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Biomedical subjects

M Heil

Publications and source records attributed to M Heil.

At least 19 recordsLinked to original sources

A case of childhood acute myeloid leukemia associated with inversion (7)(p21q31).

We describe a case of acute myeloid leukemia in a 2 1/2-year-old boy presenting with a mediastinal tumor causing respiratory distress, and lymph node enlargement in the cervical and inguinal regions. Apart from myeloid markers CD13 and CD33, blast cells also expressed stem cell marker CD34 and megakaryocytic marker CD61. Cytogenetically, inv(7)(p21q31) was found in 9/25 and 15/25 analyzed metaphases from short-term cultures of lymph node and bone marrow cells, respectively. The patient is in continued complete remission 26 months post diagnosis. The case demonstrates that chromosome aberrations other than inv(16), t(8;21), and t(9;11) may be associated with extramedullary disease, and that not all chromosome 7 aberrations are prognostic adverse findings.

Child, Preschool

Mental rotation, memory scanning, and the central bottleneck.

Two reaction-time experiments using the psychological refractory period paradigm examined whether two prominent tasks, i.e., mental rotation and memory scanning, require access to a single-channel mechanism and must therefore be performed sequentially with other operations requiring the same mechanism. On each trial, subjects made speeded responses to a tone (Exp. 1) or a character (Exp. 2, with symbolic SR-compatibility of the character manipulated) as Task 1 and to a letter (for blocks with mental rotation) or a digit (for blocks with memory scanning) as Task 2. The set-size effect was constant across SOAs, suggesting that memory scanning cannot be performed in parallel with response selection of Task 1. The effect of orientation, however, decreased with decreasing SOA. The decrease was even intensified if Task 1 bottleneck processes were prolonged by symbolic SR-compatibility. The exact pattern of underadditivity, however, was not predicted by current theories of dual-task performance. The results contradict a central bottleneck model but are in line with extensions of the model proposed by Meyer and Kieras.

Female

On separating processes of event categorization, task preparation, and mental rotation proper in a handedness recognition task.

We investigated the nature of event-related potential (ERP) effects in a handedness recognition task requiring mental rotation. Thirty subjects were tested with rotated and sometimes reflected alphanumeric characters while ERPs were recorded from 18 electrodes. On each trial, a cue provided valid information about the angular displacement of the following probe. This design allowed a distinction between three processing episodes: evaluation of the difficulty of the forthcoming task, preparation for the task, and the mental rotation task itself. The three episodes were accompanied by distinct ERP effects having distinct polarities, a different rank order of amplitudes for different probe orientations, and a different topography. These data confirm previous findings showing that mental rotation is accompanied by a parietal negativity. However, they also suggest that the rotation-related negativity found after tilted stimuli in standard mental rotation tasks is most likely overlapping with another, simultaneously triggered ERP effect functionally related to an evaluation of task difficulty.

Adult

4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease.

Maple syrup urine disease is an autosomal recessive inherited disorder of branched-chain amino acid metabolism due to deficiency of the branched-chain alpha-keto acid dehydrogenase complex. The disease was originally named after the characteristic sweet aroma, reminiscent of maple syrup, present in the body fluids of affected patients. Until now, the substance responsible for the odour has not been positively identified. Using enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS), we could demonstrate that 4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone), a well-known flavour impact compound present in fenugreek and lovage, was present in urine from seven patients with maple syrup urine disease. Urine samples from healthy control persons lacked sotolone. We have shown that sotolone is responsible for the characteristic odour of maple syrup urine disease and, since maple syrup also contains sotolone, the naming of this disease appears to be correct.

Furans

Airway closure: occluding liquid bridges in strongly buckled elastic tubes.

This paper is concerned with the airway closure problem and investigates the quasi-steady deformation characteristics of strongly collapsed (buckled) airways occluded by liquid bridges of high surface tension. The airway wall is modeled as a thin-walled elastic shell, which deforms in response to an external pressure and to the compression due to the surface tension of the liquid bridge. The governing equations are solved numerically using physiological parameter values. It is shown that axisymmetric configurations are statically unstable, as are buckled tubes whose opposite walls are not in contact. The quasi-steady deformation characteristics of strongly collapsed airways whose walls are in opposite wall contact show a pronounced hysteresis during the collapse/reopening cycle. Buckling is shown to occur over a short axial length with moderate circumferential wavenumbers. Finally, further implications of the results for the airway collapse/reopening problem are discussed.

Elasticity

Enantioselective multidimensional gas chromatography-mass spectrometry in the analysis of urinary organic acids.

