Biomedical subjects

H J Müller

Publications and source records attributed to H J Müller.

At least 19 recordsLinked to original sources

PubMed2001

X-ray diffraction and foam film investigations of PC head group interaction in water/ethanol mixtures.

The influence of ethanol on single phospholipid monolayers at the water/air interface and in foam films has been investigated. Grazing incidence X-ray diffraction investigations (GIXD) of Langmuir monolayers from 1,2-distearoyl-phosphatidylcholine (DSPC) spread on water subphases with different amounts of ethanol were performed. The thickness and free specific energy of formation of foam films stabilized by 1,2-dimyristoyl-phosphatidylcholine (DMPC) at different concentrations of ethanol in the film forming dispersions were measured. The GIXD investigations show that the tilt angle of the alkyl chains in the PC lipid monolayer decreases with increasing concentration of ethanol caused by a decrease of the diameter of the head groups. With increasing ethanol content of the solution also the thickness of the aqueous core of PC lipid foam films decreases. We assume that ethanol causes a decreasing probability for the formation of hydrogen bonds of water molecules to the PC head groups. The distinct difference between the effects of ethanol on lipid bilayers as described in the literature and on monolayers and foam films found in this study is discussed. Whereas PC monolayers at the water/air interface become unstable above 25 vol.% ethanol, the PC foam films are stable up to 50 vol.% ethanol. This is related to the decrease of the surface excess energy per lipid molecule by the interaction between the two film surfaces.

Ethanol↗

PubMed2001

Visual search for motion-form conjunctions: is form discriminated within the motion system?

Motion-form conjunction search can be more efficient when the target is moving (a moving 45 degrees tilted line among moving vertical and stationary 45 degrees tilted lines) rather than stationary. This asymmetry may be due to aspects of form being discriminated within a motion system representing only moving items, whereas discrimination of stationary items relies on a static form system (J. Driver & P. McLeod, 1992). Alternatively, it may be due to search exploiting differential motion velocity and direction signals generated by the moving-target and distractor lines. To decide between these alternatives, 4 experiments systematically varied the motion-signal information conveyed by the moving target and distractors while keeping their form difference salient. Moving-target search was found to be facilitated only when differential motion-signal information was available. Thus, there is no need to assume that form is discriminated within the motion system.

Adolescent↗

PubMed2001

Monitoring of Erwinia asparaginase therapy in childhood ALL in the Nordic countries.

AIMS: Evaluation of L-asparaginase therapy in the NOPHO-92 ALL-protocol (treatment protocol of acute lymphoblastic leukaemia of the Nordic Society of Paediatric Haematology and Oncology, initiated in 1992) after intravenous and intramuscular administration of Erwinia asparaginase during induction and re-induction therapy. METHODS: Forty children with newly diagnosed acute lymphoblastic leukaemia received Erwinia asparaginase (30 000 IU/m2 i.v. or i.m.) during induction therapy (every day for 10 days), and 19 children received Erwinia asparaginase (30 000 IU/m2 i.v. or i.m.) during re-induction therapy (twice a week for 2 weeks). Within the treatment periods asparaginase trough activity (using a spectrophotometric assay) was determined on specific days. The goal of therapy is complete L-asparagine depletion, which asparaginase activities above 100 IU l(-1) have been shown to ensure. Therefore determination of L-asparagine (using a h.p.l.c. method) was performed only in plasma samples with asparaginase activities below 100 IU l(-1). RESULTS: During induction therapy 92.2% of the trough enzyme activities were above 500 IU l(-1) for the i.v.-treated patients, and 92.4% of the trough enzyme activities were above 500 IU l(-1) for the i.m.-treated patients. During re-induction therapy 64.7% of the trough enzyme activities were below 100 IU l(-1) in the i.v.-treated group, and 73.3% of the trough enzyme activities were below 100 IU l(-1) in the i.m.-treated group. For trough enzyme activities below 100 IU l(-1) L-asparagine depletion was complete in two thirds of the samples. CONCLUSIONS: In the NOPHO-92 ALL-protocol L-asparaginase treatment during induction therapy was unnecessarily intense, but during the re-induction phase it appeared inadequate.

