RESUMO
Both alpha- and beta-adrenergic receptors have been identified in human myometrium by radioligand binding. Both types of receptors mediate uterine contractility: alpha-adrenergic agonists cause uterine contraction, whereas beta-adrenergic agonists induce relaxation. We studied the possible regulatory effects of gonadal steroids on the affinity, concentration, subtype distribution, and linkage to adenylate cyclase of beta-adrenergic receptors in human myometrium removed during different phases of the menstrual cycle, from postmenopausal women and during depo-progestin (medroxyprogesterone acetate) therapy. We identified beta-adrenergic receptors in human myometrial membranes using the radiolabeled antagonist (--)-[3H]-dihydroalprenolol (DHA). The binding of this radioligand was rapid, reversible, of high affinity (KD = 0.71 nM) and stereo-selective. Total beta-receptor concentration was determined by Scatchard analysis of DHA saturation binding and the ratio of receptor subtypes determined by computer-assisted analysis of beta 2 selective antagonist ICI 118 551/DHA competition binding curves. The fraction of receptors functionally coupled to adenylate cyclase was determined by the agonist/N-ethylmaleimide inactivation method. The affinity of DHA and the fraction of receptors undergoing functional coupling was similar under all hormonal conditions. However, whereas the net concentration of beta-receptors was the same in all groups, beta 1-adrenoreceptors could only be detected in myometrial particulate fractions from uteri obtained in the midfollicular phase, indicating the importance of considering adrenoreceptor subtypes as separately regulatable receptors.
Assuntos
Fase Folicular , Miométrio/metabolismo , Receptores Adrenérgicos beta/análise , Antagonistas Adrenérgicos beta/metabolismo , Ligação Competitiva , Computadores , Di-Hidroalprenolol/metabolismo , Feminino , Humanos , Técnicas In Vitro , Propanolaminas/metabolismo , Ensaio RadioliganteRESUMO
Adrenergic receptors have been shown to be involved in uterine contractility. alpha-Adrenergic receptors cause uterine contraction, whereas beta-adrenergic receptors induce relaxation. In animals, myometrial alpha-adrenergic receptors are regulated by gonadal steroids. We have identified alpha 1- and alpha 2-adrenergic receptors in myometrial membranes using the newly developed radiolabeled specific antagonists [3H]prazosin and [3H]rauwolscine. This allowed characterization of both receptor subclasses individually and study of them in various physiological and pharmacological conditions in the human, i.e. during different phases of the menstrual cycle, in postmenopausal women, term pregnancy, and during depo-progestin (medroxyprogesterone acetate) therapy. The affinity and number of alpha 1-adrenergic receptors were unchanged in all conditions, whereas the number of alpha 2-adrenergic receptors increased concomitantly with circulating plasma estradiol levels. However, this latter effect was counteracted by progesterone. These results are an example of the heteroregulation of membrane receptors by estrogens and progesterone and throw new light on the regulatory mechanisms involved in uterine contractility in the human.
Assuntos
Estrogênios/fisiologia , Miométrio/metabolismo , Progesterona/fisiologia , Receptores Adrenérgicos alfa/metabolismo , Ligação Competitiva , Estradiol/sangue , Feminino , Humanos , Medroxiprogesterona/análogos & derivados , Medroxiprogesterona/uso terapêutico , Acetato de Medroxiprogesterona , Menopausa , Menstruação , Prazosina/metabolismo , Gravidez , Estereoisomerismo , Ioimbina/metabolismoRESUMO
PURPOSE: A modified teletherapy unit to achieve total body irradiation with a vertical beam in a conventional treatment room. METHODS AND MATERIALS: A standard 60C teletherapy unit has been modified to achieve total body irradiation with a vertical beam in a conventional treatment room. Patients are treated in prone and supine positions. Removal of the adjustable collimator assembly of this standard machine provides a circular field of 196 cm in diameter at 167 cm from the source. Second, the machine has been elevated by about 50 cm on a metallic base to enlarge irradiation field to obtain 248 cm in diameter at 210 cm from the source, and to encompass tall patients under better conditions. A special lead conical beam flattening filter, 10-mm thick at the center, was designed to compensate the spatial inhomogeneity of the beam. An instantaneous dose rate of 6.10(-2) Gy/min is attained at the L4 level (midplane) in an average 20-cm thick patient with a source activity of 5099 RHM (air kerma rate of 44.8 Gy.h-1.m2). Between February 2, 1984 and December 27, 1990, 244 total body irradiations were performed either by single dose (n = 69, 10 Gy were given to midplane at L4 level in about 6 to 8 h, 8 Gy to the lungs), or by fractionated dose (n = 175, 12 Gy were given in 6 fractions over 3 consecutive days to midplane at L4 level, 9 Gy to the lungs). RESULTS: The dose distribution is similar than the ones obtained by a linear accelerator with patients lying on their sides. CONCLUSION: Patients were treated in a comfortable and highly reproductible position. Organ shielding was easily achievable. This could be a less expensive and reasonable alternative to linear accelerator.
