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Biomedical subjects

H Steinmetz

Publications and source records attributed to H Steinmetz.

At least 19 recordsLinked to original sources

fMRI study of bimanual coordination.

Eleven right-handed subjects performed uni- and bimanual tapping tasks. Hemodynamic responses as measured with functional magnetic resonance imaging (fMRI) in the primary somato-motor cortex (SMC) showed that during bimanual activity the SMC contralateral to the hand taking the faster rate was more strongly activated than the SMC contralateral to hand taking the slower rate. There were no asymmetries, left SMC activation during the right fast/left slow tapping condition was comparable to the right SMC activation during the left fast/right slow condition. A given SMC showed similar activation levels for bimanual and unimanual activity (i.e. left SMC activation for right fast/left slow was similar to left SMC activation for the right fast unimanual condition). In contrast, a given supplementary motor area (SMA) showed significantly more activation for the bimanual than for the unimanual activity. In addition, an asymmetry was observed during bimanual activities: during the right fast/left slow activity, the left SMA showed more activation than the right SMA, but during the left fast/right slow activity, the right SMA was not significantly more activated than the left SMA. For unimanual activities, a clear rate effect (greater activation for faster rate) was seen in the SMC but not in the SMA.

Adult

Interhemispheric asymmetry of the human motor cortex related to handedness and gender.

Most people are right-handed, preferring the right hand for skilled as well as unskilled activities, but a notable proportion are mixed-handed, preferring to use the right hand for some actions and the left hand for others. Assuming a structural/functional correlation in the motor system we tested whether asymmetries in hand performance in consistent right and left handers as well as in mixed handers are associated with anatomical asymmetries in the motor cortex. In vivo MR morphometry was used for analyzing interhemispheric asymmetry in the depth of the central sulcus in the region of cortical hand representation of 103 healthy subjects. Subjects were tested both for hand preference and hand performance. As expected, left-right differences in hand performance differed significantly between consistent right, consistent left and mixed handers and were independent on gender. Male consistent right handers showed a significant deeper central sulcus on the left hemisphere than on the right. Anatomical asymmetries decreased significantly from male consistent right over mixed to consistent left handers. Sixty two per cent of consistent left handers revealed a deeper central sulcus on the right than on the left hemisphere, but for the group as a whole this rightward asymmetry was not significant. No interhemispheric asymmetry was found in females. Thus, anatomical asymmetry was associated with handedness only in males, but not in females, suggesting sex differences in the cortical organization of hand movements.

Adolescent

Role of the distal half of the c-Mpl intracellular domain in control of platelet production by thrombopoietin in vivo.

The cytokine thrombopoietin (TPO) controls the formation of megakaryocytes and platelets from hematopoietic stem cells. TPO exerts its effect through activation of the c-Mpl receptor and of multiple downstream signal transduction pathways. While the membrane-proximal half of the cytoplasmic domain appears to be required for the activation of signaling molecules that drive proliferation, the distal half and activation of the mitogen-activated protein kinase pathway have been implicated in mediating megakaryocyte maturation in vitro. To investigate the contribution of these two regions of c-Mpl and the signaling pathways they direct in mediating the function of TPO in vivo, we used a knock-in (KI) approach to delete the carboxy-terminal 60 amino acids of the c-Mpl receptor intracellular domain. Mice lacking the C-terminal 60 amino acids of c-Mpl (Delta60 mice) have normal platelet and megakaryocyte counts compared to wild-type mice. Furthermore, platelets in the KI mice are functionally normal, indicating that activation of signaling pathways connected to the C-terminal half of the receptor is not required for megakaryocyte differentiation or platelet production. However, Delta60 mice have an impaired response to exogenous TPO stimulation and display slower recovery from myelosuppressive treatment, suggesting that combinatorial signaling by both ends of the receptor intracellular domain is necessary for an appropriate acute response to TPO.

Animals

The relation between forebrain volume and midsagittal size of the corpus callosum in children.

Applying in vivo magnetic resonance (MR) morphometry in healthy adults we have recently discovered that the relationship between forebrain volume (FBV) and the midsagittal size of the corpus callosum (CC) follows a geometrical rule according to which larger brains have a relatively smaller midsagittal CC. This allometric relation was taken as support for the hypotheses of Ringo and co-workers suggesting that brain size may be an important factor influencing interhemispheric connectivity and lateralization. In this paper we examined whether the aforementioned relation between FBV and CC size also holds for healthy children between 3 and 14 years of age. We confirmed this relationship as previously found for adults. Thus, the geometrical rule and the implications associated with it apply for a wide age range. In addition we found significant correlations with age for posterior and mid-parts of the CC even when FBV was controlled for, suggesting an anterior to posterior maturation gradient of CC development.

Adolescent

Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis.

