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Biomedical subjects

A Lorenz

Publications and source records attributed to A Lorenz.

At least 19 recordsLinked to original sources

[Prostate cancer diagnosis using ultrasound elastography. Introduction of a novel technique and first clinical results].

During the last decade screening has improved prostate cancer detection. The main reason for this development is a better understanding of the margins of prostate-specific antigen (PSA) serum levels and the classification of PSA subtypes. In contrast, the introduction of transrectal ultrasound has not led to a measurable change in the prostate cancer detection rate. Our aim was to develop a novel ultrasound system for the acquisition of elastographic images of the prostate and evaluate the system regarding its clinical applicability. We used a technically modified conventional ultrasound system and analyzed the high-frequency ultrasonic data with a computer program. The first patient-based results suggest that elastography allows an accurate measurement of tumor size and localization in contrast to conventional transrectal ultrasound. Elastography visualizes different tissue elasticities to distinguish benign and cancerous tissue. Thus, we were able to even correctly classify prostate cancer lesions which are iso- or hyperechoic in B-mode sonography.

Aged↗

Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.

BACKGROUND: Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. METHODS: In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. RESULTS: Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. CONCLUSION: Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.

Adjuvants, Immunologic↗

Laser disintegration of cyanoacrylate clot with successful endoscopic removal of sclerotherapy needle from gastric varix.

Intravariceal cyanoacrylate injection is a highly effective and safe procedure for the treatment of bleeding gastric varices. Nevertheless, some cases of severe cyanoacrylate-specific complications due to embolization have been described. Technical difficulties, including risk of sclerotherapy needle clogging, and cyanoacrylate sticking to the tip and the accessory channel of the endoscope, have been mentioned in other reports. We report a case in which a sclerotherapy needle that remained stuck in gastric valves after bucrylate injection was successfully removed by laser disintegration of the cyanoacrylate clot.

Aged↗

[Ultrasound elastography of the prostate. A new technique for tumor detection].

AIM: Prostate tumours are often of harder consistency than the surrounding tissue. During digital rectal examination, this fact can be used not only to detect hypertrophy but also localized hardenings. The examination by digital palpation is inaccurate and, even in combination with PSA-value and a transrectal ultrasonic examination, the result is often not reliable. Ultrasound elastography enables us to measure and visualize the elastic properties of a tissue region and is a useful supplement to the examination by digital palpation. Ultrasound elastography is able to measure and visualize the elastic properties of a tissue region, therefore it is a useful supplement to commonly used diagnostic procedures. METHOD: We have developed a new system for elastographic prostate diagnosis which can be used during the transrectal ultrasonic examination. During the examination a sequence of ultrasonic images is acquired while the organ is slightly compressed by the ultrasound probe. Using numerical analysis of image pairs for the acquired sequence we calculate the tissue strain which represents the spatial elasticity distribution of a specific cross-section of the organ. This enables us to distinguish hard areas in the tissue. Image artifacts resulting from lateral motion components, i.e., orthogonal to the direction of the applied force, are compensated for by a special approach. RESULTS: We present results obtained from a typical elastography phantom and also the first in vivo images from patients who were undergoing radical prostatectomy. Our images prove that ultrasound elastography has the potential to detect malignant tissue areas, which are inconspicuous in the B-mode image. Our findings are confirmed by the corresponding histological specimens.

Elasticity↗

New real-time strain imaging concepts using diagnostic ultrasound.

Two real-time strain imaging concepts and systems are presented. Both systems are based on a conventional ultrasound scanner that is connected to a PC with an A/D converter card for real-time data acquisition of rf data. Differential strain between successively acquired rf frames are estimated using phase root seeking. The first concept uses a special real-time implementation of manual elastography. In the second concept, denoted 'vibrography', the static compression is replaced by low-frequency axial vibration of the probe, still operating in quasistatic acquisition mode. The properties of both concepts are discussed with regard to noise and motion artefacts, and it is shown, using simulations and phantom experiments, that both imaging concepts yield the same kind of strain images. Vibrography has the advantage that no manual compression has to be applied, total compression can be very low and some motion artefacts are better suppressed.

