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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

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

GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy.

OBJECTIVES: To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV-1. METHODS: Patients with a viral load>1000 HIV-1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno-pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load<200 copies/mL at week 12. RESULTS: A total of 134 patients were randomized in the study, with 67 in each group, and included in the intent-to-treat (ITT) analysis. At baseline, median values were as follows: viral load (log(10) copies/mL): G=4.1, GP=4.0; CD4 cell count (cells/microL): G=292, GP=294; and number of prior drugs: G=7, GP=8. The median number of resistance mutations was five in the G group [nucleoside reverse transcriptase inhibitors (NRTIs)=three; non-nucleoside reverse transcriptase inhibitors (NNRTIs)=one; protease inhibitors (PI)=one] and seven in the GP group (NRTI=four; NNRTI=two; PI=one). At week 8, treatment was adjusted according to the TDM in 13 of the 67 patients in the GP group (19%). By ITT missing equal failure analysis at week 12, and after only one intervention according to plasma concentration results, a viral load<200 copies/mL was achieved in 30 of the 67 patients (45%) in the G group and in 29 of the 67 patients (43%) in the GP group (not significant). In the multivariate analysis, only prior exposure to at least two PIs at baseline gave a poor response to subsequent antiretroviral therapy. At week 24, a viral load<200 copies/mL was achieved in 35 of the 67 patients (52%) in the G group and in 40 of the 67 patients (60%) in the GP group. CONCLUSIONS: A statistically significant benefit of using TDM was not found in this short-term study where patients appeared to be adherent. However, combining genotypic resistance testing with the use of an expert committee to monitor subsequent therapy individually in patients with multiple resistance mutations was associated with high antiviral efficacy.

Adolescent↗
PubMed2004

Inhibition of neutrophil activity in cardiac surgery with cardiopulmonary bypass: a novel strategy with the leukocyte inhibition module.

Recently, we showed that the arterial in-line application of the leukocyte inhibition module (LIM) within the heart-lung machine limits overshooting leukocyte activity and cardiac tissue damage. Moreover, significantly better cardiac function was found in an experimental animal model when LIM was used. In the meantime, the first promising clinical data exist. LIM has to be regarded as an essential tool in extracorporeal circulation, in the future, to improve postoperative clinical outcome and to reduce costs. This review summarizes the biological background of LIM and the current experience obtained in experimental models and clinical studies.

Animals↗
PubMed2004

Heterogeneous cell mechanical properties: an atomic force microscopy study.

Atomic force microscopy (AFM) is a non-invasive microscopy to explore living biological systems like cells in liquid environment. Thus AFM is an appropriate tool to investigate surface chemical modification and its influence on biological systems. In particular, control over biomaterial surface chemistry can result in a regulated cell response. This report investigates the influence of adhesive and non-adhesive surfaces on the cell morphology and the influence of the cytoskeleton structure on the local mechanical properties. In this study, the main work concerns a thorough investigation of the height images obtained with an AFM as therecorded images provide the evolution of the mechanical properties of the cell as function of its local structure. Information on the cell elasticity due to the cytoskeleton organization is deduced when comparing the AFM tip indentation depth versus the distance between the cytoskeleton bundles for the different samples.

Cell Adhesion↗
PubMed2003

Synthesis of a Möbius aromatic hydrocarbon.

The defining feature of aromatic hydrocarbon compounds is a cyclic molecular structure stabilized by the delocalization of pi electrons that, according to the Hückel rule, need to total 4n + 2 (n = 1,2, em leader ); cyclic compounds with 4n pi electrons are antiaromatic and unstable. But in 1964, Heilbronner predicted on purely theoretical grounds that cyclic molecules with the topology of a Möbius band--a ring constructed by joining the ends of a rectangular strip after having given one end half a twist--should be aromatic if they contain 4n, rather than 4n + 2, pi electrons. The prediction stimulated attempts to synthesize Möbius aromatic hydrocarbons, but twisted cyclic molecules are destabilized by large ring strains, with the twist also suppressing overlap of the p orbitals involved in electron delocalization and stabilization. In larger cyclic molecules, ring strain is less pronounced but the structures are very flexible and flip back to the less-strained Hückel topology. Although transition-state species, an unstable intermediate and a non-conjugated cyclic molecule, all with a Möbius topology, have been documented, a stable aromatic Möbius system has not yet been realized. Here we report that combining a 'normal' aromatic structure (with p orbitals orthogonal to the ring plane) and a 'belt-like' aromatic structure (with p orbitals within the ring plane) yields a Möbius compound stabilized by its extended pi system.

