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Biomedical subjects

H Zimmermann

Publications and source records attributed to H Zimmermann.

At least 19 recordsLinked to original sources
PubMed2006

Beyond counting cases: public health impacts of national Paediatric Surveillance Units.

Paediatric Surveillance Units (PSUs) have been established in 14 countries and facilitate national, prospective, active surveillance for a range of conditions, with monthly reporting by child health specialists. The International Network of Paediatric Surveillance Units (INoPSU) was established in 1998 and facilitates international collaboration among member PSUs and allows for sharing of resources, simultaneous data collection and hence comparison of data from different geographical regions. The impact of data collected by PSUs, both individually and collectively as members of INoPSU, on public health outcomes, clinical care and research is described.

Child↗
PubMed2006

[Evidence of new foci of tick-borne encephalitis in the French speaking part of Switzerland].

The incidence of tick-borne encephalitis (TBE) has more than doubled in Switzerland in recent years. In the French part of Switzerland several patients seem to have acquired the infection outside of known endemic foci. Thirty patients with TBE living or having acquired the infection in the French speaking part of Switzerland between 2000 and 2005 were identified. For one patient it wasn't possible to obtain precise information about the place of acquisition of the infection and 16 patients were infected in known endemic foci. Among the 13 remaining patients, 6 were infected on the southern shores of the lake of Neuchâtel and 7 in the plaine of Orbe. We conclude that there are new foci of TBE in the northern regions of the canton of Vaud. Vaccination should be proposed to the population at risk of these regions. In addition it is important that persons with outdoor activities in this regions respect the preventive

Adolescent↗
PubMed2006

Relaxation in the glass former acetylsalicylic acid studied by deuteron magnetic resonance and dielectric spectroscopy.

Supercooled liquid and glassy acetylsalicylic acid was studied using dielectric spectroscopy and deuteron relaxometry in a wide temperature range. The supercooled liquid is characterized by major deviations from thermally activated behavior. In the glass the secondary relaxation exhibits the typical features of a Johari-Goldstein process. Via measurements of spin-lattice relaxation times the selectively deuterated methyl group was used as a sensitive probe of its local environments. There is a large difference in the mean activation energy in the glass with respect to that in crystalline acetylsalicylic acid. This can be understood by taking into account the broad energy barrier distribution in the glass.

Journal Article↗
PubMed2006

Swelling-activated pathways in human T-lymphocytes studied by cell volumetry and electrorotation.

Small organic solutes, including sugar derivatives, amino acids, etc., contribute significantly to the osmoregulation of mammalian cells. The present study explores the mechanisms of swelling-activated membrane permeability for electrolytes and neutral carbohydrates in Jurkat cells. Electrorotation was used to analyze the relationship between the hypotonically induced changes in the electrically accessible surface area of the plasma membrane (probed by the capacitance) and its permeability to the monomeric sugar alcohol sorbitol, the disaccharide trehalose, and electrolyte. Time-resolved capacitance and volumetric measurements were performed in parallel using media of different osmolalities containing either sorbitol or trehalose as the major solute. Under mild hypotonic stress in 200 mOsm sorbitol or trehalose solutions, the cells accomplished regulatory volume decrease by releasing cytosolic electrolytes presumably through pathways activated by the swelling-mediated retraction of microvilli. This is suggested by a rapid decrease of the area-specific membrane capacitance C(m) (microF/cm2). The cell membrane was impermeable to both carbohydrates in 200 mOsm media. Whereas trehalose permeability remained also very poor in 100 mOsm medium, extreme swelling of cells in a strongly hypotonic solution (100 mOsm) led to a dramatic increase in sorbitol permeability as evidenced by regulatory volume decrease inhibition. The different osmotic thresholds for activation of electrolyte release and sorbitol influx suggest the involvement of separate swelling-activated pathways. Whereas the electrolyte efflux seemed to utilize pathways preexisting in the plasma membrane, putative sorbitol channels might be inserted into the membrane from cytosolic vesicles via swelling-mediated exocytosis, as indicated by a substantial increase in the whole-cell capacitance C(C) (pF) in strongly hypotonic solutions.

