Increased trimipramine plasma levels during fluvoxamine comedication.

A depressive patient, a non-responder to trimipramine (TRI), was comedicated first with citalopram (CIT) and then with fluvoxamine (FLUV). Both the TRI-CIT and TRI-FLUV combination treatments led to a worsening of the depressive state and to the appearance of panic attacks. The addition of FLUV to TRI resulted in a twofold increase of the plasma levels of TRI and to a slight increase of its N-demethylated and 2-hydroxylated metabolites. These results suggest that the interaction between FLUV and TRI occurred at the level of cytochrome P-450IID6 and cytochrome P-450meph in this patient, phenotyped as an extensive metabolizer of both dextromethorphan and mephenytoin. The adverse effects were possibly due to (a) a pharmacokinetic interaction between CIT and FLUV with TRI and/or (b) alterations in serotonergic and/or dopaminergic neurotransmission.

Plant growth and phosphorus uptake in mycorrhizal rangpur lime seedlings under different levels of phosphorus

The objective of this work was to evaluate the response of rangpur lime (Citrus limonia) to arbuscular mycorrhiza (Glomus intraradices), under P levels ranging from low to excessive. Plants were grown in three levels of soluble P (25, 200 and 1,000 mg kg-1), either inoculated with Glomus intraradices or left noninoculated, evaluated at 30, 60, 90, 120 and 150 days after transplanting (DAT). Total dry weight, shoot P concentration and specific P uptake by roots increased in mycorrhizal plants with the doses of 25 and 200 mg kg-1 P at 90 DAT. With 1,000 mg kg-1 P, mycorrhizal plants had a transient growth depression at 90 and 120 DAT, and nonmycorrhizal effects on P uptake at any harvesting period. Root colonization and total external mycelium correlated positively with shoot P concentration and total dry weight at the two lowest P levels. Although the highest P level decreased root colonization, it did not affect total external mycelium to the same extent. As a result, a P availability imbalance affected negatively the mycorrhizal symbiosis and, consequently, the plant growth.

Cytokines and hs-CRP levels in individuals treated with low-dose aspirin for cardiovascular prevention: a population-based study (CoLaus Study).

Pro-inflammatory cytokines and high-sensitive C-reactive protein (hs-CRP) are associated with increased risk for cardiovascular disease. Low-dose aspirin for CV prevention is reported to have anti-inflammatory effects. The aim of this study was to determine the association between pro-inflammatory cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention in a population-based cohort (CoLaus Study). We assessed blood samples in 6085 participants (3201 women) aged 35-75years. Medications' use and indications were recorded. Among aspirin users (n=1'034; 17%), overall low-dose users (351; 5.8%) and low-dose for cardiovascular prevention users (324; 5.3%) were selected for analysis. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α were assessed by a multiplex particle-based flow cytometric assay and hs-CRP by an immunometric assay. Cytokines and hs-CRP were presented in quartiles. Multivariate analysis adjusting for sex, age, smoking status, body mass index, diabetes mellitus and immunomodulatory drugs showed no association between cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention, either comparing the topmost vs. the three other quartiles (OR 95% CI, 0.84 (0.59-1.18), 1.03 (0.78-1.32), 1.10 (0.83-1.46), 1.00 (0.67-1.69) for IL-1β, IL-6, TNF-α and hs-CRP, respectively), or comparing the topmost quartile vs. the first one (OR 95% CI, 0.87 (0.60-1.26), 1.19 (0.79-1.79), 1.26 (0.86-1.84), 1.06 (0.67-1.69)). Low-dose aspirin use for cardiovascular prevention does not impact plasma pro-inflammatory cytokine and hs-CRP levels in a population-based cohort.

Effects of a nonpressor dose of neuropeptide Y on cardiac output, regional blood flow distribution and plasma renin, vasopressin and catecholamine levels.

