Biomedical subjects

Patrick Hunziker

Publications and source records attributed to Patrick Hunziker.

18 recordsLinked to original sources

PubMed2007

Screening cell surface receptors using micromosaic immunoassays.

This report presents a general method for screening cell surface receptors using so-called micromosaic immunoassays. This method employs a microfluidic chip having n (n = 11) independent flow paths to move cells over m (m = 11) lines of surface-patterned antibodies for screening individual cells in a parallel, combinatorial, fast and flexible manner. The antibodies are patterned as 30-microm-wide lines on a poly(dimethylsiloxane) layer used to seal the area of the chip in which screening is being monitored. Mouse hybridoma cells having CD44 cell surface receptors and anti-CD44 antibodies were used to establish a proof-of-concept for this method. Both the capture antibodies and the cells were fluorescently labelled to allow the position of the cells to be accurately tracked over the binding sites using an inverted fluorescence microscope. The chips and cells were maintained at a constant temperature between 20 to 37 degrees C, and flow velocities of the cells over the capture areas were 100-280 microm s(-1), resulting in a approximately 0.1-0.3 s residency time of the cells on each of the eleven 30 x 30 microm s2 capture areas. Binding of the cells appeared to be specific to the capture areas, with a yield of 30% when the assay was performed at a temperature of 37 degrees C and with a slow flow velocity. We suggest that this proof-of-concept is broadly applicable to the screening of cells for medical/diagnostic purposes as well as for basic research on the interaction of cells with surfaces.

Animals↗

PubMed2006

Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents.

OBJECTIVES: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. BACKGROUND: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. METHODS: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivitäts Trial). The primary focus of this observation was cardiac death/MI. RESULTS: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. CONCLUSIONS: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis.

Aged↗

PubMed2006

Capillary pumps for autonomous capillary systems.

Autonomous capillary systems (CSs), where liquids are displaced by means of capillarity, are efficient, fast and convenient platforms for many bioanalytical applications. The proper functioning of these microfluidic devices requires displacing accurate volumes of liquids with precise flow rates. In this work, we show how to design capillary pumps for controlling the flow properties of CSs. The capillary pumps comprise microstructures of various shapes with dimensions from 15-250 microm, which are positioned in the capillary pumps to encode a desired capillary pressure. The capillary pumps are designed to have a small flow resistance and are preceded by a constricted microchannel, which acts as a flow resistance. Therefore, both the capillary pump and the flow resistance define the flow rate in the CS, and flow rates from 0.2-3.7 nL s(-1) were achieved. The placement and the shape of the microstructures in the capillary pumps are used to tailor the filling front of liquids in the capillary pumps to obtain a reliable filling behaviour and to minimize the risk of entrapping air. The filling front can, for example, be oriented vertically or tilted to the main axis of the capillary pump. We also show how capillary pumps having different hydrodynamic properties can be connected to program a sequence of slow and fast flow rates in a CS.

Journal Article↗

PubMed2006

Survival of severe amlodipine intoxication due to medical intensive care.

We report the case of attempted suicide with amlodipine, chlorthalidone and mefenamic acid and subsequent medical intensive care measures which resulted in total recovery of a 42-year-old male. After admission to the medical intensive care unit the intoxicated patient was deeply hypotensive and needed fluid replacement, dobutamine and norepinephrine. Additionally insulin and calcium gluconate were given. Since hypotension persisted and the patient developed oliguria, terlipressin was applied and finally showed an effect on blood pressure and on urinary output. A volume overload of 7 L in the first 24 h resulted in a pulmonary edema. The patient was started on non-invasive ventilation with continuous positive airway pressure (CPAP) and frusemide was added to the therapy with good success. Quantitative determination of amlodipine in plasma samples was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The highest amlodipine concentrations was measured in the plasma sample collected approximately 8 h after ingestion of the drug, and was 393 microg/L. Four days later, it was possible to stop the treatment with catecholamines, at that time the amlodipine plasma concentration had declined to 132 microg/L, still tenfold higher than therapeutic (5-18 microg/L). Elimination half-life of amlodipine is approximately 55 h. After 6 days in the intensive care unit the patient was transferred to psychiatric treatment. Intensive care management and plasma levels in this intoxication case are compared to data from literature on other cases.

