[From dream vacation to trauma. "Again and again images of the events"].
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Biomedical subjects
Publications and source records attributed to C Kraft.
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Despite new approaches in biochemical testing, radiologic and nuclear medicine and advances in surgical techniques, the problem of diagnosis and therapy of acute and chronic osteitis has not been finally solved. Clinical research on osteitis is problematic as there are many variables influencing the inflammatory process and a wide spectrum in therapeutic options exists, hampering research under defined conditions. Consequently, there was an early need for animal models. In vivo experimental settings were established to gain reproducible and reliable results under standardized conditions on the pathogenesis and therapy of osteitis. In this article, an overview of the hitherto established experimental animal models and the results of osteitis research on these models is given.
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The bacterium Helicobacter pylori colonizes the gastric mucosa of half of the human population, resulting in chronic gastritis, ulcers, and cancer. We sequenced ten gene fragments from pairs of strains isolated sequentially at a mean interval of 1.8 years from 26 individuals. Several isolates had acquired small mosaic segments from other H. pylori or point mutations. The maximal mutation rate, the import size, and the frequency of recombination were calculated by using a Bayesian model. The calculations indicate that the last common ancestor of H. pylori existed at least 2,500-11,000 years ago. Imported mosaics have a median size of 417 bp, much smaller than for other bacteria, and recombination occurs frequently (60 imports spanning 25,000 bp per genome per year). Thus, the panmictic population structure of H. pylori results from very frequent recombination during mixed colonization by unrelated strains.
Bioassay-guided fractionation of the leaves from Andira inermis was undertaken as part of a screening program to verify the traditional use of herbal remedies against malaria. Among the isolated phenolic compounds three novel 2-arylbenzofuran-3-carbaldehydes, andinermal A-C, were obtained together with a new flavanonol glycoside, taxifolin-3-O-(3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranoside.
In 1992, the American Society of Echocardiography published a report of the Sonographer Education and Training Committee's recommendations for education of sonographers who perform echocardiographic procedures. Since the publication of the original document, there has been continual progress in technology with the development of more sophisticated diagnostic applications that allow more information to be obtained from echocardiographic procedures. These recent changes in the clinical application of echocardiography should be included in all cardiac sonographer education programs. The American Society of Echocardiography, a professional society that currently represents approximately 2500 cardiac sonographers, provides these updated guidelines.
The aim of the present study was to establish an animal model for Helicobacter pylori (H. pylori) infection at the German Primate Centre in rhesus monkeys (Macaca mulatta). During the experiments the susceptibility of three animals to different H. pylori strains of human origin was tested. In a follow-up study gastric biopsies from three different sites were investigated in regular intervals using microbiological, histological, electron microscopical and molecular biological methods to evaluate the presence of bacterial colonization and the occurrence of gastritis. It was possible to establish a persistent experimental infection. The rather long follow-up period of 18 months offered the possibility to demonstrate a permanent H. pylori infection in the gastric mucosa of the test animals. The three animals have now been successfully colonized with H. pylori for 18 months and presented a chronic active gastritis confirmed by microbiological and histological methods. By molecular typing, the identity of the isolates recovered from the animals was shown. It was possible to demonstrate that one infection strain outcompeted the second one. Taken together, prerequisites exist for making use of an attractive and useful animal model in rhesus monkeys especially for long term observations.
BACKGROUND: Tumor cells require specific proteolytic enzymes for invasion and metastasis, including lysosomal peptidases--cathepsins. Cathepsin B is a lysosomal cysteine peptidase, which appears to play a major role in invasion and metastasis of human tumors. In this study, the authors focused on the possible role of cathepsin B in lymphogenic metastasis by investigating the enzyme localization and its activity in lung tumors and corresponding tumor-infiltrated lymph nodes. METHODS: Cathepsin B activity was determined in lung tumors, lung parenchyma, and tumor cell-infiltrated and noninfiltrated regional lymph nodes of the same patient. The authors investigated 35 cancer patients suffering from nonsmall cell lung carcinoma. Cathepsin B throughout activity was measured by cleavage of the fluorogenic substrate Z-Arg-Arg-AMC at pH 6.0. RESULTS: The median specific cathepsin B activity was highest in tumors, followed by the infiltrated lymph nodes, noninfiltrated lymph nodes, and lung parenchyma. The authors showed a significant 1.8-fold increase in cathepsin B activity in tumor-infiltrated lymph nodes compared with noninfiltrated regional lymph nodes and a 4.5-fold increase in lung tumor tissue compared with lung parenchyma. High cathepsin B activity, both in tumors and tumor cell-infiltrated lymph nodes, indicated poor prognosis for overall survival. Immunohistochemical analysis showed the presence of cathepsin B in histiocytes and tumor cells but not in lymphocytes of lymph node tissue. CONCLUSIONS: The authors' findings on higher cathepsin B levels in tumor cell-infiltrated lymph nodes show that increased level of cathepsin B activity is characteristic of the invasive tumor cell phenotype. This corroborates the hypothesis, that tumor cell associated cathepsin B may play a role in lymphogenic metastasis. The authors' results support the use of lymph node associated cathepsin B as a prognostic factor for survival of patients with lung carcinoma.
