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Biomedical subjects

M Anliker

Publications and source records attributed to M Anliker.

At least 19 recordsLinked to original sources
PubMed2004

Familial cutaneous mycosis fungoides: successful treatment with a combination of gemcitabine and alemtuzumab.

We report a familial cutaneous T-cell lymphoma in father and son. After different treatment modalities without lasting responses, the son was treated with gemcitabine as single agent and due to insufficient effect with alemtuzumab monotherapy. Only after the two drugs had been combined did we observe a remarkable response of the skin lesions and disappearance of enlarged lymph nodes. The combined treatment with gemcitabine and alemtuzumab was well tolerated, and no increased toxicity was noted. The combination of these two active agents may provide an additional option in the treatment of cutaneous T-cell lymphoma.

Adult↗
PubMed2000

[Ant venoms: a rare cause of allergic reactions in Switzerland].

In Switzerland, unlike other countries, allergic reactions to ants are a rare phenomenon when compared to the well known allergies to bee and wasp venom. In this report we present a series of case reports and a review of the different types of allergy to ants. Due to increased travel and heterogeneity of the population, we have observed several patients with sensitisation or allergy to the venom of imported fire ants (Solenopsis), a species of ant found in the Americas. Furthermore, allergic reactions to bites of the mound-building wood ant (Formica rufa), whose habitat is Central and Northern Europe, have been documented. Whereas reactions to fire ants can be life-threatening, reactions to mound-building wood ants have led to marked local reactions and in 2 cases to dyspnoea and wheezing. These reactions could be due either to primary sensitisation to ant venom or cross-reactivity in the presence of an allergy to wasp venom. Evaluation of patients presenting with a potential ant venom allergy includes a detailed personal history, skin testing and determination of specific IgE. However, to date only extracts from fire ants are commercially available for diagnostic tests. In the light of our observations we assume cross-reactivity between the venoms of fire ants and mound-building wood ants, and it therefore seems appropriate to use fire ant diagnostics in determining sensitisation to mound-building wood ants. In patients with severe fire ant-venom allergy we recommend desensitisation by immunotherapy, whereas in patients presenting with minor allergic reactions, e.g. after bites by mound-building wood ants, we provide the patients with emergency medication. Since current knowledge of ant allergies in Europe is limited, further studies are warranted.

Animals↗
PubMed1996

Subtraction procedure for the registration of tissue perfusion with Doppler ultrasound.

Tissue perfusion, i.e., in muscles or parenchymatous organs, is of both physiological and pathophysiological interest. The measurement of tissue perfusion is an unsolved problem. The Doppler ultrasound method is well suited to this purpose. However, measurements using this technique may be disturbed by movements or vibrations such as heart motion, muscle trembling or vibration of the subsoil (i.e. the examination table). These interfering movements produce Doppler frequencies in the same frequency range as slowly flowing erythrocytes, causing artifacts to appear in the measured data. The goal of this project was to suppress such artifacts with the help of a subtraction procedure. The mathematical theory of this subtraction procedure and its implementation in a newly developed two channel Doppler system are presented. This system was successfully tested on a phantom which is able to generate flow and movement artifacts. Preliminary measurements in the forearms of volunteers showed that movement artifacts can be at least partially suppressed.

Adult↗
PubMed1995

Transdermal iontophoresis and solute penetration across excised human skin.

The potential of transdermal iontophoresis to facilitate drug delivery was evaluated by studying the transport kinetics of model compounds salicylate (anion), phenylethylamine (cation), mannitol (polar neutral compound of low molecular weight), and inulin (polar neutral compound of high molecular weight) using an excised human skin model. The transport kinetics of solutes were determined across both intact and cellophane-tape-stripped dermatomed skin both in the presence and absence of applied current to probe the mechanisms of iontophoretic delivery. Iontophoresis effectively enhanced delivery of all compounds relative to passive transport. The skin is shown to be both ion selective and size selective. On the basis of results from present work and other studies, the "aqueous pathway" of iontophoretic transport is further reinforced.

Administration, Cutaneous↗
PubMed1994

Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: I. Concept and theoretical evaluation.

The concept of a flow cytometer suited for the time-resolved measurement of lanthanide chelate luminescence with a decay time on the order of 10 microseconds to 2 ms is presented and evaluated. The instrument proposed encompasses a continuous-wave laser for fluorescence excitation and an optical switch for the elimination of cellular autofluorescence decaying within 1 ns to 1 microseconds during the luminescence detection period. The slowly decaying fluorescence is to be quantified by a photon-counting system, whereas light scatter and prompt fluorescence parameters are acquired by a conventional detection system. The detection limit of the method, in terms of the smallest detectable number of fluorescing chelates per cell, is examined. It was found to be nearly 30,000 complexes of a europium chelate with a decay time of 1.6 ms and a quantum efficiency of 17%, independent of fast decaying cellular autofluorescence or prompt dye emission intensity. The probability of cells passing through the instrument without being detected while the laser beam is turned off was estimated, and the implications for cell throughput and sorting performance of the instrument were assessed. At typical fluorescence detection intervals of 500 microseconds to 1 ms, cell flow rates of 100-200 particles per second lead to detection probabilities of more than 90% and sorting purities comparable to those found in conventional fluorescence-activated cell sorting.