Adolescent↗

PubMed2001

Drug monitoring of low-dose PEG-asparaginase (Oncaspar) in children with relapsed acute lymphoblastic leukaemia.

Use of asparaginase (ASNase) in the treatment of relapsed childhood acute lymphoblastic leukaemia (ALL) is associated with a high rate of hypersensitive reactions. 'Silent' inactivation may additionally reduce treatment intensity. Therefore, PEG-ASNase (Oncaspar), a polyethylene glycol conjugate of the native Escherichia coli-ASNase, was introduced into the Berlin-Frankfurt-Münster (BFM) 96 treatment protocol for relapsed ALL under drug monitoring conditions. A single i.v. dose of 500 IU/m2 PEG-ASNase, substituted for the native ASNases, was administered to supply a plasma activity of 100 IU/l for 1 week. From November 1997 to March 2000, 35 patients from 23 BFM-associated hospitals, with or without a previous allergic reaction to one or both native preparations, underwent monitoring. After 82 applications, a total of 270 samples were submitted to be tested for ASNase activity. The ASNase activity on the day of the administration and the following day ranged between < 20 and 693 IU/l, with a median of 413 IU/l (53 samples). The median on d 7 +/- 1 was 199 IU/l (range <20--421 IU/l; 41 samples) and on d 14 +/- 1, 105 IU/l (range <20--188 IU/l; 19 samples). An ASNase activity of > 100 IU/l was seen on d 7 in 36 activity time courses of 52 interpretable applications (69%). Intraindividual variability of activity time courses was low. However, a rapid decrease in ASNase activity after repeated applications was observed in 4 out of 20 children. Previously experienced allergic reactions to native ASNases did not influence PEG-ASNase pharmacokinetics. PEG-ASNase is a useful alternative to the native ASNases in children with relapsed ALL. Whenever possible, drug monitoring should be performed to identify patients with 'silent' inactivation.

Adolescent↗

PubMed2001

Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment.

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol, 10 000 U/m2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.

Adolescent↗

PubMed2001

Efficient search for size targets on a background texture gradient: is detection guided by discontinuities in the retinal-size gradient of items?

Six visual search experiments were carried out to investigate the processing of size information in early vision. The apparent size of display items was manipulated independently of their retinal size by placing items on a textured surface which altered the perceived distance in depth of the items. Overall, these experiments demonstrate that a target item differing from non-target items in terms of apparent size can be detected efficiently. However, the pattern of results indicates that, rather than deriving apparent-size information, target detection is guided by discontinuities in the 'retinal-size gradient' of items, in particular between items at the same 'depth'. Although the arrangement of items on the texture surface strongly influenced search, this was largely due to the retinal size of items and the retinal separation between items. The implications of these experiments for the nature of the pre-attentive representation of size are discussed.

Depth Perception↗

PubMed2001

Anaerobic exercise induces moderate acute phase response.

PURPOSE: It was intended to compare the immune reaction after single and repeated short bouts of anaerobic exercise. METHODS: Twelve unspecifically trained male subjects (27 +/- 2 yr, 75 +/- 2 kg, VO(2peak) 52 +/- 2 mL x min(-1) x kg(-1)) performed one 60-s all-out test (SMT) on a cycling ergometer and the same test followed by eight 10-s all-out tests every 5 min (AN-TS). These tests and one control day (Co-Day) were applied in randomized order. At rest and 15 min, 2 h, and 24 h after cessation of exercise the following venous blood parameters were determined: concentration of neutrophils and (CD16(+ -)) premacrophages (both flow-cytometrically), interleukin 6 and 8 (IL-6, IL-8), C-reactive protein (CRP) and cortisol. RESULTS: Two hours after cessation of exercise the neutrophils increased stronger after AN-TS than after SMT (P < 0.01). The peak in the number of premacrophages occurred earlier after SMT (15 min post; P < 0.01 to Co-Day) than after AN-TS (2 h post; P < 0.05 to Co-Day). IL-6 was elevated at 15 min and 2 h after AN-TS (P < 0.01 to SMT and Co-Day) but only slightly 2 h after SMT (P < 0.01 to Co-Day). There were no significant changes in IL-8. CRP was the only elevated parameter 24 h postexercise exclusively after AN-TS (P < 0.05 to Co-Day). CONCLUSIONS Repeated short anaerobic bouts of cycling lead to an acute phase response, which is more pronounced than after a single bout. Athletes should take care in performing such training sessions several times a week because signs of inflammation are detectable even 24 h after cessation of exercise.

Acute-Phase Reaction↗

PubMed2001

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.

OBJECTIVE: Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not been analyzed. The aim of our study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis with long-term follow-up and to see whether patients with mutations have a clinically different natural course compared to those without mutations. METHODS: Eighty two patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of our well defined pancreatitis cohort were screened for the 31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed. RESULTS: A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis. The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis. The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status. CONCLUSION: Our data indicate a significantly increased frequency of cystic fibrosis gene mutations both in patients with alcoholic and idiopathic-juvenile chronic pancreatitis. The natural course was similar in patients with mutations compared to those without mutations.

Adult↗

PubMed2001

Visual search for dimensionally redundant pop-out targets: evidence for parallel-coactive processing of dimensions.

In two visual search experiments, the detection of singleton feature targets redundantly defined on multiple dimensions was investigated. Targets differed from the distractors in orientation, color, or both (redundant targets). In Experiment 1, the various target types were presented either in separate blocks or in random order within blocks. Reaction times to redundant targets significantly violated the race model inequality (Miller, 1982), but only when there was constancy of the target-defining dimension(s) within trial blocks. In Experiment 2, there was dimensional variability within blocks. Consistent with Experiment 1, constancy of the target-defining dimension(s), but this time across successive trials (rather than within blocks), was critical for observing violations of the race model inequality. These results provide evidence for parallel-coactive processing of multiple dimensions, consistent with the dimension-weighting account of Müller, Heller, and Ziegler (1995).

Adolescent↗

PubMed2000

The loci of oscillatory visual-object priming: a combined electroencephalographic and reaction-time study.

The detection of reaction-times (RTs) to a target Kanizsa-type square (an illusory square defined by the colinear arrangement of 90 degrees corner junctions) within a matrix of distractor junctions are expedited when the target display is preceded by a 40-Hz flickering display of premask crosses presented prior to, and at the locations subsequently occupied by the junctions of the target display. Priming effects were obtained when four crosses (which together matched the Gestalt arrangement of the target) were presented at the display locations subsequently occupied by the junctions forming the target Kanizsa square (Elliott and Müller, 1998, 2000). The present study was conducted with the aim of replicating the 40-Hz RT priming effects, while simultaneously recording the observers EEG in order to establish the presence and location of Gestalt priming in the brain. The statistical pattern obtained in the RT data corresponded well with previous studies and was matched by the pattern of target P300 latencies across bilateral central and posterior electrodes. Planned analyses focused upon the evoked 40-Hz activity that co-occurs with the P300, revealing a more specific pattern of 40-Hz priming over the visual cortex. A subsequent series of cross-correlational analyses examined the cortical distribution and timing of Gestalt-prime generation during and subsequent to premask-display presentation. Correlations were revealed between stimulus related 40-Hz activity over a range of cortical loci, including the right temporal lobe, which is considered important for figure coding. Taken together, these findings not only support the role of a distributed 40-Hz mechanism during Gestalt-figure priming, but also suggest that patterns of oscillatory brain activity may be directly influenced by, and interpretable in terms of equivalent temporal patterns of stimulus activity.

Adult↗

PubMed2000

Enhanced GABA(A) inhibition enhances synchrony coding in human perception.