Cell Membrane↗
PubMed2006

Isotope selection in distance measurements between nitroxides.

Self-assembly of spin-labeled synthetic macromolecules or biomacromolecules can lead to structures that contain more than two nitroxide radicals. Label-to-label distance distributions are then poorly resolved since established electron paramagnetic resonance techniques for distance measurements cannot select between the different pairs of nitroxides. A separation into different contributions can be achieved by partially labeling the nitroxide radicals by (15)N or by deuterium and applying pulse electron electron double resonance techniques. With (15)N labeling, strong suppression of either the (14)N or the (15)N contribution can be achieved by suitable choices of the excitation bandwidths and frequencies of the observer subsequence and pump pulse and linear combination of data sets. With deuterium labeling, interactions between only the isotope-labeled nitroxides can be selected by a two-dimensional version of the four-pulse double electron electron resonance experiment. This selection is based on the deep electron spin echo envelope modulation of deuterated nitroxides.

Electron Spin Resonance Spectroscopy↗
PubMed2006

Interventional magnetic resonance imaging: an alternative to image guidance with ionising radiation.

At present, interventional procedures, such as stent placement, are performed under X-ray image guidance. Unfortunately with X-ray imaging, both patient and interventionalist are exposed to ionising radiation. Furthermore, X-ray imaging is lacking soft tissue contrast and is not capable of true 3-D displays of either interventional device or tissue morphology. Magnetic resonance imaging (MRI) offers excellent soft tissue contrast, 3-D acquisition techniques, as well as rapid image acquisition and reconstruction. Despite these advantages, MR-guided interventions are challenging owing to the limited access to the patient, strong magnetic and radio-frequency fields that require special interventional devices, inferior image frame rates and spatial resolution, and high MRI scanner noise. For MR-guided intravascular interventions, where access to the target organ is achieved through catheters, dedicated hardware and automated image slice positioning techniques have been developed. We illustrate that MR-guided renal embolisations can be performed in closed-bore high-field MR scanners.

Animals↗
PubMed2006

Targeted-HASTE imaging with automated device tracking for MR-guided needle interventions in closed-bore MR systems.

Percutaneous MR-guided interventions with needles require fast pulse sequences to image the needle trajectory with minimal susceptibility artifacts. Spin-echo pulse sequences are well suited for reducing artifact size; however, even with single-shot turbo spin-echo techniques, such as rapid acquisition with relaxation enhancement (RARE) or half-Fourier acquisition single-shot turbo spin-echo (HASTE), fast imaging remains challenging. In this work we present a HASTE pulse sequence that is combined with inner-volume excitation to reduce the scan time and limit the imaging field of view (FOV) to a small strip close to the needle trajectory (targeted-HASTE). To compensate for signal saturation from fast repeated acquisitions, a magnetization restore pulse (driven equilibrium Fourier transform (DEFT)) is used. The sequence is combined with dedicated active marker coils to measure the position and orientation of the needle so that the targeted-HASTE image slice is automatically repositioned. In an animal experiment the coils were attached to an MR-compatible robotic assistance system for MR-guided interventions. Needle insertion and infusion via the needle could be visualized with a temporal resolution of 1 s, and the needle tip could be localized even in the presence of a stainless steel mandrel.

Animals↗
PubMed2005

Combining high-field EPR with site-directed spin labeling reveals unique information on proteins in action.

