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Biomedical subjects

D Fischer

Publications and source records attributed to D Fischer.

At least 19 recordsLinked to original sources

Prognostic significance of clusterin immunoreactivity in breast cancer.

Clusterin (CLU) is involved in a variety of biological processes and has been found to be expressed even in many human malignancies, including breast cancer. Currently, there are only few data on the prognostic value of CLU in breast cancer. We therefore evaluated the relationship between CLU expression and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 141 breast cancer patients using the monoclonal antibody 7D1. CLU expression was found in 26% of cases and correlated significantly with high histological tumor grade and high Ki-67 labeling index (p=0.026 and p=0.010, respectively). Univariate Cox regression analysis revealed that CLU expression was tendentiously associated with RFS (p=0.068; relative risk [RR]: 1.77) and MFS (p=0.122; RR: 1.57). In a multivariate analysis, tumor grade, stage, estrogen receptor status and patients age (concerning RFS) as well as grade and lymph node status (concerning MFS) were identified as significant independent prognosticators. CLU expression showed an independent prognostic relevance concerning prediction of RFS by trend (p=0.110; RR: 1.81). We conclude from our data that estimation of CLU immunoreactivity may be helpful as a supplementary criterion to better assess the tumors propensity to relapse in selected cases of breast carcinoma.

Adult↗

Muscle imaging in dominant core myopathies linked or unlinked to the ryanodine receptor 1 gene.

OBJECTIVE: To characterize the muscle involvement of patients with central core disease (CCD) caused by mutations in the ryanodine receptor 1 gene (RYR1) and to compare these findings with those from patients with core myopathies unlinked to the RYR1 gene. METHODS: We performed a systematic muscular imaging assessment in 11 patients with an RYR1 gene mutation and compared these findings with those of 5 patients from two unrelated families with autosomal dominant core myopathies not linked to RYR1, ACTA1, or MYH7 gene loci. RESULTS: All patients with RYR1 CCD had a characteristic pattern with predominant involvement of the gluteus maximus, adductor magnus, sartorius, vastus intermediolateralis, soleus, and lateral gastrocnemius muscles. In contrast, muscle CT in the first family not linked to RYR1 showed predominant affection of the gluteus minimus and hamstring muscles, whereas the second family presented with predominant involvement of the gluteus minimus, vastus intermediolateralis, tibialis anterior, and medial gastrocnemius muscles. In addition to muscle imaging data, we present detailed information on the clinical and pathologic findings of these novel phenotypes of core myopathies not linked to RYR1. CONCLUSIONS: Our data suggest genetic heterogeneity in autosomal dominant core myopathies and the existence of additional unidentified genes.

Chromosome Disorders↗

Genetic structure of a foundation species: scaling community phenotypes from the individual to the region.

Understanding the local and regional patterns of species distributions has been a major goal of ecological and evolutionary research. The notion that these patterns can be understood through simple quantitative rules is attractive, but while numerous scaling laws exist (e.g., metabolic, fractals), we are aware of no studies that have placed individual traits and community structure together within a genetics based scaling framework. We document the potential for a genetic basis to the scaling of ecological communities, largely based upon our long-term studies of poplars (Populus spp.). The genetic structure and diversity of these foundation species affects riparian ecosystems and determines a much larger community of dependent organisms. Three examples illustrate these ideas. First, there is a strong genetic basis to phytochemistry and tree architecture (both above- and belowground), which can affect diverse organisms and ecosystem processes. Second, empirical studies in the wild show that the local patterns of genetics based community structure scale up to western North America. At multiple spatial scales the arthropod community phenotype is related to the genetic distance among plants that these arthropods depend upon for survival. Third, we suggest that the familiar species-area curve, in which species richness is a function of area, is also a function of genetic diversity. We find that arthropod species richness is closely correlated with the genetic marker diversity and trait variance suggesting a genetic component to these curves. Finally, we discuss how genetic variation can interact with environmental variation to affect community attributes across geographic scales along with conservation implications.

Animals↗

[Extramedullary manifestation of plasmocytoma in ENT].

