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Biomedical subjects

K Witt

Publications and source records attributed to K Witt.

At least 19 recordsLinked to original sources

Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor.

OBJECTIVE: To investigate cerebellar gray matter volume in patients with essential tremor (ET). METHODS: We used voxel-based morphometry (VBM) based on high-resolution T1-weighted MRI to compare gray and white matter density between 27 patients with ET and 27 age- and sex-matched healthy control subjects. Fourteen patients had only postural tremor, whereas 13 patients showed additional intention tremor. RESULTS: VBM failed to demonstrate regional decreases in gray and white matter volume in patients with ET. There was, however, an expansion in gray matter depending on the type of tremor. Compared with age-matched control groups, patients with intention tremor showed a relative expansion of gray matter bilaterally in the region of the temporoparietal junction and the right middle occipital cortex. CONCLUSIONS: The lack of a consistent decrease in gray and white matter density argues against a progressive neurodegenerative process in essential tremor that leads to a substantial decrease in cerebellar gray matter volume. Patients with predominant intention tremor show a relative expansion of gray matter areas involved in higher order visuospatial processing, which might represent a long-term result of adaptive reorganization compensating the higher demands on the visuospatial control of skilled movements in case of trembling.

Adult↗

How to read a paper: critical appraisal of studies for application in healthcare.

Finding and using research results to support your professional decisions must be a systematic process, based on the principles of evidence-based medicine and healthcare. This article takes you through a critical appraisal exercise using a recent article from the British Medical Journal as an example. It describes how you decide whether to read and use an article that may be relevant to your decision. The reading is guided by a series of questions. First you evaluate the validity of the article: is the study conducted and reported so that you may trust the results? The second set of questions discusses the outcomes, the effect of the intervention and describes the use of confidence intervals for this. The possibility of using the research results in the reader's setting and patient population is then evaluated.

Education, Medical, Continuing↗

Mutations in DYT1: extension of the phenotypic and mutational spectrum.

BACKGROUND: Most cases of early-onset primary torsion dystonia (PTD) are caused by the same three-base pair (bp) (GAG) deletion in the DYT1 gene. Exon rearrangements are a common mutation type in other genes and have not yet been tested for in DYT1. Several lines of evidence suggest a relationship of the DYT1 gene with Parkinson disease (PD). OBJECTIVE: To investigate the frequency and type of DYT1 mutations and explore the associated phenotypes in a mixed movement disorders patient cohort and in controls. METHODS: The authors screened 197 patients with dystonia (generalized: n = 5; focal/segmental: n = 126; myoclonus-dystonia: n = 34; neuroleptic-induced: n = 32), 435 with PD, and 42 with various other movement disorders, along with 812 healthy controls, for small deletions in exon 5 of DYT1 and tested for exon rearrangements by quantitative, duplex PCR in 51 GAG deletion-negative dystonia cases. RESULTS: The GAG deletion was detected in five patients: three with early-onset PTD, one with generalized jerky or clonic dystonia, and one with generalized dystonia and additional features (developmental delay, pyramidal syndrome). A novel out-of-frame four-bp deletion (934_937delAGAG) in exon 5 of the DYT1 gene was found in a putatively healthy blood donor. No exon rearrangements were identified in DYT1. CONCLUSIONS: In this mixed patient sample, the GAG deletion was rare and in two out of five cases associated with an unusual phenotype. In addition, a novel DYT1 truncating mutation of unknown clinical relevance was found in a putatively unaffected individual. DYT1 exon rearrangements, however, do not seem to be associated with PTD.

Adolescent↗

Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients.

OBJECTIVES: We examined whether the finding of glycosuria and its level in themselves give information of clinical relevance, apart from being an unreliable indicator of glycemic control. METHODS: Subjects were a population-based sample of 1,284 newly diagnosed type 2 diabetic patients. Median age was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p<0.001, chi2-test). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function, this would lead to an increased renal threshold for glucose in patients with PVD.

Aged↗

Rate dependency of the human cortical network subserving executive functions during generation of random number series--a functional magnetic resonance imaging study.

