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Biomedical subjects

C Rau

Publications and source records attributed to C Rau.

At least 19 recordsLinked to original sources

[Headache after a stay in the Dominican Republic].

CASE HISTORY: In a 27-year-old female German patient severe headache and wandering paresthesias appeared one week after returning from a holiday in the Dominican Republic. After 3 weeks of ongoing symptoms she was admitted to our hospital with the suspicion of an inflammatory or infectious disease of the central nervous system. Upon admission slight stiffness of the neck, fever (38.2 C) and paresthesias of the right elbow and the right thigh were noticed. LABORATORY FINDINGS: Cerebrospinal fluid (CSF) revealed an eosinophilic pleocytosis. In the acute phase of the disease, antibodies against nematodes were found in CSF, without corresponding antibody-reactivity in serum. In the course levels of nematode antibodies in CSF increased and antibody-reactivity in serum was observed. Thorough investigation for other infectious or inflammatory causes of eosinophilic meningitis revealed no abnormalities. DIAGNOSIS, TREATMENT AND COURSE: Symptoms, onset within the typical incubation period and the eosinophilic meningitis lead to the diagnosis of a suspected Angiostrongyliasis. Successful treatment was achieved with a combination of oral albendazole and corticosteroids given for 4 weeks. CONCLUSION: Infection with larvae of Angiostrongylus cantonensis is one of the main causes of eosinophilic meningitis worldwide. Human infection can occur after ingestion of intermediate hosts or contaminated vegetables. Angiostrongyliasis has been endemic to Southeast Asia and the Pacific Basin and only recently cases from the Caribbean have been described. Headache, paresthesias and the finding of an eosinophilic meningitis in patients returning from tropical or subtropical regions should lead to the suspicion and eventually the treatment of an Angiostrongyliasis.

Adult↗

Visualizing soft tissue in the mammalian cochlea with coherent hard X-rays.

This paper concerns an important aspect of current developments in medical and biological imaging: the possibility for imaging soft tissue at relatively high resolution in the micrometer range or better, without tedious and/or entirely destructive sample preparation. Structures with low absorption contrast have been visualized using in-line phase contrast imaging. The experiments have been performed at the Advanced Photon Source, a third generation source of synchrotron radiation. The source provides highly coherent X-ray radiation with high photon flux (>10(14) photons/s) at high photon energies (5-70 keV). Thick gerbil cochlear slices have been imaged and were compared with those obtained by light microscopy. Furthermore, intact gerbil cochleae have been imaged to identify the soft tissue structures involved in the hearing process. The present experimental approach was essential for visualizing the inner ear structures involved in the hearing process in an intact cochlea.

Animals↗

Noninvasive bone replacement with a new injectable calcium phosphate biomaterial.

The use of injectable calcium phosphate (CaP) biomaterials in noninvasive surgery should provide efficient bone colonization and implantation. Two different kinds of injectable biomaterials are presently under development: ionic hydraulic bone cements that harden in vivo after injection, and an association of biphasic calcium phosphate (BCP) ceramic granules and a water-soluble polymer vehicle (a technique particularly investigated by our group), providing an injectable CaP bone substitute (IBS). In our study, we compared these two approaches, using physicochemical characterizations and in vivo evaluations in light microscopy, scanning electron microscopy, and three-dimensional microtomography with synchrotron technology. Three weeks after implantation in rabbit bone, both biomaterials showed perfect biocompatibility and bioactivity, but new bone formation and degradation of the biomaterial were significantly greater for BCP granules than for ionic cement. Newly formed bone developed, binding the BCP granules together, whereas new bone grew only on the surface of the cement, which remained dense, with no obvious degradation 3 weeks after implantation. This study confirms that BCP granules carried by a cellulosic polymer conserve bioactivity and are conducive to earlier and more extensive bone substitution than a carbonated-hydroxyapatite bone cement. The presence of intergranular spaces in the BCP preparation, as shown on microtomography imaging, seems particularly favorable, allowing body fluids to reach each BCP granule immediately after implantation. Thus, the IBS functions as a completely interconnected ceramic with total open macroporosity. This new bone replacement approach should facilitate microinvasive bone surgery and local delivery of bone therapy agents.

