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D Noel

Publications and source records attributed to D Noel.

At least 19 recordsLinked to original sources
PubMed2002

Adenovirus-mediated gene transfer of urokinase plasminogen inhibitor inhibits angiogenesis in experimental arthritis.

Plasmin is essential for metalloproteases activation, endothelial cell migration and degradation of the extracellular matrix. The process is common to neoangiogenesis pannus formation and cartilage degradation within arthritic joints. Since 80% of synovial cells express urokinase plasminogen activator receptor (uPAR), we investigated the inhibition of plasmin activation in a collagen-induced arthritis (CIA) mice model, by expressing a uPA/uPAR antagonist molecule (ATF) fused to human serum albumin (HSA) to extend its serum half-life. Overexpression was obtained with an adenoviral vector expressing the chimeric murine ATF-HSA. We showed that the genetic coupling did not significantly reduce the ability of the ATF moiety to interact with its receptor uPAR. The chimeric protein was detectable in the sera of injected mice 7 days following Ad-mATF-HSA injection, then decreased in parallel with the anti-HSA titer increase. Systemic Ad-mATF-HSA injection performed on day 25 following CIA induction decreased the incidence of arthritis and the severity of the disease. Moreover, synovial angiogenesis in arthritic paws was decreased after Ad-mATF-HSA gene transfer, as assessed by smooth muscle actin immunostaining. The preventive effect observed on arthritis was related to the decrease in angiogenesis, rather than inhibition of extracellular matrix degradation.

Adenoviridae↗
PubMed2001

[How to manage very elderly patients in the emergency room? Evaluation of 150 very elderly patients at the Rouen university hospital center].

OBJECTIVES: There are few data in the literature concerning care provided to very elderly subjects referred to emergency care units. The emergency room setting would not be particularly adapted to management of this rising population. The purpose of our work was to assess the frequency of referral to emergency care units, the characteristics of the elderly population, and patient management. PATIENTS AND METHODS: One hundred fifty consecutive patients aged over 90 years addressed to the emergency unit of the Charles Nicolle hospital in Rouen France were studied. These patients were cared for by the medical and surgical teams. We recorded, type of referral, hour and reason for admission, degree of handicap and residence, gravity at admission using the clinical classification for emergency care patients (CCMU), complementary tests performed in the emergency unit, duration of stay in the unit and subsequent referral. The characteristics of these "very" elderly patients aged over 90 years were compared with those of "elderly" patients aged 75-90 years. RESULTS: Over a period of 33 days, the unit cared for 4888 patients, including 150 very elderly patients aged over 90 years (mean age 92.6 years). Daily, 4.4 patients were referred by a primary care physician (76.), mainly between 8 a.m. and 8 p.m. (81.3%). Forty-two percent of the patients had a surgical problem. Two-thirds were unable to walk, one-third had cognitive disorders, and one-third had urinary incontinence. However, half of these very elderly patients lived in a private home. According to the CCMU classification, 14.6% of the patients had a life-threatening disorder. Complementary tests were ordered for most patients (85%). Mean duration of stay in the emergency unit was 3.6 +/- 2.6 days. One quarter of the patients returned to their former residence, with a higher percentage among the surgery patients (37%) than among the medical patients (14.6%). There was no significant difference between the "very elderly" and "elderly" patients in terms of type of referral, duration of stay in the unit and subsequent referral. CONCLUSION: "Very elderly" patients are frequently addressed to emergency care units by their primary care physician. They have severe conditions with major handicaps that largely explain their hospitalization. Our results point out possible improvements for care in the emergency unit.

Activities of Daily Living↗
PubMed2001

A rapid reversed phase high performance liquid chromatographic method for determination of etoposide (VP-16) in human plasma.