Enantioselective multidimensional gas chromatography-mass spectrometry is a valuable tool for the enantioselective analysis of compounds from complex matrices. Samples are separated initially on a precolumn and selected substances then transferred on-line to a main-column coated with suitable chiral stationary phase for enantioselective analysis with subsequent mass selective detection. In this paper the method is used as an adjunct to urinary organic acid analysis to provide information in patients with suspected inborn errors of metabolism. Lactic acid, alpha-hydroxyisocaproic acid, 3-phenyllactic acid and 3-(4-hydroxyphenyl)-lactic acid are separated in a single run. In addition, the enantioselective analysis of pyroglutamic acid is presented. D-Enantiomers of amino acids and alpha-hydroxycarboxylic acids derived from amino acids, point to a bacterial origin whereas the L-enantiomer is predominantly of endogenous origin. Therefore the enantiomeric ratio of chiral metabolites is an important parameter for the understanding of metabolic processes.

Carboxylic Acids

What is improved if a mental rotation task is repeated--the efficiency of memory access, or the speed of a transformation routine?

The present study contrasts 3 theories which provide explanations for performance improvement in mental rotation tasks. Wallace and Hofelich conjectured that the process as such may be executed more rapidly after training, while Bethell-Fox and Shepard attributed practice effects to the fact that images may be transformed first elementwise, but later as a Gestalt. In contrast, Tarr and Pinker assumed that a transformation of an image will no longer be computed after training but simply be retrieved from memory. Thirty-seven subjects participated in 3 test sessions in which they had to decide on the parity of 3-D block figures presented from different perspectives. Experimental group subjects underwent 4 additional practice sessions in which a subset of the figures and a subset of perspective views were used. Tests adapted to the predictions of the 3 theories revealed specific learning effects but no transfer, neither to old objects presented in new perspectives nor to new objects. This supports an instance-based explanation of practice effects which states that objects are represented in multiple perspective views.

Adult

Chiral compounds in metabolism: a look in the molecular mirror.

UNLABELLED: We know that many familiar objects such as gloves, shoes and screws are non identical with their mirror images. The same applies to certain chemical compounds. These compounds show a degree of asymmetry in their structure which means that when looked at in a mirror, their images are not superimposable--they are chiral compounds and have two forms (enantiomers). Until recently biochemists have only been concerned with perhaps one form, other forms having been ignored primarily due to analytical difficulties. We now know of inborn errors of metabolism where one form of a pathological metabolite predominates, thus requiring precise enantiomeric analysis. This article provides a background to the field of enantiomers and their analysis as demonstrated by examples of inborn errors of metabolism and hints at the possible discovery of as yet unidentified metabolic pathways. CONCLUSION: Recent advances in the field of enantiomeric metabolite analysis, in particular the use of enantioselective gas chromatography-mass spectrometry, have an increasingly important role to play, not only in the diagnosis of inborn errors of metabolism, but also to increase our understanding of normal physiological processes.

Adult

Response preparation begins before mental rotation is finished: evidence from event-related brain potentials.

Behavioral data (response time (RT) and accuracy) and psychophysiological data (event-related brain potentials of ERPs, and lateralized readiness potential or LRP) were studied in an experiment in which rotated alphanumeric characters were presented normally or mirror-reversed. In half of the trials, character classification (letter versus digit) determined whether or not the response was to be executed (go versus nogo) and parity determined the responding hand. In the other half, classification determined the responding hand and parity determined go versus nogo. LRP data indicated that response preparation occurred before mental rotation was finished. These data contradict strictly sequential discrete models of information processing and suggest continuous flow of information.

Adult

Slow negative brain potentials as reflections of specific modular resources of cognition.

The paper summarizes a series of experiments in which the topography and the amplitude of slow event-related brain potentials (slow ERPs) was studied in cognitive tasks which imposed different amounts of load on functionally distinct processing modules. The results suggest that the topography of slow ERPs reflects the relative activation/inactivation of distinct cortical cell assemblies while the absolute amplitude of the negative maximum seems to reflect how much a particular cell assembly is activated at a particular time. Translated into the terminology of cognitive resource theories one could say that tasks which evoke distinct slow wave patterns draw on independent resources. Likewise, the amplitude of a slow wave pattern could be related to the construct of resource allocation, i.e. the larger the amplitude of a slow wave pattern the more resources of a particular type are allocated to a task. These findings are discussed with respect to possible generator mechanism of slow waves and in relation to possible causes of capacity limitations of the human information processing system.

Brain

Topography of brain electrical activity dissociates the retrieval of spatial versus verbal information from episodic long-term memory in humans.