Journal Article↗
PubMed2003

Characterization of dynamic cellular adhesion of osteoblasts using atomic force microscopy.

BACKGROUND: Atomic force microscopy (AFM) can be used to visualize the cell morphology in an aqueous environment and in real time. It also allows the investigation of mechanical properties such as cell compliance as a function of cell attachment. This study characterized and evaluated osteoblast adhesion by AFM. METHODS: Human bone marrow stromal cells were cultured on two types of surface to induce weak and strong cellular adhesions. RESULTS: Cells were considered as spreading if they had a flattened and lengthened shape and a cytoskeletal organization in the submembrane cytosolic region. Cell detachment demonstrated different adhesion states between adherent cells to be distinguished. The stability of the cytoskeletal fibers indicated that cells were adherent. The elastic modulus was estimated by two complementary approaches. The values deduced were between 3 x 10(2) and 2 x 10(5) Nm(-2) according to the state of cell adhesion and the approaches used to measure this elastic modulus. CONCLUSIONS: Although the results were qualitative, a relation may be deduced between the elasticity of living cells as demonstrated by cytoskeletal organization and the state of cell adhesion. The technique could be used to determine the adhesion state of an adherent osteoblast observed under AFM.

Bone Marrow Cells↗
PubMed2003

Perioperative elastase activity in cardiac surgery and its role in endothelial leakage.

OBJECTIVE AND DESIGN: The functional activity and pathophysiological effects of polymorphonuclear elastase (PMNE) in cardiac surgery patients are unknown. This in vitro study was done to evaluate whether PMNE activity in patient blood samples may be correlated with decreased endothelial wall integrity. METHODS AND SUBJECTS: PMNE was serially analyzed by PMNE activity in plasma samples from 40 high risk cardiac surgery patients. Endothelial cell cultures were used to study the influence of patient serum on the intercellular integrity. RESULTS: Ex vivo, samples with high PMNE activity (>1.0 mg/ ml), found in 14 patients (35%), neither induced hyperpermeability in cultured endothelial cells nor resulted in intracellular redistribution of the junction molecules cadherin-5 or beta-catenin. However, pretreatment of endothelial cells with these samples but not with low activity (<0.5 mg/ml) samples augmented neutrophil transendothelial migration (>20-fold) in conjunction with formation of intercellular gaps and irregular membrane-associated beta-catenin staining. Neutrophil transmigration was inhibited by blocking neutrophil beta1 integrin but not by the proteinase inhibitor methoxysuccinyl-Ala-Ala-Pro-Ala. CONCLUSIONS: Augmented PMNE activity in cardiac surgery patients does not directly induce endothelial leakage but may indirectly promote neutrophil extravasation and thus perioperative endothelial hyperpermeability.

Blood-Air Barrier↗
PubMed2002

Gas phase infrared spectroscopy of selectively prepared ions.

The first example of direct structural characterization of polyaromatic ions by coupling a Fourier transform ion cyclotron resonance mass spectrometer with an infrared free-electron laser is presented. Measurement of the IR spectra of selectively prepared ionic reactive intermediates is allowed by the association of the high peak power and wide tunability of the laser with the flexibility of the spectrometer, where several mass selection and ion reaction steps can be combined, as demonstrated in the case of iron cation complexes of hydrocarbons. The present experimental setup opens the way to understanding chemical reaction paths.

Journal Article↗
PubMed2002

Study of two grafting methods for obtaining a 3-aminopropyltriethoxysilane monolayer on silica surface.

In order to establish a 3-aminopropyltriethoxysilane (APTES) grafting procedure with limited number of APTESs noncovalently linked to the silica surface, two different methods of grafting (in acid-aqueous solution and in anhydrous solution) were compared. The grafted surface state was investigated by atomic force microscopy (AFM). The stability of the grafting was checked at different temperatures by AFM. Continuous and plane APTES grafted surfaces were successfully prepared using both grafting preparations. The grafting in an anhydrous solution behaves homogeneously and stably compared to the grafting in an acid-aqueous solution. Moreover, with anhydrous solution, results showed that a unique monolayer of APTES was grafted.

