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Cardiac toxicity of the new anthracycline antitumour antibiotics violamycin BI (V) and carminomycin (C) was studied in comparison with daunorubicin (D). Rabbits were intravenously given total doses of 0.1-1.5 mg/kg V or C, and 0.64-18 mg/kg D, respectively, twice weekly for one month. When examined two to six days, two and four weeks, respectively, after the last drug administration the gross findings consisted of hydropericard, hydrothorax and ascites in some animals. Histologically, loss of striation and focal necrosis of cardiac muscle cells and subsequently chronic inflammatory reactions and/or proliferation of mesenchyma cells were mostly found. These alterations were somewhat more pronounced in rabbits treated with V than in animals received D or C. At equitoxic doses of the antibiotics tested the ultrastructural lesion in the myocardial cells were altogether less marked after treatment with D than with C or V.

Summary. Did the biodiversity of dinosaurs decline, or did it remain more or less constant before their mass extinction 65 million years ago? Sheehan et al. (1991, Science, 835–839) reported that the biodiversity of families of dinosaur species remained more or less constant preceding their extinction, suggesting extinction due to a cataclysmic event such as an asteroid strike. But that claim was based on the incorrect interpretation that a large p value associated with a test of null hypothesis of equality supports that null hypothesis. To assess whether there is a basis for such a claim, we formulate the problem as one of practical equivalence, in analogy to bioequivalence. We then develop reliable practical equivalence confidence intervals for differences of entropies by applying the bootstrap-t technique to a nearly pivotal quantity. Confidence intervals for changes in the biodiversity of dinosaurs are then computed, allowing the reader to assess whether there is evidence of near constancy of dinosaur biodiversity before extinction.

A monoclonal antibody was developed for detection of Helicobacter pylori in gastric tissue sections in a direct immunofluorescence test. On a comparison of the immunofluorescence test with standard methods for detection of Helicobacter pylori, i.e. culture, the urease activity test and histological examination of tissue sections, using 158 biopsy specimens, 30 specimens were positive in all methods and 64 negative. In the remaining cases comparison was not possible because either immunofluorescence (29 specimens) or the standard methods (16 specimens) gave ambiguous results. The direct immunofluorescence test may have potential as an alternative to standard methods, but further testing in a defined patient population is necessary.

The instruments currently used in endoscopic surgery are limited by several factors, in particular their reduced working space. In order to develop instruments with manifold degrees of freedom (DOF), the elementary actions performed by the existing instruments must be defined.We have broken down into elementary movements the actions performed by the currently used instruments and analyzed them by measuring the strain on the instruments and on their working volume. The elementary actions were performed in vitro (Pelvitrainer) on an animal model (pig) and also in the course of clinical practice. A total of 6,750 measurements were carried out for the following actions: grasping, cutting, dissecting, suturing and knotting.The largest working volumes were measured for the knotting and suturing actions (198 degrees in axial rotation and 69 degrees in lateral translation). The range of the working space was between 8 degrees and 52 degrees. Forces exerted on the instrument were between 0.5 and 12 Newton (N). Forces exerted on the headpoint were between 0.4 and 10.5 N whereas the friction forces were between 0.5 and 1.5 N.By analyzing the elementary actions of endoscopic surgery, we were able to quantify the directions and dimensions of forces sustained by the instruments and were also able to measure the working volume involved when performing the main actions in endoscopic surgery. The results obtained provide a basis for the development of more sophisticated instruments.

Most laparoscopic procedures require the creation of a pneumoperitoneum. In order to evaluate the potential hazards of bacteriemia related to insufflation, we conducted a study in the rat. Two groups of 20 Wistar rats were used for this study. Peritonitis was induced by opening the terminal ileum. Twenty-four hours later, 20 rats were insufflated at a mean pressure of 6 mm Hg (Group I). After one hour of insufflation, an hemoculture was performed via direct intracardiac puncture and in the other group of 20 non-insufflated rats (Group NI). Five of the 18 hemoculture were positive in the Gr. I (27.7%) and 6 out of 20 in the Gr. NI (30%) (chi 2 = 0.238 p = 0.62 non significant difference). These results suggest that insufflation does not facilitate hematogenous dissemination of bacteria from intraperitoneal sepsis in this animal model.

