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Biomedical subjects

P Bey

Publications and source records attributed to P Bey.

At least 163 records · Page 9Linked to original sources
PubMed1978

Analogues of ornithine as inhibitors of ornithine decarboxylase. New deductions concerning the topography of the enzyme's active site.

Fourteen structural analogues of ornithine were synthesized and evaluated as inhibitors of preparations of the enzyme L-ornithine carboxylase (ODC) (E.C. 4.1.1.17) obtained from rat liver, rat hepatoma cells in culture, or bull prostate. The synthesis of these compounds was achieved either via a Bucherer type reaction or via alkylation of carbanions derived from ethyl acetamidocyanoacetate, methyl isocyanoacetate, benzyl alpha-isocyanopropionate, methylbenzaldimine alanate, and the azlactone derivative of ornithuric acid. (+)-alpha-Methylornithine, which was assigned the L configuration on the basis of rotational criteria, was found to be the most potent reversible inhibitor of ODC among the synthesized compounds. From the degree of inhibition of ODC activity in the presence of the various ornithine analogues, it has been possible to delineate some of the structural features of the substrate L-ornithine which are required for binding to the mammalian ODC active site.

Animals↗
PubMed1976

Alpha-methyl ornithine, a potent competitive inhibitor of ornithine decarboxylase, blocks proliferation of rat hepatoma cells in culture.

A biphasic increase of putrescine concentration occurs in rat hepatoma tissue culture cells induced to proliferate. DL-alpha-Methyl ornithine, a competitive inhibitor of ornithine decarboxylase ( L-ornithine carboxylyase, EC 4.1.1.7) of hepatoma tissue culture cells, blocks the usual increases of putrescine and spermidine concentrations in these cells, and causes a rapid fall in the levels of putrescine which is followed by a striking decrease of spermidine. In parallel with the depletion of these amines, incorporation of [3H]thymidine into DNA and cell proliferation are inhibited. Addition of putrescine, spermidine, or spermine results in an immediate resumption of cell proliferation. Cell proliferation is also restored by L-ornithine presumably due to in situ competitive inhibition of ornithine decarboxylase. These findings of hepatoma tissue culture cells support the concept that polyamines play an essential function in the cell division processes.

Cell Division↗
PubMedDate not supplied

[Comparative dosimetry study of two methods of intensity modulation performed on the same accelerator].

Intensity modulated radiation therapy (IMRT) is an advanced method of conformal radiotherapy. It permits optimal dose distribution to the target volume while preserving surrounding normal tissues. IMRT, with a multileaf collimator, can be realised in two different ways: either the segmented mode, which consists of combining small elementary static field, or the dynamic mode, which consists of moving the leaves while irradiating. The purpose of this work was to study these two methods of modulation on a Varian linear accelerator equipped with a collimator consisting of 40 pairs of one-centimetre-wide leaves. The measurements, obtained by using a diode array, showed that the quality of the irradiation in the dynamic mode does not depend on either the dose rate or the duration of the irradiation. In the segmented mode, weak magnitude segments are preferable, but increase the errors in the delivered dose. Comparisons of various profiles showed that the measured profiles are consistent with those programmed. Both modes seem to be equivalent for step-shaped profiles. In the case of profiles with constant slope, the segmentation generated by the segmented method deteriorates the profile. Even though the choice of technique is strongly dependent on the material available, the dynamic mode presents greater flexibility of use and has been chosen in our institution for IMRT.

Calibration↗
PubMedDate not supplied

[Conformal radiotherapy of prostatic cancer: a general review].

Recent progress in radiotherapeutic management of localized prostate cancer is reviewed. Clinical aspects--including dose-effect beyond 70 Gy, relative role of conformal radiation therapy techniques and of early hormonal treatment--are discussed as well as technical components--including patient immobilization, organ motion, prostate contouring, beam arrangement, 3-D treatment planning and portal imaging. The local control and biological relapse-free survival rates appear to be improved by high dose conformal radiotherapy from 20 to 30% for patients with intermediate and high risk of relapse. A benefit of overall survival is expected but not yet demonstrated. Late reactions, especially the rectal toxicity, remain moderate despite the dose escalation. However, conformal radiotherapy demands a high precision at all steps of the procedure.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

[Conformal radiotherapy in cancer of the upper aerodigestive tract].

The outcome of head and neck malignancies is closely related to the achievement of local tumor control. The occurrence of severe late complications is the consequence of the anatomic vicinity between dose-limiting normal tissues and the tumor, thus reducing the curative potential of radiotherapy. Conformal radiotherapy is presently actively investigated as a way to improve the dose distribution in head and neck malignancies (especially when originating from the nasopharynx or the sinuses) while protecting healthy organs. Such an approach requires a chain of sophisticated procedures, including efficient quality assurance programs, in order to achieve the proper degree of safety. The relatively limited clinical studies published to-date have already confirmed the advantage of conformal radiotherapy in terms of dose delivery. The development of beam intensity modulation is likely to further contribute to the improvement of the therapeutic ratio.

Adult↗
PubMedDate not supplied

[Practical determination of volume and doses in conformal radiotherapy].

The determination of the target volumes and the dose to be delivered are critical medical steps in order to locally control the disease and to limit the risks of normal tissues injury. While many clinical situations are compatible with standardised technique and beam arrangements, the tools provided by modern medical diagnostic imaging procedures and tridimensional dosimetry allow an improved conformation of the irradiated volume and the administered dose to the clinical target volume. However, this approach requires an increased precision in tumour and normal tissues delineation, based on patient immobilisation devices, standardisation of mobile organs repletion status and image acquisition procedures, explicit definition of the biological and physical safety margins, definition of acceptable levels of dose heterogeneity in the planning target volume and appropriate quality assurance procedures.

Dose-Response Relationship, Radiation↗
PubMedDate not supplied

[Radiotherapy of stage T1-T2 M0 prostatic adenocarcinoma. Analysis of the carcinologic results of a multicenter study of 610 patients. Groupe Radiothérapie de la Commission de Coopération Médicale Intercentres (CCMI)].

PURPOSE: Retrospective analysis of the results of radiotherapy in localized prostatic adenocarcinoma. Complications were excluded. PATIENTS AND METHODS: Six-hundred-and-ten T1-T2 adenocarcinomas of the prostate were treated with continuous courses of external beam radiation therapy in 19 participating Institutes between January 1983 and January 1988. The mean follow-up was 10.4 years; the mean age of patients at the beginning of radiotherapy was 68.5 years. RESULTS: A 10-year, local control had been achieved in 86% of T1-T2 (81.4% for T2). The 5- and 10-year metastatic relapse rates were 25.3% and 30% (29% and 38.1% for T2), respectively. At 10 years, 62.4% of T1-T2 were recurrence-free; overall survival rate was 45.8% and cause-specific survival rate was 70.5%; 29.9% of T1-T2 patients were alive and disease-free. T category (TNM), pathologic grade, pelvic lymph node status, local tumor control, and obstructive ureteral symptoms were correlated with survival. The influence of pelvic nodes radiation, dose, overall treatment time, previous endocrine treatment, and transuretral resection was not significant for disease-free survival (alive and disease-free) and other endpoints. CONCLUSION: There was no difference between the French series (1975-1982 and 1983-1988). The results of the literature are comparable to ours. As far as prognostic factors are concerned, this report provides evidence that the explainable variables which influence survival depend on the tumor and patient status.

Adenocarcinoma↗
PubMedDate not supplied

[Tolerance and role of irradiation in the treatment of epithelial cancer of the ovary].

PURPOSE: In a retrospective analysis, our aim was to evaluate the immediate tolerance and the early and late complications of abdomino-pelvic radiotherapy in the Centre Alexis-Vautrin (France). PATIENTS AND METHODS: From 1st January 1983 to 31st December 1993, 117 patients were treated at Centre Alexis Vautrin in Nancy for epithelial ovarian cancer by abdominal and/or pelvic irradiation after surgery. They were aged from 24 to 85 with a median of 56 years. There were ten patients with stage I (9%), 28 patients with stage II (24%), 60 patients with stage III (61%) and 19 patients with stage IV (16%) disease. Results of surgery were determined as follows: satisfactory with absence of tumoral residuum in 26% cases (30 patients) and with residuum inferior to 20 mm in 46% cases (52 patients; incomplete in 26% cases (31 patients) either because of residuum superior in 20 mm and/or incomplete surgery; and not evaluable in 3% cases (four patients). Seventy-seven patients were sent to the Centre for postoperative treatment (66% patients of the series), 48 of them (62.4%) after non-satisfactory surgery, 29 after satisfactory surgery (37.6%). Chemotherapy was administered to only 104 patients (89% cases), and contained platinum salts and cyclophosphamid for 87% of these patients. Fourteen patients (12%) received a single irradiation dose after surgery: three in stage I, three with poor evaluation of the disease in the initial stage, three with medical contraindications to chemotherapy treatment, six with contraindications due to advanced age (?? Makes 15 ). Histologically, 46% of patients had a serous adenocarcinoma, 9% a mucinous adenocarcinoma, 11% an endometrioid adenocarcinoma, 2% a clear cell adenocarcinoma, 1% an undifferentiated adenocarcinoma, and 31% an epithelial carcinoma without any other indication. The histological grade which was recently introduced was rarely indicated. Complementary radiotherapeutic treatment consisted of pelvic irradiation for 14 patients (12%), abdomino-pelvic irradiation for 63 patients (54%), and total abdominal irradiation with a pelvic boost for 40 patients (34%). RESULTS: The immediate tolerance to irradiation can be considered as globally satisfactory since 9% of the patients (ten cases) had no problems and 64% of the patients developed a minor intolerance easily controlled by symptomatic treatments. There were also digestive complications: nausea, vomiting and diarrhea for 66% of the patients (50 cases); to a lesser extent, 20% of the cases experienced associated digestive and hematological complications (15 patients); 9% isolated hematological troubles such as anemia (seven patients); 4% digestive complications (three patients) and 1% hematological and urinary digestive troubles (one patients). Late irradiation sequelae were evaluated for 89 patients with a follow-up lasting from 4 months to 11 years. Sixty-six patients had no sequelae, eleven patients had minor tolerability problems--mainly digestive for more than half of them. Five patients presented severe complications, including hematological problems such as chronic thrombopenia in two cases, urinary-problems in two other cases, and one patient presented with a case of histologically proven malabsorption. Two patients presented major problems; one case of radic cystitis and one of radic bowel. Two patients died of iatrogenic causes: one of induced leukemia, the other of treatment-induced digestive and renal complications. The overall survival rate was 30% at 5 years and 22% at 10 years. It was 90% at 5 and 10 years for stage I patients, 60% at 5 years and 30% at 10 years for stage II patients, 22% at 5 years and 8% at 10 years for stage III patients, and finally 10% at 5 years for stage IV patients. CONCLUSION: In this retrospective analysis of 117 epithelial ovarian cancers, treated over 10 years and which all received pelvic and/or abdominal irradiation, we can conclude that this treatment is globally well tolerated and that it yields a

