Les récepteurs aux œstrogènes dans le testicule et l’appareil reproducteur du primate et de l’homme

The impact of oestrogens on the male reproductive system remains the subject of intensive research activity and debate. Oestrogen action is mediated via high affinity intracellular receptors expressed in target tissues. Two subtypes of oestrogen receptor known as REα (NR3A1) and ERß (NR3A2) have been cloned and hERß variant isoforms identified. In target cells these receptors can exist as homo- or heterodimers. We have used immunohistochemistry to examine the patterns of expression of ERs in human and non-human primates as a first step in determining the cellular targets for oestrogen action in the male. REα was detected in the epithelial cells of efferent ductules (ED) occasionally in epithelial and stromal cells within the epididymis but was undetectable in human or primate testes. Using a polyclonal antibody raised against the hinge domain of ERß, immunopositive staining was detected in multiple cell types within the testis and in epithelial and stromal cell nuclei throughout the male reproductive system (ED, epididymis, vas deferens, seminal vesicles, prostate) and in the bladder. We have also used monoclonal antibodies that distinguish between wild type, full-length ERß (ERß1), and a splice variant isoform called ERßcx/ERß2 that does not bind oestrogens. ERß1 and ERß2 proteins were both detected in human testis and have distinct but overlapping patterns of expression. ERß1 was also detected in ED, epididymis and vas. In conclusion, oestrogen receptors are widely expressed in the male urogenital system and with the exception of the ED there are more cells that express ERß than REα. In the adult human the testicular cells most likely to be targets for oestrogens are round spermatids in which levels of expression of full-length wild type receptor (ERß1) are high.     

TOPASE-MED : comment repenser l’imagerie TEP grâce aux détecteurs semiconducteurs

This paper presents the main outcomes of the TOPASE-MED project, a feasibility study of a semiconductor-based PET imaging system, using CdTe as detection material. This project has followed three main goals: dimensioning a CdTe-based imager by simulation, developing technological bricks needed to build such a system and demonstrating experimentally the potential of the technology with a small scale mock-up.     

Place de l’imagerie dans l’évaluation de l’efficacité des traitements dans le cancer du sein

This paper describes, from the current literature, the role of various imaging methods to assess the response to therapy in breast cancer. Two different clinical situations are considered: neoadjuvant chemotherapy of locally advanced breast cancer and the metastastic breast cancer. Significant clinical data are available for three criteria: the volume of the tumour, the uptake of fluorodeoxyglucose using PET and the perfusion of the tumor evaluated either by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) or by PET using ¹⁵O water. ¹⁸F FDG PET allows prediction of the response after one or two cycles of neoadjuvant chemotherapy. New approaches will offer opportunities to refine the role of imaging in monitoring the response to chemotherapy. PET using thymidine as biomarker is promising in assessing the tissular proliferation. Estrogen analogs could be used to predict hormonally responsive breast cancer. Many other approaches, although less developed, might offer new insights in the response to therapy of breast cancer like magnetic resonance spectroscopy or optical imaging of hemoglobin oxygenation. Imaging also offers potential of monitoring the down-regulation of specialized receptors of the cell membrane in response to treatment: the most studied receptor in preclinical model has been the human epidermal growth factor receptor type 2 (HER2). Integrin, a family of cell adhesion receptor, is also an important target for imaging. Apoptosis, multidrug resistance and hypoxia can also be studied using appropriate biomarkers. To allow reliable multicenter trials of new drugs, these different imaging approaches still require an improved standardization of image acquisition and processing.     

Rôle de la TEP FDG dans l’évaluation de l’extension locorégionale et à distance du mélanome

FDG PET/CT is a relevant examination for patients with high-risk melanoma. For early stages with thickness ≥ 1 mm, lymph node ultrasound, and when negative, lymphoscintigraphy for determination of sentinel lymph node, remain necessary. For more advanced stages, FDG PET can map the lesions and guide the therapeutic strategy, either with surgical management, or systemic therapy (or sometimes both). In patients with high-risk melanoma, it allows to detect relapses early, including in asymptomatic patients, with a potential impact on therapeutic decisions. Beside the detection of classical secondary localizations, FDG PET has the advantage of allowing whole-body imaging, the identification of soft tissue lesions, frequent in melanomas, as well as rarer sites of involvement, such as those of the gastro-intestinal tract. For the assessment of cerebral and leptomeningeal involvement, MRI remains mandatory. Evolutions in the therapeutic management of advanced melanomas, and the search for biomarkers to guide the therapeutic strategy, ask for more refined analyses of PET, with metabolic tumour volume analysis and radiomics. The combination of metabolic imaging data with biological and molecular data, and the development of new PET tracers may improve the assessment of prognosis and the prediction of response to therapies, in order to tailor the therapeutic strategy to each patient. Further studies are needed to consolidate the role of PET/CT in this disease for which numerous therapeutic innovations are emerging.     

