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Biomedical subjects

R Lehmann

Publications and source records attributed to R Lehmann.

At least 55 records · Page 3Linked to original sources

Cell migration in invertebrates: clues from border and distal tip cells.

Recent studies in two invertebrate systems, border cells in Drosophila melanogaster and distal tip cells in Caenorhabditis elegans, have provided important insight into the mechanisms of directed cell migration. These migrating cells are guided by extracellular signals, such as EGF, TGF-beta and netrin. In addition, metalloproteases alter the extracellular matrix of the tissue through which these cells migrate. Along the migratory path, migrating cells respond to changes in guidance signals by altering the expression of receptor signaling pathways. Finally, Dock180, CrkII and the GTPase Rac link the extracellular signals to the cellular machinery that controls cell motility.

Animals↗

Assessment of selective arterial calcium stimulation and hepatic venous sampling to localize insulin-secreting tumours.

OBJECTIVE: Non-invasive localization modalities such as ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) often fail to localize insulinomas smaller than 2 cm in diameter. Recent studies have shown that the selective arterial stimulation and hepatic venous sampling (ASVS) technique using intra-arterial calcium as the insulin secretagogue facilitates the regionalization of such occult insulinomas. This study assesses the sensitivity of ASVS in localizing insulin-secreting tumours. SUBJECTS AND METHODS: Eleven consecutive patients (8 women), aged 29-82 years, were studied over the past 4 years at our hospital. Hyperinsulinaemic hypoglycaemia due to an insulin-secreting tumour was proven in all patients. Calcium gluconate (0.025 mEq/kg body weight) was injected directly into the arteries supplying the pancreas and the liver. Insulin levels were measured in samples taken from the right hepatic vein before and 30, 60 and 120 s after each injection. The ASVS technique was performed in all 11 patients; the results were compared with the surgical findings in 10 patients and the autopsy findings in 1 case. The ASVS results were also compared with the findings of other, previously performed imaging modalities. RESULTS: ASVS correctly localized 4 insulin-secreting tumours to the head, 3 to the body, 1 to the tail, 2 to the tail or body of the pancreas and 1 to the liver. Thus, the sensitivity was 100% (11/11) whereas other localization techniques were less sensitive: 7/11 tumours were detected by angiography, 4/8 by endosonography, 3/8 by CT and 1/6 by MRI. Insulinomas (confirmed by histological examination), sized 4-25 mm, were found in 10 patients. All were cured by selective surgery and remained free of hypoglycaemia over the next 1-4 years of follow-up. An insulin-secreting neuroendocrine tumour in the liver was documented in 1 case at autopsy. CONCLUSIONS: Arterial stimulation and hepatic venous sampling is a very sensitive technique for preoperative localization of insulin-producing tumours. It can help to plan minimally invasive surgery and to select an appropriate strategy for patients suffering from malignant tumours in others.

Adult↗

Alterations of lipolytic enzymes and high-density lipoprotein subfractions induced by physical activity in type 2 diabetes mellitus.

OBJECTIVE: This study investigates the effects of regular moderate physical activity on lipolytic enzymes and plasma lipid concentration, particularly high-density lipoprotein cholesterol (HDL-C) subfractions, in patients with type 2 diabetes mellitus. DESIGN: Ten patients participated in a 3-month exercise programme without any changes in current medical therapy. The control group consisted of six patients who were matched with regard to sex, age, diabetes duration and diabetes therapy. RESULTS: Mean (+/- SE) physical activity in the intervention group increased from 70 +/- 21 to 220 +/- 28 min per week, which resulted in an increase in total HDL-C from 1.04 +/- 0.07 to 1.28 +/- 0.12 (P < 0.001). The HDL3-C subfraction increased from 0.71 +/- 0.08 to 0.86 +/- 0.08 mM (P = 0.01) with no significant changes in the HDL2-C subfraction (0.33 +/- 0.04 vs. 0.42 +/- 0.05). These changes were paralleled by an 85% increase in hepatic lipase (HL) activity, from 25.7 +/- 5.1 to 47.4 +/- 4.9 micromol x mL(-1) x h(-1) (P < 0.001) and a 45% increase in lipoprotein lipase (LPL) activity, from 16.8 +/- 3.0-24.3 +/- 2.7 micromol x mL(-1) x h(-1) (P = 0.01). Lecithin-cholesterol acyl-transferase (LCAT) activity increased by 32%, from 156 +/- 26 to 206 +/- 32 nmol x mL(-1) x h(-1) (P < 0.001). In the control group there were no significant changes in any of the variables assessed. CONCLUSIONS: Regular moderate physical activity in patients with type 2 diabetes led to an overall increase in HL, LPL, and LCAT. HL showed a more pronounced increase than LPL and LCAT. The changes in lipolytic and transferase enzyme pattern resulted in a significant increase of plasma HDL-C, mainly of the HDL3-C subfraction.

