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F Lewin

Publications and source records attributed to F Lewin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized phase III study.

BACKGROUND AND PURPOSE: In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. METHODS: Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. RESULTS: Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. CONCLUSIONS: No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment.

Adult↗
PubMed1997

Single-institution effectiveness assessment of open-heart surgery in octogenarians.

OBJECTIVE: To determine short- and long-term outcome of open-heart surgery in octogenarians. METHODS: We reviewed the medical charts of 130 consecutive octogenarians undergoing open-heart surgery. Patients with significant comorbidity were excluded from the study. The effect of cardiac and operative risk factors on mortality and morbidity was evaluated. General practitioners and cardiologists were contacted in order to obtain information on the patients' current medical and functional status. RESULTS: Operative mortality for valve replacement (VR) and coronary artery bypass grafting (CABG) was 11.5%. Four-year survival was 73.5% with 75.9% still living independently. The relative risk for operative mortality was 4.3 in case of extracorporeal bypass time exceeding 95 min and 3.6 in case of significant left main stem disease. The risk of late death increased 2.5 times at a left ventricular ejection fraction lower than 50%. CONCLUSIONS: Our data match the results of similar studies involving large numbers of patients. When a multicenter data bank is missing, the evaluation of a relatively small patient group can yield information that may be as useful to patient and physician as information obtained by large studies. Open-heart surgery in octogenarians carries an acceptable mortality risk and its effectiveness in terms of improved quality of life is good.

Aged↗
PubMed1997

Congenital adenomatoid disease of the lung: prenatal diagnosis and perinatal management.

Prenatal ultrasonographic (US) detection of congenital adenomatoid malformation (CAM) was made in 18 fetuses at 17 - 36 weeks' gestation and managed in our institution during a 10-year period (1985-1994). The lesion was left-sided in 13 cases, right-sided in 4, and bilateral in 1. According to Stocker's classification, 12 cases were type I, 4 type II, and 2 type III. The prenatal course was followed with serial US examinations in 13 cases; the size of the lesion was stable in 8 and decreased in 5. Mediastinal shift was usually observed, and amniotic fluid volume was increased in 4 cases. One fetus was aborted. Six infants presented with respiratory distress syndrome and required neonatal surgery; delayed surgery was performed in 9 cases. Spontaneous regression of the lesion was observed on follow-up in 2 cases. Surgery consisted in lobectomy in 8 cases and segmentectomy in 6. The presence of fetal hydrops, type III lesions, and bilateral lung involvement are prenatal factors known to be associated with a poor prognosis. However, this series and a review of the literature suggest that caution should be observed with regard to the initial impression when counseling the parents regarding prognosis.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1997

[Prenatal MRI of the brain. Retrospective study apropos of 34 tests].

We performed 34 antenatal MRI, in utero in 29 foetuses with cerebral malformations depicted by US. For five patients, a second antenatal MRI was performed because of a technical failure or of diagnosis doubt. We considered that MRI is a valuable imaging method. We have observed 2 false negatives (myelomeningocele, gyration abnormality) on MR study (n = 34). MRI is more contributive that US for the etiological diagnosis of ventricular enlargement: 83% versus 46%. MRI depicted corpus callosum agenesis misdiagnosed in 5 patients by US. MR results modified the therapeutic procedure in 37% of our patients. We think that the optimal term to perform MRI study is after 28 weeks gestational age because of the size of the fetus and for the timing of cerebral development. Ventricular dilatation (criteria: occipital horn size more that one centimeter at 25 weeks of term) is the main indication of MR study.

Brain↗
PubMed1996

Absence of misincorporation of pyrimidines in DNA after treatment with a combination of cisplatin (CIS-diammine-dichloro-platinum) amd 5-fluorouracil of mouse sarcoma cells.

The effects on incorporation into DNA of the deoxyribonucleotides dCTP and dTTP and the DNA synthesis rate after treatment with cisplatin (CDDP), 5-fluorouracil (5-FU) or a combination of CDDP and 5-FU were studied in ascites sarcoma (Bp8) growing in mice. Single administration of CDDP gave an early (1 h) transient increase in the DNA-synthesis followed by a decrease. 5-FU as single agent did increase the rate of DNA synthesis after 6 h with a maximum at 10 h. The combination of CDDP and 5-FU markedly increased the rate of DNA synthesis up to 6 h as compared to single drug treatment. Although the dCTP pool increased after combined treatment, while the dTTP pool was unchanged, no alterations in the proportions of dTTP and dCTP incorporated into DNA could be detected. Hence, misincorporation of pyrimidines is not the mechanism for the synergistic effect of the combination of CDDP and 5-FU.

