Biomedical subjects

H Walter

Publications and source records attributed to H Walter.

At least 19 recordsLinked to original sources

PubMed2006

[The concept of working memory in schizophrenia: current evidence and future perspectives].

Working memory (WM) deficits are core symptoms of cognitive impairment in schizophrenia. The psychological concept of WM offers a theoretical and empirical framework for the investigation of perceptual and attentional dysfunction as well as of deficits of higher cognitive functions in schizophrenia. From a theoretical perspective, schizophrenic psychopathology and cognitive dysfunction can be both integrated and experimentally validated within the concept of WM-impairment. In the last years investigation of WM has been a major issue in neuropsychiatric research, not least because of the association of prefrontal cortex and WM-function. The advent of functional imaging techniques, e. g. functional magnetic resonance imaging (fmri) has additionally contributed in generating neurobiological WM-models. Regarding the neuronal basis of WM-deficits in schizophrenia, prefrontal cortex dysfunction has been of major interest. This review provides a short overview on the concept of WM and its relevance for cognitive psychology, discussing both recent behavioral and functional neuroimaging evidence on WM-dysfunction in schizophrenia.

Cognition Disorders↗

PubMed2005

Severe HIV-1 encephalitis and development of cerebral non-Hodgkin lymphoma in a patient with persistent strong HIV-1 replication in the brain despite potent HAART -- case report and review of the literature.

A 39 year old patient with HIV-1 infection, who was asymptomatic without antiretroviral therapy (HAART) for ten years, developed severe encephalopathy. Despite therapy with a four drug antiretroviral combination regimen including two protease-inhibitors (PI), plasma viral load could not be suppressed sufficiently with persistence of low level viremia of 3.08-3.40 log copies/ml, even after addition of two other antiretroviral drugs. On therapy the patient showed improvement of clinical symptoms, however with severe persisting cognitive deficits. Repeated parallel measurements of viral load showed a far higher viremia in the cerebrospinal fluid than in the plasma. Resistance testing provided no evidence of relevant PI-mutations and analysis of protease inhibitor levels demonstrated good plasma levels. 17 months after start of HAART, the patient developed a cerebral Non-Hodgkin lymphoma, leading to his death despite radiation therapy. There has been a dramatic reduction in the prevalence of HIV-1 associated CNS events in the post-HAART era. Nevertheless, subgroups of patients are infected with neurotropic viral variants which could cause progressive neurological pathology as they can not be reached sufficiently by the available drugs. These patients require the development of new drugs that achieve a better penetration into the brain.

AIDS Dementia Complex↗

PubMed2005

[Emotional dysfunction, psychopathy and cognitive neuroscience. What is new and what are the consequences].

This article provides a review of recent findings in the cognitive neurosciences on antisocial personality disorders. There is accumulating evidence that the subtype of psychopathy is characterized by emotional dysfunction not only on the behavioral level but also by structural and functional abnormalities of the brain. Although the findings are not yet conclusive, they are already being discussed controversially with respect to the question of accountability of persons with psychopathy. False conclusions dominating these considerations are discussed and corrected. The findings open a new discussion of the relevance of emotional function and dysfunction for accountability.

Affective Symptoms↗

PubMed2004

[Conversion disorders. From neurobiology to treatment].

The two international systems of diagnostic classification for psychiatric disorders, ICD-10 and DSM-IV, differentiate a variety of disorders or syndromes characterized by the common feature of the presence of physical symptoms without "organic correlate." Conversion disorders (DSM) or dissociative disorders (ICD) are historically related to the concept of hysteria. Like psychoanalytical theories, the DSM and ICD refer to a psychological conflict preceding the onset of physical symptoms, although in a purely descriptive manner. The etiology of these disorders is still not very well understood. This article summarizes present knowledge from clinical and epidemiological studies. Functional neuroimaging studies on conversion disorders, although still very rare, allow testing of hypotheses about neuronal mechanisms. Such studies question the traditional and often misinterpreted dichotomy between organic and psychogenic diseases.

Cerebral Cortex↗

PubMed2004

Intensive training of patients with hypertension is effective in modifying lifestyle risk factors.

