Biomedical subjects

H Steinmetz

Publications and source records attributed to H Steinmetz.

At least 37 records · Page 2Linked to original sources

PubMed2003

S100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artery occlusion.

OBJECTIVES: The astroglial protein S100B is a marker of cerebral tissue damage. This study investigated whether the serum kinetic of S100B may serve as a surrogate marker of successful clot lysis and early recanalisation (<6 hours) in hyperacute proximal middle cerebral artery (MCA/M1) occlusion. METHODS: The authors prospectively included 23 patients (mean (SD) age, 70.2 (11.0) years) presenting with MCA/M1 occlusion on magnetic resonance angiography (n=18), intra-arterial angiography (IA; n=2), or transcranial Doppler sonography (TCD; n=3) within five hours after symptom onset. Rates of recanalisation and their point of time were determined using TCD or IA. Individual S100B values were determined at hospital admission, every eight hours within the first three days, and at 12 hour intervals from day 4 to day 6. Additionally, the S100B area under the curve (AUC) and the S100B peak value were obtained. RESULTS: Early recanalisation (<6 hours after symptom onset, n=7) was associated with a significantly lower mean S100B AUC compared with no recanalisation (22.2 (40.1) versus 406.8 (284.4) micro g/l per hour; p<0.001). Using receiver operating calculations, a single S100B value obtained 48-96 hours after stroke onset of less than 0.4 micro g/l (cut off point) provided a 86% sensitivity and 100% specificity for sufficient MCA/M1 clot lysis <6 hours. The overall accuracy for a single S100B value obtained in the 48-96 hours time window was as high as for the AUC (95.7%). CONCLUSION: A single S100B value <0.4 micro g/l obtained 48-96 hours after stroke onset indicates successful clot lysis <6 hours in MCA/M1 occlusion with a high degree of accuracy. Thus, determination of a single S100B value may serve as a surrogate marker of early and sufficient MCA/M1 recanalisation in large scale thrombolytic studies.

Acute Disease↗

PubMed2003

[Recanalizing therapies in acute stroke].

Systemic thrombolysis with rt-PA within 3 hours after symptom onset has developed into a standard therapy for acute stroke patients. Recombinant t-PA is now licensed in Europe for this indication. Within 3 to 6 hours, no general therapeutic standard has been established yet. Currently, the available data are in favor of intra-arterial thrombolysis for patients with proximal occlusions of the middle cerebral artery. Systemic thrombolysis is not generally recommended in this time window, but is used in some centers for selected patients. In addition to thrombolysis and new strategies to improve thrombolysis (including patient selection with MRI), several interventional and surgical recanalization techniques are discussed.

Acute Disease↗

PubMed2002

Division of the corpus callosum into subregions.

Various attempts have been made to subdivide the corpus callosum (CC) into anatomically and functionally distinct subareas. A promising current approach is the use of factor analytic techniques in conjunction with traced MRI images. The traced images are divided into 99 percentile slices, where the widths of the percentile slices are used as variables that are entered into the analysis (Denenberg, Kertesz & Cowell, 1991). Studies that use this technique agree broadly between 6 and 7 factors, but available factor solutions contain inconsistencies and large gaps, which arise when many of the percentile slices do not load appreciably on any of the factors. The present study uses a larger number of brains (N = 184), all normalized, and some methodological refinements in the analysis of the traced MRI images of the CC. A stable 7 factor solution was found, and the factor structure for males and females was very similar.

Adult↗

PubMed2002

[Recommendations for the management of unruptured intracranial aneurysms].

Optimal management of patients with unruptured intracranial aneurysms (UIAs) remains controversial. Recent studies have found conflicting data regarding the natural history and the treatment outcome of UIAs. Based on the recommendations published by the American Heart Association, the Section of Vascular Neurosurgery of the German Society of Neurosurgery has formed a task force to summarize the available data and to develop a practical framework for the management of UIAs. For UIAs, only evidence from nonrandomized historical cohort comparisons and case series without control subjects are available, supporting only grade C recommendations (options), but no standards (grade A) and no guidelines (grade B). The present recommendations have been developed as a neurosurgical, neuroradiological and neurological consensus. They are based on the existing data of both treatment risks and the risks of the natural history of UIAs.

Autoradiography↗

PubMed2002

Efficiency of SBR technology in municipal wastewater treatment plants.

Four wastewater treatment plants running with sequencing batch reactor (SBR) technology have been evaluated in view of their effluent quality, treatment efficiency and energy demand. The plants are designed for approximately 5,000, 8,000, 15,000 and 25,000 population equivalents (p.e.). Although two of the plants were overloaded during the investigation time the effluent concentrations of nitrogen, especially ammonia, and phosphorus were low. The results show, that SBR plants which are designed according to German standards have additional capacities for degradation of organic matter and removal of nitrogen and phosphorus. Furthermore SBR plants with combined sewer systems are able to treat combined sewage very well. Thus SBR technology proves to be a good alternative for municipal sewage plants and can help to save investment costs.

Bioreactors↗

PubMed2001

Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small-vessel disease.