Algorithms↗

Degradation of pectins with different degrees of esterification by Bacteroides thetaiotaomicron isolated from human gut flora.

A complete human fecal flora and cultures of defined species obtained from fecal flora were investigated in vitro to determine their ability to ferment the dietary fiber pectin. Bacteroides thetaiotaomicron was tested as a pectin-degrading microorganism alone and in coculture with Escherichia coli. Macromolecular pectins with different degrees of esterification were used as substrates in microbial degradation studies. The levels of oligogalacturonic acids formed in batch cultures were estimated during a 24- or 48-h incubation period by using high-performance thin-layer chromatography and high-performance anion-exchange chromatography. The spectrum and the amount of unsaturated oligogalacturonic acids formed as intermediate products of pectin fermentation changed permanently in the culture media during incubation with the complete fecal flora. After 24 h, no oligogalacturonic acids were detected. The pectin-degrading activities of pure cultures of B. thetaiotaomicron were lower than the pectin-degrading activity of a complete fecal flora. Cocultures of B. thetaiotaomicron and E. coli exhibited intermediate levels of degradation activity. In pure cultures of E. coli no pectin-degrading activity was found. Additionally, the rate of pectin degradation was affected by the degree of esterification of the substrate. Saturated oligogalacturonic acids were not found during pectin fermentation. The disappearance of oligogalacturonic acids in the later stages of fermentation with both the complete fecal flora and B. thetaiotaomicron was accompanied by increased formation of short-chain fatty acids.

Bacteroides↗

Synergistic interaction of ultrasonic shock waves and hyperthermia in the Dunning prostate tumor R3327-AT1.

Pulsed high-energy ultrasound shock waves (PHEUS), similar to those used for clinical lithotripsy, can deposit energy deep in tissue and thereby destroy the microvasculature of solid tumors. We investigated the potential of PHEUS, generated by an electromagnetic shockwave source (19 kV capacitor voltage, 1 Hz pulse frequency), as a local cancer-therapy modality alone and in combination with local tumor hyperthermia (43.5 +/- 0.1 degrees C, 30 min). Copenhagen rats transplanted with the anaplastic Dunning-prostate-tumor sub-line R3327-AT1 received 1000 PHEUS pulses, which delayed tumor growth by one tumor-doubling time (5 days). Histopathology revealed hemorrhage, disruption of tumor vasculature, and necrosis in the focus of the sound field. Bromodeoxyuridine (BUdR) incorporation was significantly lower in PHEUS-treated tumors than in controls. Dynamic magnetic resonance imaging (MRI) studies using gadolinium-DTPA as contrast agent showed a strong reduction of tumor perfusion after PHEUS treatment, although this effect was partly reversible within 3 days after PHEUS. While hyperthermia alone produced no significant delay in tumor growth, the combination of PHEUS and hyperthermia produced tumor-growth delay by 2 tumor-volume-doubling times. The maximum growth delay was achieved when PHEUS and hyperthermia were separated by 24 hr at the time of maximum perfusion reduction indicated by MRI. Thus, the cytotoxic effect of PHEUS was enhanced by hyperthermia in the anaplastic prostate tumor R3327-AT1 grown on Copenhagen rats in a synergistic manner, due to blood-flow reduction. In conjunction with other agents, such as hyperthermia, PHEUS might become a local cancer-therapy modality in solid tumors accessible to ultrasound.

Animals↗

Butyrate inhibits and Escherichia coli-derived mitogen(s) stimulate DNA synthesis in human hepatocytes in vitro.