BACKGROUND: Chronic Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis but whether it plays a role at an early stage in the disease is uncertain. An early estimate of atherosclerosis can be obtained by ultrasonic imaging of the carotid artery to determine intima-media thickness (IMT) and the thickness of any atheroma plaques. METHODS AND RESULTS: In 983 normal population individuals aged 30 to 70 years, we measured common carotid artery (CCA) and carotid bulb IMT, and also carotid plaque thickness and the degree of internal carotid artery (ICA) stenosis. C. pneumoniae IgA titers of >/=16 and IgG titers of >/=64 were taken as positive. There was no association between C. pneumoniae IgA or IgG seropositivity with right, left, or mean CCA or bulb IMT, or with the presence of carotid plaques. There was a significant association between IgA seropositivity and >50% mean carotid stenosis with an odds ratio of 5.24 (95% CI 1.24 to 22.21, P=0.0245) after controlling for age and sex; after controlling for other cardiovascular risk factors, this was not significant 3.96 (95% CI 0. 84 to 18.78, P=0.082). No association was found between IgA or IgG seropositivity and markers of fibrinogen, log C-reactive protein, or leukocyte count. CONCLUSIONS: We found no evidence that serological evidence of C. pneumoniae infection is associated with early atherosclerosis. It is possible that IgA seropositivity is associated with more advanced disease but this hypothesis needs to be examined in a population with a higher prevalence of advanced atherosclerosis. We found no evidence that C. pneumoniae results in a chronic systemic inflammatory state.

Adult

Child age and planum temporale asymmetry.

Investigations using in vivo magnetic resonance (MR) morphometry have shown that left-right asymmetry of the planum temporale (PT) is a structural correlate of hemispheric functional asymmetries in adult humans (e.g., handedness, language representation). Postmortem studies of brains of fetuses and newborns have demonstrated that PT asymmetry becomes visible as early as in the last gestational trimester. The same studies could not clarify when the full (adult) degree of PT asymmetry is reached during brain development and whether this process may be influenced by functional specialization during childhood. We examined 61 neuropsychiatrically normal right-handed children aged 3 to 14 years (mean age +/-SD, 8.4 +/- 2. 7 years; cross-sectional study). MR morphometry showed no change in PT or planum parietale asymmetry with increasing age or brain volume. An unexpected gender difference of unknown significance emerged, with girls displaying a stronger leftward PT asymmetry, independently of age. For the age range studied, the results suggest that functional differentiation follows a structural asymmetry that is already "preset."

Adolescent

Triple spontaneous cervical artery dissection.

A 39-year-old healthy man had several transient ischaemic attacks suggesting left internal carotid artery (ICA) occlusion. There were no vascular risk factors and no preceding trauma. Colour-coded duplex sonography suggested a pseudo-occlusion of the left ICA, and cerebral angiography demonstrated dissection of the left ICA and both vertebral arteries. Angiography 6 months later was completely normal. This underlines the importance of four vessel angiography in young patients with dissections of cervical arteries.

Adult

Bilateral reductions of hippocampal volume, glucose metabolism, and wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy.

In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 +/- 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.

Adolescent

Reliability and validity of noninvasive imaging of internal carotid artery pseudo-occlusion.

BACKGROUND AND PURPOSE: Our study evaluated noninvasive tests for the diagnosis of atheromatous internal carotid artery (ICA) pseudo-occlusion. METHODS: Twenty patients (17 men, 3 women; mean age +/-SD, 64.3+/-11.6 years) with angiographically proven atheromatous ICA pseudo-occlusion (20 vessels) were prospectively examined with MR angiography (MRA; 2D and 3D time-of-flight techniques), color Doppler-assisted duplex imaging (CDDI) and power-flow imaging (PFI) with and without an intravenous ultrasonic contrast agent. As a control group, 13 patients (13 men; mean+/-SD age, 63.0+/-9.0 years) with angiographically proven ICA occlusion (13 vessels) were studied with the same techniques. For the determination of interobserver agreement (kappa statistics), the findings of each diagnostic technique were read by 2 blinded and independent observers who were not involved in patient recruitment and initial data acquisition. Specificity and sensitivity were calculated for all noninvasive techniques (observer consensus) in comparison to the standard of reference (intra-arterial angiography). RESULTS: Interobserver reliabilities were kappa=0.86 for intra-arterial angiography, kappa=0.90 for unenhanced CDDI, kappa=0. 93 for enhanced CDDI, kappa=0.93 for unenhanced PFI, kappa=1.0 for enhanced PFI, kappa=0.93 for 2D MRA, and kappa=0.77 for 3D MRA, respectively (P<0.0001). Specificities and sensitivities were 0.92 and 0.70 for unenhanced CDDI, 0.92 and 0.83 for enhanced CDDI, 0.92 and 0.95 for unenhanced PFI, 1.0 and 0.94 for enhanced PFI, 1.0 and 0.65 for 2D MRA, and 0.89 and 0.47 for 3D MRA, respectively. CONCLUSIONS: Advanced ultrasonographic techniques, especially PFI (with only 1 false-positive diagnosis of occlusion in the present series), can provide reliable and valid data to differentiate between ICA pseudo-occlusion and complete occlusion. In contrast, time-of-flight MRA at its present state is not capable of predicting minimal residual flow within a nearly occluded ICA.

