Epidémiologie du risque cardio-vasculaire

L’épidémiologie des maladies cardio-vasculaires est étonnante, et apparemment contradictoire.     

Radiosensibilité individuelle et risque aux faibles doses médicales

Individual radiosensitivity to high doses of ionizing radiations has been known for a long time by radiation oncologists. It is responsible for the side effects and complications of radiation therapy in the absence of errors in dose delivery. Immunofluorescence techniques have lowered by a factor 100 the threshold of detection of DNA double-strand breaks, to the level of 1 mGy. The effects of a simple radiography, e.g. a mammography, can be measured. Thus the phenomenon of individual radiosensitivity at low-doses has been assessed in mammary epithelium cell cultures exposed in the conditions of mammography. The mechanisms of individual radiosensitivity are linked to abnormalities of DNA damage signalling and repair. This suggests a link between cancer proneness and radiosensitivity. Individual radiosensitivity has a prevalence of 5 to 15% in the population. Thus, it is a key phenomenon to take into account in public health and in future recommendations of the radioprotection system.     

Le cancer du testicule : facteurs de risque génétiques et environnementaux

The incidence of testicular cancer (TC) has a distinct geographic distribution but is increasing in most countries, including France. The most likely origin of TC is a lack of normal germ cell differentiation in the foetal testis. The maintained immature germ cells could proliferate after puberty to induce testicular tumor. Because of its frequent association with cryptorchidism and infertility, TC could be part of the testicular dysgenesis syndrome. The role of genetic factors is suggested by the frequency of familial TC cases, but no responsible gene has been clearly identified until now. Among the various studied genes, those regulating the KITLG/KIT pathway involved in primordial germ cell proliferation seem to play an important role. Studies made in immigrants and twins suggest the influence of environmental factors on the origin of TC. Hormonal deregulation occurring during prenatal life or puberty could facilitate the development of TC. However, the role of exogenous substances acting as endocrine disruptors has not been demonstrated yet.     

Evolution du risque infectieux chez l'enfant atteint de leucémie.

Infection is the leading cause of illness and death in children with leukemia. The risk of infection may change over time as regimens of therapy are modified. A review of the hospital charts of 166 infants in whom leukemia had been diagnosed between 1976 and 1980 revealed an increased number of deep fungal infections (20 v. 3) during this period in comparison with the number between 1969 and 1976 in 164 patients treated at the same hospital whose leukemia was diagnosed between 1969 and 1975. The 20 severe fungal infections between 1976 and 1980 were characterized by difficulty of diagnosis (a definite diagnosis having been made three times out of four only at autopsy), an important role of Candida but also of Aspergillus (the latter having been isolated almost as often as the former) and a grave prognosis (the mortality being very high [75%] and much above that for gram-positive septicemia [6%] and that for gram-negative septicemia [31%]). This increase in frequency of fungal infections was concurrent with the introduction of phase-1 chemotherapy, which was often responsible for prolonged neutropenia. To reduce the risk of infection in children with leukemia it appears to be essential to improve diagnostic methods and approaches to therapy.     

Le développement de l’inventaire de dépistage ERIraos: un outil global d’appréciation du risque d’évolution psychotique

Adequate identification of patients for early intervention programmes requires reliable and valid assessment tools. Within the German Schizophrenia Network (Kompetenznetz Schizophrenie) a set of schedules for early detection of schizophrenia has been proposed: the Early Recognition Inventory ERIraos. ERIraos is a two-step procedure with a 17-item checklist used at step 1 by GPs, psychologists, teachers, while a comprehensive 110-item symptom list is applied at early intervention centres at the expert level. In addition, ERIraos allows the assessment of several risk factors for psychosis such as familial load, childhood deficiencies, alcohol and drug use by special modules. Some preliminary results are presented here. The frequency of the 17 checklist symptoms increases from the early to the late prodrome, and more specific symptoms occur over time. The 17 checklist symptoms are grouped by factor analysis to 5 factors (psychotic, depressive, disorganised, withdrawn, dysphoric). In addition to prodromal symptoms, most patients (86.2%) report at least one additional risk factor (mean: 1.7 risks). 68% demonstrate some schizotypal features, 53% report alcohol and/or drug consumption, 24% demonstrate some deficiency or delay in childhood development, 21% report definite obstetric or birth complications, and 10% have a family history of schizophrenia or some schizophrenia-like diagnosis in first degree relatives. So far, the results are of a preliminary nature, and when sufficient information on psychotic transitions is available, the predictive value of ERIraos will be determined.     