Bacterial constituents and products of the bacterial metabolism pass from the gut lumen to the portal vein and may influence the homeostasis of the liver. Our aim is to examine whether DNA synthesis of human hepatocyte cell lines is affected by constituents of Escherichia coli species as well as by intracolonic products of bacterial fermentation that reach the liver via the portal vein. Supernatant solutions and bacterial cell fractions (containing either whole dead bacteria, cell walls, cytosol or non-soluble intracellular components) of E. coli K12 and of E. coli species from rat fecal flora were separated by multi-step centrifugation, French press, and microfiltration. The supernatant solution and the cell fractions were incubated with a human hepatoma cell line (Hep-G2) and with a cell line derived from non-malignant human liver cells (Chang cells) for 24 h. The cells were labeled with tritiated thymidine before processing to autoradiography. DNA synthesis was estimated by the labeling index (LI%). DNA synthesis was also estimated following incubation of Hep-G2 cells with short chain fatty acids (acetic, propionic, butyric and succinic acid), acetaldehyde, and ammonium chloride. Epidermal growth factor and a water extract of Helicobacter pylori were used as references. The fractions of E. coli from rat fecal flora containing cytosol and non-soluble intracellular components significantly increased the labeling index in both Hep-G2 and Chang cells (p < 0.05). In addition, the supernatant solution significantly increased the LI in Chang cells (p < 0.05). Epidermal growth factor increased the LI of Hep-G2 cells dose-dependently (p < 0.05). Butyric acid reduced DNA synthesis at 10(-4) M (p < 0.05). The highest doses of acetaldehyde were cytotoxic and reduced the LI. Escherichia coli species contain mitogenic factors to human hepatocytes. The mitogen(s) are present in the supernatant solution, in the cytosol and in non-soluble intracellular components. Butyrate, which is a product of bacterial fermentation of colonic substrates inhibit DNA synthesis in the hepatocyte cell lines. Our findings suggest that soluble mitogen(s) that diffuse from the microorganism to the outer environment, intracellular bacterial constituents, and products of the bacterial metabolism that reach the liver via the portal vein may influence the cell kinetic steady-state of hepatic cells.

Acetaldehyde↗

Unsaturated oligogalacturonic acids are generated by in vitro treatment of pectin with human faecal flora.

Pectins with a degree of esterification (DE) of 95, 66, 34 and 0%, respectively, were incubated in vitro with human faecal flora (pH 7.8). The concentration and composition of oligogalacturonic acids (oligoGalA) generated were determined using high-performance thin-layer chromatography (HPTLC) with UV and colorimetric detection. In the first period of the anaerobic degradation, the pectin macromolecules were fragmented into unsaturated oligoGalA as intermediate products by the action of bacterial pectate lyases. Depending on the incubation time and the DE of pectin, the amount of unsaturated oligoGalA having different degrees of polymerization changed continuously. These oligoGalA were present in the cultures for some hours. Mixtures of unsaturated di-, tri- and tetraGalA were the end products of a pectate lyase action. Later, the oligoGalA disappear as a result of their further fermentation by the gastrointestinal microflora under formation of short-chain fatty acids (SCFA). Low-esterified pectins were depolymerized and fermented faster than the highly esterified by the human faecal flora in vitro. Furthermore, a mixture of unsaturated oligoGalA prepared from pectic acid by the action of pectate lyase from Erwinia carotovora was completely fermented by human faecal flora.

Chromatography, Thin Layer↗

[A multicenter study of diagnostic criteria in ultrasound mammography. Statistical pitfalls and ways out of the data jungle].

This paper demonstrates the statistical processing of data from a multicentric study. Seventy-seven patients with a suspicious, solid breast mass were included in a two-center study, using clinical breast examination, mammography, and ultrasound. The assessment was formalized using a uniform evaluation sheet. The prospective results of the examinations were compared with the histologic report. The degree of interdependence between an examiner's diagnosis and diagnostic criteria used was assessed using the kappa statistics. We found that despite standardized assessment, the criteria used for differential diagnosis were at least partially different. The criteria valid for diagnosis at both centers were whether a mass fitted well into the surrounding tissue or led to destruction or architectural distortion, whether it was fixed to the surrounding tissues, as assessed by sonopalpation maneuvers, and whether it borders were sharp or unsharp.