Chelating Agents↗
PubMed1994

Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: II. Instrument design and experimental results.

A time-resolved flow cytometer capable of measuring a luminescence with a decay time in the range of 10 microseconds to 2 ms, typical for some lanthanide chelates, is presented. The instrument permits acquisition of conventional light scatter and prompt fluorescence signals as well as detection of slowly decaying luminescence by a photon counting unit for a selectable time period of 1 microsecond to 1 ms. During photon counting, the laser beam is turned off by an acoustooptic deflector. The design of a flow chamber with an average geometrical light collection efficiency of 35% over a distance of 1.7 mm is presented and analyzed by ray tracing. A pulse processing system featuring digital integration of the conventional signals and a transputer system for the acquisition and the transfer of the measured parameter values to a host computer is described. Instrument function is verified with lyophilized human lymphocytes stained for the CD8 antigen with dye-loaded liposomes. Quantitation of cell-associated europium chelate fluorescence, displaying a decay time of 1.6 ms, is demonstrated. Elimination of fast decaying background emission generated by DNA-associated ethidium bromide is shown. The background generated by instrument components in the time-gated measurement channel is characterized, and measures for its complete elimination are discussed.

Chelating Agents↗
PubMed1993

T2 relaxation time in patients with Parkinson's disease.

Postmortem studies of patients with Parkinson's disease (PD) reveal an increase in iron concentration in the substantia nigra. Iron content in the brain is associated with decreased signal intensity on T2-weighted MRI. We measured in vivo the T2 relaxation time in 30 PD patients and 33 healthy volunteer subjects, using a 1.5-T whole-body MRI system. In comparison with healthy controls, T2 values in PD patients were reduced in the following brain regions: substantia nigra, caudate nucleus, and putamen. Due to the overlap between patients and control subjects, we could not differentiate, in a given patient, healthy from diseased state on the basis of T2 relaxation time. Our findings support the notion of increased iron deposition in the substantia nigra of patients with PD. However, the shortening of T2 values in the substantia nigra did not correlate with disease duration nor with clinical severity.

Adult↗
PubMed1992

Monte Carlo docking of oligopeptides to proteins.

A new two-step procedure has been developed for the docking of flexible oligopeptide chains of unknown conformation to static proteins of known structure. In the first step positions and conformations are sampled and the association energy minimized starting from an approximate preselected docking position. The resulting conformations are further optimized in the second step by a Metropolis Monte Carlo minimization, which optimizes each of these structures. The method has been tested on the HIV-1 aspartic proteinase complex with an inhibitor, whose crystallographic structure is known at 2.3 A resolution. Furthermore, the application of this method to the docking of the hendecapeptide 58-68 of the influenza A virus matrix protein to the HLA-A2 molecule produced results which are in agreement with experimental observations in identifying side chains critical for T cell recognition and residues responsible of MHC protein binding.

Algorithms↗
PubMed1992

Monte Carlo minimization with thermalization for global optimization of polypeptide conformations in cartesian coordinate space.

A new minimization procedure for the global optimization in cartesian coordinate space of the conformational energy of a polypeptide chain is presented. The Metropolis Monte Carlo minimization is thereby supplemented by a thermalization process, which is initiated whenever a structure becomes trapped in an area containing closely located local minima in the conformational space. The method has been applied to the endogenous opioid pentapeptide methionine enkephalin. Five among 13 different starting conformations led to the same apparent global minimum of an in-house developed energy function, a type II' reverse turn, the central residues of which are Gly-3-Phe-4. A comparison between the ECEPP/2 global minimum conformation of methionine enkephalin and the apparent one achieved by the present method shows that minimum-energy conformations having a certain similarity can be generated by relatively different force fields.

Amino Acid Sequence↗
PubMed1992

[A Doppler ultrasound device for determining blood volume flow].

A novel ultrasonic quantitative Doppler procedure has been developed which allows for the measurement of real-time volume flow in large blood vessels. It makes use of a 2D array transducer, which enables parallel sampling of a measuring slice placed in normal position to the sound beam. With this arrangement, volume flow can be computed without measuring the angle of incidence. Moreover, the 2D velocity distribution can be assessed within intervals of 10 to 30 ms.

Blood Flow Velocity↗
PubMed1992

Fluorescence spectroscopy for identification of atherosclerotic tissue.

