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Biomedical subjects

D Niemann

Publications and source records attributed to D Niemann.

10 recordsLinked to original sources

Physiologic and anatomic assessment of a canine carotid artery stenosis model utilizing phase contrast with vastly undersampled isotropic projection imaging.

BACKGROUND AND PURPOSE: Noninvasive assessment of the hemodynamic significance of carotid stenosis is often performed with MR angiography and supplemented with carotid Doppler sonography. Phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR), a novel MR imaging technique, accelerates phase-contrast MR flow imaging and provides both images of the vessels and measurements of blood-flow velocities. For this study, we determined the accuracy of PC-VIPR blood-flow velocity measurements to determine pressure gradients across an experimental carotid stenosis. MATERIALS AND METHODS: A focal stenosis was surgically created in each common carotid artery of 6 canines. Digital subtraction angiography (DSA) was performed, and the degree of stenosis was determined using the North American Symptomatic Carotid Endarterectomy Trial methodology. A microcatheter was positioned in the carotid artery proximal and distal to the stenosis, and pressures were measured in the vessel through the catheter. PC-VIPR was then performed on a 1.5T MR imaging scanner with parameters producing 0.8-mm isotropic voxel resolution. From the velocity measurements, pressure gradients were calculated from the Navier-Stokes relationship to compare with the pressures measured by a catheter. RESULTS: Carotid stenoses in the 50%-85% range were produced in the 12 arteries. Pressure gradients across the stenoses ranged from 6 to 26 mm Hg. The pressure gradient calculated from the PC-VIPR data correlated (r = 0.91, P < .0001) with the actual pressure measurements. CONCLUSION: With PC-VIPR, a novel MR imaging technique, the hemodynamic effect of a stenosis on flow and pressure can be evaluated.

Animals↗

Embolisation of spinal dural arteriovenous fistulae with Onyx.

Surgery is currently the standard treatment for spinal dural arteriovenous fistulae (DAVF). Endovascular embolisation of these lesions using N-butyl cyanoacrylate (NBCA) has a high success rate. Onyx is a new liquid embolic agent whose viscosity makes it suitable for treatment of spinal DAVF where penetration into the proximal radicular vein is required. It is delivered with greater control than NBCA without the necessity for rapid withdrawal of the catheter and may therefore overcome some of the drawbacks of NBCA. We report two patients who underwent Onyx embolisation of spinal DAVF; to our knowledge this is the first such report.

Angiography↗

Kinetically assisted potential sputtering of insulators by highly charged ions.

A new form of potential sputtering has been found for impact of slow ( < or = 1500 eV) multiply charged Xe ions (charge states up to q = 25) on MgO(x). In contrast to alkali-halide or SiO2 surfaces this mechanism requires the simultaneous presence of electronic excitation of the target material and of a kinetically formed collision cascade within the target in order to initiate the sputtering process. This kinetically assisted potential sputtering mechanism has been identified to be present for other insulating surfaces as well.

Journal Article↗

Regulation of human immunodeficiency virus type 1 infection, beta-chemokine production, and CCR5 expression in CD40L-stimulated macrophages: immune control of viral entry.

Mononuclear phagocytes (MP) and T lymphocytes play a pivotal role in the host immune response to human immunodeficiency virus type 1 (HIV-1) infection. Regulation of such immune responses can be mediated, in part, through the interaction of the T-lymphocyte-expressed molecule CD40 ligand (CD40L) with its receptor on MP, CD40. Upregulation of CD40L on CD4+ peripheral blood mononuclear cells during advanced HIV-1 disease has previously been reported. Based on this observation, we studied the influence of CD40L-CD40 interactions on MP effector function and viral regulation in vitro. We monitored productive viral infection, cytokine and beta-chemokine production, and beta-chemokine receptor expression in monocyte-derived macrophages (MDM) after treatment with soluble CD40L. Beginning 1 day after infection and continuing at 3-day intervals, treatment with CD40L inhibited productive HIV-1 infection in MDM in a dose-dependent manner. A concomitant and marked upregulation of beta-chemokines (macrophage inhibitory proteins 1alpha and 1beta and RANTES [regulated upon activation normal T-cell expressed and secreted]) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) was observed in HIV-1-infected and CD40L-treated MDM relative to either infected or activated MDM alone. The addition of antibodies to RANTES or TNF-alpha led to a partial reversal of the CD40L-mediated inhibition of HIV-1 infection. Surface expression of CD4 and the beta-chemokine receptor CCR5 was reduced on MDM in response to treatment with CD40L. In addition, treatment of CCR5- and CD4-transfected 293T cells with secretory products from CD40L-stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to inhibition of viral entry. In conclusion, we demonstrate that CD40L-mediated inhibition of viral entry coincides with a broad range of MDM immune effector responses and the down-modulation of CCR5 and CD4 expression.

CD40 Ligand↗

[Comparison of two different educational concepts in general practice].

In a postgraduate training course in general practice in Hamburg two different educational concepts were used and compared with each other. One was oriented more towards problem-based learning, the other more towards lectures. The participants were asked to fill in a written questionnaire after each day (n = 970) and at the end of the course (n = 26). Both courses achieved good results. On a five point scale the median of the general satisfaction was 4. The problem oriented course, however, was judged better than the other in many respects.

Education, Medical, Continuing↗

Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia.

The mechanism(s) by which HIV-1 affects neural injury in HIV-1-associated dementia (HAD) remains unknown. To ascertain the role that cellular and viral macrophage products play in HAD neurotoxicity, we explored one potential route for neuronal demise, CXCR4. CXCR4, expressed on lymphocytes and neurons, is both a part of neural development and a co-receptor for HIV-1. Its ligand, stromal cell-derived factor-1alpha (SDF-1alpha), affects neuronal viability. GTP binding protein (G-protein) linked signaling after neuronal exposure to SDF-1alpha, virus-infected monocyte-derived macrophage (MDM) secretory products, and virus was determined. In both human and rat neurons, CXCR4 was expressed at high levels. SDF-1alpha/beta was detected predominantly in astrocytes and at low levels in MDM. SDF-1beta/beta was expressed in HAD brain tissue and upregulated in astrocytes exposed to virus infected and/or immune activated MDM conditioned media (fluids). HIV-1-infected MDM secretions, virus and SDF-1beta induced a G inhibitory (Gi) protein-linked decrease in cyclic AMP (cAMP) and increase inositol 1,4, 5-trisphosphate (IP3) and intracellular calcium. Such effects were partially blocked by antibodies to CXCR4 or removal of virus from MDM fluids. Changes in G-protein-coupled signaling correlated, but were not directly linked, to increased neuronal synaptic transmission, Caspase 3 activation and apoptosis. These data, taken together, suggest that CXCR4-mediated signal transduction may be a potential mechanism for neuronal dysfunction during HAD.

AIDS Dementia Complex↗

Lymphotropic virions affect chemokine receptor-mediated neural signaling and apoptosis: implications for human immunodeficiency virus type 1-associated dementia.

Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis.

AIDS Dementia Complex↗

[General practice quality circles in the large city. Participation by Hamburg general physicians].

Quality circles (peer review) will play an increasing and important role in ambulatory care when they are based on voluntary participation and in a setting of open discussion. Goal is the further qualification of physicians by critical reflections on their practice based on learning processes and the experiences of the participants. Reported are experiences from the unit for primary care and health service research of the Hamburg University on implementing quality circles. Engagement in quality assurance may be helpful in the shaping and professionalisation of general practice.

Attitude of Health Personnel↗