A rapid, simple and sensitive isocratic High Performance Liquid Chromatography (HPLC) method was developed to measure the concentration of etoposide in plasma samples with UV detection at 220 nm. The method uses a Bondapac C18 column at 60 degrees C. The mobile phase consists of Methanol: water (45:55 v/v) at a flow rate of 2.8 ml/min. Phenacetin was used as an internal standard. The plasma samples were extracted using ether with the organic layer evaporated under nitrogen. The residue was dissolved in 200 microl methanol with 20 microl injected into the HPLC column. The extraction method showed a recovery of 91.5+/-3% for etoposide. In this system, the retention time of phenacetin and etoposide were 3.3 and 4.4 min, respectively. The limit of detection of etoposide in plasma is 20 ng/ml and the limit of quantitation is 40 ng/ml. This analytical method has very good reproducibility (8.1% between-day variability at a concentration of 50 ng/ml). It is a fast, sensitive and economic method applicable for clinical and pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMed2000

[Is cognitive change related to hypothyroidism reversible with replacement therapy?].

PURPOSE: Although cognitive impairment related to hypothyroidism has been investigated, issues regarding treatment have been less extensively studied. The aim of this study was to assess cognitive function in patients with hypothyroidism just before treatment and after hypothyroidism had resolved. METHODS: Standardized psychometric assessment (including ten tests) was done in 30 outpatients with biochemical evidence of hypothyroidism (TSH = 92.1 mU/L, range: 11.4-400) and in 30 control subjects matched for age and gender with normal thyroid function. These tests were repeated twice before treatment and after hypothyroidism had been cured. Statistical analysis was done using the Mann-Whitney U test. RESULTS: The baseline characteristic of patients with hypothyroidism showed that attention, motor speed, memory and visual-spatial organization were significantly impaired. Cognitive decline was significantly greater with increasing age. Cognitive impairment significantly decreased after hypothyroidism had been cured, reaching values obtained in age-matched control subjects. CONCLUSION: Attention, motor speed, memory and visual-spatial organization are significantly impaired in hypothyroidism, particularly in the elderly, suggesting that ageing could have potential effects on cognitive functions. Hormone-replacement therapy leads to normalization of the cognitive functions.

Age Factors↗
PubMed1999

Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer.

PURPOSE: This study was undertaken to address the influence of concurrent administration on the pharmacokinetics of UFT (uracil plus tegafur) and leucovorin (LV), and to measure the antitumor activity of a 28-consecutive-day oral regimen of UFT plus LV in patients with relapsed or refractory colorectal cancer. METHODS: Patients with advanced measurable colorectal cancer who had failed previous therapy with intravenous bolus 5-fluorouracil (5-FU) were eligible. Patients were treated with UFT 300 mg/m2 per day plus LV 90 mg per day in three divided doses every 8 h for 28 days, repeated at 35-day intervals. In addition, a three-treatment by three-period crossover bioavailability comparison of oral LV 30 mg plus UFT 200 mg versus either LV or UFT alone was scheduled for the 8 days preceding the first cycle of therapy. RESULTS: Of 19 patients enrolled, 18 were assessable for pharmacokinetics and response. When LV was coadministered with UFT, there were no statistically significant effects on tegafur, uracil, or 5-FU Cmax, AUC, or Tmax with the exception of a delayed Tmax for tegafur (P=0.03). No statistically significant differences were found in LV and 5-methyltetrahydrofolate plasma levels when LV was administered alone or with UFT. However, wide interpatient variability was observed for all parameters. There were no antitumor responses seen. CONCLUSIONS: Although the Tmax for tegafur is delayed with the concurrent administration of LV, there were no differences (P > 0.05) in any pharmacologic parameters that are of likely clinical significance. However, the great interpatient variability observed in UFT and LV pharmacology may have obscured true bioavailability effects in this small patient population. Daily oral UFT plus LV is inactive as second-line therapy in patients who have failed bolus 5-FU.

Adult↗
PubMed1999

Pediatric heparin-induced thrombocytopenia: management with Danaparoid (orgaran).

Heparin-induced thrombocytopenia is a rare and serious complication of anticoagulation therapy. There remains a paucity of information pertaining to alternative anticoagulation strategies for use during cardiopulmonary bypass concomitant with heparin-induced thrombocytopenia, especially in children. We report the successful treatment of heparin-induced thrombocytopenia and subsequent hemorrhagic complications postoperatively in a 2-year-old child with Danaparoid (orgaran). Emergent conduit revision with cardiopulmonary bypass was required for a thrombosed systemic-venous to pulmonary-arterial connection (completion modified Fontan procedure). Required doses of Danaparoid were consistently twofold that previously reported for adults.

