Conséquences de la chimiothérapie anticancéreuse sur la fertilité de la femme

Sterility is a potential toxic effect of chemotherapy. This risk is well established for alkylating agents, but is less clearly defined for anthracyclines, methotrexate and fluorouracil and poorly defined for alkaloids, platinum, etoposide and taxanes. The main predictive factors for ovarian toxicity are the additive effect of cytotoxic drugs, the cumulative dose of each drug and the patient’s age. This effect of chemotherapy is evaluated on menstrual cycles, hormonal assays and the number of pregnancies observed in patient cohorts. Chemotherapy induces destruction of oocytes and granulosa cells. In mice, it has been shown that adriamycin may induce oocyte apoptosis, which can be prevented by modulation of cycle cell signalling (dysregulation of Bax gene or, on the contrary, expression of its antagonist gene Bcl-2 or inhibition of apoptosis with sphingosine-1-phosphate or caspase inhibitors). Clinical data in the literature are usually based on retrospective studies and are somewhat confused: global fertility after MOPP chemotherapy for Hodgkin’s disease is about 20%, adjuvant chemotherapy with CMF, F(A)C or TAC for breast cancer induces amenorrhea in 50% to 70% of cases, PVB or BEP chemotherapy for ovarian germ cell tumors has little effect on fertility when the uterus and one ovary can be preserved, and the majority of women treated with methotrexate, actinomycin D or various combinations for persistent trophoblastic disease remain fertile. Preservation of fertility is a major goal for cancer patients receiving chemotherapy: in vitro fertilization could preserve the couple’s fertility, but is usually not feasible as it would delay initiation of chemotherapy until after stimulation of ovulation; oocyte or ovarian tissue cryopreservation is at the stage of research; oral contraceptives have not been demonstrated to be effective to preserve ovarian function; gonadotropin releasing hormone (GnRH) agonists prevent cyclophosphamide toxicity in rat and monkey ovaries, and a few pilot clinical studies suggest that chemotherapy-induced amenorrhea could be prevented by administration of GnRH analogues simultaneously to chemotherapy, but randomised studies are necessary.     

Étude de la variabilité de la clairance hépatique de la mébrofénine-99mTc en scintigraphie hépatobiliaire

AimThe purpose of this study was to investigate some of the parameters likely to influence mebrofenin-^99mTc hepatic clearance calculation and inter-and intra-observers reproducibility.Materials and methodsHepatic clearance (%/min m²) of 30 scintigraphies was calculated from the values of hepatic, cardiac, and total activities, according to the method recommended in the literature. We studied: 1) impact of injection–acquisition delay variations; 2) acquisition type: anterior face only (FA) or geometric mean (GM); 3) clearances calculated according to four different body surface area (BSA) formulas; 4) intra-and inter-observers reproducibility for three observers (two evaluations for each observer).Results1) Clearance differences between different studied intervals were statistically significant, more important if the studied interval was far from reference interval (150–350 secondes) and even more when the interval studied was too early (110–310 secondes). 2) There was a statistically significant difference between clearance calculated using either FA or GM datasets (0.85 %/min m²). 3) There were small but statistically significant differences for four of the clearance comparisons using different BSA formulas. 4) Despite differences in size of cardiac and hepatic regions of interest (ROI), intra-observer reproducibility of hepatic clearance was excellent for each observer. Inter-observers reproducibility was also excellent (r = 0.982).ConclusionHepatic clearance of mebrofenin-^99mTc appears to be a highly reproducible method provided that acquisition and clearance calculation are standardized. It provides additionnal functional information to morphological and biological data usually performed before major hepatectomy. Thereby, the definition of a standardized protocol would enable realization of multicentric studies.     