Artifacts↗

Limitations for three-dimensional ultrasound imaging through a bore-hole trepanation.

The intraoperative shift of neuroanatomical landmarks that serve as reference points is an unsolved problem in current neuronavigation. Monitoring the position of these landmarks requires repeated intraoperative imaging. We analyzed the effectiveness of a 3-D ultrasound system for imaging through a bore-hole trepanation. A tissue-mimicking ultrasound phantom and plastic pads with bore-holes were utilized for in vitro tests of the system. Reducing the diameter of the simulated bore-hole decreased the image quality and reduced the field of view. The multiple plane mode of the 3-D ultrasound system allows reconstruction of images in arbitrary imaging planes on the basis of intraoperatively acquired 3-D datasets. Selecting planes that are coplanar with preoperative MRI scans, we were able to identify neuroanatomical landmarks in the reconstructed ultrasound images. Repeated 3-D ultrasound during a procedure might, therefore, allow recognition of a shift of these landmarks.

Artifacts↗

Localization of somatostatin receptor subtype mRNA in the rat gastrointestinal tract and regulation of SSTR1 gene expression.

Somatostatin and its receptors are widely distributed in the central nervous system and peripheral tissues including those of the gastrointestinal tract (GI tract). The expression patterns of the five known SSTR genes have been analysed in detail by reverse transcription polymerase chain reaction amplifications and in situ hybridizations using tissues dissected from different parts of rat stomach and gut. While SSTR1 mRNA is present at relatively high amounts throughout the gastrointestinal tract, the levels of SSTR2, 3 and 4 mRNAs vary in different regions and SSTR5 mRNA has not been detected. In situ hybridizations revealed the presence of SSTR3 mRNA in enterocytes and in neurons of the myenteric and submucous plexus. These findings are consistent with a role of SSTR3 in the observed somatostatin-mediated inhibition of acetylcholine release from myenteric neurons and of secretomotor neuron activity in the submucous plexus. Sequence analyses of the SSTR1 gene promoter revealed the absence of the canonical TATA and CAAT motifs and the presence of a variety of potential binding sites for transcriptional regulators. Among these are binding sites for GCF, AP-2, AP-4, response elements for somatostatin (SOM-RE), epidermal growth factor (EGF-RE) and cytocines (GAS and NFIL) as well as for tissue-specific factors such as Pit-1 (pituitary) and IDX-1 (pancreatic cells). Mobility shift assays have confirmed that nuclear proteins of pancreatic RIN1046-38 and pituitary GH3 tumour cells bind to oligonucleotides containing the overlapping Pit-1 and IDX-1 binding sites. Thus, the Pit-1/IDX-1 sites may be critical for the activation of the SSTR1 gene in these cell-types.

Animals↗

Initiation of the tissue factor pathway of coagulation in the presence of heparin: control by antithrombin III and tissue factor pathway inhibitor.

Activation of factor X by both the unactivated tissue factor:factor VII complex (TF:VII) and the activated tissue factor:factor VIIa complex (TF:VIIa) has been studied in the presence of tissue factor pathway inhibitor (TFPI), antithrombin III (ATIII), and heparin. At near-plasma concentrations of TFPI, ATIII, and factor X, factor X activation that occurs in response to TF:VII is essentially abolished in the presence of heparin (0.5 micromol/L). This effect requires both inhibitors, acting on different targets: (1) ATIII, which in the presence of heparin blocks the activation of TF:VII, and (2) TFPI, which inhibits the TF:VIIa that is generated. In the absence of ATIII, TFPI alone with heparin reduces but does not abolish factor X activation. Conversely, in the absence of TFPI, ATIII + heparin reduces but does not abolish TF:VIIa generation and allows continuing activation of factor X. These results indicated that when the unactivated TF:VII complex is the initiating stimulus, heparin-dependent reduction in the rate and extent of factor X activation requires both ATIII and TFPI. In contrast, if TF:VIIa is used to initiate activation, only TFPI is involved in its regulation.

Amino Acid Chloromethyl Ketones↗