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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 37 records · Page 2Linked to original sources
PubMed2005

The effect of quetiapine in psychotic Parkinsonian patients with and without dementia. An open-labeled study utilizing a structured interview.

OBJECTIVES: We studied the effect of quetiapine in drug induced psychosis (DIP) in Parkinson's disease (PD) patients with dementia (PDDEM) and without dementia (PDNODEM) in a 6-month open study. METHODS: Thirty five consecutive PD patients with DIP (19 of them demented [DSMIV criteria]) were examined. Assessment included Mini-Mental State Examination (MMSE), UPDRS (motor part), Brief Psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGIS) and Hamilton test (for depression). Quetiapine was administered in a flexible dose 25-600 mg daily. Out of the 35 patients included in the study, 24 completed treatment with quetiapine (14 demented and 10 without dementia). Treatment was stopped in 11 patients (5 demented). RESULTS: Intention to treat patient (ITT) analysis did not show a significant quetiapine effect (BPRS), although in about 30% a good outcome was reported by the family (CGIS). Among the patients who completed the study (n = 24), in the PDNODEM group (n = 10) BPRS improved almost significantly (p = 0.06) while in the PDDEM group the BPRS did not change. According to the CGIS, a good improvement was observed in 50% of the PDDEM group (7/14) and 40% of the PDNODEM group (4/10). Motor features of PD patients worsened mildly (p = 0.05) in the PDDEM group. CONCLUSION: In this open trial, quetiapine was not beneficial in the ITT group using the BPRS, although families reported improvement in about 30% of patients (CGIS). Among patients who completed the study, quetiapine was more effective in the PDNODEM group. A double blind study with quetiapine is required.

Aged↗
PubMed2005

The use of impulse oscillometry for separate analysis of inspiratory and expiratory impedance parameters in horses: effects of sedation with xylazine.

AIM: To improve the outcome of parameters measured by the impulse oscillometry system (IOS) in horses by separate assessment of inspiratory and expiratory impedance spectra in the frequency range between 1 and 10 Hz. As basis for further studies, the influence of sedation with xylazine on respiratory impedance was also investigated. METHODS: (i) The respiratory impedance of 11 horses was measured using IOS before and 6 min after sedation (xylazine; 0.6 mg/kg b.w.). (ii) The time course of impedance parameters in a period of 24 min after administration of xylazine was evaluated in 12 horses at regular intervals of 3 min. Resistance (R(rs)), reactance (X(rs)), and coherence (Co) were calculated as mean spectra (R(rs),X(rs),Co) of the entire measurement as well as separated into inspiration (Ri(rs),Xi(rs),Coi) and expiration (Re(rs),Xe(rs),Coe) at frequencies of 1, 5, and 10 Hz. RESULTS: (i) R(rs), X(rs) as well as Re(rs) and Xe(rs) revealed no significant influence of sedation. However, separate analysis of inspiration and expiration revealed a significant influence of sedation on all inspiratory impedance parameters. (ii) During the 24 min period after sedation, almost all inspiratory parameters were found significantly dependent on the time course of sedation whereas expiratory parameters Re10, Xe1, and Xe5 were not influenced. These results indicate that confounding factors due to sedation act mainly during inspiration. Muscle relaxation in upper airways due to xylazine is suspected to be the main cause of these phenomena.

Animals↗
PubMed2005

Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism.

Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.

Adult↗
PubMed2005

[Evaluation of non-invasive scores in the follow-up of chronic hepatitis].

To differentiate biliary diseases the biopsy of liver tissue for histological examination is still the method of choice (golden standard). By histology the exact grading (inflammatory activity) and staging (of fibrosis) is possible. Hereby, the severity of liver disease and the progress of fibrosis can be determined. None of the various fibrosis marker like hyaluronate or collagen III peptid are able to replace the histology, neither alone nor as score. These biochemical marker and clinical parameter are suitable to follow up the progress of the detected fibrosis using the so-called noninvasive staging and to reduce the number of follow up biopsies. In fast progression of liver fibrosis the follow up by biopsy is almost more affirmative. For non-invasive follow ups the particular parameter hyaluronate is qualified best, according to the actual literature. Scores must keep on being evaluated on its value.

Algorithms↗
PubMed2005

High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening.

Mutations in GTP cyclohydrolase I (GCHI) are found in 50 to 60% of cases with dopa-responsive dystonia (DRD). Heterozygous GCHI exon deletions, undetectable by sequencing, have recently been described in three DRD families. We tested 23 individuals with DRD for the different mutation types by conventional and quantitative PCR analyses and found mutations, including two large exon deletions, in 87%. The authors attribute this high mutation rate to rigorous inclusion criteria and comprehensive mutational analysis.

Adolescent↗
PubMed2005

Engineering of a novel ruthenium sensitizer and its application in dye-sensitized solar cells for conversion of sunlight into electricity.

A novel ligand 4,4'-bis(carboxyvinyl)-2,2'-bipyridine (L) and its ruthenium(II) complex [Ru(II)L(2)(NCS)(2)] (K8) were synthesized and characterized by analytical, spectroscopic, and electrochemical techniques. The performance of the K8 complex as a charge transfer photosensitizer in nanocrystalline TiO(2) based solar cells was studied. When the K8 complex anchored onto a nanocrystalline TiO(2) film, we achieved very efficient sensitization yielding 77 +/-5% incident photon-to-current efficiencies (IPCE) in the visible region using an electrolyte consisting of 0.6 M methyl-N-butyl imidiazolium iodide, 0.05 M iodine, 0.05 M LiI, and 0.5 M 4-tert-butylpyridine in a 50/50 (v/v) mixture of valeronitrile and acetonitrile. Under standard AM 1.5 sunlight, the complex K8 gave a short circuit photocurrent density of 18 +/- 0.5 mA/cm(2), and the open circuit voltage was 640 +/- 50 mV with fill factor of 0.75 +/- 0.05, corresponding to an overall conversion efficiency of 8.64 +/- 0.5%.

Journal Article↗
PubMed2005

Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study.

Parkinson's disease (PD) is a neurodegenerative disorder in which relatives of the probands are affected approximately 4 times as frequently as relatives of control subjects. Several genes have been implicated as genetic risk factors for PD. We investigated the presence of six reported genetic variations in the SCNA, NR4A2, and DJ-1 genes in 292 cases of familial Parkinson's disease from the GenePD study. None of the variants were found in the GenePD families. Our results suggest that other variants or genes account for the familial risk of PD within the GenePD study.

Aged↗
PubMed2005

[Treatment of sialorrhea with botulinum toxin: an overview].

Hypersalivation (sialorrhea) is a common complaint of patients with neurodegenerative disorders such as Parkinson's disease or amyotrophic lateral sclerosis and a frequently disabling side effect of atypical antipsychotic drugs. Conventional treatment including oral anticholinergic or antihistamine medication is often limited by adverse effects and lack of efficacy. Over the past few years, several studies reported decreased drooling after injections of botulinum toxin into the salivary glands. This review describes the current state of treatment of sialorrhea with botulinum toxin.

Botulinum Toxins↗
PubMed2005

[Pharmacological strategies for clozapine-induced hypersalivation: treatment with botulinum toxin B in one patient and review of the literature].

Hypersalivation is frequently observed in patients treated with clozapine. Current strategies to counteract sialorrhea include the introduction of antimuscarinergic (anticholinergic) and alpha(2)-agonistic treatment. However, the use of these substances is limited in part by lack of efficacy and by adverse side effects. In cases of intractable sialorrhea, the application of botulinum toxin may be a new and safe therapeutic option. We here present an overview on current treatment strategies for sialorrhea and describe a patient who received botulinum toxin B for clozapine-induced hypersalivation.

Adult↗
PubMed2005

Movement disorders: classifications.

Movement disorders (ataxia, dystonic disorders, gait disorders, Huntington disease, myoclonus, parkinsonism, spasticity, tardive dyskinesia, tics and tremor) are clinically, pathologically and genetically heterogeneous and are characterized by impairment of the planning, control or execution of movement. Current classifications of these disorders have inherent shortcomings due to the complex nature of movement disorders and the lack of diagnostic tests for the majority. Undiscriminating terminology, as well as the clinical, pathological and genetic heterogeneity, further complicate the development of comprehensive categorizations. Modern classification schemes tend to focus on clinical, pathological or genetic/molecular criteria, but more recent attempts have been made to integrate across these levels. From a historical perspective, two 'golden ages' have shaped the current and evolving classification schemes: (1) the definition of clinical pathological entities in the early twentieth century and (2) the application of molecular neurogenetics in the past 10-15 years. However, the classification of movement disorders on clinical grounds (according to age at onset, distribution of symptoms, disease course, provoking factors and therapeutic response) remains one of the most useful modes of categorization. Postmortem criteria have been employed to distinguish between degenerative and nondegenerative disorders, and specific hallmarks may be required to establish or confirm a diagnosis. Genetic features used for classification purposes include mode of inheritance and molecular genetic data, such as linkage to a known gene locus or identification of a specific genetic defect. A final classification scheme is based on alterations in molecular mechanisms (e.g. trinucleotide expansions) or protein function (e.g. channelopathies). Despite recent advances, it may not be possible to develop the 'ultimate' classification of movement disorders, and different patterns of lumping and splitting may be useful for the clinician, the pathologist or the geneticist/molecular biologist. Furthermore, certain individual cases with unique features may not fit into any particular category. Continued research by both clinicians and basic scientists is necessary in order to refine and redefine classification schemes of movement disorders.

Dystonia↗
PubMed2005

Immunosurveillance of childhood ALL: polymorphic interferon-gamma alleles are associated with age at diagnosis and clinical risk groups.

Interferon-gamma (IFN-gamma) has been implicated as an important mediator of antitumor immunity in murine model systems. To determine whether a CA-repeat associated with differential NFkappaB-binding and IFN-gamma-expression levels may influence the incidence, manifestation and early clinical treatment response of childhood acute lymphoblastic leukemia, we performed PCR-based genotyping of 393 patients with ALL and 207 healthy controls. We could not find any differences in the allele distribution comparing patients and controls. However, when we further analyzed the allele frequencies with respect to age of clinical manifestation, we found that patients with B-lineage ALL showing the IFN-gamma high-expressing genotype presented at a more advanced age compared to those patients with intermediate and low-expressing genotypes (median 6 vs 4.4 years, P=0.01). Furthermore, we found a significantly higher number of low expressors in the group of high-risk patients (HR n=32 and MR/SR n=266, P=0.025, defined by prednisone response, cytological remission and minimal residual disease (MRD)) with B-lineage ALL. Thus, we provide evidence that polymorphic IFN-gamma alleles are associated with age at clinical presentation and risk groups such as prednisone response in B-lineage ALL, suggesting distinct effects of IFN-gamma in immunosurveillance and early response to steroid therapy.

Cell Lineage↗
PubMed2005

The effects of acute loading with levodopa and levodopa with selegiline on blood pressure and plasma norepinephrine levels in chronic Parkinson's disease patients.

OBJECTIVES: Contradictory possible cardiovascular side effects of selegiline have been reported. Therefore, we studied the effect of acute administration of selegiline with levodopa (LD) compared with LD alone, on blood pressure, pulse and norepinephrine (NE) plasma levels, during an orthostatic test on chronically treated Parkinson's disease patients (PDpts) and controls. MATERIALS AND METHODS: Twelve PDpts treated with LD (group D), 12 PDpts treated with selegiline and LD (group S) and eight volunteers (CTRL) underwent the orthostatic test. Patients repeated the test twice, before and after acute loading with 125 mg LD (group D) and 125 mg LD +5 mg selegiline (group S). RESULTS: Group S showed more episodes of postural hypotension (n = 10; two symptomatic) than group D (n = 4) and CTRL (n = 2), however not statistically significant. Plasma NE also rose significantly higher (P < 0.001) in group S. CONCLUSION: PD patients treated with selegiline showed more orthostatism and higher plasma NE after submission to the orthostatic test. These findings may be relevant to explain its deleterious effect.

Aged↗
PubMed2005

Cardiac magnetic resonance imaging: long term reproducibility of the late enhancement signal in patients with chronic coronary artery disease.

OBJECTIVE: To determine long term reproducibility of the late enhancement (LE) signal in contrast enhanced magnetic resonance imaging (MRI) and potential changes of the signal after revascularisation. METHODS: 33 patients (29 men, mean (SD) 61 (11) years) with coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30 (7)%) underwent two contrast enhanced MRI procedures within 9 (3) months. Fifteen patients (group A: 14 men, 59 (12) years) had no interventions between the two studies. Eighteen patients underwent revascularisation after MRI 1 (group B: 15 men, 62 (9) years). Changes in the LE signal between the first and second MRIs were investigated in both groups as well as intraobserver and interobserver variabilities for delineation of the signal. RESULTS: The LE signal was highly reproducible in groups A and B for segmental analysis (concordance 86% v 82%, respectively; kappa = 0.70 v 0.67) and summed scores (group A: r = 0.97, p < 0.001; group B: r = 0.93, p < 0.001). The LE signal was quantified as 27 (27) cm3 in group A versus 30 (16) cm3 in group B in the first MRI and 26 (25) cm3 versus 30 (15) cm3, respectively, for the second MRI (both not significant). Moreover, low intraobserver and interobserver variabilities were observed in segmental analysis (kappa = 0.86 and 0.74, respectively, for group A, and kappa = 0.87 and 0.82, respectively, for group B). CONCLUSION: In patients with chronic CAD, the LE signal in contrast enhanced MRI is very stable over an extended time period. These results further characterise contrast enhanced MRI as a useful tool for myocardial viability assessment. Low intraobserver and interobserver variabilities promise robustness of the method for clinical application.

Aged↗
PubMed2005

Genetic heterogeneity in rapid onset dystonia-parkinsonism: description of a new family.