A propos de l'intervention des aéroions dans les processus de régulation de la lipémie et de la cholestérolémie

Resume Les expériences ont porté sur des lapins repartis en deux groupes parallèles — un groupe étant traité avec des aéroions négatifs en concentrations moderées (n^– = 10 – 40.000; n⁺ = 1.000) et l'autre sans aéroionothérapie (témoins). Par rapport aux animaux témoins (pas exposés aux aéroions),on a enregistré,sous l'influence de l'aéroionothérapie, que: (1)il y a une tendence de normalisation de la motilité spontanée, deprimée par une alimentation contenant un excès de cholestérol(0,3 g/kg/jour); (2) la lipémie et la cholestérolémie sont restées à un niveau plus bas chez les animaux alimentés au cholestérol; (3) la lipémie et la cholestérolémie, de même que l'iode thyroïdien, sont restées aux valeurs voisines de celles normales,chez les animaux nourris avec un excès (20 mg/kg/jour), de substances antithyroïdiennes naturelles (provenant du chou).

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Groups of rabbits were exposed to negative air ions of moderate concentrations (n^– = 10 – 40,000; n⁺ = 1,000) while others served as controls. (1) When rabbits were fed a cholesterol-rich diet (0.3 g/kg/day)causing reduction of motility in the control animals, their motility was normalized under air ion treatment. (2) The blood cholesterol and lipid levels of rabbits on a cholesterol-rich diet were lower with air ion treatment than in controls.(3) When rabbits were fed a diet with thyroid blocking agents from cabbage the blood cholesterol and lipid levels and the thyroid iodine content remained unchanged with air ion treatment.

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Zusammenfassung Gruppen Kaninchen wurden mit negativen Luftionen in mässigen Konzentrationen (n^– = 100 000 – 40 000; n⁺ = 1 000) behandelt, während andere als Kontrollen dienten. (1) Die durch Fütterung von cholesterinreicher Diät (0,3 g/kg/Tag) verminderte Motilität der Tiere wurde unter der Luftionenbehandlung normalisiert. (2) Der durch Fütterung von cholesterinreicher Diät erhöhte Blutcholesterin- und-fettspiegel fiel durch Luftionenbehandlung ab. (3) Der durch Fütterung von strumipriven Substanzen aus Kohl erhöhte Cholesterin- und Fettspiegel im Blut und verminderte Jodgehalt der Schilddrüse wurde durch Luftionenbehandlung nicht beeinflusst.

     

Quelques considérations sur l'enseignement de la médecine physique et de la réhabilitation

Particularly since World War II physical medicine and rehabilitation have assumed a growing importance. The efforts of the Canadian Association of Physical Medicine and Rehabilitation, following a survey of Canadian universities, to increase the theoretical and practical teaching of physiatrics are emphasized. It is considered important that the teaching of physical medicine and rehabilitation should be carried out concurrently with other medical and surgical teaching programs. Paramedical and auxiliary rehabilitation personnel should participate in the teaching program. The number of hours devoted to physiatrics should be increased, and the medical student should be permitted to choose physical medicine and rehabilitation as a part of his internship program.     

Principes de la lecture critique de la littérature médicale: Illustration urologique

There has been an enormous expansion in scientific literature, especially in the area of health and medicine. At the same time the complexity of the research has increased. Through the reading of medical literature of his field of interest, the physician is in search of useful information. However, reading medical papers is very time consuming and most physicians, for their usual literature review, content themselves with the titles and the abstracts. Moreover, quality and relevancy of the publications vary greatly and the reader must be able to “separate the wheat from the chaff”. Thus the reading of literature needs selection and evaluation. As a result, physicians require critical appraisal skills. The principle of appraisal of medical literature is to assess the value of publications which will influence the medical practice of the reader. The reader has a double objective: to assess the credibility of the publications, and to define the applicability of the publication information. By following eight steps the reader is able to quickly rule out from his reading what is not valid and have an objective look at the quality of the results which are proposed to him. These eight steps comprise the assessment of the study objectives, the study design, the study factor(s), the outcome factor(s), the study population and sample, the confounding factor(s) and bias, the results with their statistical and clinical significance and the power of the study, and, lastly, the synthesis of the reader's judgment. The last word belongs to the clinician facing his patient.     

