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Biomedical subjects

E Roux

Publications and source records attributed to E Roux.

At least 19 recordsLinked to original sources

[Prognostic value of BNP for hospital mortality in elderly subjects hospitalised for acute diastolic cardiac failure].

The aim of this study was to evaluate the prognostic value of BNP in elderly patients hospitalised for acute diastolic cardiac failure. 108 consecutive subjects were included, aged at least 70 years old, hospitalised for isolated acute diastolic cardiac failure. All of them had a left ventricular ejection fraction > or = 50% and evidence of diastolic dysfunction on echocardiography performed shortly after admission. The plasma BNP concentration measured in the emergency department on admission was >100 pg/ml in all of the patients except five. It was positively correlated with age (R = 0.29, p = 0.002), with the plasma creatinine level (R = 0.37, p < 0.0001) and the plasma urea level (R = 0.41, p < 0.0001). On univariate analysis, compared to the patients who survived, the 20 patients who died before discharge were significantly older (88.6 versus 84.4 years, p = 0.01), and were more often residents of a care home (60 versus 31%. p = 0.02), had a lower systolic blood pressure on admission (127 +/- 33 versus 154 +/- 30 mm Hg), a higher plasma urea level (16.8 +/- 12 versus 8.9 +/- 5 mmol/l, p = 0.002) and a higher BNP (median = 1290 pg/ml, interquartile range: 721, 3026 pg/ml versus 430 pg/ml, interquartile range: 243, 886 pg/ml). On multivariate analysis, the only factors that remained significantly associated with mortality were the BNP levels (p = 0.005) and the systolic blood pressure (p = 0.01). The negative predictive value of a BNP level < 631 pg/ml (median) for death was 94% (95% confidence interval: 91 to 97%). We conclude that BNP does have an independent prognostic value for in-hospital death in elderly subjects with acute diastolic cardiac failure.

Aged, 80 and over↗

[A new area for radiotherapy with favourable features].

Radiotherapy is a complex medical speciality involving technology research, biology research and clinical research. All these basic researches are performed in order to optimise the management of cancer treatment patients. The aim of the present review is to present radiotherapy as a moving speciality whatever the concerned section. It will be particularly described the new approaches in terms of technology but also clinical developments.

Humans↗

INK4a-ARF mutations in skin carcinomas from UV irradiated hairless mice.

To characterize further the role of the INK4a-ARF locus in the multistep process of skin carcinogenesis, we performed a mutational analysis of this locus in skin lesions from hairless mice either irradiated with UVB alone or with a solar simulator delivering UVA + B. INK4a-ARF mutations were present in five of 57 squamous cell carcinomas (9%), but no mutation was detected in precancerous lesions. All mutations were C:G > T:A transitions located at dipyrimidic sites, the hallmark of UVB mutagenesis. Three mutations affected only the p19(ARF) reading frame, whereas two mutations affected only the p16(INK4a) transcript. This study demonstrates for the first time UV-induced mutations of INK4a-ARF that occur in a small percentage in late stages skin tumors.

Animals↗

[Novel Doppler indexes of estimation of pulmonary capillary pressure: influence of age, feasibility in the acute setting and reproducibility].

BACKGROUND: The Doppler indexes E/Vp, E/Ea, 1000/(2 x IRT + Vp), 1000/(2 x IRT + Ea) and DTd (E: peak E mitral velocity; Vp: flow propagation velocity by color M-mode; Ea: peak early diastolic velocity at lateral mitral annulus by tissue Doppler; IRT: isovolumic relaxation time; DTd: deceleration time of the pulmonary venous diastolic wave) have been proposed for the non-invasive prediction of left ventricular filling pressures. However, the influence of age, the feasibility in acute setting and the reproducibility of these Doppler indexes have never been simultaneously investigated. OBJECTIVE: The present study was conducted to evaluate the influence of age in 56 healthy subjects (57 +/- 20 years of age), the feasibility in 40 critically ill patients (72 +/- 13 years of age; 21 with decompensated heart failure) and the reproducibility in 15 patients. RESULTS: Only the indexes E/Vp (R = 0.37, P = 0.005) and E/Ea (R = 0.72, P < 0.001) were correlated with age. The feasibility was 92, 90, 72, 72 and 45% for E/Ea, 1000/(2 x IRT + Ea), E/Vp, 1000/(2 x IRT +Vp) and DTd, respectively. The best reproducibility was observed for the Doppler parameters E and Ea. CONCLUSION: Despite it is influenced by age, E/Ea appears to be the most useful index for predicting left ventricular filling pressures routinely.

