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Biomedical subjects

I Martin

Publications and source records attributed to I Martin.

At least 37 records · Page 2Linked to original sources
PubMed2004

Quantum-limited sensitivity of single-electron-transistor-based displacement detectors.

We consider a model of a quantum-mechanical resonator capacitively coupled to a single electron transistor (SET). The tunnel current in the SET is modulated by the vibrations of the resonator, and thus the system operates as a displacement detector. We analyze the effect of the backaction noise of charge fluctuations in the SET onto the dynamics of the resonator and evaluate the displacement sensitivity of the system. The relation between the "classical" and "quantum" parts of the SET charge noise and their effect on the measured system are also discussed.

Journal Article↗
PubMed2004

Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy.

BACKGROUND: Approximately 25 per cent of patients with oesophageal cancer who undergo neoadjuvant chemoradiotherapy have no evidence of tumour in the resected specimen (complete pathological response). Those who do not respond have a poor 5-year survival compared with complete responders, regardless of whether or not they undergo surgery. Selecting for surgery only those who have a response to neoadjuvant therapy has the potential to improve overall survival as well as to rationalize the management of non-responders. This study assessed the accuracy of oesophagogastroscopy in this setting. METHODS: A prospective database of 804 patients undergoing oesophageal resection for carcinoma was reviewed. Endoscopic assessment of the response to neoadjuvant therapy in 100 consecutive patients was compared with the pathological assessment of response. The survival for each level of response was compared. RESULTS: At endoscopy 30 patients were considered to have had a complete response. This was confirmed pathologically in 15 patients. Survival was improved in those with a pathologically confirmed complete response (3-year survival rate 62.4 (s.e. 12.9) per cent) compared with non-responders (16.3 (s.e. 6.6) per cent). Those with microscopic residual disease also had an improved 3-year survival rate (46.3 (s.e. 12.2) per cent); however, oesophagogastroscopy failed to identify this subset. CONCLUSION: Oesophagogastroscopy may be useful in the assessment of tumour response to neoadjuvant therapy. However, owing to its poor accuracy patients should not be excluded from further therapeutic intervention on the basis of this assessment alone.

Adenocarcinoma↗
PubMed2004

[Engineering and characterization of functional osteochondral replacement tissue].

Extensive osteochondral lesions require repair of the cartilage and underlying bone. We generated osteochondral repair tissue by tissue engineering. Standardized defects, 7 x 5 x 5 mm, were created in femoropatellar grooves of adult rabbits. Engineered cartilage, generated in vitro starting from chondrocytes and a biodegradable scaffold, was implanted using Collagraft as subchondral support. Cell-free implants, defects left empty, and unoperated knee joints served as controls. Explants were characterized morphologically and mechanically. Engineered cartilage implants were superior to cell-free implants and to natural healing of empty defects with respect to the histologic score and Young's modulus of the 6-month repair tissue. These data suggest that engineered cartilage can provide primary stability for the treatment of critical osteochondral defects.

Bone Remodeling↗
PubMed2004

[Prospective follow-up of hospital-acquired diarrhoea in 28 paediatric wards of the south-east part of France during a winter season].

The aim of this study was to evaluate the risk of hospital-acquired diarrhoea during an epidemic period through a prospective multicentre observational study. A systemic investigation of the hospital-acquired diarrhoea (occurring at least 48 h after hospital admission) was conducted through a standardised questionnaire from January to March 1999 in patients of 5 years old or less hospitalised in 28 wards (620 beds) belonging to 20 hospitals located in the south-east part of France. Overall, 241 cases of hospital-acquired diarrhoea were collected, corresponding to a prevalence of 3.3% (3.6% after exclusion of patients admitted for diarrhoea) and a density of incidence of 0.81 per 100 days of hospitalisation. The mean stay duration of hospital-infected patients was greater than 10 days, versus 3.9 days for the other children (P < 0.001). A readmission was required in 27% of the infected children. Rotavirus was involved in 97.8% of microbiologically documented cases (88%). In 50% of the cases, the hospital-acquired diarrhoea was seen in patients with bronchiolitis. Contact isolation measures were prescribed in 88.4% of the cases. These results stress that hospital-acquired diarrhoea represent an important medical and economic load for paediatric units and could be used as reference data to evaluate the impact of preventive measures, especially to reduce readmission and mean stay duration.

Child, Preschool↗
PubMed2004

Maternal serum screening for trisomy 21 in women with a false positive result in last pregnancy.

