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.     

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.     

Efficacité de la mémoire associative inhérente à la potentiation post-tétanique

An associative memory is modeled in networks of cells that are assumed to have the short-term plasticity of the neuromuscular junction of the frog. The data relating synaptic transmission efficiency and stimulation frequency for post-tetanic potentiation of the neuromuscular junction are represented by polynomial expansions. Simulation of storage and retrieval demonstrates that functional associative memory is feasible based on this particular synaptic plasticity. Retrieval reaches a maximum efficiency at a delay of three minutes after storage and is lost after about 9 min. The signal to noise ratio of the retrieved pattern drops steadily as additional associations are stored in memory but retrieval appears to be possible with up to four stored associations. Although the data are derived from synapses not normally proposed as a basis for memory functions, the results here will generalize to other synaptic junctions located more centrally that have similar characteristics. This simulation technique allows the efficiency of associative memory based on various types of synaptic plasticity to be evaluated.     

Contribution a la connaissance des propriétés du virus de la densonucléose

Résumé Le virus de la densonucléose est thermorésistant. Il n'est pas inactivé après traitement avec des solvants de lipides. Aucun pouvoir hémagglutinant n'a été mis en évidence avec des érythrocytes d'espèces variées. Ces propriétés sont comparées à celles desParvovirus.

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Summary The densonucleosis virus is thermoresistant. It is not inactivated after treatment with lipid solvents. Attempts to demonstrate hemagglutination of DNV, using different erythrocytes, were unsuccessful. These properties are compared to those of Parvoviruses.

     

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.     

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.     

Intérêt de la TEP au 18F-FDG préthérapeutique pour prédire la réponse à la radio-immunothérapie dans les lymphomes non hodgkiniens

PurposeRadioimmunotherapy (RIT) is a new treatment option for patients with non-Hodgkin lymphoma (NHL). Response to RIT currently remains difficult to predict using conventional prognostic factors and could be refined using functional imaging. The goal of this work is to evaluate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting response to yttrium 90-labeled monoclonal antibodies for patients with NHL.MethodThirty-five patients with NHL who had undergone 18F-FDG PET prior to RIT with either 90Y-ibritumomab tiuxetan or 90Y-epratuzumab tetraxetan were included in this retrospective study. Four functional criteria (SUVmax, SUVmean, volume and the product of the volume and the SUVmean-TLG-) were analyzed on a per-lesion basis.ResultsA total of 154 lesions were analysed. The per-lesion analysis revealed significant differences (P < 0.05) between responders and non-responders for several criteria and above all for the SUV.ConclusionOur results suggest a predictive role of 18F-FDG PET prior to RIT by giving a useful indication of the radiosensitivity of the lymphoma.     

Déficit androgénique: effet de la substitution sur la composition corporelle

Male hypogonadism is responsible for an increase in fat body mass and a decrease in lean body mass. Similar changes are observed in aging men. Aging is also frequently associated with a decrease in testicular function. Androgen replacement therapy in adult men with hypogonadism has been shown to reverse these changes in body composition. Androgens stimulate protein synthesis, especially in muscles, leading to a gain of muscle mass and muscle strength. In contrast, androgen therapy inhibits tissue utilization of lipids, predominantly in visceral fat and consecutively induces a decrease in fat body mass. As the same changes in body composition are observed in aging and in hypogonadal adult men, the value of androgen replacement therapy was evaluated in aging men with an age-related decrease in androgen production. About ten studies have included human males over the age of 65. The results obtained indicate the benefit of such therapy in terms of improvement in body composition in aging men due to a rise in plasma testosterone levels up to the normal range of young adult men.     

Gestion informatisée de la biologie délocalisée

La prise en charge par le biologiste de certaines analyses délocalisées se trouve grandement facilitée par la mise en place d’un système informatique reliant l’analyseur délocalisé et le laboratorie. Elle apporte un niveau de sécurité nécessaire pour la prise de responsabilité du laboratoire dans l’acte de biologie délocalisé. L’architecture réseau de la plupart de h?pitaux permet maintenant de transmettre très facilement et de manière fiable des données entre plusieurs services voire entre établissements. Les analyseurs de gazométrie sanguine permettent cette connexion, de plus en plus d’industriels développent d’autres paramètres en plus des simples gaz du sang comme dernièrement l’urée et la créatinine. Les analyseurs permettant de doser les marqueurs cardiaques, ceux réalisant l’hémostase sont désormais fréquemment connectables. Chaque industriel du diagnostic proposant des analyseurs de glycémie a ou va prochainement commercialiser un modèle connectable. Il en est de même pour les bandelettes urinaires. Il est donc probable, et les biologistes sont les premiers demandeurs, que la connexion informatique d’analyseurs de biologie installés dans les unités de soins, soit un pré-requis pour la gestion des analyses délocalisées par le biologiste, et sa prise de responsabilité dans les résultats biologiques issus de ces analyseurs.     