Adenocarcinoma↗
PubMedDate not supplied

[Low-dose postoperative vaginal brachytherapy of adenocarcinoma of the endometrium].

PURPOSE: Surgery is the primary treatment for endometrial carcinoma. Methods of complementary treatment are still debated, with the potential association of external radiotherapy and/or brachytherapy before or after surgery. This study was aimed at evaluating local control and complications rates in a series of patients treated by hysterectomy followed by postoperative vaginal low-dose rate brachytherapy (BT) combined with pelvic irradiation in case of poor prognosis factors. PATIENTS AND METHODS: From 1978 to 1993, 101 patients were treated at the Centre Alexis-Vautrin, France according to this scheme. Forty five had deep myometrial invasion, and thirteen cervical involvement. Fifty patients received pelvic irradiation (median dose 46 Gy) combined with BT (dose 14 Gy, median volume 127 cm3); 51 patients had BT alone (dose 60 Gy, median volume 71 cm3). RESULTS: The 5-year overall survival rate was 83% and the local control rate 97% with a median follow-up of 7 years. Multivariate analysis showed two factors of bad prognosis, i.e., deep myometrial invasion and cervical involvement. Three severe complications occurred in two patients for whom the treated volume was larger than the theoretical target volume. Eleven patients developed metastases. CONCLUSION: Results obtained from this series are comparable with those of previous studies, particularly in regard to pre-operative BT. The complication rate is also satisfactory and depends on the irradiation precision and the definition of the target volume.

Adenocarcinoma↗
PubMedDate not supplied

Preliminary technical, experimental and clinical results of the use of the HPLR 27 system for the treatment of deep-seated tumours by hyperthermia.

Based on the theoretical deep penetration of radio frequencies, we have developed several 27.12 MHz ridged wave guides, with large apertures, and filled with circulating deionized water. Different low impedance matching networks have been tested and a 0-800 W power generator has been designed for this particular clinical use. This can be driven easily by a microcomputer which is used to regulate the temperature at depth by varying the sequencing time and/or by adjusting the RF power. The complete system, known as HPRL 27, is manufactured by Sairem Ets. Studies of the spatial power density distributions show a relatively homogeneous RF field for an aperture greater than 30 X 14 cm. Preliminary heating patterns studied in phantoms indicate the possibility of treating volumes greater than 2000 cm3 within the 50 per cent isotherm. Maximum heating is observed between 2 and 5 cm deep with passive cooling, and between 3 and 6 cm deep with active cooling, in which case the 50 per cent isotherm is situated between 2 and 10 cm deep. Preliminary phase I clinical results on 20 patients with pelvic or thoracic carcinomas show the possibility of heating deep-seated tumours to above 42 degrees C with a good patient tolerance. Temperature is controlled by implantable catheters or in the case of pelvic heating, by inserting catheters into the vagina, the rectum and the bladder. This new device is well adapted for the treatment of pelvic tumours.

Aged↗