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Biomedical subjects

J Simon

Publications and source records attributed to J Simon.

At least 55 records · Page 3Linked to original sources
PubMed2004

Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen induced arthritis: influence on macrophage activation.

OBJECTIVE: To investigate the indirect effects of anti-CD4 treatment on the functions of macrophages (CD4(-) in mice) in the acute and early chronic phase of mouse antigen induced arthritis (AIA). METHODS: C57BL/6 mice with AIA were treated intraperitoneally with the anti-CD4 mAb GK1.5 or control rat IgG on days -1, 0, 1, 3, 5, and 7. Proinflammatory cytokines (IL1 beta, IL6, and TNF alpha) were quantified by sandwich ELISA in joint extracts, serum, and supernatants of ex vivo stimulated spleen/lymph node cells or peritoneal macrophages (+LPS/IFN gamma). Nitric oxide (NO) levels in supernatants of ex vivo stimulated peritoneal macrophages were measured by the Griess reaction. Proteolytic activity in joint homogenates was analysed by gelatin, casein, and elastin zymography, and substrate assays. RESULTS: Anti-CD4 treatment significantly reduced joint swelling in acute (days 3, 5) and early chronic AIA (day 7) and diminished inflammation and destruction scores in late chronic AIA (day 21). On day 3, anti-CD4 treatment significantly reduced IL6 levels in all compartments. IL1 beta was reduced in joint extracts, unaffected in serum or cells from lymphoid organs, and increased in stimulated peritoneal macrophages. TNF alpha was significantly increased in the joints, decreased in serum, and otherwise unchanged. NO production by stimulated peritoneal macrophages was significantly reduced by anti-CD4 treatment. Lower activity of matrix metalloproteinases and neutrophil elastase was seen in joint extracts of anti-CD4 treated animals than in IgG treated AIA controls. CONCLUSION: CD4(+) T cell directed treatment had strong local and systemic effects on macrophages. These indirect effects may contribute to the reduction of destructive mediators/joint destruction in AIA.

Animals↗
PubMed2004

Educational level and risk profile of cardiac patients in the EUROASPIRE II substudy.

STUDY OBJECTIVE: To ascertain, whether, conventional risk factors and readiness of coronary patients to modify their behaviour and to comply with recommended medication were associated with education in patients with established coronary heart disease. DESIGN AND METHODS: EUROASPIRE II was a cross sectional survey undertaken in 1999-2000 in 15 European countries to ascertain how effectively recommendations on coronary preventions are being followed in clinical practice. Consecutive patients, men and women </=71 years who had been hospitalised for acute coronary syndrome or revascularisation procedures, were identified retrospectively. Data were collected through a review of medical records, interview, and examination at least six months after hospitalisation. The education reached was ascertained at the interview. MAIN RESULTS: A total of 5556 patients (1319 women) were evaluated. Significantly more patients with ischaemia had only primary education, in contrast with the remaining diagnostic groups. Body mass index and glucose were negatively associated with educational level, while HDL-cholesterol was positively associated. Men with highest education had significantly lower systolic blood pressure and total cholesterol. The prevalence of current smoking decreased significantly from primary to secondary and high education only in men. Both men and women with primary educational level were more often treated with antidiabetics, and antihypertensives, but less often with lipid lowering drugs. The effectiveness of treatment was virtually the same in all education groups. CONCLUSIONS: Patients with higher education had lower global coronary risk, than those with lower education. This should be considered in clinical practice. Particular strategies for risk communication and counselling are needed for those with lower education status.

Adult↗
PubMed2004

A guideline for simulation studies of wastewater treatment plants.

A guideline for simulation studies of wastewater treatment plants is proposed. The aim of the HSG-guideline is to define a reference quality level that helps to make the results of simulation studies comprehensible and comparable and therefore increases the quality and reliability of mathematical modelling in wastewater treatment. The paper gives a summary of the HSG-guideline, written by a group of university members from Germany, Austria and Switzerland.

Bioreactors↗
PubMed2003

Individually weight-adapted examination protocol in retrospectively ECG-gated MSCT of the heart.

The standard protocol in multislice spiral CT (MSCT) angiography for coronary arteries with fixed tube current-time settings leads to an overexposure and thus to an unnecessary high radiation dose in patients with lower weight when compared to heavier patients. The purpose of this study was to estimate the effect of reducing the radiation dose by adapting the tube current-time settings individually. Fifty patients underwent retrospectively ECG-gated MSCT of the heart. In 25 patients (group A1) a standard protocol with constant tube current-time settings was used (4 x 1-mm collimation, 120 kV, 400 mAs(eff)). Subsequently, artificial image noise was added to the data of these patients simulating a directive for weight-adapted tube current-time settings (group A2). In the other 25 patients (group B) an alternative protocol with individually weight-adapted tube current-time settings was applied. The data of all groups were evaluated by a regression analysis. The image quality was assessed objectively by measuring the CT attenuation in standardised regions of interest and subjectively by three radiologists using a five-point scoring system in a consensus reading. Applying the weight-adapted tube current-time settings the effective radiation dose was reduced by 17.9% for men and 26.3% for women. The standard protocol leads to an overexposure in light patients as seen in the plot of noise vs weight (slope 0.16+/-0.07 HU/kg). By applying the weight-adapted tube current-time settings a weight-independent, constant image noise is achieved (slope 0.04+/-0.1 HU/kg). Diagnostic image quality was preserved in all patients. Individually weight-adapted tube current-time settings allow for a substantial dose reduction when performing retrospectively ECG-gated MSCT angiography for coronary arteries without impairment of diagnostic image quality.

Aged↗
PubMed2003

Timing of menopause and patterns of menstrual bleeding.

Age at menopause is associated with a variety of health outcomes. Menstrual histories, both as markers of physiologic function and through their potential association with age at menopause, have also been investigated for their links to health outcomes. This study used data from a cohort of women from the United States who provided prospectively recorded data on their menstrual cycles for many years. Dr. Alan Treloar (University of Minnesota) originally recruited the women in the 1930s; the authors used data reported by these women from 1930 through 1977. They identified nuanced characteristics of menstrual histories that were strongly predictive of the onset of menopause, focusing on measures of central tendency (the mean), variability (standard deviation), and serial irregularity (approximate entropy), the last of which quantifies a continuum that ranges from totally ordered to completely random. They controlled for other characteristics known to affect age at menopause, including use of exogenous hormones, number of births, and extent of breastfeeding. Although cycle length and variability increased with the approach of menopause, the authors found that serial irregularity decreased and was a strong predictor of its onset. This finding constitutes an important piece of information not attainable with conventional statistical summaries of menstrual histories.

Adolescent↗
PubMed2003

Apolipoprotein E Pittsburgh variant is not associated with the risk of late-onset Alzheimer's disease in a Spanish population.

The objective of this study was to assess whether the APOE(Pittsburgh) variant (APOE*4P) is associated to Alzheimer's disease (AD) in a population from Madrid (Spain). APOE*4P variant is caused by an exonic mutation which results in the substitution of proline-28 for leucine-28, only present in APOE*4 alleles. A study in a US population associated this APOE variant with an increased risk for AD, about five times higher than the risk attributed to APOE*4 carriers overall. One hundred and seventeen cases of late-onset AD and 121 matched control subjects from Madrid (Spain) were included. We studied the APOE polymorphism and the APOE*4P occurrence, by PCR and restriction analysis, and plasma lipids levels using standard protocols. As expected, APOE*4 was significantly overrepresented in AD cases. The APOE*4P mutation was observed in heterozygous state in four subjects, two AD (1.71%) and two controls (1.65%). APOE*4P did not confer higher risk for AD, globally (odds ratio 0.14; 95% confidence interval (CI) 0.02-1.12) or respect to APOE*4 carriers (odds ratio 0.14; 95% CI 0.02-1.24). There were no differences in plasma lipids levels among genotype groups. The mutation frequency in controls was higher in our sample than in the US one (1.65 and 0.18%, respectively; Fisher test P = 0.049). Our results suggest that this variant is not so uncommon in our population and is not directly related to AD, contrary to what has been proposed for other populations.

Age of Onset↗
PubMed2003

[Chemotherapy of bladder cancer. Systemic therapy with reduced toxicity].

For many years, MVAC chemotherapy has been the standard treatment for patients with advanced bladder cancer. Since only a small proportion of patients with advanced disease may be cured by chemotherapy, the expected toxicity profile has to be balanced against the clinical benefit. It is of importance to select patients who may probably respond to chemotherapy. The treatment-associated toxicity needs to be considered especially in unfit and elderly patients. The introduction of innovative new compounds and combinations for the treatment of advanced bladder cancer has opened new avenues. In particular, the good activity of the synthetic nucleoside analogue gemcitabine has improved chemotherapeutic approaches for older patients. For this group of patients, monotherapy with gemcitabine or paclitaxel as well as combinations with cisplatin, carboplatin, or methotrexate is feasible with acceptable side effects.

Aged↗
PubMed2003

Systems-wide chicken DNA microarrays, gene expression profiling, and discovery of functional genes.

