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Biomedical subjects

P Fischer

Publications and source records attributed to P Fischer.

At least 19 recordsLinked to original sources
PubMed2006

Molecular phylogeny of the filaria genus Onchocerca with special emphasis on Afrotropical human and bovine parasites.

Filarial parasites of the genus Onchocerca are found in a broad spectrum of ungulate hosts. One species, O. volvulus, is a human parasite that can cause severe disease (onchocerciasis or 'river blindness'). The phylogenetic relationships and the bionomics of many of the nearly 30 known species remain dubious. Here, the phylogeny of 11 species representing most major lineages of the genus is investigated by analysing DNA sequences from three mitochondrial genes (ND5, 12S and 16S rRNA) and portions of the intergenic spacer of the nuclear 5s rRNA. Special emphasis is given to a clade containing a yet unassigned specimen from Uganda (O. sp. 'Siisa'), which appears to be intermediate between O. volvulus and O. ochengi. While the latter can be differentiated by the O-150 tandem repeat commonly used for molecular diagnostics, O. volvulus and O. sp.'Siisa' cannot be differentiated by this marker. In addition, a worm specimen from an African bushbuck appears to be closely related to the bovine O. dukei and represents the basal taxon of the human/bovine clade. At the base of the genus, our data suggest O. flexuosa (red deer), O. ramachandrini (warthog) and O. armillata (cow) to be the representatives of ancient lineages. The results provide better insight into the evolution and zoogeography of Onchocerca. They also have epidemiological and taxonomic implications by providing a framework for more accurate molecular diagnosis of filarial larvae in vectors.

Africa South of the Sahara↗
PubMed2006

Association study of BDNF and CNTF polymorphism to depression in non-demented subjects of the "VITA" study.

BACKGROUND: Neurotrophic factors are known to play an important role in the survival and differentiation of many types of neurons during development. Both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) may act cooperatively in modulating the development and functioning of synapses. Both these neurotrophic factors were intensely investigated with regard to depression without conclusive results. METHODS: We have investigated the possible use of both CNTF null-mutation and BDNF polymorphism C270T as biomarkers for depression in the Vienna Transdanube Aging (VITA) study. The VITA is a prospective community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. RESULTS: We found no association between CNTF null-mutation and BDNF C270T polymorphism to any depressive symptoms after exclusion of demented subjects. CONCLUSION: These results call in question the hypothesis that either BDNF or CNTF can be used as molecular markers for depression or late onset depression in the elderly.

Age Factors↗
PubMed2006

Noise exposure and children's blood pressure and heart rate: the RANCH project.

BACKGROUND: Conclusions that can be drawn from earlier studies on noise and children's blood pressure are limited due to inconsistent results, methodological problems, and the focus on school noise exposure. OBJECTIVES: To investigate the effects of aircraft and road traffic noise exposure on children's blood pressure and heart rate. METHODS: Participants were 1283 children (age 9-11 years) attending 62 primary schools around two European airports. Data were pooled and analysed using multilevel modelling. Adjustments were made for a range of socioeconomic and lifestyle factors. RESULTS: After pooling the data, aircraft noise exposure at school was related to a statistically non-significant increase in blood pressure and heart rate. Aircraft noise exposure at home was related to a statistically significant increase in blood pressure. Aircraft noise exposure during the night at home was positively and significantly associated with blood pressure. The findings differed between the Dutch and British samples. Negative associations were found between road traffic noise exposure and blood pressure, which cannot be explained. CONCLUSION: On the basis of this study and previous scientific literature, no unequivocal conclusions can be drawn about the relationship between community noise and children's blood pressure.

Aircraft↗
PubMed2006

Data from the VITA Study do not support the concept of vascular depression.

OBJECTIVE: Cerebrovascular lesions that are apparent in magnetic resonance scans and regioselective atrophy of the brain have been proposed as a causative or exacerbating factor in depression with late-life onset. The objective of this study was to investigate whether deep white matter or periventricular hyperintensities, small ischemic lesions, and brain atrophy contribute to late-onset depression in the nondemented elderly. METHOD: Based on a group of 606 individuals of identical age (75.8 years, standard deviation: 0.45 years) residing in two districts of Vienna, the authors built a case-control cohort (ratio: 1:4) consisting of 51 individuals with late-onset major or minor depression matched with 204 subjects of identical gender and education status without depression, resulting in two groups that were homogenous with respect to age, place of residence, gender, and education. Scores for focal brain lesions, mediotemporal lobe atrophy, and ventricular enlargement as well as risk factors for vascular disease were compared with cognition and depression status. RESULTS: Depressed individuals had significantly lower scores than nondepressed subjects in all measures of cognitive and executive function. No significant relation was found between a diagnosis of depression and any type of discrete brain lesions, but measures of brain atrophy (Cella Media indices, mediotemporal atrophy) showed a clear statistical relation to depression. No relationship was found between depression and lipid parameters. CONCLUSION: The authors found no indication that white matter hyperintensities or minor ischemic lesions played a role in our depressed cohort, casting doubt on the vascular hypothesis of late-onset depression.

Aged↗
PubMed2006

Relation between vascular risk factors and cognition at age 75.

OBJECTIVE: Recent trends in dementia research emphasize that not only cerebrovascular events but also vascular risk factors induce, favour or cause cognitive impairment and Alzheimer's disease. MATERIAL AND METHODS: We evaluated vascular risk factors (blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, HbA1c, homocysteine, lipoprotein(a), fibrinogen, C-reactive protein and smoking habits) in a community-based cohort of 75-year-old individuals of two districts in Vienna (247 men, 359 women) and correlated these risk factors with overall cognition. RESULTS: Pathological vascular risk factors were found frequently in the age cohort. However, the expected associations between the Mini-Mental State Examination and any cardiovascular risk factors were missing. Only individuals with a positive history of smoking showed lower cognitive capacities. CONCLUSIONS: We assume that cognitive dysfunction in old age is connected to factors other than the known classical and novel risk factors for the development of cardiovascular disease.

Aged↗
PubMed2006

Recombinant variants of antibody 138H11 against human gamma-glutamyltransferase for targeting renal cell carcinoma.

The monoconal antibody 138H11 recognizes human renal gamma-glutamyltransferase (GGT), an antigen shown to allow targeting primary and metastatic renal cell carcinoma (RCC). We determined the primary structure of the antigen binding region of mAb 138H11 and generated several different recombinant antibody variants. First, monomeric single-chain Fv antibody fragments, diabodies and triabodies were obtained by constructing linker variants consisting of 18, 10, 8, 5, 3, 2, 1 and zero amino acid residues, resulting in significant differences in yield and molecular architecture. Second, two variants of disulphide bond-stabilised Fv fragments (dsFvs) were generated using two different pairs of complementary framework amino acid positions of VH and VL for disulphide stabilisation. The binding activities of diabodies to human GGT located on its tissue decreased when using shorter linker lengths. The scFv dimer containing a 3 amino acid residue linker peptide and one of the dsFv variants were not functional. Further, the work paves the way for generating new effector constructs and a systematic optimisation of the pharmacokinetics of this tumor targeting antibody by offering variants with a broad range of valencies and molecular masses.

Amino Acid Sequence↗
PubMed2005

Magnetic microstructures and their dynamics studied by X-ray microscopy.

Full-field soft X-ray microscopy in combination with X-ray magnetic circular dichroism as contrast mechanism is a powerful technique to image with elemental specificity magnetic nanostructures and multilayered thin films at high lateral resolution down to 15nm by using Fresnel zone plates as X-ray optical elements. Magnetization reversal phenomena on a microscopic level are studied by recording the images in varying external magnetic fields. Local spin dynamics at a time resolution below 100ps can be addressed by engaging a stroboscopic pump-and-probe scheme taking into account the time pattern of synchrotron storage rings. Characteristic features of magnetic soft X-ray microscopy are reviewed and an outlook into future perspectives with regard to increased lateral and temporal resolution is given.

