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Biomedical subjects

F Pinguet

Publications and source records attributed to F Pinguet.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Analysis of natural family planning failures. In 7007 cycles of use].

MATERIALS AND METHODS: The analysis concerned 626 users using NFP in order to avoid a conception during a total of 6740 cycles. Participation in the study did not interfere with their plan of conception, and they were invited to behave, as far as possible, as though they ignored the study. Of these 626 couples, 530 were french, 61 belgian and 35 swiss. On the whole, 39.3% used birth control to limit births and 60.7% to space them. RESULTS: The observed pregnancy rates are 1.13, 6.47 and 17.58 for one year in actuarial method respectively for method, method + user and total pregnancy rate. The pregnancy rate was higher for women before 35 years (RR: 3.8; 95 p100 confidence interval: 1.4-10.3), during the six months after delivery (RR: 2.5; 1.0-4.6) and, of course, for couples with inprotected sexual intercourse in fertile phase (RR: 4.8; 2.1-11.2). DISCUSSION: NFP can be placed among methods of great theorical effectiveness. But pregnancies as a result of intercourses during the fertile phase despite its identification are frequent: couples have to be informed.

Actuarial Analysis↗
PubMed1998

[Analysis of hematopoietic growth factor prescriptions in 19 french cancer centers].

Medical prescription of hematopoietic growth factors (HGF) was analysed in 19 anticancer french centers during 2 months. About 4% of anticancer chemotherapeutic cycles prescribed during this period were supported by HGF prescription. The mean duration of treatment was 8 days. Among the 755 collected prescriptions, two tumor localizations represented about 50% of the prescriptions: malignant non Hodgkin lymphomas and breast cancer. The other main localizations concerned adult or pediatric soft tissue sarcomas (18%), testicular cancer (7%) and gynecologic tumors (6%). The prescription for primary prophylaxis for febrile neutropenia remains the main use of HGF (44%). The respect of the guidelines established by the F|d|ration nationale des centres de lutte contre le cancer was analyzed. Overall, 66% of the prescriptions were in adequation with these guidelines. Whereas the consommation of HGF decreased in the 19 considered institutions, it did not reach a plateau and could decrease in institutions which are awaked to the international and national recommendations.

Adult↗
PubMed1997

High-performance liquid chromatographic assay for methyl-beta-cyclodextrin in plasma and cell lysate.

This paper describes a high-performance liquid chromatographic method with fluorescence detection for the analysis of methyl-beta-cyclodextrin (MEBCD) in plasma and cell lysate, after in situ complexation with 1-naphthol. The size-exclusion HPLC column packed with TSK 3000 SW gel, was equilibrated with an eluent mixture composed of methanol and purified water (2:98, v/v) containing 10(-4) M 1-naphthol as a fluorophore. The detection is based on fluorescence enhancement caused by the formation of inclusion complexes and was performed at 290 and 360 nm for excitation and emission, respectively. The method involved a simple treatment of the samples with chloroform. Daunorubicin was used as internal standard. Limits of quantitation were 0.8 microM in plasma and 0.5 microM in cell lysate. Detection limits of 0.5 microM (50 pmol) and 0.3 microM (30 pmol) were obtained for MEBCD in the two media, respectively. Linear detection response was obtained for concentrations ranging from 1 to 100 microM in plasma and cell lysate. Recovery from plasma proved to be more than 40%. Precision, expressed as C.V. was in the range of 4 to 11%. Accuracy ranged from 89 to 105%.

Cell Line↗
PubMed1997

Determination of 5-fluorouracil and its main metabolites in plasma by high-performance liquid chromatography: application to a pharmacokinetic study.