Profil lipidoprotéinique,isotopique et risque athérogène dans la drépanocytose en Côte d’Ivoire

The principal goal of this study was to assess the possible disturbances of lipids and lipoproteins in sickle cell disease and establish a relationship between painful crisis and atherogenic risks by the atherogenicity index in Ivoirian adults. We analysed serum plasma lipid and lipoprotein profiles of 126 subjects with sickle cell anemia, and 55 “Hb AA” healthy individuals. The lipid and lipoprotein parameters studied were total cholesterol, triglycerids, HDL, LDL, apoproteins A1 and B, electrophoresis of lipoproteins and haemoglobin. In painful crisis, levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, apoproteins A1 (apo A1) in sickle cell anemia patients were shown to be significantly lower and levels of triglycerides higher than that of control group and steady state. The electrophoresis profile showed a significant fall of α lipoproteins while β lipoproteins were significantly high in period of crisis. The atherogenicity index (total cholesterol/HDL ratio) was also significantly high, just as LDL/HDL ratio in period of crisis. The overview of these results might hypothesize a high relatively atherogenic risk during the sickle-cell anemia crisis. A special monitoring of the patients in crisis is also necessary in order to prevent the risk of cardiovascular diseases.     

Existe-il, dans la population générale masculine un risque plus fort de développer des délétions du chromosome Y qui entraîneraient une infertilité?

The role of the Y-chromosome in spermatogenesis remains one of the hottest topics in andrology. Three non overlapping recurrently deleted regions on Yq (AZFa, AZFb, AZFc) have been defined, each of them containing several genes that are candidates for male infertility. The causes and mechanisms leading to microdeletion formation on the Y are largely unknown. Theoretically, it could be possible that some groups of Y-chromosomes (haplogroups) currently distributed in the population could confer a selective advantage/disadvantage towards deletion formation. A precedent in the field is the recent identification of a Y-chromosome haplotype that confers a selective advantage against a translocation of Yp leading to another form of male infertility, the Y+XX-male phenotype. In order to test if selection is acting on Y-chromosome haplotype distribution, we have defined and compared Y-chromosome haplotypes in a group of around 60 individuals with Y microdeletions from North-Western Europe using 10 biallelic Y-markers (SRY-2627, SRY-1532, SRY-8299, 92R7, Tat, YAP, sY81, LLY22g, M9, DYS257). The defined heplotypes were compared to a control normospermic population of the same ethnic/geographic origin (in the framework of the European Biodiversity Project). We evaluatte the relationship between different Y-chromosome backgrounds and microdeletions, and to which extent selection on this chromosome could have influenced fifness of certain individuals/populations. We also discuss the selective forces that are acting on this chromosome and speculate on the mechanisms underlying deletion formation.     

Epidémiologie de la dysfonction érectile (2ème partie). Facteurs de risque

Epidemiological studies in the general population or target populations in several countries in the world have revealed a large number of risk factors for erectile dysfunction: diabetes mellitus, hypertension, smoking, dyslipidaemia, cardiovascular diseases, psychological disorders, certain medications, chronic renal failure, socioeconomic factors and lifestyle, obesity, lower urinary tract symptoms, poor health and bicycling. Cardiovascular risk factors are predictors of erectile dysfunction and erectile dysfunction is now considered to be a manifestation of vascular disease. Further studies are necessary to establish the pathophysiological mechanisms of certain risk factors and the possible value of preventive measures.     

La gangrène des organes génitaux externes de I’homme: Facteurs de risque et de pronostic

The objective of this study, based on 20 cases of necrotizing fasciitis of the male genitalia, is to identify the risk factors and prognostic factors of this disease. Most cases of necrotizing fasciitis of the male genitalia occurred in elderly men with a poor socio-economic level including 9 diabetics. There was no identifiable cause in 8 cases (Fournier’s gangrene). All patients underwent surgical excision and systematic antibiotic therapy. This series comprised 5 deaths (25%) in patients over the age of 69 years with extensive lesions and a very poor general state on admission. The outcome of survivors was favourable after a prolonged hospital stay (mean stay: 1 month). The clinical context therefore appears to play an essential role in the development of this disease and its subsequent prognosis, which could be improved by rapid and appropriate prevention and treatment.     