Neuropeptide Y (NPY) is a peptide with vasoconstrictor properties known to be present in the central nervous system as well as in sympathetic nerve endings and the adrenal medulla. The purposes of this study were to investigate in normotensive conscious rats the effects of nonpressor doses of NPY on cardiac output and regional blood flow distribution (using radiolabeled microspheres) as well as on plasma renin activity, plasma catecholamine and vasopressin levels. NPY (0.1 microgram/min) infused i.v. for 30 min modified neither blood pressure nor heart rate. Cardiac index was at comparable levels in NPY- as in vehicle-treated rats (17.7 +/- 1.6, n = 8, vs. 21.3 +/- 0.9 ml/min/100 g, n = 8, mean +/- S.E.M.). There was no significant difference in regional blood flow distribution between the two groups of rats, except for the large intestine (0.42 +/- 0.06 vs. 0.71 +/- 0.1 ml/min/g in NPY- and vehicle-treated rats, respectively, P less than .05). Basal plasma renin activity and catecholamine levels were not modified by NPY whereas plasma vasopressin levels were lower (P less than .05) in rats given NPY (0.76 +/- 0.3 pg/ml, n = 8) than in those having received the vehicle (2.2 +/- 0.4 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of a Mendelian randomization approach to assess the causal relation of gamma-Glutamyltransferase with blood pressure and serum insulin levels.

Elevated levels of γ-glutamyltransferase (GGT) have been associated with elevated blood pressure (BP) and diabetes. However, the causality of these relations has not been addressed. The authors performed a cross-sectional analysis (2003-2006) among 4,360 participants from the population-based Cohorte Lausannoise (CoLaus) Study (Lausanne, Switzerland). The rs2017869 variant of the γ-glutamyltransferase 1 (GGT1) gene, which explained 1.6% of the variance in GGT levels, was used as an instrument for Mendelian randomization (MR). Sex-specific GGT quartiles were strongly associated with both systolic and diastolic BP (all P's < 0.0001). After multivariable adjustment, these relations were attenuated but remained significant. Using MR, the authors observed no positive association of GGT with BP (systolic: β -5.68, 95% confidence interval (CI): -11.51, 0.16 (P = 0.06); diastolic: β = -2.24, 95% CI: -5.98, 1.49 (P = 0.24)). The association of GGT with insulin was also attenuated after multivariable adjustment but persisted in the fully adjusted model (β = 0.07, 95% CI: 0.04, 0.09; P < 0.0001). Using MR, the authors also observed a positive association of GGT with insulin (β = 0.19, 95% CI: 0.01, 0.37; P = 0.04). In conclusion, the authors found evidence for a direct causal relation of GGT with fasting insulin but not with BP.

Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels.

The extended use of brentuximab-vedotin was reported for CD30(+) nonanaplastic peripheral T-cell lymphomas (PTCLs) with promising efficacy. CD30 status assessment is thus a critical factor for therapeutic decision, but the reliability of immunohistochemistry (IHC) in evaluating its expression remains to be defined. This prompted us to investigate the correlation between semiquantitative CD30 protein assessment by IHC and messenger RNA (mRNA) assessment by microarrays in a cohort of 376 noncutaneous PTCLs representative of the main entities. By IHC, CD30 expression was heterogeneous across and within entities and significantly associated with large tumor cell size. In addition to 100% anaplastic large-cell lymphomas, 57% of other PTCL entities were CD30-positive at a 5% threshold. CD30 protein expression was highly correlated to mRNA levels. mRNA levels were bimodal, separating high from low CD30-expressing PTCL cases. We conclude that IHC is a valuable tool in clinical practice to assess CD30 expression in PTCLs.

Haemodialysis acutely reduces the plasma levels of ADMA without reversing impaired NO-dependent vasodilation.

End-stage renal disease patients have endothelial dysfunction and high plasma levels of ADMA (asymmetric omega-NG,NG-dimethylarginine), an endogenous inhibitor of NOS (NO synthase). The actual link between these abnormalities is controversial. Therefore, in the present study, we investigated whether HD (haemodialysis) has an acute impact on NO-dependent vasodilation and plasma ADMA in these patients. A total of 24 patients undergoing maintenance HD (HD group) and 24 age- and gender-matched healthy controls (Control group) were enrolled. The increase in forearm SkBF (skin blood flow) caused by local heating to 41 degrees C (SkBF41), known to depend on endothelial NO production, was determined with laser Doppler imaging. SkBF41 was expressed as a percentage of the vasodilatory reserve obtained from the maximal SkBF induced by local heating to 43 degrees C (independent of NO). In HD patients, SkBF41 was assessed on two successive HD sessions, once immediately before and once immediately after HD. Plasma ADMA was assayed simultaneously with MS/MS (tandem MS). In the Control group, SkBF41 was determined twice, on two different days, and plasma ADMA was assayed once. In HD patients, SkBF41 was identical before (82.2+/-13.1%) and after (82.7+/-12.4%) HD, but was lower than in controls (day 1, 89.6+/-6.1; day 2, 89.2+/-6.9%; P<0.01 compared with the HD group). In contrast, plasma ADMA was higher before (0.98+/-0.17 micromol/l) than after (0.58+/-0.10 micromol/l; P<0.01) HD. ADMA levels after HD did not differ from those obtained in controls (0.56+/-0.11 micromol/l). These findings show that HD patients have impaired NO-dependent vasodilation in forearm skin, an abnormality not acutely reversed by HD and not explained by ADMA accumulation.

