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Biomedical subjects

K Maurer

Publications and source records attributed to K Maurer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Main risk factors for schizophrenia: increased familial loading and pre- and peri-natal complications antagonize the protective effect of oestrogen in women.

Women fall ill with schizophrenia 3 to 4 years later than men. The neurobiological mechanism, explaining the delay of onset in women until menopause, is presumably due to a sensitivity reducing effect of oestrogen on central d(2) receptors, as we have previously shown in animal experiments and in a controlled clinical study. The gender difference in age at onset seems to disappear in familial cases with schizophrenia, but it increases to highly significant values of 5 years or more in isolated cases according to a recent study by Albus and Maier (Schizophrenia Research 18:51-57, 1995). We tried to replicate these findings and to test the hypothesis of a functional antagonism between genetic predisposition to illness and the protective effect of oestrogen in a population-based sample of 232 first illness episodes of schizophrenia. In women with at least one first-degree relative suffering from schizophrenia, age at onset defined by first psychotic symptom was significantly reduced by several years and the difference with men disappeared. In sporadic female cases (no mental disorder in first-degree relatives) the age at onset was slightly increased compared with the total sample, which was in accordance with our hypothesis. In men with familial schizophrenia, but without a protective agent like oestrogen, the age at onset was only slightly and non-significantly reduced compared with the total group and with sporadic cases. This was in line with Albus and Maier and with our hypothesis that only the protective effect of oestrogen could be antagonized by a strong genetic disposition. The second main risk factor for schizophrenia is pre- and peri-natal complications. We compared men and women from our sample of first illness episodes with a history of pre- and peri-natal complications with those without a history of obstetric complications. In women the age at first psychotic symptom was markedly reduced, but due to small case numbers not significantly, compared with women without the risk factor and with the total group. Again, schizophrenic men with a history of pre- and peri-natal complications showed only a small, non-significant reduction of age at onset compared with the total and the group without the risk factor. Therefore, we concluded that the degree of genetically determined vulnerability and, presumably to a slightly lesser extent, the degree of pre- and peri-natal brain injury antagonizes the onset delaying effect of oestrogen in schizophrenia.

Adolescent↗
PubMed2000

[Therapy of Alzheimer dementia. Current status and prospects].

In recent years, considerable progress has been made both in the diagnosis and treatment of dementia. Drugs have been developed which enhance cognitive performance in a large percentage of those afflicted, delay impairment of the ability to cope with the tasks of daily life, and avoid premature admission to a nursing home. In the practical medical care setting, however, these advantages are being utilized to only a limited extent, and this despite the fact that numerous therapeutic options are now available for the treatment of AD. New therapeutic approaches are aimed at inhibiting the pathological cleavage and extracellular and intracellular deposition of amyloid, preventing the toxic effects of amyloid accumulation around the neurons, and re-establishing intracellular transport deranged by the aggregation of neurofibrils. A further approach is the use of combinations of available substances with differing, possibly synergic, effects. Over and beyond this, treatment of AD in the "presymptomatic stage", or in the stage of only mild cognitive disturbance, is currently the subject of clinical trials.

Aged↗
PubMed2000

Carbonyl J Derivatives: A New Class of HIV-1 Integrase Inhibitors.

Integration of a DNA copy of the HIV-1 genome is required for viral replication and pathogenicity, and this highly specific molecular process is mediated by the virus-encoded integrase protein. The requirement for integration, combined with the lack of a known analogous process in mammalian cells, makes integrase an attractive target for therapeutic inhibitors of HIV-1 replication. While many reports of HIV-1 IN inhibitors exist, no such compounds have yet emerged to treat HIV-1 infection. As such, new classes of integrase inhibitors are needed. We have combined molecular modeling and combinatorial chemistry to identify and develop a new class of HIV-1 integrase inhibitors, the Carbonyl J [N,N'-bis(2-(5-hydroxy-7-naphthalenesulfonic acid)urea] derivatives. This new class includes a number of compounds with sub-micromolar IC(50) values for inhibiting purified HIV-1 integrase in vitro. Herein we describe the chemical characteristics that are important for integrase inhibition and cell toxicity within the Carbonyl J derivatives. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment.