Animals↗
PubMed1995

The effect of 5-fluorouracil on cisplatin induced DNA interstrand cross-linking in a mouse ascites tumor growing in vivo.

In earlier studies we showed that a supra-additive cytotoxic effect was obtained with combined treatment with cisplatin and 5-fluorouracil (5-FU) of Bp8 ascites tumor growing in vivo in mice. We therefore studied the DNA interstrand cross-linking after single drug treatment with cisplatin, 5-FU and the drugs combined. The alkaline elution technique was used. 5-FU induced no measurable DNA cross-linking. Cisplatin caused a dose-dependent increase in DNA cross-links 6 h after treatment. When combining cisplatin and 5-FU, no significant change in the number of DNA cross-links was found for this time. The removal of DNA interstrand cross-links was studied after 24 and 36 h. There was no difference in the removal rate between single drug treatment with cisplatin as compared with the combined treatment with the two drugs. Also, the number of DNA single strand breaks (SSB) possibly created when the cisplatin induced cross-links or UV-induced DNA damage were repaired were measured with the alkaline elution technique. No increase in the amount of SSB was seen after combined treatment. Thus, we found no interaction of 5-FU and cisplatin in terms of DNA damage. Other mechanisms for the supra-additive effect found when combining cisplatin and 5-FU have to be considered.

Animals↗
PubMed1994

[Fetal surgery].

Explore the source record for details and available documents.

Animals↗
PubMed1994

Amniotic fluid digestive enzymes: diagnostic value in fetal gastrointestinal obstructions.

The diagnostic value of amniotic fluid gamma-glutamyl-transpeptidase (GGTP) and intestinal alkaline phosphatase (iALP) was evaluated in 55 patients who underwent amniocentesis for karyotyping because fetal gastric or small bowel dilatation had been detected by ultrasound. Gastrointestinal malformation was confirmed in 46 cases and there was no gastrointestinal anomaly in nine cases. Prenatal ultrasound was suggestive of gastroduodenal dilatation in 34 cases (group I) and small bowel dilatation in 21 cases (group II). In group I, amniotic fluid GGTP above the 99th percentile was 71 per cent sensitive and 100 per cent specific for a true anatomical defect of the digestive tract (mainly duodenal atresia). In group II, high levels of GGTP and/or iALP were 69 per cent sensitive and 83 per cent specific for a fetal digestive tract anomaly. In other words, when digestive tract dilatations were diagnosed by prenatal sonography, abnormal amniotic fluid enzyme activities were strongly suggestive of such an anomaly, the possibility of which was not precluded by normal amniotic fluid iALP and GGTP activities. But amniotic fluid digestive enzyme activities do not help in defining the prognosis.

Alkaline Phosphatase↗
PubMed1994

Management of ovarian cyst detected by prenatal ultrasounds.

As a result of refinements in Prenatal Ultrasonography (US), neonatal ovarian cysts are more frequently encountered than in the past. Between January 1981 and December 1990, 21 consecutive fetuses with ovarian cysts were followed up by ultrasonography. 23 ovarian cysts were diagnosed between 28 and 38 weeks gestation. 18 cysts were initially large cysts (more than 50 mm in diameter). In 9 cases, an anechoic cyst was observed and a US-guided needle aspiration of the cyst was performed (2 antenatally and 7 postnatally). Ultrasonographic patterns of complicated cyst were observed in 3 fetuses. After a postnatal ultrasound control, 11 infants were operated on: 8 surgical interventions were required for complicated cysts (torsion: 4, hemorrhage: 4), 3 cases irrespective of their sonographic appearance in our initial experience. In the remaining cases, spontaneous resolution was followed by repeated ultrasonographic examination. Prenatal ultrasonography today allows diagnosis of ovarian cysts and may suggest antenatal complications. To preserve as much ovarian tissue as possible, cysts greater than 50 mm in diameter should be candidates for percutaneous aspiration and complex cystic masses should be operated on.

Female↗
PubMed1994

DNA synthesis after combined treatment with cisplatin and 5-fluorouracil of a mouse ascites tumor growing in vivo.

