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Biomedical subjects

M Schöning

Publications and source records attributed to M Schöning.

At least 19 recordsLinked to original sources
PubMed2005

A novel TITF-1 mutation causes benign hereditary chorea with response to levodopa.

Presented is a pedigree with infancy-onset benign hereditary chorea (BHC) caused by a novel nonsense mutation in exon 3 (523G-->T, E175X) of the TITF-1 (Nkx2.1) gene. Four confirmed mutation carriers showed the typical movement disorder of BHC and congenital hypothyroidism. Surprisingly, treatment with levodopa improved gait dramatically and reduced chorea in two patients. Dopaminergic drugs should be considered a useful therapeutic option in BHC.

Child↗
PubMed2004

MRI for the management of neonatal cerebral infarctions: importance of timing.

PURPOSE: Focal ischemic stroke in neonates is a rare occurrence. Diagnosis with most imaging modalities is difficult, but necessary for initiating an anticoagulatory treatment. The purpose of this study was to evaluate the sensitivity of MRI sequences within the first 14 days of birth. PATIENTS AND METHODS: Four patients with neonatal stroke presenting as seizures were examined using a standard MRI protocol including diffusion-weighted images (DWI) and magnetic resonance angiography (MRA) within 72 h of birth. The time between the onset of symptoms and MRI ranged from 6 h to 48 h. Follow-up examinations were performed on days 5 ( n=1), 7 ( n=2), and 14 ( n=1) for the control of a treatment with low-molecular heparin. RESULTS: Eight infarctions were detected in the four patients, 5 in the middle cerebral artery (MCA), three in the posterior cerebral artery (PCA) territory. All lesions were visible using DWI, four on T2-weighted images. Whereas in two patients small lesions contralateral to a large stroke were missed on T2-weighted images, the diagnosis would have been missed altogether without DWI in one patient. On follow-up, the visibility of the infarctions had declined using DWI after 5 days and the lesions were invisible after 1 week. Fourteen days after the stroke, an increased diffusion was detected in the infarcted brain tissue. By this time, all lesions were visible on T2-weighted images. CONCLUSION: In neonates, infarcted brain tissue can be detected using DWI with high sensitivity during the first 2 days after stroke and before other sequences are diagnostic. However, the diffusion restriction does not persist beyond 1 week. After 5 days, diagnosis has to rest mainly on T2-weighted images.

Brain Mapping↗
PubMed2003

Isolated internal cerebral venous thrombosis in a neonate with increased lipoprotein (a) level: diagnostic and therapeutic considerations.

Background. Internal cerebral venous thrombosis is a life-threatening condition, which requires immediate therapy. Being infrequent in childhood, internal venous thrombosis is very rare in the neonate and has never been observed without concomitant occlusion of further dural sinuses. Case Description. We report a neonate born at term, who developed seizures on the third day of life after normal pregnancy and uneventful delivery. Ultrasound and CT disclosed bilateral intraventricular and intracerebral hemorrhage with an unusual distribution for germinal matrix hemorrhage. MRI disclosed thrombotic occlusion of the straight sinus and the internal cerebral veins with concomitant bleeding into the ventricles, the basal ganglia, thalamus and the periventricular hemispheres. The other sinuses were not affected. The clinical condition of the child improved after initiation of a low-dose heparin treatment with subsequent partial recanalization of the occluded vessels. The screening for risk factors disclosed an elevated lipoprotein (a) level, also present in both parents. Conclusion. Internal cerebral venous thrombosis may be encountered in neonates and must be included in the list of differential diagnosis of perinatal intraventricular and intracerebral bleeding. MRI allows the diagnosis even in the absence of widespread dural sinus occlusion. Low dose heparin may be a therapeutic option in these cases. This is the first report of neonatal internal venous thrombosis due to hereditary lipoprotein (a) level elevation, which must be included in the list of possible predisposing conditions.

Humans↗
PubMed2003

The development of cerebral perfusion in healthy preterm and term neonates.

