Quantitative Assessment of T1 Relaxation and Diffusion as a Prognostic Tool for Brain Development: A Longitudinal Preliminary Study on Preterm Babies

BACKGROUND: Despite major advances in care of premature infants, survivors exhibit mild cognitive deficits in around 40%. Beside severe intraventricular haemorrhages (IVH) and cystic periventricular leucomalacia (PVL), more subtle patterns such as grade I and II IVH, punctuate WM lesions and diffuse PVL might be linked to the cognitive deficits. Grey matter disease is also recognized to contribute to long-term cognitive impairment.¦OBJECTIVE: We intend to use novel MR techniques to study more precisely the different injury patterns. In particular MP2RAGE (magnetization prepared dual rapid echo gradient) produces high-resolution quantitative T1 relaxation maps. This contrast is known to reflect tissue anomalies such as white matter injury in general and dysmyelination in particular. We also used diffusion tensor imaging, a quantitative technique known to reflect white matter maturation and disease.¦DESIGN/METHODS: All preterm infants born under 30 weeks of GA were included. Serial 3T MR-imaging using a neonatal head-coil at DOL 3, 10 and at term equivalent age (TEA), using DTI and MP2RAGE sequences was performed. MP2RAGE generates a T1 map and allows calculating the relaxation time T1. Multiple measurements were performed for each exam in 12 defined white and grey matter ROIs.¦RESULTS: 16 patients were recruited: mean GA 27 2/7 w (191,2d SD±10,8), mean BW 999g (SD±265). 39 MRIs were realized (12 early: mean 4,83d±1,75, 13 late: mean 18,77d±8,05 and 14 at TEA: 88,91d±8,96). Measures of relaxation time T1 show a gradual and significant decrease over time (for ROI PLIC mean±SD in ms: 2100.53±102,75, 2116,5±41,55 and 1726,42±51,31 and for ROI central WM: 2302,25±79,02, 2315,02±115,02 and 1992,7±96,37 for early, late and TEA MR respectively). These trends are also observed in grey matter area, especially in thalamus. Measurements of ADC values show similar monotonous decrease over time.¦CONCLUSIONS: From these preliminary results, we conclude that quantitative MR imaging in very preterm infants is feasible. On the successive MP2RAGE and DTI sequences, we observe a gradual decrease over time in the described ROIs, representing the progressive maturation of the WM micro-structure and interestingly the same evolution is observed in the grey matter. We speculate that our study will provide normative values for T1map and ADC and might be a predictive factor for favourable or less favourable outcome.

Correlation between placental bacterial culture results and histological chorioamnionitis: a prospective study on 376 placentas.

OBJECTIVE: To study the correlation between the bacteriological and histopathological findings in placentas from women with suspected or proven chorioamnionitis (CA). METHODS: Over a 1-year period, 376 placentas were prospectively collected and processed for bacteriological and pathological studies in cases of confirmed or suspected maternal or neonatal infection. RESULTS: Histological CA was diagnosed in 26.9% of placentas (101/376), and 27.7% (28/101) of these placentas had positive bacteriological cultures. A monomicrobial culture, mainly represented by Gram-positive cocci and Gram-negative bacilli, was identified in 27% of the positive bacterial cultures. The proportion of positive cultures was higher (p=0.03) when CA was associated with funisitis, as compared with placental samples with early CA. In placentas without histological CA, bacteriological cultures were mostly negative (230/275), although pathogenic bacteria were identified in 16.3% of them (45/275). CONCLUSIONS: The histological and bacteriological results were concordant in about 70% of the examined placentas, with 61.1% negative cases (CA absent and negative bacterial cultures), and only 7.4% placentas with positive histological and bacteriological results. Discordant results (positive histology with negative bacteriology) were obtained in placentas with early CA documented by histology although possibly in relation with antibiotic prophylaxis and the presence of fastidious bacteria. Conversely, negative histology with positive bacteriology could be explained by the presence of an early-stage bacterial infection that has not yet led to detectable microscopic lesions.

Pharmacogenetic Study on Risperidone Long-Acting Injection: Influence of Cytochrome P450 2D6 and Pregnane X Receptor on Risperidone Exposure and Drug-Induced Side-Effects.