OBJECTIVE: Vessel perforation and limited steerability of the laser light are the major limitations of laser angioplasty. To improve steerability fluorescence spectroscopy has been proposed for identification of atherosclerotic plaques. The aim was to investigate this. METHODS: Fluorescence spectroscopy with three different excitation wavelengths (325 nm, 380 nm, 450 nm) was tested in an emission range of 400 nm to 600 nm. Intensity ratios at 480/420 nm were determined in different types of blood vessels. Necropsy material from 40 patients (punch biopsies of 4 mm diameter from the coronary and carotid artery as well as from the ascending and descending aorta) was studied spectroscopically. Histological alterations of the vessel wall were assessed by a semiquantitative score (0 to 10 points): (a) normal tissue, 0 to 2 points (mean = 0.25; n = 38); (b) mild atherosclerotic lesions, 3 to 5 points (mean = 3.35; n = 39); (c) severe atherosclerotic lesions, greater than or equal to 6 points (mean = 6.75; n = 43). RESULTS: Best spectroscopic results were obtained with an excitation wavelength of 325 nm. In samples with severe atherosclerotic lesions the fluorescence spectra showed a significant reduction of the emitted wavelength intensities when compared to normal tissue. There was a clear separation of the fluorescence spectra between normal and mild as well as between normal and severe atherosclerotic lesions; normal tissue showed an increased intensity in the range from 420 nm to 540 nm, whereas atherosclerotic lesions had no or only a small peak at 480 nm. There was a significant correlation between the semiquantitative score (n = 120) and the fluorescence ratio at 480/420 nm (excitation wavelength 325 nm) with a correlation coefficient of 0.87. The spectroscopic results showed no differences between the samples taken from different types of vessels. CONCLUSIONS: Fluorescence spectroscopy allows a reliable identification of normal and atherosclerotic lesions. The close correlation between the emitted light intensity ratio at 480/420 nm and the histological alterations of the vessel wall suggests a relationship between vessel wall fluorescence and the atherosclerotic alterations of the wall.

Adolescent↗
PubMed1991

Left ventricular wall thickness measurements by magnetic resonance: a validation study.

Left ventricular (LV) wall thickness was determined by magnetic resonance (MR) in 15 patients (7 controls and 8 patients with coronary artery disease). End-diastolic (ed) and end-systolic (es) wall thickness were measured in a short axis view perpendicular to the LV long axis. Wall thickness measurements were compared to data obtained by digital subtraction angiography (DSA) and M-mode echocardiography (Echo). End-diastolic and end-systolic wall thickness were significantly overestimated by MR (34% and 37%, respectively) when compared to DSA. In contrast, LV end-diastolic and end-systolic chamber diameter were significantly underestimated by MR (25% and 30%, respectively) when compared to DSA. However, fractioned shortening was similar (all NS) for MR (48 +/- 22%), DSA (54 +/- 15%) and Echo (44 +/- 10%), respectively. The mean difference (= accuracy) and the standard deviation of difference (= precision) for LV wall thickness was 0.4 +/- 0.2 cm between MR and DSA, 0.4 +/- 0.3 cm between MR and ECHO and 0.03 +/- 0.1 cm between DSA and ECHO. The correlation of wall thickness between MR and DSA (correlation coefficient r = 0.74, p less than 0.001) and between MR and Echo (r = 0.70, p less than 0.001) was good although the standard error of estimate (SEE) was 17% for MR vs. DSA and 21% for MR vs. Echo. The corresponding SEE for chamber diameter was 16% between MR and DSA and 19% between MR and Echo, respectively. Intraobserver variability for wall thickness determination by MR was excellent (correlation coefficient r = 0.99, p less than 0.001) SEE of 4%. Interobserver variability was also good (correlation coefficient r = 0.90, p less than 0.001) with a SEE of 12%. It is concluded that LV wall thickness and chamber diameter (short axis plane) can be determined by MR with good precision but only satisfactory accuracy. LV wall thickness is significantly overestimated probably due to signals from static blood which might be indistinguishable from the subendocardium.

Angiography, Digital Subtraction↗
PubMed1990

The poststenotic vessel segment during dynamic exercise: effect of oral isosorbide-dinitrate.