OBJECTIVE: The aim of the present study was to compare the efficacy and safety of tiapride versus haloperidol and placebo in the treatment of agitation and aggressiveness in elderly patients with mild or moderate mental impairment. METHOD: This international, multicentre, randomized, double blind, three parallel groups study compared efficacy and safety of a 21 -day regimen of tiapride 100-300 mg/day versus haloperidol 2-6 mg/day and placebo in 306 elderly patients with mild or moderate dementia according to DSM III R and behavioural troubles with the Multidimensional Observation Scale for the Elderly Subjects (MOSES) irritability/aggressiveness subscore ranging from 16 to 30. RESULTS: The percentage of responders (defined as patients with at least a 25% MOSES irritability/aggressiveness subscore decrease between the inclusion and the end of the treatment) was significantly greater in the tiapride (63%, P=0.04) and haloperidol (69%, P=0.004) groups than in the placebo group (49%), with no significant difference between the active drugs. Similar results were observed for the mean MOSES irritability/aggressiveness subscores on D7, D21 and at D(end) which were significantly smaller in the tiapride and haloperidol groups than in the placebo group. The decrease between D0 and D(end) was significantly greater in the tiapride (6.57, P=0.009) and haloperidol groups (6.75, P=0.005) than in the placebo group (4.71). The global improvement CGI was significantly better in the tiapride and haloperidol groups than in the placebo group (P=0.03 and P=0.02). No significant difference was observed between the two active drugs or among the three treatment groups for the Folstein's Mini Mental Status scale (MMS) total score, and there was no notable change during treatment. The number of patients with adverse events, assessed on the Udvalg Kliniske Undersogelser scale (UKU), and the number of UKU symptoms were smaller in the tiapride group (62 patients, 61%, 212 events) than in the haloperidol group (77 patients, 76%, 305 events) and identical to that observed in the placebo group (69 patients, 67%, 234 events). Of interest, the number of patients with at least one extrapyramidal symptom was significantly lower (P=0.003) in the tiapride group (16 patients, 16%) than in the haloperidol group (34 patients, 34%) and similar to that of the placebo group (18 patients, 17%); the difference observed between the haloperidol and placebo groups was significant (P=0.008). CONCLUSION: Tiapride is not different from haloperidol in the treatment of agitation and aggressiveness in elderly patients and better tolerated, in particular with significantly fewer extrapyramidal symptoms.

Aged↗
PubMed2000

Spatial pattern of cerebral glucose metabolism (PET) correlates with localization of intracerebral EEG-generators in Alzheimer's disease.

BACKGROUND: Since the measurement of human cerebral glucose metabolism (GluM) by positron emission tomography (PET) and that of human cerebral electrical activity by EEG reflect synaptic activity, both methods should be related in their cerebral spatial distribution. Healthy subjects do indeed demonstrate similar metabolic and neuroelectric spatial patterns. OBJECTIVE: The aim of the study was to show that this similarity of GluM and EEG spatial patterns holds true in a population with a high variability of glucose metabolism. METHODS: We investigated healthy control subjects and patients with varying degrees of cognitive dysfunction and varying GluM patterns by applying [18F]FDG PET and EEG. RESULTS: We demonstrated that the localization of intracerebral generators of EEG correlates with spatial indices of GluM. CONCLUSION: These results indicates that EEG provides similar spatial information about brain function as GluM-PET. Since EEG is a non-invasive technique, which is more widely available and can be repeated more often than PET, this may have important implications both for neuropsychiatric research and for clinical diagnosis. However, further studies are required to determine whether equivalent EEG dipole generators can yield a diagnostic specificity and sensitivity similar to that of GluM-PET.

Aged↗
PubMed1999

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects.

RATIONALE: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. OBJECTIVE: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. METHODS: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. RESULTS: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. CONCLUSIONS: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity.

Adult↗
PubMed1999

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

Atrophy↗
PubMed1999

Trends in infection morbidity in a pediatric oncology ward, 1986-1995.