Adult↗

[Virtual rendering techniques in otologic imaging].

UNLABELLED: Virtual postprocessing techniques combine the advantages of condensing the large amounts of data provided by high-resolution (HR) cross-sectional imaging modalities with those of three-dimensional (3D) imaging. The techniques and indications for virtual representations in imaging of the middle ear (ME), internal ear (IE), and cerebellopontine angle (CPA) are presented together with practical examples. MATERIAL AND METHODS: HR data sets acquired by computed tomography (CT) and magnetic resonance imaging (MRI) in patients with ME, IE, and CPA pathologies were transferred to a workstation via an internal network to generate endo- or extraluminal 3D views by means of the volume rendering technique (VRT). The source data were acquired using scanners and imaging protocols with the highest resolution available at present: a multislice spiral CT (MSCT) with a slice thickness of 0.5 mm and a reconstruction increment of 0.2 mm and a 3D CISS sequence with a slice thickness of 0.5 mm for MRI. RESULTS: Virtual endoscopy was superior to cross-sectional images for assessing ME pathologies like dysplasia, postoperative changes, and destructive bone processes with extensive soft-tissue involvement; fibrous obliterations of the internal ear and labyrinthine dysplasia were depicted with a superior image quality on 3D renderings compared to conventional reconstruction techniques. Virtual endoscopy of the CPA and external acoustic meatus (EAM) was helpful in detecting and visualizing neurovascular conflicts and in assigning small intrameatal tumors to components of the acousticofacial bundle. A common feature of all applications was that the large numbers of source images could be reduced to a few 3D reconstructions for documentation and optimized communication of the findings between the radiologist and otologist. CONCLUSION: Virtual rendering makes an important contribution towards establishing, presenting, and documenting the findings when certain otologic pathologies have to be assessed. It can be used for routine imaging and allows for more efficient handling of the large amounts of imaging data generated by high-resolution cross-sectional imaging modalities.

Cerebellopontine Angle↗

A post-processing protocol for three-dimensional visualization of the inner ear using the volume-rendering technique based on a standard magnetic resonance imaging protocol.

A superior diagnostic quality compared to other post-processing (PP) techniques for three-dimensional (3D) inner ear imaging has been attributed to volume rendering (VR). We defined and assessed a VR protocol for 3D visualization of the inner ear in a routine imaging setting. Following definition of a VR protocol by using lower threshold values, surface shading, perspective views and related parameters, standardized 3D views of the inner ear were generated and evaluated in 32 patients suffering from sensorineural or combined hearing loss. Comprehensive inner ear visualization was achieved in 28 patients by means of two 3D shaded-surface views. Incomplete data acquisition (1/32), motion and pulsation artefacts (2/32) and interposed fluid-retaining mastoid cells (1/32) were responsible for non-diagnostic image quality in 4/32 patients. In 5/32 patients modifications of the PP protocol involving the threshold value and depth-cueing parameters helped to establish diagnostic image quality. Mean post-processing time amounted to 5.8 min per site. 3D imaging with the VR technique is suitable for routine inner ear assessment if direct VR, predefined PP protocols and standardized labyrinthine views are used.

Artifacts↗

High-resolution petrous bone imaging using multi-slice computerized tomography.

Multi-slice computerized tomography (MSCT) is considered to provide superior image quality. We defined a data acquisition protocol for high-resolution (HR) temporal bone imaging using MSCT and assessed its impact on data acquisition and post-processing (PP). The data acquisition protocol was defined in cadaveric phantom studies performed by MSCT and subsequently applied to 38 patients referred for temporal bone assessment. The parameters image quality and diagnostic value of MSCT data were assessed for the cross-sectional source images as well as for 2-dimensional (2D) reformations and 3-dimensional (3D) reconstructions by 3 radiologists by comparison with incremental HR scans of 17 patients with suspected middle ear disorders. The data acquisition protocol yielded HR images with an excellent detail resolution and a comparable image quality of cross-sectional scans and related orthogonal reformations. MSCT achieved higher scores for image quality and diagnostic value (p < 0.001, t-test) than incremental HR CT with regard to both 2D and 3D reconstructions. MSCT improves the image quality of HR cross-sectional scans as well as that of 2D and 3D PP techniques in petrous bone imaging. The radiation exposure of the eye lenses is increased by MSCT as gantry angulation is not yet possible in the helical scan mode.