Journal Article↗
PubMed2005

On the imaging of the flux-line lattice of a type-II superconductor by soft X-ray absorption microscopy.

A new method is proposed for the imaging of the flux-line lattice of a type-II superconductor by soft X-ray absorption microscopy. It is shown that the method is very demanding but probably realisable in the foreseeable future. The new method has the potential to image in real space static and dynamical properties of the flux-line lattice at arbitrary external fields and with single-flux-line resolution.

Journal Article↗
PubMed2005

VITA: subtypes of mild cognitive impairment in a community-based cohort at the age of 75 years.

BACKGROUND: Mild cognitive impairment (MCI) is defined to diagnose prodromal dementia and prodromal Alzheimer dementia, in particular. OBJECTIVE: The main aim of this study is to identify subtypes of MCI in comparison to the frequency of Petersen's MCI-amnestic in an elderly age-cohort. PARTICIPANTS: The study is based on the cross sectional data from the Vienna-Transdanube-Aging (VITA) study. The data refer to the age cohort of 592 individuals at age 75 to 76 years who completed extensive neuropsychological examination. RESULTS: Dementia was present in 15 subjects (2.5%, CI: 1.4-4.1). 141 subjects (23.8%, CI: 20.4-27.5) of the entire age cohort 75 (n = 592) showed cognitive impairment without dementia concerning one or more cognitive functions (1.5 SD paradigm). These subjects were assigned to three subtypes of MCI: Selective Memory Impairment: n = 22 (3.7%, CI: 2.3-5.6), Memory Impairment+Non-Memory Impairment: n = 31 (5.2%, CI: 3.6-7.4) and Non-Memory Impairment: n = 88 (14.9%, CI: 12.1-18.0). CONCLUSIONS: The frequency of MCI-amnestic, the so-called prestage of AD according to Petersen, was very low (0.5%, CI: 0.1-1.5) compared to the estimated incidence rates of AD at this age. Established criteria of MCI could be modified in order to include a higher percentage of high-risk subjects for later developing Alzheimer dementia.

Activities of Daily Living↗
PubMed2005

[Occurrence of chloroquine-induced myopathy after low-dose treatment of rheumatoid arthritis for seven years].

The myotoxicity of chloroquine and hydroxychloroquine has been known for decades. Limb-girdle weakness due to a vacuolar myopathy may occur occasionally in a dose-dependent manner during the first 24 months on chloroquine. However, we report on a case in which muscular weakness developed after a daily intake of 250 chloroquine phosphate (= 155 mg chloroquine base) for a period of 7 years. Even after long-term and apparently well-tolerated chloroquine treatment, the occurrence of severe side-effects is possible.

Antirheumatic Agents↗
PubMed2005

Oxidative stress related markers in the "VITA" and the centenarian projects.

Oxidative stress seems to play an important role in the pathophysiology of Alzheimer's disease (AD). At present there are no easily accessible biochemical markers for AD. We performed activity assays for platelet MAO-B and erythrocyte Cu/Zn-SOD as well as Western blotting for these two proteins. Moreover, we assessed plasma lactoferrin and performed RFLP-analysis for the MAO-B-intron-13-polymorphism in patients from the Vienna-Transdanube Aging (VITA) and from the so called centenarian project. The first one, VITA, is a community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. The centenarian project investigates chronic care in-old patients suffering from AD. In both sexes platelet MAO-B activity increased significantly in the AD group, and Cu/Zn-SOD activity decreased, but the latter effect was significant only in females. No significant difference was found regarding plasma lactoferrin. No correlation was found between MAO-Bi13 and MAO-B platelet activity or allele MAO-Bi13 and disease frequency. These results point to the possibility that a combination of MAO-B and SOD activity levels might be useful tools for an early diagnosis of AD.