Adult↗

PubMed2006

Unsupervised image classification of medical ultrasound data by multiresolution elastic registration.

Thousands of medical images are saved in databases every day and the need for algorithms able to handle such data in an unsupervised manner is steadily increasing. The classification of ultrasound images is an outstandingly difficult task, due to the high noise level of these images. We present a detailed description of an algorithm based on multiscale elastic registration capable of unsupervised, landmark-free classification of cardiac ultrasound images into their respective views (apical four chamber, two chamber, parasternal long axis and short axis views). We validated the algorithm with 90 unselected, consecutive echocardiographic images recorded during daily clinical work. When the two visually very similar apical views (four chamber and two chamber) are combined into one class, we obtained a 93.0% correct classification (chi2 = 123.8, p < 0.0001, cross-validation 93.0%; chi2 = 131.1, p < 0.0001). Classification into the 4 classes reached a 90.0% correct classification (chi2 = 205.4, p < 0.0001, cross-validation 82.2%; chi2 = 165.9, p < 0.0001).

Algorithms↗

PubMed2006

Toward intelligent nanosize bioreactors: a pH-switchable, channel-equipped, functional polymer nanocontainer.

To develop an intelligent sensor-effector functionality on the nanoscale, a pH-switchable, controlled nanoreactor based on amphiphilic copolymer membranes was built. The nanovesicles were equipped with bacterial transmembrane ompF pore proteins and the pH-sensitive enzyme acid phosphatase, resulting in a switchable substrate processing at pH 4-6.5. Ideal pH and substrate concentrations for the reaction were determined experimentally. In future, the reactor might be used for self-regulating targeted diagnostic and therapeutic applications in medicine.

Bioreactors↗

PubMed2005

Continuous flow in open microfluidics using controlled evaporation.

This paper presents a method for programming the flow rate of liquids inside open microfluidic networks (MFNs). A MFN comprises a number of independent flow paths, each of which starts with an open filling port, has a sealed microchannel in which assays can be performed, and an open capillary pump (CP). The MFN is placed over Peltier elements and its flow paths initially fill owing to capillary forces when liquids are added to the filling ports. A cooling Peltier element underneath the filling ports dynamically prevents evaporation in all filling ports using the ambient temperature and relative humidity as inputs. Another Peltier element underneath the CPs heats the pumps thereby inducing evaporation in the CPs and setting the flow rate in the microchannels. This method achieves flow rates in the microchannels ranging from approximately 1.2 nL s(-1) to approximately 30 pL s(-1), and is able to keep 90% of a 0.6 microL solution placed in an open filling port for 60 min. This simple and efficient method should be applicable to numerous assays or chemical reactions that require small and precise flow of liquids and reagents inside microfluidics.

Capillary Action↗

PubMed2005

Cell targeting by a generic receptor-targeted polymer nanocontainer platform.

Nanotechnology promises new avenues to medical diagnosis and treatment. Of special interest are injectable nanovehicles that are programmable towards specific targets, are able to evade the immune defense, and are versatile enough to be suited as carriers of complex functionality. Biotin-functionalized (poly(2-methyloxazoline)-b-poly(dimethylsiloxane)-b-poly(2-methyloxazoline) triblock copolymers were self-assembled to form nanocontainers, and biotinylated targeting ligands were attached by using streptavidin as a coupling agent. Specifically, fluorescence-labeled nanocontainers were targeted against the scavenger receptor A1 from macrophages, an important cell in human disease. In human and transgenic cell lines and in mixed cultures, receptor-specific binding of these generic carriers was followed by vesicular uptake. Low nonspecific binding supported the "stealth" properties of the carrier while cytotoxicity was absent. This versatile carrier appears promising for diagnostic or therapeutic medical use.