Quantitative measurement of cerebral blood flow (CBF) volume was performed by sonographic flowmetry of both internal carotid (ICA) and vertebral arteries (VA) in 113 healthy preterm and term infants of 32 - 42 weeks postmenstrual age (PA) in order to delineate the physiological characteristics of brain perfusion in a time period very sensitive to brain injury. Mean CBF volume increased with PA, beginning with 33 +/- 9 ml/min in neonates of 32 - 34 weeks and rising to 45 +/- 10, 58 +/- 13, 69 +/- 14, and 83 +/- 16 ml/min, respectively, in the PA groups of 35 - 36, 37 - 38, 39 - 40 and 41 - 42 weeks. There was no difference in CBF volume between the sexes. The bilateral sum of flow volumes in both ICA and VA rose markedly with PA. The relative contribution of bilateral VA flow volume to total CBF volume was 26 +/- 8 % and remained constant with PA. In addition, we calculated the approximate CBF (ml/100 g brain weight/min) using the brain weights of each child as estimated by means of an equation based on head circumference measurements. Estimated CBF correlated significantly with PA (r = 0.49; p </= 0.0001), reflecting the rising metabolic demand of the growing brain during the time period examined.

Age Factors↗
PubMed2003

A complex chromosomal rearrangement with a translocation 4;10;14 in a fertile male carrier: ascertainment through an offspring with partial trisomy 14q13-->q24.1 and partial monosomy 4q27-->q28 [corrected].

Complex chromosomal rearrangements (CCRs) are usually associated with infertility or subfertility in male carriers. If fertility is maintained, there is a high risk of abnormal pregnancy outcome. Few male carriers have been identified by children presenting with mental retardation/congenital malformations (MR/CM) or by spontaneous abortions of the spouses. We report a de novo CCR with five breakpoints involving chromosomes 4, 10 and 14 in a male carrier who was ascertained through a son presenting with MR/CM due to an unbalanced karyotype with partial trisomy 14 and partial monosomy 4. The child has a healthy elder brother. In the family history no abortions were reported. No fertility treatment was necessary. Cytogenetic analysis from the affected son showed a reciprocal translocation t(4;10) with additional chromosomal material inserted between the translocation junctions in the derivative chromosome 10. The father showed the same derivative chromosome 10 but had additionally one aberrant chromosome 14. Further molecular cytogenetic analyses determined the inserted material in the aberrant chromosome 10 as derived from chromosome 14 and revealed a small translocation with material of chromosome 4 inserted into the derivative chromosome 14. Thus the phenotype of the son is supposed to be associated with a partial duplication 14q13-->q24.1 and a partial monosomy 4q27-->q28. Including our case we are aware of eleven CCR cases with fertile male carriers. In eight of these families normal offspring have been reported. We propose that exceptional CCRs in fertile male carriers might form comparatively simple pachytene configurations increasing the chance of healthy offspring.

Adult↗
PubMed2002

Measurement of volume of cerebral blood flow in healthy preterm and term neonates with ultrasound.

Changes in cerebral blood flow are important in the pathogenesis of ischaemic brain damage, but standard methods cannot measure volume of cerebral blood flow quantitatively in neonates. We used colour duplex sonography of the extracranial cerebral arteries to measure volume of global cerebral blood flow in 67 healthy preterm and term neonates. Volume of cerebral blood flow increased between the postmenstrual ages of 34 weeks (median 33 mL/min [range 23-43]) and 42 weeks (85 mL/min [57-104]). However, intersession and interobserver variability was quite large. This non-invasive method will allow quantitative bedside monitoring of global brain perfusion in preterm and term neonates with pathological disorders, and could also be used to monitor effects of neuroprotective measures.

Blood Flow Velocity↗
PubMed2002

Clinically significant persistence and enlargement of an antenatally diagnosed isolated choroid plexus cyst.

Isolated choroid plexus cysts are usually diagnosed at the time of screening ultrasonography during the second trimester. While they raise the question of underlying chromosomal abnormalities, their clinical course is almost invariably benign with complete resolution often by the third trimester. We report the highly unusual case of a choroid plexus cyst diagnosed at 14 weeks of gestational age with subsequent further enlargement of the cyst, necessitating postpartum neurosurgical intervention.

Adult↗
PubMed2001

Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker.

