3,335 research outputs found

    Cerebral venous hemodynamic abnormalities in episodic and chronic migraine

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    Alterations of cerebral venous drainage have been demonstrated in chronic migraine (CM), suggesting that cerebral venous hemodynamic abnormalities (CVHAs) play a role in this condition. The aim of the present study was to look for a correlation between CM and CVHAs. We recruited 33 subjects suffering from CM with or without analgesic overuse, 29 episodic migraine (EM) patients with or without aura, and 21 healthy subjects as controls (HCs). CVHAs were evaluated by transcranial and extracranial echo-color Doppler evaluation of five venous hemodynamic parameters. CVHAs were significantly more frequent in the CM and EM patients than in the HCs. In the migraine patients, CVHAs were not correlated with clinical features. Cerebral venous hemodynamic abnormalities in episodic and chronic migraine The significantly greater frequency of CVHAs observed in the migraineurs may reflect a possible relationship between migraine and these abnormalities. Prospective longitudinal studies are needed to investigate whether CVHAs have a role in the processes of migraine chronification

    Glossing Ancient Egyptian. Suggestions for adapting the Leipzig Glossing Rules

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    Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition

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    Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B6, or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects

    Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

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    Objectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. Methods. The l-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or l-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or l-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. Results. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with l-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and endsystolic volumes from admission to 3-, 6- and 12-mouth evaluation was significantly reduced in the l-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the l-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. Conclusions. l-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event

    Klebsiella pneumoniae bacteraemia complicating rotavirus gastroenteritis in two infants with glucocorticoid deficiency

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    Rotavirus gastroenteritis was complicated by Klebsiella Pneumoniae bacteraemia in two infants with glucocorticoid deficient conditions who were treated with 'stress dose' hydrocortisone during their illness. Delayed healing in the context of glucocorticoid administration combined with damage from rotavirus infection may result in increased risk of mucosal invasion by gastrointestinal bacteria and subsequent enteric gram-negative bacteraemia

    The role of antimicrobial stewardship programmes in children: a systematic review.

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    The United Nations and the World Health Organization have designated antimicrobial resistance (AMR) as a major health priority and developed action plans to reduce AMR in all healthcare settings. Establishment of institutional antimicrobial stewardship programmes (ASPs) is advocated as a key intervention to reduce antibiotic consumption in hospitals and address high rates of multi-drug resistant (MDR) bacteria. We searched PUBMED and the Cochrane database of systematic reviews (1/2007-3/2017) to identify studies reporting about the effectiveness of ASPs in general paediatric wards and paediatric intensive care units (PICU), on reducing antibiotic consumption, on using broad spectrum/restricted antibiotics, and on antibiotic resistance and healthcare-associated infections (HAIs). Neonatal units and antifungal agents were excluded. Of 2509 titles and abstracts, nine articles were eligible to be included in the final analysis. All studies reported on the reduction of broad spectrum/restricted antibiotics or antibiotic consumption. One study reported on the reduction of HAI in a PICU, and another evaluated bacterial resistance, showing no effect following ASP implementation. Prospective audit on antibiotic use was the most common ASP core component (eight of nine studies). Antibiotic pre-authorisation was described in two articles. Other described interventions were providing guidelines or written information (five of nine articles), and training of healthcare professionals (one article). There is limited evidence about reducing antibiotic consumption and broad-spectrum/restricted agents following ASP implementation, specifically in PICU. Data evaluating the impact of ASPs on HAI and AMR in PICU is lacking. In addition, there is limited information on effective components of a successful ASPs in PICUs

    PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

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    We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.M A Di Biase, A Zalesky, G O'keefe, L Laskaris, B T Baune, C S Weickert, J Olver, P D McGorry, G P Amminger, B Nelson, A M Scott, I Hickie, R Banati, F Turkheimer, M Yaqub, I P Everall, C Pantelis and V Crople

    Cardiovascular health in migrants: current status and issues for prevention. A collaborative multidisciplinary task force report.

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    OBJECTIVES: To review information on cardiovascular health and migration, to stress the attention of researchers that much needs to be done in the collection of sound data in Italy and to allow policy makers identifying this issue as an important public health concern. BACKGROUND: In Italy, the rate of immigrants in the total number of residents increased from 2.5% in 1990 to 7.4% in 2010, and currently exceeds 10% in regions such as Lombardia, Emilia Romagna and Toscana. METHODS: A consensus statement was developed by approaching relevant Italian national scientific societies involved in cardiovascular prevention. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. To obtain a widespread consensus, drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft was finally approved by scientific societies. RESULTS: In several western European countries, the prevalence of hypertension, diabetes, chronic kidney disease, obesity and metabolic syndrome was found to be higher among immigrants than in the native population. Although migrants are often initially healthier than non-migrant populations in their host countries, genetic factors, and changing environments with lifestyle changes, social exclusion and insufficient medical control may expose them to health challenges. Cultural reasons may also hamper both the dissemination of prevention strategies and migrant communication with healthcare providers. However, great diversity exists across and within different groups of migrants, making generalizations very difficult and many countries do not collect registry or survey data for migrant's health. CONCLUSIONS: In the present economic context, the European Union is placing great attention to improve data collection for migrant health and to support the implementation of specific prevention policies aimed at limiting the future burden of cardiovascular and renal disease, and the consequent load for health systems. Wider initiatives on the topic are awaited in Italy
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