Maternal serum screening for Down syndrome is a common practice in the United Kingdom. A number of factors have been shown to influence the chance of a false positive test result. Analysis of routinely collated information stored on an electronic database in a district general hospital has shown that women with a previous false positive maternal screen are at much greater chance of having a false positive result in their next pregnancy. Overall, there was a fivefold increased risk attributed to biological variation in their serum concentrations of alpha-feto protein (AFP) and human chorionic gonadotrophin (hCG). The potential effect of this was to increase the chance of such women having an unnecessary amniocentesis. Women should be advised of this effect in subsequent pregnancies. Ideally a correction factor should be applied which would reduce the false positive rate without affecting adversely the sensitivity of the test.

Adult↗
PubMed2004

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia.

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Adult↗
PubMed2003

The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells.

In the present study, we investigated the role of the phytoestrogen genistein and 17beta-estradiol in human bone marrow stromal cells, undergoing induced osteogenic or adipogenic differentiation. Profiling of estrogen receptors (ERs)-alpha, -beta1, -beta2, -beta3, -beta4, -beta5, and aromatase mRNAs revealed lineage-dependent expression patterns. During osteogenic differentiation, the osteoblast-determining core binding factor-alpha1 showed a progressive increase, whereas the adipogenic regulator peroxisome proliferator-activated receptor gamma (PPARgamma) was sequentially decreased. This temporal regulation of lineage-determining marker genes was strongly enhanced by genistein during the early osteogenic phase. Moreover, genistein increased alkaline phosphatase mRNA levels and activity, the osteoprotegerin:receptor activator of nuclear factor-kappaB ligand gene expression ratio, and the expression of TGFbeta1. During adipogenic differentiation, down-regulation in the mRNA levels of PPARgamma and CCAAT/enhancer-binding protein-alpha at d 3 and decreased lipoprotein lipase and adipsin mRNA levels at d 21 were observed after genistein treatment. This led to a lower number of adipocytes and a reduction in the size of their lipid droplets. At d 3 of adipogenesis, TGFbeta1 was strongly up-regulated by genistein in an ER-dependent manner. Blocking the TGFbeta1 pathway abolished the effects of genistein on PPARgamma protein levels and led to a reduction in the proliferation rate of precursor cells. Overall, genistein enhanced the commitment and differentiation of bone marrow stromal cells to the osteoblast lineage but did not influence the late osteogenic maturation markers. Adipogenic differentiation and maturation, on the other hand, were reduced by genistein (and 17beta-estradiol) via an ER-dependent mechanism involving autocrine or paracrine TGFbeta1 signaling.

Adipocytes↗
PubMed2003

Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity.

We developed a bioreactor for automated cell seeding of three-dimensional scaffolds by continuous perfusion of a cell suspension through the scaffold pores in oscillating directions. Using quantitative biochemical and image analysis techniques, we then evaluated the efficiency and uniformity of perfusion seeding of Polyactive foams as compared to conventional static and spinner flask methods. Finally, we assessed the efficacy of the perfusion seeding technique for different scaffolds and cell types. Perfusion seeding of chondrocytes into Polyactive foams resulted in "viable cell seeding efficiencies," defined as the percentages of initially loaded cells that were seeded and remained viable, that were significantly higher (75 +/- 6%) than those by static (57% +/- 5%) and spinner flask seeding (55% +/- 8%). In addition, as compared to static and spinner flask methods, cells seeded by perfusion were respectively 2.6-fold and 3.8-fold more uniformly distributed and formed more homogeneously sized cell clusters. Chondrocytes seeded by perfusion into Hyaff-11 nonwoven meshes were 26% and 63%, respectively, more uniformly distributed than following static and spinner flask seeding. Bone marrow stromal cells seeded by perfusion into ChronOS porous ceramics were homogeneously distributed throughout the scaffold volume, while following the static method, cells were found only near the top surface of the ceramic. In summary, we demonstrated that our cell seeding perfusion bioreactor generated constructs with remarkably uniform cell distributions at high efficiencies, and was effective for a variety of scaffolds and different mesenchymal cell types.

Animals↗
PubMed2003

Dynamic compression of cartilage constructs engineered from expanded human articular chondrocytes.