Membranes, Artificial↗
PubMed2002

Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty-five adult patients.

OBJECTIVE: Polymyositis is a rare inflammatory muscular disease of unknown cause. Corticosteroids and immunosuppressive drugs are the first choice of therapy but are not always effective and may cause serious side effects. Many studies have shown that polyvalent intravenous immunoglobulin (IVIG) may be of interest for the treatment of dermatomyositis. We carried out an open, prospective study to evaluate the efficacy of IVIG in subjects with polymyositis that was refractory to traditional treatments, and we evaluated the benefits of this therapy over a long-term period of followup. METHODS: Thirty-five adult white patients (20 female, 15 male, mean age 43.5 years [SD 16.8]) with chronic, refractory polymyositis were treated with high doses of IVIG, after the patients had received the following traditional treatments: prednisone (n = 35), methotrexate (n = 24), azathioprine (n = 13), cyclophosphamide (n = 4), cyclosporine (n = 7), chlorambucil (n = 1), plasmapheresis (n = 8), lymphopheresis (n = 1), and total body irradiation (n = 1). There had been no changes in the patients' treatment in the 2 months before the initiation of IVIG therapy, and doses were not increased during IVIG treatment. We used preparations of polyvalent human IVIG with increased concentrations of intact IgG. The patients received 1 gm/kg/day for 2 consecutive days per month. The mean course of treatment was 4-6 months. The clinical assessment involved the evaluation of proximal muscle power, muscle disability scale score, and esophageal disorders. The biochemical evaluations carried out before each treatment period were compared by Student's t-test and nonparametric Wilcoxon test. Results were considered to be significant at P = 0.05. RESULTS: In the short-term, significant clinical improvement was noted in 25 of the 35 patients (71.4%). Mean muscle power was estimated before and after IVIG therapy and was found to be significantly improved (P < 0.01). All patients had a significant biochemical response. Mean creatine kinase levels during IVIG therapy decreased significantly before the fourth IVIG perfusion (P < 0.01). Side effects, usually minor, were noted in 6 patients. This benefit allowed the initial prednisone dose to be reduced by >50% in all patients. The mean (+/- SD) followup time for the 25 patients who responded favorably to IVIG treatment was 51.4 +/- 13.1 months. Twelve of these 25 patients remained in full remission following their initial course of IVIG, resulting in complete stoppage of medication in 5 patients or low doses of steroids in 7 patients. The condition of 6 patients remained improved and no other drugs were prescribed, but the patients remained dependent on IVIG infusions. Seven of the 25 patients who responded well to IVIG treatment relapsed at an average of 17.1 months (range 4-23 months) after the discontinuation of IVIG. CONCLUSION: IVIG is an interesting therapy for the treatment of polymyositis, with results showing that the condition of approximately 70% of the patients tested improved. After the discontinuation of the IVIG therapy, the efficacy remained stable in 50% of the patients, with a followup of over 3 years.

Adult↗
PubMed2002

In vitro antimicrobial activity of 3,4-dihydro-s-triazinobenzimidazole derivatives.

Among 31 3,4-dihydro-s-triazinobenzimidazole derivatives tested 12 compounds showed in vitro antimicrobial activity against G+ bacteria. Best results were obtained with substances containing naphthyl or halogenated phenyl group on the triazine ring. The tested derivatives had no significant in vitro antimicrobial activity against either the used G- species or fungi.

Anti-Bacterial Agents↗
PubMed2002

Leukocyte filtration fails to limit functional neutrophil activity during cardiac surgery.

