Vers un rapprochement du syndrome de Klinefelter et de la psychopathie en psychiatrie légale

Klinefelter syndrome (KS) (47,XXY) is the most common aneuploidy (1/650) of sexual chromosome among male (0,1 à 0,2 % of male population) (Hong and Reiss, 2014). Because its large physical phenotypic variability (high tall, sparse hairiness, gynecomastia), this syndrome is largely underdiagnosed (less than 25 % of affected persons) (Samango-Sprouse et al., 2018). Nevertheless, cognitive variability is smaller. Normal to low average total IQ, low verbal IQ, social problems and high levels of psychiatric comorbidities including early aggressiveness are commonly described (Hong and Reiss, 2014). In Denmark, higher risks of committing sexual crime and arson (compared to criminal controls) was recently reported (Stochholm et al., 2012). Quite a few clinically relevant cases reports scattered in the literature, suggests the presence of a pattern of a specific subtype of KS inpatients among forensic population (Bénézech, 1975). However, very few studies provide quantitative or qualitative pertaining to robust results. KS well-documented neurobiological (van Rijn, 2018) (e.g. low levels of testosterone), neuropsychological (Bénézech, 1975; Hong and Reiss, 2014; Samango-Sprouse et al., 2018; Savic, 2012; Seara-Cardoso et al., 2016; Senon, 2005; Stochholm et al., 2012; van Rijn, 2018; van Rijn et al., 2008; van Rijn et al., 2018; van Rijn et al., 2014; van Rijn et al., 2012) [29] (e.g. alterations of both complex cerebral — attention, empathy — and behavioral regulation functions - inhibition, mental flexibility, emotional response modulation, control of own actions) and neuroanatomical (Hong and Reiss, 2014; Itti et al., 2003; Savic, 2012; van Rijn et al., 2008; van Rijn et al., 2012) [29] (e.g. limbic system and temporal lobe abnormal volume, hemispheric specialization shortcoming) features may be helpful to understand comorbid symptoms psychopathology. Numbers of recent studies conduct on KS pediatric or adult population provide interesting results on conduct, anxiety, psychotic and autism spectrum disorders. In addition, some authors use genetic and epigenetic specific features of sex chromosome aneuploidies (e.g. X genes neurodevelopmental role; imprinting) in order to clarify genotype-phenotype links of comorbid symptoms (Bruining et al., 2011; Zitzmann et al., 2004;). With Belgian colleagues from the Social Defense Research Center (CRDS, Tournai, Belgium), we are currently recruiting KS inpatients from security hospitals or psychiatric units in Belgium and France. We aim to assess psychopathic traits with the Psychopathy Checklist Revised (PCL-R, Hare) (Hare, 2003). Our first results concerning 3 KS males outline that PCL-R is useful for the characterization of clinical phenotype among KS forensic sample. While three of them present psychopathic traits, two of them present categorical double diagnose “psychopathy-KS” (total PCL-R score > = 30/40 (Delannoy et al., 2017)). Moreover, dimensional analysis support our hypothesis of a higher prevalence of “explosive profile” in comparison to other psychopathic profiles in our sample (Delannoy et al., 2017). The present article summarizes historic background (e.g. “psychopathy” disappearance of mental disorder reference classification schemes, “crime chromosome” (Bénézech, 1975)) and current context argues (e.g. French psychiatrists court experts widely refer to psychopathy concept despite a lack of consensual definition (Senon, 2005), weak knowledge and training of PCL-R and its related biopsychological recent findings (Blair, 2013; de Oliveira-Souza et al., 2008; Dotterer et al., 2017; Glenn and Raine, 2014; Hosking et al., 2017; Korponay et al., 2017; Pham, 1995; Pham, 2005; Raine, 2008; Raine et al., 2003); stigma and discrimination apprehensions of KS and psychopath) that motivate our research project. Finally, we discuss the advantages of our research protocol on KS participants assessed with PCL-R, such as tackling stigma and discrimination, better understanding psychopathology, and clarifying murky interactions of biological, psychological and social factors entangled in the development of these two fascinating troubles.     

