildenafil, within and far beyond the human therapeutic range, were given to dogs and rodents for up to 1 and 2 y, respectively. Plasma analyses were conducted to determine the exposure to sildenafil. We found species-specific effects in dogs (Beagle pain syndrome), mice (marked intestinal dilatation) and rats (adaptive reversible hepatocellular hypertrophy associated with secondary thyroid hypertrophy). All these effects in rodents and dogs have no relevance to humans. Morphometric thickness measurements of the retinal layers carried out in response to clinical observations of visual disturbances in humans indicated no difference between treated and control rats and dogs after up to 24 months of treatment. There was no evidence of histopathologic damage to any structures of the visual pathway. Sildenafil had no effects on fertility, no teratogenic potential, was not genotoxic and has no carcinogenic potential. In rats and dogs, safety ratios were 40:1 and 28:1, respectively, in terms of exposure over 24 h (AUC24 h) and 19:1 and 8:1, respectively, in terms of peak plasma concentration (Cmax). These safety ratios illustrate the separation between exposure to sildenafil of animals at large nontoxic doses and the much smaller human therapeutic exposure. This profile highlights the very low risk of human toxicity for sildenafil. The favourable results of the nonclinical safety evaluation of sildenafil in established animal models have been confirmed by many years of clinical experience during the development and marketing of sildenafil.

Fluconazole is an orally active bis-triazole antifungal agent that acts by selective inhibition of lanosterol 14 alpha-demethylase, a key enzyme for maintenance of the fungal cell wall. It is not genotoxic. In a 2 year carcinogenicity study in Sprague-Dawley rats, fluconazole decreased mammary fibroadenomas in females and adrenal pheochromocytomas in males, and increased hepatic adenomas in males. The pattern of these changes is explicable in terms of a hormonal imbalance, corroborated in other studies with fluconazole in rats by changes in the weights of hormone-sensitive organs and circulating levels of 17 beta-estradiol. The decreases in mammary tumors are probably a consequence of aromatase inhibition by fluconazole at high dose levels. The tumor effects observed in this study are extremely unlikely to be of relevance to humans, since the hormone effects observed in this study do not occur in humans treated with therapeutic dose levels of fluconazole. This study illustrates the importance of seeking a mechanistic interpretation of rodent tumor findings, which may then be assessed for its relevance to the clinical use of a drug.