Aged

The neural circuitry involved in the reading of German words and pseudowords: A PET study.

Silent reading and reading aloud of German words and pseudowords were used in a PET study using (15O)butanol to examine the neural correlates of reading and of the phonological conversion of legal letter strings, with or without meaning. The results of 11 healthy, right-handed volunteers in the age range of 25 to 30 years showed activation of the lingual gyri during silent reading in comparison with viewing a fixation cross. Comparisons between the reading of words and pseudowords suggest the involvement of the middle temporal gyri in retrieving both the phonological and semantic code for words. The reading of pseudowords activates the left inferior frontal gyrus, including the ventral part of Broca's area, to a larger extent than the reading of words. This suggests that this area might be involved in the sublexical conversion of orthographic input strings into phonological output codes. (Pre)motor areas were found to be activated during both silent reading and reading aloud. On the basis of the obtained activation patterns, it is hypothesized that the articulation of high-frequency syllables requires the retrieval of their concomitant articulatory gestures from the SMA and that the articulation of low-frequency syllables recruits the left medial premotor cortex.

Adult

Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties.

New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.

Acrylates

[Emergency heart valve replacement after acute cerebral embolism during florid endocarditis].

BACKGROUND: The indication for urgent cardiac surgical interventions in patients with active infective endocarditis has to be considered carefully following thromboembolic events, because of the high recurrence rate of such complications. In the case of brain embolisms the prognostic benefit of urgent surgery has been discussed controversially as effective anticoagulation during open heart surgery may result in secondary cerebral hemorrhages. PATIENTS AND METHODS: Between 1978 and 1993 infective endocarditis (IE) was proven in 288 consecutive and prospectively followed patients (131 females, 157 males; mean age 53.6 +/- 8.7 [9 to 81] years). To analyze potential benefits and risks of an urgent surgical intervention early after embolic cerebral infarction, cumulated survival rates were calculated for patients with and without surgical intervention with special reference to incremental risk factors and the timing of surgery. RESULTS: In 50 patients (17.4%) the clinical course was complicated by one, and in 58 patients (20.2%) by recurrent embolic events. In 80% the first embolism occurred within 33 days following the first manifestation of typical signs and symptoms of IE. 80% of recurrent events were observed within 32 days following the initial embolism. 71% of all embolic events were cerebral. In patients with cerebral embolism corroborated by computed tomography (CCT), the clinical course was complicated by intracranial hemorrhage in 12.5% while it was only 1.5% for patients without cerebral embolism. Because of a lack of therapeutic alternatives, 22 of 49 patients with recurrent embolic events, of which at least one was cerebral, underwent urgent cardiac surgery within 4 to 366 hours after the first cerebral manifestation. The cumulated survival rate of patients operated within 72 hours after the initial cerebral embolism was significantly more favorable (p < or = 0.000) than for unoperated patients or those who were operated after more than 8 days. CONCLUSION: An embolic event during IE carries a more than 50% risk of recurrence. In patients with short duration of signs and symptoms of IE and postembolic echocardiographic demonstration of persistent vegetations the probability is > 80%. At least for those patients urgent surgical intervention to remove the source of infection and embolic hazard seems to be beneficial. Surgical intervention using the heart-lung-machine should be performed within 72 hours. Such early timing results in a significant lower rate of secondary cerebral hemorrhages (p < or = 0.00) than a postponed operation. To exclude early reperfusion hemorrhage due to spontaneous thrombus fragmentation, CCT should be repeated directly preoperatively.

Adolescent

Unsolved problems in comparing brain sizes in Homo sapiens.

When brain size is compared across taxonomic levels, there is a clear relation between body parameters and brain size. It is generally stated that the correlation between brain size and body parameters becomes very small at the species level (Aboitiz, 1996), but this is not the case for Homo sapiens where there is a strong correlation between brain size and body size across racial groups that differ in body size. The control for body size across racial groups (and sexes) is rendered difficult because bodies do not just differ only in height and weight. Within groups different studies show weak and inconsistent brain size/body height correlations. A better understanding of brain size/body height relations must await better quality data and a better understanding of how exactly body parameters should be scaled between groups and sexes. We attribute the clear between-group and weak within-group correlations to the large variety of body sizes and body types in our species, a variety which is only equalled in selectively bred species of animals. At present, there is no meaningful basis for the comparison of brain sizes within and between racial groups and sexes.