This paper describes a relatively simple and sensitive high-performance liquid chromatographic assay (HPLC) with ultraviolet absorbance detection for 5-fluorouracil (5-FUra) and its two main metabolites, 5-fluorouridine (5-FUrd) and 5-fluoro-2'-deoxyuridine (5-FdUrd), in plasma. In this study, two plasma clean-up procedures involving addition of internal standard, solid-phase and liquid-liquid extractions have been developed. A reversed-phase Kromasil C18 column was used. The detection was performed at 268 nm for 5-FUra and at 275 nm for the two metabolites. Linear detection responses were obtained for concentrations ranging from 25 to 1000 ng/ml. The average recovery from plasma was 35, 42 and 48% for 5-FUra, 5-FUrd and 5-FdUrd, respectively. Precision, expressed as C.V., ranged from 2.7 to 13% and the mean recovery from 94 to 105%. The limits of quantitation and detection of the three analytes were 20 and 10 ng/ml, respectively. The method was used to monitor the pharmacokinetic profile of 5-FUra and its two metabolites in patients with metastatic colorectal cancer.

Antimetabolites, Antineoplastic↗
PubMed1997

Methyl-beta-cyclodextrin in HL-60 parental and multidrug-resistant cancer cell lines: effect on the cytotoxic activity and intracellular accumulation of doxorubicin.

The purpose of this work was to determine the role of methyl-beta-cyclodextrin (MEBCD) in combination with doxorubicin (DOX) on the cellular proliferation of a sensitive parental and a multidrug-resistant human cancer cell line (HL-60 S and HL-60 R) and to study the effect of MEBCD on DOX intracellular accumulation. The cytotoxicity of DOX at five concentrations (50-50,000 nM) was evaluated with or without the coadministration of four fixed noncytotoxic concentrations of MEBCD (100, 200, 500, and 1,000 microM). Intracellular DOX concentrations were determined by a high-performance liquid chromatography (HPLC) method with fluorescence detection. MEBCD applied at 500 and 1000 microM in combination with doxorubicin (DOX) significantly potentiated the activity of DOX used alone on both sensitive and multidrug-resistant cell lines; 50% growth-inhibitory (IC50) ratios (IC50 MEBCD-DOX/IC50 DOX) were about 3:4 and 1.6:4 for HL-60 S and HL-60 R, respectively. Moreover, intracellular DOX accumulation, determined by HPLC during 6 h of drug exposure, was about 2-4 times higher for cells treated with MEBCD in combination with DOX than in those treated with DOX alone. Similar results were obtained using other paired MCF 7 sensitive and resistant cell lines. Correlation between these results and an MEBCD-cell membrane interaction was discussed. These initial data provide a basis for the potential therapeutic application of MEMBCD in cancer therapy.

Antibiotics, Antineoplastic↗
PubMed1997

Four-step high-dose sequential chemotherapy with hematopoietic progenitor-cell support as induction treatment for patients with solid tumors.

BACKGROUND: Despite recent progress in modern chemotherapy, metastatic solid tumors still have a poor outcome. The delivery of increased dose intensities of cytotoxic agents could improve response rates. We assessed the feasibility and safety of a high-dose sequential chemotherapy program in chemotherapy-naive patients with solid tumors. PATIENTS AND METHODS: Thirty patients (14 with carcinoma of unknown primary site, seven with metastatic breast cancer, six with small-cell lung cancer, and three with other diseases) were treated by an induction therapy regimen consisting of four cycles of high-dose chemotherapy with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 microg/kg/d) was given until engraftment. Cycles were scheduled to be delivered every three weeks. RESULTS: A total of 108 cycles of chemotherapy were administered. Six patients went off study before the end of the program (three because of progressive disease, three because of toxicity). After the first cycle, a median number of 10 x 10(6)/kg CD34+ cells (range 8-30) were collected. The median number of apheresis procedures was 1 (range 1-3). From cycle 2 to cycle 4, the median number of days when there was an absolute neutrophil count of less than 500/microl increased from three to five, and the median number of days when the platelet count was less than 25,000/microl increased from three to six. Episodes of febrile neutropenia occurred in 36%, 50% and 46% of cycles during cycles 2, 3 and 4, respectively. The median numbers of days between cycle 1 and cycle 2, cycle 2 and cycle 3, cycle 3 and cycle 4 were 24 (range 20-30), 22 (range 20-36) and 22 (range 18-35), respectively. There were no treatment-related deaths. Non-hematologic toxicity included severe (WHO grades 3 or 4) nausea/vomiting in 19 (18%) cycles, mucositis in 8 (7%) cycles and diarrhea in 7 (6%) cycles. CONCLUSION: Support with hematopoietic progenitor cells and growth factors allows the timely administration of repetitive cycles of high-dose chemotherapy in chemotherapy-naive patients, resulting in a significant increase in dose intensity. Toxicity is noteworthy but manageable and does not compromise further therapy.

