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Baseline Sample (baseline + sample)
Selected AbstractsEffect of celecoxib on cyclooxygenase-2 expression and possible variants in a patient with Barrett's esophagusDISEASES OF THE ESOPHAGUS, Issue 3 2007G. A. Jacobson SUMMARY., Cyclooxygenase-2 (COX-2) expression is increased in metaplastic and dysplastic Barrett's esophageal epithelium and it is thought that selective COX-2 inhibitors could offer hope as chemoprevention therapy. The aim of the study was to investigate the in vivo effect of celecoxib on COX-2 expression in patients with Barrett's esophagus and no recent history of non-steroidal anti-inflammatory drug use. Endoscopic mucosal biopsy specimens were collected at baseline and after 28 days of therapy in a patient treated with celecoxib 200 mg twice daily. Samples were analyzed for COX-2 expression by immunoblot analysis with chemiluminescence detection. COX-2 expression was found to decline 20% and 44% at two different biopsy sites compared to the baseline sample. Longer exposures revealed a number of previously unidentified proteins above and below the 67 kDa COX-2 protein including 38 kDa and 45 kDa proteins which were present only at study completion consistent with up-regulation after celecoxib therapy. Further investigations of the 38 kDa and 45 kDa proteins were undertaken using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) with immunoblot and MALDI-TOF (matrix assisted laser desorption ionization , time of flight) analysis but no matches were found and results were inconclusive. Unmatched masses from MALDI-TOF peptide mass fingerprinting were compared with human COX-2 (67 kDa) and COX-2b (39 kDa) using unspecific cleavage. Peptide sequence homology with COX-2 and COX-2b was found for a length of 19 amino acids. Based on immunodetection, molecular weight and equivical MALDI-TOF results, one of these up-regulated proteins may be COX-2b. [source] Mental disorders as risk factors for substance use, abuse and dependence: results from the 10-year follow-up of the National Comorbidity SurveyADDICTION, Issue 6 2010Joel Swendsen ABSTRACT Aims The comorbidity of mental disorders and substance dependence is well documented, but prospective investigations in community samples are rare. This investigation examines the role of primary mental disorders as risk factors for the later onset of nicotine, alcohol and illicit drug use, abuse and dependence with abuse. Design The National Comorbidity Survey (NCS) was a nationally representative survey of mental and substance disorders in the United States carried out in 1990,92. The NCS-2 re-interviewed a probability subsample of NCS respondents in 2001,03, a decade after the baseline survey. Participants A total of 5001 NCS respondents were re-interviewed in the NCS-2 (87.6% of baseline sample). Results Aggregate analyses demonstrated significant prospective risks posed by baseline mental disorders for the onset of nicotine, alcohol and illicit drug dependence with abuse over the follow-up period. Particularly strong and consistent associations were observed for behavioral disorders and previous substance use conditions, as well as for certain mood and anxiety disorders. Conditional analyses demonstrated that many observed associations were limited to specific categories of use, abuse or dependence, including several mental disorders that were non-significant predictors in the aggregate analyses. Conclusions Many mental disorders are associated with an increased risk of later substance use conditions, but important differences in these associations are observed across the categories of use, abuse and dependence with abuse. These prospective findings have implications for the precision of prevention and treatment strategies targeting substance use disorders. [source] Socio-demographic risk factors for alcohol and drug dependence: the 10-year follow-up of the national comorbidity surveyADDICTION, Issue 8 2009Joel Swendsen ABSTRACT Aims Continued progress in etiological research and prevention science requires more precise information concerning the specific stages at which socio-demographic variables are implicated most strongly in transition from initial substance use to dependence. The present study examines prospective associations between socio-demographic variables and the subsequent onset of alcohol and drug dependence using data from the National Comorbidity Survey (NCS) and the NCS Follow-up survey (NCS-2). Design The NCS was a nationally representative survey of the prevalence and correlates of DSM-III-R mental and substance disorders in the United States carried out in 1990,2002. The NCS-2 re-interviewed a probability subsample of NCS respondents a decade after the baseline survey. Baseline NCS socio-demographic characteristics and substance use history were examined as predictors of the first onset of DSM-IV alcohol and drug dependence in the NCS-2. Participants A total of 5001 NCS respondents were re-interviewed in the NCS-2 (87.6% of baseline sample). Findings Aggregate analyses demonstrated significant associations between some baseline socio-demographic variables (young age, low education, non-white ethnicity, occupational status) but not others (sex, number of children, residential area) and the subsequent onset of DSM-IV alcohol or drug dependence. However, conditional models showed that these risk factors were limited to specific stages of baseline use. Moreover, many socio-demographic variables that were not significant in the aggregate analyses were significant predictors of dependence when examined by stage of use. Conclusions The findings underscore the potential for socio-demographic risk factors to have highly specific associations with different stages of the substance use trajectory. [source] An 8-Year Prospective Study of the Relationship Between Cognitive Performance and Falling in Very Old AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2006Kaarin J. Anstey PhD OBJECTIVES: To determine whether cognitive performance, as distinct from cognitive impairment, predicts falling during an 8-year follow-up in a community-based sample of very old adults and to evaluate how cognitive change is associated with falling. DESIGN: Prospective cohort study including three waves of data collected in 1992, 1994, and 2000. SETTING: Population based, with the baseline sample drawn from the electoral roll. PARTICIPANTS: Inclusion criteria were completion of at least three cognitive tests at baseline and completion of the falls questionnaire at Wave 6 (N=539). MEASUREMENTS: Assessments of health and medical conditions, visual acuity, cognitive function, functional reach, semitandem stand, and grip strength were conducted in 1992 (baseline), 1994, and 2000. Self-report information on falls in the previous 12 months was obtained on each of these occasions. Marginal models using generalized estimating equations were used to assess the association between baseline cognitive performance and falling over 8 years, adjusting for sociodemographic, health, and sensorimotor variables. Random effects models were used to assess the relationship between change in cognitive performance and change in fall rate and fall risk over 8 years. RESULTS: Mini-Mental State Examination and verbal reasoning at baseline predicted rate of falling over an 8-year period. Within individuals, declines in verbal ability, processing speed, and immediate memory were associated with increases in rates of falling and fall risk. CONCLUSION: Cognitive performance is associated with falling over 8 years in very old adults and should be assessed in clinical practice when evaluating short- and long-term fall risk. [source] Handgrip Strength and Mortality in Older Mexican AmericansJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2002Soham Al Snih MD OBJECTIVES: To examine the association between handgrip strength and mortality in older Mexican American men and women. DESIGN: A 5-year prospective cohort study. SETTING: Five southwestern states: Texas, New Mexico, Colorado, Arizona, and California. PARTICIPANTS: A population-based sample of 2,488 noninstitutionalized Mexican-American men and women aged 65 and older. MEASUREMENTS: Maximal handgrip strength, timed walk, and body mass index were assessed at baseline during 1993/94. Self-reports of functional disability, various medical conditions, and status at follow-up were obtained. RESULTS: Of the baseline sample with complete data, 507 persons were confirmed deceased 5 years later. Average handgrip strength ± standard deviation was significantly higher in men (28.4 kg ± 9.5) than in women (18.2 kg ± 6.5). Of men who had a handgrip strength less than 22.01 kg and women who had a handgrip strength less than 14 kg, 38.2% and 41.5%, respectively, were dead 5 years later. In men in the lowest handgrip strength quartile, the hazard ratio of death was 2.10 (95% confidence interval (CI) = 1.31,3.38) compared with those in the highest handgrip strength quartile, after controlling for sociodemographic variables, functional disability, timed walk, medical conditions, body mass index, and smoking status at baseline. In women in the lowest handgrip strength quartile, the hazard ratio of death was 1.76 (95% CI = 1.05,2.93) compared with those in the highest handgrip strength quartile. Poorer performance in the timed walk and the presence of diabetes mellitus, hypertension, and cancer were also significant predictors of mortality 5 years later. CONCLUSION: Handgrip strength is a strong predictor of mortality in older Mexican Americans, after controlling for relevant risk factors. [source] Incidence and outcome of acquisition of human papillomavirus infection in women with normal cytology,A population-based cohort study from TaiwanINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Angel Chao Abstract Little is known about acquisition of human papillomavirus (HPV) and its outcome among older women with negative HPV testing and normal cytology. A longitudinal 3-yr follow-up of nested-cohort subjects (n = 8825) from a population-based cervical cancer screening study whose Pap and HPV tests were negative at baseline were conducted. Every active HPV-negative (n = 413) participant had 12-mo follow-ups of Pap smear and HPV testing. Colposcopy was performed if either HPV-positive or cytology was abnormal. The cytology and histology information of the remaining subjects (passive HPV-negative, n = 8412) was obtained from national registry database. Median age of participants was 45 yr (range, 30,73 yr). The incidence of new acquisition was 4.2/100 woman-years. The 3-yr cumulative total HPV acquisition rate was 11.1% (95% confidence interval [CI]: 8.1,14.1). Increased number of sexual partners (,2 vs. 1) of the participant was associated with risk of acquisition (odds ratio [OR]: 5.0, 95% CI: 2.0,12.6) by multivariate analysis. Three cases of , cervical intraepithelial neoplasia (CIN) 2 were identified in 3-yr follow-up in active HPV-negative subjects. HPV genotypes in the dysplastic tissue were actually present at baseline samples after reanalysis. From the passive HPV-negative group, only 1 case progressed to CIN2 probably after HPV acquisition. Negative Pap and HPV tests assured a very low risk of developing , CIN2 within 3 yr despite incident HPV infection. [source] Effects of Ethanol on Extracellular Levels of Adenosine in the Basal Forebrain: An In Vivo Microdialysis Study in Freely