Risperidone is metabolized by polymorphic enzymes, and a large variability in plasma concentration and therapeutic response is observed. Risperidone long-acting injection (RLAI) avoids the first-pass effect, and little is known about the influence of gene polymorphisms involved in its pharmacokinetics. The influence on plasma concentrations of risperidone (RIS), its metabolite 9-hydroxy-risperidone, and on adverse effects were investigated for polymorphisms of cytochrome P450 2D6 (CYP2D6) (*3, *4, *5, *6), CYP3A (CYP3A4*1B, CYP3A4 rs4646437, CYP3A5*3, CYP3A7*1C), ABCB1 (1236C>T, 2677G>T, 3435C>T), NR1/2 coding for pregnane X receptor (rs1523130, rs2472677, rs7643645), and for CYP3A activity measured by a phenotyping test. Forty-two patients with at least 4 consecutive unchanged doses of RLAI were included in a multicenter cross-sectional study. A 55% lower dose-adjusted plasma levels of RIS were observed for CYP2D6 ultrarapid metabolizers (n = 5) as compared with CYP2D6 intermediate metabolizers (P < 0.007). NR1/2 polymorphism (rs7643645A>G) influenced RIS exposure with a 2.8-fold lower active moiety (P = 0.031) in GG compared with the AA genotype. This was confirmed in a second independent cohort (n = 16). Furthermore, high-density lipoprotein cholesterol was positively correlated with CYP3A activity (P = 0.01), and the NR1/2 (rs2472677) polymorphism was associated with different adverse effects including prolactin plasma levels adjusted for age and sex. In conclusion, our results confirmed the influence of CYP2D6 genotype on plasma levels of RIS. This is the first report on the influence of NR1/2 polymorphisms on RLAI exposure and on drug-induced adverse effects. These results should be validated in larger cohorts.

Observational study on the consumption of recreational drugs and alcohol by Swiss travelers.

BACKGROUND: Studies carried out on specific travelers' groups such as students describe an increase in the consumption of alcohol and drugs during travel and vacation time. The present study investigates the risk behaviors (alcohol and drugs) in a general adult population in Switzerland travelling abroad who visited a travel clinic before departure. METHODS: This retrospective study was conducted in a travel clinic between January 2006 and December 2008. 14,496 patients came to the clinic for a pre-travel consultation. 3,537 of them answered a questionnaire about their life habits in Switzerland and during their last trip. The only exclusion criterion was an age inferior to 18 years old.The consumption habits of drugs and at-risk alcohol intake (8 standard drinks (SD) per week for women and 15 SD for men) was analyzed according to gender, sex, destination and profession. Predictors of adopting a risky behavior between habits in Switzerland and during their previous trip were also analyzed. RESULTS: 7% (229/3477) of participants declared having at-risk alcohol consumption in Switzerland and 14% (473/3275 [95% CI 13-16]) during their trip. 9% (332/3527) of the participants used drugs in Switzerland and 5% (178/3481) during their trip. Risk factors for at-risk alcohol consumption during a trip were: at-risk alcohol consumption in Switzerland (OR 31[95% CI 21-45]), smoking (1.7 [95% CI 1-2]), use of drugs in Switzerland (OR 2.2 [95% CI 2-3]), leisure travel (OR 1.6 [95% CI 1-2]) and managerial professions (OR 1.8 [95% CI 1-3]). Risk factors for the use of drugs during a trip were: alcohol consumption in Switzerland (OR 2.1 [95% CI 1-4]), smoking (OR 1.9 [95% CI 1-3]), and use of drugs in Switzerland (OR 29.7 [95% CI 19-45]). CONCLUSIONS: At-risk alcohol consumption and, to a lesser extent, use of drugs, affect a large number of travelers which expose them to health problems during a trip. Exploring the alcohol and drugs consumption patterns of people visiting a travel clinic should be part of the pre-travel routine consultation and would allow to identifying people who would benefit most from a specific prevention.

Biodiversity study of arthropods collected on rat carrion in Yaounde, Cameroon: first study on forensic entomology in Central Africa

The first investigation of arthropods associated with carrion in Cameroon was carried out within the campus of the University of Yaounde I (Cameroon) from 17thJanuary to 3rd April 2008. Carcasses of rats (Rattus norvegicus Berkenhout, 1769 var WISTAR) were exposed to colonization by the local fauna of arthropods. The invading organisms were collected daily during the study period. 2287 individuals of arthropod belonging to 3 classes, 16 orders, 37 families and 7 subfamilies were identified. The insects assessed were mainly Diptera, Coleoptera and Acari. This study illustrates the high diversity of the necroentomofauna in Cameroon and provides an insight approximation into the succession pattern of invading insect and a weekly estimation of the time of death.