Animals↗

Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials.

This study used synchrotron X-ray microtomography on a micron scale to compare three-dimensional (3D) bone ingrowth after implantation of various calcium phosphate bone substitutes in a rabbit model. The advantage of using this new method for the study of biomaterials was then compared with histomorphometry for analysis of interconnection and bone ingrowth. The study focused on the newly formed bone-biomaterial interface. Macroporous Biphasic Calcium Phosphate (MBCP) ceramic blocks and two different injectable calcium phosphate biomaterials [an injectable bone substitute (IBS) consisting of a biphasic calcium phosphate granule suspension in hydrosoluble polymer and a calcium phosphate cement material (CPC)] were studied after in vivo implantation. Absorption or phase-contrast microtomography was performed with the dedicated set-up at beamline ID22. Experimental spatial resolution was between 1 and 1.4 microm, depending on experimental radiation. All calcium phosphates tested showed osteoconduction. IBS observations after 3D reconstruction showed interconnected bioactive biomaterial with total open macroporosity and complete bone ingrowth as early as 3 weeks after implantation. This experimentation was consistent with two-dimensional histomorphometric analysis, which confirmed its suitability for biomaterials. This 3D study relates the different types of bone substitution to biomaterial architecture. As porosity and interconnection increase, bone ingrowth becomes greater at the expense of the bone substitute: IBS>MBCP>CPC.

Animals↗

[Technique of pancreatic anastomosis].

Postoperative morbidity after pancreatic resection is primarily due to leakage of the pancreatic anastomosis. The duct-to-mucosa pancreatico-jejunostomy either as an end-to-end or end-to-side anastomosis is the preferred technique in our hands. The use of a temporarily catheter to drain the main pancreatic duct is optimal. The pancreatic leakage rate depends in many series on the consistence of the pancreatic parenchyma, the diameter of the major pancreatic duct and the local perfusion. A meticulous, standardized technique, the possibility to adapt the technique in case of unexpected findings and the operative routine of the surgeon are of paramount importance for achieving a low leakage rate. In so called "high volume" centers the pancreatic fistula rate today is in the range of 3 to 13% and the mortality of pancreatic head resection varies between 0.5 and 3%.

Anastomosis, Surgical↗

Elevation of vascular endothelial growth factor-A serum levels following acute myocardial infarction. Evidence for its origin and functional significance.

Following the onset of acute myocardial infarction (AMI), a number of serum parameters show well-defined changes reflecting myocardial injury. During the consecutive repair phase, compensatory processes are initiated including the formation of a collateral circulation on the basis of angiogenesis and arteriogenesis. An important angiogenic factor is vascular endothelial growth factor-A (VEGF-A), shown to be upregulated in the ischemic myocardium. It is unclear, however, whether acute myocardial ischemia leads to a detectable elevation of VEGF-A serum concentrations. With the use of an immunoradiometric assay, we measured the levels of VEGF-A in the serum of patients after AMI at defined time intervals, of patients with unstable angina pectoris (UAP) and of healthy individuals. In addition, in a small group of patients with subacute myocardial infarction VEGF-A concentrations were measured in coronary sinus blood. The data are given as median followed by the 25th and 75th percentiles. In the group with AMI serum VEGF-A measured 105 [78; 176] pg/ml on day 1 and 114 pg/ml [72; 163] pg/ml on day 3 after onset of AMI. Serum levels of VEGF-A significantly increased on day 7 after AMI to 189 [119; 373] pg/ml (P=0.0103) and on day 10 to 255 [162; 371] pg/ml (P=0.0007). The VEGF-A serum level in healthy controls and in patients with UAP measured 98 [75; 137] pg/ml and 116 [57; 140] pg/ml, respectively. Serum at day 10 after AMI contained VEGF-A at a biologically relevant concentration capable of stimulating proliferation of endothelial cells. Surprisingly, VEGF-A serum levels were similar in samples taken from the coronary sinus with 61 [43; 83] pg/ml. Therefore the main source for VEGF-A in the blood stream is not the infarcted myocardium. However, the number of platelets, a rich source of VEGF-A, is significantly increased after myocardial infarction, i.e. 284 [252; 363] x 10(9)/litre v 220 [177; 250] x 10(9)/litre. In conclusion, the time course of VEGF-A elevation following AMI strongly suggests that VEGF-A plays a role as an endogenous activator of coronary collateral formation in the human heart. The most likely source of the elevated VEGF-A are platelets, rather than the infarcted myocardium.