In a random number generation (RNG) task subjects are instructed to generate the numbers 1-10 in a random fashion. RNG performance is assumed to involve executive functions, as it requires controlled response generation and suppression of habitual responses. To investigate cerebral structures involved in RNG associated executive functions we investigated functional magnetic resonance imaging in eight healthy subjects while performing an RNG task at two different response rates (1 and 2 Hz). During the 1 Hz condition an activation was detected bilaterally in the dorsolateral prefrontal cortex (BA 9/46), the lateral premotor cortex (BA 6), the anterior cingulate (BA 32), the inferior and superior parietal cortex (BA 7/40) and the cerebellar hemispheres. In the 2 Hz condition behavioural data showed higher counting tendencies reflecting poorer executive control. In parallel, a homogenous diminution of the activity in the involved cortical areas was obtained. This finding would support the theory of a cortical network involved in executive functions consisting of distinct brain regions working together rather than a distinct fronto-cortical functional localisation.

Adult↗

Dissociation of habit-learning in Parkinson's and cerebellar disease.

Damage to the medial-temporal region is known to result in declarative (explicit) memory deficits but nondeclarative (implicit) memory is largely unaffected by such lesions. Earlier studies have shown that some forms of implicit learning depend on cerebellar circuits but remain preserved following affections of the basal ganglia circuits. It is unknown which forms of implicit learning persist in patients with cerebellar pathology but are affected after basal ganglia lesions. Therefore, we determined if a test sensitive for habit-learning (probabilistic classification task) resulted in normal values for patients with cerebellar disease but resulted in affected results in patients with Parkinson's disease (PD). To this end, 23 patients with PD, 16 patients with familial or idiopathic cerebellar degeneration (CD), and 20 controls were tested for habit-learning. There was no impairment of patients with CD for the early learning period but there was abnormal learning in the PD group. For a later learning period, the patients with the PD showed improved performance. We conclude that the probabilistic learning task is an implicit, nonmotor learning task which is sensitive for basal ganglia pathology but remains unaffected in the case of cerebellar pathology. Such a test may be of special interest for the detection and possible neurobehavioral treatment of cognitive and motor deficits.

Aged↗

Intact artificial grammar learning in patients with cerebellar degeneration and advanced Parkinson's disease.

In an artificial grammar learning task, subjects were asked to memorise short lists of letter strings formed according to complex rules for letter order. After an interval they were unexpectedly asked to discriminate new grammatical strings from strings which used the same letters but violated the sequential constraints of the grammar. Artificial grammar learning can be mastered successfully by amnesic patients and is considered to be an implicit learning task independent of declarative learning and memory mechanisms. In this study, 10 patients with cerebellar degeneration (CD), 21 Parkinson's disease (PD) and 15 control subjects were tested on artificial grammar learning. Additionally PD patients with advanced disease were examined under adequate medication and dopaminergic withdrawal. All patient groups showed intact artificial grammar learning. Neither cerebellar damage nor basal ganglia dysfunction nor dopaminergic medication impairs or affects artificial grammar learning. Although the patients showed significant executive dysfunction, implicit learning remains intact. The conclusion is that cerebellar and basal ganglia circuits play no essential part in this kind of implicit learning. The results suggest that artificial grammar learning is a cortically mediated function comparable to the mechanism of visual priming.

Aged↗

Typical features of cerebellar ataxic gait.

BACKGROUND: Although gait disturbance is one of the most pronounced and disabling symptoms in cerebellar disease (CD), quantitative studies on this topic are rare. OBJECTIVES: To characterise the typical clinical features of cerebellar gait and to analyse ataxia quantitatively. METHODS: Twelve patients with various cerebellar disorders were compared with 12 age matched controls. Gait was analysed on a motor driven treadmill using a three dimensional system. A tandem gait paradigm was used to quantify gait ataxia. RESULTS: For normal locomotion, a significantly reduced step frequency with a prolonged stance and double limb support duration was found in patients with CD. All gait measurements were highly variable in CD. Most importantly, balance related gait variables such as step width and foot rotation angles were increased in CD, indicating the need for stability during locomotion. The tandem gait paradigm showed typical features of cerebellar ataxia such as dysmetria, hypometria, hypermetria, and inappropriate timing of foot placement. CONCLUSIONS: Typical features of gait in CD are reduced cadence with increased balance related variables and an almost normal range of motion (with increased variability) in the joints of the lower extremity. The tandem gait paradigm accentuates all the features of gait ataxia and is the most sensitive clinical test.