OBJECTIVE AND DESIGN: The beneficial effects of leukocyte filtration on the outcome of cardiac surgery with cardiopulmonary bypass (CPB) is probably due to the limitation of pathogenesis mediated by over-stimulated neutrophils. However, the influence of leukocyte filtration on the functional neutrophil activity has not been studied in detail. Therefore, by using different filtration timing strategies we determined neutrophil effector functions before and after the filter passage as well as blood surrogate markers for neutrophil activation. METHODS: We randomly assigned 80 cardiac surgery patients to four groups (n = 20 each) without (1) and with three different filtration timing strategies (II-IV). As functional end points neutrophil phagocytic activity and oxidative burst upon ex vivo stimulation with E.coli were analyzed from blood of 31 patients whereas polymorphonuclear elastase (PMNE), myeloperoxidase, and malondialdehyde (MDA), a marker for lipid peroxidation was determined in plasma samples from 80 patients. Blood was harvested immediately before and behind the filter (Pall LG6) at different times during CPB. RESULTS: We found that none of the filtration strategies either reduced the number of neutrophils capable of eliciting phagocytic activity and oxidative burst or the activity per cell. In contrast, PMNE and MPO levels in peripheral venous blood were found to be significantly increased in groups II-IV compared with group I throughout the entire filtration period in all patients. MDA was not enhanced in the filter groups. CONCLUSIONS: Our results show that the leukocyte depletion filter in the arterial line of the heart-lung machine failed to limit neutrophil stimulation but rather augmented PMNE plasma levels. We speculate that augmented PMNE and MPO levels mainly stem from neutrophils that are captured within the mesh of the leukocyte filter.

Aged↗
PubMed2002

Interference-free sample preparation for the determination of plasma oxalate analyzed by HPLC-ER: preliminary results from calcium oxalate stone-formers and non-stone-formers.

BACKGROUND: Oxalate generation at pH-values above 5.0 and an oxalate-protein binding in acidified plasma would appear to complicate the determination of oxalate in plasma. METHODS: To avoid complex sample preparation we used a high-performance liquid chromatographic system with an inline enzyme reactor (HPLC-ER) containing immobilised oxalate oxidase. The detection limit was 0.68 micromol/l. Blood was drawn in lithium-heparin vessels and immediately centrifuged at 4 degrees C. The yielded plasma was ultrafiltered using a Centrisart-I-tube. To inhibit oxalate generation by ascorbic acid, the ultrafiltrate was acidified with 1 mol/l hydrochloric acid during ultrafiltration at 4 degrees C. The liquid thus yielded was used for HPLC-ER analysis. Blood samples were obtained from 133 healthy adults (63 men, 70 women, aged 20-94 years) with no history of renal disorder and from 79 patients (53 men, 26 women, aged 19-77 years) with a history of calcium oxalate stone formation. RESULTS: Mean plasma oxalate was 2.65 +/- 2.31 micromol/l for healthy subjects and 4.21 +/- 0.56 micromol/l for stone formers. CONCLUSIONS: Analysis yielded no significant differences between males and females. A correlation between age and plasma oxalate was found for the healthy adults (p < 0.001).

Adult↗
PubMed2002

Modeling MHC class II molecules and their bound peptides as expressed at the cell surface.

A detailed insight to the structure of a given major histocompatibility complex (MHC)-peptide complex can strongly support and also improve the analysis of the peptide binding capabilities of the MHC molecule and the characterization of the developing T cell response. The number of MHC class II-peptide crystal structures is limited, therefore constructing and analyzing computer models can serve as efficient complementary tools when someone deals with experimentally determined binding and/or functional data. Commercial programs are available for modeling protein and protein-protein complexes, in general. However, more accurate results can be obtained if the parameters are directly optimized to a given complex, especially in the case of special proteins as MHC class II, an integral membrane protein, whose functional parts behave like regular globular proteins. Here, we present the optimization of an approach used for modeling MHC class II molecules complexed with various peptides fitting into the binding groove and several ways to analyze them with the help of experimental data.

Amino Acid Sequence↗
PubMed2002

Pseudothrombocytopenia: a report of a new method to count platelets in a patient with EDTA- and temperature-independent antibodies of the IgM type.

Pseudothrombocytopenia is usually associated with blood specimens anticoagulated with ethylenediamine tetraacetic acid (EDTA) or other anticoagulants. It may be caused by temperature-independent, EDTA-dependent antibodies of the immunoglobulin-M (IgM) type. Here a patient with EDTA-independent and temperature-independent pseudothrombocytopenia mediated by IgM or IgM-containing immune complex is reported, and a reliable method is described for a proper counting of platelets in such cases.

Antibody Specificity↗