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Selected AbstractsCytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemiaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2002Catherine A. M. Stedman Abstract Aims The aims of this study were to determine if patients with SSRI-related hyponatraemia were (1) genetically poor metabolizers of CYP2D6, and/or (2) had excessive plasma concentrations of the SSRI antidepressant. Methods Plasma DNA from 20 people with hyponatraemia attributable to fluoxetine or paroxetine was analysed for the CYP2D6 alleles *1,*16. Trough plasma concentrations of fluoxetine and norfluoxetine, or paroxetine were assayed in nine people who remained on the antidepressant. Results Genotype results were compared with those published in a large population study. The poor metabolizer PM/PM genotype was present in one subject only, or 5% of the study population, compared with 7.2% of a general population. The 95% Cl of this result was 0,21%, suggesting that it is most unlikely that hyponatremia is related to the PM/PM genotype. The intermediate IM/PM genotype was present in 5% compared with 19.7% of a general population. All differences were not statistically significant. Antidepressant concentrations of fluoxetine (n,=,5, all EM) and paroxetine (n,=,1,IM/PM and n,=,3,EM) were all within the lower half of the reference range. Conclusions These results do not support the hypothesis that SSRI-related hyponatraemia is linked to genetically poor metabolizers, or excessive drug concentrations. Copyright © 2002 John Wiley & Sons, Ltd. [source] Development and Experimental Identification of a Biomechanical Model of the Trunk for Functional Electrical Stimulation Control in ParaplegiaNEUROMODULATION, Issue 4 2008Ingenieur Michele Vanoncini ABSTRACT Objectives., Theoretic modeling and experimental studies suggest that functional electrical stimulation (FES) can improve trunk balance in spinal cord injured subjects. This can have a positive impact on daily life, increasing the volume of bimanual workspace, improving sitting posture, and wheelchair propulsion. A closed loop controller for the stimulation is desirable, as it can potentially decrease muscle fatigue and offer better rejection to disturbances. This paper proposes a biomechanical model of the human trunk, and a procedure for its identification, to be used for the future development of FES controllers. The advantage over previous models resides in the simplicity of the solution proposed, which makes it possible to identify the model just before a stimulation session (taking into account the variability of the muscle response to the FES). Materials and Methods., The structure of the model is based on previous research on FES and muscle physiology. Some details could not be inferred from previous studies, and were determined from experimental data. Experiments with a paraplegic volunteer were conducted in order to measure the moments exerted by the trunk-passive tissues and artificially stimulated muscles. Data for model identification and validation also were collected. Results., Using the proposed structure and identification procedure, the model could adequately reproduce the moments exerted during the experiments. The study reveals that the stimulated trunk extensors can exert maximal moment when the trunk is in the upright position. In contrast, previous studies show that able-bodied subjects can exert maximal trunk extension when flexed forward. Conclusions., The proposed model and identification procedure are a successful first step toward the development of a model-based controller for trunk FES. The model also gives information on the trunk in unique conditions, normally not observable in able-bodied subjects (ie, subject only to extensor muscles contraction). [source] Acidosis and Catecholamine Evaluation Following Simulated Law Enforcement "Use of Force" EncountersACADEMIC EMERGENCY MEDICINE, Issue 7 2010Jeffrey D. Ho MD ACADEMIC EMERGENCY MEDICINE 2010; 17:E60,E68 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Law enforcement authorities are often charged with controlling resisting suspects. These encounters sometimes result in the sudden and unexpected death of the suspect. Drug intoxication, excited delirium syndrome, or excessive uses of force are factors that are often blamed, but sometimes the mechanism of these deaths is not fully understood. It is possible that worsening acidosis or excessive catecholamine release play a part. The objective of this study was to determine the effect on markers of acidosis and catecholamines of various tasks intended to simulate common arrest-related situations. Methods:, Subjects were assigned to one of five task groups: 1) a 150-meter sprint and wall hurdle (simulated flight from arrest); 2) 45 seconds of striking a heavy bag (simulated physical resistance); 3) a 10-second TASER X26 electronic control device exposure; 