We examined whether an increase in the salvage and/or the de novo synthesis of thymidine (TdR) can explain the elevated DNA synthesis rate found up to 15-20 h after combined treatment with cisplatin and 5-fluorouracil (5-FU), compared with single-drug regimen. The salvage and the de novo pathways of TdR in Bp8 mouse ascites tumor cells were reduced equally after the combined treatment and the single-drug treatments. The inhibition of the de novo pathway of TdR was confirmed by a reduced thymidylate synthase activity, as measured in cell extract. A marked imbalance of the deoxyribonucleotide triphosphates were found, in particular between the deoxypyrimidines. These imbalances were similar between the 5-FU single-drug treatment and combined treatment. We conclude that neither the extracellular TdR salvage nor the de novo synthesis of TdR explain the relatively elevated DNA synthesis rate after combined treatment. We suggest that the supra-additive effect of the combined treatment is due to an interaction between the elevated DNA synthesis, the imbalanced deoxyribonucleotides and the cisplatin-induced DNA cross-links, and possibly also due to a higher concentration of 5-FU incorporated into DNA.

Animals↗
PubMed1994

[Embryo reduction in multiple pregnancies. A French multicenter study].

OBJECTIVE: To study the outcome of multifetal pregnancy embryo reductions (MFPR) in France. STUDY DESIGN: A retrospective questionnaire multicenter survey was conducted in 11 French centers. 262 consecutive MFPR were collected. Miscarriage and prematurity rates were analyzed as a function of the starting number of embryos, the finishing number after MFPR, and the technique of MFPR. RESULTS: There were 41 pregnancy losses before 24 weeks (16%), and 221 deliveries at 25 menstrual weeks or later (84%). Prematurity was significantly correlated to the finishing number of embryos following MFPR. However, even when a single embryo was left, there were 30% of premature deliveries. CONCLUSION: MFPR decreases the risk of prematurity in multifetal pregnancies of high order, and this is best achieved when a single embryo is left.

Abortion, Induced↗
PubMed1991

First-trimester diagnosis of hypophosphatasia. Importance of gestational age and purity of CV samples.

Prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villous sample taken in the first trimester. Very low activities of the LBK isoenzymes indicated an affected fetus. Diagnosis was confirmed at 12 weeks of gestation by measurement of LBK isoenzyme activities in fetal bone tissue. In control chorionic villous samples an inverse relation was observed between LBK and placental ALP percentage during gestational age. High LBK ALP activities are observed in decidual tissue. Chorionic villous tissue must not be sampled after 12 weeks of gestation and decidual tissue must be excluded from the sample.

Alkaline Phosphatase↗
PubMed1990

The use of the antiprogestin RU486 (mifepristone) as an abortifacient in early pregnancy--clinical and pathological findings; predictive factors for efficacy.

RU486, a potent antiprogesterone steroid was administered to 124 women requesting therapeutic abortion. All were less than 49 days from their last menstrual period. Ten of these subjects (Group I) received high doses of RU486 in a decremental dose regimen (400, 300, 200 and 100 mg/day) over 4 successive days and 14 received 50 mg/day for 7 days (Group II). A further 50 subjects (Group III) received 100 mg/day for seven days and the remaining 50 subjects (Group IV) received 450 mg in a single dose. In the first three groups, half the daily dose was given in the morning and the remainder in the evening. Blood was collected before, and on Days 4 and 7 and then once a week after commencing therapy until disappearance of circulating beta HCG. In addition to beta HCG, estradiol-17 beta (E2), progesterone (P), cortisol, and various metabolic and hematological parameters were measured. Plasma RU486 concentrations were also assayed in Group II, III and IV subjects on Day 7 of therapy and in some cases on Days 14 and 21. Ultrasonography was performed in all cases on Day 1 and on Day 14. All the patients bled within five days following RU486 administration, for 1 to 21 days. A complete abortion occurred in 60% in Group I, 50% in Group II, 86% in Group III, and 80% in Group IV. The difference between the last two groups and the first two was significant at p less than 0.01. The non-responders were submitted to a uterine vacuum aspiration. A stepwise discriminant analysis was performed and indicated that the best predictors of the outcome of therapy were beta HCG values and the gestational sac diameter. With these criteria, the prediction was accurate in 86.4% of the cases. The best results were obtained in the cases where the ultrasonic measurement of gestational sac was under 10 mm in diameter and the initial beta HCG values under 15,000 mIU/ml. Among the observed side effects were moderate pelvic cramps (20.9%), nausea (27%), fainting (4.8%); 61.3% of the women complained of fatigue. Heavy bleeding occurred in 15.3% of the women but only one of them required blood transfusion. In the patients with complete abortion, beta HCG values decreased to below 500 mIU/ml by Day 14 (but in 11 cases values fell below 2,000 mIU/ml only by Day 21). Plasma estradiol and progesterone also fell. Cortisol levels increased during therapy especially in subjects of Group I, but returned to basal values after termination of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortifacient Agents↗
PubMed1990

Cell death in relation to cell cycle in a mouse ascites tumor growing in vivo after combined treatment with cisplatin and 5-fluorouracil.

