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P Bey

Publications and source records attributed to P Bey.

At least 73 records · Page 4Linked to original sources
PubMed1995

Detection of errors in individual patients in radiotherapy by systematic in vivo dosimetry.

We report 5 years of systematic measurements of the dose delivered to each patient undergoing radiotherapy treatment with photon beams in order to detect any systematic error that may have escaped the different checks performed at each step of planning and calculation prior to the first treatment session, or may have arisen during the set-up or the treatment delivery. For each patient the target-absorbed dose is derived from the entrance and exit doses measured by silicon diodes, on the beam axis at the patient's skin. Depending on the discrepancies observed between the measured and expected doses we have set decision levels for the corrective actions to be taken. In addition these measurements allow us to obtain information on the overall accuracy or on the quality of a specific treatment. During 5 years, 7519 patients have been measured and 79 errors were detected. Half could have induced a variation of over 10% in the dose delivered. Seventy-eight out of 79 errors were of human origin. As part of an overall quality assurance programme, it is of the utmost importance to check the dose delivered for each patient undergoing radiotherapy treatment in order to avoid systematic underdosing or overdosing.

Absorption↗
PubMed1995

Epidermoid carcinomas of the floor of mouth treated by exclusive irradiation: statistical study of a series of 207 cases.

PURPOSE: Our aim was to study the results and the complications of this series of 207 patients treated from 1976 to 1992 and to compare them with the results of the literature. MATERIAL AND METHODS: The treatment consisted of a combination of external beam irradiation (EBI) (to the tumor and the node areas) and complementary brachytherapy to the primary tumor in 105 cases. In 102 cases, brachytherapy only was delivered to the tumor with or without neck dissection of the node areas. The brachytherapy was performed mostly with the hairpin technique in the beginning (in 61 cases) and subsequently the plastic tube technique with iridium wires. The dosimetry followed the Paris system rules. There were 41% T1, 48% T2, 8% T3, 2% T4 and 1% Tx with 83% N0, 12% N1, 3% N2, 2% N3. Ninety-one percent of patients were male and 9% were female. RESULTS: The local control at 5 years is 97, 72 and 51%, respectively, for T1, T2, T3. The specific survival (without the patients dead of intercurrent disease or second cancer) was 88, 47 and 36%, and the overall survival at 5 years was 71, 42 and 35%. Of note, approximately one third of patients died of intercurrent disease or second cancers (70 patients = 34%). Significant factors that can influence the results are: for local control, the size of the lesion T1/T2/T3 (p < 0.0001); for the locoregional control, the absence of node involvement. The following factors are not significant: age and sex (age significant for survival). The significant treatment factors are the safety margin (p < 0.0003), brachytherapy only on T for T2N0 (p = 0.01). A total duration of treatment of less than 50 days is also significant. The spacing and the total dose (higher dose for large tumors) were not found to be significant. The complications were classified into four grades: grade 1, 17% (median healing, 2 months for soft tissue complications and 5 months for bone complications); grade 2, 12%; grade 3, 6% (frequently requiring surgical resection); grade 4, 0.5% (death, one case). In this series, for the complications, the dose rate, the spacing and the total dose were found not to be significant. CONCLUSION: Carcinomas of the floor of mouth treated by exclusive irradiation have a rather good prognosis and the number of grade 2 and 3 complications remains acceptable. Exclusive brachytherapy is preferable to the combination of EBI plus brachytherapy for T1T2N0.

Brachytherapy↗
PubMed1995

Radiosensitivity of multicellular tumour spheroids obtained from human ovarian cancers.

The radioresponsiveness of immunologically characterised (KL1, antivimentin and OC125) human ovarian carcinoma cells, obtained from effusions or solid tumours, was assayed in vitro using the multicellular tumour spheroids (MTS) three-dimensional model. Great interspecimen variabilities were observed in MTS doubling time (1.0-8.5 days), as well as in the doses inducing a 50% decrease in the MTS individual volume (ID50) (0.56-9.15 Gy), or in the overall population MTS number (SCD50) (1.9-15.7 Gy) and the residual/initial MTS individual volume ratio after 2 Gy irradiation (RSV2) (10-88%). The doubling time, DNA-ploidy and S-phase fraction did not correlate with the ID50. Significant correlations were found between the new parameters defined (RSV2 and ID50) and the SCD50, a well-accepted local control parameter. These parameters demonstrated their usefulness for studying the radiosensitivity of MTS prepared from human ovarian tumour biopsies.

Adult↗
PubMed1995

[Conformal radiation therapy. Fédération nationale des centres de lutte contre le cancer (FNCLCC)].

The authors present the summary of a workshop of a group of radiation oncologists and radiation physicists on three dimensional treatment planning and conformal radiation therapy with multileaf collimator. It appears that this technic must be considered as experimental and that it cannot be promoted in all radiotherapy departments without scientific and clinical evaluation.