Animals↗

PubMed2005

Modeling and optimization of high-sensitivity, low-volume microfluidic-based surface immunoassays.

Microfluidics are emerging as a promising technology for miniaturizing biological assays for applications in diagnostics and research in life sciences because they enable the parallel analysis of multiple analytes with economy of samples and in short time. We have previously developed microfluidic networks for surface immunoassays where antibodies that are immobilized on one wall of a microchannel capture analytes flowing in the microchannel. This technology is capable of detecting analytes with picomolar sensitivity and from sub-microliter volume of sample within 45 min. This paper presents the theoretical modeling of these immunoassays where a finite difference algorithm is applied to delineate the role of the transport of analyte molecules in the microchannel (convection and diffusion), the kinetics of binding between the analyte and the capture antibodies, and the surface density of the capture antibody on the assay. The model shows that assays can be greatly optimized by varying the flow velocity of the solution of analyte in the microchannels. The model also shows how much the analyte-antibody binding constant and the surface density of the capture antibodies influence the performance of the assay. We then derive strategies to optimize assays toward maximal sensitivity, minimal sample volume requirement or fast performance, which we think will allow further development of microfluidic networks for immunoassay applications.

Antigen-Antibody Complex↗

PubMed2005

Myocardial motion analysis from B-mode echocardiograms.

The quantitative assessment of cardiac motion is a fundamental concept to evaluate ventricular malfunction. We present a new optical-flow-based method for estimating heart motion from two-dimensional echocardiographic sequences. To account for typical heart motions, such as contraction/expansion and shear, we analyze the images locally by using a local-affine model for the velocity in space and a linear model in time. The regional motion parameters are estimated in the least-squares sense inside a sliding spatiotemporal B-spline window. Robustness and spatial adaptability is achieved by estimating the model parameters at multiple scales within a coarse-to-fine multiresoluion framework. We use a wavelet-like algorithm for computing B-spline-weighted inner products and moments at dyadic scales to increase computational efficiency. In order to characterize myocardial contractility and to simplify the detection of myocardial dysfunction, the radial component of the velocity with respect to a reference point is color coded and visualized inside a time-varying region of interest. The algorithm was first validated on synthetic data sets that simulate a beating heart with a speckle-like appearance of echocardiograms. The ability to estimate motion from real ultrasound sequences was demonstrated by a rotating phantom experiment. The method was also applied to a set of in vivo echocardiograms from an animal study. Motion estimation results were in good agreement with the expert echocardiographic reading.

Algorithms↗

PubMed2005

Variational image reconstruction from arbitrarily spaced samples: a fast multiresolution spline solution.

We propose a novel method for image reconstruction from nonuniform samples with no constraints on their locations. We adopt a variational approach where the reconstruction is formulated as the minimizer of a cost that is a weighted sum of two terms: (1) the sum of squared errors at the specified points and (2) a quadratic functional that penalizes the lack of smoothness. We search for a solution that is a uniform spline and show how it can be determined by solving a large, sparse system of linear equations. We interpret the solution of our approach as an approximation of the analytical solution that involves radial basis functions and demonstrate the computational advantages of our approach. Using the two-scale relation for B-splines, we derive an algebraic relation that links together the linear systems of equations specifying reconstructions at different levels of resolution. We use this relation to develop a fast multigrid algorithm. We demonstrate the effectiveness of our approach on some image reconstruction examples.

Algorithms↗

PubMed2005

Spatio-temporal nonrigid registration for ultrasound cardiac motion estimation.

We propose a new spatio-temporal elastic registration algorithm for motion reconstruction from a series of images. The specific application is to estimate displacement fields from two-dimensional ultrasound sequences of the heart. The basic idea is to find a spatio-temporal deformation field that effectively compensates for the motion by minimizing a difference with respect to a reference frame. The key feature of our method is the use of a semi-local spatio-temporal parametric model for the deformation using splines, and the reformulation of the registration task as a global optimization problem. The scale of the spline model controls the smoothness of the displacement field. Our algorithm uses a multiresolution optimization strategy to obtain a higher speed and robustness. We evaluated the accuracy of our algorithm using a synthetic sequence generated with an ultrasound simulation package, together with a realistic cardiac motion model. We compared our new global multiframe approach with a previous method based on pairwise registration of consecutive frames to demonstrate the benefits of introducing temporal consistency. Finally, we applied the algorithm to the regional analysis of the left ventricle. Displacement and strain parameters were evaluated showing significant differences between the normal and pathological segments, thereby illustrating the clinical applicability of our method.