Assuntos
Radioisótopos de Cobalto/uso terapêutico , Teleterapia por Radioisótopo/instrumentação , Irradiação Corporal Total/instrumentação , Desenho de Equipamento , Humanos , Proteção Radiológica , Teleterapia por Radioisótopo/métodos , Irradiação Corporal Total/métodosRESUMO
Chordomas are rare malignant neoplasms representing less than 3% of all primary bone tumors. They usually have a benign histological appearance and a slow growth rate. Their locoregional progression nearly always causes suffering and eventually death. Efforts to increase local control have included aggressive surgery, radiation therapy or combined approaches but locally free survival rates remain relatively low and have not exceeded 30% at 5 years. Sacrococcygeal chordomas, which represent approximately 50% of the localizations, have been investigated less frequently than those at the base of the skull or cervical region with primary or post-operative radiation therapy. The disappointing results with photon therapy in a multimodality approach and the good results reported by Schoenthaler with charged particles in the Lawrence Berkeley laboratory led us to propose fast neutron therapy in the management of inoperable or recurrent sacrococcygeal chordomas. Preliminary results obtained from only 12 patients indicate that high linear energy transfer (LET) therapy seems to be a good alternative for radical treatment of chordomas in the case of microscopic or macroscopic residual tumor.
Assuntos
Cordoma/radioterapia , Neoplasias Pélvicas/radioterapia , Cordoma/mortalidade , Humanos , Transferência Linear de Energia , Neoplasias Pélvicas/mortalidade , Região Sacrococcígea , Taxa de SobrevidaRESUMO
Osteopetrosis was induced in lethally irradiated normal rats by cell infusion prepared from spleens of the osteopetrotic (op) mutant littermates. However, similar attempts to induce osteopetrosis in another strain of osteopetrotic rats, namely the "toothless" (tl) rats, were unsuccessful. This discrepancy between op and tl rats with regard to the transmission of the disease to normal littermates, parallels the response of the respective mutants to treatment by normal bone marrow cells: the op rat is cured, not the tl rat. The present findings confirm the cellular origin of osteopetrosis in the op rat, whereas the origin of the defect in the tl mutant remains obscure.
Assuntos
Osteopetrose/genética , Ratos Mutantes/genética , Animais , Feminino , Masculino , Osteopetrose/etiologia , Osteopetrose/patologia , Ratos , Baço/transplanteRESUMO
The purpose was to evaluate the use of the CT option for simulator during a 14-month period in the radiotherapy department. The CT option has been adapted on the Philips simulator SL23. The virtual tunnel diameter is 92 cm which allows slice acquisition regardless of the contention device used. This system is connected to the treatment planning system through an Ethernet link. Three fields of view are available which cover the standard radiotherapy use. Four hundred and twenty-seven patients benefited from this system over a 14-month period of use. The number of slices acquired per patient regularly increased. The use of the system was rapidly extended to all the standard treatments. Those slices were also used as additional information for these high technology treatments. The good quality of the images and the reliability of this system involved a rapid integration in the treatment preparation procedure. It will not replace the use of the scanner but will significantly improve the treatment quality.
Assuntos
Simulação por Computador , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X , Estudos de Avaliação como Assunto , França , Humanos , Serviço Hospitalar de Radiologia , Radiometria , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricosRESUMO
Dosimetry studies, employing a model, were conducted under the technical conditions established by one of the authors for exploration of the infant and child pelvis during diagnosis and treatment of congenital dislocation of the hip. Based on this data, it was confirmed that the dose applied to the various organs of a patient can be evaluated by using a relation identical to that employed for calculating the dose during radiotherapy. The results measured experimentally or calculated from the proposed formula, were comparable to those in the published literature. This method of dose assessment is valid not only in pediatric radiology, and whatever the region explored, but also for radiodiagnosis in adults.