Topography and amplitude of slow event-related potentials (ERPs) of the electroencephalogram (EEG) were studied during acquisition and recall of spatial and verbal associations. Subjects learned associations between line drawings and two types of mediators. The latter were either positions in a grid or concrete nouns. In a cued recall test subjects had to decide whether two drawings were linked to each other or not via an associated position or noun. The topography of slow ERPs 1-4 s after stimulus presentation obtained from 18 scalp electrodes dissociated the memory processes: The maximum potential was found over the parietal cortex with spatial and over the left frontal cortex with verbal information. The same topographic pattern emerged during both anticipation learning and cued recall. Moreover, the amplitude at the topographic maximum increased when more associations had to be retrieved. These results are compatible with the idea that memory representations are reactivated in localized cortical cell assemblies specialized for particular codes.

Adult

[Malignant degeneration of juvenile laryngeal papillomatosis?].

BACKGROUND: Spontaneous malignant transformation of laryngeal papillomatosis was in the past mostly negated, or the discussion in literature was rather toned down and reserved. Therefore, from a biological and prognostic point of view, HPV infection of the larynx seems to carry a different weight than a viral infection in genital region. According to general consensus, secondary, malignant transformation in juvenile papillomatosis occurs in irradiated patients and leads to the conclusion that radiation therapy of this disease is presently contraindicated. Because there is as yet no causal and curative treatment, repeated and frequent removal of papillomatous tissue by microlaryngoscopy may often be necessary to keep the airway patent. PATIENT, METHOD AND RESULTS: We diagnosed and treated an advanced laryngeal squamous cell carcinoma with lymphatic metastasis in a 50-year old male. Juvenile papillomatosis had been diagnosed already at the age of five, and at the patient's last presentation 5 years ago (age 45), typical clinical and histological features of laryngeal papillomatosis had been observed. Furthermore, virus infection of the papillomatous tissue (HPV-6/11) was proved by using the technique of in-situ hybridisation. Risk factors for malignant transformation, such as smoking, alcohol or radiation, were denied by the patient. CONCLUSIONS: From these aspects, a spontaneous, malignant transformation of laryngeal papillomatosis must be considered with regard to six similar observations in the German and English literature. In the reported case, a tumoural origin in the flat laryngeal mucosa in close neighbourhood to the former site of papillomas, is less probable, albeit not ruled out completely, since continuous changes from benign squamous papilloma to atypical, invasive tumour and a HPV-infection in the carcinomatous tissue could not be proved by in-situ hybridisation.

Carcinoma in Situ

[Memory traces in EEG].

The paper gives a brief overview of five experimental approaches in which memory processes were studied by means of event-related brain potentials (ERPs). Some of the results were already published in English (Study 1), while others are new and will be reported in greater length as full paper elsewhere (Studies 2, 3, 4, and 5). Study 1 revealed that retrieval of information from episodic long-term memory is accompanied by a systematic slow negative potential. The topography of this slow wave depends on the quality of the reactivated information (spatial vs. verbal), and its amplitude reflects the difficulty of the retrieval process. In experiment 2 ERPs were recorded while subjects acquired either explicit or implicit knowledge about a sequential stimulus-response pattern. The data suggest that explicit learners who posses verbalizable knowledge about sequential dependencies have formed both perceptual and motor representations, while implicit learners have formed motor representations only. In study 3 fact retrieval in mental arithmetic was activated by a verification task. Incongruent solutions evoked an arithmetic N400-effect whose amplitude varied with the associative distance between an expected and an actually perceived solution to a multiplication problem. In study 4 ERPs were recorded during mental rotation tasks. A set of experiments revealed that mental rotation is always accompanied by a systematic negative variation over the parietal cortex. The amplitude of this "rotation specific negativity" increases with an increasing angular disparity between a perceived sign and its normal upright template. It was shown that this negativity is functionally distinct from a P300-complex which is often superimposed on it within the same latency window. Finally, study 5 examined ERPs in a sentence reading task in which grammatically legal but infrequent sentence constructions had to be processed. A left-anterior negativity was observed whenever an explicit case marker (the definite article in German) signalled a nominal phrase at a noncanonical position. The LAN phenomenon appears to be a manifestation of a syntax processor which performes a first-pass formal analysis of a sentence and which possibly allocates working memory resources whenever a word cannot be assigned immediately to an expected propositional role.

Brain

Topographically distinct cortical activation in episodic long-term memory: the retrieval of spatial versus verbal information.