In the last decade, joint efforts of biologists, chemists and physicists have helped in understanding the dominant factors determining specificity and directionality of transmembrane transfer processes in proteins. In this endeavor, electron paramagnetic resonance (EPR) spectroscopy has played an important role. Characteristic examples of such determining factors are hydrogen-bonding patterns and polarity effects of the microenvironment of protein sites involved in the transfer process. These factors may undergo characteristic changes during the reaction and, thereby, control the efficiency of biological processes, e.g. light-induced electron and proton transfer across photosynthetic membranes or ion-channel formation of bacterial toxins. In case the transfer process does not involve stable or transient paramagnetic species or states, site-directed spin labeling with suitable nitroxide radicals still allows EPR techniques to be used for studying structure and conformational dynamics of the proteins in action. By combining site-directed spin labeling with high-field/high-frequency EPR, unique information on the proteins is revealed, which is complementary to that of X-ray crystallography, solid-state NMR, FRET, fast infrared and optical spectroscopic techniques. The main object of this publication is twofold: (i) to review our recent spin-label high-field EPR work on the bacteriorhodopsin light-driven proton pump from Halobacterium salinarium and the Colicin A ion-channel forming bacterial toxin produced in Escherichia coli, (ii) to report on novel high-field EPR experiments for probing site-specific pK(a) values in protein systems by means of pH-sensitive nitroxide spin labels. Taking advantage of the improved spectral and temporal resolution of high-field EPR at 95 GHz/3.4 T and 360 GHz/12.9 T, as compared to conventional X-band EPR (9.5 GHz/0.34 T), detailed information on the transient intermediates of the proteins in biological action is obtained. These intermediates can be observed and characterized while staying in their working states on biologically relevant timescales. The paper concludes with an outlook of ongoing high-field EPR experiments on site-specific protein mutants in our laboratories at FU Berlin and Osnabrück.

Bacteriorhodopsins↗
PubMed2005

Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation.

The concept of encapsulated-cell therapy is very appealing, but in practice a great deal of technology and know-how is needed for the production of long-term functional transplants. Alginate is one of the most promising biomaterials for immunoisolation of allogeneic and xenogeneic cells and tissues (such as Langerhans islets). Although great advances in alginate-based cell encapsulation have been reported, several improvements need to be made before routine clinical applications can be considered. Among these is the production of purified alginates with consistently high transplantation-grade quality. This depends to a great extent on the purity of the input algal source as well as on the development of alginate extraction and purification processes that can be validated. A key engineering challenge in designing immunoisolating alginate-based microcapsules is that of maintaining unimpeded exchange of nutrients, oxygen and therapeutic factors (released by the encapsulated cells), while simultaneously avoiding swelling and subsequent rupture of the microcapsules. This requires the development of efficient, validated and well-documented technology for cross-linking alginates with divalent cations. Clinical applications also require validated technology for long-term cryopreservation of encapsulated cells to maintaining a product inventory in order to meet end-user demands. As shown here these demands could be met by the development of novel, validated technologies for production of transplantation-grade alginate and microcapsule engineering and storage. The advances in alginate-based therapy are demonstrated by transplantation of encapsulated rat and human islet grafts that functioned properly for about 1 year in diabetic mice.

Alginates↗
PubMed2005

Real-time 3-D dark-field microscopy for the validation of the cross-linking process of alginate microcapsules.

Alginate-based microencapsulation is a promising method for long-term maintenance of cellular and membrane function of the cells and tissue fragments required for in vitro and in vivo biosensors, for tissue engineering and particularly for immunoisolation of non-autologous transplants. Microcapsules of high mechanical strength and optimum permeability can be produced by injection of BaCl2 crystals into alginate droplets before they come into contact with external Ba2+. A key requirement is that the system parameters (number of crystals, speed of the crystal stream etc.) are properly adjusted according to the mannuronic and guluronic acid ratio and the average molecular mass of the alginate as well as to the diameter of the microcapsules. Robust, reliable, rapid and low-cost validation tools are, therefore, needed for assurance of the microcapsule quality. Here, we describe a novel three-dimensional (3-D) dark-field microscopy that allows the real-time measurement of the number and spatial distribution of the injected Ba2+ ions throughout the microcapsules after treatment with sulphate. This novel method requires only a conventional microscope equipped with three polarising filters and a double aperture stop. In contrast to confocal laser scanning microscopy images, peripherally attached BaSO4 precipitates can clearly be distinguished from internal ones. The data also demonstrate that several steps of the alginate gelling process must be improved before such immunoisolation can be used in patients.