Anticoagulants↗
PubMed1999

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

Adult↗
PubMed1998

Affinity of recombinant antibody and antibody fragment binding to human thyroglobulin: potential applications in gene therapy.

Recombinant antibodies and antibody fragments are currently being produced. They can be used in vitro for the structural study of antigen-antibody interactions for instance, but their in vivo production may have applications for gene therapy of certain cancers and severe viral diseases and in developing new animal models of autoimmune disease. We report here these two types of applications using a recombinant antihuman thyroglobulin (hTg) antibody.

Animals↗
PubMed1997

Phase I and pharmacokinetic study of etoposide phosphate by protracted venous infusion in patients with advanced cancer.

PURPOSE: Etoposide has schedule-dependent cytotoxic activity, and clinical resistance may be overcome with prolonged low-dose therapy. Oral bioavailability is variable, and protracted intravenous administration is limited by water insolubility, which requires large infusion volumes. Etoposide phosphate (EP) is a water-soluble prodrug that is rapidly converted in vivo to etoposide, and may be administered in concentrated solution. A phase I study was conducted to determine the toxicity, pharmacokinetics, and pharmacodynamics of EP administered as a protracted venous infusion in the ambulatory setting. METHODS: Twenty-three patients with advanced cancer were treated with a continuous infusion of EP using ambulatory pumps for 6 weeks followed by a 2-week rest. Cohorts were treated with EP at 10, 20, 25, and 30 mg/m2/d. Steady-state plasma etoposide levels (Css) and stability of EP in infusion pumps were measured using high performance liquid chromatography (HPLC). RESULTS: Myelosuppression, mucositis, and fatigue were dose-limiting. The maximum-tolerated dose (MTD) of EP was 20 mg/m2/d. The mean Css (+/- SD) of etoposide were 0.67 +/- 0.25, 1.14 +/- 0.24, 1.38 +/- 0.64, and 2.19 +/- 0.52 microg/mL at daily EP doses of 10, 20, 25, and 30 mg/m2, respectively. Neutropenia correlated with Css (r = 0.65, P = .008). EP was stable in infusion pumps for at least 7 days. Partial responses were observed in patients with hepatoma and non-small-cell lung cancer (one each). CONCLUSION: EP may be conveniently and safely administered as a low-volume protracted venous infusion in the ambulatory setting. Cytotoxic plasma concentrations of etoposide are obtained at the MTD. The pharmacodynamic relationships observed suggest the possibility of pharmacologically based dosing of EP.

Adult↗
PubMed1997

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer.

A pilot phase II study examined the feasibility of 75 mg/m2 of docetaxel (Taxotere) in combination with 50 mg/m2 of doxorubicin and 500 mg/m2 of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation. Patients were divided into three groups: one group received 8 courses of docetaxel/doxorubicin/cyclophosphamide; the second received 4 to 6 courses of the same combination with cell sampling, followed by high-dose chemotherapy with autologous peripheral blood stem-cell transplantation; and the third group's regimen was identical to that of the second, with additional granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]). Of 28 patients (149 courses) evaluable for toxicity and response, the overall response rate was 82%, with 5 (18%) complete responses and 18 (64%) partial responses. The most frequent hematologic toxicity was neutropenia; grade 4 neutropenia occurred in 86% of patients, with febrile neutropenia in 9 patients (18%). There was no incidence of infection, possibly because of the administration of oral ciprofloxacin (Cipro) from days 5 to 15 of each cycle. Nonhematologic adverse events were not severe; there was no significant cardiotoxicity. Future randomized trials of docetaxel/doxorubicin/cyclophosphamide as first-line adjuvant therapy of high-risk patients and as induction chemotherapy are in development.

Adult↗
PubMed1997

Oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer.

Therapeutic options for patients with advanced colorectal cancer who have failed treatment with fluorouracil (5-FU) are limited. Responses have been reported in this setting with a protracted venous infusion of 5-FU. Daily oral therapy with tegafur and uracil (UFT) plus leucovorin (LV) has the potential to mimic the pharmacology of continuous infusion 5-FU. Therefore, we undertook a phase II study of a 28-day schedule of a combination chemotherapy regimen containing oral UFT/leucovorin in patients with measurable metastatic colorectal cancer who had failed treatment with bolus 5-FU. In addition, we sought to determine whether coadministration of UFT and leucovorin alters the bioavailability of these agents. In a pretreatment phase, each patient underwent sequential pharmacokinetic sampling following a single dose of UFT alone, leucovorin alone, and the combination of UFT plus leucovorin. The preliminary results of this trial suggest that tegafur pharmacokinetics are not affected by coadministration of leucovorin and that folate pharmacokinetics are not affected by UFT.

Adult↗
PubMed1997

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer.

Preliminary results from phase I trials suggest that the use of docetaxel (Taxotere) and doxorubicin (Adriamycin) is a well tolerated and highly active combination regimen for patients with metastatic breast cancer. The maximum tolerated dose of this combination was 50 mg/m2 of doxorubicin given as an intravenous bolus followed 1 hour later with 75 mg/m2 of docetaxel given as a 1-hour intravenous infusion. Because cardiotoxicity was not observed with this combination, we added cyclophosphamide (Cytoxan, Neosar) in a phase II trial to determine the antitumor activity and tolerability of this 3-drug combination as first-line therapy in patients with metastatic breast cancer. Preliminary results from this study indicate that the Taxotere/ Adriamycin/Cyclophosphamide (TAC) combination produces response rates of up to 80%. However, frequent grade 4 neutropenia was seen in 68% of cycles, febrile neutropenia in 5.5% of cycles, and grade 3 to 4 infection in .8% of cycles. Cardiac toxicity was rare, with 1 case of reversible congestive heart failure (2%), which occurred 2 months after completion of chemotherapy. These preliminary data show that TAC is highly active and that docetaxel did not significantly increase the cardiotoxicity of doxorubicin. Phase III studies in both the first-line and adjuvant settings are warranted.

Adult↗
PubMed1997

Gene transfer to human rheumatoid synovial tissue engrafted in SCID mice.

OBJECTIVE: To assess the feasibility of gene therapy in rheumatoid arthritis (RA) and determine the appropriate vector. METHODS: Human rheumatoid synovial tissue from 6 patients with RA was transduced ex vivo with a recombinant retroviral vector (pMFG.nlsLacZ) containing the Escherichia coli beta-galactosidase (beta-gal) gene in a coculture assay in the presence of 20 ng/ml tumor necrosis factor alpha (TNF-alpha) for promoting cell division. We also conducted in vitro infection experiments using an adenoviral vector (AdCMVSpl.LacZ) containing the beta-gal gene. After gene transduction, the synovial tissue was engrafted subcutaneously in 8-week-old severe combined immunodeficiency (SCID) CB17 mice. Beta-gal expression was then monitored as a function of time (up to 21 days) and of virus dose [up to 50 colony forming units (cfu)/cell]. The efficacy of direct in vivo gene transfer was also tested by injection of 10(6) cfu of pMFG.nlsLacZ into rheumatoid synovial tissue engrafted in SCID mice. RESULTS: When recombinant retroviral vector was used, 30 +/- 5% of ex vivo infected synovial cells were positive for staining. In synovial tissue implanted in SCID mice, beta-gal expression declined to 5% after one week, but persisted for at least 21 days. Direct injection of pMFG.nlsLacZ vector into the rheumatoid synovial tissue implanted in SCID mice allowed efficient and stable in vivo infection of the synovial tissue. Ex vivo gene transfer with adenoviral vector resulted in a 98% infection rate of the synovial lining cells. However, beta-gal activity declined 7 days after subcutaneous implantation. CONCLUSION: Highly efficient gene transfer in rheumatoid synovial tissue is achievable with both adenoviral and retroviral vectors, but the results were transient. Exogenous gene transfer through retroviral vectors required stimulation with TNF-alpha for synovial cell division and proviral integration. Direct in vivo gene transfer with recombinant retrovirus was shown to be efficient. Transduction of human synovial tissue engrafted in SCID mice is a potent tool for developing preclinical models of gene therapy in RA.