4) a fleeing and resistance exercise involving a law enforcement dog (K-9); or 5) an oleoresin capsicum (OC) exposure to the face and neck. Baseline serum pH, lactate, potassium, troponin I, catecholamines, and creatine kinase (CK) were evaluated. Serum catecholamines, pH, lactate, and potassium were sampled immediately after the task and every 2 minutes for 10 minutes posttask. Vital signs were repeated immediately after the task. Serum CK and troponin I were evaluated again at 24 hours posttask. Results:, Sixty-six subjects were enrolled; four did not complete their assigned task. One subject lost the intravenous (IV) access after completing the task and did not have data collected, and one subject only received a 5-second TASER device exposure and was excluded from the study, leaving 12 subjects in each task group. The greatest changes in acidosis markers occurred in the sprint and heavy bag groups. Catecholamines increased the most in the heavy bag group and the sprint group and increased to a lesser degree in the TASER, OC, and K-9 groups. Only the sprint group showed an increase in CK at 24 hours. There were no elevations in troponin I in any group, nor any clinically important changes in potassium. Conclusions:, The simulations of physical resistance and fleeing on foot led to the greatest changes in markers of acidosis and catecholamines. These changes may be contributing or causal mechanisms in sudden custodial arrest-related deaths (ARDs). This initial work may have implications in guiding applications of force for law enforcement authorities (LEAs) when apprehending resisting subjects. [source] FSH and ovarian response: spontaneous recovery of pituitary,ovarian activity during the pill-free period vs. exogenous recombinant FSH during high-dose combined oral contraceptivesCLINICAL ENDOCRINOLOGY, Issue 4 2002A. M. Van Heusden Summary ojbective Compare spontaneous recovery of pituitary,ovarian activity during the pill-free period following the correct use of low-dose oral contraceptives and subsequent ovarian function during the administration of exogenous recombinant FSH (recFSH) after switching to continued Lyndiol® (2·5 mg lynestrenol + 0·05 mg ethinyl-oestradiol) medication. design Prospective, randomized, group-comparative, single-centre study. Following the monitoring of the pill-free period (week 1) and subsequent treatment with Lyndiol® (for a total of 5 weeks), all subjects were randomly allocated to one of four groups receiving daily FSH injections for 1 week [75, 150, 225 IU recFSH or 150 IU purified urinary FSH (uFSH)] during the fourth week of Lyndiol® use. patients Thirty-six healthy volunteers aged 18,39 years, prestudy oral contraceptive use for at least 3 months, cycle length between 24 and 35 days. measurements Serum FSH, LH and oestradiol (E2) concentrations as well as transvaginal ultrasound assessment of the number and diameter of follicles > 2 mm were used to monitor pituitary ovarian function. results At the start of the pill-free period following the prestudy contraceptive medication, 67% of the women presented with LH and FSH levels < 1 IU/l and only one follicle > 10 mm was observed. Initial levels of LH and FSH correlated (P < 0·05) with the extent of pituitary,ovarian activity during the pill-free period. At the end of the pill-free period a follicle > 10 mm had emerged in one subject only. During the first 3 days of Lyndiol® use, seven women (19%) eventually showed at least one follicle > 10 mm. During combined exogenous FSH and Lyndiol® administration, LH levels remained completely suppressed (, 0·5 IU/l) in all women studied. FSH levels and number and size of follicles increased with increasing doses of exogenous FSH in a dose-dependent manner. E2 levels remained low in all groups (< 150 pmol/l). During the week following FSH administration, FSH levels and E2 levels decreased gradually while the number of follicles > 10 mm still increased. conclusions We have confirmed that dominant follicles > 10 mm are present at the end of the pill-free period and during the first days after resumption of pill intake. Once follicles > 10 mm arose at the end of the pill-free period, continued use of Lyndiol® did not reduce follicle diameters. One week of Lyndiol® reduces pituitary,ovarian activity to levels observed after 3 weeks of low-dose pills. FSH administration during Lyndiol® resulted in dose-dependent follicle growth despite extremely low LH levels. E2 secretion (56 ± 51 pmol/l) occurred to a limited and variable extent along with extremely low serum LH concentrations. Recovery of pituitary,ovarian activity at the end of the pill-free period is comparable to FSH levels and follicle dynamics following 7 days of 75,150 IU/l recFSH. [source] Pulmonary diffusion and aerobic capacity: is there a relation?ACTA PHYSIOLOGICA, Issue 4 2010Does obesity matter? Abstract Aim:, We sought to determine whether pulmonary diffusing capacity