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Biomedical subjects

M Clausen

Publications and source records attributed to M Clausen.

At least 91 records · Page 5Linked to original sources
PubMed1993

Hormone-inducible expression and metal affinity chromatography of recombinant proteins in Saccharomyces cerevisiae.

An economical method to express recombinant protein in yeast (Saccharomyces cerevisiae) was developed. We combined two principles: Ni(2+)-agarose-based affinity purification of fusion proteins and expression from a cassette regulated by steroid hormones. After induction by desoxycorticosterone, > 90% pure protein was obtained after a single round of metal affinity chromatography. Gentle lysis conditions allowed the preservation of enzymatic activity. Average yields of 10 mg protein per liter of culture were obtained at a fraction of the cost of other eukaryotic expression systems.

Base Sequence↗
PubMed1993

[Dramatic remission of a multiple metastasized melanoma caused by chemo-immunotherapy].

A 47 year old woman underwent excision of a malignant melanoma on the right shoulder. Nine years later she was attacked by intense pain in the back. Computed tomography, bone scans and immunohistochemical study of a liver biopsy specimen revealed metastases from the malignant melanoma in the liver, spleen and skeleton. Her Karnovsky score was 50%. Chemoimmunotherapy given for five cycles consisting of dacarbazine (800 mg/m2 body surface area every 4 weeks) together with ambulatory cytokine therapy (interferon alpha-2b subcutaneously, 5 million I.U. on days 1 and 3 to 7 in the first week, days 1, 3 and 5 in the second and third weeks and interleukin 2.9 million I.U. on days 1 to 5 in the second and third weeks; no treatment was given in the fourth week) raised the Karnovsky score to 90% and abolished the pain. Lactate dehydrogenase activity, originally 3372 U/l, dropped to normal. Computed tomography demonstrated definite shrinkage of the liver metastases and some regression of the splenic and bony deposits. This improvement has now been maintained for a total of eight cycles of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Iodine-123 labelling of atrial natriuretic peptide and its analogues: initial results.

Receptors for atrial natriuretic peptide (ANP) are known to be present in many organs, e.g. brain, liver and kidney. The aim of this study was to optimize the labelling method for ANP analogues with iodine-123 and to describe their pharmakokinetics. ANP 99-126, atriopeptin III, Tyr-atriopeptin II and urodilatin were labelled by the Iodogen method. Of the various labelling conditions tested, the Iodogen procedure with 10 micrograms Iodogen, 10 micrograms peptides in 100 microliters phosphate buffer (pH 7.2) and a reaction time of 60 min proved to be optimal. Separation was performed using a Sep-pak reversed-phase extraction cartridge. In all cases quality control by thin-layer chromatography resulted in a radiochemical purity higher than 98%. After intravenous administration of 15 MBq/kg kinetic profiles of various organs in rabbits were investigated by whole-body scintigraphy with a gamma camera. Organ kinetics showed accumulation and excretion via the kidney. No bowel accumulation was observed. Interestingly, increasing tracer uptake in the head region was registered with three of the four tested tracers. Liver accumulation decreased rapidly during the first 40 min. No tracer degradation was registered over the whole time period, as shown by the low thyroid accumulation with a maximum of only 1%. Thus, labelling of ANF and its analogues is possible. These compounds seem to be of interest for further experiments and perhaps clinical studies because of their potential for brain receptor imaging.

Animals↗
PubMed1993

Abnormal ventricular contraction patterns in patients with arrhythmogenic substrates using three-dimensional phase analysis.

Arrhythmogenic substrate diagnosis has been achieved by electrophysiological studies and best localized by successful radiofrequency ablation. Pre-invasive localization procedures have been based on surface ECGs and more recently on biomagnetism, but in addition to these electric and magnetic signals a mechanical signal may be utilized: the initial site of contraction may be detected by phase analysis during radionuclide ventriculography. Generation of three-dimensional data set of phases is achieved by incorporating the new emission tomography technique. The performance of this modified phase analysis has been investigated for the detection of the normal contraction pattern during sinus rhythm, the arrhythmogenic substrate of the WPW syndrome and ventricular tachycardia, and further, to define the limitations of the method in experimental studies on pigs. In 30 out of 44 patients with normal sinus rhythm and no ventricular lesion, a characteristic phase pattern was found. Physiologically, the initial site of contraction appeared to be paraseptal and in the anterior wall of the right ventricle close to the apex. In 13 patients with WPW syndrome and in seven with ventricular tachycardia, the phase data were compared to the electrophysiological study. In 14 of 20 there was a complete match, in 3 of 20 a mechanical focus was found in the area adjacent to the electric focus. From experimental pig studies with simulated stimulation, a spatial precision of at least 20 mm was found at a pre-excitation of 20 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Non-invasive three-dimensional localisation of arrhythmogenic foci in Wolff-Parkinson-White syndrome and in ventricular tachycardia by radionuclide ventriculography: phase analysis of double-angulated integrated single photon emission computed tomography (SPECT).

