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Biomedical subjects

D Roux

Publications and source records attributed to D Roux.

At least 37 records · Page 2Linked to original sources
PubMed2001

The relationship between introduction of American society of clinical oncology guidelines and the use of colony-stimulating factors in clinical practice in a Paris university hospital.

BACKGROUND: Clinical practice guidelines are issued periodically by professional medical societies or committees to assist practitioners in clinical decision making. However, it is unclear whether such guidelines have any lasting impact on clinical practice. OBJECTIVE: The purpose of this study was to assess the impact of the American Society of Clinical Oncology (ASCO) guidelines regarding use of hematopoietic colony-stimulating factors (CSF) on cancer care in a university hospital in Paris. METHODS: The study was performed at Hĵpital Tenon, an 830-bed university hospital in Paris, in 1996 and 1997, both before and after the ASCO guidelines were implemented. The guidelines were first disseminated as a continuing medical education program and then actively implemented using a CSF prescription order form summarizing the guidelines. This form had to be used during the patient consultation and was sent to the Hĵpital Tenon pharmacy for CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the pharmacy filled the prescription. Seven other university hospitals in Paris, where the ASCO guidelines were not actively implemented, comprised the control group. The main outcome measure was the proportion of prescriptions in compliance with the 1996 update of the ASCO guidelines. Secondary outcome measures were the proportions of prescriptions in compliance with ASCO guidelines regarding primary prophylactic, secondary prophylactic, and therapeutic CSF administration. RESULTS: Before implementation of the ASCO guidelines, CSF use in compliance with the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control sites (P > 0.05). Six months after dissemination and implementation of the guidelines, the proportion of CSF prescriptions complying with ASCO guidelines increased significantly versus baseline (P = 0.003) in the study group, to 61% (50/82). However, even after the guidelines were implemented, compliance with guidelines on primary prophylactic CSF administration did not change significantly versus before implementation in the study group (12% [5/41] before implementation vs 6% [2/33] after implementation; P > 0.05). CONCLUSIONS: The results suggest an association between the active implementation strategy (continuing medical education and CSF prescription reminder form) and physician compliance with the ASCO guidelines. Implementation of the ASCO guidelines appears to have had some impact on medical practice.

Colony-Stimulating Factors↗
PubMed2001

Diagnosis of Helicobacter pylori infection: noninvasive methods compared to invasive methods and evaluation of two new tests.

OBJECTIVES: Current guidelines recommending Helicobacter pylori eradication treatment without performing endoscopy in certain patients highlight the importance of noninvasive tests. Our aim was to determine the accuracy of two new tests: the antigen stool test and Helicoblot 2.1 (an immunoblot used on serum) as well as the 13C urea breath test and ELISA serology in comparison to invasive tests for the pretreatment diagnosis of H. pylori infection. METHODS: Helicobacter pylori infection was diagnosed prospectively in 104 untreated patients using eight different tests. Invasive tests included culture, urease test (CLOtest), histology, and PCR; noninvasive tests included the 13C urea breath test, IgG serology (Pyloriset EIA-G), immunoblot (Helicoblot 2.1), and antigen stool detection (Premier Platinum HpSA). A predefined gold standard based on biopsy tests was used to define H. pylori status, as well as an empirical approach. RESULTS: There was no statistically significant difference between the different tests. The sensitivity of the noninvasive tests ranged between 88.9% and 95.6% (stool test: 88.9%, 95% CI: 82.7-95.1, and Helicoblot 2.1: 95.6%, 95% CI: 91.5-99.6) and the specificity ranged between 92.6 and 98.1% (stool test: 94.4%, 95% CI: 84.6-98.8, and Helicoblot 2.1: 92.6%, 95% CI: 91.5-96.2) when a predefined gold standard was used. CONCLUSIONS: Most tests had sensitivities, specificities, and predictive values >90%. The noninvasive tests are accurate for the diagnosis of H. pylori infection. Helicoblot 2.1 performed as well as the best ELISA kit. The HpSA is a promising direct noninvasive test that can be applied easily to evaluate H. pylori status.

Breath Tests↗
PubMed2000

Signaling angiogenesis via p42/p44 MAP kinase and hypoxia.