The goal of our current consortium project is to launch a new era--functional genomics of poultry--by providing genomic resources [expressed sequence tags (EST) and DNA microarrays] and by examining global gene expression in target tissues of chickens. DNA microarray analysis has been a fruitful strategy for the identification of functional genes in several model organisms (i.e., human, rodents, fruit fly, etc.). We have constructed and normalized five tissue-specific or multiple-tissue chicken cDNA libraries [liver, fat, breast, and leg muscle/epiphyseal growth plate, pituitary/hypothalamus/pineal, and reproductive tract (oviduct/ovary/testes)] for high-throughput DNA sequencing of EST. DNA sequence clustering was used to build contigs of overlapping sequence and to identify unique, non-redundant EST clones (unigenes), which permitted printing of systems-wide chicken DNA microarrays. One of the most promising genetic resources for gene exploration and functional gene mapping is provided by two sets of experimental lines of broiler-type chickens developed at INRA, France, by divergent selection for extremes in growth traits (fast-growing versus slow-growing; fatness versus leanness at a similar growth rate). We are using DNA microarrays for global gene expression profiling to identify candidate genes and to map growth, metabolic, and regulatory pathways that control important production traits. Candidate genes will be used for functional gene mapping and QTL analysis of F2 progeny from intercrosses made between divergent genetic lines (fat x lean lines; fast-growing x slow-growing lines). Using our first chicken liver microarray, we have already identified several interesting differentially expressed genes in commercial broilers and in divergently selected broiler lines. Many of these candidate genes are involved in the lipogenic pathway and are controlled in part by the thyrotropic axis. Thus, genome-wide transcriptional profiling is a powerful tool used to visualize the cascade of genetic circuits that govern complex biological responses. Global gene expression profiling and QTL scans should enable us to functionally map the genetic pathways that control growth, development, and metabolism of chickens. This emerging technology will have broad applications for poultry breeding programs (i.e., use of molecular markers) and for future production systems (i.e., the health and welfare of birds and the quality of poultry products).

Animal Husbandry↗
PubMed2003

Image reconstruction and image quality evaluation for a 16-slice CT scanner.

We present a theoretical overview and a performance evaluation of a novel approximate reconstruction algorithm for cone-beam spiral CT, the adaptive multiple plane reconstruction (AMPR), which has been introduced by Schaller, Flohr et al. [Proc. SPIE Int. Symp. Med. Imag. 4322, 113-127 (2001)] AMPR has been implemented in a recently introduced 16-slice CT scanner. We present a detailed algorithmic description of AMPR which allows for a free selection of the spiral pitch. We show that dose utilization is better than 90% independent of the pitch. We give an overview on the z-reformation functions chosen to allow for a variable selection of the spiral slice width at arbitrary pitch values. To investigate AMPR image quality we present images of anthropomorphic phantoms and initial patient results. We present measurements of spiral slice sensitivity profiles (SSPs) and measurements of the maximum achievable transverse resolution, both in the isocenter and off-center. We discuss the pitch dependence of image noise measured in a centered 20 cm water phantom. Using the AMPR approach, cone-beam artifacts are considerably reduced for the 16-slice scanner investigated. Image quality in MPRs is independent of the pitch and equivalent to a single-slice CT system at pitch p approximately 1.5. The full width at half-maximum (FWHM) of the spiral SSPs shows only minor variations as a function of the pitch, nominal, and measured values differ by less than 0.2 mm. With 16 x 0.75 mm collimation, the measured FWHM of the smallest reconstructed slice is about 0.9 mm. Using this slice width and overlapping image reconstruction, cylindrical holes with 0.6 mm diameter can be resolved in a z-resolution phantom. Image noise for constant effective mAs is nearly independent of the pitch. Measured and theoretically expected dose utilization are in good agreement. Meanwhile, clinical practice has demonstrated the excellent image quality and the increased diagnostic capability that is obtained with the new generation of multislice CT systems.

Algorithms↗
PubMed2003

Image reconstruction and performance evaluation for ECG-gated spiral scanning with a 16-slice CT system.