Alginates↗
PubMed2005

[Epidemiology of tick-borne encephalitis (TBE) in Switzerland 1984 to 2004].

From 1984 to 2004 a total of 1370 TBE cases have been reported to the Federal Office of Public Health through the notification system. A significant increase of cases was observed in the nineties. Since 1999 the yearly average of reported cases was 101, corresponding to a yearly incidence of 1.4/10(5) inhabitants for all of Switzerland or to an incidence of approximately 6/10(5) if only the population living in endemic regions is taken into account. Male cases were twice as frequent as female ones. The age distribution showed two peaks in the age ranges of 6 to 14 and 60 to 69 years. Cases in children under 6 years of age were very rare with a yearly average of two hospitalised children. The severity of the disease increased with age. In 86% of the patients CNS involvement was present while 14% showed only flu-like symptoms. Ninety percent of patient with CNS involvement were hospitalised, 1,3% died (on average one death per year since 1999). Cases in fully vaccinated persons were very rare. The majority of patients had most probably been infected at their place of residence or in the nearer surroundings. The incidence in the large cities was low (< or = 1/10(5)/year). In smaller towns located directly in an endemic region, the incidence rose to as much as 18/10(5)/year. During the 21 years of observation, the endemic regions in four cantons known in the early eighties had clearly expanded and new infected regions appeared in seven other cantons. A frequent recreational or occupational exposure in wooded areas was mentioned by 85% of the patients. Although 80% of these concerned leisure time activities (mainly walking), the incidence is most probably still higher in occupationally exposed persons. This indicates that not only persons with leisure time exposure but also occupationally exposed persons are still insufficiently vaccinated to achieve an optimal control of this disease in Switzerland.

Adolescent↗
PubMed2005

[Polytrauma on the way. Simple measures for efficient life-saving care!].

The General Practitioner (GP) doesn't usually treat polytrauma often. However in Switzerland there are many remote areas where he is first on the scene of the accident. Thus it is important that he knows basic treatment principles in this situation such as the ABC according to the ATLS guidelines. We give a short overview of these important principles.

Algorithms↗
PubMed2005

[Abdominal pain in emergency service--what should I not forget?].

Abdominal pain for the General Practitioner (GP) is an important problem and presents as a significant challenge since the complaint emerges to the primary care provider as one of the 3 most important complaints. This paper serves as a facilitator and guide in helping the General Practitioner differentiate between the so-called normal abdominal pain versus severe abdominal pain which should be referred to a specialist. One of the most important messages the paper attempts to convey is that patients have to be seen and personally examined by the General practitioner. This is a paramount feature in establishing course of severity and outcome. Since approximately 25% of all presenting abdominal pain complaints are unclear, even to the experienced specialist, the authors attempt to direct a focused exam by means of a thorough history and physical examination and then to formulate a decision tree regarding the question of referral or continued primary care by the provider.

Abdominal Pain↗
PubMed2004

Electric-field driven director oscillations in a nematic liquid crystal: a NMR investigation.