for nitric oxide (DLNO), carbon monoxide (DLCO) and pulmonary capillary blood volume (Vc) at rest predict peak aerobic capacity (O2peak), and if so, to discern which measure predicts better. Methods:, Thirty-five individuals with extreme obesity (body mass index or BMI = 50 ± 8 kg m,2) and 26 fit, non-obese subjects (BMI = 23 ± 2 kg m,2) participated. DLNO and DLCO at rest were first measured. Then, subjects performed a graded exercise test on a cycle ergometer to determine O2peak. Multivariate regression was used to assess relations in the data. Results:, Findings indicate that (i) pulmonary diffusion at rest predicts O2peak in the fit and obese when measured with DLNO, but only in the fit when measured with DLCO; (ii) the observed relation between pulmonary diffusion at rest and O2peak is different in the fit and obese; (iii) DLNO explains O2peak better than DLCO or Vc. The findings imply the following reference equations for DLNO: O2peak (mL kg,1 min,1) = 6.81 + 0.27 × DLNO for fit individuals; O2peak (mL kg,1 min,1) = 6.81 + 0.06 × DLNO, for obese individuals (in both groups, adjusted R2 = 0.92; RMSE = 5.58). Conclusion:, Pulmonary diffusion at rest predicts O2peak, although a relation exists for obese subjects only when DLNO is used, and the magnitude of the relation depends on gender when either DLCO or Vc is used. We recommend DLNO as a measure of pulmonary diffusion, both for its ease of collection as well as its tighter relation with O2peak. [source] Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparumEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010Linda J. Wammes Abstract Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum -parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4+CD25hiFOXP3+ T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4+CD25hi T-cell depletion in geohelminth-infected subjects only. In addition, IFN-, production in response to both BCG and parasitized RBC was increased after removal of CD4+CD25hi T cells. These data demonstrate that geohelminth-associated Treg influence immune responses to bystander Ag of mycobacteria and plasmodia. Geohelminth-induced immune modulation may have important consequences for co-endemic infections and vaccine trials. [source] PAX9 polymorphisms and susceptibility to sporadic tooth agenesis: a case,control study in southeast ChinaEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2008Yongchu Pan Tooth agenesis is one of the most common developmental disorders in humans. The PAX9 gene, which plays an important role in odontogenesis, is associated with familial and sporadic tooth agenesis. A case,control study was performed in 102 subjects with tooth agenesis (cases) and 116 healthy controls. We genotyped four PAX9 gene polymorphisms using a polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) assay. The allele and genotype frequencies of the four polymorphisms were not significantly different between the controls and the subjects with tooth agenesis. Similar results were observed in a subgroup analysis of test subjects only with mandibular incisor agenesis. Further analysis showed no significant difference in the haplotype distribution between the controls and the subjects with tooth agenesis or mandibular incisor agenesis. However, we found that the AGGC haplotype was associated with a decreased risk of tooth agenesis, compared with the most common haplotype, AGCC (odds ratio, 0.14; 95% confidence interval: 0.00,0.95). These results suggest that the four PAX9 polymorphisms alone have a non-significant main effect on the risk of tooth agenesis but that the AGGC haplotype may have a protective effect associated with a decreased risk of tooth agenesis. [source] Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus,coinfected patients,,HEPATOLOGY, Issue 1 2006Giovanni Raimondo Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is often associated with severe forms of liver disease. However, comprehensive studies are lacking, and scant information is available regarding the virological behavior over time in coinfected patients. This study enrolled 133 untreated HBV/HCV-positive patients (male/female = 102/31; median age 51 years [range: 22-83 years]) who were longitudinally followed up for 1 year with bimonthly evaluation of HBV/HCV viremia levels and liver biochemistry. Thirty of these patients had triple infection with hepatitis Delta virus (HDV), while 103 patients were HDV-negative. In the HDV-negative group, active infection with both HBV and HCV was revealed in 24 cases, inactive infection by both viruses was seen in 15 cases, active HBV/inactive HCV was seen in 15 cases, and inactive HBV/active HCV was seen in 49 cases. However, 32 subjects (31%) presented dynamic virological profiles characterized by fluctuation of HBV and/or HCV viremia levels that at different time points were over or under the cutoff limits. Consequently, a correct diagnosis could be performed in these subjects only by serially repeating the virological tests 1 year apart. Similarly, 15 of the 30 HDV-positive subjects showed active HBV and/or HCV infection, with fluctuating virological patterns in 8 cases. In conclusion, this study showed that the virological patterns in HBV/HCV coinfection are widely divergent and have dynamic profiles. A careful longitudinal evaluation of the viremia levels of both viruses is essential for making a correct diagnosis and tailoring the appropriate therapeutic schedule in coinfected patients. (HEPATOLOGY 2005.) [source] Frontal White Matter and Cingulum Diffusion Tensor Imaging Deficits in AlcoholismALCOHOLISM, Issue 6 2008Gordon J. Harris Background:, Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. Methods:, Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. Results:, Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. Conclusions:, The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism. [source] A Novel Single Nucleotide Polymorphism of the Neuropeptide Y (NPY) Gene Associated With Alcohol DependenceALCOHOLISM, Issue 5 2005Salim Mottagui-Tabar Background: Neuropeptide Y (NPY) is a major endogenous regulator of anxiety-related behaviors and emotionality. Transgenic work with NPY and null-mutant mice have implicated NPY in the control of alcohol consumption, suggesting that genetic variation of the prepro-NPY gene may also contribute to the heritability of alcoholism. The aim of this study was to examine whether polymorphic variants of the NPY gene are associated with the diagnosis of alcohol dependence. Methods: We compared allele frequencies of 5 NPY polymorphisms (,883-ins/del, ,602, ,399, ,84, and +1128) in a Nordic population of alcohol-dependent individuals (n= 428 males; n= 149 females) and ethnically matched controls (n= 84 males; n= 93 females) for whom alcohol dependence or any diagnosis of substance disorder was excluded. Patients were further subtyped into type I (late-onset) and type II (early-onset) alcoholics. Results: The ,602 marker showed a significant association with alcohol dependence (p= 0.0035; OR, 2.3; 95% CI, 1.3-4.0); a trend level association was further observed for the ,399 marker (p= 0.058; OR, 1.3; 95% CI, 0.99-1.7) and the +1128 marker (p= 0.053; OR, 1.8; 95% CI, 0.99-3.1). The association for the ,602 marker remained and was strengthened when analyzed in type I subjects only, although this association was not seen in type II patients, and there also was a significant association in the female subjects but not in males. The ,602 single nucleotide polymorphism was in strong linkage dysequilibrium (r2= 0.7; p < 0.0001) with the +1128 single nucleotide polymorphism, which has previously been reported to be associated with a diagnosis of alcoholism. Haplotype-based association confirmed these results. Conclusions: We report a novel polymorphism at position ,602 in the 5, region of the NPY gene that is significantly associated with alcohol dependence. We also describe the haplotype frequencies and linkage dysequilibrium pattern of four variations in that region. [source] Distribution of Bacteroides forsythus genotypes in a Japanese periodontitis populationMOLECULAR ORAL MICROBIOLOGY, Issue 4 2003Y. Huang Bacteroides forsythus is an important pathogen in periodontal diseases and has been associated with advanced and refractory periodontitis. The difficulties associated with culturing this species have meant that the distribution and pathogenic mechanisms of B. forsythus remain unclear. In this study, the arbitrarily primed polymerase chain reaction (AP-PCR) method was used to investigate the genotype distribution of B. forsythus in a Japanese periodontitis population, as well as the relationship between AP-PCR genotypes and periodontal status. B. forsythus reference strain, ATCC 43037T and 137 clinical bacterial isolates from 64 subjects were separated into 11 distinct AP-PCR genotypes using a single randomly-sequenced primer, 5,-CCGGCGGCG-3, (A-05). The majority (80.9%) of B. forsythus strains examined belonged to AP-PCR genotypes I, II, III and IV (accounting for 39.7%, 20.6%, 10.3% and 10.3%, respectively). Types I and III primarily consisted of isolates from chronic periodontitis subjects (80.8% and 85.7%, respectively), while Types II and IV consisted mainly of isolates from aggressive periodontitis subjects (85.7% and 100%, respectively). Except for three subjects who harbored two different B. forsythus genotypes in the oral cavity, all subjects only infected with one genotype intraindividually. These results demonstrate that the AP-PCR method is useful for genotypic analysis of B. forsythus. This species showed a genetic diversity among the investigated population. A clonal nature of B. forsythus infection is suggested. Furthermore, different AP-PCR genotypes of B. forsythus appear to be associated with different types of periodontitis. [source] | ||||||||||