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Biomedical subjects

B Chevallier

Publications and source records attributed to B Chevallier.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Epidemiologic survey of infants hospitalized for bronchiolitis. Survey conducted by the ERBUS medical network].

BACKGROUND: Acute infant bronchiolitis is a frequent seasonal disease which peaks in December. It often requires hospital care in Paris and in its surroundings. The exceptional bronchiolitis epidemic of December 1991 brought about a temporary saturation of hospital bed space at the Assistance Publique-Hôpitaux de Paris (AP-HP). Hereafter, in order to organize care more efficiently, an epidemiological observation network called ERBUS was set up. METHODS: Thanks to daily reports of emergency pediatric admissions through the Minitel network, it has been possible to get real time information on the course of the past five epidemics in each of the 11 AP-HP hospitals with pediatric emergency units. RESULTS: Globally the results point to a similar situation every year: approximately 60% boys, 35% babies under 6 months; the ratio of very young patients who are admitted to hospital is multiplied by 1.5 at the mid-point of and at the end of the epidemic compared with the beginning; 70% of the babies under 3 months are admitted to hospital. The ratio of patients who come and are admitted to hospital has been on the decrease every year since 1991: globally from 36.8% down to 28.6% in five years (from 75.1% down to 65.3% among babies under 3 months). The rhythm and intensity of the epidemic have risen sharply: in five years, the number of patients has increased by 119% and that of patients admitted to hospital by 69%, while the epidemic peaks are earlier and higher. CONCLUSION: These statistics have actually been used to allocate additional resources in AP-HP hospitals during the epidemics. To avoid the saturation of bed space in the future, ambulatory care of patients not admitted to hospital should be favored.

Bronchiolitis↗
PubMed1997

A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy.

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (> or = 80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.

Acute Disease↗
PubMed1997

Major circadian variations of glucose homeostasis in a patient with Rabson-Mendenhall syndrome and primary insulin resistance due to a mutation (Cys284-->Tyr) in the insulin receptor alpha-subunit.

We have performed clinical, in vitro biochemical, and genetic studies of a patient with severe insulin resistance, considerable growth restriction, and Rabson-Mendenhall syndrome (patient RM-3). The blood IGF-I level was undetectable in this patient, although the GH level was moderately decreased. During the postprandial period, glycemia, ketonuria, and plasma glucagon were very elevated despite high doses of exogenous insulin (glucose levels up to 30 mmol/L). In the postabsorptive state, blood glucose was normalized with small amounts of insulin; ketonuria, and glucagon levels were reduced but remained supranormal. Erythrocytes and cultured skin fibroblasts from the patient displayed a decrease in cell surface insulin receptors (IRs). The ability of physiologic concentrations of insulin to stimulate metabolic processes was altered in patient fibroblasts. Analysis of the IR gene by denaturing gradient gel electrophoresis and direct sequencing showed a homozygous missense mutation in exon 3, replacing Cys284 by Tyr in the alpha-subunit. In conclusion, marked primary insulin resistance was evidenced in patient cells as a result of a structural alteration in the IR alpha-subunit. The in vitro studies could not account alone for the in vivo metabolic alterations because glucose homeostasis varied considerably during the day in the patient.

Amino Acid Sequence↗
PubMed1997

Docetaxel: a new active agent in the therapy of metastatic breast cancer.

Breast cancer is the most common malignancy in women, accounting for about 18% of female cancers, and over half a million new cases are diagnosed worldwide each year. Its incidence increases with age and is currently rising. Although the increased availability of screening programs has allowed earlier detection and treatment of primary breast cancers, many patients relapse with metastases after apparently successful treatment of their primary tumor and over 15,000 women in the UK and about 50,000 in the USA die from advanced disease each year. The natural course of breast cancer is very variable even after the development of metastases, and depends on a variety of tumor characteristics and prognostic factors. This is reflected in the large number of treatments currently employed. However, despite this wide choice and considerable research over the years, treatment of metastatic breast cancer (MBC) prolongs average survival times only slightly. Current therapy is aimed at achieving a balance between producing maximal tumor shrinkage to produce the most effective possible palliation of symptoms, and minimizing adverse effects. Anticancer chemotherapy is the preferred option in patients who do not respond to hormones, those with hormone-independent tumors, those with aggressive breast cancer subtypes. A variety of anticancer chemotherapy regimens, using both single and combined agents, have been shown to be effective in achieving tumor regression in MBC. Anthracyclines (doxorubicin, epirubicin) are the most active of the established monotherapies, typically producing response rates of 50-60% during initial (first-line) treatment for metastatic disease, but being effective in fewer than 25% of patients requiring second-line therapy. The drawbacks of anthracyclines include dose-limiting cumulative cardiotoxicity and the development of resistant tumor clones after the use of anthracyclines for adjuvant or first-line therapy, especially if subsequent courses are required within a year. The success of these established chemotherapeutic agents depends greatly on the number and location of metastatic sites. Lymph node and soft tissue secondaries tend to respond well, while visceral metastases (especially in the liver) carry a particularly poor prognosis despite treatment. The outlook for patients with metastases involving more than two organ systems is also bleak. Although some patients can live for years with metastatic disease, the average survival time in patients with MBC is 18-24 months, while in those with liver metastases, life expectancy averages only 6 months. High-dose anticancer chemotherapy with granulocyte-colony stimulating factor (G-CSF) or autologous bone marrow transplantation has allowed the dose intensity of anthracyclines to be increased, and has improved the response rate to about 70% in selected patients with MBC. However, this approach has not been proven to improve survival, involves the risk of greater toxicity and drug-related mortality, and patients with reduced clearance of anthracyclines due to hepatic dysfunction from liver metastases may not be suitable candidates. A number of new anticancer agents have also recently been introduced in an attempt to improve on the performance and avoid the tolerability problems associated with anthracyclines. Among these, antitubulin agents (taxoids and vinorelbine) have shown highly promising activity in MBC. This paper reviews the preclinical, phase I and phase II data for one taxoid, docetaxel. Docetaxel (Taxotere) belongs to the taxoid class of cytotoxic agents, the development of which began more than 20 years ago. In 1971, paclitaxel (Taxol) was identified as the active compound of the crude extract of the bark of the Pacific Yew tree Taxus brevifolia. However, at that time the development of paclitaxel was hampered because of the limited source of the drug and difficulties with isolation, extraction and formulation. The second active taxoid, docetaxel, was isolated by Potier et al. in 1986. Docetaxel is prepared from a non-cytotoxic precursor, extracted from the needles of the European Yew tree Taxus baccata, that is condensed with a chemically-synthesized side-chain. As the docetaxel precursor is freely available because of the regenerating capacity of the needles the development of docetaxel has thus been rapid.

Journal Article↗
PubMed1996

A multicentre phase II study of docetaxel 75 mg m-2 as first-line chemotherapy for patients with advanced breast cancer: report of the Clinical Screening Group of the EORTC. European Organization for Research and Treatment of Cancer.

In this phase II study, 39 women (median age 51 years) with advanced breast cancer received docetaxel (75 mg m-2) intravenously over 1 h every 3 weeks as first-line chemotherapy for advanced disease, without routine premedication for hypersensitivity reactions. In 31 evaluable patients, an overall response rate of 52% (95% CI 33-70%) was achieved, including a complete response rate of 13%. The median time to first response was 12 weeks (range 3-35+), the median duration of response was 34 weeks (range 11-42+) and the median time to progression was 24 weeks (range 0-42+). Docetaxel showed considerable activity in patients with visceral involvement (52% response), including lung (67%) and liver (44%) metastases. The safety profile was acceptable. Grade 4 neutropenia occurred in 82% of patients (53% of cycles); febrile neutropenia (grade 4 neutropenia with fever > 38 degrees C, requiring antibiotics) occurred in only three (7.7%) patients (1.4% of cycles) and none of these required hospitalisation. Acute adverse events were generally well tolerated, with only two grade 3 events and no grade 4 events reported. Despite no prophylactic premedication, the incidence of acute hypersensitivity reactions was only 13%. Fluid retention was widely experienced (72% of patients) but was severe in only five (12.8%) patients and was the reason for discontinuation of treatment in 16 patients. Nevertheless, patients were able to receive a median cumulative dose of approximately 592 mg m-2 before discontinuing treatment, and the syndrome was slowly reversible after treatment withdrawal. In conclusion, docetaxel, even at a dose of 75 mg m-2, is confirmed to be an active agent in breast cancer. Compared with an earlier study of first-line docetaxel at the usual dose of 100 mg-2, it appears that 75 mg m-2 produces a lower response rate (52% vs 68%), although this still compares favourably with that of doxorubicin monotherapy in a similar patient population (43%). This difference is particularly striking in subgroups of patients with particularly poor prognostic factors, such as liver metastases or involvement of more than two organs. The incidence of fluid retention appears to be similar at the two doses and, it is likely that premedication with corticosteroids will be preferable to dose reduction for managing this adverse event.