Adenoviridae↗
PubMed1996

Analysis of the individual contributions of immunoglobulin heavy and light chains to the binding of antigen using cell transfection and plasmon resonance analysis.

We have cloned the Tg10 murine monoclonal antibody, which is specific for a human thyroglobulin (hTg) epitope targeted by autoantibodies in several thyroid pathologies. Transfection of COS-7 cells with plasmids expressing Tg10H and -kappa chains combined with surface plasmon resonance analysis (BIAcore) of culture supernatants showed that the entire cloned Tg10 antibody displays an affinity comparable to that of the parental antibody. This approach also permitted determination of the probable role of each chain to the recognition of the cognate epitope due to the ability of COS-7 cells to secrete independently each of the two constituting immunoglobulin chains. Tg10 heavy chain recognizes hTg in the absence of the light chain, but with a ten-fold lower affinity mainly due to an increase in kappaoff. In contrast, the light chain is unable to bind hTg on its own. This suggests that the latter is probably involved in stabilization rather than in initiating the formation of the antibody/antigen complex and that the specificity of Tg10 is mostly, if not exclusively, carried by the heavy chain. The potential applications of combined cell transfection and surface plasmon resonance to our understanding of antigen/antibody interactions are discussed.

Amino Acid Sequence↗
PubMed1996

Tobacco use prevalence and correlates among adolescents in a clinician initiated tobacco prevention trial in California, USA.

OBJECTIVES: Baseline data for the clinician initiated, tobacco prevention trial, the first non-school based clinician mediated tobacco prevention study, were used to explore the degree to which young people receiving orthodontic treatment use tobacco and the differences in use rates between national, California, and patient samples. Correlates of tobacco use were identified and these correlates were contrasted with findings from the published reports. DESIGN AND SETTING: A 26 item telephone survey assessed demographic information, tobacco use, selected health related behaviours, and variables based on social learning theory. The study was conducted among 11 to 18 year old orthodontic patients from San Diego, Orange, Riverside, San Bernardino, and Los Angeles Counties, California, USA. PARTICIPANTS: Of the 17925 patients who were eligible, 16915 (> 94%) completed the survey. MEASUREMENTS AND MAIN RESULTS: Multivariate analyses were conducted using a logistic mixed effects model. Although the 30 day prevalence rate of tobacco use (6%, n = 1010) proved lower than California and national samples, the rates for the age, gender, and race ethnicity subgroups showed trends similar to those seen in California and national samples. Ten variables were significantly associated with tobacco use (p < 0.05), including 30 day alcohol use (OR = 7.88), age (OR = 1.32), and living with a tobacco user (OR = 1.72). CONCLUSIONS: Because 6% of orthodontic patients use tobacco, interventions are warranted to reach the health "Objectives for the Nation". Patterns of correlates of tobacco use were essentially the same for orthodontic patients, California, and national samples, suggesting that these associations are generalisable.

Adolescent↗
PubMed1996

An adolescent tobacco-use prevention trial in orthodontic offices.

OBJECTIVES: This study examined the effect of an orthodontist-delivered tobacco-use prevention program for adolescents. METHODS: Southern California orthodontic offices were randomly assigned to experimental (n = 77) and control (n = 77) groups. Randomly selected adolescents were interviewed at baseline and 2 years later (n = 15,644). Experimental offices received tobacco prevention training, anti-tobacco materials, and 50 cents for each anti-tobacco "prescription" written. RESULTS: The 30-day tobacco use 2-year incidence rates for the control and experimental groups were 12.6% and 12.0%, respectively; incidence rates for using tobacco more than 100 times were 7.6% and 6.8%. Differences between the groups did not reach significance. Mean prescription compliance was 64.4%. A multivariate logistic model, showed a significant dose response: patients who received more prescriptions had lower incidence rates than those who received few or none (10% vs 14%). CONCLUSIONS: Training, payment, and support did not ensure clinician compliance with prevention services. The dose effect suggests that replication under conditions that would ensure clinician compliance and statistical power would more thoroughly test clinicians' ability to prevent tobacco use.

Adolescent↗