The burden of insufficiently treated arterial hypertension is still underestimated. In addition to pharmacological therapy, patient training is a valuable therapeutic option. During 1998-1999, the Institute for Preventive Medicine conducted an intensive training programme in cooperation with regional practitioners. The goal of this programme was to educate patients about their disease and motivate them to comply with the therapy. To evaluate the effectivity of this programme, 126 patients with arterial hypertension were trained. They received eight training sessions of 90 min each. In 90 patients blood pressure measurements before and 6 months after training were available. In addition, data concerning health status and lifestyle risk factors were analysed with standardised questionnaires. There was a marked reduction in blood pressure after 6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by 0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline of blood pressure was also greater in obese patients, but did not reach statistical significance. The activity score for physical exercise increased overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about hypertension increased as well (P<0.01). Of all the quality life measurements, the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the patients' self-estimation. In conclusion, training of hypertensive patients has a profound effect on blood pressure control. It motivates patients to change lifestyle risk factors, namely to lose weight, and increases the patients' physical activity level, thereby decreasing the patients' blood pressure. Thus, intensive training programmes are effective and should be used on a widespread basis.

Adult↗

PubMed2003

Gender-specific differences in alcoholism: implications for treatment.

Alcohol abuse and alcoholism cut across gender, race and nationality. In general, more men than women are alcohol dependent or have alcohol problems, but women are at greater risk for adverse effects and alcohol-related diseases. Death rates among female alcoholics are 50 to 100 percent higher than those of men. Major physiological impairments, the diagnostic distribution, the psychosocial consequences and their implication on treatment will be outlined.

Alcohol-Related Disorders↗

PubMed2003

Water quality objectives for mixtures of toxic chemicals: problems and perspectives.

The need to develop water quality objectives not only for single substances but also for mixtures of chemicals seems evident. For that purpose, the conceptual basis could be the use of the two existing biometric models: concentration addition (CA) and independent action (IA), which is also called response addition. Both may allow calculation of the toxicity of mixtures of chemicals with similar modes of action (CA) or dissimilar modes of action (IA), respectively. The joint research project Prediction and Assessment of the Aquatic Toxicity of Mixtures of Chemicals (PREDICT) within the framework of the IVth Environment and Climate Programme of the European Commission, provided the opportunity to address (a) chemometric and QSAR criteria to classify substances as supposedly similarly or dissimilarly acting; (b) the predictive values of both models for the toxicity of mixtures at low, statistically nonsignificant effect concentrations of the individual components; and (c) the predictability of mixture toxicity at higher levels of biological complexity. In this article, the general outline, methodological approach, and some preliminary findings of PREDICT are presented. A procedure for classifying chemicals in relation to their structural and toxicological similarities has been developed. The predictive capabilities of CA and IA models have been demonstrated for single species and, to some extent, for multispecies testing. The role of very low effect concentrations in multiple mixtures has been evaluated. Problems and perspectives concerning the development of water quality objectives for mixtures are discussed.

Animals↗

PubMed2003

Verbal storage in a premotor-parietal network: evidence from fMRI-guided magnetic stimulation.

Phonological rehearsal helps to keep selected information consciously in mind for further processing. This part of short-term storage takes place during the delay period of verbal working memory tasks and involves a frontoparietal network as functional magnetic resonance imaging (fMRI) studies have shown. The involved cortical areas can be further investigated by interfering with the local information processing using transcranial magnetic stimulation (TMS). On a single subject level, we identified predominantly left-sided premotor, prefrontal, and parietal areas active during the delay period of a verbal working memory task using event-related fMRI. In a pilot approach, TMS was neuronavigated to the individually active areas by using a stereotaxic device. Then, TMS was applied during the delay period of similar tasks as in fMRI. Error rates increased significantly upon stimulating left premotor cortex, but not upon parietal or prefrontal stimulation. The contribution of the premotor cortex to storage and rehearsal is discussed as an active top-down storage process within the frontoparietal network.

Adult↗

PubMed2003

Enhanced soluble interleukin-5 receptor alpha expression in nasal polyposis.

BACKGROUND: Alternative splicing of the interleukin-5 receptor alpha (IL-5Ralpha)-subunit leads to the generation of a signalling, membrane-anchored (TM) isoform, or a secreted [soluble (SOL)], antagonistic variant. Given the key role of IL-5 in eosinophil function, we investigated SOL IL-5Ralpha expression pattern in an eosinophil-associated disease such as nasal polyposis (NP). METHODS: An SOL IL-5Ralpha enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR) were established and applied in serum, nasal secretion and nasal tissue of controls (n = 12), and NP patients (n = 42) with or without asthma. RESULTS: Analysis of serum, nasal secretion, and nasal tissue samples revealed that SOL IL-5Ralpha protein concentrations were significantly increased in NP vs control tissue. Within the NP group, there was a significant up-regulation of SOL IL-5Ralpha in patients with systemic airway disease. These findings were confirmed at the mRNA level, using an optimized real-time reverse-transcriptase PCR procedure. CONCLUSIONS: This report demonstrates SOL IL-5Ralpha transcript and protein up-regulation in NP. Soluble IL-5Ralpha differentiates nasal polyps with or without concomitant asthma. As SOL IL-5Ralpha is strongly up-regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti-IL-5.