Adenocarcinoma↗
PubMed1996

A multicentre phase II study of the efficacy and safety of docetaxel as first-line treatment of advanced breast cancer: report of the Clinical Screening Group of the EORTC.

BACKGROUND: Two previous phase II trials of docetaxels as first line chemotherapy of advanced breast cancer have been conducted by the Clinical Screening Group of the EORTC. In these 2 studies, docetaxel 100 mg/m2 and 75 mg/m2 were administered without routine premedication and produced overall response rates of 68% and 52% respectively. Fluid retention was the most problematic adverse event in these 2 studies in which premedication was not routinely administered. This study investigated the efficacy and safety profile of docetaxel with a 1-day prophylactic premedication. PATIENTS AND METHODS: Docetaxel 100 mg/m2 was administered intravenously over 1 hour, every 3 weeks, to 37 women (aged 29-65 years) with advanced breast cancer. A 1-day regimen of intravenous antihistamine and oral corticosteroids was given with each dose. Full doses of docetaxel were administered in 179 of 200 cycles (89.5%), giving a median relative dose intensity of 0.98. RESULTS: Tumour regression was achieved in 25 patients (7.66%) after a median of 7 weeks, and 2 patients (5.4%) had a complete response. Response rates were 67.9% in patients with visceral metastases, 76.9% in liver metastases and 83.3% in patients with > 2 organs involved. The median time to progression was 31 weeks (range 1-36+). After a median follow-up time of 6.9 months (range 4.6-9.4), 31 patients (83.7%) were still alive. The most common adverse events (AE) were neutropenia (97%), alopecia (97%, grade 1-2), fluid retention (89%, mainly mild to moderate) and neurosensory disorders (81%, mainly mild to moderate). Only 5 patients experienced febrile neutropenia requiring hospitalisation and/or antibiotic therapy. Sixteen patients discontinued treatment because of fluid retention; nevertheless, 13 of these achieved an objective antitumour response and none had any significant deterioration in performance status. AEs were generally reversible and easily managed, and there were no deaths attributable to docetaxel-related AEs. CONCLUSIONS: Docetaxel produces very effective tumour response with acceptable tolerability when used as first-line chemotherapy in patients with advanced breast cancer. The 1-day premedication regimen used in this study was less effective in reducing the incidence and severity or delaying the onset of fluid retention than the currently recommended 5-day corticosteroid premedication. The optimum premedication regimen remains to be defined.

Adult↗
PubMed1996

A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.

This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.

Adult↗
PubMed1995

[Maternal serum markers of fetal trisomy 21].

Down's syndrome is the most frequent genetic disease. Each year, in France, there are 1,100 trisomy 21-affected newborns. this chromosomal disease is the most frequent cause of mental retardation raising an important public health problem. Prenatal diagnosis of chromosomal anomalies is based on fetal karyotyping, but cannot be proposed in all situations because of the cost and the risk of fetal death due to amniocentesis. The aim of screening is to define patients at increased risk for trisomy 21. Three criteria are currently used to define an at risk-population: maternal age, ultrasound anomalies, and maternal serum markers. In France, amniocentesis is proposed to patients over 38 years of age. Ultrasound signs for trisomy 21 are often difficult to identify at routine echography. Based on a prospective study of 51,048 women under 38 years of age, we observed that maternal serum hCG at 15 weeks can detect 59% of all trisomy 21 cases while the yield for amniocentesis is 6.1%.

Adult↗
PubMed1995

Current status of Taxotere (docetaxel) as a new treatment in breast cancer.

Therapy for advanced breast cancer has not improved significantly in recent years, remaining strictly palliative in nature and intent. One approach to increase the effectiveness of the treatment is the introduction of active new drugs. Taxotere (docetaxel) is a taxoid derivative isolated from the needles of the European yew, Taxus baccata. Taxotere promotes the assembly of microtubules and inhibits their depolymerization. One EORTC Clinical Screening Group (CSG) phase II trial using Taxotere at 100 mg/m2, 1 hour infusion without routine premedication for hypersensitivity reactions, in first line chemotherapy, indicates a high anti-tumor activity: 5 complete and 18 partial responses in 32 patients assessable for response (overall response rate 72%, 95% CI 53%-86%). Other studies confirm this activity in first line and second line chemotherapy for advanced disease and in patients who are refractory to anthracycline containing regimens. Grades III and IV neutropenia without major infection, and grades I and II skin toxicity, were frequently observed adverse events. A fluid retention syndrome (chronic cumulative and non life-threatening toxicity) has been noted in patients treated with Taxotere. Methods for controlling fluid retention--dose reduction to 75 mg/m2 (which has little effect) or routine premedication from the start of treatment--are currently being studied.