Adolescent↗

[Precipitating factors associated with diastolic heart failure in the elderly].

BACKGROUND: Beside basal myocardial dysfunction, acute heart failure involves associated factors, which increase pulmonary capillary pressure or decrease colloid osmotic pressure. The aim of this study was to evaluate the prevalence of these precipitating factors in a population presenting with acute heart failure with preserved left ventricular systolic function. METHODS: Forty-eight patients (25 men, 78 +/- 10 years) presenting pulmonary edema with a left ventricular ejection fraction > 45% were included. All had a Doppler echocardiography at the time of intravenous loop diuretics initiation. Patients with severe valve disease or symptomatic coronary disease were excluded. RESULTS: A history of heart failure, coronary disease, hypertension and diabetes was present in 62%, 42%, 64% and 33% of patients, respectively. On admission, mean left ventricular ejection fraction was 61 +/- 9% and 79% of patients had critical elevation in Doppler filling pressures. Associated factors were renal failure (creatinine clearance < 30 ml/min) in 33% patients, silent myocardial ischemia (troponin I > 0.5 ng/ml) in 31%, atrial fibrillation in 29%, high systolic blood pressure (> or = 160 mmHg) in 27%, major sepsis in 25%, severe hypoalbuminemia (< or = 2.5 g/dl) in 23%, and severe anemia (< 10 g/dl) in 17%, respectively. Four patients had no aggravating factor, whereas 34 and 10 patients had 1-2 and 3-4 associated factors, respectively. CONCLUSION: Besides diastolic dysfunction, factors leading to a critical decrease in the oncotic pressure such as pulmonary capillary pressure gradient are found in most of the elderly patients presenting acute diastolic heart failure and must be checked systematically.

Aged↗

[Value of Doppler indices of diastolic left ventricular dysfunction in acute cardiac insufficiency].

OBJECTIVE: To examine the prevalence of diastolic dysfunction by Doppler study in acute cardiac failure. CONTEXT: A recent study showed that diastolic dysfunction is constant in stable cardiac failure with preserved systolic function and suggested that its measurement was not necessary for the diagnosis of diastolic cardiac failure, but the prevalence of diastolic dysfunction in acute cardiac failure is not known. METHOD: The mitral and pulmonary venous profiles, the propagation velocity Vp of colour filling flow, and the lateral velocity Ea of the mitral ring in DTI were studied at the time of treatment initiation in 28 patients in sinus rhythm and in acute cardiac failure (11 NYHA IV and 17 with pulmonary oedema), of whom 18 had an ejection fraction greater than 50%. RESULTS: Diastolic dysfunction was present in the combined study of mitral and pulmonary profiles in 95% and 100% respectively of patients in cardiac failure with preserved systolic function and altered systolic function, and Vp < 45 and/or Ea < 8 cm/s was observed in 55% and 100% respectively of these patients. At respective pathological threshold values of 1.5 and 10, the combined indices E/Vp and E/Ea were concordant with the evaluation of filling pressures in 83% of patients with preserved systolic function and 100% of the systolic cardiac failure cases. CONCLUSION: Diastolic dysfunction is almost constant in acute cardiac failure independently of the ejection fraction value. However, normal values of Ea and Vp do not exclude the diagnosis of diastolic cardiac insufficiency in the acute situation.

Acute Disease↗

[Silent ischemia and acute cardiac insufficiency with normal systolic function: diagnostic value of troponin I measurement].

The physiopathological mechanisms resulting in increased left ventricular pressures in acute cardiac failure with normal systolic function are not well understood. Although coronary artery disease is commonly associated with acute episodes, the diagnostic value of troponin I measurement and the prevalence of ischaemia as the predisposing factor are not known. Twenty coronary patients (mean age 77 +/- 9 years) in acute cardiac failure with left ventricular ejection fractions of 50% or over and without angina, were studied retrospectively. The diagnostic value of troponin I (cTnI, AxSYM, method) was assessed by comparing with a control group of 16 acute cardiac failure patients without coronary disease. The frequency of hypertension and diabetes in the coronary group was 50 and 45% respectively. At the time of investigation, the pulmonary capillary and systemic arterial pressures were comparable in the coronary patients irrespective of the cTnl value. At threshold levels of 0.5 microgram/l, cTnl had a specificity of 100% and confirmed ischaemia in 60% of the coronary patients. Ischaemia was the commonest predisposing factor for increased cardiac pressures. Over a 268 +/- 101 days follow-up period, half the coronary patients were readmitted for acute cardiac failure and a third of them died. The authors conclude that silent ischaemia is a common predisposing factor for acute cardiac failure in coronary patients with normal systolic function and troponin I measurement is a useful diagnostic help.