The interaction of 5-fluorouracil (5-FU) and cisplatin (CDDP) was studied in Bp8 ascites sarcoma cells growing in mice. By density gradient centrifugation in Percoll solution, non-viable cells were separated from viable cells. Single drug treatment with doses of 12 and 36 mg/kg body weight of 5-FU and 0.4 and 0.8 mg/kg body weight of CDDP did not yield non-viable cells during the time period studied (96 h). Combination of the drugs increased the non-viable cells to about 10-25% depending on the doses given. This indicates a supra-additive cytotoxic effect. Analysis of the distribution of viable cells in the different cell cycle phases by flow cytometry showed an accumulation of cells in the S-phase after 5-FU and in the S- and G2-phases of the CDDP or combined 5-FU-CDDP treatment. Similar analysis of non-viable cells showed a similar cell cycle distribution, which suggests that supra-additive cytotoxicity is not cell cycle specific. By labeling the DNA of the tumor cells with [125T]-deoxyuridine and using whole body measurement, the cell loss was studied. No changes in cells loss after single drug and combined treatment were found during the observation time. The molecular basis for the interaction between 5-FU and CDDP should be elucidated.

Animals↗
PubMed1989

[Chorionic villi sampling. Results with the first 500 samples].

531 chorionic villi forceps biopsies were carried out, to look for genetic diseases. Sampling was impossible in 24 cases (4.5%). The following indications were chosen: maternal age over 38 years: 361 cases; parental chromosome abnormality: 28 cases; previous history of chromosome abnormality: 21 cases; X-linked disease: 77 cases; metabolic disease: 32 cases; hemoglobinopathy: 7 cases; blood group determination: 5 cases. An elective abortion was carried out in 44 cases (8.7%), whereas 465 pregnancies were not interrupted. Full term has been reached in 327 pregnancies. The rate of miscarriage in this group is 3.9% (13 miscarriages out of 327 pregnancies followed). The results obtained at the Saint-Vincent-de-Paul Hospital show that the cytogenetic technique is reliable, and that the low risk of sampling allows its application in the diagnosis of chromosome anomalies.

Adult↗
PubMed1987

Effect of 5-fluorouracil on the cell growth and cell cycle kinetics of a mouse ascites tumor growing in vivo.

The effect of 12, 24 and 36 mg/kg body weight doses of fluorouracil (5-FU) on the Bp 8 ascites sarcoma growing in vivo was studied. From sequential studies of the total number of cells together with the composition of cells in the cell cycle, the cell cycle flow was calculated and correlated to the pharmacokinetics, which was determined by using 3H-5-FU. The dose of 12 mg/kg 5-FU affected cell growth between 24 and 72 hours, while the effect of higher doses was immediate. An early block in outflow of cells from G1 was followed by an increased outflow, indicating an early inhibition followed by an enhancement of the initiation of the DNA synthesis. This increased outflow from G1 together with the decrease in outflow from the early S-phase, i.e. decreased DNA synthesis, resulted in an accumulation of cells in the early part of the S-phase. The prolonged effects on the cell growth and the cell cycle flow despite the very fast decline in the drug concentration both in the ascites fluid and within the cells, together with a constant level of the drug in the macromolecular fraction, suggest an interaction between 5-FU and RNA/DNA at later times rather than an inhibition of the thymidylate synthetase activity.

Animals↗
PubMed1976

[Hyperthyroidism induced by iodine in an apparently normal thyroid gland. A new iatrogenic disease].

Iodine-induced thyrotoxicosis was reported to occur in patients with previously altered thyroid gland. Evidence is presented here from 23 cases that iodine-induced thyrotoxicosis may also occur in patients with no prior thyroid desorder and is characterized by: a) an almost undetectable 131I uptake, wich can be activated by TSH; b) a spontaneous improvement within a few weeks or months after withdrawing the high intake of iodine; c) the absence of any detectable thyroid abnormality after recovery.

Diagnosis, Differential↗