Cytogenetic analysis in a girl with multiple congenital anomalies indicating Pallister-Killian syndrome (PKS) showed a supernumerary marker chromosome in 1/76 lymphocytes and 34/75 fibroblast metaphases. GTG-banding pattern was consistent with the chromosomal region 12pter-12q11. While fluorescence-in-situ hybridisation (FISH) with a whole chromosome 12 painting probe confirmed the origin of the marker, a chromosome 12 specific alpha-satellite probe did not hybridise to it. FISH analysis with a specific subtelomeric probe 12p showed hybridisation to both ends of the marker chromosome. High-resolution multicolour-banding (MCB) studies revealed the marker to be a der(12)(pter-->p12.3::p12.3-->pter). Summarising the FISH information, we defined the marker as an inverted duplication of 12pter-12p12.3 leading to partial tetrasomy of chromosome 12p. In skin fibroblasts, cultured at the patient's age of 1 year and 9 years, the marker chromosome was found in similar frequencies, even after several culture passages. Therefore, we consider the marker to have a functional centromere although it lacks detectable centromeric alpha-satellite sequences. To the best of our knowledge, this is the first proven analphoid marker of chromosome 12. Molecular genetic studies indicated that this marker is of paternal origin. The finding of partial tetrasomy 12pter-12p12.3 in our PKS patient allows to narrow down the critical region for PKS.

Abnormalities, Multiple↗
PubMed2001

Late detection of neuroblastoma in a patient with prolonged cerebellar ataxia without opsoclonus.

A 19-month-old boy presented with acute-onset cerebellar ataxia following immunisation. Ataxia was prolonged with a fluctuating course over a period of two years. Opsoclonus was never observed. Extensive diagnostic studies were negative during this time. Finally, a neuroblastoma was discovered. Ataxia disappeared completely during polychemotherapy. This report suggests that occult neuroblastoma must be considered in any child with unexplained prolonged cerebellar ataxia. Specific investigations are recommended for such cases.

Adrenal Gland Neoplasms↗
PubMed2000

Flow velocity and flow volume measurements in the extracranial carotid and vertebral arteries in healthy adults: reference data and the effects of age.

To establish reference data and to investigate the development of haemodynamics in the extracranial carotid and vertebral arteries, we performed a prospective study in 78 age- and gender-matched healthy adults from 20 to 85 y old. Angle-corrected flow velocities and luminal diameters were measured and waveform parameters and flow volumes calculated in all the arteries. Side-to-side differences and the influence of age on these parameters were also investigated. In the common carotid arteries, the internal carotid arteries and the vertebral arteries (CCA, ICA and VA, respectively) all flow velocities decreased significantly during ageing. The luminal diameter remained constant in all the carotid arteries, but increased slightly with age in the VA. An age-related decline of intravascular flow volume was observed in the ICA. Due to a pronounced decrease in end-diastolic flow velocity, the resistance index decreased in ICA and VA during ageing. There were no significant side-to-side differences in flow velocities and flow volumes in any of the extracranial arteries. The luminal diameters of the CCA, ICA and ECA were significantly smaller in women than in men. No relevant gender-related differences in flow velocities or waveform parameters were found in the extracranial arteries. There was no gender-linked difference in the flow volumes of the brain-feeding arteries and, in the ECA, flow volumes were significantly higher in men. Reference data on all flow velocities and waveform parameters, luminal diameters and flow volumes were established for different age groups between 20 and 85 y old. These data allow us to outline the development of cerebral haemodynamics during "benign ageing" and to utilise flow volume measurements in clinical practice, especially in patients with cerebrovascular diseases.

Adult↗
PubMed2000

Microdeletion 4p16.3 in three unrelated patients with Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome caused by partial monosomy of 4p16.3. Pitt-Rogers-Danks syndrome, first thought to be a distinct entity, is a similar condition associated with a microdeletion overlapping the WHS critical region. In this paper we evaluate three WHS patients showing a microdeletion of 4p and remarkable development with respect to the clinical spectrum of WHS.

Abnormalities, Multiple↗
PubMed2000

Color duplex measurement of cerebral blood flow volume in healthy adults.