Evaluation Studies as Topic↗
PubMed1994

Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active PG-Val-Pro-Val pentafluoroethyl ketones.

Valylprolyvalyl pentafluoroethyl ketones with different N-protecting groups were evaluated in vitro and in vivo as inhibitors of human neutrophil elastase (HNE). Several of these compounds were found to be orally active in HNE-induced rat and hamster lung hemorrhage models. The compound with 4-(4-morpholinylcarbonyl)benzoyl as the protecting group, 71 (MDL 101,146), was studied in greater detail. Hydration and epimerization studies were performed on 71 and related compounds in various media, including human blood serum. High-performance liquid chromatography studies on a reversed-phase system as a measure of the lipophilicity of 71 and related compounds revealed a small range of relative retention times wherein the orally active compounds fell. The Ki value determined for 71 vs HNE was 25 nM.

Administration, Oral↗
PubMed1994

Influence of tumoral, radiobiological, and general factors on local control and survival of a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam irradiation+brachytherapy or brachytherapy alone)

PURPOSE: To evaluate statistically the factors influencing the therapeutic results. METHODS AND MATERIALS: A statistical study was carried out concerning 361 patients treated from 1977 to 1991 for velotonsillar carcinoma. They received either brachytherapy alone (18) or a combination of external beam irradiation and brachytherapy (343 patients) using an afterloading iridium technique in plastic tubes. The distribution of patients according to the localization was: 128 tonsils, 134 soft palates, 9 posterior pillars, 63 anterior pillars, and 27 glossotonsillar sulcus. The patients were staged as follows: 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3, and 9 Nx. RESULTS: The results at 5 and 10 years show: local control 80% and 74%, locoregional control 75% and 70%, overall survival 53% and 27%, specific survival 63% and 52%, respectively. The univariate study shows at 5 years a better local control for T1T2 (87%) compared with T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (55%) with p = 0.002. This is the same for the overall survival (59% vs. 42%, p = 0.002). Tumors with an extension to the mobile tongue or the base have a poor prognosis (p < 0.002). The radiobiological factors show less recurrences if the total duration of the treatment is < 55 days, the number of days between External Beam Irradiation and brachytherapy is < 20. The security margin seems important also. CONCLUSIONS: For the combination external irradiation and brachytherapy, the multivariate study for local control shows that ony T, localization, and the total duration of treatment are significant. For complications, classified into four grades, only the dose rate is significant.

Adult↗
PubMed1994

The study of tumoral, radiobiological, and general health factors that influence results and complications in a series of 448 oral tongue carcinomas treated exclusively by irradiation.

PURPOSE: Our aim was to study the different factors that influence the results and complications in a series of 448 carcinomas of the oral tongue treated from January 31, 1972 to December 31, 1986, by brachytherapy (Br) +/- neck dissection (181 cases) or combination of external beam irradiation and brachytherapy (EBI + Br) (267 cases). METHODS AND MATERIALS: The patients distribution (TNM classification 1979) was: 125 T1, 186 T2, 128 T3, 9 T4Tx, 78% N0, and 22% N+. We used guide gutter or plastic tubes technique (Paris system dosimetry). Results at 5 and 10 years are: local control 68% and 64%, locoregional control 58% and 53%, specific survival 45% and 39%, and overall survival 44% and 27%. RESULTS: In the univariate analysis for local control (LC) and overall survival (OS), we considered the tumoral factors. At 5 years, the LC for T1, T2, T3 are 93%, 65%, and 49%, and the OS 69%, 41%, and 25%, respectively (p < 0.002). The lesions of the undersurface of the tongue have a better LC (77%) than other localizations (64%) (p = 0.02). For general factors, the index of general health condition, age, and sex were not significant for LC, but proved significant for OS (p = 0.01). Significant radiobiological factors: the safety margin (expressed by the ratio treated surface on tumoral surface > or = 1.2) is significant for LC and OS. This is the same if the interval between EBI and Br is < or = 20 days. Neither the dose rate, the spacing between the sources, the total dose, nor Br dose were significant, but the last two were adapted according to the infiltration. In the univariate study for grade 2 and 3 complications (tissue and bone), the surface treated (> 12 cm2), and the dose rate > 0.7 Gy/h were significant. CONCLUSION: The multivariate study showed that the small size of the lesion is the most important factor for local control, with brachytherapy alone for T1T2N0 and the number of days between EBI and brachytherapy < or = 20 days. For the complications, the most important factors are the total dose > 80 Gy and a treated surface > 12 cm2.

Adult↗
PubMed1994

Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: results in 73 cases.