Transmission héréditaire de l’information épigénétique par le gamète mâle

What determines phenotype is one of the most fundamental questions in biology. Historically, most studies have focused on genetics but more recent studies have revealed the existence of epigenetic modifications that are not based on DNA sequencing but are essential for appropriate gene expression. Importantly, these epigenetic modifications can be inherited by the offspring. Thus, both male and female gametes contain inherited epigenetic information.     

Intérêt du dosage de l’inhibine B et de l’AMH dans le plasma séminal: étude préliminaire

Objectives

The aim of this study was to establish reference values for seminal inhibin B and AMH concentrations in patients with normal and abnormal sperm parameters. Preliminary analysis was performed to evaluate the predictive value of these markers for retrieving testicular sperm in non-obstructive azoospermic men.

Methods

Seminal inhibin B and AMH concentrations were assayed by an enzyme-linked immunoassay in three groups of men: 47 patients with normal sperm parameters, 28 oligospermic men and 68 patients with azoospermia.

Results

Inhibin B and AMH concentrations varied considerably in the three groups, but were significantly higher in normospermic men (inhibin B: 714.36±522.66 ng/l, AMH: 97.08±135.15 pmol/l) than in oligospermic men (inhibin B: 417.5±386.9 ng/l, AMH: 62.02±93.33 pmol/l) and azoospermic men (59.61±2.65 ng/l et 13.12±31.94 pmol/l, respectively) (p<0.001). A significant correlation (p=0.0054) was observed between seminal inhibin B concentration and sperm production. Testicular biopsy allowed sperm retrieval in 11 out of 21 patients (52.3%). The predictive value of seminal inhibin B was analyzed using receiver operating characteristics (ROC) curve analysis. The best discriminating inhibin B concentration was 30 ng/l with an area under the curve (AUC) of 0.63.

Conclusion

This study confirms the correlation between seminal inhibin B and AMH concentrations and spermatogenesis. However, the significance of these two markers as predictors of the presence of testicular sperm in men with non-obstructive azoospermia is limited. This analysis shows that AMH and inhibin B, either alone or in combination with serum FSH, fail to predict the presence of sperm in men with non-obstructive azoospermia undergoing testicular sperm extraction.     

Le Paléolithique supérieur dans l’ouest de l’île principale du Japon

The Kinki, Chugoku and Shikoku regions are located in the western part of the Japanese mainland. This area lacks the Pleistocene volcanic soil except a part of Chugoku Mountains. For this reason, the chronology of the late Paleolithic stone industries has been mainly studied by technology and typology of the fields excavated. However, after the late 1980s, the analysis of volcanic ash that contained the Paleolithic sediments had remarkable development. As a result, the cultural layer between the distant Paleolithic sites is compared by several widespread volcanic ashes such as Aira-Tanzawa (in short AT) as key bed. In this paper, we offered chronological order of the late Paleolithic culture in these regions by comparing cultural layers on the basis of the widespread volcanic ashes, referring to typological analysis of industries. The Sétoüchi technique and Ku industry characterize the late Paleolithic culture in these regions. The Sétoüchi technique is the unique one to produce the Ku type backed knife blunting on only one side, using the particular side-blow flaking technology based on physical characteristics of sanukite stone which is a kind of andesite. However, a hypothesis named the “Sétoüchi concept” was proposed in 2001, and it has been used as a substitute of the “Sétoüchi technique” by a few Japanese researchers. So we point out the mistake of the Sétoüchi concept relying on the fact which yielded stratigraphically two different industries in the Suncheon site.     