Disability Evaluation↗

Rescue lifting system (RLS) might help to prevent death after rescue from immersion in cold water.

OBJECTIVE: In order to prevent sudden death after rescue from immersion in cold water, victims should be handled carefully avoiding additional cardiovascular stress. In this study we investigated if a new double-sling rescue system ("Rescue Lifting System-RLS) was superior to conventional single-sling techniques. METHODS: We studied 14 healthy male subjects in good physical condition aged 21 to 40 years. They were lifted up from the ground with the new RLS and two conventional techniques ("Lifesling" and a navy rescue system used in SAR helicopters). Heart rate was determined by QRS detection (Polar Precision Performance device; Polar Electro Oy, Kempele, Finland) and blood pressure by sphygmomanometry. RLS and "Lifesling" were tested under conditions of dry land and immersion in 18 degrees C water. RESULTS: Rescue with RLS induced only moderate heart rate changes which were significantly lower (about 30 bpm) than with conventional techniques. These findings could be reproduced under "wet" condition. DISCUSSION: RLS enables rescue in a supine position avoiding extensive orthostatic stress. It might therefore be favourable in preventing sudden death after rescue from immersion in cold water.

Adult↗

Isolation and characterization of the human forkhead gene FOXQ1.

We have isolated a human genomic and cDNA clone that encodes a protein of 403 amino acids and belongs to the family of the FOX transcription factors (previously called HNF-3/forkhead transcription factors). The 2.7-kb transcript of the human FOXQ1 gene is expressed predominantly in the stomach, trachea, bladder and salivary gland. Additionally, overexpression of human FOXQ1 was shown in colorectal adenocarcinoma and lung carcinoma cell lines. The FOXQ1 gene is located on chromosome 6p23-25. Databank analysis shows 82% homology with the mouse Foxq1 gene (formerly Hfh-1L) and with a revised sequence of the rat FoxQ1 gene (formerly HFH-1). The DNA-binding motif, named HNF-3/forkhead domain, is well conserved, showing 100% identity in human, mouse, and rat. The human protein sequence contains two putative transcriptional activation domains, which share a high amino acid identity with the corresponding mouse and rat domains.

Amino Acid Sequence↗

The purpose of the general practice consultation from the patient's perspective--theoretical aspects.

BACKGROUND: Medical practice and research are paying increasing attention to what patients want, as reflected by the growth of routine surveys of patients' satisfaction and more formal studies of patients' views of medical care. However, the field lacks conceptual clarity. OBJECTIVES: The aim of this study was to propose a theoretical clarification of the concept of the patients' purpose of a consultation by presenting a patient-centred definition, applicable for clinical work and research in general practice. METHODS: An extensive literature review was conducted to explore presumptions and definitions reported by previous studies. Most authors failed to define or distinguish the concept under investigation. We took these shortcomings as our starting point, added some significant dimensions drawn from a few selected authors who had discussed relevant perspectives in their work and arrived at a proposed working definition of the 'purpose' concept. RESULTS: The proposed definition allows for multiple purposes for the consultation. We incorporate what the patient hopes to gain from the consultation, as opposed to their 'expectations of the most likely outcome'. Our working definition aims to identify patients' a priori wishes and hopes for a specific process and outcome, while acknowledging that these may not be voiced and may be modified by the patient during the consultation. General characteristics of the doctor, such as being considerate or professionally skillful, are not included.

Communication↗

Gendered health resources and coping--a study from general practice.

AIM: The aim of this study was to explore gender and coping in primary health care patients, by comparing self-assessed health resources in men and women. METHODS: Female and male patients' self-assessed health resources were identified by mean of key questions, developed separately for men and women. Patients' answers were audiotaped and analyzed qualitatively. An explorative gender comparative analysis was done. The setting comprised two women GPs and their consultations. The subjects were 37 consecutive female patients and 39 consecutive male patients aged 19-85 years. RESULTS: The analysis indicated notable differences in spite of apparent similarities in self-assessed personal health resources in men and women. In men, personal strength was part of a proud identity, while women reported that they were able to manage because they just had to. Work was often mentioned as a health resource, but while men emphasized their well-being at work and a capacity to relax at home, women handled stressful tensions by diving into household activities. While men spoke of gaining health from being with others, women talked about social relations as contexts for gaining as well as giving health. CONCLUSION: None of the phenomena described by the respondents can be reasonably categorized as respectively problem-focused, emotion-focused or avoidance coping strategies. Asking people about their own ideas regarding health resources may provide more complex understandings of coping and gender. In a clinical setting skilful listening can prevent gender essentialism, where all men are regarded as different from all women.

