381 research outputs found

    Addiction to the nicotine gum in never smokers

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    Abstract Background Addiction to nicotine gum has never been described in never smokers or in never users of tobacco. Methods Internet questionnaire in 2004–2006 in a self-selected sample of 434 daily users of nicotine gum. To assess dependence on nicotine gum, we used modified versions of the Nicotine Dependence Syndrome Scale (NDSS), the Fagerström Test for Nicotine Dependence and the Cigarette Dependence Scale. Results Five never smokers used the nicotine gum daily. They had been using the nicotine gum for longer than the 429 ever smokers (median = 6 years vs 0.8 years, p = 0.004), and they had higher NDSS-gum Tolerance scores (median = 0.73 vs = -1.0, p = 0.03), a difference of 1.5 standard deviation units. Two never smokers had never used smokeless tobacco, both answered "extremely true" to: "I use nicotine gums because I am addicted to them", both "fully agreed" with: "after a few hours without chewing a nicotine gum, I feel an irresistible urge to chew one" and: "I am a prisoner of nicotine gum". Conclusion This is to our knowledge the first report of addiction to nicotine gum in never users of tobacco. However, this phenomenon is rare, and although the long-term effect of nicotine gum is unknown, this product is significantly less harmful than tobacco.</p

    Seasonal Dynamics of Mobile Carbon Supply in Quercus aquifolioides at the Upper Elevational Limit

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    Many studies have tried to explain the physiological mechanisms of the alpine treeline phenomenon, but the debate on the alpine treeline formation remains controversial due to opposite results from different studies. The present study explored the carbon-physiology of an alpine shrub species (Quercus aquifolioides) grown at its upper elevational limit compared to lower elevations, to test whether the elevational limit of alpine shrubs (<3 m in height) are determined by carbon limitation or growth limitation. We studied the seasonal variations in non-structural carbohydrate (NSC) and its pool size in Q. aquifolioides grown at 3000 m, 3500 m, and at its elevational limit of 3950 m above sea level (a.s.l.) on Zheduo Mt., SW China. The tissue NSC concentrations along the elevational gradient varied significantly with season, reflecting the season-dependent carbon balance. The NSC levels in tissues were lowest at the beginning of the growing season, indicating that plants used the winter reserve storage for re-growth in the early spring. During the growing season, plants grown at the elevational limit did not show lower NSC concentrations compared to plants at lower elevations, but during the winter season, storage tissues, especially roots, had significantly lower NSC concentrations in plants at the elevational limit compared to lower elevations. The present results suggest the significance of winter reserve in storage tissues, which may determine the winter survival and early-spring re-growth of Q. aquifolioides shrubs at high elevation, leading to the formation of the uppermost distribution limit. This result is consistent with a recent hypothesis for the alpine treeline formation

    Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

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    INTRODUCTION: MRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging. METHODS: Phase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences. RESULTS: SNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14-26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible. CONCLUSION: We were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence

    Identification of a large rearrangement in CYLD as a cause of familial cylindromatosis

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    Pathogenic mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma. To date, only technologies which are able to identify small point mutations in CYLD, such as sequence and WAVE analysis, were used. Here we describe the identification of a larger rearrangement identified by Quantitative PCR analysis of CYLD, indicating that a combination of these technologies is necessary when searching for pathogenic mutations in CYLD

    Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

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    IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

    Copy number variation in Williams-Beuren syndrome: suitable diagnostic strategy for developing countries

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    <p>Abstract</p> <p>Background</p> <p>Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis (SVAS), mental retardation, and overfriendliness comprise typical symptoms of WBS. Although fluorescence in situ hybridization (FISH) is considered the gold standard technique, the microsatellite DNA markers and multiplex ligation-dependent probe amplification (MLPA) could be used for to confirm the diagnosis of WBS.</p> <p>Results</p> <p>We have evaluated a total cohort of 88 patients with a suspicion clinical diagnosis of WBS using a collection of five markers (D7S1870, D7S489, D7S613, D7S2476, and D7S489_A) and a commercial MLPA kit (P029). The microdeletion was present in 64 (72.7%) patients and absent in 24 (27.3%) patients. The parental origin of deletion was maternal in 36 of 64 patients (56.3%) paternal in 28 of 64 patients (43.7%). The deletion size was 1.55 Mb in 57 of 64 patients (89.1%) and 1.84 Mb in 7 of 64 patients (10.9%). The results were concordant using both techniques, except for four patients whose microsatellite markers were uninformative. There were no clinical differences in relation to either the size or parental origin of the deletion.</p> <p>Conclusion</p> <p>MLPA was considered a faster and more economical method in a single assay, whereas the microsatellite markers could determine both the size and parental origin of the deletion in WBS. The microsatellite marker and MLPA techniques are effective in deletion detection in WBS, and both methods provide a useful diagnostic strategy mainly for developing countries.</p

    Complement C1 Esterase Inhibitor Levels Linked to Infections and Contaminated Heparin-Associated Adverse Events

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    Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS) has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics. OSCS-induced kallikrein activity was dramatically increased after C1inh was depleted, while the addition of C1inh completely attenuated kallikrein activity. In addition, actual clinical infection can lead to increased C1inh levels. Plasma from patients with sepsis had higher average levels of functional C1inh and decreased OSCS-induced kallikrein activity. Lastly, descriptive data on adverse event reports suggest cases likely to be associated with contaminated heparin are inversely correlated with infection. Our data suggest that low C1inh levels can be a risk factor and high levels can be protective. The identification of risk factors for contact system-mediated adverse events may allow for patient screening and clinical development of prophylaxis and treatments
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