Recherche de facteurs de risque de la thrombopénie induite par le 177Lu-DOTATATE dans le bilan de suivi standard

PurposeThe thrombocytopenia induced by the ¹⁷⁷Lu-DOTATATE is one of its frequent, adverse effects. Its persistence causing problems in the subsequent management of patients, especially when the disease progression occurs, predicting it is a major issue. Due to the lack of knowledge about this subject, we searched to determine the existence of predisposing factors concerning the platelet toxicity in the standard follow-up.Material and methodsThis monocentric retrospective study included 20 patients with gastroenteropancreatic neuroendocrine tumors. Various parameters were analyzed, including: the standard blood analysis, the osteomedullary invasion factor, the spleen's volume and the estimated activity in the bone marrow or the spleen 24 hours post-injection.ResultsFour patients had a persistent grade 2 thrombocytopenia, one year after the last treatment. A decrease in platelet count after the first treatment above 30% and an osteomedullary invasion factor above 30% were highlighted as risk factors odds-ratio = ∞ (P = 0.0379) and odds-ratio = ∞ (P = 0.003) respectively. The initial platelet count, splenic length and estimated activity in the spleen after 24 h were correlated with platelet nadir value r = 0.5459 (P = 0.0128); r = − 0,8105 (P < 0,0001) and r = − 0.467; (P < 0.0001) respectively.ConclusionThis study has shown that the decrease of platelet's count after the first round of treatment and the scale of osteomedullary invasion are risk factors for thrombocytopenia and has brought to light that the spleen acts as a factor impacting the severity of this thrombocytopenia.     

Le risque chromosomique pour un patient porteur d'une translocation t(X;2) concerne non seulement la translocation mais aussi la ségrégation XY

In men, translocations involving sex chromosomes usually result in azoospermia or sometimes oligospermia. We report the case of a man with oligospermia with a 46,Y,t(X;2)(p21;p25.3) translocation and the specific modalities of management of the couple before ICSI. After genetic counselling, we proposed spermatozoa chromosomal analysis using FISH to evaluate the mode of segregation of the translocation and the risk for the embryo and descendants. This study showed that 34% of spermatozoa were normal or balanced for the chromosomes studied, and 66% of spermatozoa presented a chromosome imbalance related to the translocation and/or involving X and Y chromosome non-disjuction. In view of this result, we decided to perform another FISH analysis to define the increased risk related to the non-disjunction of X and Y chromosomes. Only 60% of 1,000 spermatozoa were normal for X and Y. The chromosome risk for the offspring is not limited to the translocation, as the risk of Klinefelter and Turner syndrome is also increased. In view of these results and the woman's age (42 years old), we advised the couple against ICSI at another genetic counselling session. This case illustrates the value of spermatozoa FISH analysis to evaluate the consequences of a translocation on spermatogenesis. The study should not be limited to the translocation alone, but should also evaluate anomalies of non-disjunction of sex chromosomes that are frequent during normal spermatogenesis, but the risk increases in the case of translocations, especially involving the sex chromosomes.     

Génétique moléculaire des dysgénésies testiculaires

The first step of male differentiation is the testis determination which is genetically controled. The key role of SRY gene is now established. However, a number of clinical and genetic data favoured the role of other genes taking place upstream or downstream SRY. Most of 46, XX males possess a translocated SRY gene and thus develop testis, but SRY gene is not found in 10% of such patients. Likewise, the molecular study of 46, XY females participated in the identification of SRY as testis determining factor, but 80% of XY gonadal dysgenesis are not explained by an abnormality of SRY gene. Several clinical situations permitted to suspect the role of autosomal (chromosome 1, 9, 10 17 …) and X chromosome loci in the pathology of sex determination. Some recent works concern, in particular, the testis determining factor of the X chromosome (TDF-X) that could act as a repressor of the testis differentiation. In conclusion, molecular mechanisms of sexual determination appear to be much complex, involving probably several genes in a pathway that remain to be elucidated.     

Cancer et Hérédité

Sans résumé     

Chromosomes et hétérochromosomes de ténébrionidés

Sans résumé Avec 81 figures dans le texte