We present an image reconstruction approach and a performance evaluation for ECG-gate cardiac spiral scanning with recently introduced 16-slice CT equipment. We present an extension of the Adaptive Cardio Volume (ACV) reconstruction approach for ECG-gated multislice spiral scanning. We discuss the image z reformation introduced to control the spiral slice width of the final images and give an overview of the reformation functions chosen. We investigate image quality and discuss the maximum number of slices that can be reconstructed without severe cone-beam artifacts. Slice sensitivity profiles (SSPs) and transverse resolution are evaluated as a function of the patient's heart rate. We demonstrate the influence of slice width on the visualization of stents and plaques and show the impact of reduced gantry rotation time (0.42 s) on temporal resolution. Deviating from general purpose spiral scanning cone-beam reconstruction is not required for ECG-gated cardiac CT with up to 16 slices. Using the ACV approach with image reformation, SSPs are well defined and independent of the patient's heart rate. With 0.75 mm collimated slice width, the measured full width at half-maximum (FWHM) of the smallest reconstructed slice is about 0.83 mm. Using this slice width and overlapping image reconstruction, cylindrical holes 0.6-0.7 mm in diameter can be resolved in a z-resolution phantom. Adequate visualization of the coronary arteries requires reconstruction slice widths not larger than 1.5 mm. Visualization of stents and severe calcifications is significantly improved with sub-mm slice width. Experimental evidence for the theoretically predicted temporal resolution and for the variation of temporal resolution depending on the position in the field of measurement (FOM) is presented. With 0.42 s gantry rotation temporal resolution reaches its optimum of 105 ms in the center of the FOM at 81 bpm. First scans on human subjects demonstrate the potential to expand the range of heart rates accessible to routine clinical examinations. A 16-slice platform can cover the heart with sub-mm slices within short breath-hold times, allowing for improved cardiac imaging due to isotropic sub-mm spatial resolution.

Algorithms↗
PubMed2003

The P2Y nucleotide receptors in the human genome.

Since the first identification of P2Y receptor sequences in 1993, it has quickly become apparent that this family of the G-protein coupled receptors is very diverse. Members of this receptor family are activated extra-cellularly by a wide variety of adenosine and uridine nucleotides including sugar-nucleotides. The recent decipherment of the Human Genome has enabled us to search for new, yet undiscovered P2Y receptor subtypes. In this article we examine the relationships of six orphan G-protein coupled receptor (GPCR) sequences which show considerable sequence homology to various P2Y receptors. The clustering at a few chromosomal loci of P2Y receptor genes and their related orphan genes further suggests that particular P2Y subsets were derived from the same ancestral gene during evolution.

Amino Acid Sequence↗
PubMed2003

Detection of coronary calcifications: feasibility of dose reduction with a body weight-adapted examination protocol.

OBJECTIVE: The purpose of this study was to assess the applicability of individual body weight-adapted tube current time settings in multidetector CT for detection of coronary calcifications and to evaluate the effect of reducing the radiation dose on the coronary calcium score. SUBJECTS AND METHODS. One hundred patients underwent retrospectively ECG-gated MDCT for detection of coronary calcifications. First, fixed tube current time settings were used in 50 patients. Second, image noise corresponding to body weight-adapted tube current time settings was added to these images. Finally, body weight-adapted tube current time settings were applied to another 50 patients. For each patient group, the radiation dose was calculated. Coronary calcium scores were compared for the patient groups with the fixed tube current time settings with and without artificially added image noise. In all image series, image noise was assessed by a region-of-interest methodology. Image noise was analyzed using a regression analysis. RESULTS: The effective radiation dose was reduced by 11.6% for men and 24.8% for women using the body weight-adapted tube current time settings. There were no statistically significant changes in the coronary calcium score after the addition of artificial image noise (p = 0.84). Adaptation of the tube current time settings did not lead to a relevant increase in image noise. The radiation doses for the plotted noise-to-body weight (slope, 0.081) and noise-to-body mass index (slope, 0.378) ratios for the standard protocol proved relatively high for patients of lower weight. An improved noise-to-body weight (slope, 0.054) and noise-to-body mass index (slope, 0.190) ratio was achieved by application of the body weight-adapted tube current time settings, resulting in nearly constant image noise related to body weight. CONCLUSION: Individual body weight-adapted current time settings are applicable for coronary calcium scoring without a change of the coronary calcium score or relevant increase of the image noise.

Body Mass Index↗
PubMed2002

First observation of the doubly charmed baryon Xi(+)(cc).

We observe a signal for the doubly charmed baryon Xi(+)(cc) in the charged decay mode Xi(+)(cc)-->Lambda(+)(c)K-pi(+) in data from SELEX, the charm hadroproduction experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1+/-0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is 3519+/-1 MeV/c(2). The Gaussian mass width of this state is 3 MeV/c(2), consistent with resolution; its lifetime is less than 33 fs at 90% confidence.

Journal Article↗
PubMed2002

New technical developments in multislice CT--Part 1: Approaching isotropic resolution with sub-millimeter 16-slice scanning.