Plasmocytomas are non-Hodgkin's tumors which occur with an incidence of 4/100,000. Malignant plasma cells in bone marrow produce monoclonal antibodies which are typically found in urine and blood samples. In rare instances plasmocytoma occur exclusively in extramedullary locations preferring head and neck region. We report about two patients with extramedullary plasmocytoma, one of them with an extremely rare triple manifestation in the upper airway.

Adult↗

A dynein mutation attenuates motor neuron degeneration in SOD1(G93A) mice.

Cu/Zn SOD1(G93A) transgenic mice develop phenotypical hallmarks of ALS and serve therefore as an established model to study the molecular mechanisms underlying this disease. Recent reports demonstrate that mutations in the motor protein dynein in Legs at odd angles (Loa) and Cramping (Cra1) mice lead to similar but milder phenotypes. Surprisingly, double transgenic mice (Loa/SOD1(G93A)) have been recently shown to attenuate rather than to accelerate the phenotypical expression of motor neuron degeneration. These results raise the question whether other functional relevant mutations in dynein cause a similar effect. To address this question, we have cross-bred SOD1(G93A) with Cra1/+ mice. These double transgenic mice show an attenuated decline of both motor activity and body weight and an increase of survival time compared to SOD1(G93A) mice. Thus, this study confirms that mechanisms associated with dynein such as retrograde axonal transport may play an important role in SOD1(G93A-) toxicity on motor neurons.

Animals↗

Prevention of sudden infant death syndrome (SIDS) due to an active health monitoring system 20 years prior to the public "Back to Sleep" campaigns.

BACKGROUND: Before reunification, the post-neonatal mortality rate was lower in East Germany than in West Germany. Moreover, the incidence of SIDS (sudden infant death syndrome) was much lower in the East. METHODS: Mortality data on sudden infant death syndrome (SIDS) from West and East Germany since 1980 as well as post-neonatal mortality data for both states since 1970 were examined. 95% Confidence intervals were calculated for the rates. Witnesses from the former East Germany who were involved at the time were also interviewed and archives were searched. RESULTS: We found that as early as 1972 active monitoring of infant and child mortality rates in East Germany had shown that the prone sleeping position was dangerous for infants: the post-neonatal mortality rate was approximately 1 per 1000 live births lower in East than in West Germany during the 20 years before reunification. In contrast, in the West, prone sleeping was only discovered to be a risk factor for SIDS in the early 1990s. CONCLUSIONS: Active monitoring is an effective tool in the early detection of risk factors and serves to prevent unnecessary deaths.

Autopsy↗

[Polyglycosan body myopathy].

We report two patients with polyglycosan body disease manifesting in adulthood. Clinical, electrophysiological, and histopathological characteristics of their disorders are summarized, and diagnostic classification is discussed.

1,4-alpha-Glucan Branching Enzyme↗

Misleading positioning of a Foley catheter balloon.

Indwelling catheters in the urinary bladder are associated with numerous and various complications, e.g. infection, haemorrhage, epididymo-orchitis and perforation. Abdominopelvic CT is frequently performed in hospitalized patients, with the bladder being included in the examination. Familiarity with the various bladder pathologies and a routine and meticulous search for them are indicated in every case. Moreover, an awareness of certain pitfalls may prevent over-diagnosis and over-treatment. We present a case in which a Foley catheter balloon inflated in a bladder diverticulum simulates sealed bladder perforation with extraluminal location of the balloon. This potentially misleading diagnosis should be considered in the presence of apparent extraluminal position of catheter tip or balloon not substantiated by the clinical presentation.

Aged, 80 and over↗

Case Study Part 1: How to calculate appropriate deterministic long-term toxicity to exposure ratios (TERs) for birds and mammals.

In the European Union, first-tier assessment of the long-term risk to birds and mammals from pesticides is based on calculation of a deterministic long-term toxicity/exposure ratio (TER(lt)). The ratio is developed from generic herbivores and insectivores and applied to all species. This paper describes two case studies that implement proposed improvements to the way long-term risk is assessed. These refined methods require calculation of a TER for each of five identified phases of reproduction (phase-specific TERs) and use of adjusted No Observed Effect Levels (NOELs) to incorporate variation in species sensitivity to pesticides. They also involve progressive refinement of the exposure estimate so that it applies to particular species, rather than generic indicators, and relates spraying date to onset of reproduction. The effect of using these new methods on the assessment of risk is described. Each refinement did not necessarily alter the calculated TER value in a way that was either predictable or consistent across both case studies. However, use of adjusted NOELs always reduced TERs, and relating spraying date to onset of reproduction increased most phase-specific TERs. The case studies suggested that the current first-tier TER(lt )assessment may underestimate risk in some circumstances and that phase-specific assessments can help identify appropriate risk-reduction measures. The way in which deterministic phase-specific assessments can currently be implemented to enhance first-tier assessment is outlined.

Animals↗

Case Study Part 2: Probabilistic modelling of long-term effects of pesticides on individual breeding success in birds and mammals.

Long term exposure of skylarks to a fictitious insecticide and of wood mice to a fictitious fungicide were modelled probabilistically in a Monte Carlo simulation. Within the same simulation the consequences of exposure to pesticides on reproductive success were modelled using the toxicity-exposure-linking rules developed by R.S. Bennet et al. (2005) and the interspecies extrapolation factors suggested by R. Luttik et al. (2005). We built models to reflect a range of scenarios and as a result were able to show how exposure to pesticide might alter the number of individuals engaged in any given phase of the breeding cycle at any given time and predict the numbers of new adults at the season's end.

Animals↗

Relativistic electron correlation, quantum electrodynamics, and the lifetime of the 1s(2)2s(2)2p2p0(3/2) level in boronlike argon.

The lifetime of the Ar13+ 1s(2)2s(2)2p2p0(3/2) metastable level was determined at the Heidelberg Electron Beam Ion Trap to be 9.573(4)(5). The accuracy level of one per thousand makes this measurement sensitive to quantum electrodynamic effects like the electron anomalous magnetic moment (EAMM) and to relativistic electron-electron correlation effects like the frequency-dependent Breit interaction. Theoretical predictions, adjusted for the EAMM, cluster about a lifetime that is approximately shorter than our experimental result.

Journal Article↗

[Diagnosis of spontaneous ascites infection in patients with cirrhosis: reagent strips].

AIM: To evaluate the sensitivity, specificity, and predictive values of dipstick testing (DT) for detecting spontaneous bacterial peritonitis (SBP), defined by an ascites neutrophil polymorphonuclear cell count > or = 250/mm3, in patients with cirrhosis. METHODS: The study includes all patients with cirrhosis and ascites admitted to our general hospital on the southern outskirts of the Paris metropolitan area (France) from June 2003 to May 2004 (n = 47:27 men and 20 women). Diagnostic abdominal paracentesis was performed on admission, and a Multistix SG (Bayer Pharma) reagent strip was immersed in one ascitic sample from each patient. Readings after 120 s were either negative (DT-) or positive (DT+, with 4 levels of positivity: trace, +, ++, or +++). In case of cytologically-proven SBP, patients were treated with cefotaxime, and subsequent paracentesis with DT and cytologic testing took place every 48 hours, until recovery. RESULTS: Six of the 47 patients had proven SBP, all with clinical signs of SBP (fever and/or abdominal pain); five of these patients were DT+ and one was DT-. In the five patients initially DT+, the DT became negative at the same time as the cytologic criteria for SBP disappeared. Forty-one patients did not meet the cytologic criteria for SBP: 34 were DT- and 7 were DT+ (traces: 4, ++: 2, +++:1); two of these had clinical signs suggestive of SBP. CONCLUSION: Although the sensitivity (83%), specificity (83%) and negative predictive value (97%) of DTwere satisfactory, its positive predictive value (42%) was low. Dipstick testing of ascitic fluid is easy to perform and inexpensive and may be recommended for diagnosis and follow-up of SBP, especially in emergency settings.