Création d'une lignée homozygote pour une translocation réciproque chez l'Amphibien Pleurodeles waltlii

Résumé Chez le Pleurodèle, une étude cytogénétique portant sur quatre géné-rations successives a permis d'obtenir une lignée stable d'individus féconds homozygotes pour une translocation réciproque.L'anomalie a d'abord été décelée à l'état hétérozygote chez une femelle résultant du croisement entre une femelle normale et un mâle irradié aux rayons X. Le remaniement chromosomique initial consiste en un échange réciproque de segments inégaux entre le bras court d'un chromosome 5 et le bras long d'un chromosome 6. Il en résulte un allongement du bras court d'un chromosome 5 correspondant à un raccourcissement d'égale amplitude du bras long d'un chromosome 6, soit la formule 24, t(5p+; 6q-) par analogie avec le système utilisé pour les caryotypes humains.Contrairement à ce que l'on aurait pu supposer, la ségrégation des chromosomes remaniés n'est pas perturbée au cours de la méïose des animaux 24, t(5p+;6q–).Lors des croisements entre un individu hétérozygote pour la trans-location et un individu normal ou entre deux hétérozygotes, la descendance est constituée de germes phénotypiquement normaux ou anormaux selon leur constitution chromosomique.Les sujets 24, t(5p+; 6q–) et 24, 2(5)–, 2(6)–,2(5p+) +, 2(6q–)+ ont un caryotype équilibré, leur phénotype est normal. Les formules déséquilibrées sont par contre léthales ou semi-léthales.Les embryons 24, 6–, (6q–)+ et 24, 5–, 2(6)–, 5p+, 2(6q–)+ présentent rigoureusement le même syndrome. Ils meurent peu de temps après l'éclosion sans pouvoir se nourrir. Les ébauches branchiales sont pratiquement inexistantes, l'il est malformé et la bouche reste béante.Les deux formules 24, 5–, (5p+)+ et 24, 2(5)–, 6–, 2(5p+)+, (6q–)+ déterminent de même un autre syndrome caractéristique. Dans ce cas, chez les embryons âgés et les jeunes larves, les malformations sont discrètes et transitoires. Elles se situent au niveau des yeux et des branchies. Il est difficile d'élever ces animaux jusqu'à l'âge adulte. Ceux qui survivent ont un corps disproportionné et des anomalies du squelette vertébral.Les deux formules 24, 2(6–), 2(6q–)+ et 24, 2(5)–, 2(5p+)+ ont un déséquilibre tel que les embryons ne dépassent pas le stade de la gastrula.L'examen des figures méïotiques de mâles hétérozygotes pour l'anomalie confirme les résultats obtenus à partir de l'étude des phénotypes et des caryotypes des descendants. La première division méïotique comporte 10 bivalents et un tétravalent tandis que l'examen des caryotypes établis à partir des métaphases II montre qu'il ne se forme que quatre types différents de gamètes.Le chromosome 6q– se reconnaissant aisément à l'examen microscopique direct, la translocation constitue un marqueur nucléaire facilement utilisable car les individus homozygotes pour l'anomalie ont une croissance et une méïose normales.

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A homozygous reciprocal translocation in a strain of the newt Pleurodeles waltlii

A cytogenic study dealing with four generations of the newt Pleurodeles waltlii has lead us to a stock of fertile homozygotes for a reciprocal translocation. —The chromosomal rearrangement has first been detected at the heterozygous state in a female resulting from a cross between a normal female and a male submitted to X ray-irradiation. The initial aberration consists of a reciprocal exchange of unequal segments between the short arm of a chromosome 5 and the long arm of a chromosome 6. Consequently, the short arm of chromosome 6 grows shorter in the same proportion (formula 24, t(5p+; 6q–), on the analogy of the human chromosome standardization).—Against all expectation, meiosis in 24, t(5p+;6q–) animals leads to a normal segregation of abnormal chromosomes.—When a heterozygote for translocation is bred with a normal individual or when two heterozygotes are crossed, the offspring is composed of phenotypically normal or abnormal animals, depending on their karyotypes.—The subjects 24, t(5p+; 6q–) and 24, 2(5) –, 2(6) –, 2(5p+) +, 2(6q–)+ have balanced karyotypes; their phenotype is normal. On the other hand, the unbalanced types are lethal or semi-lethal.— The 24, 6–, (6q–)+ and 24, 5–, 2(6) –, 5p+, 2(6q–)+ embryos show a strictly identical syndrome. They die soon after the hatching stage without having been able to eat. The branchial outlines are almost inexistant, the eyes are poorly-formed and the mouth stays wide-open.—The two formulas 24, 5-, (5p+)+ and 24, 2(5) –, 6 –, 2(5p+)+, (6q–)+ produce the same phenotypic aberrations as well. In this case, malformations in older embryos and young larvae are discrete and transient. They are localized at the eye and branchial levels. It is difficult to rear these animals until adulthood. Those that survive, have a disproportionate body and malformations of the vertebral skeleton.—The two formulas 24, 2(6) –, 2(6q–)+ and 24, 2(5) –, 2(5p+) + are so unbalanced that the embryos do not survive beyond the gastrula stage.—The study of the meiotic slides of male heterozygotes bring a cytologie confirmation to the results obtained from the study of the phenotypes and karyotypes established on the offspring. The first meiotic division shows 10 bivalents and one quadrivalent, whereas the study of the karyotypes from the metaphases of the second meiotic division prooves that only four types of different gametes can be formed.—The 6q– chromosome is easily recognizable under direct microscopic study. This translocation constitutes a nuclear marker which can be easily used because the homozygotes for the aberration grow normally and show a normal meiosis.

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Cet article recouvre en partie le travail d'une thèse de Doctorat d'Etat de Sciences naturelles qui sera soutenue dans le courant de l'année 1971.