Acute Disease↗

Evaluation of the global optimisation method within the upper limb kinematics analysis.

The aim of this study is to assess the performances of the global optimisation (GO) method (Bone position estimation from skin marker co-ordinates using GO with joint constraints. Journal of Biomechanics 32, 129-134) within the upper limb kinematics analysis. First the model of the upper limb is presented. Then we apply GO method in order to reduce skin movement artefacts that imply relative movement between markers and bones. The performances of the method are then evaluated with the help of simulated movements of the upper limb. Results show a significant reduction of the errors and of the variability due to skin movement.

Artifacts↗

In vitro effect of air pollutants on human bronchi.

A useful approach for constructing dose-response relationships and for studying the underlying mechanisms by which a xenobiotic agent enhances airway reactivity is to measure the response of an isolated airway following ex vivo exposure to a pollutant. We have in this way determined the dose-response relationship between ex vivo exposure to pollutants such as nitrogen dioxide (NO2), the aldehyde acrolein, and ozone (O3) and the reactivity to agonists in human isolated bronchial smooth muscle. We have also investigated the underlying alteration in the cellular mechanisms of airway smooth-muscle contraction induced by such exposure and found that it is related to alteration in calcium signaling at the site of the airway smooth-muscle cell. Finally, although there is epidemiological evidence that an increase in allergic diseases such as asthma may be linked to air pollution, there are few experimental data to address this issue. The final aim of this study was therefore to investigate the interaction between passive sensitization and exposure to pollutants in human isolated airways. We have examined (i) the effect of a pre-exposure to pollutants on the contraction of sensitized bronchi in response to a specific antigen and (ii) the effect of passive sensitization on the contraction in response to nonspecific agonists in bronchi pre-exposed to pollutants. The results indicate a combined effect of immunological sensitization and exposure to pollutants; that is, passive sensitization and exposure to pollutants act in a synergistic manner on human bronchial smooth-muscle reactivity in response to both specific antigens and nonspecific agonists.

Acrolein↗

[Origin and evolution of the respiratory tract in vertebrates].

The description of the evolution of Vertebrate lung is based on comparative anatomy and physiology, combined with phylogenetics. An air-breathing organ (ABO), in addition to gill respiration, appeared in fishes about 400 M years ago. It consisted of a single primitive lung ventilated by a buccal pump. This breathing system was adopted by the first terrestrial tetrapods, and is largely preserved in current amphibians. In the Amniotes, the buccal pulsing pump has been replaced with a costal aspiration pump. In mammals, this ABO evolved into a bronchoalveolar lung. In "Reptiles", the ABO is a partitioned lung with one or several cavities. It serves as a gas exchanger but also as an O(2) reserve, which allows for long periods of apnoea. In birds, the ABO is a tubular structure ventilated by unidirectional airflow. Such a breathing system allows for high rates of O(2) consumption. The diversity of structure and function of the Vertebrate lung should not be analysed as a progression of increasing complexity towards mammal lungs, but rather as diverse responses to varying environmental conditions and phylogenic constraints, and to the challenge of acquiring oxygen necessary for aerobic metabolism.

Animals↗

Early chimerism of macrophages and lymphocytes in lung transplant recipients is predictive of graft tolerance.

BACKGROUND: The persistence of donor cells derived from the graft (chimerism) has been documented in various tissues after organ transplantation. It was suggested that stable chimerism might reflect a state of donor-specific tolerance. Chimerism of macrophages and lymphocytes were studied over time after lung transplantation as well as its impact on graft tolerance. MATERIAL AND METHODS: Macrophages and lymphocytes were purified from bronchoalveolar lavage sequentially obtained from 24 patients between 1 and 41 months posttransplantation (20, 22, 24, and 17 patients at, respectively, 1, 3, 6, and 12 months). DNA was extracted from these cells and their recipient-donor origin was evaluated by PCR amplification of highly polymorphic DNA regions (minisatellites). RESULTS: We show that the remaining donor cells over the first month vary from 10 up to 50% and 5 up to 55% for lymphocytes and macrophages respectively (+/-2 SD). All patients presented some chimerism up to the 6th postoperative month. Good correlation was observed between the residual amount of donor lymphocytes and macrophages during the first 3 months (P<0.001). Patients with at least 30% donor lymphocytes at 1 month after transplantation had less rejections (> or =stage II) in the follow up (P=0.0007). The same observation is true for donor macrophages although to lower extend (P=0.02). The chimerism lost its predictive value beyond 3 months. CONCLUSIONS: These data demonstrate that a level of chimerism above 30% of either donor lymphocytes or macrophages at 1 month is related to a better state of graft tolerance. However, chimerism decreases markedly beyond 3 months and has then no predictive value.