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Preparation and tumor affinity testing of the radioiodinated tetrahydroisoquinoline derivative [123I]TIC(OH) for targeting prostate cancer.

This work describes the synthesis and tumor affinity testing of 8-[123I]iodo-l-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid [ITIC(OH)], a cyclic non-naturally occurring amino acid as an imaging probe for prostate cancer. Parameters for labelling were optimized with regard to the amount of precursor, the temperature and time. Thereafter, ITIC(OH) was evaluated in terms of its uptake in primary human PC-3 and DU-145 prostate cancer cells, followed by analysis of the underlying mechanisms of the radioactivity accumulation in tumor cells. No-carrier-added ITIC(OH) was obtained in 80+/-15% radiochemical yield and >98% radiochemical purity by a one-step radioiodination, using IODO-GEN as oxidant. The total synthesis time was less than 30 min, and compatible with a clinical routine production. ITIC(OH) accumulated intensively in primary human prostate cancer cells. The radioactivity incorporation in tumor following a 10-min incubation at 37 degrees C/pH 7.4 varied from 35% to 58% of the total loaded activity per 10(6) tumor cells (355-540 cpm/1000 cells). Inhibition experiments revealed that ITIC(OH) was taken up into tumor by an active transport different from the common amino acid carrier systems, including the sodium-dependent system A and B+,0, and the sodium-independent L- and ASC-type transporter. In contrast, the cellular incorporation was dependent on the membrane potential and correlated with the activity of the mitochondria. In conclusion, the specific and high-level accumulation of ITIC(OH) in human prostate carcinoma cells, indicates that the new radiopharmaceutical is a good candidate for further in vivo investigations to ascertain its potential as an imaging probe for prostate cancer by SPET.     

PDT in clinics: indications, results, and markets.

Photodynamic therapy (PDT) is based on the selective light activation of an exogenously given drug to patients. PDT acts mainly on cell membranes either of neovascular endothelial cells or of cancer cells leading to cancer cell death. Six drugs are now marketed based on clinical assays in various indications, which showed a clear cost efficiency as compared to other classical procedures. PDT is easy to handle and can be performed in medical installations fitting the conditions of health care in developing countries. Its cost effectiveness could represent an appropriate solution to the increasing number of cancers of various origin. However despite all the clinical results now available, PDT development remains slow. The reasons for this situation include cost of development, intellectual property, and competition between pharmaceutical companies.     

Gestion des risques et choix de maintenance à l'hôpitalRisks management and maintenance choices at the hospital

Regulations evolve and risks management becomes one of the biomedical engineers' preoccupations. Thus, risks are various, and consequently it is difficult to identify, to manage and to bring them under control. Furthermore, regulations exist for sectors like healthcare technology monitoring, but it is not the same thing for instance for the risks linked to the maintenance. Thus regulation in the sector of maintenance evolves and the decree of the 1^st July law of health safety is going to modify the biomedical environment. The goal of this work is to study the tools and the methods of risks management that have been used for several years in the industrial field and to use them for some biomedical equipment like monitors or IV pumps. These methods adapted to these equipment will allow us to determine some appropriate rules of maintenance.     

Severe hypoglycorrhachia after subarachnoid hemorrhage. Two cases with spontaneous recovery in adults

We report two patients with severe hypoglycorrhachia after a subarachnoid hemorrhage. They had no obvious meningeal infection, and they spontaneously recovered within a few weeks. Such cases have previously been reported in neonates, but exceptionally in adults. Contrary to detailed cases from the literature, our patients recovered without antibiotics, and hypoglycorrhachia was very severe.     

Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers.

Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 microg of SCT orally, a placebo, and a 10-microg (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5-1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 microg exceeding those of 10 microg intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases.