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Biomedical subjects

C Fischer

Publications and source records attributed to C Fischer.

At least 19 recordsLinked to original sources
PubMed2007

[Extracorporeal shock-wave lithotripsy induced ultrastructural changes to the renal parenchyma under aspirin use. Electron microscopic findings in the rat kidney].

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.

Animals↗
PubMed2006

Principles and therapeutic implications of angiogenesis, vasculogenesis and arteriogenesis.

The vasculature is the first organ to arise during development. Blood vessels run through virtually every organ in the body (except the avascular cornea and the cartilage), assuring metabolic homeostasis by supplying oxygen and nutrients and removing waste products. Not surprisingly therefore, vessels are critical for organ growth in the embryo and for repair of wounded tissue in the adult. Notably, however, an imbalance in angiogenesis (the growth of blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischaemic, infectious and immune disorders. During the last two decades, an explosive interest in angiogenesis research has generated the necessary insights to develop the first clinically approved anti-angiogenic agents for cancer and blindness. This novel treatment is likely to change the face of medicine in the next decade, as over 500 million people worldwide are estimated to benefit from pro- or anti-angiogenesis treatment. In this following chapter, we discuss general key angiogenic mechanisms in health and disease, and highlight recent developments and perspectives of anti-angiogenic therapeutic strategies.

Angiogenesis Inhibitors↗
PubMed2006

Neuropsychological functioning and delusions in dementia: a pilot study.

The present pilot study investigated the pattern of neuropsychological functioning associated with the presence of delusions in mild-to-moderate dementia. Participants, all of whom met criteria for dementia, were divided into two groups, delusional (n = 9) and non-delusional (n = 9). Individuals with hallucinations were excluded. Participants completed a neuropsychological test battery. Global cognitive functioning (MMSE) and behavioral disturbance (BEHAVE-AD) were also assessed. Differences between the delusional and non-delusional group were most marked for immediate recall of stories, which was higher in the non-delusional group. Scores on semantic fluency, attention (mental control), and overall cognitive functioning (MMSE) were also lower in the delusional group. Conversely, simple attention span (Digit Span) was within normal limits in both groups. Floor effects were noted on measures of delayed recall and alternating attention. This study supports previous findings of greater neuropsychological impairment in delusional as compared to non-delusional individuals with dementia. However, some areas of cognitive functioning may be relatively preserved. Future research should examine semantic processing in persons with dementia with and without delusions.

Aged↗
PubMed2006

Modelling germline mosaicism and different new mutation rates simultaneously for appropriate risk calculations in families with Duchenne muscular dystrophy.

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.

Female↗
PubMed2006

RISCALW: a Windows program for risk calculation in families with Duchenne muscular dystrophy.

RISCALW is a novel convenient Windows program for risk calculation in families with Duchenne muscular dystrophy. It is based on an extended genetic model which includes germline mosaicism and different new mutation rates depending on sex and mutation type. Arbitrary family structures and additional diagnostic information such as genotypes from intragenic and flanking genetic markers of the dystrophin gene, creatin kinase values, and female deletion test results can be taken into account. Comprehensive online help is available. RISCALW has been extensively tested in more than 100 families. The user is able to perform risk calculations in large families in an easy way, and thus explore the dependence of the results on different model assumptions, for example different mutation rates in males and females. A detailed handbook and example files are distributed with the program. RISCALW is freely available for scientific use at http://www.riscalw.uni-hd.de.

Genetic Markers↗
PubMed2006

Aspirin resistance in secondary stroke prevention.

BACKGROUND: We investigated the platelet function in stroke patients treated with aspirin [acetylsalicylic acid (ASA)] for secondary stroke prevention during a follow-up period of 1 year. METHODS: In this prospective study 291 patients with first initiated aspirin therapy (300 mg/day) for secondary stroke prevention were included. Platelet aggregation measurements were performed 24 h, 3, 6, and 12 months after starting medication. RESULTS: Twenty-one of 291 patients (7.2%) were identified as primary ASA-non-responders (initial insufficient platelet inhibition) and 4.1% as secondary ASA-non-responders (insufficient platelet inhibition during follow-up). There were no significant differences between ASA-responders and ASA-non-responders concerning age, gender, risk factors, and stroke characteristics. CONCLUSION: Aspirin resistance in stroke patients is not uncommon. The clinical usefulness of routine platelet function tests needs to be proved by further trials.

Aged↗
PubMed2005

[Diagnosis of vitamin B12 deficiency revised].

