Alterations of In-vitro 5-HT Receptor Pharmacology as a Function of Multiple Treatment with 5-Hydroxytryptamine or 8-Hydroxy-2-(di-N-propylamino) Tetralin in Rat Isolated Aorta,Uterus and Fundus,and Guinea-pig Isolated Trachea

Abstract— The effects of single and multiple (5, 10, or 15 days) administration of the 5-HT_1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (3 mg kg^?1, i.p.) or 5-HT (3 mg kg^?1, i.p.) in-vivo on the response of selected isolated smooth muscles to 5-HT in-vitro were investigated. Single dosing with 8-OH-DPAT did not alter the responses of the isolated tissues (rat aorta, uterus or fundus, or guinea-pig trachea) to 5-HT, while multiple dosing with 8-OH-DPAT produced rightward shifts and a suppression of the maximum response of all these tissues to 5-HT, with the exception of the rat stomach fundus. Multiple administration of 5-HT had no effect on the in-vitro response of the tissues to 5-HT. These data indicate that multiple administration of 8-OH-DPAT desensitizes or down-regulates the peripheral 5-HT₂ receptors found on the rat aorta and uterus, and guinea-pig trachea.     

Quantitative MRI assessment of leukoencephalopathy.

Quantitative MRI assessment of leukoencephalopathy is difficult because the MRI properties of leukoencephalopathy significantly overlap those of normal tissue. This report describes the use of an automated procedure for longitudinal measurement of tissue volume and relaxation times to quantify leukoencephalopathy. Images derived by using this procedure in patients undergoing therapy for acute lymphoblastic leukemia (ALL) are presented. Five examinations from each of five volunteers (25 examinations) were used to test the reproducibility of quantitated baseline and subsequent, normal-appearing images; the coefficients of variation were less than 2% for gray and white matter. Regions of leukoencephalopathy in patients were assessed by comparison with manual segmentation. Two radiologists manually segmented images from 15 randomly chosen MRI examinations that exhibited leukoencephalopathy. Kappa analyses showed that the two radiologists' interpretations were concordant (kappa = 0.70) and that each radiologist's interpretations agreed with the results of the automated procedure (kappa = 0.57 and 0.55).The clinical application of this method was illustrated by analysis of images from sequential MR examinations of two patients who developed leukoencephalopathy during treatment for ALL. The ultimate goal is to use these quantitative MR imaging measures to better understand therapy-induced neurotoxicity, which can be limited or even reversed with some combination of therapy adjustments and pharmacological and neurobehavioral interventions.     

Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial

OBJECTIVE: To investigate the acute efficacy and adverse side effects of methylphenidate (MPH) among survivors of childhood cancer [acute lymphoblastic leukemia (ALL) or brain tumor (BT)] with learning impairments. METHODS: Participants (N = 122) completed a two-day, in-clinic, double-blind, cross-over trial during which they received MPH (0.60 mg/kg of body weight) and placebo that were randomized in administration order across participants. Performance was evaluated using measures of attention, memory, and academic achievement. RESULTS: A significant MPH versus placebo effect was revealed on a measure of attention, cognitive flexibility, and processing speed (Stroop Word-Color Association Test). Male gender, older age at treatment, and higher intelligence were predictive of better medication response. No significant differences were found for number or severity of adverse side effects as a function of active medication. CONCLUSIONS: MPH shows some neurocognitive benefit and is well tolerated by the majority of children surviving ALL and BT.     

Disparities in care for patients with curable hepatocellular carcinoma

BackgroundThe incidence of hepatocellular carcinoma (HCC) is increasing, but surgical management continues to be underutilized. This retrospective review investigates treatment decisions and survival for early stage HCC.MethodsThe National Cancer Database (NCDB) was queried for all patients with curable HCC (Stage I/II) from 1998 to 2011 (n = 43 859). Patient and tumour characteristics were analysed to determine predictors of having surgery and of long-term survival.ResultsOnly 39.7% of patients received surgery for early stage HCC. Surgical therapies included resection (34.6%), transplant (28.7%), radiofrequency ablation (27.1%) and other therapies. Surgery correlated with improved median survival (48.3 versus 8.4 months), but was only performed on 42% of stage I patients and 50% of tumours smaller than 2 cm. Patients were more likely to receive surgery if they were Asian or white race, had private insurance, higher income, better education, or treatment at an academic centre (P < 0.05). However, private insurance and treatment at an academic centre were the only variables associated with improved survival (P < 0.05).ConclusionFewer than half of patients with curable HCC receive surgery, possibly as a result of multiple socioeconomic variables. Past these barriers to care, survival is related to adequate and reliable treatment. Further efforts should address these disparities in treatment decisions.     

Invasion of erythrocytes by Plasmodium falciparum malaria parasites: evidence for receptor heterogeneity and two receptors

Plasmodium falciparum malaria parasites with different capabilities of invading sialic acid-deficient erythrocytes were identified. Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase-treated and Tn erythrocytes twice as efficiently as Thai-2 parasites cultured in normal erythrocytes and seven to ten times more efficiently than a cloned line of Camp parasites cultured in normal erythrocytes. All three parasite lines required sialic acid for optimal invasion, but Thai-2 parasites cultured in Tn erythrocytes invaded neuraminidase- treated erythrocytes with 45% efficiency whereas Camp parasites invaded neuraminidase-treated erythrocytes with less than 10% efficiency. P falciparum malaria parasites probably possess two receptors: one that binds to a sialic acid-dependent ligand and another that binds to a sialic acid-independent ligand. Parasites may differ in the quantity or affinity of their receptors for the sialic acid-independent ligand.     

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

Introduction  

The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve.