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Biomedical subjects

M Schöning

Publications and source records attributed to M Schöning.

At least 19 recordsLinked to original sources

IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.

The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of IL-4 for 48 h downregulated the surface expression of the integrin subunits alpha 2, alpha 3, beta 1 and beta 4 after 48 h, whereas the alpha 1 subunit was upregulated. In contrast, 100 U/ml to TNF-alpha selectively upmodulated the expression of alpha v. Attachment to fibronectin of cells treated with IL-4 increased twofold (63.5% vs 32.4%). Adhesion to fibronectin (54.0% vs 32.4%) and vitronectin (37.9% vs 16.4%) was elevated in the case of TNF-alpha stimulation. Using an experimental metastasis model, HT-29 cells showed a significant reduction of their lung-colonizing potential in nude mice when preincubated with IL-4 for 48 h before intravenous injection. The decrease also observed for TNF-alpha-treated cells was less pronounced. The data indicate that the cytokines IL-4 and TNF-alpha can act as direct regulators of adhesive mechanisms of tumor cells bearing adequate receptors, thus influencing lung-colony formation.

Animals

Transcranial color duplex sonography of basal cerebral arteries: reference data of flow velocities from childhood to adulthood.

A prospective study on transcranial color duplex sonography (TCCD) was performed with 94 healthy children and adolescents between 3 and 18 years of age (age and sex evenly distributed) in order to provide normal data on angle-corrected ("true") flow velocities and wave-form parameters of the main supra- and infratentorial basal cerebral arteries. Using a 2.0 MHz transducer of a computed sonography system, we examined the anterior, middle, and posterior cerebral arteries of either side transcranially, and the vertebrobasilar system suboccipitally. In all arteries, flow velocities decreased continuously from early childhood to adulthood, while wave-form parameters remained constant. There was no difference in flow velocities, and wave-form parameters between girls and boys. On the average, the angle-corrected flow velocities measured by TCCD were about 10%-20% higher than the reference data provided in "blind" transcranial Doppler studies by other groups for the anterior and posterior cerebral arteries as well as the basilar artery, while there were only small differences in the values for the middle cerebral artery. Side-to-side differences in flow velocities were lower in the middle and posterior cerebral arteries than in the anterior cerebral and the vertebral arteries. The reference data presented here provide a basis for the clinical application of the TCCD method in children and adolescents.

Adolescent

Late remission of congenital hemiparesis: the value of MRI.

In our department of neuropediatrics we made a definite diagnosis of congenital hemiparesis in a total of 123 patients born between 1974 and 1985. This diagnosis was always made or confirmed at a point after the patient's first birthday. Recently, we were able to follow up on 102 of them (83%) to determine whether their symptoms persist, that is, if the initial diagnosis of cerebral palsy (CP) was correct or not. Now, at the age of 9 to 18 years, 94 of these 102 patients (92%) still suffer from hemiparesis. We were able to perform MRI on 44 of them. A lesion consistent with the neurological symptoms was found in 43. Only one patient had normal findings-a false negative, so to speak. Of the 102 patients, eight (8%) had no hemiparesis, i.e. no disability at all at the time of the follow-up. All eight had in common the fact that the former functional involvement had been slight and not arm-dominated. Seven of them were also examined with MRI. Six had normal findings; MRI revealed a periventricular lesion consistent with the earlier hemiparetic symptoms in only one patient (a false positive, so to speak). We conclude that some children "outgrow" a hemiparetic cerebral palsy, even in later childhood years. In our patient group this happened between the ages of 3 and 10. We further propose that MRI could be useful in distinguishing between transitory and persistent hemiparesis.

Cerebral Palsy

Color duplex measurement of cerebral blood flow volume: intra- and interobserver reproducibility and habituation to serial measurements in normal subjects.

Color duplex flowmetry of internal carotid and vertebral arteries permits estimation of intravascular flow volumes and global cerebral blood flow volume (CBFV) by summing the flow volumes measured in each of the four extracranial vessels. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. The reliability of this new method was tested in a prospective, intra- and interdiane, intra- and interobserver reproducibility study of 32 healthy subjects aged 7-57 years. In each subject, CBFV was tested by each observer twice on day 1 and once on day 2 in consecutive recordings. In each artery, both examiners found closely similar mean intravascular flow volumes. Intradiane interobserver reproducibility of CBFV was high on both days (correlation coefficient, CC, 0.90 and 0.85, p < or = 0.0001; coefficient of variance, CV, 10.0 and 10.4%, respectively), as was the interdiane comparison (CC = 0.81, p < or = 0.0001; CV < or = 13.3%). Intraobserver reproducibility was even higher. On both days, there was a progressive decrease in CBFV from each subject's first to the last examination within a 1-h examination period (day 1: 717 +/- 150 ml/min to 690 +/- 120 ml/min; difference, p < or = 0.05; day 2: 700 +/- 120 ml/min to 665 +/- 126 ml/min; difference, p < or = 0.01). This habituation effect was more pronounced in subjects with high initial CBFV. Reproducibility of CBFV is comparable to that of mean CBF measurements with 133Xe inhalation and H2 15(O) positron emission tomography techniques reported by other groups. This method makes serial bedside-monitoring of CBFV feasible without posing the risks of radiation exposure.

Adolescent

Age dependence of total cerebral blood flow volume from childhood to adulthood.

In a prospective study of the natural development of total cerebral blood flow volume (CBFV), the common, external and internal carotid and vertebral arteries were examined in 94 healthy children and adolescents between 3 and 18 years of age (sex and age evenly distributed) using a 7.0-MHz transducer of a computed sonography system. Intravascular flow volumes were calculated with the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the vessel. CBFV was determined as the sum of flow volumes in the internal carotid and vertebral arteries of both sides. CBFV increased significantly between 3 and 6.5 years of age (from 687 +/- 85 to 896 +/- 110 ml/min; age correlation, p < or = 0.01) and declined thereafter (p < or = 0.001) to a constant level of approximately 700 ml/min at 15 years of age. There was no difference in CBFV between sexes. The proportion of bilateral vertebral artery flow volume in total CBFV decreased significantly between the ages of 3 and 18 years (p < or = 0.001). As the flow volumes of the external carotid arteries increased markedly from childhood to adulthood, flow volumes of the common carotid arteries were not representative of CBFV. Intrasession test-retest correlation of CBFV was high (r = 0.89, p < or = 0.0001). Reference data for the childhood years presented here and previously described results from healthy adults allow us to outline the natural evolution of CBFV in humans. The reliability of the method has already been demonstrated. Thus, it may now be introduced into clinical application.

Adolescent

Growth hormone (GH), insulin-like growth factors (IGFs), and IGF-binding protein-3 (IGFBP-3) in a child with Proteus syndrome.

Proteus syndrome is a congenital hamartomatous disorder characterized by partial overgrowth involving all germ layers. A somatic mutation model has been proposed since familial cases are extremely rare. We report on a 3-year-old girl with typical manifestations of Proteus syndrome, including local, asymmetric hypertrophy of various parts of the body. Total body length was reduced. Serum levels of IGF-I and especially IGF-II and their major growth hormone dependent binding protein (IGFBP-3) were significantly reduced, although growth hormone secretion after a pharmacological stimulus was normal. In vitro studies of fibroblasts derived from hypertrophied tissue showed normal IGF-I production and somewhat reduced IGF-II and IGFBP-3 production as compared to normal human skin fibroblasts. Affinity cross-linking experiments showed that fibroblasts of the affect tissue in Proteus syndrome produced an unusual pattern of IGF bindings proteins containing large amounts of an IGFBP with high affinity to IGF-II. The data suggest that IGF production is generally disturbed in Proteus syndrome with imbalanced levels of specific IGFBP in affected tissue.

Adult

Duplex sonography of renal arteries as a diagnostic tool in hypertensive children.

Computed duplex sonography was used to examine the renal arteries in 36 hypertensive children and adolescents (ages 4-17 years) with arterial hypertension of either renal or non-renal origin. Time-averaged flow velocities, maximum blood flow velocities as well as absolute renal blood flow and renal blood flow per gram kidney weight were measured. Normal flow velocities and normal to elevated renal blood flow volume was found in patients with acute glomerulonephritis and those with signs of chronic glomerulonephritis onset. Patients having advanced stages of chronic glomerulonephritis, on the other hand, were characterized by lower levels of all parameters. Unilateral renal artery stenosis was diagnosed correctly in four patients, although one intra-renal artery stenosis escaped imaging. Scarred kidneys exhibited low-normal or reduced flow velocities and renal blood flow volumes corresponded roughly to kidney size and preservation of normal kidney structure. Hypertension in some patients with normal kidneys showed a tendency to cause higher renal blood flow without consistent acceleration of blood flow velocities. We conclude that duplex sonography is a suitable primary diagnostic tool in measuring blood flow velocities and absolute renal blood flow volume in hypertensive children, thus facilitating the choice of the next diagnostic step.