We have investigated the oscillatory behavior of the nematic director for 4-pentyl-4'-cyanobiphenyl (5CB) when it is subjected to a static magnetic field and a sinusoidal electric field. In these experiments the two fields were inclined at about 50 degrees and the frequency of the electric field was varied from several hertz to approximately 1000 Hz. The director orientation was measured using time-resolved deuterium NMR spectroscopy since this has the advantage of being able to determine the state of director alignment in the sample. In fact, for all of the frequencies studied the director is found to remain uniformly aligned. Since the diamagnetic and dielectric anisotropies are both positive the director oscillates in the plane formed by the two fields. These oscillations were observed to continue for many cycles, indicating that the coherence in the director orientation was not lost during this motion. The maximum and minimum angles made by the director with the magnetic field were determined, as a function of frequency, from the NMR spectrum averaged over many thousand cycles of the oscillations. At low frequencies (several hertz) these limiting angles are essentially independent of frequency but as the frequency increases the two angles approach each other and become equal at high frequencies, typically 1000 Hz. Our results are well explained by a hydrodynamic theory in which the sinusoidal time dependence of the electric field is included in the torque-balance equation. This analysis also shows that, for a range of frequencies between the high and low limits, these NMR experiments can give dynamic as well as static information concerning the nematic phase.

Journal Article↗
PubMed2004

Intracellular delivery of carbohydrates into mammalian cells through swelling-activated pathways.

Volume changes of human T-lymphocytes (Jurkat line) exposed to hypotonic carbohydrate-substituted solutions of different composition and osmolality were studied by videomicroscopy. In 200 mOsm media the cells first swelled within 1-2 min and then underwent regulatory volume decrease (RVD) to their original isotonic volume within 10-15 min. RVD also occurred in strongly hypotonic 100 mOsm solutions of di- and trisaccharides (trehalose, sucrose, raffinose). In contrast to oligosaccharide media, 100 mOsm solutions of monomeric carbohydrates (glucose, galactose, inositol and sorbitol) inhibited RVD. The complex volumetric data were analyzed with a membrane transport model that allowed the estimation of the hydraulic conductivity and volume-dependent solute permeabilities. We found that under slightly hypotonic stress (200 mOsm) the cell membrane was impermeable to all carbohydrates studied here. Upon osmolality decrease to 100 mOsm, the membrane permeability to monomeric carbohydrates increased dramatically (apparently due to channel activation caused by extensive cell swelling), whereas oligosaccharide permeability remained very poor. The size-selectivity of the swelling-activated sugar permeation was confirmed by direct chromatographic measurements of intracellular sugars. The results of this study are of interest for biotechnology, where sugars and related compounds are increasingly being used as potential cryo- and lyoprotective agents for preservation of rare and valuable mammalian cells and tissues.

Biological Transport↗
PubMed2004

2D TRIPLE in orientationally disordered samples--a means to resolve and determine relative orientation of hyperfine tensors.

The two-dimensional (2D) TRIPLE experiment provides correlations between electron-nuclear double resonance (ENDOR) frequencies that belong to the same electron-spin manifold, M(S), and therefore allows to assign ENDOR lines to their specific paramagnetic centers and M(S) manifolds. This, in turn, also provides the relative signs of the hyperfine couplings. So far this experiment has been applied only to single crystals, where the cross-peaks in the 2D spectrum are well resolved with regular shapes. Here we introduce the application of the 2D TRIPLE experiment to orientationally disordered systems, where it can resolve overlapping powder patterns. Moreover, analysis of the shape of the cross-peaks shows that it is highly dependent on the relative orientation of the hyperfine tensors of the two nuclei contributing to this particular peak. This is done initially through a series of simulations and then demonstrated experimentally at a high field (W-band, 95 GHz). The first example concerned the (1)H hyperfine tensors of the stable radical alpha,gamma-bisdiphenylene-beta-phenylallyl (BDPA) immobilized in a polystyrene matrix. Then, the experiment was applied to a more complex system, a frozen solution of Cu(II)-bis(2,2':6',2'' terpyridine) complex. There, the 2D TRIPLE experiment was combined with the variable mixing time (VMT) ENDOR experiment, which determined the absolute sign of the hyperfine couplings involved, and orientation selective ENDOR experiments. Analysis of the three experiments gave the hyperfine tensors of a few coupled protons.

Journal Article↗