Effets de la radiothérapie sur la fonction testiculaire de l'adulte

Radiation therapy plays a major role in the curative management of numerous neoplasms, such as Hodgkin's disease or testicular cancer. However, the adverse effects of low-dose radiation scattered to radiosensitive normal tissues adjacent to the radiation fields, such as the testes, have been recognized. Experimental studies performed on healthy volunteers showed that no lesion was detectable on sperm counts or testicular biopsies after single doses of less than 10 cGy. Oligospermia has been reported after 15 cGy and 100 cGy result in a 90% incidence of azoospermia. In the radiotherapy of cancer, fractionated regimens are used to increase the differential effect between normal and tumoral tissues. For the same dose, a fractionated radiation regimen results in a higher incidence and a longer period of azoospermia than a single dose irradiation. Fractionated doses of >50 cGy result in a 100% incidence of azoospermia. For doses up to 200 cGy, recovery occurs but normal sperm production remains uncertain. Although the recovery time can be very long (more than 10 years), there is a risk of definitive azoospermia after doses of >200 cGy. Spermatogonia are the most radio-sensitive cell type and their depletion after small irradiation doses explain the effect of radiotherapy on fertility. Clinical hypogonadism is very unfrequent in usual practice, what seems to prove a relative radio-resistance of the Leydig cells. However, functionals studies show that there is a rise in serum LH with increasing dose to the testes. A decrease in testosterone levels has been reported after high testicular doses.     

Étude de la cohorte nord-finlandaise de 1966: facteurs prédictifs et conséquences de la schizophrénie

Subtle motor, emotional, cognitive and behavioural abnormalities are often present in apparently healthy children and adolescents who later develop schizophrenia. This suggests that some aspects of causation are established long before psychosis becomes manifest. We aim to assess the factors contributing to the development of schizophrenia focusing mainly on genetic factors, pregnancy and delivery complications, early development and scholastic performance, as well as later educational, social and health consequences. This is done by reviewing the Northern Finland 1966 Birth Cohort, its scientific activities, publications and work in progress.     

Fonctions histoenzymatiques lors de l'évolution et de la lutéolyse du corps jaune de la lapine

Résumé Trente cinq enzymes sont recherchées lors de l'étude comparative de la lutéinisation et la lutéolyse. Vingt six sont histochimiquement décelables dans les corps jaunes gestatifs leur permettant de stocker et métaboliser glucides, corps gras, nucléotides, amines, phosphates, sulfates et d'autres métabolites. Les activités importantes des enzymes de la voie des pentoses, des diaphorases et de la stéroïde 3 ol DH témoigneraient d'une stéroïdogenèse active. Les cellules lutéiniques thécales semblent histoenzymatiquement mieux pourvues au début de la luteinisation; les cellules lutéiniques granuleuses le sont pendant les stades ultérieurs.La lutéolyse est marquée par une diminution de la plupart des activités enzymatiques. Les activités tant qu'elles existent, sont topographiquement limitées (ilôts actifs extra lutéaux) et surtout métaboliquement restreintes. L'équipement enzymatique des structures lutéales très involuées suggère plutôt qu'une stéroïdogenèse même résiduelle des processus typiques et une activité des éléments conjonctifs (fibrillogenèse).

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Histoenzymatic functions of the evolution and the luteolysis of the corpus luteum of the rabbit

Summary 35 enzymes were investigated in the course of a comparative study on the luteinisation and luteolysis. 26 of them were found in the corpora lutea during gestation. They were able as a consequence to stock and the metabolize glucides, lipides, nucleotides, amines, phosphates, sulphates as well as other metabolites. The strong activities of the pentose shunt's enzymes, of the tetrazolium reductases and ⁵ 3 OH-steroide DH indicated most probably an active steroidogenesis. The theca-luteinic cells appeared having a stronger histoenzymatic activity in the beginning of the luteinisation; the granuloso-luteinic cells showed a stronger activity in the later stades.The luteolysis is characterized by a decrease of the activity of the preponderant number of the enzymes mainly in the degenerated luteal cells. The enzymes activities as far as such existed were topographically limited (active extraluteal islands) and restricted mainly in their metabolizing possibilities. The author's results suggested as more probable the existence of a process of lysis and an activity of the connective tissue elements (fibrillogenesis) than a steroidogenesis, even though in a residual or terminal form.