Lymphomatoid granulomatosis is a rare human disease that has been recently reported in young dog^.',^.^.^ Lymphomatoid granulomatosis, as originally described in human beings by Liebow et al.,5 is an angiocentric and angiodestructive lymphoreticular proliferative and granulomatous disease that predominantly involves the lungs. Pathologically, it is a peculiar angiocentric lymphoid lesion with a lymphomalike appearance (lymphomatoid) in some areas and necrosis (granulomatosis) in others. The proliferative infiltrate is composed of atypical lymphoreticular cells admixed with variable proportions of lymphocytes, plasma cells, and histiocytes. A clinically normal, 8-month-old, male Beagle was not included in drug safety studies owing to a persistent eosinophilia (3.2-4.2 103/mm3). The dog was euthanatized at 15 months of age as a result of a sudden deterioration of its condition: a marked abdominal enlargement, a 3.7 kg increase in body weight during the last 2 weeks, and severe respiratory problems, including coughing. At necropsy, the abdomen contained about 2.5 liters of a clear fluid; the liver was congested. The accessory lobe of the right lung was enlarged (1 2 x 13 cm), firm, and pale yellow. The overlying pleura was smooth and dull. Cut sections revealed coalescing multinodular pale tissue centered around bronchi that compressed the remaining lung peripherally. Grey or dark-red patches were scattered throughout all lobes. A white, firm tissue replaced the markedly enlarged tracheobronchial lymph nodes (5 x 3 cm) and was found focally in the sternal lymph node. Other organs were unremarkable. Tissues were fixed in 10% neutral buffered formalin, routinely processed to paraffin sections, and stained with hematoxylin and eosin, and Gomori's trichrome stain with Weigert's stain for elastin fibers. Sections were stained immunocytochemically by the peroxidase anti-peroxidase technique using rabbit anti-bovine S100 protein (Dakopatts, Issy-les-Moulineaux, France) with a silver amplification (Amersham, Les Ulis, France), and by peroxidase-labeled protein A (New England Nuclear, Paris, France) with trypsinization, using goat anti-human a1 -anti-trypsin, goat antihuman lysosyme followed by a rabbit anti-goat immunoglobulin G (Nordic, Le Perray en Yvelines, France). For negative controls, duplicate sections were incubated with normal, nonimmune rabbit or goat serum instead of the primary antibody. Lymph node and brain were used as positive controls. Formalin-fixed portions of the accessory lobe of the right lung were divided into 1 mm3, immersed in 2.5% glutaraldehyde in 0.1 M phosphate buffer (pH 7.37), post-fixed in 2% osmium tetroxide, and embedded in epoxy resin. U1trathin sections were stained with uranyl acetate and lead citrate and examined with a Zeiss EM109 electron microscope. Microscopically, the tumor was composed of sheets of dense infiltrates of atypical pleomorphic lymphoid cells that obliterated normal structures (Fig. 1). Most cells were polygonal to oval and had a faintly basophilic, moderately abundant cytoplasm. Nuclei varied from rounded to slightly elongated. Chromatin was predominantly stippled and occasionally coarse. Many cells had up to four round amphophilic nucleoli. There were atypical vesicular or cleft nuclei. Scattered binucleated cells were present. The fine fibrovascular stroma was predominantly infiltrated by eosinophils, fewer plasmocytes, and occasional Mott cells. Individual cell necrosis was observed throughout the tissue. No immunoreactivity for lysozyme, a-I-antitrypsin or S-100 protein was seen in tumor cells. Many large blood vessels were infiltrated by pleomorphic lymphoid cells and eosinophils. Their centers were occupied by a variously-shaped fibrous tissue that delineated vascular channels and was connected to the fibrous wall that merged with the surrounding stroma (Fig. 2). They had no elastic lamina. There were occasional epithelial remnants of airways and necrotic foci up to 3 mm in diameter. The overlying pleura was thickened and fibrotic. Sections at the margins of the tumor revealed that the process originated from pulmonary arteries and compressed adjacent airways (Fig. 3). The intimae of some affected pulmonary arteries were thickened by edema, fibrosis, eosinophils, and atypical lymphoid cells. Histologic lesions of allergic bronchitis3 with a few, small, foreign-body granulomas corresponded to the patches seen at necropsy in the other lobes. Blood vessels in these areas were spared. The sternal lymph node was multifocally invaded by tumor cells. Histologic liver changes were consistent with acute passive congestion. Heart, kidney, spleen, thyroid, and muscle were unremarkable. Ultrastructurally, tumor cells lacked intercellular junctional complexes and pericellular basement membrane material (Fig. 4). A limited amount of cellular interdigitations was observed. Nuclei were ovoid or variably folded and had large, often multiple, nucleoli. The cytoplasm contained moderately abundant profiles of granular endoplasmic retic-

Ten thyroid C-cell complexes from five male and five female Beagle dogs, 1 to 2 years old, were studied using single and double immunocytochemical staining with the peroxidase-antiperoxidase technique. The antigens tested included thyroglobulin, calcitonin, calcitonin gene-related peptide, somatostatin, neuron specific enolase, and neurotensin. All C-cell complexes contained four cell types in various proportions: 1) follicular cells staining for thyroglobulin; 2) C-cells staining for calcitonin, calcitonin gene-related peptide, and neuron specific enolase; 3) stellate cells and cuboidal cells in follicle-like structures staining positively for somatostatin; and 4) undifferentiated cells staining negatively for all antigens. No positive immunoreactivity for neurotensin was detected. These findings support the hypothesis that thyroid C-cell complexes are ultimobranchial remnants that can give rise to thyroid follicles and C-cells.

Cardiotoxicity is often a limiting factor in doxorubicin (D) treatment (Herman 1981). D causes damage in several cellular components such as mitochondria, cell membranes, lysosomes, and myofibrils (Buja et al. 1973). In order to diminish the cardiotoxicity of D, several compounds have been coadministered. However, results have been inconsistent (Rabkin et al. 1983; Wikman-Coffelt et al. 1983), partly because the extent of cardiac damage is not quantified in detail. As part of a more systematic approach, the quantification of cardiac damage induced by D was attempted using histochemistry and morphometry.

In cryostat sections of kidney biopsies, lysosomes were visualized for light microscopy by staining for acid phosphatase. Twenty patients treated with the antibiotics gentamycin, tobramycin, amikacin or netelmicin during four days were compared to ten untreated control biopsies. Because of the marked heterogeneity of enzyme reaction product through the nephron, the most strongly stained tubular sections were used for comparison. With the exception of one biopsy, all treated kidneys display heavier staining than all controls; the difference is significant. Biochemical assays of acid phosphatase activity in homogenates have not revealed this difference. The cytochemical method may be used to detect early alterations caused by nephrotoxic drugs.