Angiogenesis is associated with a number of pathological situations. In this study, we have focused our attention on the role of p42/p44 MAP (mitogen-activated protein) kinases and hypoxia in the control of angiogenesis. We demonstrate that p42/p44 MAP kinases play a pivotal role in angiogenesis by exerting a determinant action at three levels: i) persistent activation of p42/p44 MAP kinases abrogates apoptosis; ii) p42/p44 MAP kinase activity is critical for controlling proliferation and growth arrest of confluent endothelial cells; and iii) p42/p44 MAP kinases promote VEGF (vascular endothelial growth factor) expression by activating its transcription via recruitment of the AP-2/Sp1 (activator protein-2) complex on the proximal region (-88/-66) of the VEGF promoter and by direct phosphorylation of hypoxia-inducible factor 1 alpha (HIF-1 alpha). HIF-1 alpha plays a crucial role in the control of HIF-1 activity, which mediates hypoxia-induced VEGF expression. We show that oxygen-regulated HIF-1 alpha protein levels are not affected by intracellular localization (nucleus versus cytoplasm). Finally, we propose a model which suggests an autoregulatory feedback mechanism controlling HIF-1 alpha and therefore HIF-1-dependent gene expression.

Animals↗
PubMed2000

The spherulites(TM): a promising carrier for oligonucleotide delivery.

Concentric multilamellar microvesicles, named spherulites(TM), were evaluated as an oligonucleotide carrier. Up to 80% oligonucleotide was encapsulated in these vesicles. The study was carried out on two different spherulite(TM) formulations. The spherulite(TM) size and stability characteristics are presented. Delivery of encapsulated oligonucleotide was performed on a rat hepatocarcinoma and on a lymphoblastoid T cell line, both expressing the luciferase gene. We showed that spherulites(TM) were able to transfect both adherent and suspension cell lines and deliver the oligonucleotide to the nucleus. Moreover, 48-62% luciferase inhibition was obtained in the rat hepatocarcinoma cell line when the antisense oligonucleotide targeted to the luciferase coding region was encapsulated at 500 nM concentration in spherulites(TM) of different compositions.

Animals↗
PubMed2000

In vitro and in vivo stability of new multilamellar vesicles.

Factors affecting multilamellar vesicles transport to the blood compartment after oral administration to rats were evaluated first in vitro. A high entrapment of protein A was obtained when the vesicles were prepared by shearing a lyotropic lamellar phase composed of soybean phosphatidylcholine, cholesterol and polyoxyethylene alcohol (C12H25(OCH2CH2)4OH) as neutral detergent. In vitro tests showed that these vesicles (spherulites) were stabled in 50% of fetal calf serum, in acidic (pH 3) or basic (pH 10) buffers, in pancreatin but are partially lysed in 20mM bile salts. Oral administration of spherulites entrapping 111In-NTA in fasting rats showed a increase of radioacticivity in blood. This could be explained by passage of some spherulites in the enterocytes.

Administration, Oral↗
PubMed2000

Interaction of cationic colloids at the surface of J774 cells: a kinetic analysis.

We have characterized the binding of multilamellar colloids to J774 cells. Cationic colloids were shown to bind much more efficiently than neutral ones. Particle uptake by cells was followed by flow cytometry and fluorescence microscopy. Analysis of the kinetics of uptake of cationic particles indicated that binding on the cell surface occurred with two characteristic times. Analysis of the dissociation properties allowed discriminating between several alternative models for adsorption and led us to propose a mechanism that involved two independent classes of binding sites on the cell surface. One class of sites appeared to be governed by a classic mass action law describing a binding equilibrium. The other sites were populated irreversibly by particles made of 10% cationic lipids. This was observed in the absence of endocytosis, under conditions where both the equilibrium and the irreversible binding occurred at the cell surface. We determined the rate constants for the different steps. We found that the reversible association occurred with a characteristic time of the order of tens of seconds, whereas the irreversible binding took a hundred times longer. The presence of serum proteins in the incubation medium did not drastically affect the final uptake of the particles. In contrast, the capture of the particles by cells significantly dropped when the fraction of positively charged lipids contained in the colloids was decreased from 10% to 5%. Finally, the results will be discussed within a comprehensive model where cationic particles find labile binding sites in the volume of the pericellular network (glycocalyx and extracellular matrix) and less-accessible irreversible binding sites at the cell membrane itself.

Animals↗
PubMed2000

Accuracy of estimation of dental treatment need in special care patients.

OBJECTIVES: To assess the ability of carers and dental professionals to estimate treatment need in a group of children and adults with special needs. METHOD: A retrospective study of a series of 103 special needs patients who had received restorative dental treatment under general anaesthetic was undertaken. The initial reason for attendance and the time lapse between first symptoms and decision to consult were established. The parent or carer was asked to estimate treatment need and to assess the degree of discomfort suffered by the patient. The dentist evaluated treatment need by means of a pre-operative treatment plan. These results were compared to actual treatment performed. RESULTS: Treatment need was severely underestimated by both carer and dentist. The degree of advanced pathology found in the population would suggest that pain suffered was also underestimated. CONCLUSIONS: Access of patients with special needs to dental care may be limited by the ability of their carers to evaluate their oral condition and/or by the persons inability to express their pain or discomfort.

