Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β2-Glycoprotein I

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti–β₂-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.     

Efectividad de un nuevo modelo de derivación telefónica compartida entre atención primaria y atención hospitalaria

Aim

The purpose of this study is to find out whether telephone referral from Primary Health Care to Internal Medicine Consult manages to reduce waiting days as compared to traditional referral. This study also aims to know how acceptable is the telephone referral to general practitioners and their patients.

Volume et profil de consommation d’alcool des élèves et des camarades scolaires comme prédicteurs de l’agression et de la victimisation: une analyse multiniveaux auprès d’adolescents suisses

Volume and profile of alcohol consumption among students and classmates as predictors of aggression and victimization: a multilevel analysis among Swiss adolescents

Objective:  

To test the effects of the volume of alcohol consumption and drinking patterns on alcohol-related aggression and victimization, both at the individual and class levels.     

Fruits and vegetables moderate lipid cardiovascular risk factor in hypertensive patients

Hyperlipidemia is a major risk factor in etiology of cardiovascular disease. Previous studies have shown association between vegetarian diet and low total serum cholesterol as well as LDL-cholesterol which is a pointer to low risk of cardiovascular disease. Dietary fiber, antioxidants and other classes of nutrients have been reported to ameliorate cardiovascular risk factors. Fruits and vegetables being rich sources of fiber and antioxidants have been the focus in intervention studies. The current work reports the effect local fruits and vegetables on cardiovascular risk factors in African hypertensive subjects in an 8 week study. Though there was no significant difference in the Body Mass Index and HDL-cholesterol at the end of the eighth week, there were significant reductions (P < 0.05) in serum triglycerides (125.87 ± 6.0 to108.27 ± 5.49 mgdL^-1); total serum cholesterol (226.60 ± 6.15 to 179.20 ± 5.78) and LDL-cholesterol (135.69 ± 5.56 to 93.07 ± 7.18 mgdL^-1). We concluded that consumption of combination of local fruits and vegetables may reduce the incidence of cardiovascular risk factors in Africans.     

PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

Frequency, nature and determinants of pharmaceutical consultations provided in private by Dutch community pharmacists

OBJECTIVE: According to a report published by the federation of Dutch patients' associations, patients would like to see a pharmacist, who acts more as a personal adviser. This raised the question, how often Dutch community pharmacists have personal consultations with their patients in daily practice, on which factors this depends, and what kind of topics are discussed during these meetings. SETTING: Community pharmacies in the Netherlands. METHOD: A questionnaire was distributed among 800 randomly selected pharmacies. Questions were restricted to consultations characterized by one-to-one contact, drug therapy related content, and adequate privacy. These consultations were labelled as pharmaceutical consultations in private to distinguish them from other contacts between pharmacists and patients. MAIN OUTCOME MEASURE: Number, content, and character of consultations. RESULTS: 198 (24.8%) community pharmacies responded. The pharmacists provide an average of roughly 1.2 consultations in private per working day. The vast majority of respondents provided face-to-face and telephone consultations (94.4 and 91.9%, respectively), only a minority gave consultations by e-mail (30.8%). These consultations primarily dealt with topics related to medication safety. The mean overall time spent was 290 min per month. A relatively high frequency of personal consultations was significantly associated with the absolute number of full-time equivalent pharmacists in the pharmacy. CONCLUSION: The frequency of pharmaceutical consultations in private is low, but may be improved by reorganisation of the pharmacist's activities. The possibility of personal consultations by e-mail is not yet well-developed. Further research is needed to assess the patient's view of pharmaceutical consultations in private.     

Biologic effects of parathyroid hormone metabolites: implications for renal bone disease.

PTH fragments consisting of the C-terminal portion of the molecule may have biologic effects and may modify the actions of PTH. Evidence for the presence of a C-terminal PTH receptor further supports a biologic role for such fragments. Because C-PTH fragments accumulate in patients with renal insufficiency, it is possible that they may contribute to renal bone disease. The precise role of circulating C-PTH fragments in the pathogenesis, diagnosis, and management of renal osteodystrophy, however, remains to be determined. Future studies of the biologic effects and regulation of these fragments may lead to better understanding of skeletal biology and may also improve our approach to the diagnosis and treatment of renal bone disease.     

Pycnogenol® as an Adjunct in the Management of Childhood Asthma

A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol® (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol® or placebo. Subjects were instructed to record their peak expiratory flow with an Assess® Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C₄/D₄/E₄ was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol® had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol® group. The results of this study demonstrate the efficacy of Pycnogenol® as an adjunct in the management of mild-to-moderate childhood asthma.