Correction procedures are proposed for the nuclear volume fraction (Vvn) and the specific surface area (Svc) of single cell populations which allow to calculate true values of Vvn and Svc from biased samples of nucleated sections. The methods can be applied on the understanding that the cells have an approximately spherical basic shape and that cells of eventually existing different size classes are geometrically similar; any regular shape of the nucleus is not necessary. The correction formulas are especially suitable for cells with an extremely folded cell membrane surface. The procedures are tested on four populations of peritoneal cells and the results are compared with those of correction formulas derived from the sphere-in-sphere model.

The effects of two 1,2-substituted 5-bis-(beta-chloroethyl)-amino-benzimidazole derivatives on the course of phagocytosis in murine peritoneal macrophages after intraperitoneal injection of bovine fibrin has been investigated by means of quantitative ultrastructural stereologic methods. One of the compounds, IMET 3164, is a strong immunosuppressive agent with membrane-stabilizing effects while the other one, IMET 3393 (Cytostasan) is an effective cytostatic drug with weak immunological effects. From the results the following conclusions can be drawn. After stimulation by intraperitoneal injection of fibrin, macrophages of untreated animals show a rapid antigen uptake and digestion as well as a formation of new lysosomes. Simultaneously, an immigration into the peritoneal cavity of monocytes and an emigration of strongly storing macrophages takes place. After treatment with either benzimidazole-N-mustard derivative, most pronounced after IMET 3164, a delayed antigen phagocytosis and digestion and an inhibition of formation of new lysosomes can be observed. Likewise, the intraperitoneal cell fluctuation is strongly reduced after IMET 3164. The findings lend support to the hypothesis that immunosuppression may be induced, among other mechanisms, by an inhibition of phagocytosis and antigen processing by means of membrane-stabilizing compounds.

An empirical graphical method is described for the correction of the nuclear volume fraction and the specific cell surface area after stereological estimations on nuclear-biased samples of cell profiles. The method is basing on the assumption that from equatioral sections of representative cells of a given population informations can be obtained about the volume relations and surface relations of tme fraction and the specific cell surface area after stereological estimations on nuclear-biased samples of cell profiles. The method is basing on the assumption that from equatioral sections of representative cells of a given population informations can be obtained about the volume relations and surface relations of tme fraction and the specific cell surface area after stereological estimations on nuclear-biased samples of cell profiles. The method is basing on the assumption that from equatioral sections of representative cells of a given population informations can be obtained about the volume relations and surface relations of the (analysed) "cell stumps" containing nuclear profiles and the "cell caps" lacking nuclear profiles (which were excluded from the stereological estimation). Prerequisites for the application of the method are an approximately spherical shape of the basic cell body and the geometrical similarity of eventually occuring size classes of the cells. The graphical method was checked on peritoneal macrophages and lymphocytes as well as on corresponding cell model systems. The results have been compared with mathematical methods derived from sphere-in-sphere geometrical models. The graphical methods gave results generally comparable to those from methematical methods. Provided that the shape and position of the nucleus inside the cell as well as the structure of the cell surface showed considerable differences to the geometrical models underlying the mathematical corrections, the graphical method was superior, and should be favoured in such cases. On ideal sphere-in-sphere models, the mathematical methods derived from those models should be applied.

The shrinkage of peritoneal cell during the electron microscopical preparation was investigated by means of a special device. Independently of the procedure of fixation after critical point drying the cells exhibit only 54 to 59% of the original diameter (residual volume about 18%). The reduction of cell diameter after Epon embedding is about 25%, corresponding to a residual volume of 40%.