Adolescent

Antiphospholipid antibodies in cerebrovascular ischemia and stroke in childhood.

We report on eight children who suffered from cerebrovascular ischemia or stroke at the age of 2 or up to 11 years. Antiphospholipid antibodies (APLA) were detected in two cases during the ischemic event and in six cases during follow-up examinations (after six weeks or within a span of six years). In two patients multiple stenoses of basal cerebral arteries were found; one of them suffered from moyamoya syndrome. The acute hemiplegia in one patient was linked to an asymptomatic mycoplasmal infection and APLA. In three cases, one of the parents was also APLA-positive. Seven patients were treated with acetylsalicylic acid, and in four cases immunoglobulin infusions were given. Transient ischemic attacks subsided after the child with the moyamoya syndrome received immunoglobulins. No effect of medication could be established in the other children. The concept of the antiphospholipid syndrome is still evolving. As none of the common risk factors pertaining to strokes in adults apply to children, pediatric research may offer a suitable platform for specific investigations on the causal, pathogenetic role of APLA. We propose that all children suffering from stroke or transient ischemic attacks should be tested for APLA.

Antibodies, Antiphospholipid

Estimation of cerebral blood flow through color duplex sonography of the carotid and vertebral arteries in healthy adults.

BACKGROUND AND PURPOSE: To noninvasively estimate cerebral blood flow volume, a prospective study of color duplex sonography of the common, external, and internal carotid arteries and vertebral arteries of healthy adults was done. Cerebral blood flow was calculated with the sum of flow volumes in the internal carotid and vertebral arteries of both sides. METHODS: Using a 7.0-MHz linear transducer of a computed sonography system, cervical arteries of 48 volunteers (23 women, 25 men; mean age, 35 +/- 12 years) were examined. We measured angle-corrected time-averaged velocities and the diameter of the vessels and calculated the flow volumes of all arteries. In addition, peak systolic, maximum end-diastolic, and time-averaged maximum velocities and the resistance, pulsatility, and spectral broadening indexes were determined. Furthermore, we analyzed the side-to-side difference, age dependence, and long-term reproducibility of these parameters. RESULTS: The mean +/- SD values of flow volumes in the common, internal, and external carotid and vertebral arteries were 470 +/- 120, 265 +/- 62, 160 +/- 66, and 85 +/- 33 mL/min on either side, respectively. Total cerebral blood flow was 701 +/- 104 mL/min (corresponding to 54 +/- 8 mL/100 g per minute), with no variation in age or sex. Long-term reproducibility of cerebral blood flow and flow volumes in all vessels was significant (P < .01). CONCLUSIONS: We conclude that color duplex sonography of cervical arteries is potentially a practical method for estimating total cerebral blood flow. This noninvasive technique may be ideally suited for bedside and follow-up examinations of the critically ill patient. In future studies it should be compared with established radionuclide techniques.

Adult

[Early indications for partial learning disorders--anamnestic and diagnostic strategies].

A surprisingly small amount of information exists about early symptoms of learning disorders becoming evident during the first years at school. Only one relation seems to carry some degree of reliability: Early language deficits and/or retardation of language acquisition and later learning disorders including dyslexia. Because of these limitations, a more pragmatic approach is recommended. Questionnaires can be used asking for specific and age-related skills, involving the existence and good functioning of strategically working and concept-building central structures. Children with deficits in these structures will develop and experience dysfunctions in their cognitive, social and motor abilities. Consequently, they present behavioural problems. Children whose questionnaires offer suspicion in respect of specific dysfunctions should be tested by means of structured play tests or by appropriate developmental tests, to determine their individual patterns of talents and specific shortcomings. An early therapeutic intervention, aimed at the child's specific and individual deficits, may prevent or reduce learning problems at school.

Child

Demonstration of giant MCA aneurysm by transcranial duplex sonography and color Doppler imaging.