PURPOSE: The salvage brachytherapy performed in patients presenting velotonsillar carcinoma in a previously irradiated field is evaluated in terms of local control, complications and survival. METHODS AND MATERIALS: Between 1976 and 1990, 73 patients presenting with velotonsillar squamous cell carcinoma in a previously irradiated area were treated at Center Alexis Vautrin with brachytherapy along using an 192Ir implant (afterloading technique) with curative intent. According to the UICC 1987 TNM classification, there were 45 T1 N0, 20 T2 N0, one T3 NO, one T3 N2 and six Tx Nx. RESULTS: The 5-year actuarial local control for T1 N0 and T2 N0 are 80% and 67% respectively. The regional relapse rate was 10% in both groups. Grade 2 complications occurred in 13% of patients and these were neither related to the volume treated nor the dose rate. There were no Grade 3 or 4 complications. The 5-year specific survival is 64%, with a plateau after the 5th year, but the 5-year overall survival is only 30%. Fourty-two percent of the patients in this series died from another carcinoma. All but two of these were related to continued alcohol and tobacco intoxication. CONCLUSION: We conclude that brachytherapy alone (60 Gy) is optimal treatment for patients presenting with velontonsillar carcinoma in a previously irradiated field. The greatest challenge is the screening of these patients and the prevention of subsequent head and neck cancers. Recognizing the fact that these patients are at high risk for subsequent malignancies of upper aerodigestive tract, lung and esophagus, close surveillance is necessary for: (a) early diagnosis and prompt treatment; and (b) development of prevention strategies of field cancerization.

Aged↗
PubMed1994

Radiotherapy in the SIOP (International Society of Pediatric Oncology) nephroblastoma studies: a review.

For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral tumors of standard histology and free of metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less ruptures, lower stage) of preoperative radiation and actinomycin D (AMD) in SIOP-2, with all children having radiation therapy either preoperatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative radiation therapy and AMD were compared with preoperative chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined.

Adolescent↗
PubMed1994

Haloallylamine inhibitors of MAO and SSAO and their therapeutic potential.

Based on mechanistic understandings, molecular modeling and extensive quantitative structure-activity relationships, appropriately substituted haloallylamine derivatives were designed as potential mechanism-based inhibitors of MAO and/or SSAO. Potent inhibition of MAO-B and SSAO occurred with fluoroallylamines whereas chloroallylamines, such as MDL 72274A ((E)-2-phenyl-3-chloroallylamine hydrochloride), were selective and potent inhibitors of SSAO. MDL 72974A (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride is a potent (IC50 = 10(-9) M) inhibitor of both MAO-B and SSAO, with 190-fold lower affinity for MAO-A. In clinical studies, oral doses as low as 100 micrograms produced substantial inhibition of platelet MAO-B. Essentially complete inhibition occurred at 1 mg with the effect lasting 6-10 days. One or 4 mg MDL 72974A given daily for 28 days to 40 Parkinson's patients treated with L-dopa produced statistically significant reductions in the Unified Parkinson's Disease Rating Scale. MAO-B inhibitors, such as MDL 72974A and L-deprenyl, offer the potential of being neuroprotective in Parkinson's Disease and other neurogenerative disorders. Concommitant inhibition of SSAO may provide additional, but as yet unproven, advantages over pure inhibitors of MAO-B.

Allyl Compounds↗
PubMed1993

A glossary for reporting complications of treatment in gynecological cancers.

Reporting and scoring treatment complications in gynecological cancers is difficult because of the variety of normal tissues, anatomical structures and treatment disciplines involved, making it impossible to compare series of patients treated in different institutions even with the same strategy. An international group of experts (gynecologists, radiotherapists and surgeons) developed a multidisciplinary database to identify, score and report early and late normal tissue damage regardless of treatment strategy. The principles involve: (1) The identification of relevant organs and tissues; (2) An accurate definition of the type and score of each complication; (3) Reporting combinations of complications of various degrees; (4) A computerized format for data acquisition, update and retrieval. In the present version, the "Glossary" describes five degrees of increasing severity (0 to 4) in 14 organs and/or normal tissues. The rationale of the glossary leaves it open for as yet undescribed types of complications. This paper contains the definition and scoring for each type of complication, general guidelines for their use.

Databases, Factual↗
PubMed1993

An alternative mechanism for the inhibition of cholesterol biosynthesis in HepG2 cells by N-[(1,5,9)-trimethyldecyl]-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta-ol (MDL 28,815).