Ultracytochemical visualization of specific carbohydrate receptors by means of lectins can provide valuable topological information about the functional status of cell surfaces in normal and transformed cells. In addition to the concanavalin A (Con A) rection and precoupling of lectin--peroxidase (PO) a new method is suggested using precoupling of the marker enzyme (PO) with an appropriated glycoprotein (glycopeptide) containing a lectin-specific carbohydrate. Furthermore, quantitative estimations of Con A reaction by means of automatic umage analysis are performed on peritoneal macrophages which point out a cluster formation, but give no hints for a loss of glycocalyx during the preparation process contrary to tumor cells.

Contrary to homogeneous tissues, "mixed" tissues or cell suspensions are composed of different cell individuals. They have been characterized as heterogeneous cell populations (composed of cells of different cytogenetical source) and heteromorphous or inhomogeneous cell populations (of cells of the same type but of different individual functional state). Certain problems may arise during ultrastructural morphometrical investigations of heteromorphous populations. Because of the different size of planes of sectioning of individual cells, morphometrical results should be treated by means of modifications of the t-test [4]. Furthermore, the unambiguous classification of individual cell profiles necessitates a conscious selection of cell profiles containing a nuclear profile. This non-random sampling approach leads to systematic errors of computed parameters for the whole cell as the nuclear volume fraction and the specific cell surface area which should be corrected. Besides correction procedures derived from regular geometrical models we have presented correction methods for cells with non-spherical nucleus and a cell surface with marked surface projections [13, 21]. On the other hand, on heteromorphous cell populations, more detailed information about functional events can be gained, in comparison the customary stereological mean values, by means of frequency distributions of morphometrical data of individual cell profiles as well as by correlation of data of different cell organelles.

The cardiotoxic and myelosuppressive effects of the potential antitumor antibiotics violamycin BI (VBI) and violamycin BII (VBII) were studied in rats in comparison with daunorubicin (DAU), doxorubicin (ADR) and carminomycin (CAR). Rats were intravenously given the compounds 10 times for three weeks at total doses of 0.4 to 3 times of the acute LD50. Cardiac toxicity was measured using ECG (widening of the QRS complex), and screening parameters for bone marrow suppression were white blood cell counts, hematocrit and hemoglobin values. Following the drug injections the myocardium and the bone marrow were additionally investigated by light microscopy. With the exception of ADR, all the anthracyclines tested showed a more or less strong dissociation of cardiotoxic and myelotoxic activities. VBI was found to be only toxic on the heart but not on the bone marrow, whereas DAU, VBII and CAR were predominantly toxic on the bone marrow. Only ADR showed strong cardiac toxicity as well as distinct myelosuppression. A final evaluation of VBI and VBII has to include both the antineoplastic and the toxic properties of the compounds.

Isolated atria of guinea-pigs showed negative inotropic and negative chronotropic responses after violamycin B I (V), carminomycin (C) and daunomycin (D), respectively. The mean effective concentrations in reducing amplitude (IC50) were 5.9 x 10(-4) mol x 1(-1) for V and 1.3 x 10(-4) mol x 1(-1) for C and D. In rabbits, intravenous injections of different doses of the antibiotics twice weekly for one month produced histopathological alterations in the myocardial tissue, which were smaller after D than after C or V.

Tetrahymena pyriformis GL is a suitable model to study the influence on phagocytotic activity of two membrane-stabilizing benzimidazole nitrogen mustard derivative, ZIMET 3164 and ZIMET 3393 (cytostasan). Treatment by both compounds causes a gradual inhibition of food vacuole formation dependent on the concentrations used. Complete cessation of phagocytosis is observed by 5 micrograms/ml ZIMET 3164 and 50 micrograms/ml ZIMET 3393. Additionally, disturbances of ciliary movement including immobilization and changes of cell shape are induced. The cells resume food vacuole formation and ciliary movement after being rinsed with control solution. The results correspond well with those described recently in mammalian mononuclear phagocytes.