Transcranial color Doppler sonography is a new diagnostic technique which allows real-time, color-coded imaging of basal cerebral arteries, with simultaneous demonstration of parenchymal structures in the B-mode scan. With this technique we were able noninvasively to show a giant fusiform aneurysm of the middle cerebral artery (MCA) in an 11-year-old boy. Transcranial color Doppler sonography through the intact temporal bone demonstrated the size and location of the aneurysm and provided real-time imaging of the pulsating intra-aneurysmal flow. Additionally, duplex sonographic measurements of intravascular flow velocities within the aneurysm and the feeding and draining artery were possible. Postoperatively, patency of the MCA with reduced flow velocities after excision of the aneurysm could be shown. This is the first transcranial color Doppler report in a patient with an intracerebral aneurysm. In our opinion, transcranial color Doppler sonography offers new diagnostic possibilities in patients with cerebrovascular disorders.

Blood Flow Velocity

Proton spectroscopy in five patients with Leigh's disease and mitochondrial enzyme deficiency.

Five children with Leigh's disease and progressive neurological symptoms were compared with 14 control children. In all patients, MRI showed bilateral lesions of the putamina and caudate heads. Serum lactate was normal for four of the children, and CSF lactate slightly elevated for three. Volume-selective proton MR spectroscopy (1H-MRS) of the basal ganglia in the Leigh patients revealed elevated lactate, giving further evidence for a defect of energy metabolism in the brain. 1H-MRS is an important tool for non-invasive brain tissue analysis in Leigh's disease, particularly in the absence of peripheral lactate elevation.

Acidosis, Lactic

Transcranial color duplex sonography in childhood and adolescence. Age dependence of flow velocities and waveform parameters.

BACKGROUND AND PURPOSE: Transcranial color duplex sonographic examinations in children and adolescents without cerebrovascular disease were evaluated retrospectively. Flow velocities and waveform parameters were determined and their side-to-side differences and age dependence analyzed and, finally, compared with analogous data of a previously described group of healthy adults. METHODS: With a 2.0-MHz sector transducer of a computed sonographic system, the anterior, middle, and posterior cerebral arteries were examined in 64 children and adolescents between 1.5 and 17.5 years of age. Angle-corrected systolic peak, end-diastolic maximum, time-averaged, and time-averaged maximum velocities, and the resistance, pulsatility, and spectral broadening indexes were determined in all vessels. RESULTS: Mean +/- SD values for time-averaged maximum velocity (and time-averaged velocity) were 92.2 +/- 13.0, 79.9 +/- 17.7, and 63.9 +/- 13.6 (55.3 +/- 11.7, 40.4 +/- 10.4, and 34.2 +/- 9.2) cm/s, respectively, in the middle, anterior, and posterior cerebral arteries in children under 10 years of age; values were 83.2 +/- 11.9, 69.4 +/- 13.8, and 55.6 +/- 10.1 (50.8 +/- 9.0, 39.9 +/- 10.5, and 33.1 +/- 6.3) cm/s, respectively, in children 10 years of age and older. Time-averaged maximum velocity decreased significantly with age in all vessels (P < .001). Although time-averaged velocity did not change significantly during childhood and adolescence, a clear decline occurred from adolescence to adulthood (P < .0001 in the middle and posterior cerebral arteries; P < .01 in the anterior cerebral artery). The spectral broadening index decreased significantly from childhood to adolescence in the anterior and posterior cerebral arteries (P < .0001). The resistance and pulsatility indexes remained stable throughout childhood. CONCLUSIONS: Transcranial color duplex sonography allows angle-corrected measurements of "true" flow velocities in basal cerebral arteries. Additional determination of time-averaged velocity permits more detailed evaluation of flow characteristics for all age groups. The transcranial color duplex technique may provide deeper insights on normal cerebral perfusion and its disorders.

Adolescent

Comparative study of transcranial color duplex sonography and transcranial Doppler sonography in adults.

