Prompt-gamma compensation in Rb-82 myocardial perfusion 3D PET/CT

Objective  

To compare the diagnostic accuracy of Rb-82 myocardial perfusion three-dimensional (3D) PET with and without prompt-gamma compensation (PGC).     

Neoadjuvant sorafenib,gemcitabine, and cisplatin administration preceding cystectomy in patients with muscle-invasive urothelial bladder carcinoma: An open-label,single-arm,single-center,phase 2 study

Background

Outcomes of neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder carcinoma (MIUBC) should be improved. Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) in an open-label, single-arm, phase 2 trial (NCT01222676).

High-performance liquid chromatographic (HPLC) analysis of methenolone esters in pharmaceutical formulations

A specific high-performance liquid chromatographic (HPLC) procedure suitable as a stability-indicating assay for the methenolone esters (the acetate and enanthate) analysis in pharmaceutical formulations was investigated. The analysis was carried out under isocratic and reversed-phase conditions using a UV detector (240 nm). A RP8-HPLC system was of choice for the methenolone enanthate analysis.     

Effect of hypobaric hypoxia on lamb intrauterine growth: comparison between high- and low-altitude native ewes

The present studies assessed the effect of hypobaric hypoxia on fetal lamb growth in high-altitude (HA) and low-altitude (LA) native ewes. Growth patterns of fetal biparietal diameter (BPD), abdominal diameter (AD) and thorax height (TH) were described by consecutive ultrasound measurements throughout the entire pregnancy. Three groups of animals were used: (1) pregnant LA ewes kept at LA (control; 'LL' group); (2) pregnant LA ewes moved to HA immediately after confirmation of pregnancy ('LH' group); and (3) pregnant HA ewes kept at HA throughout the entire pregnancy ('HH' group). The slope of the BPD curve was higher in LL fetuses followed by that in LH fetuses. During the last month of pregnancy, TH was higher in LH and HH fetuses, whereas AD was higher in LL than in LH fetuses. The length of gestation was longer in HH ewes (153.2 +/- 4.3 days) than in LH and LL ewes (146.0 +/- 5.5 and 145.0 +/- 3.0 days, respectively). Bodyweight at birth was higher for LL newborns (4.2 +/- 0.3 kg) than for LH and HH newborns (3.0 +/- 0.5 and 3.2 +/- 0.8 kg, respectively), whereas placental weight was higher in the HH group (396 +/- 80 g) than in the LH (303 +/- 64 g) and LL (280 +/- 40 g) groups. In conclusion, an HA environment modifies fetal growth and pregnancy outcome with the magnitude of effects depending on the time of residence at HA.     

Peripheral markers of the gamma-aminobutyric acid (GABA)ergic system in Angelman's syndrome

It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three gamma-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in the deleted region, a possible modification of peripheral markers of the GABAergic system was investigated in 12 subjects with Angelman's syndrome and 20 age-matched subjects (8 with idiopathic epilepsy and 12 not affected by neurologic diseases). The results confirmed a more severe clinical picture, and epilepsy syndrome in particular, in Angelman's syndrome patients with deletions versus patients without deletions. In contrast, biochemical study (based on dosage of plasma levels of GABA and diazepam binding inhibitor, an endogenous ligand of GABAA and peripheral benzodiazepine receptors, showed contradictory results: patients with Angelman's syndrome showed significantly higher levels of GABA and diazepam binding inhibitor than patients without neurologic impairment but significantly lower levels than epileptic controls.     

Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality

Serum phosphorus levels in the general population have beenreported to be associated with cardiovascular morbidity andmortality and increased carotid intima-media thickness. Theauthors examined gender heterogeneity in the association ofphosphorus with all-cause mortality and incident coronary arterydisease using data from the Atherosclerosis Risk in CommunitiesStudy (1987–2001). Baseline phosphorus levels were higherin women and were associated differently among men and womenwith traditional atherosclerosis risk factors such as age, lowdensity lipoprotein cholesterol, diabetes mellitus, and hypertension.In a multivariable-adjusted model, men in the highest quintileof serum phosphorus level (>3.8 mg/dL) had an increased mortalityrate (hazard ratio = 1.45, 95% confidence interval: 1.12, 1.88),while women did not (hazard ratio = 1.18, 95% confidence interval:0.89, 1.57). The multivariable likelihood ratio test of effectmodification by gender was significant at = 0.1 (P = 0.085)for all-cause mortality. Although the associations of phosphoruswith coronary artery disease also appeared to differ substantiallyby gender, the multivariable test for effect modification suggestedthat the difference was consistent with random variation (P= 0.195). These results suggest the need for further investigationinto gender differences in the contribution of mineral metabolismto cardiovascular disease in the general population. cardiovascular diseases; coronary artery disease; mortality; phosphorus; risk; sex factors     

Ketoconazole-associated preferential increase in dopamine D2 receptor occupancy in striatum compared to pituitary in vivo: role for drug transporters?

Membrane transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are efflux pumps that remove drugs from the brain back to the peripheral blood compartment, serving as a functional component of the blood-brain barrier (BBB). We report here that coadministration of the P-gp and BCRP inhibitor ketoconazole with risperidone may preferentially increase D2 receptor occupancy in the striatum compared to pituitary. Four male patients with schizophrenia or schizoaffective disorder who had received at least 4 prior injections of the long-acting risperidone at a stable dose of 25 to 50 mg participated in this positron emission tomography study. Multiple-dose ketoconazole coadministration reduced the P-gp activity as shown by fexofenadine oral challenge. Importantly, we found a strong statistical trend in this sample of 4 subjects who consistently showed a decrease in striatal fluorine 18 (F)-fallypride binding (an indication of increased D2 receptor occupancy) after ketoconazole coadministration (P = 0.057), whereas the pituitary (a region that lies outside the BBB) F-fallypride binding did not change (P = 0.99). These observations warrant further research with selective drug transporter inhibitors. We suggest that in neuroimaging studies, the pituitary drug occupancy can serve as a useful new "positive control" to evaluate whether drug occupancy is preferentially increased in brain regions that fall inside the BBB after cotreatment with P-gp and BCRP inhibitors. This is a noteworthy study design consideration regarding the future clinical testing of novel adjunct interventions aimed at modulating membrane transporter function at the BBB, with the goal of augmenting drug access into the brain compartment, particularly in treatment-resistant psychiatric illness.