To say or not to say: a qualitative study on the disclosure of their condition by human immunodeficiency virus-positive adolescents.

PURPOSE: Human immunodeficiency virus (HIV)-positive adolescents face a number of challenges in dealing with their disease, treatment, and developmental tasks. This qualitative study describes some of the reasons why, and the extent to which, adolescents may or may not disclose their condition to others. METHODS: A semistructured interview lasting 40-110 minutes was conducted with each of 29 adolescents 12-20 years old, 22 female and seven male) living in Switzerland. Interviews were tape recorded and transcribed verbatim. The analysis of the content of interviews allowed us to identify salient topics (e.g., disclosure), which were then explored in detail. RESULTS: Of 29 participants, eight had not disclosed their condition to anyone outside the family, 19 had disclosed it to good friends, and 16 had disclosed it to some teachers. Four participants had engaged in public disclosure, and six of 10 sexually active teenagers disclosed their status to their partners. The attitudes toward disclosure among younger adolescents were mostly related to those of the parents, particularly the mother. Older adolescents, engaged in their search for autonomy, tended to decide independently what to say and to whom. Although foster/adoptive parents would often encourage disclosure, biological parents, especially HIV-positive mothers, insisted on not disclosing the adolescent's status for fear of stigma. CONCLUSION: The health care team should systematically address the issue of disclosure with the adolescent and his family (or foster parents), the aim being to balance the right of the adolescent and that adolescent's family to maintain privacy against the concerns of sexual partners, as well as the adolescent's interest in divulging HIV status to relatives, school staff, and friends.

Correlations between trabecular bone score, measured using anteroposterior dual-energy x-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae.

Developing a novel technique for the efficient, noninvasive clinical evaluation of bone microarchitecture remains both crucial and challenging. The trabecular bone score (TBS) is a new gray-level texture measurement that is applicable to dual-energy X-ray absorptiometry (DXA) images. Significant correlations between TBS and standard 3-dimensional (3D) parameters of bone microarchitecture have been obtained using a numerical simulation approach. The main objective of this study was to empirically evaluate such correlations in anteroposterior spine DXA images. Thirty dried human cadaver vertebrae were evaluated. Micro-computed tomography acquisitions of the bone pieces were obtained at an isotropic resolution of 93μm. Standard parameters of bone microarchitecture were evaluated in a defined region within the vertebral body, excluding cortical bone. The bone pieces were measured on a Prodigy DXA system (GE Medical-Lunar, Madison, WI), using a custom-made positioning device and experimental setup. Significant correlations were detected between TBS and 3D parameters of bone microarchitecture, mostly independent of any correlation between TBS and bone mineral density (BMD). The greatest correlation was between TBS and connectivity density, with TBS explaining roughly 67.2% of the variance. Based on multivariate linear regression modeling, we have established a model to allow for the interpretation of the relationship between TBS and 3D bone microarchitecture parameters. This model indicates that TBS adds greater value and power of differentiation between samples with similar BMDs but different bone microarchitectures. It has been shown that it is possible to estimate bone microarchitecture status derived from DXA imaging using TBS.

A theoretical and practical study on linear reforms of dual taxes

[cat] En aquest treball extenem les reformes lineals introduïdes per Pfähler (1984) al cas d’impostos duals. Estudiem l’efecte relatiu que els retalls lineals duals d’un impost dual tenen sobre la distribució de la desigualtat -es pot fer un estudi simètric per al cas d’augments d’impostos-. Tambe introduïm mesures del grau de progressivitat d’impostos duals i mostrem que estan connectades amb el criteri de dominació de Lorenz. Addicionalment, estudiem l’elasticitat de la càrrega fiscal de cadascuna de les reformes proposades. Finalment, gràcies a un model de microsimulació i una gran base de dades que conté informació sobre l’IRPF espanyol de l’any 2004, 1) comparem l’efecte que diferents reformes tindrien sobre l’impost dual espanyol i 2) estudiem quina redistribució de la riquesa va suposar la reforma dual de l’IRPF (Llei ’35/2006’) respecte l’anterior impost.

Prices of medicines: a case-study on the impact of the rate-of-return regulation in the United Kingdom

This work carries out an empirical evaluation of the impact of the main mechanism for regulating the prices of medicines in the UK on a variety ofpharmaceutical price indices. The empirical evidence shows that the overall impact of the rate of return cap appears to have been slight or even null, and in any case that the impact would differ across therapeutic areas. These empiricalfindings suggest that the price regulation has managed to encourage UK-based firms¿ diversification in many therapeutic areas

Cannabis and tobacco use: where are the boundaries? A qualitative study on cannabis consumption modes among adolescents.