Adolescent↗

N-isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles.

Hydrophobically-modified copolymers of N-isopropylacrylamide bearing a pH-sensitive moiety were investigated for the preparation of pH-responsive liposomes and polymeric micelles. The copolymers having the hydrophobic anchor randomly distributed within the polymeric chain were found to more efficiently destabilize egg phosphatidylcholine (EPC)/cholesterol liposomes than the alkyl terminated polymers. Release of both a highly-water soluble fluorescent contents marker, pyranine, and an amphipathic cytotoxic anti-cancer drug, doxorubicin, from copolymer-modified liposomes was shown to be dependent on pH, the concentration of copolymer, the presence of other polymers such as polyethylene glycol, and the method of preparation. Both polymers were able to partially stabilize EPC liposomes in human serum. These polymers were found to self-assemble to form micelles. The critical association concentration was low (9--34 mg/l) and influenced by the position of the alkyl chains. In phosphate buffered saline, the micelles had a bimodal size distribution with the predominant population having a mean diameter of 35 nm. The polymeric micelles were studied as a delivery system for the photosensitizer aluminum chloride phthalocyanine, (AlClPc), currently evaluated in photodynamic therapy. pH-Responsive polymeric micelles loaded with AlClPc were found to exhibit increased cytotoxicity against EMT-6 mouse mammary cells in vitro than the control Cremophor EL formulation.

Acrylamides↗

Cerebrospinal fluid contains biologically active bone morphogenetic protein-7.

Bone morphogenetic proteins (BMPs) regulate the development and function of many types of neurons. However, little is known of the actual concentrations of BMPs in the various parts of the brain. In this study, we considered the possibility that BMPs might be present in cerebrospinal fluid (CSF). Western blot analysis of normal adult bovine CSF revealed the presence of dimeric and monomeric forms of BMP-7, and the concentration of this molecule was found to be approximately 12 ng/ml in a radioimmunoassay. Since BMP-7 is known to induce dendritic growth in rat sympathetic neurons, this was used as a bioassay to examine the biological activity of the BMP-7 present in CSF. Addition of normal bovine CSF to cultures of sympathetic neurons produced a dose-dependent increase in dendritic growth and the magnitude of this response approximated that obtained with maximally effective concentrations of exogenous BMP-7. Moreover, CSF-induced dendritic growth was inhibited by follistatin, a protein that can sequester BMPs, and by either of two monoclonal antibodies that react with BMP-7. These results show that, unlike most other neurotrophic factors, BMP-7 is a constituent of normal CSF and is present at concentrations sufficient to elicit a near maximal biological response.

Activins↗

Modelling of Ca2+-activated chloride current in tracheal smooth muscle cells.

Stimulation of airway myocytes by contractile agents such as acetylcholine (ACh) activates a Ca2+-activated Cl- current (I(ClCa)) which may play a key role in calcium homeostasis of airway myocytes and hence in airway reactivity. The aim of the present study was to model I(ClCa) in airway smooth muscle cells using a computerised model previously designed for simulation of cardiac myocyte functioning. Modelling was based on a simple resistor-battery permeation model combined with multiple binding site activation by calcium. In order to validate the model, a combination of equations, used to mimic [Ca2+]i response to ACh stimulation, were incorporated into the model. The results indicate that the model developed in this article accounts for experimental recordings and electrophysiological characteristics of this current in airway smooth muscle cells, with parameter values consistent with those calculated from experimental data. Such a model may thus be used to predict I(ClCa) functioning, though additional experimental data from airway myocytes would be useful to more accurately determine some parameter values of the model.

Acetylcholine↗

Effect of chronic hypoxia on agonist-induced tone and calcium signaling in rat pulmonary artery.