BACKGROUND AND PURPOSE: Global cerebral blood flow (CBF) is an important yet largely unknown quantity in the treatment of neurological intensive care patients. Color duplex sonography of the extracranial cerebral arteries can be used to measure global CBF volume directly at the bedside. To establish reference data on global CBF volume and to test the influence of sex and age on this parameter, a prospective study was performed in a group of 78 healthy adults aged 20 to 85 years (39 women, 39 men; mean age, 52+/-19 years in either sex). METHODS: The common, external, and internal carotid arteries and the vertebral arteries were examined with the use of a 7.0-MHz transducer of a computed sonography system. Angle-corrected time-averaged flow velocity and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of angle-corrected time-averaged flow velocity and the cross-sectional area of the circular vessel. CBF volume was determined as the sum of flow volumes in the internal carotid and vertebral arteries of both sides. RESULTS: From 20 to 85 years of age, CBF volume decreased significantly (P</=0.0001), on average by approximately 3 mL/min per year. There were no sex-linked differences in CBF volume. The mean relative contributions of the internal carotid artery and the vertebral arteries to global CBF volume remained constant with age (76% versus 24%). The reference data on CBF volume established for the groups aged 20 to 39 years, 40 to 59 years, and 60 to 85 years were 727+/-102, 656+/-121, and 603+/-106 mL/min, respectively. CONCLUSIONS: The data presented here provide additional information on the natural development of global cerebral perfusion in "benign aging." CBF volume reference data for different age groups were also established. These data provide a basis for the clinical application of CBF volume measurements at the bedside, especially in the monitoring of CBF volume in neurological intensive care patients.

Adult↗
PubMed1999

Diagnostic impact of cerebral transit time in the identification of microangiopathy in dementia: A transcranial ultrasound study.

BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy.

Aged↗
PubMed1998

The development of hemodynamics in the extracranial carotid and vertebral arteries.

To investigate the development of hemodynamics in the extracranial carotid and vertebral artery system, a prospective color duplex sonography study was performed in 94 healthy children and adolescents between 3 and 18 y old. Angle-corrected flow velocities and luminal diameters were measured; waveform parameters and flow volumes were calculated. Side-to-side differences of volumetric data were analyzed. In 53 children, an intrasession test-retest flowmetry of the internal carotid and vertebral arteries was performed. From 3 to 18 y old, flow volumes decreased significantly in the vertebral arteries (p < or = 0.01) and increased in the external carotid artery (p < or = 0.0001); the luminal diameter increased in all the carotid arteries (p < or = 0.0001) and remained constant in the vertebral arteries; mean flow velocities declined in the common and internal carotid arteries and in the vertebral arteries (p < or = 0.0001), but increased in the external carotid arteries (p < or = 0.01). Flow volume rate was lower in the right than the left vertebral artery (p < or = 0.0001), and there was no side difference in any of the carotid arteries. The test-retest correlation of volumetric data was high (0.81 < or = r < or = 0.97; p < or = 0.0001). By comparing the reference data presented here with analogous adult data, we were able to delineate the physiologic development of extracranial and cerebral hemodynamics from childhood to adulthood. These data make possible the clinical application of quantitative flowmetry in extracranial cerebral arteries of children and adolescents.

Adolescent↗
PubMed1998

Integrin alpha5beta1: a potent inhibitor of experimental lung metastasis.

The integrin alpha5beta1 seems to be the most relevant receptor of tumor cells for binding to fibronectin. Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities. We addressed this question by transfection of the integrin alpha5beta1 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin alpha5beta1. Similar to other reports, expression of the integrin alpha5beta1 in HT-29 tumor cells exerted an inhibitory action on cell proliferation as indicated in our study by formation of fewer colonies in soft agar. The tumor growth inhibitory property of the integrin alpha5beta1 was also shown by reduction of subcutaneous xenograft growth in nude mice to approximately 50% of that of control transfectants. For the first time, we found that several clones of integrin alpha5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injection into nude mice. While most animals inoculated with control transfectant cells formed macroscopically visible lung colonies ranging from 12.6 +/- 2.6 to 22.0 +/- 6.6 (mean colony number +/- SEM), mice inoculated with HT-29 cell clones expressing the integrin alpha5beta1 were almost completely free of lung colonies (ranging from 0.0 +/- 0 to 0.2 +/- 0.1). Our results imply that integrin alpha5beta1 expression inhibits circulating tumor cells in pursuing late steps of the metastatic process as represented by the artificial metastasis (lung colonisation) model.

Animals↗
PubMed1996

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↗