The benzodiazepine, lorazepam enhances the efficiency of local, inhibitory GABA(A) synapses in the cortex, which stabilize postsynaptic, excitatory activity by synchronizing their own discharges at around 40 Hz. Treatment with lorazepam has also been shown to adversely influence detection performance in perceptual tasks, suggesting a role for GABA(A)-mediated synchronization during visuo-perceptual organization. Consistent with these findings we report that reaction times to target stimuli were slower following lorazepam treatment. However, when targets followed presentation of a synchronized prime, presented within a flickering 40-Hz display matrix, the effects of priming were amplified relative to baseline and control conditions. We conclude that enhanced GABA(A)-induced inhibition enhances stimulus-evoked synchronization with differential effects upon mechanisms of perceptual segmentation and grouping.

Adult↗

PubMed2000

Regression of left ventricular hypertrophy by AT1 receptor blockade in renal transplant recipients.

AT1 receptor antagonists control blood pressure (BP) effectively and reduce left ventricular hypertrophy in patients with essential hypertension. Because left ventricular hypertrophy is very common in renal transplant recipients, we examined the cardiovascular effects and the safety profile of the AT1 receptor antagonist losartan in hypertensive renal transplant recipients. In 20 renal transplant recipients with stable renal graft function 50 mg of losartan was added to the preexisting antihypertensive treatment (no angiotensin-converting enzyme inhibitors) at least 6 months after renal transplantation. Twenty-four-hour ambulatory BP, two-dimensional-guided M-mode echocardiography, and duplex sonography, as well as renal function, red blood cell count, cyclosporine A and FK 506 levels, erythropoetin, and angiotensin II concentration were determined at baseline and after 6 months of therapy. With 24-h ambulatory BP measurement, systolic blood pressure (SBP) was reduced by 7.5 +/- 2.4 mm Hg and diastolic blood pressure (DBP) by 4.5 +/- 1.8 mm Hg (P < .01 and P < .05, respectively). Posterior, septal, and relative wall thickness decreased by 0.95 +/- 0.2 mm, 0.91 +/- 0.2 mm and 0.04 +/- 0.01 mm, respectively (all P < .001). Left ventricular mass index decreased by 18.1 +/- 4.7 g/m2 (P < .01). Ejection fraction and midwall fractional fiber shortening as systolic parameters and the relation of passive-to-active diastolic filling of the left ventricle were unaltered. Serum creatinine and cyclosporine A concentration remained stable in all patients. Hemoglobin and hematocrit decreased by 1.0 +/- 0.3 g/dL and 3.6% +/- 0.9%, respectively (P < .002 and P < .001) without a change in serum erythropoetin level. In renal transplant recipients the AT1 receptor antagonist losartan reduces left ventricular hypertrophy without altering systolic or diastolic function. It is safe with regard to renal function and immunosuppression, but slightly decreases hemoglobin level.

Adult↗

PubMed2000

Dimension-based visual attention modulates dual-judgment accuracy in Duncan's (1984) one- versus two-object report paradigm.

Four experiments, adapting the object-judgment paradigm developed by J. Duncan (1984), examined the relationship between object-based and domain-based mechanisms of visual attention. The experiments demonstrated a cross-domain cost, in terms of accuracy, when observers made dual color-form judgments to one or two overlapping objects presented briefly, relative to within-domain, dual-color and dual-form judgments. This domain-based selection effect was additive to an object-based effect, a cost of making dual judgments to separate objects, as reported by J. Duncan (1984). The pattern of object- and domain-based effects points to a capacity limitation in how multidimensional features are bound into a coherent object representation, consistent with the dimension-weighting account of H. J. Miller, D. Heller, and J. Ziegler (1995), which postulates that there is a limit to the total selection weight available to be allocated to an object's dimensions.

Adolescent↗

PubMed2000

Probing distractor inhibition in visual search: inhibition of return.