A new tomographic technique combined with phase analysis was used to detect premature and ectopic ventricular contraction patterns in 15 patients with Wolff-Parkinson-White syndrome and during ventricular tachycardia in seven patients. Data generated by gated single-photon emission computed tomography (SPECT) were analysed by backprojection of the Fourier coefficients, double-angulation, and integration to thick slices containing the ventricles, thus allowing visualisation of the contraction patterns in three perpendicular views. The results were compared with those of catheter mapping. In nine patients with Wolff-Parkinson-White syndrome the site of initial contraction detected was identical with the site of the accessory pathway found by catheter mapping. The sites of origin of the ventricular tachycardias determined by catheter mapping were within 3 cm of the sites detected by the new technique. This new technique seems to be a promising non-invasive method for localising ectopic ventricular activity that will considerably shorten the time required for subsequent invasive procedures.

Adult↗
PubMed1993

Gated blood pool SPECT and phase analysis to assess simulated Wolff-Parkinson-White syndrome in the baboon.

This study assesses the diagnostic potential of a tomographic technique with phase analysis to detect premature electroventricular contraction patterns simulated by pacing in the baboon. The data of gated SPECT were analysed by backprojection of the Fourier coefficients, followed by angulation and integration to thick slices of the entire ventricular mass yielding separate ventricular contraction patterns in three perpendicular views. Electrodes were implanted in each baboon: at the sinoatrial node; posterior, left ventricular; anterior left ventricular; on the left and the right lateral ventricular walls. The atrium was stimulated throughout at a fixed rate. Subsequent ventricular stimuli followed during the QRS complex, such to invoke the appearance of pre-excitation QRS morphology. The first points of activation (FPA) from this algorithm were correctly detected for the RV, for the anterior and posterior sites, although the latter two manifested first points in the RV. LV pacing manifested also as a FPA in the RV, but was followed by a true subsequent point in the LV.

Algorithms↗
PubMed1993

[A simple method of digitizing analog scintigrams for quantification and digital archiving].

This study was undertaken to evaluate a quick, reliable and cheap method of digitizing analog scintigrams. 40 whole-body bone scintigrams were obtained simultaneously in analog and genuine digital format. The analog scans on x-ray film were then digitized secondarily by three different methods: 300 dpi flat-bed scanning, high-resolution camera scanning and camcorder recording. A simple exposure approach using a light box, a cheap camcorder, a PC and image grabber hard- and software proved to be optimal. Visual interpretation showed no differences in clinical findings when comparing the analog images with their secondarily digitized counterparts. To test the possibility of quantification, 126 equivalent ROIs were drawn both in the genuine digital and the secondarily digitized images. Comparing the ROI count to whole-body count percentage of the corresponding ROIs showed the correlation to be linear. The evaluation of phantom studies showed the linear correlation to be true within a wide activity range. Thus, secondary digitalization of analog scintigrams is an easy, cheap and reliable method of archiving images and allows secondary digital quantification.

Analog-Digital Conversion↗
PubMed1993

[The "white hole" phenomenon--a potential functional parameter in non-gated 201Tl-myocardial scintigraphy].

In 50 patients with a "white hole" in their scintigram--among them 44 patients with a history of myocardial infarction--the relation between its relative volume and the ventriculographically determined ejection fraction was studied retrospectively. A relative volume of the "white hole" larger than 13.7% showed a specificity of 93% and a sensitivity of 45% for a decreased ejection fraction and had a significant correlation of r = -0.54 (alpha = 0.01) with the ejection fraction. Thus the relative volume of the "white hole" derived automatically from 201Tl-SPECT is an easy-to-determine additional parameter which allows an at least semiquantitative statement about the function of the left ventricle.