Adult↗

PubMed2003

Flupenthixol versus risperidone: subjective quality of life as an important factor for compliance in chronic schizophrenic patients.

OBJECTIVE: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end "haloperidol" to its atypical end "clozapine", flupenthixol has typical and atypical characteristics. METHODS: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30). RESULTS: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories "control of their thoughts", concentration and "feeling better in general" ameliorated in both groups. In the flupenthixol group, the "ability to cope with stress", "feel more relaxed" and the "ability to achieve something" improved significantly more than in the risperidone group. CONCLUSIONS: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups.

Adolescent↗

PubMed2002

Initiation of HAART in drug-naive HIV type 1 patients prevents viral breakthrough for a median period of 35.5 months in 60% of the patients.

The introduction of potent combinations of antiviral drugs is a major breakthrough in the treatment of HIV. We investigated the long-term virologic outcome and the development of resistance after initiating highly active antiretroviral therapy (HAART) in drug-naive patients in daily clinical practice. Twenty-five treatment-naive HIV-1 patients were started on HAART. Fifteen patients responded with a drop in viral load below the limit of detection during 35.5 (interquartile range: 7) months of therapy. In 6 of 10 patients with virologic failure, virus with resistance-related mutations against the received drugs emerged. Compared with responders (R), nonresponding (NR) patients were in a later disease stage at therapy start (p = 0.0089) with lower CD4 cell counts at baseline (p = 0.040), and a lower proportion of nonresponders showed protease inhibitor (PI) levels above C(min) (p = 0.049). More NR patients showed secondary PI mutations at baseline (p = 0.079), and the CCR2-64I coreceptor polymorphism was absent among NR patients, compared with 38.5% of R patients displaying CCR2-64I (p = 0.053), although the differences were not significant. In conclusion, starting HAART in antiretroviral drug-naive HIV-infected patients followed in daily clinical practice prevented viral breakthrough for up to 44 months in 60% of the patients. Virologic failure was associated with the development of resistance-related mutations, a later stage of disease at start of therapy and lower PI drug levels.

Acquired Immunodeficiency Syndrome↗

PubMed2002

[Historical review and recent research trends of the antidepressant repetitive transcranial magnetic stimulation (rTMS)].

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been studied intensively over the last years. Numerous studies worldwide yielded variable results ranging from ineffectivity to an efficacy rate of more than 50 % for the reduction of depressive symptoms. A comparison of the effectiveness of TMS across studies is difficult due to the variety of chosen stimulation parameters, different inclusion criteria, and different designs. The discrepancies in results could be partially in account to these factors. From a pathophysiological point of view, there are no empirically justified parameters published carrying out an antidepressant TMS. Further studies are required to find optimal stimulation parameters using complementary methods like functional imaging techniques or regarding other factors that could interfere with its efficacy. An overview of studies published in the last ten years, a critical analysis of stimulation procedures and protocols, and possible future perspectives of this method are reviewed in this article.

Brain↗

PubMed2002

The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy.

Weight gain induced by long-term psychopharmacotherapy has emerged as a relevant clinical issue because it is a major problem affecting compliance and long-term outcome. The novel antiobesity drug orlistat inhibits gastrointestinal lipases, thus lowering the absorption of dietary fat and raising the possibility of decreased absorption of fat-soluble vitamins and certain concomitantly administered drugs in some individuals. We monitored plasma levels of several psychotropic agents in eight psychiatric patients receiving orlistat to determine the potential influence of orlistat on the bioavailability of these drugs. We found no clinically relevant changes in plasma concentrations of haloperidol, clozapine, clomipramine, desipramine, or carbamazepine over an 8-week period in orlistat recipients. We therefore consider orlistat to be compatible with use during long-term pharmacotherapy. Our preliminary findings suggest that orlistat may offer a pharmacological treatment option to support dietary efforts in obese and overweight psychiatric patients. However, so far no data about the potential influence of orlistat on pharmacokinetics of psychotropics have been published; therefore, plasma level monitoring is recommended.

Adult↗

PubMed2001

Further characterization and population data for the pentanucleotide STR polymorphism D10S2325.