BACKGROUND AND PURPOSE: Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. METHODS: In 16 patients (mean age 68+/-10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. RESULTS: Relative CBFV increase was significantly greater after pravastatin treatment (41.9+/-23.7% versus 55.7+/-18.3%, P=0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences. There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (beta=-0.64, P=0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. CONCLUSIONS: This pilot study provides the first evidence for a significant improvement of cerebral vasomotor reactivity by statin therapy in patients with cerebral small-vessel disease. The results may help to elucidate the preventive effect of statins and provide insights into the pathophysiology of cerebral small-vessel disease.

Acetazolamide↗

PubMed2001

New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13: isolation, structure elucidation, and SAR studies.

In addition to epothilones A (1) and B (2), 37 natural epothilone variants and epothilone-related compounds were isolated from the culture broth of a 700 L fermentation of Sorangium cellulosum, strain So ce90/B2. Of these, only the 12,13-desoxyepothilones, epothilone C (14) and D (15), were produced in significant amounts (3-6 mg/L); the 21-hydroxy derivatives and epothilones E (3) and F (4), in low and variable amounts due to further degradation by the producing organism. Most of the other epothilone variants were produced only in 1-100 microg/L amounts. The new compounds are very similar in structure to the parent compounds 1, 2 and 14, 15 and are presumably the result of the imperfect selectivity of the biosynthetic enzymes for acetate and propionate. Further, epothilones containing an oxazole moiety (10-13) in the side chain instead of a thiazole as well as ring-expanded 18-membered macrolides, epothilones I (30-35), and a ring contracted 14-membered macrolide, epothilone K (36), were found as very minor metabolites. The mutant strain, So ce90/D13, instead of macrolactones, produced short-chain carboxylic acids 40, 41, and 42 bearing the characteristic thiazole side chain. The structures of the new epothilones were elucidated on the basis of comprehensive NMR and MS data. The new epothilone variants were tested in a cytotoxicity assay with mouse fibroblasts (cell line L929), and structure-activity relationships were established. Several new natural epothilones showed activity comparable to 1 and 2, but in no case exceeded that of 2.

Animals↗

PubMed2001

Dissociating neural correlates of cognitive components in mental calculation.

Mental calculation is a complex cognitive operation that is composed of a set of distinct functional processes. Using functional magnetic resonance imaging (fMRI), we mapped brain activity in healthy subjects performing arithmetical tasks and control tasks evoking a comparable load on visuo-constructive, linguistic, attentional and mnemonic functions. During calculation, as well as non-mathematical tasks, similar cortical networks consisting of bilateral prefrontal, premotor and parietal regions were activated, suggesting that most of these cortical areas do not exclusively represent modules for calculation but support more general cognitive operations that are instrumental but not specific to mental arithmetic. Significant differences between calculation and the non-mathematical tasks were found in parietal sub-regions, where non-arithmetic number or letter substitution tasks preferentially activated the superior parietal lobules whereas calculation predominantly elicited activation of the left dorsal angular gyrus and the medial parietal cortices. We interpret the latter activations to reflect sub-processes of mental calculation that are related to the processing of numerical representations during exact calculation and to arithmetical fact retrieval. Finally, we found that more complex calculation tasks involving the application of calculation rules increased activity in left inferior frontal areas that are known to subserve linguistic and working memory functions. Taken together, these findings help to embed the specific cognitive operation of calculation into a neural framework that provides the required set of instrumental components. This result may further inform the cognitive modeling of calculation and adds to the understanding of neuropsychological deficit patterns in patients.

Adult↗

PubMed2001

Endovascular treatment of symptomatic carotid stenosis using stent placement: long-term follow-up of patients with a balanced surgical risk/benefit ratio.

BACKGROUND AND PURPOSE: Carotid endarterectomy (CEA) is not necessarily beneficial in all patients with symptomatic high-grade (>/=70%) internal carotid artery (ICA) stenosis. Independent risk factors modulate both the individual stroke risk under medical treatment and the combined stroke and death risk after CEA. Endovascular stenting of symptomatic ICA stenosis may be an alternative to CEA in patients with a balanced surgical risk/benefit ratio. METHODS: We included 43 patients (71% men; median age, 67 years) with a recently symptomatic ICA stenosis with >/=70% luminal narrowing in whom the individual sum of medical and surgical risk factors suggested a balanced surgical risk/benefit ratio (risk-modeling appraisal derived from the European Carotid Surgery Trial). After stenting of the stenosed ICA with distal balloon protection, the mean+/-SD follow-up, including clinical and ultrasonographic examinations, was 20+/-11.8 months, with a median number of examinations of 5 per patient. RESULTS: Recanalization of ICA stenoses was technically successful in 40 of 43 procedures (93%). Within the 30-day postinterventional period 1 death occurred (2.5%), and the combined stroke and death rate within follow-up was 5%. Except for 1 asymptomatic ICA occlusion, no restenosis >/=70% occurred during follow-up. CONCLUSIONS: ICA stenting in symptomatic patients with a balanced surgical risk/benefit ratio is technically feasible, with a low periprocedural risk of stroke or death. Furthermore, the risk of future stroke and rate of significant restenosis during long-term follow-up appears to be low, suggesting that ICA stenting may be useful in carotid revascularization and stroke prevention.