Adaptation, Psychological↗

Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers.

PURPOSE: The purpose of this study was to evaluate whether infusion lines are able to leach plasticizers in substantial amounts and thus be a candidate substance for hepatotoxic effects during long-term total parenteral nutrition (TPN). METHODS: TPN solutions, blood products, and selected drugs typical for preterm infants concerning amount, content, and infusion time were perfused through common polyvinylchloride (PVC) infusion lines. Concentration of diethylhexyl-phthalate (DEHP) before and after perfusion was determined by gas chromatography/mass spectrometry. RESULTS: Daily quantities of DEHP by 24-hour infusions were Lipid emulsion 20%: 10185.6 microg; aminoacid/glucose-solution: 116.2 microg; midazolaminfusion for sedation: 26.4 microg; fentanyl for sedation: 132.5 microg; propofol for sedation: 6561.0 microg. The amount of DEHP by single doses of blood products (20 mL) were packed red blood cells: 144-608 microg; platelet rich plasma: 928 microg; and fresh frozen plasma: 552-8108 microg. The dose of DEHP for a typical preterm neonate requiring TPN and additional therapy like sedation or blood products is at minimum 10 mg and can easily reach 20 mg/d. CONCLUSION: This large amount of DEHP is especially disturbing, because it effects the most vulnerable patients (neonates). Whether there is a relation to TPN-induced hepatobiliary dysfunction remains to be elucidated and is under investigation. With respect to recent literature, a biological effect of these doses must be assumed.

Diethylhexyl Phthalate↗

Is there a correlation between organochlorine compounds and undescended testes?

Some pesticides and synthetic chemicals are known to act as hormonal modulators, often possessing oestrogenic activity (xenooestrogens). They are persistent and accumulate in fatty tissue. Aim of our study is to address the question, whether a selection of such compounds is to be found in the fatty tissue of children undergoing surgical procedures and whether there are differences in values obtained from patients with or without undescended testes. Fat samples of 48 patients, 18 of whom had undescended testes, were examined by high-resolution gas chromatography and mass spectrometry for DDT and metabolites, polychlorinated biphenyls (PCB), toxaphenes, hexachlorocyclohexane (HCH), chlorinated cyclodienes and chlorinated benzenes. We were able to find accumulation of all substances in every patient. Statistical analysis revealed a highly significant difference between patients from the control group and those from the undescended testes group for two compounds, namely heptachloroepoxide (HCE) and hexachlorobenzene (HCB), increased values being found in the patients with undescended testes. Since the aetiology of this entity is unknown in most of the cases, prenatal exposure to exogenous oestrogens is an attractive and plausible hypothesis. In order to confirm this, some questions will have to be answered in further studies: effect of exposure to xenooestrogens during a specific period of development, probable role of other substances with proven or suspected hormonal activity, potential synergism of such compounds and differences in individual susceptibility.

Adipose Tissue↗

Men's self-assessed personal health resources: approaching patients' strong points in general practice.

OBJECTIVE: To explore resource-oriented, gender-sensitive approaches in general practice by identifying what men perceive to be their personal health resources. METHODS: A key question was developed to invite men to tell their GPs about personal health resources during ordinary visits. The answers of 39 consecutive male patients (aged 19-84 years) visiting two female GPs were audio taped and analysed, qualitatively inspired by Giorgi's phenomenological approach, supported by theories on salutogenesis, patient-centredness and gender perspectives. The main outcome measures were personal qualities and strategies considered by men to be their health resources. RESULTS: Men considered that the following were personal health resources: optimism, good self-esteem, job satisfaction, ability to cope with stress at work, leisure activities and relaxation with friends producing energy, and fitness and lifestyle activities. CONCLUSION: A key question can give a doctor access to men's thoughts about their strong points. Self-assessed personal health resources can be identified and mobilized by the GP and support a salutogenic approach, which contrasts with the tendency of contemporary medical practice to focus on risk. Asking people about their own ideas may reveal that coping patterns are more complex than reflected in prevailing research.

Adaptation, Psychological↗