Adult

Focal grey matter heterotopias in monozygotic twins with developmental language disorder.

UNLABELLED: We describe 9-year-old monozygotic male twins with a developmental language disorder of the phonologic-syntactic type and learning difficulties. High-resolution MRI revealed bilateral parieto-temporal grey matter heterotopias in both twins, on the left more than on the right, and more pronounced in the more affected twin. This suggests a causal relationship between the heterotopias and the neuropsychological findings in this twin pair. CONCLUSION: Neuronal migration defects and ensuing focal heterotopias may be causally related to developmental language disorders.

Cerebral Cortex

Normal intrasylvian anatomical asymmetry in children with developmental language disorder.

Symmetry of posterior intrasylvian cortices (e.g., planum temporale, planum parietale) has been suggested to represent a risk factor for developmental disorders of language and reading. Using high-resolution magnetic resonance morphometry, we studied 21 right-handed children with developmental language disorder of the phonologic-syntactic type, and found normal left-right asymmetry of the planum temporale and planum parietale when compared with 21 matched controls. The planum temporale was bilaterally smaller in the affected children, a finding accounted for by their approximately 7% smaller forebrain size. Our data do not support a role of gross visible unilateral or bilateral abnormalities of posterior intrasylvian ontogenesis in this disorder.

Analysis of Variance

Differential magnetic resonance signal change in human sensorimotor cortex to finger movements of different rate of the dominant and subdominant hand.

Functional magnetic resonance tomography (fMRI) analysis of unimanual and bimanual sequential movements in righthanders showed the following effects. First, a rate-dependent activation of the somato-motor cortex was confirmed, with faster movement rates producing higher activation both in terms of signal intensity and number of activated voxels. Second, the right hemisphere showed more activation than the left hemisphere during unimanual tasks. Third, during bimanual movements, the left hemisphere showed greater activation than the right hemisphere. Finally, while the left hemisphere showed a marked change in activation patterns from unimanual to bimanual task, the right hemisphere activation patterns were not sensitive to task changes. The hemispheric asymmetries suggest substantial left hemisphere involvement in the coordination of bimanual tasks.

Adult

Central auditory processing, MRI morphometry and brain laterality: applications to dyslexia.

We review data from our laboratory related to a view of dyslexia as a biological disorder, or deficit, caused by both structural and functional brain abnormalities. The review is focused on central auditory processing in dyslexia, and the possibility that impairments in the auditory or acoustic features of the phonological code may be at the heart of the impairments seen in dyslexia. Three methodological approaches by which to investigate central auditory processing deficits are outlined: dichotic listening (DL) to consonant-vowel syllables; magnetic resonance imaging (MRI), and the use of event-related potentials (ERPs). Consonant-vowel syllable DL is a technique for probing the functional status of phonological processing areas in the superior temporal gyrus, particularly in the left hemisphere. MRI is a corresponding structural, or morphological, measure of anatomical abnormalities in the same brain region, particularly covering the planum temporale area. The ERP technique, and particularly the mismatch negativity (MMN) component, reveals cortical dysfunctions in sensory processing and memory related to basic acoustic events. For all three approaches, the dyslexic children were seen to differ from their control counterparts, including absence of modulation of the right ear advantage (REA), in DL through shifting of attention, smaller left-sided planum temporale asymmetry, and prolonged latency in the MMN ERP complex, particularly in the time-deviant stimulus condition.

Auditory Diseases, Central

Modifiable stroke risk factors in volunteers willing to participate in a prevention program.

The current trends in stroke incidence require continued efforts to improve primary prevention. Compared to large-scale public health approaches, more limited programs targeting volunteers may offer some advantages. We invited all 12,824 members of a health insurance company program who lived within 50 km form one of two study sites to participate in a vascular screening program and aimed at reducing modifiable risk factors. 1,837 persons registered and participated (14.3%, mean age 53 +/- 12 years, 50% men). Using the Framingham stroke risk profile for persons aged 55 years or above (n = 961, 52.3%), 97 stroke events can be predicted for this age group within 10 years. The majority of these 97 events will occur in those with men resting blood pressure values +/- 140mm Hg (systolic) or +/- 90 mm Hg (diastolic; 420 persons, mean age 64 +/- 7 years, 60 expected events), or with a particularly high age- and sex-adjusted risk (288 persons, mean age 68 +/- 7 years, 60 expected events). Our pilot study provides an estimate of the prevalence of modifiable vascular risk factor among volunteer participants of a prevention program. Possible benefits of this approach will be investigated in a second step using a randomized intervention.

Aged