Acute Disease↗

Scanning tunneling microscopy study of poly-L-proline.

Differences in its peptide bonds allow the imino acid poly-L-proline to exist in two significantly different geometric structures. Form I with cis peptide bonds is supposed to be a right-handed helix and form II with trans peptide bonds a left-handed helix. Cis/trans isomerization about the proline imide is believed to cause the denaturation of a number of proteins and may be a key step in protein folding. Using scanning tunneling microscopy (STM), we present high-resolution images of air-dried poly-L-proline. It is found that the electric conductivity of one monolayer of poly-L-proline is sufficient to allow for STM imaging without significant tip-sample interaction. Only at locations where stacking of poly-L-proline chains occurs, a direct contact of the probing tip to the molecules becomes apparent and prevents us, at present, from resolving the atomic structure of the topmost layer. Our STM images of poly-L-proline show that form II is relatively rigid and forms aggregates in most cases. Form I, which is occasionally observed, is very flexible and exhibits sharp bends as well as 180 degrees backfolding. These observations confirm theoretical predictions on the existence of two peptide bond conformations of poly-L-proline.

Isomerism↗

Proposed antagonists at GABAB receptors that inhibit adenylyl cyclase in cerebellar granule cell cultures of rat.

The effects of various proposed GABAB receptor antagonists on baclofen-mediated inhibition of adenylyl cyclase were studied in cultured cerebellar granule cells from rat. (+/-)-Baclofen maximally inhibited adenylyl cyclase by approximately 60% of the basal enzyme activity with an EC50 value of 10 microM. 3-Aminopropane sulfonic acid (3-APS) and 5-aminovaleric acid (5-AVA) produced similar responses to that seen with (+/-)-baclofen. Saclofen reversed the action of (+/-)-baclofen, 50 microM, with a half maximal inhibitory concentration (IC50) of about 1.0 mM. The most effective antagonist in blocking the action of (+/-)-baclofen was 3-aminopropyl-diethoxy-methyl-phosphonic acid (CGP 35,348). In the presence of (+/-)-baclofen, 50 microM, the IC50 for CGP 35,348 was 290 microM and its inhibitory constant (KA) was 180 microM. The agonist-like actions of 3-APS and 5-AVA were antagonized by CGP 35,348 suggesting that 3-APS and 5-AVA may act as weak agonists at the GABAB receptor that inhibits adenylyl cyclase. All antagonists tested, except the new compound CGP 35,348, have very low potencies at GABAB receptors that inhibit adenylyl cyclase, though these compounds have been quite effective at other GABAB receptor-mediated events. Thus, the GABAB receptor which inhibits adenylyl cyclase differs pharmacologically from other reported GABAB receptor/effector systems and supports the existence of multiple receptor subtypes.

Adenylyl Cyclase Inhibitors↗

High-resolution, real-space imaging of conformational structures of poly-L-proline helixes.

In 1954, Edsall postulated that the imino-acid proline, which is a frequently found constituent of protein molecules, is a key determinant to the three-dimensional architecture of proteins. It not only should play a fundamental role in stabilizing helical structures of polypeptides, it should allow for sharp bends and even for a complete reversal of the direction of a helix looping back on itself. No direct evidence has yet been published to prove this prediction. Using scanning tunneling microscopy, we have presented high-resolution, real-space images of two conformations of poly-L-proline, where one structure clearly exhibits the predicted 180 degrees back-folding behavior. The measured length, 1.89 nm, of the repeating unit cells agrees with available X-ray data for poly-L-proline I with cis-peptide bonds. We further observe aggregated poly-L-proline II, consisting of highly-ordered, periodically and parallel-linked trans-peptide chains which are 2.4 nm apart from each other. Stacking of these aggregates with their orientation rotated by 90 degrees is also observed.

Microscopy, Scanning Tunneling↗