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H J Müller

Publications and source records attributed to H J Müller.

At least 19 recordsLinked to original sources
PubMed2004

Exclusion of an extracolonic disease modifier locus on chromosome 1p33-36 in a large Swiss familial adenomatous polyposis kindred.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited colorectal cancer predisposition syndrome, displays considerable inter- and intrafamilial phenotypic heterogeneity, which represents a major problem in genetic counselling of APC mutation carriers. The Min mouse model indicated a putative disease modifier locus on chromosome 4, which is syntenic to human chromosome 1p35-36. This finding was subsequently supported by parametric and nonparametric linkage analyses in FAP families, however, without identifying functional variants in candidate genes. Recently, germline mutations in the base-excision repair gene MYH (1p33-34) have been described in patients with multiple adenomas, pointing to a possible role as disease modifier in FAP. Here, we present critical reassessment of one of the largest FAP kindreds published, which was previously used in linkage mapping of 1p35-36. In this family, all affected members harbour the same APC germline mutation (5945delA), but display marked phenotypic variability, in particular regarding the occurrence of extracolonic disease that segregates in several branches of the family tree. Using updated clinical information, additional mutation carriers and polymorphic markers, fine mapping of the critical region as well as mutation analysis of the MYH gene were performed. These investigations allowed us to significantly exclude (i) the 1p33-36 region as a modifier locus and (ii) MYH as a modifier gene for extracolonic disease in this FAP kindred. Our results do not eliminate 1p33-36 from suspicion in other families, but clearly indicate that in our family linkage analysis of further putative candidate regions is necessary to identify a disease modifier locus in FAP.

Adenomatous Polyposis Coli↗
PubMed2003

Pegylated asparaginase in combination with high-dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study.

The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra-individual comparison of two different doses of PEG-ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. 'Pharmacokinetic' monitoring was performed to evaluate the effect of an intra-individual dose escalation of PEG-ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at > or =100 U/l for 1 week and > or =50 U/l for 10 d. The second course of PEG-ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG-ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG-ASP activity >70% was observed in 65% of the patients. PEG-ASP was well tolerated. Despite the long half-life of PEG-ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.

Adolescent↗
PubMed2002

Top-down controlled visual dimension weighting: an event-related fMRI study.

Target detection in visual singleton feature search is slowed when consecutive targets are defined in different visual dimensions. Behavioral data provide evidence that attentional weight needs to be shifted between dimension-specific processing modules. We found similar dimension-specific change effects in a conjunction search task, in which observers searched for an odd-one-out target defined by a unique combination of size and color or, respectively, size and motion direction. Changes of the secondary target dimension (color or motion) across trials, but not target feature changes within a dimension, increased the time required to detect the target. Dimensional change costs were greatly increased for singleton conjunction search compared to singleton feature search. This suggests involvement of top-down control processes in dimensional change in conjunction search, in contrast to stimulus-driven dimensional change in singleton feature search. The functional anatomical correlates of top-down controlled visual dimension changes were investigated in two event-related functional magnetic resonance imaging (fMRI) experiments. In Experiment 1, dimensional change in singleton conjunction search was accompanied by transient activations in a fronto-posterior network of brain areas that was largely non-overlapping with the general network activated during visual search. Experiment 2, which contrasted singleton feature and conjunction search within the same session, revealed a double dissociation in anterior prefrontal cortex: left frontopolar cortex was selectively involved in stimulus-driven dimension changes but not in top-down controlled dimension changes, whereas the reverse was observed in frontomedian cortex.

Adult↗
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

Comparison of intramuscular therapy with Erwinia asparaginase and asparaginase Medac: pharmacokinetics, pharmacodynamics, formation of antibodies and influence on the coagulation system.

Asparaginase comes from different biological sources and the various preparations have different pharmacokinetic properties, and their tendency to induce side-effects is different. Erwinia asparaginase (ASNase) has a shorter half-life than the Escherichia coli preparations, and it has been reported to be less immunogenic than the E. coli preparations and to induce fewer coagulation disorders. Children with newly diagnosed acute lymphoblastic leukaemia (ALL) were included in this study. Twenty-seven patients were treated with Erwinia ASNase (induction therapy 30.000 IU/m2/d i.m. for 10 d, and re-induction therapy 30.000 IU/m2 twice a week for 2 weeks) and 15 were treated with ASNase Medac (induction therapy 1.000 IU/m2/d i.m. for 10 d, and re-induction therapy 5.000 IU/m2 i.m. twice a week for 2 weeks). Blood samples were drawn to determine enzyme activity, l-asparagine, anti-asparaginase antibodies, and coagulation parameters. After i.m. administration, Erwinia ASNase displayed a protracted absorption phase compared to ASNase Medac. The mean bioavailability after i.m. administration was 27% for Erwinia ASNase and 45% for ASNase Medac respectively. Mean trough enzyme activities during induction therapy were Erwinia ASNase 1748 IU/l and ASNase Medac 272 IU/l, and during re-induction therapy Erwinia ASNase 83 IU/l and ASNase Medac 147 IU/l. We conclude that in this setting, therapy with ASNase Medac resulted in sufficient treatment during both phases of therapy, whereas treatment with Erwinia ASNase resulted in unnecessarily intense therapy during the induction phase and insufficient treatment during the re-induction phase. There was no significant difference in the incidence of antibody formation, and therapy with Erwinia ASNase resulted in a more pronounced influence on the coagulation parameters than therapy with ASNase Medac.

Absorption↗
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↗