Adolescent↗
PubMed1996

High-performance liquid chromatographic assay for melphalan in human plasma. Application to pharmacokinetic studies.

This paper describes a simple, rapid and reproducible high-performance liquid chromatographic method (HPLC) with ultraviolet absorbance detection for the analysis of melphalan in plasma. The HPLC column was an Ultrasphere ODS (5 microns) and the eluent was composed of methanol, purified water and acetic acid (49.5:49.5:1, v/v). The detection was performed at 261 nm. The method involved a simple treatment of the samples with methanol. The propylparaben was used as internal standard. Linear detection response was obtained for concentrations ranging from 50 to 2500 ng/ml. Recovery from plasma proved to be more than 90%. Precision, expressed as C.V., was in the 0.5 to 9% range. Accuracy ranged from 95 to 102%. This method was used to determine the pharmacokinetic parameters of melphalan following high-dose (140 mg/m2) intravenous administration in patients with advanced malignancies undergoing peripheral blood hematopoietic progenitor-cell transplantation.

Antineoplastic Agents, Alkylating↗
PubMed1996

High-performance liquid chromatographic determination of granisetron in human plasma.

This paper describes a high-performance liquid chromatographic method (HPLC) with fluorometric detection for the analysis of granisetron in plasma. The detection is performed at 305 nm for excitation and 365 nm for emission. The method involves sample clean-up by liquid-liquid extraction. N-(1-Naphthyl) ethylenediamine dihydrochloride is used as internal standard. Toluene and phosphate buffer were added to 0.5 ml of plasma added to the internal standard. After extraction, the organic layer was separated and then evaporated to dryness. The residue was reconstituted in eluent mixture. An aliquot was injected onto the HPLC column, Spherisorb CN, equilibrated with an eluent mixture constituted by acetonitrile-phosphate buffer (pH 4.5) (15:85). The proposed technique is reproducible, selective, reliable, and sensitive. Linear detector responses were observed for the calibration curve standards in the range of 0.50 to 100 ng/ml. Extraction recovery from plasma proved to be more than 90%. Precision expressed as C.V. was in the range 2 to 8%. As low as 0.3 ng of granisetron per ml of plasma can be measured with good accuracy. The method has been validated, and stability tests under various conditions have been performed. Its sensitivity is adequate for pharmacokinetic studies.

Antiemetics↗
PubMed1996

Long-term stability of 5-fluorouracil stored in PVC bags and in ambulatory pump reservoirs.

Prolonged infusions of 5-fluorouracil (5FU) have been used since the early 1960s, but recently there has been a major resurgence of interest, partly because of the advent of electronically controlled portable infusion pumps. Admixtures of new formulation 5FU were subjected to stability studies to establish the feasability of continuous infusions. In the first study, the stability of 5FU, 1 or 10 mg ml(-1), was determined in poly(vinyl chloride) (PVC) bags (0.9% sodium chloride injection or 5% dextrose injection) at 4 and 21 degrees C after storage for 0, 1, 2, 3, 4, 7 and 14 days. In the second study, the stability of undiluted 5FU was tested at different temperatures (4 or 33 degrees C) in ethylene-vinyl acetate (EVA) or PVC ambulatory pump reservoirs after storage for 0, 3, 5, 7 and 14 days. For each condition, samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, colour change and pH. Evaporative water loss from the containers was measured. The stability of 5FU in PVC bags was unaffected by 14 days of storage at either 4 or 21 degrees C. When stored in EVA reservoirs, 5FU was stable for at least 2 weeks at 33 degrees C and for 3 days at 4 degrees C (a precipitate was observed after 3 days). In PVC reservoirs, 5FU was stable for over 14 days at 33 degrees C, but at 4 degrees C a precipitate appeared after 5 days. Loss of water through the reservoirs was substantial only at 33 degrees C for 14 days, and gave falsely high readings.