The purpose of this article is to identify tobacco and cannabis co-consumptions and consumers' perceptions of each substance. A qualitative research including 22 youths (14 males) aged 15-21 years in seven individual interviews and five focus groups. Discussions were recorded, transcribed verbatim and transferred to Atlas.ti software for narrative analysis. The main consumption mode is cannabis cigarettes which always mix cannabis and tobacco. Participants perceive cannabis much more positively than tobacco, which is considered unnatural, harmful and addictive. Future consumption forecasts thus more often exclude tobacco smoking than cannabis consumption. A substitution phenomenon often takes place between both substances. Given the co-consumption of tobacco and cannabis, in helping youths quit or decrease their consumptions, both substances should be taken into account in a global approach. Cannabis consumers should be made aware of their tobacco use while consuming cannabis and the risk of inducing nicotine addiction through cannabis use, despite the perceived disconnect between the two substances. Prevention programs should correct made-up ideas about cannabis consumption and convey a clear message about its harmful consequences. Our findings support the growing evidence which suggests that nicotine dependence and cigarette smoking may be induced by cannabis consumption.

Dermoscopy of acral melanoma: a multicenter study on behalf of the international dermoscopy society.

Background: Most studies on dermoscopy of acral lesions were conducted in Asian populations. In this study, we analyzed these features in a predominantly Caucasian population. Objective: Estimate the prevalence of dermoscopic features in acral lesions, and assess their level of agreement between observers. Methods: In this retrospective multicenter study, 167 acral lesions (66 melanomas) were evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet platform. Results: Parallel furrow pattern, bizarre pattern, and diffuse pigmentation with variable shades of brown had the highest prevalence. The agreement for lesion patterns between physicians was variable. Agreement was dependent on the level of diagnostic difficulty. Conclusion: Lesions with a diameter >1 cm were more likely to be melanoma. We found as well that a benign pattern can be seen in parts of melanomas. For this reason one should evaluate an acral lesion for the presence of malignant patterns first. © 2013 S. Karger AG, Basel.

Multicenter Study on the Clinical Effectiveness, Pharmacokinetics, and Pharmacogenetics of Mirtazapine in Depression.

ABSTRACT: Pharmacogenetic tests and therapeutic drug monitoring may considerably improve the pharmacotherapy of depression. The aim of this study was to evaluate the relationship between the efficacy of mirtazapine (MIR) and the steady-state plasma concentrations of its enantiomers and metabolites in moderately to severely depressed patients, taking their pharmacogenetic status into account. Inpatients and outpatients (n = 45; mean age, 51 years; range, 19-79 years) with major depressive episode received MIR for 8 weeks (30 mg/d on days 1-14 and 30-45 mg/d on days 15-56). Mirtazapine treatment resulted in a significant improvement in mean Hamilton Depression Rating Scale total score at the end of the study (P < 0.0001). There was no evidence for a significant plasma concentration-clinical effectiveness relationship regarding any pharmacokinetic parameter. The enantiomers of MIR and its hydroxylated (OH-MIR) and demethylated (DMIR) metabolites in plasma samples on days 14 and 56 were influenced by sex and age. Nonsmokers (n = 28) had higher mean MIR plasma levels than smokers (n = 17): S(+)-enantiomer of MIR, 9.4 (SD, 3.9) versus 6.2 (SD, 5.5) ng/mL (P = 0.005); R(-)-enantiomer of MIR, 24.4 (SD, 6.5) versus 18.5 (SD, 4.1) ng/mL (P = 0.003). Only in nonsmokers, plasma levels of S(+)-enantiomer of MIR and metabolites depended on the CYP2D6 genotype. Therefore, high CYP1A2 activity seen in smokers seems to mask the influence of the CYP2D6 genotype. In patients presenting the CYP2B6 *6/*6 genotype (n = 8), S-OH-MIR concentrations were higher those in the other patients (n = 37). Although it is not known if S-OH-MIR is associated with the therapeutic effect of MIR, the reduction of the Hamilton scores was significantly (P = 0.016) more pronounced in the CYP2B6 *6/*6-genotyped patients at the end of the study. The role of CYP2B6 in the metabolism and effectiveness of MIR should be further investigated.