Assuntos
Pelve/diagnóstico por imagem , Doses de Radiação , Adolescente , Criança , Pré-Escolar , Feminino , Luxação Congênita de Quadril/diagnóstico por imagem , Humanos , Lactente , Masculino , Manequins , Métodos , Ovário/efeitos da radiação , Radiografia , Pele/efeitos da radiação , Testículo/efeitos da radiaçãoRESUMO
OBJECTIVE: To assess the accuracy of a single cervical fetal fibronectin test to predict spontaneous preterm delivery in an unselected antenatal population. DESIGN: A prospective blind cohort study. SETTING: Antenatal clinic of a teaching hospital in a Brussels semiurban area. PARTICIPANTS: An unselected group of 170 women followed at the antenatal clinic. METHODS: A single cervical sample was obtained between 24 and 33 completed weeks of pregnancy. The fibronectin test was compared with clinical evaluation and their predictive properties were assessed. RESULTS: Fifteen women were excluded from the analysis because of elective preterm delivery for medical indications or loss to follow up. Of the 155 remaining women, nine (7%) had a spontaneous preterm delivery. For a single fetal fibronectin test, the sensitivity was 26.7%, the specificity 95.7%, and the positive and negative predictive values 40.0% and 92.4%, respectively. The likelihood ratio of a positive was similar to that of clinical predictors of preterm birth (LR = 6.2; 95% CI 2.0-19.6). Sensitivities were low for both clinical criteria and the fetal fibronectin test. CONCLUSIONS: Because of low sensitivity in a low risk population, screening for preterm delivery should not be based on the result of a single fetal fibronectin test alone. However, due to its high specificity the test might be useful in avoiding unnecessary medical intervention.
Assuntos
Feto/citologia , Fibronectinas/análise , Programas de Rastreamento/métodos , Trabalho de Parto Prematuro/prevenção & controle , Esfregaço Vaginal , Adulto , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Feminino , Idade Gestacional , Humanos , Funções Verossimilhança , Razão de Chances , Gravidez , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Método Simples-CegoRESUMO
Both alpha- and beta-adrenergic receptors have been identified in the human myometrium by radioligand binding. Both adrenergic receptor subclasses have been shown to mediate the contractile response of the uterus upon catecholamine stimulation: alpha-adrenergic receptors cause uterine contraction while beta-adrenergic receptors induce relaxation. We have identified alpha 1- and alpha 2-adrenergic receptors in myometrial membranes using the newly developed radiolabelled specific antagonists [3H]-prazosin and [3H]-rauwolscine. This enabled us to characterize both receptor subclasses individually. Beta adrenergic receptors were identified using the radiolabelled antagonist (-)-[3H]-dihydroalprenolol. Binding of radioligands to the myometrial membrane receptors was rapid, readily reversible, of high affinity and stereoselective. The total number of alpha 1-, alpha 2- and beta-receptors was determined by Scatchard analysis of radioligand saturation binding and the beta/beta 2-receptor ratio was determined by computer analysis of the beta 2-selective antagonist ICI 118 551) (-)-[3H]-dihydroalprenolol competition binding curves. This enabled us to study the regulation of both alpha- and beta-receptor subclasses under various physiological and pharmacological conditions in the human, i.e., during different phases of the menstrual cycle, in postmenopausal women and during depo-progestin (Medroxyprogesterone acetate) therapy. Only the alpha 2- and beta 1-adrenergic receptor concentrations were found to be subjected to gonadal steroid regulation. The number of alpha 2- and beta 1-adrenergic receptors increased concomitantly with circulating plasma oestradiol levels. This effect was counteracted by progesterone. The number of alpha 1- and beta 2-adrenergic receptors was unaffected by the gonadal steroid environment. These results are an example of the heteroregulation of membrane receptors by oestrogens and progesterone and cast new light on the regulatory mechanisms involved in uterine contractility in the human.