Antimetabolites, Antineoplastic↗
PubMed1995

Pharmacokinetic parameters of antipyrine in dog after hepatectomy.

Pharmacokinetic studies with antipyrine were carried out on beagle dogs to determine the consequence of hepatectomy on hepatic drug metabolizing capacity, the rate of hepatic regeneration, and the possible beneficial effect of hepatocellular transplantation. The drug (250 mg) was administered by short IV infusion in three groups of dogs (first group, 65% hepatectomy; second group, 65% hepatectomy with hepatocyte transplantation; third group 80% hepatectomy). Pharmacokinetic parameters of antipyrine were evaluated before surgery and within 10 d after surgery. Blood samples were taken at frequent intervals after drug administration and antipyrine was assayed in plasma by a specific HPLC method with UV detection. Before surgery, the mean elimination half-life was about 1.1 h and total clearance averaged 6 L h-1. In dogs with 65% hepatectomy, no statistical differences in pharmacokinetic parameters of antipyrine appeared before or after surgery. When 65% hepatectomy was associated with hepatocyte transplantation, a significant increase in elimination half-life and a significant decrease in total clearance were observed. The same statistical differences in the pharmacokinetic parameters were observed in the group with 80% hepatectomy. Transplantation of isolated hepatocytes into the spleen did not correct hepatocellular insufficiency. In this study, numerous laboratory tests were performed. A significant correlation was found between serum albumin, cholesterol, factor V, ALAT, total bilirubin, and ratio of amino acids and the pharmacokinetic parameters of antipyrine.

Alanine Transaminase↗
PubMed1989

[Characteristics of the menstrual cycles during the postpartum period without breast feeding according to the nature of the first period: ovulatory or anovulatory].

The authors have analyzed the characteristics of menstrual cycles during the post-partum without breastfeeding, according to the nature of the first period. 172 women gave the thermal curve from childbirth to the first period. Among them, 118, 111, 98 and 54 women gave the self-observation data concerning, respectively, the first, second, third and the fourth cycle after the first period. They have noticed more short luteal phases and delays in ovulation after an anovulatory first period than after an ovulatory first period. The hormonal studies in the post-partum without breastfeeding seem not to explain the whole of these anomalies ascertained beyond twelve post-partum weeks. Most authors admit that the gonadotropin axis returns to a normal state within the fifth post-partum week. Because of the peculiar kinetics of follicle development, the ovary could be an important component of the "remnant effect of gestation", that is to say, of the delay of return to post-partum ovulation following the gestation state.

Adult↗
PubMed1988

[Can analysis of previous post-partum periods provide prognostic indicators on the return of fertility after delivery?].

Evaluation of self-observation signs noted during post-partum, enables to study the physiology of this period. The signs analyzed in this study are: discharge of vaginal secretions, temperature discrepancy and bleeding. The originality of the study lies in the comparison of successive post-partum periods: 2 to 6 post-partum periods were studied in 163 women; in addition, we studied 38 cases including breast feeding time details and children reactions. The authors described especially the retention effect of the pregnancy and the inhibiting effect of breast feeding on the return of the fertility, by progressively escaping these two effects, and the part of the woman's reaction.