BACKGROUND AND PROCEDURE: We retrospectively studied the type, severity, frequency, and outcome of febrile infectious complications in 217 cancer patients receiving cytotoxic chemotherapy (603 episodes) over a 10-year period in a single pediatric institution. RESULTS: A total of 48.8% of the episodes occurred in severely leukopenic patients (WBC < 1.0 x 10(9)/l, absolute neutrophil count < 500 x 10(6)/l). In the second half of the study period febrile episodes occurred at increased frequency. The number of patients with gram-positive isolates in blood cultures increased over the years, most frequently coagulase-negative staphylococci were found. Remarkably, gram-negative bacteria increasingly resistant to the administered first-line antibiotic regimen emerged, necessitating modifications of the antimicrobial strategy every 3 years. Furthermore, Clostridium difficile-associated enterocolitis posed a clinical problem at increasing frequency since 1993. As expected, the speed of leukocyte recovery within 5 days from the onset of a febrile complication had an influence on the outcome of these episodes. CONCLUSIONS: Rapid recovery of the WBC was associated with an excellent prognosis whereas persisting neutropenia was found to be a negative factor associated with fatal outcomes. The fatality rate of all febrile episodes (2.3%) remained the same throughout the study period despite the availability and wider use of recombinant hematopoietic growth factors since 1991.

Adolescent↗
PubMed1999

Generators of brain electrical activity in patients with Wilson's disease.

Electroencephalographic (EEG) generators were investigated in 13 patients suffering from hepatolenticular degeneration with and without neurological symptoms and in 13 healthy subjects for comparison by the use of FFT approximation. Quantitative assessment of motor deficits and psychiatric disturbances was correlated with EEG features. We found mainly an increase in delta activity, a decrease in alpha activity combined with a more posterior localisation of the EEG generators in the delta band and a more anterior one in the alpha band in patients compared with healthy controls. The localisation of the EEG generators in the patients with clinical apparent neurological symptoms were in all frequency bands more superficial compared with controls and patients without neurological symptoms. With longer duration of the disease, the lower the premorbid intelligence the more posterior was the delta EEG generator localised. Although the alpha EEG generator was more anteriorly localised with longer duration of the disease and more severe cognitive deficits, it was more superficial with more pronounced psychiatric symptoms, more severe cognitive deficits, lower premorbid intelligence and more pronounced motor disabilities. With more pronounced psychiatric symptoms and cognitive deficits, the beta EEG generator was more anteriorly localised. The present study demonstrated that a significant deviant EEG pattern exists between patients with and without clinical neurological symptoms and that stage-dependent alterations in psychiatric symptoms and cognitive ability are reflected on the EEG.

Adult↗
PubMed1999

Mnestic block syndrome.

The case of a patient with largely preserved intelligence, but severe and persistent memory impairments is reported. FA, a 46-year-old patient with the diagnosis of prolonged depression was investigated repeatedly over a two year period with neuroradiological, neuropsychological, neuromonitoring and other methods. While no brain damage was detectable in FA, he manifested continued and severe anterograde and retrograde memory disorders together with an inhibition in his thinking processes. Otherwise, his intellectual capabilities were in the normal range, that is he was not pseudo-demented. Various approaches with drug treatment and psychotherapy failed to improve his condition. The condition is interpreted as 'mnestic block syndrome' and is considered to be related to an altered brain metabolism which may include changes in various transmitter and hormonal systems (GABA-agonists, glucocorticoids, acetylcholine). Whether depression contributes to this syndrome is uncertain from FA's cognitive performance, but may be a possibility.

Amnesia, Retrograde↗
PubMed1999

Complications of percutaneous insertion of Hickman catheters in children.

BACKGROUND/PURPOSE: The aim of this study was a retrospective evaluation of insertion and management complications of percutaneous Hickman catheter lines in pediatric patients to investigate whether the complication rate is acceptable in comparison with other insertion methods or other age groups. METHODS: Over a period of 22 months a total of 27 Hickman catheters were inserted in 22 pediatric patients (20 oncological, 2 nononcological; age 6 weeks to 17.5 years). RESULTS: Twenty-three of 36 insertion attempts (63.9%) were successful at first attempt. In another 4 patients, catheters were placed after repeated attempts. In an additional 4 patients, catheters were inserted by surgeons after percutaneous insertion failed. As immediate complications, 1 pneumothorax and 1 malposition were seen. Late complications included 1 to 29 (median, 8) days of fever in 15 patients, corresponding to 53 of 1,000 catheter days. Fourteen patients showed 21 positive blood cultures, including 11 cases of Staphylococcus epidermides, which might be related to the catheter. Antibiotics were given for a total of 1 to 130 (median, 35) days, that is 205 of 1,000 catheter days. No catheter was removed because of infectious complications. The total life span of the Hickman catheters was 1 to 371 (median, 163) days, the patients were in the hospital from 1 to 351 (median, 102) days because of their underlying disease. At the end of the study period, 8 of 27 (29.6%) catheters remained functioning in situ; 9 (33.3%) had been selectively removed. Two patients died with the catheter (7.4%) functioning well. Another 2 patients showed catheter thrombosis. Six catheters (22.2%) in 5 patients showed inadvertent dislodgement. CONCLUSION: Percutaneous Hickman catheter insertion in pediatric patients is effective; however, complication rate is relevant, but not higher than percutaneous insertion of subclavian vein or Hickman catheters in adults.