The role of inhibition of return (IOR) in serial visual search was reinvestigated using R. Klein's (1988) paradigm of a search task followed by a probe-detection task. Probes were presented at either the location of a potentially inhibited search distractor or an empty location. No evidence of IOR was obtained when the search objects were removed after the search-task response. But when the search objects remained on, a pattern of effects similar to Klein's results emerged. However, when just the search-critical object parts were removed or when participants received immediate error feedback to prevent rechecking of the search objects, IOR effects were observed only when probes appeared equally likely at search array and empty locations. These results support the operation of object-based IOR in serial visual search, with IOR demonstrable only when rechecking is prevented (facilitating task switching) and monitoring for probes is not biased toward search objects.

Adolescent↗

PubMed2000

Evidence for 40-Hz oscillatory short-term visual memory revealed by human reaction-time measurements.

Four experiments show that presentation of a synchronous premask frame within a 40-Hz, flickering premask matrix primes subsequent detection of a Kanizsa-type square by generation of a 40-Hz prime. Reaction time (RT) priming effects indicated a 150-200-ms prime duration following premask display. RTs were also found to be sensitive to the phase relationship between offset of the premask display relative to the onset time of the target: Priming effects were maximal when the target was presented out of phase with premask presentation (i.e., at interstimulus intervals displaced by 180 degrees relative to the 40-Hz rhythm of premask-frame presentation). Taken together, these results demonstrate the existence of a very short-term visual memory that oscillates at 40 Hz. The findings are discussed in the context of complementary psychological and neurophysiological findings related to visual-object coding and the role of gamma-band activity in the brain.

Adult↗

PubMed2000

Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity.

Lack of sufficient cellular activity of asparagine synthetase (AS) in blast cells compared with normal tissue is thought to be the basis of the antileukaemic effect of L-asparaginase in acute lymphoblastic leukaemia (ALL). Although L-asparaginase is routinely used in ALL, its role and value in the treatment of acute myelogenous leukaemia (AML) is still being discussed. To evaluate the pharmacological basis for L-asparaginase treatment, we established pretreatment monitoring of the intracellular AS activity in blast cells of patients with AML and ALL. There was no general difference in AS activity between ALL and AML samples. Significantly lower AS activity, however, was found in the B-lineage ALL subgroups as well as AML-M5.

Adolescent↗

PubMed2000

Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols.

Hypersensitivity reactions are relevant adverse effects of asparaginase therapy. Therefore, children treated with native Escherichia coli asparaginase in induction therapy of acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug monitoring. Seventy children, including four patients with allergic reactions during induction, were given one dose of Oncaspar 1,000 U/m2 intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL-Berlin-Frankfurt-Münster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli asparaginase deplete asparagine for about 2-3 weeks, therefore activities of >/= 100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients without an allergic reaction during induction, the mean activity was 606 +/- 313 U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native enzymes but, in contrast to about 30% of hypersensitivity reactions with conventional reinduction therapy, no allergic reaction was seen. Substituting 4 x 10,000 U/m2 asparaginase medac for one dose of 1,000 U/m2 Oncaspar was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two-thirds of patients.

Adolescent↗

PubMed2000

A fronto-posterior network involved in visual dimension changes.

Objects characterized by a unique visual feature may pop out of their environment. When participants have to search for such "odd-one-out" targets, detection is facilitated when targets are consistently defined within the same feature dimension (e.g., color) compared with when the target dimension is uncertain (e.g., color or motion). Further, with dimensional uncertainty, there is a cost when a given target is defined in a different dimension to the preceding target, relative to when the critical dimension remains the same. Behavioral evidence suggests that a target dimension change involves a shift of attention to the new dimension. The present fMRI study revealed increased activation in the left frontopolar cortex, as well as in posterior visual areas of the dorsal and ventral streams, specific to changes in the target dimension. In contrast, activation in the striate cortex was decreased. This pattern suggests control of cross-dimensional attention shifts by the frontopolar cortex, modulating visual cortical processing by increased activation in higher-tier visual areas and suppression of activation in lower-tier areas.

Adolescent↗