Body Temperature↗
PubMedDate not supplied

Pharmaco-economic study of intensive chemotherapy with peripheral blood progenitor cell support for advanced breast cancer.

Patients with high-risk breast cancer may benefit from dose-escalated chemotherapy. The rationale for high-dose chemotherapy with stem-cell rescue (HDC-SCR) in breast cancer is based on the principles of dose response and dose intensity. However, several results of properly randomized and prospective studies are necessary to determine the interest of HDC-SCR. The objective of this study, realised in the Anticancer Center of Montpellier, was to evaluate the cost of this type of transplantation. In this retrospective study, we analysed 30 patients treated for an advanced breast cancer between October 1995 and June 1998. We collected the data from the induction chemotherapy cycle (followed by cytapheresis) to the end of the hospitalisation for autograft. The mean total cost was US $25,845 per patient: US $6453 for drugs, US $4720 for transfusions, US $1865 for laboratory services and blood tests, US $5585 for staff pay, US $774 for material, US $1211 for administration cost, US $1111 for logistic cost, US $998 for structure cost and US$1578 for other. Antibiotics, granulocyte-colony stimulating factor, chemotherapy, transfusions and nutrition represent respectively 18% (US $1962), 14% (US $1590), 13% (US $1437), 42% (US $4720), 11% (US $1191) of the medication and blood products cost. The results of this study may help in identifying targets for cost reduction.

Adult↗
PubMedDate not supplied

Individual 5FU-dose adaptation schedule using bimonthly pharmacokinetically modulated LV5FU2 regimen: a feasibility study in patients with advanced colorectal cancer.

AIM OF THE STUDY: SFU-dose adaptation optimal schedule using bimonthly LV5FU2 regimen was modulated by previously validated individual pharmacokinetic parameters, in 38 patients with advanced colorectal cancer. METHODS: At the 1st cure, 5F-U pharmacokinetic parameters (particularly the area under curve (AUC) in mg.h/l.m2) were calculated in all patients. In 19 patients (A), 5FU infusion doses were progressively increased from 25 to 50% (at every cycle), according to AUC levels from 2nd to 6th; in 19 consecutive patients (B), 5FU infusion doses were increased, at the same time, at the 2nd cure, according to a protocol taking in account AUC at the 1st cure: increase of 150% it AUC < 5, of 100% if 5 < AUC < 10, of 50% if 10 < AUC < 15, of 25% if 15 < AUC < 20 in case of toxicity < grade 3. RESULTS: a) AUC in all patients, at the beginning of the treatment averaged 9.05 +/- 3.115 (range from 3.9 to 16.41). Large interindividual variability was observed. b) FU infusion doses at the 2nd cure, increased 40% in group A and 82% in group B. Corresponding AUC increased respectively of 42% and 96%. 3-WHO toxicity 23 (per cycle) occurred not very frequently (8% haematological, 6% digestive and 2% cutaneous toxicity) and remained acceptable. CONCLUSION: This feasibility study established a 5FU-dose intensification optimal strategy within the bimonthly LV5FU2 schedule with a control for the risk of toxicity. This study constitutes the basis for a multicentre phase II trial to evaluate the importance of this approach in terms of efficacy and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Effect of mitoxantrone liposomes on multidrug-resistant breast cancer cells.

A major obstacle in efficacy of breast cancer chemotherapy is the emergence of multidrug resistance. We investigated modulation of multidrug resistance by liposome-encapsulated mitoxantrone in a drug resistant human breast MCF7R cell line and the influence of liposome composition. Neutral high phase-transition temperature and anionic low phase-transition temperature phospholipid liposomes, reduced the resistance factor from 142 to 15 and 38, respectively. The higher cytotoxicity obtained with mitoxantrone-encapsulation was not necessarily related to higher intracellular uptake. Our data suggest that liposomes, according to their lipid composition, may alter the P-glycoprotein function by plasma membrane stabilization and modulate multidrug resistance in human cancer.

Antineoplastic Agents↗