Algorithms↗

Assessment of the arteriovenous cerebrovascular system by multi-slice CT. A single-bolus, monophasic protocol.

PURPOSE: We present a protocol for the non-invasive angiographic assessment of the arterial and venous cerebrovascular (CV) system by multi-slice CT. MATERIAL AND METHODS: Data acquisition was performed in a multi-slice CT scanner with a scan range from the carotid bifurcation to the vertex and manual scan start following i.v. administration of 120 ml iodinated contrast medium with a flow rate of 4 ml/s. This protocol was applied in 12 patients with symptoms of acute CV insuffiency. RESULTS: In all patients, comprehensive imaging of the arteriovenous CV system was achieved including the common carotid bifurcation, the third segment of the major cerebral arteries, the dural sinus and the internal cerebral veins. Various CV pathologies, such as a territorial artery occlusion, a thrombotic obstruction of the internal carotid artery, an intracranial arteriovenous malformation and a sinus vein thrombosis, were successfully evaluated. CONCLUSION: Comprehensive assessment of the arteriovenous CV system is possible by the use of a single-bolus, monophasic multi-slice scan technique.

Adult↗

Visualization of inner ear dysplasias in patients with sensorineural hearing loss.

PURPOSE: We evaluated a data acquisition and post-processing protocol for inner ear (IE) assessment by MR imaging in patients, suffering from various labyrinth malformations. MATERIAL AND METHODS: MR IE studies of 158 consecutive patients (316 IEs) suffering from sensorineural hearing loss without evidence of an acoustic neurinoma were reviewed for pathologies of the IE and internal acoustic meatus. High-resolution MR data of all abnormal IE studies (n=45) were post-processed to previously standardized 3D volume rendered (VR) reconstructions. RESULTS: In 9 patients (5.7%) the following IE dysplasias were detected: malformation of the cochlea (6 IEs), vestibulum (4 IEs), semicircular canals (12 IEs) and vestibular aqueduct/endolymphatic sac (10 IEs). One patient showed evidence of an aplasia of the vestibulocochlear nerve. In 4 patients multiple IE dysplasias were encountered. Comprehensive 3D visualization of all labyrinthine dysplasias was achieved by the use of two VR reconstructions. The overall time for bilateral IE assessment amounted to 30-35 min. CONCLUSION: The imaging protocol allows for rapid and comprehensive visualization of various IE dysplasias, based on a limited number of VR reconstructions.

Adolescent↗

Virtual endoscopy of the tympanic cavity based on high-resolution multislice computed tomographic data.

OBJECTIVE: This study was designed to assess the value of high-resolution multislice computed tomography (MSCT) data of the petrous bone for the virtual endoscopic visualization of the tympanic cavity. BACKGROUND: The recently introduced MSCT technology has improved spatial resolution in the z axis as well as scan speed in computed tomography. Three-dimensional rendering of high-resolution MSCT data of the petrous bone may be expected to provide endoluminal views of superior image quality, thus competing with transtympanic endoscopy (otoendoscopy). SETTING: This study was conducted at a university teaching hospital. MATERIALS AND METHODS: Cadaveric phantom studies in a MSCT scanner were performed to define a data acquisition protocol, combining adequate detail resolution with low tube current. Subsequently, the cadaveric phantom underwent otoendoscopy. The postprocessing parameters of the three-dimensional rendering protocol were chosen to produce views closely resembling the corresponding otoendoscopic images. High-resolution data from 18 patients with pathologic conditions of the middle ear, as suggested by clinical findings and assessment of cross-sectional data, were postprocessed using the volume rendering technique to generate standardized virtual endoscopic views. A total of 36 virtual endoscopic scans of the tympanic cavity were generated. RESULTS: With regard to intermediate and high-density structures, virtual endoscopic images, based on MSCT data, yielded endoluminal views closely resembling corresponding otoendoscopic views. Virtual endoscopy seems useful for imaging ossicular pathologic conditions such as dysplasia and chain disruption as well as for assessing patient status before and after otosurgery. CONCLUSION: MSCT data sets allow for generating virtual endoscopic views closely resembling otoendoscopic images. The technique is especially useful when ossicular pathologic changes are present as well as for preoperative and postoperative imaging of otologic procedures.

Endoscopy↗

Neonate with spinal hypoplasia on T12 and a localized vertebral malformation on L4.

