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Search Results: 1 - 10 of 4979 matches for " Eva Kosek "
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Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene
Fredrik Lindstedt,Jonathan Berrebi,Erik Greayer,Tina B. Lonsdorf,Martin Schalling,Martin Ingvar,Eva Kosek
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018252
Abstract: Variation in the serotonin transporter (5-HTT) gene (SLC6A4) has been shown to influence a wide range of affective processes. Low 5-HTT gene-expression has also been suggested to increase the risk of chronic pain. Conditioned pain modulation (CPM) - i.e. ‘pain inhibits pain’ - is impaired in chronic pain states and, reciprocally, aberrations of CPM may predict the development of chronic pain. Therefore we hypothesized that a common variation in the SLC6A4 is associated with inter-individual variation in CPM. Forty-five healthy subjects recruited on the basis of tri-allelic 5-HTTLPR genotype, with inferred high or low 5-HTT-expression, were included in a double-blind study. A submaximal-effort tourniquet test was used to provide a standardized degree of conditioning ischemic pain. Individualized noxious heat and pressure pain thresholds (PPTs) were used as subjective test-modalities and the nociceptive flexion reflex (NFR) was used to provide an objective neurophysiological window into spinal processing.
Evidence for Thalamic Involvement in the Thermal Grill Illusion: An fMRI Study
Fredrik Lindstedt, Bo Johansson, Sofia Martinsen, Eva Kosek, Peter Fransson, Martin Ingvar
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027075
Abstract: Background Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures. Aim To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers. Methods We constructed a TGI-thermode allowing the rapid presentation of warm(41°C), cold(18°C) and interleaved(41°C+18°C = TGI) temperatures in an fMRI-environment. Twenty volunteers were tested. The affective-motivational (“unpleasantness”) and sensory-disciminatory (“pain-intensity”) dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected α-level <0.05. Results The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness(rho = 0.31). Conclusion/Significance To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain.
Perception of Thermal Pain and the Thermal Grill Illusion Is Associated with Polymorphisms in the Serotonin Transporter Gene
Fredrik Lindstedt,Tina B. Lonsdorf,Martin Schalling,Eva Kosek,Martin Ingvar
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017752
Abstract: The main aim of this study was to assess if the perception of thermal pain thresholds is associated with genetically inferred levels of expression of the 5-HT transporter (5-HTT). Additionally, the perception of the so-called thermal grill illusion (TGI) was assessed. Forty-four healthy individuals (27 females, 17 males) were selected a-priori based on their 5-HTTLPR/rs25531 (‘tri-allelic 5-HTTLPR’) genotype, with inferred high or low 5-HTT expression. Thresholds for heat- and cold-pain were determined along with the sensory and affective dimensions of the TGI.
Increased Sensitivity to Thermal Pain Following a Single Opiate Dose Is Influenced by the COMT val158met Polymorphism
Karin B. Jensen, Tina B. Lonsdorf, Martin Schalling, Eva Kosek, Martin Ingvar
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006016
Abstract: Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia) and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val158met) of the Catechol-O-methyltransferase (COMT) gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met158 allele have been reported to have increased pain sensitivity and there are findings of lower μ-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug. Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS) from 0 mm (no pain) to 100 mm (worst possible pain). Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug. At baseline there was no difference in pain ratings between the COMTval158met genotypes, F(2, 39)<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval158met genotype, F(2, 36) = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042) without a separating effect for genotype (n.s). We suggest that the initial response of the descending pain system is not influenced by the COMTval158met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval158met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to be proven in future studies where the impact of the COMTval158met polymorphism on opioid treatment in patients is addressed.
Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception
Fredrik Lindstedt, Bianka Karshikoff, Martin Schalling, Caroline Olgart H?glund, Martin Ingvar, Mats Lekander, Eva Kosek
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043221
Abstract: Background Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities. Methods Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C–49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed. Results Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged. Conclusion/Significance To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a ‘hypo- to hyperalgesic’ response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted.
Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans
Eva Kosek, Karin B Jensen, Tina B Lonsdorf, Martin Schalling, Martin Ingvar
Molecular Pain , 2009, DOI: 10.1186/1744-8069-5-37
Abstract: At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.Modern pain research has highlighted the importance of central nervous system mechanisms for the regulation of acute and chronic pain. The large individual differences in pain sensitivity, response to analgesic drugs and risk of developing chronic pain is partially explained by genetic factors with impact on the endogenous pain modulation that takes place within the central nervous system [1,2]. The activity of the descending pain inhibitory pathways is largely dependent on dopamine/noradrenalin as well as endogenous opioids and previous studies have shown that polymorphisms in genes coding for μ-opioid receptors and the catecholamine-degrading enzyme catechol-O-methyltransferase (COMT) influence pain responses [3,4]. However, in addition to well known opioidergic pain regulatory mechanism with a k
An Application of Low-Order Arma and Garch Models for Sea Level Fluctuations
Tomasz Niedzielski, , Wieslaw Kosek
Artificial Satellites , 2010, DOI: 10.2478/v10018-010-0003-x
Abstract: The paper presents the analysis of geographically-dependent irregular sea level fluctuations, often referred to as residual terms around deterministic signals, carried out by means of stochastic low-order autoregressive moving average (ARMA) and generalised autoregressive conditional heteroscedastic (GARCH) models. The gridded sea level anomaly (SLA) time series from TOPEX/Poseidon (T/P) and Jason-1 (J-1) satellite altimetry, commencing on 10th January 1993 and finishing on 14th July 2003, has been examined. The aforementioned models, limited to low-orders being combinations of 0,1 and 2, have been fitted to the SLA data. The root mean square and the Shapiro-Wilk test for the normal distribution have been used to calculate statistics of the residuals from these models. It has been found that autoregressive (AR) models as well as ARMA ones serve well the purpose of adequate modelling irregular sea level fluctuations, with a successful fit in some patchy bits of the equatorial Pacific. In contrast, GARCH models have been shown to be rather inaccurate, specifically in the vicinity of the tropical Pacific, in the North Pacific and in the equatorial Indian Ocean. The pattern of the Tropical Instability Waves (TIWs) has been noticed in the statistics of AR and ARMA model residuals indicating that the dynamics of these waves cannot be captured by the aforementioned linear stochastic processes.
Patients with fibromyalgia display less functional connectivity in the brain’s pain inhibitory network
Karin B Jensen, Rita Loitoile, Eva Kosek, Frank Petzke, Serena Carville, peter Fransson, Hanke Marcus, Steven C.R Williams, Ernest Choy, Yves Mainguy, Olivier Vitton, Richard H Gracely, Randy Gollub, Martin Ingvar, Jian Kong
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-32
Abstract: We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus.FM patients required significantly less pressure (kPa) to reach calibrated pain at 50?mm on a 0–100 visual analogue scale (p?<?.001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients.Patients with FM displayed less connectivity within the brain’s pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation.
The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000
Kosek,Margaret; Bern,Caryn; Guerrant,Richard L.;
Bulletin of the World Health Organization , 2003, DOI: 10.1590/S0042-96862003000300010
Abstract: current estimates of the global burden of disease for diarrhoea are reported and compared with previous estimates made using data collected in 1954-79 and 1980-89. a structured literature review was used to identify studies that characterized morbidity rates by prospective surveillance of stable populations and studies that characterized mortality attributable to diarrhoea through active surveillance. for children under 5 years of age in developing areas and countries, there was a median of 3.2 episodes of diarrhoea per child-year. this indicated little change from previously described incidences. estimates of mortality revealed that 4.9 children per 1000 per year in these areas and countries died as a result of diarrhoeal illness in the first 5 years of life, a decline from the previous estimates of 13.6 and 5.6 per 1000 per year. the decrease was most pronounced in children aged under 1 year. despite improving trends in mortality rates, diarrhoea accounted for a median of 21% of all deaths of children aged under 5 years in these areas and countries, being responsible for 2.5 million deaths per year. there has not been a concurrent decrease in morbidity rates attributable to diarrhoea. as population growth is focused in the poorest areas, the total morbidity component of the disease burden is greater than previously.
On the Probability Distribution of Earth Orientation Parameters Data
T. Niedzielski, , A. K. Sen, W. Kosek
Artificial Satellites , 2009, DOI: 10.2478/v10018-009-0017-4
Abstract: Earth Orientation Parameters (EOPs), i.e. pole coordinates (xp, yp), Universal Time (UT1-UTC), and celestial pole offsets (dX, dY), are the transformation parameters between the International Terrestrial Reference Frame (ITRF) and the International Celestial Reference Frame (ICRF). It is customarily assumed that each of the EOP time series follows the normal distribution. The normality assumption has been used specifically in EOP prediction studies. The objective of this paper is to investigate the normality hypothesis in detail. We analysed the daily time series of xp, yp, UT1-UTC, length-of-day (Δ), dX, and dY in the time interval from 01.01.1962 to 31.12.2008. The UT1-UTC data were transformed to UT1R-TAI by removing leap seconds and the tidal signal using the IERS model. The tidal effects δΔ were also removed from the Δ time series and Δ - δΔ data were obtained. Furthermore, we constructed the residuals of these time series using least-squares fit. We evaluated the skewness and kurtosis and tested their statistical significance by the D'Agostino and the Anscombe-Glynn tests, respectively. In addition, the Anderson-Darling test for the normal distribution was applied. It was found that the xp, yp time series and their residuals slightly depart from the normal distribution, but this departure is rather due to marginal flattening/narrowing of the probability density function than due to extreme values. The UT1R-TAI time series and its residuals were also classified as non-Gaussian, however, the deviations from the normal distribution are again slight. The similar results hold for the Δ - δΔ data, but some of its residuals were found to be Gaussian. We noticed that the celestial pole offsets, dX and dY, tend to deviate from the Gaussian distribution. In addition, we examined the determination errors of EOP data and found them to depart significantly from the normal distribution.
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