Artificial Intelligence↗

PubMed2004

Multiscale motion mapping: a novel computer vision technique for quantitative, objective echocardiographic motion measurement independent of Doppler: first clinical description and validation.

BACKGROUND: Objective, quantitative, segmental noninvasive/bedside measurement of cardiac motion is highly desirable in cardiovascular medicine, but current technology suffers from significant drawbacks, such as subjectivity of conventional echocardiographic reading, angle dependence of tissue Doppler measurements, radiation exposure by computer tomography, and infrastructure requirements in MRI. We hypothesized that computer vision technology could represent a powerful new paradigm for quantification in echocardiography. METHODS AND RESULTS: We present multiscale motion mapping, a novel computer vision technology that is based on mathematical image processing and that exploits echocardiographic information in a fashion similar to the human visual system. It allows Doppler- and border-independent determination of motion and deformation in echocardiograms at arbitrary locations. Correctness of the measurements was documented in synthetic echocardiograms and phantom experiments. Exploratory case studies demonstrated its usefulness in a series of complex motion analyses that included abnormal septal motion and analysis of myocardial twisting. Clinical applicability was shown in a consecutive series of echocardiograms, in which good feasibility, good correlation with expert rating, and good intraobserver and interobserver concordance were documented. Separate assessment of 2D displacement and deformation at the same location was successfully applied to elucidate paradoxical septal motion, a common clinical problem. CONCLUSIONS: This is the first clinical report of multiscale motion mapping, a novel approach to echocardiographic motion quantification. For the first time, full 2D echocardiographic assessment of both motion and deformation is shown to be feasible. Overcoming current limitations, this computer vision-based technique opens a new door to objective analysis of complex heart motion.

Algorithms↗

PubMed2004

Simultaneous detection of C-reactive protein and other cardiac markers in human plasma using micromosaic immunoassays and self-regulating microfluidic networks.

We show a proof-of-concept in which we combine our previously published concepts of micromosaic immunoassays (microMIAs) with self-regulating microfluidic networks (microFNs) to detect C-reactive protein (CRP) and other cardiac markers such as myoglobin (Mb) and cardiac Troponin I (cTnI). The microFNs are microfabricated in Si, have a well-defined surface chemistry, and are affixed to a bibulous material so as to self-regulate the displacement of an aliquot of liquid through the microFNs using capillary forces. An open section of the channels of the microFNs is covered with a hydrophobic poly(dimethylsiloxane) (PDMS) slab that acts as the substrate for a solid-phase immunoassay. Here, individual assays are conducted using independent channels. These assays are "sequential": series of samples, reagents, and buffers are displaced one after the other over the PDMS surface, and, as these assays are conducted under "microfluidic" conditions, they are fast to perform, very economical in their use of reagents, extremely integrated, and yield high-quality signals. The combinatorial character of microMIAs is exploited to optimize the assay parameters for detecting CRP. In particular, we found it optimal to deposit the capture antibody for CRP on PDMS at a concentration between 20 and 500 microg ml(-1) in PBS in 1 min and to detect captured CRP in 2 min using a detection antibody having a concentration in PBS of 120 microg ml(-1). With this method, CRP is quantitatively detected within 10 min in one microliter of human plasma down to concentrations of 30 ng ml(-1), which suggests the possibility to detect CRP at clinically relevant concentrations for the management of coronary heart disease (CHD) and systemic inflammation.

Antibodies↗

PubMed2004

Multiresolution moment filters: theory and applications.