Rapid onset dystonia-parkinsonism (RDP) is a rare movement disorder with autosomal dominant inheritance, characterised by sudden onset of dystonic spasms and slowness of movement. To date, three families have been described that share linkage to the same location on chromosome 19q13, designated DYT12. Very recently, mutations in the ATP1A3 gene at the DYT12 locus have been demonstrated in seven unrelated patients, including the three previously linked families. A large RDP family is reported here, with eight definitely and one possibly affected members, that is not linked to the DYT12 region and has no mutation in the ATP1A3 gene. Predominant cranial-cervical involvement of dystonia occurred in this family, which has also been described in patients with idiopathic torsion dystonia linked to the DYT6 region on chromosome 8 and is a rare finding in DYT1 dystonia. Molecular genetic analysis also excluded linkage to the DYT6 locus and the GAG deletion in DYT1, suggesting at least one additional RDP gene.

Child↗
PubMed2004

Targeting the p53-MDM2 interaction to treat cancer.

The tumour suppressor p53 is a transcription factor with powerful antitumour activity that is controlled by its negative regulator MDM2 (mouse double minute 2, also termed HDM2 in humans) through a feedback mechanism. MDM2, which is overproduced in many tumours, binds p53 and inhibits its function by modulating its transcriptional activity and stability. Activation of p53 in tumour cells by inhibiting its physical interaction with MDM2 has been in the focus of cancer drug discovery. However, development of nonpeptidic MDM2 antagonists turned out to be challenging. Recently, the first potent and selective small-molecule antagonists of MDM2, the Nutlins, have been identified. Studies with Nutlins provided in vitro and in vivo proof-of-principle for targeting p53-MDM2 interaction for cancer therapy.

Animals↗
PubMed2004

A major lung cancer susceptibility locus maps to chromosome 6q23-25.

Lung cancer is a major cause of death in the United States and other countries. The risk of lung cancer is greatly increased by cigarette smoking and by certain occupational exposures, but familial factors also clearly play a major role. To identify susceptibility genes for familial lung cancer, we conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with three or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity LOD score (HLOD) of 2.79 at 155 cM on chromosome 6q (marker D6S2436). A subset of 38 pedigrees with four or more affected individuals yielded a multipoint HLOD of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with five or more affected individuals yielded a multipoint HLOD score of 4.26 at the same position. The 14 families with only three affected relatives yielded negative LOD scores in this region. A predivided samples test for heterogeneity comparing the LOD scores from the 23 multigenerational families with those from the remaining families was significant (P=.007). The 1-HLOD multipoint support interval from the multigenerational families extends from C6S1848 at 146 cM to 164 cM near D6S1035, overlapping a genomic region that is deleted in sporadic lung cancers as well as numerous other cancer types. Parametric linkage and variance-components analysis that incorporated effects of age and personal smoking also supported linkage in this region, but with somewhat diminished support. These results localize a major susceptibility locus influencing lung cancer risk to 6q23-25.

Chromosome Mapping↗
PubMed2004

Amphiphilic ruthenium sensitizers and their applications in dye-sensitized solar cells.

Amphiphilic ligands 4,4'-bis(1-adamantyl-aminocarbonyl)-2,2'-bipyridine (L(1)), 4,4'-bis[5-[N-[2-(3beta-cholest-5-en-3-ylcarbamate-N-yl)ethyl]aminocarbonyl]]-2,2'-bipyridine (L(2)), 4,4'-bis[5-[N-[2-(3beta-cholest-5-en-3-ylcarbamate-N-yl)propyl]aminocarbonyl]]-2,2'-bipyridine (L(3)), and 4,4'-bis(dodecan-12-ol)-2,2'-bipyridine (L(4)) and their heteroleptic ruthenium(II) complexes of the type [Ru(II)LL(1)(NCS)(2)] (5), [Ru(II)LL(2)(NCS)(2)] (6), [Ru(II)LL(3)(NCS)(2)] (7), and [Ru(II)LL(4)(NCS)(2)] (8) (where L = 4,4'-bis(carboxylic acid)-2,2'-bipyridine) have been synthesized starting from dichloro(p-cymene)ruthenium(II) dimer. All the ligands and the complexes were characterized by analytical, spectroscopic, and electrochemical techniques. The performance of these complexes as charge-transfer photosensitizers in nanocrystalline TiO(2)-based solar cells was studied. When complexes 5-8 anchored onto a 12 + 4 microm thick nanocrystalline TiO(2) films, very efficient sensitization was achieved (85 +/- 5% incident photon-to-current efficiencies in the visible region, using an electrolyte consisting of 0.6 M butylmethylimidazolium iodide, 0.05 M I(2), 0.1 M LiI, and 0.5 M tert-butyl pyridine in 1:1 acetonitrile + valeronitrile). Under standard AM 1.5 sunlight, the complex 8 yielded a short-circuit photocurrent density of 17 +/- 0.5 mA/cm(2), the open-circuit voltage was 720 +/- 50 mV, and the fill factor was 0.72 +/- 0.05, corresponding to an overall conversion efficiency of 8.8 +/- 0.5%.

Journal Article↗