Recent works have shown that mechanical loading can alter the metabolic activity of chondrocytes cultured in 3D scaffolds. In this study we determined whether the stage of development of engineered cartilaginous constructs (expanded adult human articular chondrocytes/Polyactive foams) regulates the effect of dynamic compression on glycosaminoglycan (GAG) metabolism. Construct maturation depended on the culture time (3-14 days) and the donor (4 individuals). When dynamic compression was subsequently applied for 3 days, changes in GAG synthesized, accumulated, and released were significantly positively correlated to the GAG content of the constructs prior to loading, and resulted in stimulation of GAG formation only in the most developed tissues. Conversely, none of these changes were correlated with the expression of collagen type II mRNA, indicating that the response of chondrocytes to dynamic compression does not depend directly upon the stage of cell differentiation, but rather on the extracellular matrix surrounding the cells.

Cartilage, Articular↗
PubMed2003

Probing the spin state of a single electron trap by random telegraph signal.

We have studied the random telegraph signal (RTS) generated by a single paramagnetic spin center adjacent to a submicrometer silicon metal-oxide-semiconductor field-effect transistor. An in-plane magnetic field induces a substantial change in the statistics of the RTS. We show that a model using the grand partition theorem can qualitatively explain the change in statistics of the RTS as a function of the applied magnetic field. While the data at high temperatures can be well described by this simple model, quantitative discrepancy increases as the temperature is lowered.

Journal Article↗
PubMed2003

Attenuated total reflection IR spectroscopy as a tool to investigate the orientation and tertiary structure changes in fusion proteins.

Membrane fusion proceeds via a merging of two lipid bilayers and a redistribution of aqueous contents and bilayer components. It involves transition states in which the phospholipids are not arranged in bilayers and in which the monolayers are highly curved. Such transition states are energetically unfavourable since biological membranes are submitted to strong repulsive hydration electrostatic and steric barriers. Viral membrane proteins can help to overcome these barriers. Viral proteins involved in membrane fusion are membrane associated and the presence of lipids restricts drastically the potential of methods (RMN, X-ray crystallography) that have been used successfully to determine the tertiary structure of soluble proteins. We describe here how IR spectroscopy allows to solve some of the problems related to the lipid environment. The principles of the method, the experimental setup and the preparation of the samples are briefly described. A few examples illustrate how attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy can be used to gain information on the orientation and the accessibility to the water phase of the fusogenic domain of viral proteins. Recent developments suggest that the method could also be used to detect changes located in the membrane domains and to identify intermediate structural states involved in the fusion process.

Amides↗
PubMed2003

Direct evidence for recycling of myeloperoxidase-catalyzed phenoxyl radicals of a vitamin E homologue, 2,2,5,7,8-pentamethyl-6-hydroxy chromane, by ascorbate/dihydrolipoate in living HL-60 cells.

Myeloperoxidase (MPO)-catalyzed one-electron oxidation of endogenous phenolic constituents (e.g., antioxidants, hydroxylated metabolites) and exogenous compounds (e.g., drugs, environmental chemicals) generates free radical intermediates: phenoxyl radicals. Reduction of these intermediates by endogenous reductants, i.e. recycling, may enhance their antioxidant potential and/or prevent their potential cytotoxic and genotoxic effects. The goal of this work was to determine whether generation and recycling of MPO-catalyzed phenoxyl radicals of a vitamin E homologue, 2,2,5,7,8-pentamethyl-6-hydroxychromane (PMC), by physiologically relevant intracellular reductants such as ascorbate/lipoate could be demonstrated in intact MPO-rich human leukemia HL-60 cells. A model system was developed to show that MPO/H(2)O(2)-catalyzed PMC phenoxyl radicals (PMC*) could be recycled by ascorbate or ascorbate/dihydrolipoic acid (DHLA) to regenerate the parent compound. Absorbance measurements demonstrated that ascorbate prevents net oxidation of PMC by recycling the phenoxyl radical back to the parent compound. The presence of DHLA in the reaction mixture containing ascorbate extended the recycling reaction through regeneration of ascorbate. DHLA alone was unable to prevent PMC oxidation. These conclusions were confirmed by direct detection of PMC* and ascorbate radicals formed during the time course of the reactions by EPR spectroscopy. Based on results in the model system, PMC* and ascorbate radicals were identified by EPR spectroscopy in ascorbate-loaded HL-60 cells after addition of H(2)O(2) and the inhibitor of catalase, 3-aminotriazole (3-AT). The time course of PMC* and ascorbate radicals was found to follow the same reaction sequence as during their recycling in the model system. Recycling of PMC by ascorbate was also confirmed by HPLC assays in HL-60 cells. Pre-loading of HL-60 cells with lipoic acid regenerated ascorbate and thus increased the efficiency of ascorbate in recycling PMC*. Lipoic acid had no effect on PMC oxidation in the absence of ascorbate. Thus PMC phenoxyl radical does not directly oxidize thiols but can be recycled by dihydrolipoate in the presence of ascorbate. The role of phenoxyl radical recycling in maintaining antioxidant defense and protecting against cytotoxic and genotoxic phenolics is discussed.