Assuntos
Hormônios Esteroides Gonadais/fisiologia , Miométrio/metabolismo , Receptores Adrenérgicos alfa/fisiologia , Receptores Adrenérgicos beta/fisiologia , Ligação Competitiva , Di-Hidroalprenolol/metabolismo , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Propanolaminas/metabolismo , Receptores Adrenérgicos alfa/metabolismo , Receptores Adrenérgicos beta/metabolismo , TrítioRESUMO
In 1981, the Hôpital Tenon group and the Orléans neutron therapy team initiated a collaborative study for the treatment of grade IV astrocytomas using a combination of photons and neutrons. Neutrons were used as boost in a reduced volume. Doses were progressively increased from 6 to 7 Gy and later up to 8 Gy. Since October 1994, a neutron boost of 7.5 Gy has been delivered. At the time of evaluation, 294 patients had a minimum follow-up of 12 months. Univariate analysis indicated that clinical status, tumor location and photon fractionation scheme had no significant influence on survival. In contrast, age, surgical procedure and neutron dose were found to be prognostic factors. In a multivariate analysis, the prognostic value of the surgical procedure disappeared and the only remaining independent prognostic factors up to 11 months after treatment (P = 0.001) were age and the neutron dose. As far as neutron dose was concerned, survival increased with dose from 6 to 7 Gy up to 15 months. However, after 15 months, there was no longer any benefit in survival for the patients treated with 8 Gy, and complications related to overdosage began to appear. There was a long-term survival group: 55 patients were alive 18 months after treatment (18%). The median survival was 26.7 months. The best survival was observed for patients treated with a neutron boost of 7 Gy in eight fractions over 11 days (25 vs 18%). The present study demonstrates the feasibility of a combination of photons (30 Gy total brain) followed by a neutron boost (7 Gy) in the treatment of high-grade astrocytomas. The results are in good agreement with the published data. In the literature, age and surgical procedure are currently considered as the most important prognostic factors. The prevalence of neutron dose over these two other prognostic factors, as shown in this study, is an important additional argument in favor of the use of neutrontherapy in the management of these tumors. A possible benefit when combining external fast neutrontherapy with boron neutron capture therapy (BNCT) could reasonably be expected.
Assuntos
Astrocitoma/radioterapia , Neoplasias Encefálicas/radioterapia , Nêutrons Rápidos , Radioterapia de Alta Energia/métodos , Astrocitoma/mortalidade , Astrocitoma/patologia , Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Fótons , Prognóstico , Dosagem Radioterapêutica , Fatores de TempoRESUMO
Between 1981 and 1994, 13 patients were referred to the Orleans neutrontherapy department with inoperable or recurrent pelvic chordomas. One patient who had already been irradiated refused the treatment, fearing complications. Among the 12 patients suitable for evaluation, ten had undergone one to five previous surgical operations. The time lapse between the last surgical operation and neutrontherapy was 13 months. Neutrons were used alone or as a boost depending on the tumor volume or treatment purpose. At four years, crude survival and local control probability (Kaplan-Meier) were 61 and 54% respectively. This small series suggests that fast neutrontherapy can provide a good alternative for the treatment of inoperable sacral chordomas.
Assuntos
Cordoma/radioterapia , Nêutrons Rápidos , Radioterapia de Alta Energia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cordoma/complicações , Cordoma/mortalidade , Cordoma/patologia , Cóccix , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cuidados Paliativos , Dosagem Radioterapêutica , Sacro , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/patologia , Análise de SobrevidaRESUMO
Human myometrium contains alpha 3-adrenergic receptors which can be identified by binding of the alpha 2-adrenergic antagonist [3H]rauwolscine. Scatchard analysis of saturation binding data on myometrial membranes revealed that [3H]rauwolscine bound to a single class of noncooperative sites (262 +/- 89 fmol/mg of membrane protein) with high affinity (i.e., with an equilibrium dissociation constant of 5.3 +/- 2.2 nM). The alpha 2-adrenergic nature of these sites was derived from the order of potencies and stereospecificity of alpha-adrenergic agonists and antagonists to compete with [3H]rauwolscine binding.
Assuntos
Miométrio/metabolismo , Receptores Adrenérgicos alfa/análise , Receptores Adrenérgicos/análise , Útero/metabolismo , Ioimbina , Agonistas alfa-Adrenérgicos/metabolismo , Antagonistas Adrenérgicos alfa/metabolismo , Ligação Competitiva , Feminino , Humanos , Técnicas In Vitro , Cinética , Membranas/metabolismoRESUMO
The effects of androstenedione (AD) on cell proliferation and kinetics have been measured in MXT mouse and MCF-7 human mammary cancer cell lines using SAMBA 200 cell image analysis of Feulgen-stained nuclei. At a concentration of 0.01 microM AD inhibited the proliferation of both cell lines whereas a higher dose (1 microM) was inhibitory on MCF-7 cell proliferation but stimulatory in MXT cells. It is unlikely that these effects are due to aromization of AD into oestrogen since (a) both cell lines were devoid of aromatase and (b) both cell lines were similarly affected by oestradiol (E2), being stimulated at low concentrations and inhibited at high doses. Furthermore, inhibition by AD seems to occur, at least in part, by blockade of the cell cycle whereas that by E2 appears to be cell cycle independent.