Adult↗
PubMed1992

Measurement of mucociliary transport velocity in ventilated patients. Short-term effect of general anesthesia on mucociliary transport.

OBJECTIVES: The objectives of this study were to evaluate a method for measuring BTV in ventilated patients and to study the short-term effect of general anesthesia with midazolam, Fentanyl, pancuronium and O2:N2O on BTV. DESIGN: The study included phantom measurements on a bronchoscopy model and the determination of BTV in patients in a convenience sample trial. SETTING: The study took place in a university hospital. PATIENTS: Fourteen patients undergoing major abdominal surgery with planned postoperative mechanical ventilation were included in the study. All patients gave their written informed consent to participate in the study. INTERVENTIONS: Bronchial mucus transport velocity was measured with a small volume (0.05 to 0.08 ml) of technetium 99m-labeled albumin microspheres with an activity of 3 MBq. The radiolabeled bolus was deposited on the dorsal mucosal surface at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the microspheres toward the trachea was visualized and recorded using a scintillation camera; quantitative evaluation utilized the condensed image. MAIN MEASUREMENTS AND RESULTS: The technique was validated in a bronchoscopy model and in an intubated patient by moving a radioactive drop in a catheter through the main bronchi at velocities from 0 to 20 mm/min. The velocities determined by the image processing technique correlated well with the data by the model and patient determination (right bronchus, r = 1.0; left bronchus, r = 1.0). In seven ventilated patients, mechanical irritation by the fiberscope produced no significant effect on BTV. The BTV was measured preoperatively in seven conscious patients one day before surgery while they received local anesthesia with 10 ml of 1 percent lidocaine and postoperatively while they received intubation anesthesia. The preoperative and postoperative BTV values showed no significant differences (10.5; 5.7 to 13.7 mm/min; vs 9.7 (3.7 to 15.3) (median with range). CONCLUSION: By this method, bronchial transport velocity can be determined in a relatively short time in ventilated patients. General anesthesia with midazolam, Fentanyl, pancuronium and O2:N2O does not influence BTV.

Adult↗
PubMed1992

[The effect of Belzer and Bretschneider cardioplegia solutions on myocardial energy metabolism. A study with 31phosphorus magnetic resonance spectroscopy in an animal model].

The aim of our study was to test the effectiveness of two cardioplegic solutions and to compare the level of high energy phosphates in the myocardium. We investigated 18 hearts of pigs (obtained from a slaughter-house) with 31phosphorusmagnetic resonance spectroscopy (31P-MRS) In this experiment coronary arteries were cannulated and reperfused with arterial blood to revitalize the heart. When the heart showed regular pulsations coronary arteries were perfused for cardioplegia either with the UW-(Belzer-) or with the HTK-(Bretschneider-)solution. For 31P-MRS, a magnet with a magnetic flux density of 4.7 Tesla (T) was available. Relative concentrations from phosphocreatine (PCr/beta-ATP; high-energy phosphate) and inorganic phosphate (Pi/MDP; MDP = methylendiphosphonat = reference solution; low-energy phosphate) were calculated from the spectra. As a result of this study, the HTK-solution showed a significantly higher PCr/beta-ATP-ratio in the myocardium than the UW-solution during the examination time of 3 h. After plegia of the myocardial area from the right coronary artery PCr/beta-ATP-ratios were lower in comparison with the left coronary artery distribution area. The calculation of Pi/MDP-ratios proved that Pi was higher in the myocardium after application of the UW-solution compared to HTK-solution. The kinetics of the metabolites showed an approximately linear and parallel decrease of PCr/beta-ATP-ratios after cardioplegia with both solutions during the examination time.

Animals↗
PubMed1992

[Quantification of tricuspid insufficiency--comparison of Doppler echocardiography and radionuclide ventriculography].