Adolescent↗
PubMed2000

Structure-activity relationship of polyisoprenyl benzophenones from Garcinia pyrifera on the tubulin/microtubule system.

Microtubule disassembly inhibitory properties have been established for the known polyisoprenylated benzophenones xanthochymol (1a) and guttiferone E (1b). The compounds were isolated from the fruits of Garcinia pyrifera collected in Malaysia. A structure-activity relationship study, including natural and semisynthetic derivatives, delineated some structural features necessary for the interaction with tubulin within this compound class.

Benzophenones↗
PubMed2000

Multicenter study of the impact of prescription guidelines on the use of colony stimulating factors.

The aim of this work was to assess the impact of circulating guidelines for correct prescription practices of colony stimulating factors (CSF). Two hospital groups were compared, a 'guidelines' group (seven teaching hospitals) that circulated the guidelines and a control group (eight teaching hospitals) that did not. In addition, two periods were compared before and after distribution of the guidelines: from 17 February to 2 March 1996 and from 17 February to 2 March 1997. The assessment involved compliance with the guidelines for the following parameters: indications, dose regimen, time to start of CSF therapy and duration of CSF therapy between the control and guideline groups and also between the two periods. The population included 404 patients analyzed (209 in 1996 and 195 in 1997) for the indication of post-chemotherapy neutropenia. Total compliance in the first period (all four items) was 44.2% in the control group and 50.8% in the guideline group (nonsignificant), and during the second period was 31.9 and 59.6% in the two groups (p<0.001). During the first period, the differences in compliance with the guidelines for indication, dose regimen, time to start of treatment and duration between the groups were not significant. In the second period, this difference became significant and in favor of the guideline group for dose regimen (p = 0.009) and treatment duration (p = 0.02). The results of this study show the need to continuously define prescription reference systems according to available data, and to circulate them widely to improve the quality of health care and to control expenses.

Colony-Stimulating Factors↗
PubMed2000

[Maternal transport to the Bordeaux University Hospital: a retrospective study of 263 cases (1996-1998)].

OBJECTIVES: To describe a population of high risk pregnancies transported to a regional perinatal care centre (level III) and to analyze the advantages and limitations of the organization of this perinatal care network. METHODS: Retrospective study of 263 patients transported to the University Hospital of Bordeaux between September 1996 and September 1998. RESULTS: Maternal transport mainly came from the Gironde department (53%) and from level I care hospitals (66%). The rate of multiple pregnancies was 17%. Principal indications were preterm labor with or without rupture of fetal membranes (52%) and preeclampsia with or without intrauterine growth restriction (28%). The rate of returns to the referring care centre was 2%. The mean term at delivery was 32 WA. Forty-one percent of patients delivered within 24 hours of transport. The rate of caesarean sections was 55%. There were 303 live births. The mean duration of hospitalization of the neonates was 28 days. The rate of perinatal mortality was 6.2%. Among the 96 pregnancies beyond 32 WA, 17 (6.5%) could have been transported to some level IIb care hospitals, nearby the patient's residence, without changing maternal and neonatal prognosis. Neonatal mortality was not significantly different for maternel transport (18%) or neonatal transport (14%) in the group of premature infants born prior to 31 WA in our study. CONCLUSION: Our organization is currently trying to improve transport management (non-emergency situations, collaboration of level II care hospitals) and to increase the rate of returns to the referring care centres.

Adolescent↗
PubMed1999

p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1.

Hypoxia-inducible factor-1 (HIF-1) controls the expression of a number of genes such as vascular endothelial growth factor and erythropoietin in low oxygen conditions. However, the molecular mechanisms that underlie the activation of the limiting subunit, HIF-1alpha, are still poorly resolved. Results showing that endogenous HIF-1alpha migrated 12 kDa higher than in vitro translated protein led us to evaluate the possible role of phosphorylation on this phenomenon. We report here that HIF-1alpha is strongly phosphorylated in vivo and that phosphorylation is responsible for the marked differences in the migration pattern of HIF-1alpha. In vitro, HIF-1alpha is phosphorylated by p42 and p44 mitogen-activated protein kinases (MAPKs) and not by p38 MAPK or c-Jun N-terminal kinase. Interestingly, p42/p44 MAPK stoichiometrically phosphorylate HIF-1alpha in vitro, as judged by a complete upper shift of HIF-1alpha. More importantly, we demonstrate that activation of the p42/p44 MAPK pathway in quiescent cells induced the phosphorylation and shift of HIF-1alpha, which was abrogated in presence of the MEK inhibitor, PD 98059. Finally, we found that in a vascular endothelial growth factor promoter mutated at sites previously shown to be MAPK-sensitive (SP1/AP2-88-66 site), p42/p44 MAPK activation is sufficient to promote the transcriptional activity of HIF-1. This interaction between HIF-1alpha and p42/p44 MAPK suggests a cooperation between hypoxic and growth factor signals that ultimately leads to the increase in HIF-1-mediated gene expression.