The stem bark and seeds of Andira inermis, Fabaceae, are employed as a purgative, vermifuge, and febrifuge. In particular, the powdered bark is claimed to be efficacious in intermittent fever. Bioassay-guided fractionation of lipophilic extracts from the stems and leaves yielded six isoflavones: biochanin A, calycosin, formononetin, genistein, pratensein, and prunetin. Calycosin (3', 7-dihydroxy-4'-methoxyisoflavone) and genistein (4',5, 7-trihydroxyisoflavone) have been shown to possess in vitro activity against the chloroquine-sensitive strain poW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum.
CONTEXT: Laboratory quality indicator data, most often presented and reported as a percentage of variance, may be misleading, inasmuch as variances, and therefore percentages, appear to be low. METHOD: Current data from laboratory quality indicators and national data derived from several years of College of American Pathologists Q-Probes studies were normalized to parts-per-million defects, as commonly practiced in the manufacturing and service industries for benchmarking performance. RESULTS: Laboratory data in parts-per-million defects demonstrated opportunities for significant improvements in laboratory performance across the total testing process. CONCLUSIONS: Historical quality assurance programs do not appear to be significantly improving the total testing process. Manufacturing and service industries are using quality systems strategies, such as ISO 9000 and the Baldridge Award Criteria, to effect improvements in both productivity and cost. Quality system solutions for performance improvement may provide a systematic approach to improving laboratory performance.
Resistance to local infection after fracture fixation with plate osteosynthesis may be influenced by the implantation technique. It is known that the extent of the surgical approach to the bone can compromise the local defence capacity. We have investigated susceptibility to infection after a local bacterial challenge in rabbit tibiae using either the open surgical approach for 'biological' internal fixation of standard 2.0 dynamic compression plates or the method of minimally invasive plate osteosynthesis (MIPO), a percutaneous, tunnelling insertion technique preserving the integrity of the overlying soft tissue. After the wounds had been closed, various concentrations of Staphylococcus aureus were injected in the direct vicinity of the implants. The infection rate for the open surgical technique was 38.5% and that for the MIPO technique, 25%. This difference is not statistically significant (P > 0.05) suggesting that resistance to local infection associated with the MIPO method is at least equivalent to the open approach for plate osteosynthesis.
With the use of intravital microscopy, we demonstrate that the extent of bacterial contamination is a determinant for the microvascular response and consecutively the microvascular injury. The model of bacterial soft tissue infection used, ideally allows to study the influence of foreign materials on microvascular immune response.
With a standardised model we investigated the influence of two different surgical approaches to the rabbit tibia for plate osteosynthesis on resistance to local infection after postoperative inoculation of graduated concentrations of staphylococcus aureus at the implant. The infection rate for the minimally invasive plate osteosynthesis with insertion of the implant in closed, soft tissue tunneling technique was 25% (3/12 animals; ID50 = 6.2 x 10(6) CFU) and for the conventional open approach 38% (5/13 animals; ID50 = 2 x 10(6) CFU). This difference is statistically not significant (with P < 0.05).
Three-dimensional echocardiography has demonstrated superiority over two-dimensional techniques in the determination of left ventricular mass and volumes. We describe a technique based on a magnetic tracking system which provides rapid three-dimensional image acquisition from multiple acoustic windows. Interactive three-dimensional border tracking and reconstruction with a piecewise smooth subdivision model accurately reproduced phantom volume (calculated volume = 1.00 true volume - 0.6 ml, r = 1.000, standard error of the estimate = 1.3 ml), in vitro heart volume (calculated volume = 1.02 true volume - 1.3 ml, r = 1.000, standard error of the estimate = 0.4 ml), in vitro heart mass (calculated mass = 0.98 true mass + 1.4 gm, r = 0.998, standard error of the estimate = 2.5 gm), and in vivo stroke volume (calculated stroke volume = 1.18 Doppler stroke volume - 17.9 ml, r = 0.990, standard error of the estimate = 2.8 ml). The three-dimensional in vivo data sets, which include views from three acoustic windows, were acquired in less than 90 seconds. We conclude that this method of three-dimensional echocardiographic data acquisition and analysis overcomes limitations inherent in currently available systems.