Antineoplastic Agents, Phytogenic↗
PubMed1995

A clinical screening cooperative group phase II evaluation of lobaplatin (ASTA D-19466) in advanced head and neck cancer.

We evaluated the efficacy and tolerability of lobaplatin, a new platinum compound, given at the dose of 50 mg/m2 by i.v. bolus every 4 weeks, in 49 patients with advanced and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). One complete and 2 partial responses were observed in 43 eligible patients for an overall response rate of 7% (95% confidence interval: 1-19%). The duration of responses was 11, 16 and 32 weeks. Toxicities of WHO grade > or = 3 were hematologic: thrombocytopenia in 26%, granulocytopenia in 12% and anemia in 12% of patients. There was no therapy-related death. Nausea/vomiting, diarrhoea and paresthesia were mild and rare. In conclusion, lobaplatin was well tolerated, but its efficacy in advanced SCCHN at the presented dose and schedule, was marginal.

Adult↗
PubMed1995

[Comparative study of nebulized sambutol against placebo in the acute phase of bronchiolitis in 33 infants aged 1 to 6 months].

BACKGROUND: The therapeutic role of bronchodilators in bronchiolitis remains controversial. The aim of this study is to evaluate the safety and the clinical response to nebulized salbutamol in infants with mild acute bronchiolitis. PATIENTS AND METHODS: Thirty-three infants, aged 1 month to 5 months and 22 days (mean: 92.4 days) were included in the study. Patients received either nebulized salbutamol (0.15 mg/kg per dose: 16 infants) or a placebo (normal saline aerosol: 17 infants), delivered by an oxygen propellent, three times at intervals of 1 hour, as part of a double-blind randomized trial. Effect of treatment was evaluated by measuring respiratory and heart rate, clinical scores based on the degree of retraction and wheezing, and oxygen saturation. Clinical assessment was repeated 30 minutes after each nebulization. A nasopharyngeal swab was obtained for detection of respiratory syncytial virus (VRS) antigens by immunofluorescence assay in all patients. RESULTS: Patients in the salbutamol group exhibited significantly greater improvement in respiratory rate (P = 0.01), accessory muscle score (P < 0.001) and wheezing score (P < 0.001). There was no significant difference in oxygen saturation between both groups. Infants treated with salbutamol exhibited a non-significant increase in heart rate after the three sprays; no other adverse effects were noted. VRS was identified in 78% of the children tested. CONCLUSIONS: Salbutamol is safe and effective in relieving the respiratory distress of young infants with acute bronchiolitis. Our study confirms previous observations that infants younger than six months of age respond as well as older children when given three doses of nebulized salbutamol. Responders could not be differentiated from non responders by personal or family histories of atopy and VRS isolation. A longitudinal study could establish a correlation between response to bronchodilator therapy and later development of asthma.

Acute Disease↗
PubMed1995

Tamoxifen for the treatment of metastatic inflammatory breast carcinoma.

In this series, 65 patients with metastatic inflammatory breast carcinoma were treated with neoadjuvant chemotherapy followed by local regional treatment followed by adjuvant chemotherapy. All of these selected patients developed further metastatic disease and were treated at that time with tamoxifen alone. Measurements of hormone receptor levels were available for 46 patients. Four tumors were positive estrogen receptors and eight tumors were positive progesterone receptors. The objective response rate for tamoxifen therapy was 5% (3/65). No major side effects were observed. When the metastasis-free interval was over 19 months, the overall survival and after metastases survival rates were significantly increased. Our conclusion is that tamoxifen should not play any role in the palliative treatment of metastases in inflammatory breast carcinoma.

Adenocarcinoma↗
PubMed1995

Neuroendocrine primary small cell carcinoma of the breast. Report of a case and review of the literature.

One case of breast neuroendocrine primary small cell carcinoma with light microscopic and immunohistochemical findings is reported. The patient died of unrelated disease 21 months after diagnosis and treatment by modified radical mastectomy, radiotherapy and subsequent chemotherapy. Immunohistochemical studies revealed cytokeratin and neuroendocrine markers (chromogranin, neuron-specific enolase) immunostaining on tumoral cells. Expression for neuropeptides (met-enkephalin, leu-enkephalin, beta-endorphin) and CALLA antigen was found. Based on this case report and six other previously reported cases, breast neuroendocrine primary small cell carcinoma appears to be a very aggressive tumor for which no firm conclusions regarding treatment can be drawn.

Aged↗