     

Action de l'actinomycine D sur la différenciation cellulaire au cours de la régénération de Planaires qui viennent d'éclore

Résumé Nous avons montré, à l'aide d'actinomycine tritiée, que cet inhibiteur pénètre en quantité égale dans les cellules de planaires adultes qui ne régéénèrent pas en présence de fortes concentrations (50 g/cm³) et dans celles de jeunes planaires qui peuvent former un blastème en présence d'actinomycine D, malgré l'inhibition de nouvelles synthèses d'ARN qui en résulte. Chez les jeunes, le taux de pénétration de l'antibiotique est comparable dans les noyaux des cellules indifférenciées qui participent à la formation du blastème et dans les noyaux des cellules différenciées. Les noyaux à nucléoles dissociés ne sont pas plus radioactifs que les noyaux où le nucléole est seulement appauvri en granulations. La radioactivité diminue uniformément dans toutes les cellules si les animaux sont remis en élevage dans l'eau. La radioactivité cytoplasmique observée est probablement due à la nature des fixateurs qui favorisent la rétention de molécules non liées.Nous pouvons conclure que les noyaux de toutes les catégories cellulaires présentent la même perméabilité à l'actinomycine. Celle-ci est présente dans les cellules de régénération des jeunes qui édifient cependant un blastème où le taux de synthèse des protéines est au même niveau que dans une régénération normale.

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On the action of actinomycin D on the cellular differentiation during the regeneration in Planarians

Summary ³H actinomycin inhibitor of RNA synthesis enters equally cells of adult planarians which never regenerate when applying the drug at high concentration (50 g/cm³), and young planarians which can form a blastem in the same solution; regeneration occurs despite of the inhibition of new RNA synthesis which ensues.Ultrastructural histoautoradiographs of newly hatched Planarian tissues show that this drug enters equally nuclei of undifferentiated cells which make up the blastem of regeneration and whose nucleoli are not dissociated, and nuclei of differentiated cells whose nucleoli are very often dissociated. The radioactivity is very often located upon heterochromatin. After return of the animals into water, radioactivity becomes reduced evenly in all cells.The cytoplasmic radioactivity that we have observed probably depends on the nature of fixatives which favour the retention of non linked molecules.We can conclude that the nuclei of all cells have the same permeability to actinomycin D, whatever the state of morphological differentiation. The inhibitor is present within the regeneration cells of young Planarians which build a blastem wherein the rate of protein synthesis is at the same level as in normal regenerating tissues.

     

Influence comparée de l'(±)-acide abscissique,de la coumarine,de l'acide p-coumarique et de certains de leurs dérivés sur la croissance de la première feuille de blé

Summary The activities of (±)-abscisic acid and a number of compounds derived from p-coumaric acid and coumarin and their interaction with gibberellic acid in the control of the elongation of the first wheat leaf are examined. (±)-Abscisic acid strongly inhibits leaf growth in the presence as well as in the absence of gibberellic acid, but the inhibition is greater in the presence of gibberellic acid (3 g/l already have an observable effect). Among other compounds, only ferulic acid and coumarin significantly reduce leaf elongation, and they are effective only at high concentrations (1.44 · 10^-4 M/l).     

Action de l'actinomycine D sur la différenciation cellulaire au cours de la régénération de Planaires qui viennent d'éclore

Résumé L'utilisation de l'actinomycine D, au cours de la régénération de Planaires à l'éclosion ou de celle d'adultes, montre que ces deux groupes d'animaux réagissent différemment à l'antibiotique.La régénération se produit en présence de l'antibiotique chez les jeunes Planaires, alors que, pour la même concentration (50 g/cm³), elle est totalement bloquée chez les adultes. Elle débute dès la décapitation des animaux; le retour dans l'eau, après un traitement par l'antibiotique qui va de 1 à 4 jours, ne modifie pas son déroulement morphologique.L'examen ultrastructural montre que les cellules différenciées présentent le plus souvent des dissociations nucléolaires importantes.Les lésions s'étendent progressivement à toute la cellule qui dégénère fréquemment. Les cellules morphologiquement indifférenciées ne sont que faiblement altérées (raréfaction du composant granulaire du nucléole), et récupèrent une structure normale après retour dans l'eau.Ces résultats conduisent à envisager l'étude des synthèses d'ARN, au cours de ces expériences, au niveau des organismes entiers et au niveau cellulaire.