Adolescent↗
PubMed1999

Perceiving individuals and groups: expectancies, dispositional inferences, and causal attributions.

Two experiments investigated differences in forming impressions of individual and group targets. Experiment 1 showed that when forming an impression of an individual, perceivers made more extreme trait judgments, made those judgments more quickly and with greater confidence, and recalled more information than when the impression target was a group. Experiment 2 showed that when participants were forming an impression of an individual, expectancy-inconsistent behaviors spontaneously triggered causal attributions to resolve the inconsistency; this was not the case when the impression target was a group. Results are interpreted as reflecting perceivers' a priori assumptions of unity and coherence in individual versus group targets.

Analysis of Variance↗
PubMed1999

Effective T cell regeneration following high-dose chemotherapy rescued with CD34+ cell enriched peripheral blood progenitor cells in children.

The ex vivo enrichment for the CD34+ cell fraction of PBPC, while it retains the capacity to restore haematopoiesis and potentially reduces a contamination by tumour cells, implements a depletion of T cells. To test whether such a setting adversely affects T cell reconstitution, we monitored T cells in four paediatric patients after CD34+ selected PBPC transplantation. The dose of CD34+ cells, which were enriched to 74%, median, was 7.1 x 10(6)/kg, median, that of T cells was 0.071 x 10(6)/kg, median. The patients were homogenous with respect to features with a potential to effect T cell reconstitution (low median age, (35 years); stage IV malignant tumours in first CR, uncomplicated post-treatment course). The results of sequential FACS analyses showed that by 9 months after treatment all four patients had recovered (1) a normal T cell count (CD3+ cells 1434/microl, median); (2) a normal CD4+ cell count (816/microl, median), while CD8+ cells were recovered (>330/microl) already by 3 months; (3) a normal CD4/CD8 ratio (1.8, median), as a result of an augmented growth of CD4+ cells between 3 and 6 months (increase of CD4+ cells 4.9-fold, median, CD8+ cells 1.1-fold, median). Expansion of cells with a CD45RA+ phenotype (thymus-derived T cells) predominated; from 3 to 6 months the increase of CD4+/CD45RA+ T cells was 130-fold, that of CD4+/CD45RO+ cells was 1.7-fold; CD8+/CD45RA+ cells increased 9-fold, CD8+/CD45RO+ cells increased 2.1-fold, indicating effective thymopoiesis. The findings demonstrate that in paediatric patients the setting of HD-CTX rescued with autologous CD34+ selected PBPC per se is not predictive of an impaired T cell recovery. High thymic activity may be a key factor for the rapid restoration of T cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia.

OBJECTIVE: The aim of this study was to investigate when social consequences in schizophrenia emerge, and what conditions give rise to the social disadvantage evident in people suffering from schizophrenia. METHOD: Early course in schizophrenia was studied in a population-based sample of 232 first illness-episode cases retrospectively from onset to first admission, and in a representative subsample of 115 patients prospectively at six cross-sections over a period of 5 years. Data on non-specific and negative symptomatology and social development was compared with data from an age- and sex-matched control group drawn from the normal population. RESULTS: In total, 73% of the patients showed a prodromal phase of several years. First signs were depressive and negative symptoms. In 57% of cases social disability emerged 2 to 4 years before first admission. Social consequences depended on the level of social development at onset. An early onset involved social stagnation, and a late onset was associated with social decline. Men's poorer social outcome was determined by their lower level of social development at onset and socially adverse illness behaviour. The 5-year symptom-related course showed no gender difference. At 81% the lifetime prevalence of depressive mood until first admission was several times higher in schizophrenics than in healthy controls. Early depression predicted a lower subsequent score for affective flattening. Suicide indicators were predicted by lack of self-confidence and feelings of guilt early in the illness. CONCLUSION: Taking into account a prodromal phase of several years on average before first hospital admission, early detection, case identification and intervention are urgently needed. The intervention must be targeted at syndromes such as early depression, negative symptoms and certain forms of cognitive and social impairment.