Behaving RatsALCOHOLISM, Issue 5 2010Rishi Sharma Background:, Adenosine is implicated to play a pivotal role in mediating many neuronal responses to ethanol. While in vitro studies performed in cell culture have demonstrated that acute ethanol exposure increases extracellular adenosine levels, this effect has not been demonstrated, in vivo, in the brain. We performed an in vivo microdialysis study to examine the effects of local ethanol perfusion on extracellular levels of adenosine in the basal forebrain (BF). Methods:, Under sterile conditions and using a standard surgical protocol, adult male Sprague,Dawley rats were implanted with unilateral microdialysis guide cannula targeted toward the BF. Following postoperative recovery, the microdialysis probe was inserted. After allowing at least 12 to 16 hours for probe insertion recovery, the experiment was begun. Artificial cerebrospinal fluid (aCSF) was perfused (0.7 ,l/min) for 80 minutes, and 4 × 20-minute pre-ethanol baseline samples were collected. Subsequently, 30, 100, and 300 mM doses of ethanol were perfused. Each ethanol dose was perfused for 80 minutes, and 4 × 20-minute samples were collected. Finally, aCSF was perfused, and 4 × 20 postethanol samples were collected. Adenosine in the microdialysate was separated and measured with HPLC coupled with an UV detector. On completion, the animals were euthanized, brain removed and processed for histology. Results:, Local ethanol perfusion in the BF produced a significant increase in extracellular adenosine with the highest dose of 300 mM ethanol producing a 4-fold increase. Cresyl violet (Nissl) staining did not indicate any toxic damage in the area surrounding the probe tip. Choline acetyltransferase immunohistochemistry revealed that all microdialysis probe sites were localized in the BF. Conclusion:, Our study is the first to demonstrate that ethanol acts directly in the brain to increase extracellular adenosine. [source] Measurement of Free Thyroxine Concentration in Horses by Equilibrium DialysisJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2006Babetta A. Breuhaus The purpose of the study reported here was to validate measurement of free thyroxine (fT4) concentration in equine serum by equilibrium dialysis (fT4D), and to compare values with fT4 concentration measured directly and with total T4 (TT4) concentration. The fT4D, fT74, and TT4 concentrations were measured over a range of values in euthyroid horses and horses made hypothyroid by administration of propylthiouracil (PTU). Concentrations of fT4D (<1.8,83 pmol/L) were consistently higher than those of fT4 (<1,40 pmol/L). There was a significant (P < .001) regression of fT4D on fT4 in 503 samples from normal horses (y = 2.086x - 0.430). In baseline samples from 71 healthy euthyroid horses, fT4 concentration ranged from 6- 21 pmol/L (median, 11 pmol/L; 95% confidence interval [CI]10.5,11.8 pmol/L), and fT4D concentration ranged from 7,47 pmol/L (median, 22 pmol/L; 95% CI 20.9,25.1 pmol/L). Free T4D, fT4, and TT4 concentrations were also measured in 34 ill horses. Horses consuming PTU and ill horses had significantly (P < .05) lower serum concentration of TT4, fT4, and fT4D than did clinically normal, healthy horses. If serum samples from ill horses were further subdivided into samples from horses that lived and samples from horses that died, fT4D concentration was not significantly different in ill horses that lived, compared with that in healthy horses, whereas fT4 concentration was still significantly decreased in ill horses that died (P < 0.001). We conclude that measurement of fT4 concentration by equilibrium dialysis is a valid technique in the horse, and its use may provide improved ability to distinguish nonthyroidal illness syndrome from hypothyroidism in that species. [source] A comparison of ex vivo cytokine production in venous and capillary bloodCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007M. Eriksson Summary We performed a randomized study of the immunological effects of an early measles vaccine given at 4·5 months of age and aimed to obtain venous samples from the infants at baseline and 6 weeks later. If this was not feasible, a capillary sample was obtained. We analysed baseline samples from the first 50 children enrolled in the study to investigate the potential differences in ex vivo cytokine production between venous blood and capillary blood. We also obtained paired venous and capillary blood samples from 11 adult volunteers. Whole blood was stimulated with lipopolysaccharide (LPS) [a Toll-like receptor (TLR)-4 ligand], (S)-(2, 3-bis (palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, trihydrochloride (PAM3Cys) (a TLR-2 ligand), phytohaemagglutinin (PHA) or purified protein derivative (PPD). Cytokine concentrations in the supernatants were assessed by a multiplexed assay and were compared between venous and capillary samples in both infants and adults. The production of both the pro- and the anti-inflammatory cytokines, tumour necrosis factor (TNF)-, and interleukin (IL)-10, was higher in cultures of capillary blood compared with venous blood. This was found in non-stimulated control samples as well as in blood stimulated with PAM3Cys and PPD. Adults produced more IL-5 in venous blood than in capillary blood upon PHA stimulation. We found no other difference in the levels of IL-5 or IFN-, between venous and capillary blood. In capillary blood we found sex differences in response to PHA but this was not the case in venous blood. We found significant differences in the production of cytokines between venous and capillary blood. Such differences should be taken into account when setting up immuno-epidemiological studies. [source] | ||||||||||