Vitamin B12 (cobalamin) deficiency is a common disorder with potential irreversible haematological and neurological consequences. Currently used diagnostic tests such as the evaluation of serum vitamin B12 and the Schilling test are insufficient, e.g. the positive predictive value of a low serum vitamin B12 level for actual vitamin B12 deficiency (i.e. tissue deficiency) is low. Insufficient availability of vitamin B12 will lead to the accumulation of methylmalonic acid and homocysteine in the body. Nearly all patients with vitamin B12 deficiency also have substantially increased levels of methylmalonic acid and homocysteine. New tests of serum methylmalonic acid and homocysteine are highly sensitive for vitamin B12 deficiency and may obviate the need for the somewhat cumbersome Schilling test.

Homocysteine↗
PubMed2005

Perisaccadic mislocalization without saccadic eye movements.

Despite frequent saccadic gaze shifts we perceive the surrounding visual world as stable. It has been proposed that the brain uses extraretinal eye position signals to cancel out saccade-induced retinal image motion. Nevertheless, stimuli flashed briefly around the onset of a saccade are grossly mislocalized, resulting in a shift and, under certain conditions, an additional compression of visual space. Perisaccadic mislocalization has been related to a spatio-temporal misalignment of an extraretinal eye position signal with the corresponding saccade. Here, we investigated perceptual mislocalization of human observers both in saccade and fixation conditions. In the latter conditions, the retinal stimulation during saccadic eye movements was simulated by a fast saccade-like shift of the stimulus display. We show that the spatio-temporal pattern of both the shift and compression components of perceptual mislocalization can be surprisingly similar before real and simulated saccades. Our findings suggest that the full pattern of perisaccadic mislocalization can also occur in conditions which are unlikely to involve changes of an extraretinal eye position signal. Instead, we suggest that, under the conditions of our experiments, the arising difficulty to establish a stable percept of a briefly flashed stimulus within a given visual reference frame yields mislocalizations before fast retinal image motion. The availability of visual references appears to exert a major influence on the relative contributions of shift and compression components to mislocalization across the visual field.

Adult↗
PubMed2005

DNA polymorphisms of the prion doppel gene region in four different German cattle breeds and cows tested positive for bovine spongiform encephalopathy.

Polymorphisms of the prion protein gene PRNP have been shown to influence the susceptibility/resistance to prion infections in human and sheep. In addition, the T174M polymorphism within the flanking prion doppel gene (PRND) was thought to be involved in susceptibility to sporadic Creutzfeldt-Jacob disease. To study a possible influence of DNA polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy (BSE), previously identified and newly isolated DNA polymorphisms were genotyped in all available German cattle that tested positive for BSE. Genotypes and calculated haplotypes were compared with breeding bulls serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh (Swiss Brown) resulted in the isolation of the previously known polymorphisms R50H and R132Q and two novel synonymous single nucleotide polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype analysis of BSE and control animals revealed a significantly different distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not in the other breeds tested. No association to BSE susceptibility was detectable for polymorphisms R50H and A5063T.

Amyloid↗
PubMed2005

Temporo-mesial epilepsy surgery: outcome and complications in 100 consecutive adult patients.

BACKGROUND: We studied the surgical outcome, and the complications in a group of 100 consecutive adult patients with medically refractory epilepsy arising from the temporo-mesial structures. METHODS: Hundred patients were treated surgically between 1994 and 2003 for drug-resistant epilepsy involving the temporo-mesial structures. All of them underwent a comprehensive noninvasive presurgical evaluation. Fourty-eight of them underwent depth electrodes recordings (according to the Talairach's StereoElectroEncephaloGraphic (SEEG) methodology) because the noninvasive investigations were not congruent enough to identify the epileptic zone. The patients presenting with any space-occupying lesion, or with a cavernoma, or with a strictly lateral neocortical epileptic focus, were excluded. The MRI-examination was abnormal in 87 cases, displaying a hippocampal atrophy in 69 cases. The extent of temporal resection was planned according to the results of the presurgical investigation in each particular patient. Consequently, this "tailored" resection varied from selective amygdalo-hippocampectomy (6 cases), to anterior temporal lobectomy (76 cases), or to total temporal lobectomy (18 cases). FINDINGS: The mean post-operative follow-up period was 53 months. 85 patients were found to be in Engel's class I post-operatively (free of disabling seizures), among them 74 were in class Ia (totally seizure free). Nine patients were in Engel's class II and six were in Engel's class III or IV (failures). There was no surgical mortality. Three patients had a postoperative hematoma; two patients required a shunt insertion; in three patients meningitis occurred; and two patients had postoperative ischaemia of the anterior choroidal artery territory, which resulted in a mild permanent hemiparesis. Neuropsychological complications are not addressed in detail in this article. CONCLUSIONS: These data indicate that "tailored" resective surgery for temporo-mesial epilepsy can be performed with a low rate of morbidity, and is highly efficacious. The use of invasive presurgical investigation (SEEG) may explain this high rate of success.

Adolescent↗
PubMed2005

SDMinP: a program to control the family wise error rate using step-down minP adjusted P-values.

SDMinP is an easy-to-use program for fast calculation of empirical and adjusted P-values for correlated and uncorrelated hypotheses in multiple testing experiments. It is based on the Free Step-Down Resampling Method for controlling the family wise error rate, and implements a variation of an efficient algorithm, which reduces the originally required re-sampling effort considerably and makes the method computationally feasible. The program is independent of the underlying test statistic and works with provided observed and permutation test statistics.

Algorithms↗
PubMed2005

Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease.

BACKGROUND: Based on in vitro experiments using recombinant human thiopurine S-methyltransferase this enzyme is inhibited by sulfasalazine (sulphasalazine) and 5-aminosalicylate. Thus, during treatment with azathioprine or mercaptopurine, both metabolized by thiopurine S-methyltransferase, sulfasalazine or 5-aminosalicylate could modify the action of azathioprine/mercaptopurine. AIMS: To examine whether this interaction is effective under ex vivo conditions. METHODS: In 18 azathioprine-free patients and in 12 patients on azathioprine the inhibitory potential of sulfasalazine, 5-aminosalicylate and its metabolite (Ac-5-aminosalicylate) was assessed by ex vivo measurement of thiopurine S-methyltransferase in red blood cells. RESULTS: According to concentration response curves mean IC50 values (microm) for sulfasalazine, 5-aminosalicylate and Ac-5-aminosalicylate have been calculated in three groups of azathioprine-free patients and variable basal levels of thiopurine S-methyltransferase activity (very high, normal and intermediate). In all three groups sulfasalazine was the strongest inhibitor (IC50: 9-17 microm) if compared with 5-aminosalicylate (129-236) and Ac-5-aminosalicylate (58-74). In patients on azathioprine similar IC50 values have been calculated. CONCLUSIONS: Comparing human plasma concentrations of sulfasalazine (15-77 microm), 5-aminosalicylate (3-14 microm) and Ac-5-aminosalicylate (8-18 microm) with the IC50 values one can assume that only sulfasalazine would have the potential to inhibit thiopurine S-methyltransferase in vivo. However, the therapeutic impact should be proved by clinical studies.

Adolescent↗
PubMed2005

Haplotype sharing analysis using mantel statistics.

OBJECTIVE: The potential value of haplotypes has attracted widespread interest in the mapping of complex traits. Haplotype sharing methods take the linkage disequilibrium information between multiple markers into account, and may have good power to detect predisposing genes. We present a new approach based on Mantel statistics for spacetime clustering, which is developed in order to improve the power of haplotype sharing analysis for gene mapping in complex disease. METHODS: The new statistic correlates genetic similarity and phenotypic similarity across pairs of haplotypes for case-only and case-control studies. The genetic similarity is measured as the shared length between haplotypes around a putative disease locus. The phenotypic similarity is measured as the mean-corrected cross-product based on the respective phenotypes. We analyzed two tests for statistical significance with respect to type I error: (1) assuming asymptotic normality, and (2) using a Monte Carlo permutation procedure. The results were compared to the chi(2) test for association based on 3-marker haplotypes. RESULTS: The results of the type I error rates for the Mantel statistics using the permutational procedure yielded pointwise valid tests. The approach based on the assumption of asymptotic normality was seriously liberal. CONCLUSION: Power comparisons showed that the Mantel statistics were better than or equal to the chi(2) test for all simulated disease models.

Case-Control Studies↗
PubMed2005

[Monoaminergic transmitters in the cerebrospinal fluid of patients with acute, chronic, and intermittent pain. Interface between pain and depression?].

BACKGROUND AND STUDY PURPOSE: Pain and depression share similar neurobiological characteristics, and it is a common clinical observation that pain and depression may coincide in the same patient. They also appear to influence each other in the process of chronification. Furthermore, there is a complex coupling of pain and depression by monoaminergic transmitter system. PATIENTS AND METHODS: On the basis of these findings, norepinephrine (NE), epinephrine (E), dopamine (DOP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and vanillylmandelic acid (VMA) concentrations were determined in the cerebrospinal fluid (CSF) in patients with acute (20), chronic (27), and episodic pain syndrome (44) in a prospective study. The biochemical parameters were correlated to self-assessment pain and depression scores. The control group consisted of 13 pain-free patients with diseases affecting the muscular system. RESULTS: Patients with chronic and episodic pain syndromes had significantly more depressive and psychovegetative symptoms compared to patients with acute pain. In patients with acute pain, DOP was significantly higher than in controls and chronic and episodic pain patients. In addition DOP was positively correlated to self-assessment pain score (p*<0.05). In patients with chronic and episodic pain, NE and 5-HIAA were positively correlated to the duration of disease and were significantly lower than in the control group. In neither of these two groups could significant correlations be established between these parameters and pain or depression self-assessment scores. In all groups, positive correlations were seen between the neurotransmitter and their metabolites. CONCLUSION: The pathological decrease of NE and 5-HIAA in the CSF points to the crucial role of noradrenergic and serotonergic transmitter systems in the generation, modulation, and perpetuation of chronic and episodic pain syndromes. It indicates that antidepressants are effective drugs in these diseases. However, a discriminative neurochemical pattern between pain and depression could not be established. The demonstration of polyvalent correlations between different neurotransmitters is indicative of complex neurobiological coupling between cortical, limbic, and hypothalamic neuronal networks on the one hand and the nociceptive descending system on the other hand in the genesis of pain and depression.

Acute Disease↗
PubMed2005

[When is aftercare useful in renal cell cancer?].

Diagnosis of tumor recurrence and of therapy-related side effects as well as psychological support are the main goals of a surveillance program of cancer patients. While the latter may represent a time-consuming effort, most diagnostic procedures are expensive. Whether we can efficiently detect tumor recurrence in renal cell carcinoma depends on various parameters of the recurrent disease (e.g., frequency, localization, or therapeutic options). Available data lend support to "lean" follow-up strategies in patients with renal cell carcinoma.

Aftercare↗
PubMed2005

[Altered function of the hypothalamic-pituitary-adrenal axis in patients with acute, chronic and episodic pain].

INTRODUCTION: Complex disorders of the hypothalamic-pituitary-adrenal axis constitute phenomena whose etiopathogenetic significance is the subject of controversy. The frequent coincidence with depressive symptoms further complicates interpretation. PATIENTS AND METHODS: Daily variations in cortisol levels were measured in 20 patients with acute pain, 27 with chronic pain in the lumbar musculoskeletal system, and 44 with episodic forms of headache to determine the daily average and then correlated with differentiated algesimetric data. RESULTS: Patients with chronic and episodic pain had significantly higher scores on the McGill Pain Questionnaire and more affective items as an expression of depressive symptoms than patients with acute pain. The three groups did not however exhibit significant differences for the depression scale and list of "psychovegetative" disorders. In comparison to an age-matched pain-free control population (n=17), the average daily levels of cortisol were significantly higher in all three groups besides singularly elevated daily levels, but no correlations between the cortisol values and overall algesimetric data could be established. Chronic pain patients with high depression scores had significantly higher cortisol levels irrespective of pain intensity. DISCUSSION: Pain experiences cause increased plasma cortisol levels with significant elevation of the daily average. Whereas in cases of acute pain, a direct but unspecific stress reaction not connected with the pain seems to be likely, the underlying cause in cases of chronic and episodic pain appears to be a complex and enduring activation of the hypothalamic-pituitary-adrenal axis, likewise independent from pain, probably associated with concomitant depressive symptoms and disruption of the circadian rhythm of release controlled by the hypothalamus.

Acute Disease↗
PubMed2005

Echinococcus multlocularis infections of rural, residential and urban foxes (Vulpes vulpes) in the canton of Geneva, Switzerland.

We examined 267 red foxes (Vulpes vulpes) from the canton of Geneva, Switzerland, for intestinal infections with Echinococcus multilocularis. This region is situated in the core area of the endemic range of this zoonotic cestode in Central Europe. Several factors were taken into account and urbanisation level appeared to be the most explicative to describe observed differences. The prevalence decreased significantly from rural and residential areas (prevalence of 52%, CI 43-62%, and 49%, CI 38-59 %, respectively) to the urban area (prevalence of 31%, CI 19-42%). A few juvenile foxes harboured very high burdens up to more than 120,000 worms and were significantly more heavily infected than adults. The intensity of infection decreased from rural and residential areas to the city, suggesting a lower contamination of the urban environment.

Age Factors↗