We report a case of a neonate with sectional narrowing of the spinal cord on the level of T12 to L2 and a deformed vertebral body on a different level, L4. In previously described cases of sectional spinal dysgenesis, the vertebral and spinal cord malformations are usually found on the same level. Our case may represent a new variant of spinal dysgenesis.

Humans↗

Successful stent-graft repair of a vertebrojugular arteriovenous fistula.

PURPOSE: To describe an apparently unreported endovascular means of treating a vertebral arteriovenous fistula (AVF) using a small-caliber stent-graft to permanently reconstruct the involved vessels. CASE REPORT: A 13-year-old girl presented with tinnitus caused by a high-flow AVF between the right extracranial vertebral artery and deep jugular vein arising from repeated internal jugular vein catheterization. A 4-mm-diameter balloon-expandable Jostent coronary stent-graft was placed in the vertebral artery via a percutaneous femoral access, with immediate and complete obliteration of the AVF and resolution of the tinnitus. Follow-up duplex ultrasonography at 15 months demonstrated patency and luminal integrity of the vertebral artery. CONCLUSIONS: Vertebrojugular AVFs are rare and usually treated with transcatheter embolization techniques, but percutaneous repair using a small-caliber stent-graft appears feasible. This minimally invasive treatment might become the method of choice for AVFs in other small-bore vessels.

Arteriovenous Fistula↗

Spatially restricted activity of a Drosophila lipid phosphatase guides migrating germ cells.

Temporal and spatial controls of cell migration are crucial during normal development and in disease. Our understanding, though, of the mechanisms that guide cells along a specific migratory path remains largely unclear. We have identified wunen 2 as a repellant for migrating primordial germ cells. We show that wunen 2 maps next to and acts redundantly with the previously characterized gene wunen, and that known wunen mutants affect both transcripts. Both genes encode Drosophila homologs of mammalian phosphatidic acid phosphatase. Our work demonstrates that the catalytic residues of Wunen 2 are necessary for its repellant effect and that it can affect germ cell survival. We propose that spatially restricted phospholipid hydrolysis creates a gradient of signal necessary and specific for the migration and survival of germ cells.

Acid Phosphatase↗

Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets.

In autoimmune type 1 diabetes, Fas-to-Fas-ligand (FasL) interaction may represent one of the essential pro-apoptotic pathways leading to a loss of pancreatic beta-cells. In the advanced stages of type 2 diabetes, a decline in beta-cell mass is also observed, but its mechanism is not known. Human islets normally express FasL but not the Fas receptor. We observed upregulation of Fas in beta-cells of type 2 diabetic patients relative to nondiabetic control subjects. In vitro exposure of islets from nondiabetic organ donors to high glucose levels induced Fas expression, caspase-8 and -3 activation, and beta-cell apoptosis. The effect of glucose was blocked by an antagonistic anti-Fas antibody, indicating that glucose-induced apoptosis is due to interaction between the constitutively expressed FasL and the upregulated Fas. These results support a new role for glucose in regulating Fas expression in human beta-cells. Upregulation of the Fas receptor by elevated glucose levels may contribute to beta-cell destruction by the constitutively expressed FasL independent of an autoimmune reaction, thus providing a link between type 1 and type 2 diabetes.

Adolescent↗

Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation.

OBJECTIVE: The effects of glucose, arginine, and glucagon on beta-cell function as well as alpha-cell response to arginine were studied in a family with mitochondrial diabetes. RESEARCH DESIGN AND METHODS: The function of alpha- and beta-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test. RESULTS: The glucose disappearance constant (K(g)) value (mean +/- SEM 0.61 +/- 0.04 vs. 1.1 +/- 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0-10 min, 77.7 +/- 50.7 vs. 1,352.3 +/- 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 +/- 111.4 vs. 1,526.7 +/- 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 +/- 710.8 vs. 1,083.2 +/- 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 +/- 47.5 vs. 90.0 +/- 21.1 pmol/l, P = 0.099). CONCLUSIONS: This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.

Adult↗

Application of capillary electrophoresis in clinical chemistry: the clinical value of urinary modified nucleosides.

Urinary modified nucleosides were determined by capillary electrophoresis using a 300 mM SDS-25 mM sodium tetraborate-50 mM sodium dihydrogenphosphate buffer. The nucleosides were extracted from urine by phenylboronate affinity gel chromatography. In cancer patients the levels of the modified nucleosides are generally elevated. By an artificial neural network method breast cancer patients were differentiated from normal individuals, which indicates that the modified nucleosides could be of clinical value as tumor markers.

Case-Control Studies↗