Aged↗

PubMed2001

Studies on the biosynthesis of epothilones: the PKS and Epothilone C/D monooxygenase.

Nonproducer mutants support the assumption that epothilones A and B are synthesized by the same polyketide synthase (PKS). The endproducts of the PKS, epothilones C and D, compete for the active site of a constitutively synthesized monooxygenase which is regulated by product inhibition. The postulated C-13 hydroxy-epothilones as direct precursors of epothilones C and D were not detected.

Binding Sites↗

PubMed2000

Cerebral correlates of working memory for temporal information.

Studies of neural correlates of working memory functions in the auditory-verbal, visuo-spatial and visuo-object domain suggest a category-specific organization of working memory processes in prefrontal cortex. Here, we used fMRI to explore brain areas that underlie different working memory operations directed to the temporal domain, which so far has been widely neglected. Significant activations related to memory updating and comparison processes were found right-accentuated in prefrontal and lateral premotor cortices. Furthermore, both subvocal rhythm encoding and maintenance enhanced left-lateralized activity in Broca's and supplementary motor area as well as in the sensorimotor cortex. Hemispheric lateralization effects of brain activity during temporal processing tasks may depend on the presence or absence of subvocal rehearsal strategies.

Adult↗

PubMed2000

Planum temporale, planum parietale and dichotic listening in dyslexia.

A reduction or reversal of the normal leftward asymmetry of the planum temporale (PT) has been claimed to be typical of dyslexia, although some recent studies have challenged this view. In a population-based study of 20 right-handed dyslexic boys and 20 matched controls, we have measured the PT and the adjacent planum parietale (PP) region in sagittal magnetic resonance images. For the PT, mean left and right areas and asymmetry coefficients were compared. Since a PP area often could not be identified in one or both hemispheres, a qualitative comparison was used for this region. The total planar area (sum of PT and PP) was also compared between the two groups. A dichotic listening (DL) test with consonant-vowel syllables was administered to assess functional asymmetry of language. The results showed a mean leftward PT asymmetry in both the dyslexic and the control group, with no significant difference for the degree of PT asymmetry. Planned comparisons revealed however, a trend towards smaller left PT in the dyslexic group. In control children, but not in the dyslexic children, a significant correlation between PT asymmetry and reading was observed. A mean leftward asymmetry was also found for the total planar area, with no difference between the groups for the degree of asymmetry. Significantly fewer dyslexic children than control children showed a rightward asymmetry for the PP region. Both groups showed a normal right ear advantage on the DL task, with no significant difference for DL asymmetry. No significant correlation was observed between PT asymmetry and DL asymmetry. The present population-based study adds to recent reports of normal PT asymmetry in dyslexia, but indicates that subtle morphological abnormalities in the left planar area may be present in this condition.

Child↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

Corpus callosum size in children with developmental language disorder.

Using high-resolution in-vivo magnetic resonance morphometry of the midsagittal area of the corpus callosum (CC) and four callosal subareas in 21 children with developmental language disorder (DLD) of the phonologic-syntactic type we found no significant anatomical differences in comparison to an age- and gender-matched normal control group. There was also no significant between-group difference when the approximately 7% smaller forebrain volume among children with DLD was accounted for by relating CC measures to forebrain volume. Only a tendency towards a larger anterior and middle CC in relation to forebrain volume was found in DLD children. In our DLD children we found the same relationship between CC midsagittal size and forebrain volume as recently reported for normal adults, namely, that the CC area increases to the two-third power of forebrain volume.

Child↗

PubMed2000

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↗

PubMed2000

Studies on the biosynthesis of epothilones: the biosynthetic origin of the carbon skeleton.

The biosynthetic origin of the epothilone skeleton was studied by the incorporation of 13C and radioactively labeled precursors by Sorangium cellulosum So ce90. The carbon atoms are derived from acetate, propionate, the methyl group of S-adenosyl-methionine, and cysteine which also introduces the sulfur and nitrogen atoms. Epothilone biosynthesis starts with the formation of the thiazole part from acetate and cysteine. The incorporation of acetate or propionate units results in the formation of epothilones A and B, respectively. To introduce the epoxide function of epothilones A and B molecular oxygen is used.

Carbon↗

PubMed2000

Tubulysins, new cytostatic peptides from myxobacteria acting on microtubuli. Production, isolation, physico-chemical and biological properties.

New cytostatic compounds, tubulysins, were isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Angiococcus disciformis. The compounds are peptides partly consisting of unusual amino acids and are distantly related to the dolastatins. The tubulysins were not active against bacteria and only little against fungi, but showed high cytostatic activity against mammalian cell lines with IC50 values in the picomolar range. An incubation with 50 ng/ml tubulysin A led to a complete disappearance of the microtubuli network of the cells within 24 hours. The more active tubulysin D induced multipolar spindles: At 0.5 ng/ml all mitotic cells showed more than four spindle poles.

Animals↗