The introduction of multislice CT was a breakthrough with regard to increased scan speed, improved axial resolution and better utilization of the tube output. The new generation of multislice CT scanners offering simultaneous acquisition of up to 16 sub-millimeter slices represents an important leap on the way towards true isotropic scanning. We present an evaluation of a state-of-the-art 16-slice CT system (SOMATOM Sensation 16, Siemens AG, Forchheim, Germany). After an introduction to the detector design we discuss dose utilization and finally elaborate on multislice spiral scanning with 16 slices. Due to the increased number of slices dose utilization is improved compared to current 4-slice CT scanners, and sub-millimeter collimation needs no longer be restricted to special applications. For CT systems with 8 or more slices, the cone-beam geometry causes severe artifacts if not corrected for by a so-called cone-correction, which thus becomes mandatory in this case. With the Adaptive Multiple Plane Reconstruction AMPR, cone beam artifacts are effectively suppressed, while the benefits of Adaptive Axial Interpolation are maintained: free selection of the spiral pitch according to the clinical needs of an examination, slice width independent of the pitch, full dose utilization at all pitch values. Clinical practice will have to demonstrate the application spectrum that is opened with the new generation of multislice CT systems.

Artifacts↗
PubMed2002

New technical developments in multislice CT, part 2: sub-millimeter 16-slice scanning and increased gantry rotation speed for cardiac imaging.

Despite all promising advances, some challenges remain for ECG-gated multislice CT examinations of the heart and the coronary arteries with current 4-slice detectors: adequate visualization of stents and severely calcified coronary arteries, examination of patients with higher heart rates and patients, who cannot adequately hold their breath for at least 30 sec. The new generation of multislice CT systems offering simultaneous acquisition of up to 16 sub-millimeter slices and gantry rotation times shorter than 0.5 sec has the potential to overcome these limitations. We describe the technical principles of cardiac scanning with a state-of-the-art 16-slice CT equipment (SOMATOM Sensation 16, Siemens AG, Forchheim, Germany). We discuss an extension of the Adaptive Cardio Volume (ACV) reconstruction approach for ECG-gated multislice spiral CT. We show the impact of reduced gantry rotation time (0.42 sec) on temporal resolution, and we demonstrate the influence of slice width on the visualization of stents and plaques. Deviating from general purpose applications a cone-correction is not required for cardiac scanning with 16-slice CT systems. In addition to the absolute improvement, the temporal resolution shows a different dependence on the patient's heart rate for 0.42 sec rotation time, reaching its optimum (105 msec) at 81 BPM. This has the potential to expand the range of heart rates accessible to routine clinical examinations. Owing to sub-millimeter slice width and optimized in-plane resolution characteristics, visualization of stents and severe calcifications in coronary arteries is significantly improved. Clinical experience will be needed to fully evaluate the potential of 16-slice technology for cardiac imaging.

Artifacts↗
PubMed2002

Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers.

BACKGROUND AND AIMS: Escherichia coli heat labile enterotoxin (LT) at doses of 5 micro g or 10 micro g has adjuvant activity for oral immunisation in humans infected with Helicobacter pylori, but causes severe diarrhoea. This study was undertaken to establish a safe and effective dose of LT, to confirm the safety of recombinant urease, and to compare the immunogenicity of orally compared with enterically delivered urease. METHODS: 42 healthy adults without present or past H pylori infection were randomised to receive 60 mg recombinant H pylori urease in soluble or in encapsulated form, given with doses of LT ranging from 0 micro g to 2.5 micro g. Four oral doses were administered at day 1, 8, 29, and 57. Specific IgG, IgA, and antibody secreting cells were measured as well as total alpha4beta7 integrin positive lymphocyte responses. RESULTS: Enterically delivered urease was well tolerated and no serious adverse events occurred. Mild diarrhoea (one to four loose stools) occurred after the first immunisation in 50% (6 of 12) of the volunteers exposed to 2.5 micro g LT (p=0.06; paired t test, compared with baseline) but not in volunteers exposed to lower LT doses. Immune responses occurred in five (p=0.048; Fisher's exact test), one, two, and one of six subjects exposed to 2.5 micro g, 0.5 micro g, 0.1 micro g, and no LT, respectively. Significant CD4(+), CD69(+), and CD45RO(hi) responses occurred over time among alpha4beta7(hi) lymphocytes in volunteers receiving 2.5 micro g LT. Enterically delivered urease induced higher lymphocyte responses than soluble urease. CONCLUSIONS: The safety of H pylori urease is confirmed. Oral LT may conserve its adjuvant activity at low doses with minimal side effects.

Adjuvants, Immunologic↗