Pentanucleotide tandem repeat markers are interesting for forensic sciences, because they may present less stutter on the electrophoretic pattern. We focused on the analysis of the DNA sequence for each allele at the pentanucleotide STR locus D10S2325 in order to understand their structures in the human genome and to construct human allelic ladder, which is necessary for forensic DNA typing. In order to evaluate the forensic applicability of D10S2325 and to construct a preliminary database, the genotype distributions and allele frequencies in three major ethnic groups were investigated. The population samples included Caucasians (Germans), Africans (African Americans), and Asians (Chinese). A total of 520 samples from unrelated individuals was analyzed by Amp-FLP. An example of each allele and new alleles were sequenced. Allele determination was carried out by comparison with a sequenced human allelic ladder made in-house. This pentanucleotide STR provided easily interpretable results. A total of 15 alleles was found in our population samples. Three new alleles were observed and named as alleles 19 and 21 based on the number of repeat motifs, while allele 19 can be divided further into two alleles, 19a and 19 according to analysis of the sequence. No evidence of deviation from Hardy-Weinberg equilibrium was observed. In 64 confirmed father/mother/child triplets no mutation event was observed. Using a maximum likelihood method, the mutation rate was indirectly estimated as 2.5 x 10(-5). These results suggest that D10S2325 is a useful marker for forensic casework and paternity analysis.

Black or African American↗

PubMed2001

The navigation of transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a new method for investigating cortical information processing and for investigating therapeutic applications in psychiatry and neurology. A common problem of most studies in this field regards the localization of the magnetic coil with respect to the cortex. This article reviews the currently used methods and proposes a neuronavigational approach. The method of neuronavigated TMS is described and discussed in detail. It is used to guide the magnetic coil on an individual basis to a structurally or functionally predetermined cortical area while monitoring the location of the coil in relation to the subject's head in real time. Possible applications of TMS in combination with functional neuroimaging in clinical research within a cognitive neuroscience framework are discussed. Future applications of TMS should take individual anatomy into account, and neuronavigation provides the means to do so.

Brain Mapping↗

PubMed2001

[Craving for alcohol and prevention of relapse].

The long term course of alcohol dependence often includes one or several relapses, which can be divided into low (< 5 standard drinks = lapse, slip) and high intake of alcohol with loss of control (relapse). The biological etiology of relapse is derived from different phenomena such as alcohol craving, psychosocial reasons, development of withdrawal symptoms, different primary psychiatric diseases and "addiction memory". Moreover, the metabolism of alcohol itself substantially contributes to alcohol dependence. For about 100 years different definitions for subgroups of alcohol dependence have been described, of which the Lesch typology is internationally acknowledged, especially for medical treatment. This typology differentiates between four types of alcohol dependent patients in which prevention and treatment of relapse should be specific to the primary psychiatric disease of the patient and to alcohol related disabilities. The aim is a long term improvement of sobriety rates of alcohol dependent patients as well as quality of life and life expectancy.

Adult↗

PubMed2001

The neural correlates of driving.

We studied 12 healthy subjects with fMRI while they performed a driving simulation task. In the active condition they steered the car themselves (driving), in the passive condition a person from outside the scanner was steering the car (passive driving). Common activations in both conditions were found in occipital and parietal regions bilaterally. Activity specifically associated with driving was found only in the sensorimotor cortex and the cerebellum. Compared to passive driving, activity during driving was reduced in numerous brain regions including MT/MST. It is concluded that simulated driving requires mainly perceptual-motor integration and that the limited cognitive capacity model of driving has to be revised.

Adult↗

PubMed2001

[Possible interaction between ethanol and drugs and their significance for drug therapy in the elderly].

Even though alcohol dependence is not often found in the elderly, alcohol consumption and alcohol abuse are both common. As the elderly also often take medication on a regular basis, this group is at particularly high risk for problems resulting from the concurrent use of these substances. Physical changes as a result of the aging process (e.g. reduction of body water, decrease of hepatic blood flow) and alcohol related diseases can influence the pharmacokinetics and pharmacodynamics of both ethanol as well as other drugs. Alcohol dehydrogenase (ADH), acetaldehydede hydrogenase (ALDH) and cytochrome P450 2E1 are the enzymes responsible for the metabolism of ethanol. These enzymes are also the sites of direct pharmacological interaction between ethanol and other drugs, however, altered effects of medication can also be caused by ethanol adding to or reducing the drug's effect. Although some of these effects result from heavy use of alcohol, others can also occur with moderate use. Interactions have most frequently been described for analgetics, psychopharmacologically active drugs, antihistamines, anticoagulants antihypertensive drugs and antibiotics.

Aged↗