In 40 patients (pts) (ages 34-83 years) the severity of tricuspid regurgitation (TR) was graded by pulsed Doppler echocardiographic determination of regurgitant jet extension. Mild TR was assessed in seven pts (group I), mode-rate TR in 20 pts (group II), and severe TR in 13 pts (group III). The enddiastolic diameter of the left ventricle as measured by M-mode-echocardiography was 55 +/- 16 mm in group I, 48 +/- 6 mm in group II, and 50 +/- 10 mm in group III. The regurgitant index (RI), i.e., the ratio of left-to-right-ventricular stroke counts (normal range 0.89-1.97) and the time-activity curve over the liver area were measured by equilibrium radionuclide ventriculography (RNV). The RI differed significantly between group I (1.6 +/- 0.5), II (1.0 +/- 0.3), and III (0.8 +/- 0.3) (p less than 0.01). An RI-value below 0.89 as an index of right-ventricular volume overload was found in 14% (group I), 45%, (group II) and 77% (group III). The time-activity curve over the liver area, as graded by count variation in phase with the right atrium from 1 (no count variation) to 4 (typical count variation) showed all grades in groups I and II, but only grade 2 to 4 in group III. The RI resp. the time-activity curve over the liver is a sensitive parameter for the detection of moderate to severe TR. If TR is ascertained, severe regurgitation can be differentiated from mild regurgitation by RNV-derived RI as an index of right-ventricular volume overload.

Adult↗
PubMed1991

Reproducibility of quantitative hexakis-2-methoxyisobutylisonitrile single photon emission tomography in stable coronary artery disease.

The quantification of myocardial perfusion abnormalities is necessary to allow comparison of repeated studies, especially in the evaluation of the success of medical, interventional or combined treatment in stable coronary artery disease or in evolving myocardial infarction. The purpose of this study was to assess inter-observer reproducibility of tomographic study processing using a semi-automatic quantitative programme. Technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi) was chosen for tomographic imaging of repeated rest-stress studies in patients with stable coronary artery disease. The quantification was performed using a modification of the Cedars polar coding and comparison with the normal data base. The perfusion defects were quantified separately for each standard perfusion area [left anterior descending (LAD), right coronary (RCA) and left circumflex (LCX) arteries] and total area of hypoperfused myocardium. The inter-observer variability for 40 tomographic studies was accomplished. The defects were the largest in the LAD perfusion area (average 19.7% of the normalized LAD supply area) with an inter-observer correlation of 0.84 for this region. The greatest variability was found for the LCX region (r = 0.55) and is attributed to a small average perfusion defect (7.1%), only 18 studies having abnormal perfusion in this area. In total, an average 14.3% of the left ventricular myocardium was significantly hypoperfused, and the inter-observer correlation was 0.87. These results show good inter-observer reproducibility using semi-automatic quantitation of perfusion defects. Careful interpretation of smaller defects in the evaluation of treatment results is advised when repeated 99mTc-Sestamibi single photon emission tomography studies are processed by more than one observer.

Coronary Disease↗
PubMed1991

Localization of ectopic ventricular depolarization by ISPECT-radionuclide ventriculography and by magnetocardiography. ISPECT and MCG for ectopic mapping.

Since catheter or surgical techniques for ablating the arrhythmogenic substrate in patients with SVT due to accessory pathways or those with VT are now available, exact localization of the substrate is mandatory. We report preliminary results of two new non-invasive techniques for localizing either the site of earliest ventricular contraction using ISPECT, or the site of initial ventricular depolarization by magnetocardiography (MCG) in WPW syndrome and in VT patients. Thirteen patients with WPW syndrome and 8 patients with sustained VTs were studied with ISPECT. In 9/13, comparative catheter mapping data were available. Two patients had two Kent bundles. 13/15 Kent bundles could be localized by ISPECT. In 5/9 patients the area of Kent bundle insertion was identical with ISPECT and catheter mapping, in 3 correlation was fair, and in 2 patients with 2 Kent bundles ISPECT failed to localize their insertion. In 3/8 patients with VT catheter mapping could not be performed for hemodynamic reasons. In 2/5 patients the area of VT focus was identical with both methods, in one patient it was adjacent to each other, and in 2/5 patients a larger anatomic distance of the focus was found with both methods. In 3/7 patients with WPW the MCG showed the site of Kent bundle insertion, which was identical to that seen by catheter mapping. In one patient the area was adjacent, and in 3 more distant from the site determined by catheter mapping. In 1/2 patients with 2 Kent bundles, one of these could be detected by MCG. In 1/3 patients with VT, the site of VT focus was identical with both methods, but in the remaining two a distance of 3-4 cm was observed between the area seen with MCG and that with catheter mapping. In 4 further VT patients with stable and uniform ventricular late potentials, ventricular late magnetic activity was found with different QRS lengths within the single MCG channels. From our results we conclude that both ISPECT and MCG seem to become very promising non-invasive techniques for localizing ectopic ventricular depolarization in WPW syndrome and VT patients. However, these methods have to be refined, improved and validated by further systematical studies.