Personnages dans l’art saharien : le réel et l’imaginé

In the Sahara, wherever there are naked rock surfaces, engravings and paintings have been found in large numbers. This rock art includes various types of images — the oldest dating about ten millenniums — among which human beings, wild or domesticated animals, therianthrops and non-explicit images can be identified. According to periods and styles, the human being has been represented under extremely varied aspects from particularly realistic — similar to the reality — till very simplified, even caricatural drawings. For some realistic representations of women and men, we can observe anatomical or morphological peculiarities which, without being frequent, show cases of steatopygy and gynoïd or androïd obesity, pathological or not. For certain periods, we also find imaginary, fantastic or caricatural representations. These images characterize particularly styles previous to that called “Round Heads”. So, in the Saharan art, the human being has been represented either in his physical truth, or according to multiple stylistic conventions or graphic stereotypes, which could characterize certain ethnic groups.     

Place de l’embolisation percutanée de la varicocèle dans le traitement de l’infertilité

Objectives

To describe percutaneous embolization of varicocele and to evaluate the effect on fertility disorders.

Materials and methods

One hundred nineteen patients, aged 11 to 48 years, underwent percutaneous embolization for varicocele indicated by a fertility disorder in 23% of cases. Correction of the varicocele and resolution of associated pain, improvement of testicular trophicity and the effect on fertility were studied and a review of the literature was performed.

Results

Percutaneous embolization was performed using neuroleptanalgesia on an outpatient basis. The technique combined venous sclerotherapy and placement of coils in the gonadal vein. The technique was successful in 95% of cases and one complication was observed. At 3 months, the varicocele and related pain had resolved in 98% of treated patients. According to previous reports in the literature, the relations between varicocele and fertility disorders are still unclear, but improvement of fertility (semen quality and conception rates) after varicocele repair has been established.

Conclusion

Although the consequences of varicocele on fertility have not been fully elucidated, treatment of varicocele appears to be beneficial. Percutaneous embolization of varicocele is a safe and effective alternative to surgery. This technique, based on a urological and radiological consensus, is the first-line treatment for varicocele in our institution.     

Influence de la méthode de fixation sur l'observation des divisions cellulaires dans l'adénohypophyse du rat mâle

Résumé Les mitoses de l'adénohypophyse du rat mâle ont été examinées comparativement après fixation par perfusion et après fixation par immersion.Après fixation par perfusion la répartition topographique des mitoses dans le parenchyme est homogène, et l'index mitotique est de 1,85 pour 1 000 cellules.Après fixation par immersion, la densité des mitoses décroit de la périphérie vers le centre, et l'index mitotique n'est que de 0,80 mitoses pour 1 000 cellules.La lenteur de pénétration du fixateur pendant l'immersion est tenue pour principal responsable des différences observées. Elle entraîne une modification de l'aspect des mitoses, telle que plus de la moitié d'entre elles ne sont pas identifiables et échappent aux comptages.

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Influence of fixation on the observation of mitoses in the male rat adenohypophysis

Summary The mitoses of the adenohypophysis in male rats have been observed comparatively after fixation by perfusion and fixation by immersion.After fixation by perfusion, the topographic distribution of mitoses throughout the parenchyma is homogenous and the mitotic index is 1.85 for 1 000 cells.After fixation by immersion, the density of the mitoses is decreasing from the periphery towards the center and the mitotic index is only 0.80 for 1 000 cells.The slow penetration of the fixative during fixation by immersion is considered to be the main cause in the differences observed. This slow action causes a modification in the aspect of the mitoses, and more than fifty percent of them cannot be identified and escape to the counts.

Avec la collaboration technique de Mademoiselle J. Rameau.     

Techniques de contrôle de l’éjaculation dans l’ancienne Chine

The erotic literature of ancient China constitutes an inexhaustible source of information on ejaculation control techniques, which remain valid today and are the source of the techniques advocated by contemporary sex therapists.     

Comparaison de différents indices métaboliques et de la méthode SULTAN dans l’évaluation de la réponse thérapeutique par TEP au 18FDG dans le cancer du sein métastatique