We introduce local weighted geometric moments that are computed from an image within a sliding window at multiple scales. When the window function satisfies a two-scale relation, we prove that lower order moments can be computed efficiently at dyadic scales by using a multiresolution wavelet-like algorithm. We show that B-splines are well-suited window functions because, in addition to being refinable, they are positive, symmetric, separable, and very nearly isotropic (Gaussian shape). We present three applications of these multiscale local moments. The first is a feature-extraction method for detecting and characterizing elongated structures in images. The second is a noise-reduction method which can be viewed as a multiscale extension of Savitzky-Golay filtering. The third is a multiscale optical-flow algorithm that uses a local affine model for the motion field, extending the Lucas-Kanade optical-flow method. The results obtained in all cases are promising.

Algorithms↗

PubMed2003

A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents.

OBJECTIVES: The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up. BACKGROUND: Randomized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days. METHODS: After successful coronary stent implantation, 700 patients with 899 lesions were randomly assigned to receive a four-week course of either 500 mg ticlopidine (n = 345) or 75 mg clopidogrel (n = 355) in addition to 100 mg aspirin. Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months. RESULTS: Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel (hazard ratio with ticlopidine compared with clopidogrel, 0.30; 95% confidence interval [CI], 0.14 to 0.66; p = 0.003). After adjustment for co-variables, ticlopidine reduced the risk of cardiovascular death by 63% compared with clopidogrel. The combined end point of cardiovascular death or nonfatal myocardial infarction was present in 19 patients assigned ticlopidine, compared with 40 patients assigned clopidogrel (hazard ratio, 0.45; p = 0.005). The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 (95% CI, 0.14 to 0.64; p = 0.002). CONCLUSIONS: After the placement of coronary artery stents in unselected patients, ticlopidine was associated with a significantly lower mortality than clopidogrel. This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies.

Aged↗

PubMed2002

Impact of intracoronary ultrasound guidance on long-term outcome of percutaneous coronary interventions in diabetics--insights from the randomized SIPS trial.

BACKGROUND: The Strategy for Intravascular ultrasound (IVUS) guided PTCA and Stenting (SIPS) trial included a prospectively designed subgroup analysis to investigate whether routine IVUS-guidance during percutaneous intervention improves long-term outcome in diabetics. METHODS AND RESULTS: Consecutive diabetic patients (n = 43) with 57 lesions were randomly assigned to receive provisional stenting with angiographic guidance only (ANGIO) or with IVUS guidance provided by a combined IVUS/variable diameter balloon catheter (IVUS). The combined primary endpoint included death, nonfatal myocardial infarction and target vessel revascularisation (TVR) and was recorded for 28 months. The re-stenosis rate at 6-month follow-up angiography was defined as a secondary endpoint. A primary endpoint occurred in 6 diabetic patients (31.6%) in the IVUS-group and 11 diabetic patients (45.8%) in the ANGIO-group (relative risk for IVUS, 0.83, 95% confidence interval 0.28-2.35, p = 0.83). Kaplan-Meier analysis suggested that IVUS did slightly attenuate the negative effect of diabetes on long-term event-free survival. The quantitative assessment of follow-up angiography revealed that the incidence of re-stenosis was high in both groups (IVUS: 53% versus ANGIO: 52%, p = 0.94). There was no difference in the mean duration of hospitalisation (11.8 days with IVUS versus 11.2 days with ANGIO, p = 0.83) or total cost (US dollars 16,725 with IVUS versus US dollars 16,230 with ANGIO, p = 0.83) during follow-up. CONCLUSION: Routine IVUS-guidance during provisional stenting seems to slightly attenuate the negative effect of diabetes on long-term outcome. However, the re-stenosis rate remains very high.

Aged↗

PubMed2002

Biopsy of right atrial angiosarcoma guided by transesophageal echocardiography.

When an intracardiac mass is detected, a histologic examination is frequently needed before making critical treatment modality decisions. This demands an open-chest procedure, often with cardiopulmonary bypass, with its associated morbidity. We describe a closed-chest approach using echocardiographically guided catheter biopsy.

Biopsy↗