Action Potentials↗
PubMed1991

Upward creep of the heart in exercise thallium 201 single photon emission tomography: clinical relevance and a simple correction method.

The upward creep of the heart during myocardial single photon emission tomography (SPET) acquisition has been reported as a frequent source of false-positive results. The aim of this study was to simplify the detection and correction of this upward creep and to estimate its clinical relevance during routine patient care. To recognize the upward heart motion a straight line was fitted to the upper and lower border of consecutively displayed tomographic projection images. In this way, vertical translation of at least 1 pixel in size could be detected easily. On the assumption of a slow but continuous upward motion a fast interpolation correction method was developed. From 100 consecutive, supine, ergometric exercise studies, 1, 2 or 3 pixels of upward creep were found in 16, 4 or 3 patients, respectively. It was found that an upward creep of at least 2 pixels (7/100 cases) led to evident, mostly antero-septal defects on quantitative bull's-eyes, whereas only upward creeps of 3 pixels or more (3/100 cases) produced false-positive diagnostic results. The simple correction method offered a sufficient compensation of image and/or bull's-eye artefacts. These clinical findings could be reproduced in a computer model. Thus, it can be stated that clinically significant upward creep of the heart during stress SPET acquisition is relatively rare; it may have been overestimated in the past, and its artificial effects can be corrected by a quick and simple algorithm.

Algorithms↗
PubMed1991

Application of P-31 nuclear magnetic resonance spectroscopy to a new experimental kidney perfusion model using cadaveric porcine kidneys from slaughterhouse.

Larger NMR magnets with relatively high field strengths have become available recently, allowing the application of magnetic resonance spectroscopy (MRS) in larger mammalian organs. The aim of this study was to develop and test a new and simple kidney perfusion model from slaughterhouse swine using a new 4.7-tesla/40-cm diameter system, with the intention behind to provide a human-like mammalian experimental kidney perfusion model, and to avoid sensitive in vivo animal experiments on higher-developed mammalians, 35 pig kidneys obtained 10-15 min post mortem were studied to evaluate and define conditions for optimum metabolic preservation with the following perfusion protocols: (1) immediate plegia with cold Collins solution, 1-3 h cold storage, P-31 MRS; (2) immediate plegia, 1-3 h cold storage, blood reperfusion, P-31 MRS; (3) immediate blood reperfusion, plegia, 1-3 h cold storage, blood reperfusion, P-31 MRS; (4) immediate blood reperfusion, plegia, 24 h cold storage, blood reperfusion, P-31 MRS, P-31 MRS at 81 MHz with a double-tuned surface coil yielded the following results: [table: see text] Blood flow showed a weak correlation with beta-ATP/inorganic phosphate in protocols 3 and 4 of r = 0.64. Repeated reperfusion and ischemia experiments of this model allowed the on-line observation of the metabolic response of the energy phosphate pattern for several hours. In conclusion, slaughterhouse-harvested swine kidneys lend themselves to a simple, low-cost in vitro perfusion model, provided they are reperfused with arterial blood immediately after harvesting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

The orthopan tomoscintigram--a new application of emission computed tomography for facial bone scanning.

The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, while was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging.

Facial Bones↗
PubMed1990

Comparison of the cytotoxicity and DNA-damaging properties of 2,4-D and U 46 D fluid (dimethylammonium salt of 2,4-D).

U 46 D Fluid (the dimethylammonium salt of 2,4-dichlorophenoxyacetic acid in a commercial formulation) was more toxic to human fibroblasts than 2,4-dichlorophenoxyacetic acid (2,4-D). Moreover, U 46 D Fluid induced single-strand breaks at apurinic/apyrimidinic (AP) sites of heat-acid treated PM2 DNA while 2,4-D did not. The 1H-NMR spectrum of the dimethylammonium (DMA) salt of 2,4-D indicated the formation of a complex via a six-membered aggregate of the DMA ion and the acid group of 2,4-D. The role of complex formation of the DMA salt of 2,4-D as a cause of single-strand breaking activity and increased cytotoxicity is discussed.

2,4-Dichlorophenoxyacetic Acid↗