The anatomy of degenerative valvular aortic stenosis has been poorly represented in animal models, limiting the evaluation of noninvasive echo-Doppler measures of transvalvular volume flow rate and stenosis severity during progressive disease evolution or under conditions of changing volume flow rates. To study these issues, chronic valvular aortic stenosis, characterized by stiff leaflets without commissural fusion, was created in nine adult mongrel dogs by suturing pericardial covered Teflon-felt pads into the sinuses of Valsalva below the coronary ostia during hypothermic cardiac arrest. In the eight surviving dogs, echo-Doppler examinations were performed weekly for up to 8 wk postoperatively. Simultaneous invasive micromanometer pressure data were collected at 2-wk intervals in all subjects, with simultaneous ascending aortic transit time-volume flow measurement in four subjects. Volume flow rates were altered with saline and dobutamine infusions during invasive studies for comparison of echo-Doppler and invasive pressure gradients, volume flow, and valve areas. Serial echo-Doppler follow-up (39 +/- 11 days) demonstrated that, from baseline to final study, mean transvalvular pressure gradient increased (4 +/- 1 to 38 +/- 7 mmHg, P = 0.001), continuity equation aortic valve area decreased (2.06 +/- 0.18 to 0.54 +/- 0.04 cm2, P < 0.0001), and progressive left ventricular hypertrophy developed (62 +/- 6 to 114 +/- 9 g, P = 0.0003). Echo-Doppler and invasive data correlated well for measures of transvalvular pressure gradients (n = 98, maximum instantaneous gradient r = 0.95, mean gradient r = 0.91), volume flow (n = 75, stroke volume r = 0.86, cardiac output r = 0.86), and valve area (n = 73, r = 0.73) despite acute alterations in volume flow and progressive disease evolution. This chronic canine model, with anatomy and hemodynamics similar to clinical degenerative valvular aortic stenosis, should provide a valuable tool for investigating clinically relevant new measures of stenosis severity with use of invasive or noninvasive techniques.
There is substantial intercountry variation in the proportion of cases of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) which are attributed to specific drugs. This study was undertaken to determine whether these differences might reflect biases in diagnosis of these conditions. A total of 138 reactions in 5 countries originally diagnosed as TEN or SJS were coded on to standardised forms. A single observer blind to the original diagnosis assessed each case according to specified criteria. This observer's diagnoses were compared with the original diagnoses. Overall, 111 of the 138 cases had information adequate for assessment. The blinded observer agreed with the diagnosis for 61% of cases where the original diagnosis was TEN and 58% of cases where the original diagnosis was SJS. There was no significant difference in rates of agreement when reactions attributed to sulphonamide antibiotics were compared with reactions attributed to other drugs. There were substantial and significant differences in percentage agreement between the blinded observer's diagnosis and the original diagnoses between countries. The lowest rates of agreement between the blinded observer and the original reports occurred in the US. Our results illustrate the difficulty in comparing reaction rates based on spontaneous reports between countries where the systems for gathering such reports vary. This illustrates the need for a minimum quantity of standard data and precise definitions of reactions if spontaneous reports of adverse reactions are to provide useful information about severe adverse skin reactions associated with drugs.
Two experiments were performed to investigate the perception of peripherally presented apparent motion as a function of eccentricity of the stimulus, ambient illumination, sex, stimulus pattern, and angular extent of stimulus presentation. The experimental task for both studies was to judge the direction of apparent motion for a stimulus target lighter than the background and presented on a Braumbach perimeter. The results from Exps. 1 and 2 indicated main effects for subjects and eccentricity. The combined results of Exps. 1 and 2 indicated main effects for eccentricity and angular separation of the apparent motion, however, the interaction between the two was not significant.
This study investigated the perception of the direction of peripheral apparent motion as a function of stimulus location in the peripheral visual field, stimulus contrast, and the direction of the apparent motion. Results indicated that each of these independent variables was significant as a main effect while the interactions were not.