Two experiments are reported to study slow potentials in the EEG during reactivation of spatial and verbal information. Subjects had to learn associations between drawings and one, two, or three mediators (locations in Experiment 1, nouns in Experiment 2). During recall, subjects had to decide whether or not two drawings were linked to each other by a common mediator. EEG was recorded during learning and recall. Both experiments were completely equivalent. Irrespective of the quality of the mediators, response time proved to be a linear function of the numbers of mediators to be recalled. Negative slow potentials that accompanied the reactivation of information during anticipation learning and cued recall had a material-specific topography: The maximum was found over the parietal cortex for spatial information and over the left frontal cortex for verbal information. Moreover, the amplitude at these scalp locations varied with the amount of the to-be-retrieved information. The results support the claim of topographically distinct cell assemblies specialized for storage and retrieval of distinct kinds of information.

Adult

Stimulus-induced gamma oscillations: harmonics of alpha activity?

Event-related changes of spectral power of the EEG were studied for each integer frequency between 5 and 100 Hz in three subjects during memory storage and retrieval. Spectra were calculated for successive, overlapping time epochs in seven channels. In one subject a stimulus-locked increase of power was observed at 12 Hz, while in the other two alpha power decreased at the individual peak frequencies of 9 and 11 Hz, respectively. In all subjects corresponding changes of power appeared at frequencies which were integer multiples of the individual dominant alpha frequencies. An analysis of the cross covariance of the alpha, beta and gamma activity revealed high coefficients for harmonic frequencies only while all other covariances were negligibly small. It is argued that event-related gamma activity may be an epiphenomenon of event-related changes within the alpha band.

Adult

Exploring memory functions by means of brain electrical topography: a review.

A series of experiments is reviewed which explored whether the functional brain state of long-term memory retrieval is correlated with specific changes in slow, DC-like event-related brain potentials. The main results are: (1) Retrieving associations from long-term memory is accompanied by a slow negative shift of 5-10 microV which prevails about as long as the retrieval process lasts, i.e., in our experiments, for a period of several seconds: (2) When different types of representations have to be reactivated in memory the slow negative wave shows a clearly distinct topography. The maximum was found in a verbal condition over the left frontal, in a spatial condition over the parietal, and in a color condition over the right occipital to temporal cortex. All these conditions were completely equivalent with respect to the established associative structure, the learning procedure, and the performance criterion. (3) The amplitude of the topographic maximum increases with the number of representations which have to be reactivated. This effect is not due to a non-specific increase of effort but specifically related to the number of activated episodic memory contents which had been experimentally established. In contrast, the reactivation of a priori given semantic association did not become manifest in a specific slow wave effect. These findings are compatible with the idea that memory retrieval implies a reactivation of those cortical cell assemblies in the cortex in which the constituting features of a mnestic entity had originally been processed during perception and learning. The results are also discussed with respect to the possible advantages of EEG and MEG recordings for a cognitive psychophysiology in comparison to other brain imaging techniques as PET or fMRI.

Brain

Patterns of cerebral activation while mental images are rotated and changed in size.

Event-related brain potentials were recorded while subjects performed either a rotation or a size scaling transformation of a mental image. Images had to be rotated 0 degrees, 60 degrees, or 120 degrees or their size had to be enlarged by factors of 1:1, 1:3, or 1:5. Both tasks were accompanied by pronounced negative slow potentials, which extended over several seconds. The relative maximum of these shifts emerged at central to occipital leads. Over the occipital cortex, the negative potential had a similar amplitude level in all conditions and both tasks. However, at parietal and central areas, the negative slow wave changed in relation to the difficulty of the task. The amplitude increased with increasing rotation demands and if the scaling operation required an exact computation of the coordinates of the image. None of these effects could be attributed to an inverse change of P300.

Adult

Safety and efficacy of lifibrol upon four-week administration to patients with primary hypercholesterolaemia.

The efficacy and safety of lifibrol, a novel cholesterol-lowering drug, was investigated in a double-blind clinical study in 168 patients with primary hypercholesterolaemia. Placebo and four lifibrol dose groups (150, 300, 450 and 600 mg/day) were tested over a period of 4 weeks. The mean LDL-cholesterol changes were 5.7%, -11.1%, -27.7%, -34.5% and -35.0%, respectively, after 4 weeks of treatment. No major changes in HDL-cholesterol were seen after this period. With the present study design, a decrease in triglycerides (-28%) was significant in the highest dosage group only. Additionally, it was shown that further independent risk factors for coronary heart disease were favourably influenced. Fibrinogen decreased in all dosage groups with a maximal mean value of 18% and a tendency toward reduction in lipoprotein (a) was observed in patients with high baseline levels (> 30 mg.dl-1). Lifibrol was generally well tolerated in all dosage groups and no serious adverse events were reported. Laboratory parameters did not show any clinically relevant alterations.

Anticholesteremic Agents