Antioxidants↗
PubMed2003

Dynamical ordering of driven stripe phases in quenched disorder.

We examine the dynamics and stripe formation in a system with competing short and long-range interactions in the presence of both an applied dc drive and quenched disorder. Without disorder, the system forms stripes organized in a labyrinth state. We find that, when the disorder strength exceeds a critical value, an applied dc drive can induce a dynamical stripe ordering transition to a state that is more ordered than the originating undriven, unpinned pattern. We show that signatures in the structure factor and transport properties correspond to this dynamical reordering transition, and we present the dynamic phase diagram as a function of strengths of disorder and dc drive.

Journal Article↗
PubMed2003

A scheme for electrical detection of single-electron spin resonance.

We study a scheme for electrical detection of the spin resonance of a single-electron trapped near a field effect transistor (FET) conduction channel. In this scheme, the resonant Rabi oscillations of the trapped electron spin cause a modification of the average charge of a shallow trap, which can be detected through the change in the FET channel resistivity. We show that the dependence of the channel resistivity on the frequency of the rf field can have either peak or dip at the Larmor frequency of the electron spin in the trap.

Journal Article↗
PubMed2003

[Epidemic outbreaks control involving Staphylococcus aureus with reduced sensitivity to glycopeptides].

This study describes two epidemic outbreaks involving Staphylococcus aureus with reduced sensitivity to glycopeptides, one in 2000 involving eight patients and the other in 2001-2002 involving 16 patients. These strains were detected rapidly, thanks to routine screening for the offending organisms in the bacteriology laboratory of our hospital. The clonal character of these strains was confirmed by pulsed field electrophoresis. The management of these epidemic outbreaks confirmed (i) the need for systematic adoption of standard precautions, (ii) the importance of circulating information in combating multi-resistant bacteria, as well as the difficulties in transferring colonised patients to different hospital wards, and (iii) the intermittent nature of S. aureus carriage, resulting in a need for prolonged surveillance of colonised and/or infected patients. In addition, our study underlines the value of a multi-disciplinary approach to the management of diffusion of multi-resistant bacteria.

Anti-Bacterial Agents↗
PubMed2003

[Possible implication of student nurses in the transmission of methicillin-resistant Staphylococcus aureus during a nosocomial outbreak].

We report an outbreak of infections due to methicillin-resistant Staphylococcus aureus (MRSA) in a medical unit and the possible implication of student nurses in the dissemination of the epidemic strain. A retrospective epidemiological study looking for hospitalised patients colonised or infected with MRSA from the 1st of June to the 30th of September 2001 in the unit was conducted. An audit of delivered cares and a nasal screening of health care workers (HCW) was performed. Six patients were colonised or infected with a MRSA strain, four of them exhibiting a bacteremia. Six HCW had a nasal carriage of MRSA. Typing of the MRSA strains by pulsed field gel electrophoresis demonstrated an epidemic clone isolated from five of six patients, two student nurses and one HCW not implicated in nursing cares. This report illustrates the risk of nosocomial outbreak linked to cares delivered by student nurses.

Cross Infection↗
PubMed2003

Development and validation of a bioreactor for physical stimulation of engineered cartilage.

A bioreactor has been developed to apply different regimes of physical stimulation to tissue specimens under highly controlled conditions. The computer-controlled device exposes specimens to compressive deformation at various strains and frequencies, measures the load applied to each sample and allows simultaneous medium stirring at different velocities. Validation tests confirmed the accuracy of the system in (i) its displacement (errors averaged 0.072+/-0.051 microm), and in (ii) setting the contact with the samples utilizing micrometer screws coupled to plungers (errors averaged 1.74+/-0.36% for samples of 1.60-3.18 mm thickness), thus ensuring accurate compressive deformation. The developed bioreactor, which represents an advance in the technology for physical stimulation of tissue specimens, is currently used to apply compressive deformation and hydrodynamic forces to human chondrocytes cultured in biodegradable polymer scaffolds, with the goals of (i) engineering functional grafts for the repair of cartilage defects (ii).

Bioreactors↗