Adult↗
PubMed1998

Multimodal imaging of residual function and compensatory resource allocation in cortical atrophy: a case study of parietal lobe function in a patient with Huntington's disease.

In a case of Huntington's disease (HD) with dementia and pronounced parieto-frontal atrophy, the functional state of the affected regions was investigated using functional magnetic resonance imaging (fMRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET). It was observed that although parietal areas showed extensive atrophy and reduced resting glucose metabolism, the patient performed with similar accuracy but with longer response time in a visuospatial task compared with healthy control subjects. At the same time, the blood oxygen level-dependent (BOLD) fMRI signal in these areas, which are involved in visuospatial processing, showed a similar task-dependent modulation as in control subjects. The signal amplitude (signal percent change) of the task-dependent activation was even higher for the HD patient than in the control group. This residual functionality of parietal areas involved in visuospatial processing could account for the patient's performance in the task concerned, which contrasted with his poor performance in other cognitive tasks. The increased percent-signal change suggests that a higher neuronal effort was necessary to reach a similar degree of accuracy as in control subjects, fitting well with the longer reaction time. We propose that fMRI should be considered as a tool for the assessment of functionality of morphologically abnormal cortex and for the investigation of compensatory resource allocation in neurodegenerative disorders.

Adult↗
PubMed1998

Exposure to environmental tobacco smoke and risk factors for heart disease among never smokers in the Third National Health and Nutrition Examination Survey.

The relative risk of coronary artery disease among never smokers exposed to environmental tobacco smoke (ETS) versus never smokers not exposed to ETS is approximately 1.2 based on more than a dozen epidemiologic studies. Most of these studies have controlled for the major heart disease risk factors, but residual or uncontrolled confounding remains a possible explanation for the epidemiologic findings. The authors studied 3,338 never-smoking adults aged 17 years or older, who are representative of all US never smokers, in the 1988-1991 Third National Health and Nutrition Examination Survey (NHANES III) to determine whether selected risk factors for heart disease differ between ETS-exposed and -nonexposed persons. Both self-reported ETS exposure (at home and at work) and serum cotinine levels were available, the latter reflecting recent ETS exposure. After adjustments were made for age, sex, race, and education among adults aged 17 years or older, no significant differences were found between the ETS exposed and the nonexposed for any of 13 cardiovascular risk factors with the exception of dietary carotene, which was lower among the exposed. On the other hand, significant positive linear trends were found between serum cotinine and two risk factors (body mass index and alcohol consumption), and significant inverse trends were found with dietary carotene. There were also few differences between exposed and nonexposed never smokers among adults aged 40 years or older, who are most at risk of heart disease. In this group, however, there was an inverse linear trend between serum cotinine and high density lipoprotein cholesterol (p < 0.001). This finding could result from ETS exposure rather than be an indication of confounding; a similar inverse trend was found for children, confirming other results in the literature. Overall, these data suggest little potential for confounding by the heart disease risk factors studied here when ETS exposure is determined by self-report.

Adolescent↗
PubMed1998

Increase of optical illusion in demented patients.

Assuming a particular psychological function of optical gestalt perception, its impairment would lead to a decreasing extent of gestalt related optical illusion. An increase of optical illusion would be expected in the case of a loss of adaptability and cognitive compensation, usually revising the phenomenon of optical illusion. 16 demented out-patients were compared to 16 hospitalized schizophrenics by a 'Computerized Assessment of Change in Optical Illusion' (CACOI), measuring the extent of optical illusion by patient's assessment of 12 variations of the figure of Mueller-Lyer, differing in baseline length. The results showed a significant increase of optical illusion in demented patients compared to the schizophrenic controls (p = 0.019). Taking into account that the extent of optical illusion by the figure of Mueller-Lyer usually is decreasing with age and was found to be increased in schizophrenics, our results support the hypothesis of an early loss of adaptability and cognitive compensation in dementia.

Aged↗