Compounds that block hepatic cholesterol biosynthesis and secretion may be useful hypocholesterolemic agents. N-[(1,5,9)-trimethyldecyl]-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta-ol (MDL 28,815) has been shown to block cholesterol biosynthesis in 3T3 fibroblasts and it causes cellular accumulation of squalene 2,3-epoxide and squalene 2,3:23,24-diepoxide (squalene epoxides), which suggests that it inhibits 2,3-oxidosqualene cyclase. The purpose of the present report was to determine whether MDL 28,815 acts only at the level of 2,3-oxidosqualene cyclase or whether other enzymes in the cholesterol biosynthetic pathway are affected. HepG2 cells, grown in lipoprotein-deficient serum, were incubated with MDL 28,815 and 14C-acetate to radiolabel cholesterol and the intermediates in the cholesterol biosynthetic pathway. Blockade of cholesterol biosynthesis by MDL 28,815 in these cells was associated with the accumulation of two metabolites, one of which was 5 alpha-cholest-8-en-3 beta-ol. The other metabolite was identified by a combination of ultraviolet spectrometry, gas chromatography, mass spectroscopy and analytical high-performance liquid chromatography as 5 alpha-cholest-8,14-dien-3 beta-ol. Maximal blockade of cholesterol biosynthesis was associated with the accumulation of these two metabolites and, in particular, 5 alpha-cholest-8,14-dien-3 beta-ol, rather than with squalene epoxides. These results suggest that MDL 28,815 blocks cholesterol biosynthesis primarily by the inhibition of sterol-delta 14-reductase, and possibly sterol-delta 8-ene isomerase, rather than 2,3-oxidosqualene cyclase.

Animals↗
PubMed1993

MDL 72,974A: a selective MAO-B inhibitor with potential for treatment of Parkinson's disease.

MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride] was designed to be a selective, mechanism-based irreversible inhibitor of monoamine oxidase type B (MAO-B). The compound is a potent, selective MAO-B inhibitor in vitro and in vivo. In vitro studies revealed an IC50 value (MAO-B) of 3.6 nM with 189-fold selectivity compared to MAO-A. In rats, profound inhibition of MAO-B was achieved after a single oral dose with an ED50 of 0.18 mg/kg; a dose 44 times this amount was required to inhibit MAO-A by 50%. Selectivity was maintained following chronic dosing. MDL 72,974A had minimal sympathomimetic effects and did not potentiate the cardiovascular effects of tyramine, even at 50 times the MAO-B inhibiting dose. This inhibitor was equally effective and well-tolerated in man. In human volunteers, potent inhibition of platelet MAO-B activity was observed at submilligram doses (ED50 = 90 micrograms) following a single oral dose. Upon multiple oral doses of 100 micrograms, as much as 80% of MAO-B could be inhibited. In phase II studies, MDL 72,974A is proving to be a useful adjunct to conventional therapy. Patients (250) with Parkinson's disease, treated once daily with either 1 or 4 mg, together with L-Dopa and a decarboxylase inhibitor (MadoparR or SinemetR), saw significant improvements in symptoms compared with those on standard therapy without the inhibitor.

Allyl Compounds↗
PubMed1992

Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites.

Mouse ornithine decarboxylase (ODC) was expressed in Escherichia coli and the purified recombinant enzyme used for determination of the binding site for pyridoxal 5'-phosphate and of the residues modified in the inactivation of the enzyme by the enzyme-activated irreversible inhibitor, alpha-difluoromethylornithine (DFMO). The pyridoxal 5'-phosphate binding lysine in mouse ODC was identified as lysine 69 of the mouse sequence by reduction of the purified holoenzyme form with NaB[3H]4 followed by digestion of the carboxymethylated protein with endoproteinase Lys-C, radioactive peptide mapping using reversed-phase high pressure liquid chromatography and gas-phase peptide sequencing. This lysine is contained in the sequence PFYAVKC, which is found in all known ODCs from eukaryotes. The preceding amino acids do not conform to the consensus sequence of SXHK, which contains the pyridoxal 5'-phosphate binding lysine in a number of other decarboxylases including ODCs from E. coli. Using a similar procedure to analyze ODC labeled by reaction with [5-14C]DFMO, it was found that lysine 69 and cysteine 360 formed covalent adducts with the inhibitor. Cysteine 360, which was the major adduct accounting for about 90% of the total labeling, is contained within the sequence -WGPTCDGL(I)D-, which is present in all known eukaryote ODCs. These results provide strong evidence that these two peptides form essential parts of the catalytic site of ODC. Analysis by fast atom bombardment-mass spectrometry of tryptic peptides containing the DFMO-cysteine adduct indicated that the adduct formed in the enzyme was probably the cyclic imine S-(2-(1-pyrroline)methyl)cysteine. This is readily oxidized to S-((2-pyrrole)methyl)cysteine or converted to S-((2-pyrrolidine)methyl)cysteine by NaBH4 reduction. This adduct is consistent with spectral evidence showing that inactivation of the enzyme with DFMO does not entail the formation of a stable adduct between the pyridoxal 5'-phosphate, the enzyme, and the inhibitor.

Amino Acid Sequence↗