Animals↗
PubMed1999

Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry.

Mitogen-activated protein kinase (MAPK) modules, composed of three protein kinases activated by successive phosphorylation, are involved in the signal transduction of a wide range of extracellular agents. In mammalian cells, mitogenic stimulation triggers the translocation of p42/p44MAPK from the cytoplasm to the nucleus, whereas the other protein kinases of the module remain cytosolic. Since MAPK has been shown to phosphorylate and activate nuclear targets, such as the transcription factor Elk1, it has been proposed, but not yet demonstrated, that MAPK nuclear translocation could represent a critical step in signal transduction. In this study, we sequestered p42/p44MAPK in the cytoplasm by the expression of a catalytically inactive form of cytoplasmic MAP kinase phosphatase (MKP-3/Pyst-1). Sequestering MAPK in the cytoplasm did not alter its activation or its ability to phosphorylate cytoplasmic substrates of MAPK (p90RSK1 or an engineered cytoplasmic form of Elk1). In contrast, prevention of MAPK nuclear translocation strongly inhibited Elk1-dependent gene transcription and the ability of cells to reinitiate DNA replication in response to growth factors. Thus the relocalization of MAPK to the nucleus appears to be an important regulatory step for mitogen-induced gene expression and cell cycle re-entry.

Animals↗
PubMed1999

Impact of ASCO guidelines for the use of hematopoietic colony stimulating factors (CSFs): survey results of fifteen Paris university hospitals.

To assess whether physicians comply with American Society of Clinical Oncology (ASCO) guidelines for the use of CSFs, a prospective survey was performed in 15 Paris university hospitals involved in cancer treatment in 1997. If 45% of the prescriptions complied with the guidelines, primary prophylactic administration, which represented 52% of cases, did not comply with ASCO guidelines. These results suggested that primary prophylactic administration was one major clinical situation in which physicians could benefit from guidance to use a CSFs and that criteria defined by ASCO to allow primary prophylactic administration were not applied in clinical practice.

Adult↗
PubMed1999

[Cardiac factors predictive of 10-year survival after coronary surgery].

Although the predictive factors of postoperative mortality after coronary artery surgery are well known, those predictive of long-term survival have received less attention. This study reviews the outcome of a group of 480 patients between 50 and 65 years of age, operated between 1984 and 1986. The patients were classified in two groups according to the presence or absence of internal mammary artery bypass grafts: Group I (304 patients with saphenous vein bypass grafts alone) and group II (176 patients with an internal mammary artery +/- saphenous vein bypass grafts). The long-term results were assessed according to 3 criteria: isolated cardiac mortality: cardiac mortality associated with a repeat revascularisation procedure and cardiac mortality associated with reoperation or recurrence of angina. Cardiac survival at 10 years was significantly better after internal mammary-LAD bypass: 91.4% (CI 87.1-95.1) than after saphenous vein bypass grafting alone: 79.6% (CI 74.8-84.4) (p = 0.012). Univariate analysis identified the following poor predictive factors: three vessel disease (p = 0.03), preoperative left ventricular dysfunction with an ejection fraction inferior to 45% (p = 0.0001), incomplete revascularisation (p = 0.0003), use of venous bypass graft alone (p < 0.014) and perioperative infarction (p = 0.0254). For each criterion of survival (cardiac isolated or associated with a new revascularisation and/or recurrence of angina), multivariate analysis identified three independent predictive factors of long-term extramortality: not using internal mammary artery-LAD bypass graft, incomplete revascularisation and preoperative hypertension. This study confirms the beneficial effects of internal mammary-LAD artery grafting on long-term survival after coronary artery surgery, and also demonstrates the prejudicial effects of hypertension.

Coronary Artery Bypass↗
PubMed1998

Foveolins A and B, dammarane triterpenes from Aglaia foveolata.

Three known dammarane triterpenes, 3-epi-ocotillol, eichlerianic acid and shoreic acid, together with two new ones, foveolins A and B, have been isolated from the bark of Aglaia foveolata. Structural elucidation was achieved by 2D NMR experiments.

Journal Article↗