Kidney cortex of rats and humans treated with low doses of Gentamicin have been examined both morphologically and biochemically. Specific alterations of the lysosomes (loss of activity of phospholipases; accumulation of phospholipid-like material) was detected as early as from 2-4 days of treatment. This finding is consistent with the concept that Gentamicin exerts its toxic action on kidney through lysosomal dysfunction.

Aminoglycosides accumulate in lysosomes in the proximal tubule in the renal cortex as lamellar electron-dense bodies. Several methods have been used to detect early toxicity in man, including detection of excreted enzymes or substances usually reabsorbed. In patients given gentamicin, tobramycin or amikacin in normal doses for 3–4 days, no differences in renal function were detected and kidney tissue showed no abnormality by light microscopy. Electron microscopy showed myeloid bodies in lysosomes, less marked with amikacin, and small increases in lysosomal volume, diameter and number for gentamicin and tobramycin, together with internal lysosomal changes for all three drugs. Acid phospholipase A activity decreased with gentamicin and tobramycin but not amikacin. All three drugs thus accumulate in renal cortex, and induce lysosomal sometimes enzyme changes, most marked for gentamicin and tobramycin. Les aminoglycosides s'accumulent dans le cortex rénal au niveau du tube proximal sous forme de corps lamellaires visibles au microscope électronique. Plusieurs méthodes ont été utilisées pour mettre en évidence la toxicité précoce chez l'homme dont la recherche de l'excrétion d'enzymes ou de substances habituellement réabsorbées. Chez des malades recevant des doses normales de Gentamicine, de Tobramycine, ou d'Amikacine pendant 3 a 4 jours, il n'y a pas eu de modifications de la fonction rénale et l'histologie du rein était normale au microscope optique. Le microscope électronique, par contre, montrait: des corps myéloïdes dans les lysosomes mais de facon moins marquee avec l'Amikacine; une discrète augmentation du nombre, du diamètre et du volume des lysosomes avec la Gentamicine et la Tobramycine; des alterations de la structure interne des lysosomes avec les trois antibiotiques. L'activité de la phospholipase acide A était diminuée avec la Gentamicine et la Tobramycine, mais elle n'était pas modifiée avec l'Amikacine. Ainsi, les trois antibiotiques s'accumulent dans le cortex renal et entrainent des modifications lysosomales et parfois enzymatiques, plus intenses pour la Gentamicine et la Tobramycine.

Motivation: Die zentrale Fragestellung in dieser Entwicklungspartnerschaft zwischen der FH Kärnten und LINZ AG ist die Unterstützung von Investitionsentscheidungen für den strategischen Ausbau der Glasfasernetzinfrastruktur. Ergebnisse: Die im Rahmen des FHplus- Strukturaufbauvorhabens NETQUEST entwickelten Metho- den im Bereich der Geodatenmodellierung und der darauf basierten Generierung von gewichteten Gra- phen als Grundlage für die kombinatorische Optimierung (Steiner- bzw. Price- Collecting- Steiner- Baum Probleme) wurden an die Anforderungen eines Multi-Utility- Unternehmens (Strom, Telekommu- nikation, Gas, Verkehr, Wasser, Abwasser) erfolgreich adaptiert und weiterentwickelt. Es wurden 2 Szenarien für den Glasfasernetzausbau simuliert, die als Ergebnis (1) das optimale Investitionsvolumen für eine Neutrassierung unter Berücksichtigung des erwarteten Umsatzes resultierend aus branchen- spezifischen Kundenanschlussobjekten und (2) eine Trassenoptimierung und Simulation der Investiti- onskosten für eine Glasfaservollvernetzung von ausgewählten Produktions- und Servicestandorten der LINZ AG liefern. Schlussfolgerung: Mit der im Rahmen des FHplus Strukturaufbauvorhabens NETQUEST entwickelten interdisziplinären, szenariobasierten Methodik zur kostenoptimierten Trassenplanung auf Basis von Geodaten ist es möglich, reale Investitionsszenarien für den strategischen Ausbau der Netzinfrastruktur eines Multi-Utility Unternehmens zur Unterstützung von Investitionsentscheidungen zu berechnen.