To determine whether the frequency shift recorded in basal cerebral arteries corresponds to "true" flow velocities, a prospective comparative study of transcranial color duplex sonography (TCCD) and transcranial Doppler sonography (TCD) was performed. A 2.0-MHz transducer of a computerized TCCD system and a TCD device were used. The middle cerebral artery (MCA) and anterior cerebral artery (ACA) were examined by TCCD in 49 healthy volunteers (mean age 35 +/- 12 years). In 45 of the same volunteers a comparative TCD examination was possible. The studies were carried out blindly by different examiners at separate appointments. Peak systolic flow velocity, end-diastolic maximum flow velocity, time-averaged maximum flow velocity, and the pulsatility index were measured by both techniques. Additionally, for TCCD, time-averaged flow velocity was assessed, the resistance index and a spectral broadening index were calculated, and the energy output required for reliable measurement was analyzed. The TCCD signals were recorded in 98% of both MCA's and ACA's; with TCD, signals were recorded in 98% of MCA's and 87% of ACA's. Although in both vessels the angle-corrected peak systolic and time-averaged maximum velocities were approximately 10% to 15% higher in TCCD than in TCD measurements, correlation of flow velocities between both techniques was significant (p < 0.0001); differences between sides and age-dependency of flow velocities corresponded as well. In a reproducibility study, TCCD was repeated in 27 subjects by a third examiner with significant correlation (p < 0.0001) of both TCCD examinations. It is concluded that the advantage of TCCD is associated more with a qualitative aspect than a quantitative one. The additional visual dimension of TCCD can open new diagnostic possibilities in cerebrovascular disorders.

Adult

Evaluation of the vertebrobasilar-posterior system by transcranial color duplex sonography in adults.

BACKGROUND AND PURPOSE: The transcranial color duplex sonography technique was applied to the vertebrobasilar-posterior system to provide normal data for clinical application. METHODS: The intracranial posterior circulation was studied in 49 healthy volunteers (mean +/- SD age, 35 +/- 12 years) by a transcranial and suboccipital approach with a 2.0-MHz sector transducer of a computed sonography system. RESULTS: The posterior cerebral artery and the vertebrobasilar system were depicted clearly in the color Doppler mode. Pulsed Doppler signals could be recorded in the posterior cerebral (100%), basilar (92%), and vertebral arteries (89%). The following normal values were provided for all vessels: systolic peak, end-diastolic maximum, time-averaged, and time-averaged maximum velocities; resistance and pulsatility indexes; and a spectral broadening index. Mean +/- SD values were 45.9 +/- 9.6, 45.5 +/- 10.8, and 39.2 +/- 10.6 cm/sec for time-averaged maximum velocity, and 28.3 +/- 6.5, 30.6 +/- 7.2, and 24.7 +/- 8.4 cm/sec for time-averaged velocity in the posterior cerebral, basilar, and vertebral arteries, respectively. In a reproducibility study, duplex measurements of the posterior cerebral arteries were repeated in 27 subjects. The correlation between the two examiners was high (r = 0.56, p less than or equal to 0.0001 for time-averaged maximum velocity). CONCLUSIONS: Color duplex sonography of the vertebrobasilar-posterior system is a new, noninvasive, bedside investigative technique. It permits visualization of artery flow in real time, relating these to adjacent brain and cranial structures, as well as angle-corrected duplex measurement of "true" flow velocities at defined sites of the vessels. Thus, it will open new diagnostic possibilities in disorders of the posterior circulation.

Adult

Renal blood flow and flow velocity in children and adolescents: duplex Doppler evaluation.

The renal arteries of 62 children and adolescents aged 1-16 years without renal or renovascular disease were examined by computer Doppler duplex sonography (DDS) to measure absolute renal blood flow velocities. Maximum systolic velocity (Vmax) and time average velocity (TAV) were not age-dependent. In addition, absolute values of renal artery and renal blood flow were measured. Renal blood flow was 4.1 +/- 1.2 ml/min per gram kidney (two standard deviations), independent of age and comparable to commonly accepted physiological values. The coefficient of variation of blood flow calculations was 6%-15% depending on vessel diameter.

Adolescent

[Transcranial duplex sonography through intact bone: a new diagnostic procedure].

Transcranial duplex scanning as a new diagnostic procedure is described for the first time. This method allows Doppler sonographic registration of flow profiles of basal cerebral arteries through the intact skull with simultaneous demonstration of pulsating vessels and cerebral structures in the B-mode scan. The exact localisation of the registered Doppler profile can be demonstrated under direct visual control in a clearly defined section of the cerebral artery. Therefore, an angle correction of the recorded Doppler-shift is possible allowing determination of true flow velocity. Occlusion of basal cerebral arteries can be diagnosed visually with this method. The use procedure in 51 children and adolescents aged 18 months to 19 years is described.

Adolescent