CT radiation dose in children: a survey to establish age-based diagnostic reference levels in Switzerland

This work aimed at assessing the doses delivered in Switzerland to paediatric patients during computed tomography (CT) examinations of the brain, chest and abdomen, and at establishing diagnostic reference levels (DRLs) for various age groups. Forms were sent to the ten centres performing CT on children, addressing the demographics, the indication and the scanning parameters: number of series, kilovoltage, tube current, rotation time, reconstruction slice thickness and pitch, volume CT dose index (CTDI(vol)) and dose length product (DLP). Per age group, the proposed DRLs for brain, chest and abdomen are, respectively, in terms of CTDI(vol): 20, 30, 40, 60 mGy; 5, 8, 10, 12 mGy; 7, 9, 13, 16 mGy; and in terms of DLP: 270, 420, 560, 1,000 mGy cm; 110, 200, 220, 460 mGy cm; 130, 300, 380, 500 mGy cm. An optimisation process should be initiated to reduce the spread in dose recorded in this study. A major element of this process should be the use of DRLs.

Body fat levels in children and adolescents: effects on the prevalence of obesity

BACKGROUND AND AIMS: There is little information regarding the effect of different definitions of obesity on nutritional epidemiology. The aim was thus to assess: (a) the values of percentage of body fat (%BF) by gender and age; (b) the prevalence of obesity according to different %BF cut-offs; and (c) the sensitivity and specificity of BMI according to different %BF cut-offs used to define obesity. METHODS: Cross-sectional study on 2494 boys and 2519 girls aged 10­18 years from the Lisbon area. %BF was measured using a hand-held device. In a sub sample of 211 boys and 724 girls %BF was assessed using skin folds. RESULTS: %BF levels were higher in girls and decreased with age in both genders. Prevalence of obesity varied considerably according to the %BF cut-off used: in boys, it ranged from 4.7% (age-specific 95th percentile) to 26.5% (fixed 25% cut-off), whereas by BMI it was 5.3%. In girls, prevalence of obesity ranged from 0.4% (age-specific BMI-derived %BF values) to 25.4% (fixed 30% cut-off), whereas by BMI it was 4.7%. The specificity of BMI criteria was over 95% irrespective of the %BF cut-off used; conversely, most sensitivities were below 40%. Sensitivities over 50% were obtained for the age-specific BMI-derived %BF values in boys and the age-specific 95th %BF percentile in both genders. Using %BF derived from the skin fold measurements leads to similar results. CONCLUSIONS: Prevalence of obesity varies considerably according to the %BF cut-off used. BMI cut-offs have a low sensitivity but a high specificity. Age- and gender-specific cut-offs for %BF should be used to define pediatric obesity.

Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women.

OBJECTIVE: To define the dynamics of antimüllerian hormone (AMH) and inhibins during the physiologic menstrual cycle. DESIGN: Longitudinal study. SETTING: University hospital. PATIENT(S): 36 young, healthy, normal weight Caucasian women without medication. INTERVENTION(S): Normal ovulatory menstrual cycles were evaluated by regular blood sampling taken every other day and periovulatory every day. MAIN OUTCOME MEASURE(S): Serum concentrations of AMH, inhibin A and B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, progesterone, and free testosterone were measured in all blood samples. RESULT(S): Median AMH levels are statistically significantly higher in the late follicular compared with ovulation or the early luteal phase. There are statistically significant correlations between both AMH and FSH, and AMH and free testosterone in all cycle phases. Inhibin A increases strongly in the late follicular phase and peaks at day LH + 4. Inhibin B shows a broad midfollicular and a sharp early luteal peak, the difference being statistically significant between day LH + 4 and the earlier time points and between day LH + 2 and day LH. Although there is a negative association between inhibin A or B and the body mass index (BMI), there is no correlation between AMH and the BMI. CONCLUSION(S): Levels of AMH show a statistically significant change during the menstrual cycle and may influence the circulating gonadotropin and steroid hormone levels.

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis.

BACKGROUND: Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood. METHODS AND FINDINGS: Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations. CONCLUSIONS: Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.