Aged↗
PubMed2005

[The anatomy of the surgical treatment of migraine].

OBJECTIVE: The transpalpebral resection of the corrugator and depressor supercilii muscles is a new treatment option for migraine headaches. Hyperactive contractility of these muscles can provoke the peripheral compression of the supratrochlear nerve and induce a neurogenic inflammation triggering the symptoms of migraine. In order to gather detailed knowledge of the respective anatomy in the eyebrow region, a macroscopic cadaver study was conducted. MATERIALS AND METHODS: The relevant muscles of the forehead, glabella and eyebrow were dissected in five fresh, non-preserved heads. The supracanthal origins and dermal points of insertion were marked. Following the preparation of the neurovascular structures, the muscles were measured and weighed. The course of the supraorbital and supratrochlear nerves was demonstrated from the forehead to the orbital cavity. RESULTS: There are three, paired groups of muscles in the superomedial region of the orbital rim. They can be divided into the superficial frontalis and procerus muscle, the orbicularis muscle in a middle layer and the corrugator and depressor supercilii in a deeper layer. The corrugator measured approximately 4.5 cm, whose origin is superior and posterior to the depressor origin situated cranial to the medial canthus. The corrugator inserts lateral to the exit of the supraorbital nerve in the dermis above the eyebrow after penetrating the orbicularis and frontalis muscles and a subgaleal fat pad. The length and weight of the muscles is highly variable. The muscle is penetrated by the supratrochlear nerve whereas the supraorbital nerve runs underneath it. The corrugator is innervated medially and laterally by branches of the facial nerve. CONCLUSION: A detailed knowledge of the complex arrangement of the muscles acting upon the glabella and the different communicating subgaleal and preseptal fat pads allow the identification and resection of the corrugator and depressor muscles without damaging the supratrochlear nerve. The course of the specific nerves is variable. The double-innervation of the corrugator suggests its complete resection instead of the selective denervation of the muscle.

Cadaver↗
PubMed2005

Exposure to traffic related air pollutants: self reported traffic intensity versus GIS modelled exposure.

BACKGROUND: In epidemiological studies of the potential health effects of traffic related air pollution, self reported traffic intensity is a commonly used, but rarely validated, exposure variable. METHODS: As part of a study on the impact of Traffic Related Air Pollution on Childhood Asthma (TRAPCA), data from 2633 and 673 infants from the Dutch and the German-Munich cohorts, respectively, were available. Parents subjectively assessed traffic intensity at the home address. Objective exposures were estimated by a combination of spatial air pollution measurements and geographic information system (GIS) based modelling using an identical method for both cohorts. RESULTS: The agreement rates between self reported and GIS modelled exposure--accumulated over the three strata of self assessed traffic intensity--were 55-58% for PM(2.5), filter absorbance (PM(2.5) abs), and nitrogen dioxide in Munich and 39-40% in the Netherlands. Of the self reported low traffic exposed group, 71-73% in Munich and 45-47% in the Netherlands had low modelled exposure to these three air pollutants. Of the self assessed high exposed subgroups in Munich (15% of the total population) and the Netherlands (22% of the total population), only 22-33% and 30-32% respectively had high modelled exposure to the three air pollutants. The subjective assessments tend to overestimate the modelled estimates for PM(2.5) and NO2 in both study areas. When analysis was restricted to the portion of the Dutch cohort living in non-urban areas, the agreement rates were even lower. CONCLUSIONS: Self reported and modelled assessment of exposure to air pollutants are only weakly associated.

Adult↗
PubMed2005

Detection of filaria-specific IgG4 antibodies and filarial DNA, for the screening of blood spots for Brugia timori.