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On the action of actinomycin D on the cellular differentiation during the regeneration in PlanariansI. Morphological, histological and ultrastructural studies on the regeneration capacity in presence of the antibiotic

Summary The utilization of actinomycin D during the regeneration of young and adult Planarians shows that the two groups of animals react differently to the antibiotic.Regeneration takes place in the presence of the antibiotic in young Planarians, whereas it is entirely inhibited in adult ones, applying the same concentration (50 g/cm³). In the young animals it begins immediately after decapitation. Their return into the water, after a treatment with the antibiotic lasting from 1 to 4 days, does not interfere with the morphological differentiation. The ultrastructural investigation exhibits that in the majority of the undifferentiated cells the nucleolus is largely dissociated.The lesions gradually extend to the whole cell which frequently degenerates. The morphologically undifferentiated cells are weakly impaired (depletion of the granular component of the nucleolus), and they recover a normal structure after their return into water.These results lead us to study the RNA synthesis, during these experimentations, on the whole organism as well as the cellular level.

     

Les inhibiteurs spécifiques de la recapture de la sérotonine dans la dépression de l’enfant et de l’adolescent: revue des controverses récentes

European and US drug regulatory authorities have recently warned against the use of selective serotonin reuptake inhibitors (SSRIs) in childhood and adolescent depression. Through an extensive literature review on the use of SSRIs to treat depression in children and adolescents — including psychiatric clinical trials, pharmacology, and drug safety data — we will: i) describe the main arguments justifying various regulatory decisions; ii) present published data and subsequent meta-analyses; iii) discuss how to integrate the recommendations into daily clinical practice, freeing professionals from a Manichean approach. We reach the limits of evidence-based medicine, which provide the basis of the scientific work of the regulatory authorities.     

Effets de l'acide gibbérellique et de la kinétine sur le développement de l'activitéα-amylasique durant la croissance de l'Orge

Effects of gibberellic acid and kinetic on α-amylase production during the germination of barley. - The action of gibberellic acid and kinetin, alone or combined at different concentrations, has been studied on α-amylase production in whole barley seedlings and in embryoless endosperms in course of the six first days of development in the dark. The classic activation of α-amylase synthesis by gibberellic acid has been confirmed both in whole seeds and in embryoless endosperms. Kinetin inhibits α-amylase synthesis after the third day of germination but has no effect on isolated endosperms. When gibberellic acid and kinetin are given simultaneously gibberellic acid stimulated during the three first days just as it does alone, kinetin inhibits after the third day also as it was alone so that the two regulators act, without interactions, at different stages in the time. These effects of kinetin are be independent. A critical examination of the techniques used in the literature in the stud of amylase is made.     

La détermination sérologique de la poliomyélite asymptomatique dans la famille

Résumé Dans 4 familles où se trouvait un malade atteint de poliomyélite on a examiné les sérums de la phase aiguë et de la phase de convalescence des malades et des autres membres de famille pour chercher la présence d'anticorps neutralisant trois souches du virus poliomyélitique (Lansing, SK et MM) et le virus de la chorioméningite lymphocytaire. Dans deux familles au moins, les recherches indiquent que les anticorps contre la souche Lansing ne se forment que comme conséquence spécifique d'une infection, éventuellement asymptomatique, par un virus poliomyélitique d'une structure antigène apparentée à celle de la souche Lansing. Dans une famille le sérum de la phase aiguë d'un malade et le sérum de sa mère, contenaient des anticorps tandis que le sérum de son père et d'une soeur ne neutralisait pas la souche Lansing. Dix semaines après, les sérums du père et de la soeur avaient obtenu un pouvoir neutralisant contre cette souche, bien que ni l'un ni l'autre n'aient été malades. Ceci pourrait indiquer la possibilité d'une infection par contact direct dans la famille.