Objective18F-FDG PET is a valuable tool in the evaluation of therapeutic response in breast cancer. This retrospective study was designed to compare the performance of six metabolic indices and to define their optimal thresholds, in patients treated with chemotherapy or hormone therapy for metastatic breast cancer. The performances of a parametric analysis by SULTAN method were also evaluated.MethodsTwenty patients, who underwent from 2 to 7 PET during the follow-up were analyzed. For each target, six indices were measured: SUVmax (maximum Standardized Uptake Value), SUVpeak, SAM (Standardized Added Metabolic activity), metabolic volume (MV), SUVmean using an adaptive threshold, and TLG (total lesion glycolysis). The percentage change of each target between each PET was calculated. A method based on parametric imaging (SULTAN) was also applied to each patient. The results were compared to the gold standard, defined by clinical evaluation, biological and morphological imaging RECIST 1.1 criteria. A per-lesion and per-patient analysis were performed and the optimal thresholds for each indices were calculated.ResultsFor the per-lesion analysis, 61 targets and 111 evolutions with 67 responders (R) and 44 non-responders (NR) were studied. Using ROC curve analysis and intercomparison, SUVmax, SUVpeak and SUVmean were significantly better than SAM, TLG and VM (P < 0.05). Using the optimal thresholds of −21%, –21%, –34%, –48% and –23% for SUVmax, SUVpeak, SUVmean, SAM and TLG respectively, these five indices were significantly correlated with the gold standard. SUVmax, SUVpeak and SUVmean showed the best performances of sensitivity (88%, 87% and 78% respectively), specificity (93%, 93% and 98% respectively) and negative predictive value (NPV) (84%, 69% and 74% respectively). For the per-patient analysis, 42 pairs of PET with 22 R and 20 NR were studied. Only SUVmax and SUVpeak were correlated to gold standard with the 30%-PERCIST-threshold and with optimal thresholds with performances of sensitivity of 73% and 77%, specificity of 95% and NPV of 76% and 79%. Parametric analysis with SULTAN showed excellent performances in the per-lesion and per-patient analysis (sensitivity 84% and 82%, specificity 98% and 90%, NPV 80% and 82%, respectively).ConclusionSUVmax and SUVpeak appeared the best indices to evaluate metabolic response in metastatic breast cancer. The SULTAN method was a reliable method to assist interpretation.     

Apport de l’iode 131 dans le traitement de la maladie de Basedow dans le service de médecine nucléaire de l’hôpital Ibn Sina de Rabat

One hundred and twenty-nine Grave's Basedow diseases in any gender and variable age patients, coming from several cities of Morocco, were randomized in a study of radio-iodine treatment who took place at the nuclear medicine department of Ibn Sina Hospital (Rabat, Morocco) during the period (from January 2001 to December 2008). The radio-iodine treatment was a first, second or third option and radio-iodine activities delivered varied (from 222 to 555 MBq 6 to 15 mCi) according to the age, the thyroid volume, the degree of hyperthyroidism and socio-economical situation. The high amounts of ¹³¹I were reserved especially to the patients who live far and whose socio-economic level is low with an aim of quickly obtaining an easily controllable state of hypothyroidism by a substitute treatment. The results showed that: (1) 57.36% of patients reverted to euthyroïdism (n = 74) with a patient having received two ¹³¹I cures. The second cure was justified by recurrence of hyperthyroidism after the first cure; (2) 34.88% passed in hypothyroidism (n = 45) with three patients having received two cures of ¹³¹I, the second cure was justified by recurrence of hyperthyroidism after the first cure in two patients and by the persistence of the hyperthyroidism after the first cure for the third patient. The average time of passage in hypothyroidism was 4.5 months; (3) 7.76% had remained in hyperthyroidism after the radioactive iodine treatment. Finally, 92.24% of our patients treated by radioactive iodine had passed in euthyroïdism or hypothyroidism against 7.76% whose hyperthyroidism had persisted or occurred.     

Rôle du sens de l’effort dans le syndrome d’influence

Centrally generated signals from premotor areas play a key role in voluntary muscle force perception. Indeed, sensations of effort, rather than sensations of intramuscular tension, make it possible to evaluate the intensity of willed muscle forces. We suggest that the sense of effort is involved in agency, the cognitive process by which one is aware of one’s actions. We argue that effort awareness accompanies each action and is the key component of the feeling of will. In delusions of alien control, patients with schizophrenia do not recognize some of their acts as their own and are convinced that they are under the control of someone else. Some experimental data suggest that delusions of control are related to an altered awareness of effort and an exaggerated awareness of afferent neural information, caused by neurological disorders in the frontal and parietal lobes. This impairment could lead to the inability to identify the author of an action. In this pathological condition, the cerebral state coding for “I intend to act” might move toward the state coding for “someone else intends to act”, even in the absence of another agent.