The establishment of simple, sensitive and specific tools for the diagnosis of brugian lymphatic filariasis is a prerequisite for a successful intervention to control the disease. In the simple and rapid Brugia Rapid (BR) test, an immunochromatographic dipstick is used to detect IgG(4) antibodies that are reactive with a recombinant Brugia malayi antigen. When sera from 109 individuals with Brugia microfilaraemias (12 with B. malayi and 97 with B. timori) were investigated using the BR test, all were found positive. In contrast, all of the 150 sera from individuals with Onchocerca volvulus or Mansonella infections investigated were found negative in BR tests. Some unwelcome cross-reactions were observed, however, with sera from individuals infected with Wuchereria bancrofti (three of 12 test-positive) and Dirofilaria (one of nine test-positive). In an attempt to facilitate sample collection and detect any cross-reactions, the BR dipstick was used to screen blood spots, that had been allowed to dry on filter paper, for B. timori microfilariae, before the dipstick-positive samples were tested with a PCR-based assay. Of the 66 individuals so tested, 37 (56%) were found positive by the BR test used on dry blood spots and eight (22%) by the filtration of fresh blood samples. Only nine of the 37 dipstick-positive samples were found PCR-positive. The combined use of BR tests and PCR-based assays, for testing blood spots in areas where brugian filariasis is endemic, appears to be a promising method not only for post-treatment monitoring but also for the certification activities planned within the framework of the Global Programme to Eliminate Lymphatic Filariasis.

Animals↗
PubMed2004

Antimycobacterial activity of synthetic pamamycins.

OBJECTIVES: Early studies have indicated that pamamycins, a group of macrodiolides first isolated from Streptomyces alboniger, have potent antimicrobial activity against Gram-positive bacteria, fungi and mycobacteria but not against Gram-negative bacteria. The recent availability of highly purified and reasonable quantities of several pamamycins through their total syntheses has rendered possible more extensive studies on their effects on mycobacteria. METHODS: Bioluminescent strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis, expressing the luxA and luxB genes from Vibrio harveyi were used for the comparison of the antimycobacterial activity of the two synthetic macrodiolides pamamycin-607 and pamamycin-621A and a non-naturally occurring cyclic dimer of pamamycin-607, i.e. yukomycin. RESULTS: Pamamycin-607 was the most active of the three macrocycles and was more active against M. tuberculosis than against M. smegmatis. Twenty-five clinical isolates of M. tuberculosis were susceptible to pamamycin-607 in a narrow MIC range of 1.5-2.0 mg/L. The new assay was also validated by comparison with the BACTEC radiometric test. CONCLUSION: Rapid screening of a new class of macrocyclic antimycobacterials using bioluminescent mycobacteria identified pamamycin-607 as a potential antituberculous agent. The latter was active against clinical isolates of M. tuberculosis within a narrow MIC range of 1.5-2.0 mg/L irrespective of their resistance to isoniazid or rifampicin. Our findings warrant further investigations.

Anti-Bacterial Agents↗
PubMed2004

Mitochondrial genotype and risk for Alzheimer's disease: cross-sectional data from the Vienna-Transdanube-Aging "VITA" study.

The Vienna Transdanube Aging (VITA) study searches for early markers of Alzheimer's disease (AD) by examining the mental status in a community-based cohort of 606, 75-years old volunteers that are then related to various clinical and genetic analyses. To determine whether mutations in mtDNA are involved in expression of AD, the mtDNA of 79 "control" participants is screened for alterations by sequencing of "hot-spot-regions". This study on mtDNA mutations has eliminated the influence of aging on the occurrence of mtDNA alterations by sequencing samples from persons at the age of exactly 75 years. Thus, our cohort reveals a snap-shot of mitochondrial sequences of elderly persons. So far, a high percentage (56%) of persons with known or unknown mutations in the fragments analyzed were found. These data will be compared in due time to a cohort of participants with proven late-onset AD.

Aged↗