Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

AIMS: To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. DESIGN: In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12 years), those who initiated at a later age (13-14 years) and those who did not use cannabis by the age of 14 were compared with respect to HPA axis activity. SETTING AND PARTICIPANTS: Data were used from the first and second assessment wave of the TRacking Adolescents' Individual Lives Survey (TRAILS), that included 1768 Dutch young adolescents aged 10-12 years who were followed-up across a period of 2 years. MEASUREMENTS: Cortisol was measured in saliva samples at awakening, 30 minutes later and at 8 p.m. at age 10-12. Self-reported age at first cannabis use was used. FINDINGS: The early onset group had lower cortisol levels 30 minutes after awakening than the late onset group (OR = 0.93, 95% CI: 0.86-0.99). Furthermore, compared to non-users, the early and late onset cannabis users had higher levels of cortisol at 8 p.m. (OR = 1.25, 95% CI: 1.03-1.53 and OR = 1.21, 95% CI: 1.01-1.45, respectively). CONCLUSIONS: Some evidence was found for HPA axis hypo-activity at awakening in adolescents with early onset of cannabis use compared to late onset users, which might indicate an increased risk for early onset users of seeking stimulation to restore arousal levels by using substances.     

Pilot study: does the Five Shot Questionnaire give an indication of the severity of alcohol use-related problems?

This study explores whether the Five Shot Questionnaire reflects the severity of alcoholic inpatients' problems, such as assessed clinically by means of the EuropASI. Data were collected from 101 patients admitted to a psychiatric hospital in Belgium for alcohol use-related problems between September 2003 and December 2004. To investigate the research question, regression analyses--linear, ordinal, and binary logistic regression--have been performed. We conclude that the Five Shot Questionnaire gives an indication of the severity of alcohol use-related problems. As such, it can be recommended in general practice and emergency departments for further evaluation and treatment planning. The article ends with a discussion of its limitations and some suggestions for future research.     

hK2 and free PSA, a prognostic combination in predicting minimal prostate cancer in screen-detected men within the PSA range 4-10 ng/ml

OBJECTIVES: The purpose of screening for prostate cancer is to decrease the disease-specific mortality. However not every screen-detected prostate cancer is a threat to the patient's life. The risk of overdetection and subsequent overtreatment in prostate cancer has been recognised. The purpose of this investigation was to evaluate the role of tumour markers total PSA, free PSA, and hK2, and their combinations in predicting minimal prostate cancer. METHODS: Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, The Netherlands, prebiopsy serum samples were analysed for 100 selected men who underwent a radical prostatectomy for their screen-detected prostate cancer. All had a PSA value between 4 and 10 ng/ml prior to diagnosis. Minimal prostate cancer is defined as organ confined, Gleason score 相似文献   

A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells

Natural killer (NK) T cells using an invariant Valpha14 (Valpha14i) T cell receptor rearrangement form a distinct immunoregulatory T cell lineage. Several studies indicated that a NK1.1(-) Valpha14i NKT precursor cell differentiates and expands within the thymus before export to the peripheral tissues occurs. However, little is known about the signals that cause the emigration of Valpha14i NKT cells from the thymus to the periphery. Here we show that signaling of lymphotoxin (LT) alphabeta through the LTbeta receptor (LTbetaR) is indispensable for regulating peripheral but not thymic Valpha14i NKT cell numbers. Homing to and homeostatic proliferation of thymic Valpha14i NKT cells in peripheral organs, however, was not dependent on LTbetaR. Instead, our data indicate that a LTbetaR-expressing thymic stromal cell regulates the thymic emigration of Valpha14i NKT cells but not conventional T cell receptor alphabeta cells.     

A longitudinal twin study on IQ, executive functioning, and attention problems during childhood and early adolescence

Variation in human behavior may be caused by differences in genotype and by non-genetic differences ("environment") between individuals. The relative contributions of genotype (G) and environment (E) to phenotypic variation can be assessed with the classical twin design. We illustrate this approach with longitudinal data collected in 5 and 12-year-old Dutch twins. At age 5 data on cognitive abilities as assessed with a standard intelligence test (IQ), working memory, selective and sustained attention, and attention problems were collected in 237 twin pairs. Seven years later, 172 twin pairs participated again when they were 12 years old and underwent a similar protocol. Results showed that variation in all phenotypes was influenced by genetic factors. For IQ the heritability estimates increased from 30% at age 5, to 80% at age 12. For executive functioning performance genetic factors accounted for around 50% of the variance at both ages. Attention problems showed high heritabilities (above 60%) at both ages, for maternal and teacher ratings. Longitudinal analyses revealed that executive functioning during childhood was weakly correlated with IQ scores at age 12. Attention problems during childhood, as rated by the mother and the teacher were stronger predictors (r = -0.28 and -0.36, respectively). This association could be attributed to a partly overlapping set of genes influencing attention problems at age 5 and IQ at age 12. IQ performance at age 5 was the best predictor of IQ at age 12. IQ at both ages was influenced by the same genes, whose influence was amplified during development.     

Neoadjuvant Sorafenib Treatment of Clear Cell Renal Cell Carcinoma and Release of Circulating Tumor Fragments

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by high constitutive vascular endothelial growth factor A (VEGF-A) production that induces a specific vascular phenotype. We previously reported that this phenotype may allow shedding of multicellular tumor fragments into the circulation, possibly contributing to the development of metastasis. Disruption of this phenotype through inhibition of VEGF signaling may therefore result in reduced shedding of tumor fragments and improved prognosis. To test this hypothesis, we investigated the effect of neoadjuvant sorafenib treatment on tumor cluster shedding. PATIENTS AND METHODS: Patients with renal cancer (n = 10, of which 8 have ccRCC) received sorafenib for 4 weeks before tumor nephrectomy. The resection specimens were perfused, and the perfundate was examined for the presence of tumor clusters. Effects of the treatment on the tumor morphology and overall survival were investigated (follow-up of 2 years) and compared with a carefully matched control group. RESULTS: Neoadjuvant sorafenib treatment induced extensive ischemic tumor necrosis and, as expected, destroyed the characteristic ccRCC vascular phenotype. In contrast to the expectation, vital groups of tumor cells with high proliferation indices were detected in postsurgical renal venous outflow in 75% of the cases. Overall survival of patients receiving neoadjuvant treatment was reduced compared to a control group, matched with regard to prognostic parameters. CONCLUSIONS: These results suggest that neoadjuvant sorafenib therapy for ccRCC does not prevent shedding of tumor fragments. Although this is a nonrandomized study with a small patient group, our results suggest that neoadjuvant treatment may worsen survival through as yet undefined mechanisms.Abbreviations: ccRCC, clear cell renal cell carcinoma; VEGF, vascular endothelial growth factor