Aged↗

High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients.

High-level expression of Rad51, a key factor in homologous recombination, has been observed in a variety of human malignancies. This study was aimed to evaluate Rad51 expression to serve as prognostic marker in non-small-cell lung cancer (NSCLC). A total of 383 non-small-cell lung tumours were analysed immunohistochemically on NSCLC tissue microarrays. High-level Rad51 expression was observed in 29.4% (100 out of 340) of cases. Patients whose tumours displayed high-level Rad51 expression showed a significantly shorter median survival time of 19 vs 68 months (P<0.0001, log-rank test). Similarly T status, N status, M status, clinical stage and histological tumour grade were significant prognostic markers in univariate Cox survival analysis. Importantly, Rad51 expression (P<0.0001) together with tumour differentiation (P<0.009), clinical stage (P=0.004) and N status (P=0.0001) proved to be independent prognostic parameters in multivariate analysis. Rad51 expression predicted the outcome of squamous cell cancer as well as adenocarcinoma of the lung. Our results suggest that Rad51 expression provides additional prognostic information for surgically treated NSCLC patients. We hypothesise that the decreased survival of NSCLC patients with high-level expression of Rad51 is related to an enhanced propensity of tumour cells for survival, antiapoptosis and chemo-/radioresistance.

Carcinoma, Non-Small-Cell Lung↗

Electron impact ionization in the presence of a laser field: a kinematically complete (ngammae,2e) experiment.

Single ionization of He by 1 keV electron impact in the presence of an intense (I=4 x 10(12) W/cm(2)) laser field (lambda=1064 nm) has been explored in a kinematically complete experiment using a reaction microscope. Distinct differences in the singly to fully differential cross sections compared to the field-free situation are observed which cannot be explained by a first-order quantum calculation. Major features, such as the number of photons exchanged and the modification of the energy spectrum of emitted electrons, can be understood qualitatively within a simple classical model.

Journal Article↗

[Removal of a thoracic impaling agent without direct observation. The significance of pre-operative diagnosis].

Impalement injuries are uncommon and only occasional reports exist in the literature, resulting in non standardized approaches. Depending on the location, completely different combinations of injuries occur, making every impalement unique. Nevertheless some basic principles for dealing with impalements exist. These principles, and some controversial statements in the literature on the value of preoperative diagnostics, especially CT, are discussed using the example of a spectacular thoracic impalement by a 2 x 2 cm square metal pole. Our deviation from the principal of removing an impaling object only under direct observation in this special case is also discussed.

Adult↗

Unilateral optic nerve crush induces bilateral retinal glial cell proliferation.

The post-injury responses of retinal ganglion cells elicit a number of glial reactions which have not been completely understood. The bilateral pattern of non-neuronal retinal cell proliferation was examined in association with the differential fates of unilaterally injured adult retinal ganglion cells by means of bromodeoxyuridine (BrdU) immunocytochemistry. Lateralization of the glioproliferative events was studied by analysing both the experimental and the uninjured contralateral as well as matched retinas of sham-operated animals. Control adult rat retina included very few BrdU-positive cells within the nerve fibre and ganglion cell layers; however, experimental retinas of degenerating groups exhibited statistically significantly higher densities of newborn cells in most layers. Clusters of labelled cells were found in the inner plexiform layer related to OX-42 staining, indicating their microglial nature. Indeed, double-labelling experiments, after short-term unilateral optic nerve crushing, identified proliferating retinal glial cells in vivo. Both types of glia, astroglial and microglial cells, exhibited BrdU-positive labelling in injured as well as uninjured experimental rat retinas. Moreover, microglial proliferating cells were also identified in explanted retinal pieces after 2 days in culture. Affected and contralateral retinas responded similarly to the unilateral experimental manipulations applied with respect to BrdU labelling. The acute glial responses observed suggest that bilateral glial proliferation might represent a common response related to degeneration events in both retinas, i.e. ipsi- and contralateral to the experimental injury.

Animals↗