Coronary vasomotion of normal, stenotic, and poststenotic vessel segments was studied in 18 patients with coronary artery disease at rest, during submaximal bicycle exercise, and 5 min after sublingual nitroglycerin or oral isosorbide-dinitrate (ISDN) spray. Patients were divided into two groups: group 1 consisted of 10 patients with no premedication prior to exercise, and group 2 consisted of 8 patients receiving 120 mg long-acting ISDN orally 1 h before the procedure. Quantitative coronary arteriography was carried out in biplane projection using a semi-automatic computer system. The normal vessel segment showed a trend toward a small increase in cross-sectional area during exercise in both groups (+3% in group 1 and +4% in group 2, both NS). After sublingual nitroglycerin following exercise, there was a significant increase in group 1 (+29%, p less than 0.001 vs rest) but not after ISDN spray in group 2 (+5%, NS vs rest). The stenotic vessel segment showed exercise-induced stenosis narrowing in group 1 (-31%, p less than 0.01 vs rest) which was prevented by oral ISDN (+6%, NS vs rest). After exercise, sublingual administration of nitroglycerin or ISDN spray was associated with no significant change in stenosis area in either group. The poststenotic vessel segment showed no significant vasomotion during exercise in both groups (area change +6% in group 1 and +7% in group 2), but poststenotic luminal area increased after sublingual nitroglycerin (group 1: +15%, p less than 0.01 vs rest) or ISDN spray (group 2: +15%, p less than 0.05 vs rest). The mean pulmonary artery pressure increased during exercise from 22 to 39 mmHg (p less than 0.001) in group 1 and from 14 to 27 mmHg (p less than 0.001) in group 2. At rest (p less than 0.001) and during exercise (p less than 0.01) mean pulmonary pressure was lower in group 2 than in group 1. Thus, it is concluded that coronary vasomotion of the poststenotic vessel segment is only minimal during exercise and is not affected by coronary vasomotion of the stenotic vessel segment. Pretreatment with oral ISDN did not influence coronary vasomotion of the poststenotic vessel segment, but prevented exercise-induced stenosis narrowing. In the untreated patients, vasoconstriction of the stenotic vessel segment is limited to the site of the stenosis, and it appears that there is no release of vasoactive substances with vasoconstrictive influences on the poststenotic segment.

Administration, Oral↗
PubMed1990

Validation of a new automatic system for biplane quantitative coronary arteriography.

In a collaboration between the University of Texas (software) and the University of Zürich (hardware) a compact, automatic system for biplane quantitative coronary arteriography was developed. The system is based on a 35 mm film projector, a slow-scan CCD-camera (image digitizing) and a computer workstation (Apollo DN 3000, image storage and processing). A new calibration procedure based on two fixed reference points in the center of the image intensifier was used (isocenter technique). Contour detection of coronary arteries was carried out in biplane projection using a geometric-densitometric edge-detection algorithm. The proximal and distal luminal areas, as well as the minimal luminal area of the stenotic vessel segment were determined. Accuracy and precision were determined from precision drilled holes in a plexiglas cube which were filled with 50%, 75% and 100% contrast medium. The diameter of the holes ranged from 0.5 to 5.0 mm. The mean difference and the standard deviation of the differences between the true and the measured diameters were 0.12 +/- 0.14 mm for plane A and 0.26 +/- 0.17 mm for plane B, respectively. After a second order correction the mean difference amounted to 0.02 +/- 0.09 mm for plane A and 0.02 +/- 0.12 mm for plane B, respectively. Intra- and interobserver variability were evaluated in 5 patients (age 60 +/- 10 years) with coronary artery disease using 16 normal and 5 stenotic vessel segments (cross-sectional area ranging from 0.8 to 8.7 mm2). Two independent observers analyzed the same vessel segment twice. Intraobserver variability expressed as the standard error of estimate in percent of the mean angiographic vessel area (SEE) amounted to 2.1% for observer 1 and 4.4% for observer 2, respectively. Interobserver variability expressed as SEE was 4.1% for measurement 1 and 3.6% for measurement 2, respectively.

Aged↗
PubMed1990

Potential role of coronary vasoconstriction in ischaemic heart disease: effect of exercise.

Coronary vasomotion plays an important role in the regulation of coronary perfusion at rest and during exercise. Normal coronary arteries show coronary vasodilation of the proximal (+20%) and distal (+40%) vessel segments during supine bicycle exercise. However, patients with coronary artery disease show exercise-induced vasoconstriction of the stenotic vessel segments. The exact mechanism of exercise-induced stenosis narrowing is not clear but might be related to a passive collapse of the disease-free vessel wall (Venturi mechanism), elevated plasma levels of circulating catecholamines, an insufficient production of the endothelium-derived vasorelaxing factor or increased platelet aggregation due to turbulent blood flow with release of thromboxane A2 and serotonin. Various vasoactive drugs, such as nitroglycerin and calcium antagonists, prevent exercise-induced stenosis vasoconstriction. An additive effect on coronary vasodilation of the stenotic vessel segment was observed after combination of nitroglycerin with diltiazem. Thus, exercise-induced stenosis narrowing plays an important role in the pathophysiology of myocardial ischaemia during dynamic exercise. The antianginal effect of vasoactive substances can be explained--besides the effect on pre- and afterload--by a direct action on coronary stenosis vasomotion.

Angiography↗