The effect of chronic hypoxia (CH) for 14 days on Ca2+ signaling and contraction induced by agonists in the rat main pulmonary artery (MPA) was investigated. In MPA myocytes obtained from control (normoxic) rats, endothelin (ET)-1, angiotensin II (ANG II), and ATP induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) in 85-90% of cells, whereas they disappeared in myocytes from chronically hypoxic rats together with a decrease in the percentage of responding cells. However, both the amount of mobilized Ca2+ and the sources of Ca2+ implicated in the agonist-induced response were not changed. Analysis of the transient caffeine-induced [Ca2+]i response revealed that recovery of the resting [Ca2+]i value was delayed in myocytes from chronically hypoxic rats. The maximal contraction induced by ET-1 or ANG II in MPA rings from chronically hypoxic rats was decreased by 30% compared with control values. Moreover, the D-600- and thapsigargin-resistant component of contraction was decreased by 40% in chronically hypoxic rats. These data indicate that CH alters pulmonary arterial reactivity as a consequence of an effect on both Ca2+ signaling and Ca2+ sensitivity of the contractile apparatus. A Ca2+ reuptake mechanism appears as a CH-sensitive phenomenon that may account for the main effect of CH on Ca2+ signaling.

Adenosine Triphosphate↗

Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats.

Bronchopulmonary dysplasia is the most common cause of chronic pulmonary disease in premature infants. Airway inflammation appears to play a major pathogenetic role together with barotrauma and oxygen toxicity. The aim of the present study was to determine the effect of a 15-d exposure to moderate hyperoxia (FiO2, 50%) on airway reactivity and inflammatory response in neonatal and adult rats. We studied in isolated tracheal rings the 1) isometric contraction to cumulative concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal, smooth muscle, and connective tissue surface area; and 3) distribution of inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb. Reactivity to carbachol was significantly increased in the hyperoxic pups, in which a 13% increase in tracheal smooth muscle surface area was observed. Type-I mast cells and macrophages (submucosa and connective tissue) and granulocytes (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did not influence functional, morphometric, or cellular data in adult rats. In conclusion, exposure of newborn rats to moderate hyperoxia induces airway hyperresponsiveness and histologic changes similar to those reported in bronchopulmonary dysplasia. Hyperresponsiveness may be ascribed to an increase in smooth muscle related to the release of yet undetermined mediators by inflammatory cells infiltrating the airways. Lung immaturity definitely plays a role because similar alterations are not observed in adult rats.

Animals↗

Recovery of immune reactivity after T-cell-depleted bone marrow transplantation depends on thymic activity.

To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell-depleted bone marrow, we measured the appearance of CD4(+)CD45RA(+)RO(-) naive T cells (thymic rebound), restoration of the diversity of the T-cell-receptor (TCR) repertoire and the response to vaccinations with tetanus toxoid (TT). Repopulation by CD4(+)CD45RA(+)RO(-) thymic emigrants varied among patients, starting at approximately 6 months after transplantation. Young patients reconstituted swiftly, whereas in older patients, the recovery of normal numbers of naive CD4(+) T cells could take several years. Restoration of TCR diversity was correlated with the number of naive CD4(+)CD45RA(+)RO(-) T cells. Moreover, the extent of the thymic rebound correlated with the patient's capacity to respond to vaccinations. Patients without a significant thymic rebound at the moment of vaccination (CD4(+)CD45RA(+)RO(-) T cells less than 30 microL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after transplantation, the absence of an immune response is due mainly to the loss of an adequate T-cell repertoire. Restoration of the repertoire can come only from a thymic rebound that can be monitored by measuring the increase of CD4(+)CD45RA(+)RO(-) naive T cells. This will allow postponing revaccinations to a moment when the patient will be able to respond more effectively. This may be particularly useful in the elderly patient who, owing to low thymic activity, might not yet be able to respond 1 year after transplant when revaccinations are usually scheduled.

Adolescent↗

In vivo generation of human dendritic cell subsets by Flt3 ligand.

Dendritic cells (DCs) represent a family of ontogenically distinct leukocytes involved in immune response regulation. The ability of DCs to stimulate T-cell immunity has led to their use as vectors for immunotherapy vaccines. However, it is unclear whether and to what degree in vitro-generated DCs are representative of DCs that develop in vivo. Treatment of mice with human Flt3 ligand (FL) dramatically increases the number of DCs. We report here that administration of FL to healthy human volunteers increased the number of circulating CD11c(+ )IL-3Ralpha(low) DC (mean 44-fold) and CD11c(-) IL-3Ralpha(high) DC precursors (mean 12-fold). Moreover, the CD11c(+ )DCs were efficient stimulators of T cells in vitro. Thus, FL can expand the number of circulating, functionally competent human DCs in vivo.

Adjuvants, Immunologic↗