Effects of Alcohol on Highway Driving in the STISIM Driving Simulator

Human Psychopharmacology. Aug, 2011  |  Pubmed ID: 21823173

OBJECTIVE: The STISIM driving simulator is widely used. To enhance its usefulness in pharmacological research, a calibration study was performed to test a standardized highway driving test scenario after administration of three different dosages of alcohol and placebo. METHODS: Twenty-seven healthy young adults (14 men and 13 women; mean age (SD) = 22.8 (1.4)) participated in this randomized, single-blind crossover trial. Subjects received alcohol to gain a blood alcohol concentration (BAC) of 0.05%, 0.08%, and 0.11%, or placebo-alcohol. In each condition, subjects completed a 100-km highway driving simulator test. The standard deviation of lateral position, the weaving of the car, was the primary parameter of the test. RESULTS: Alcohol produced dose-dependent driving impairment. Standard deviation of lateral position and standard deviation of speed were significantly increased relative to placebo (p < 0.05). Subjective driving assessments were in line with the objective driving measurements. CONCLUSION: The STISIM highway driving simulator test is able to differentiate dose-dependent impairment after administration of alcohol. The highway driving test scenario is suitable for future psychopharmacological research. Copyright © 2011 John Wiley & Sons, Ltd.

Non-additive Hepatic Gene Expression Elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) Co-treatment in C57BL/6 Mice

Toxicology and Applied Pharmacology. Oct, 2011  |  Pubmed ID: 21851831

Interactions between environmental contaminants can lead to non-additive effects that may affect the toxicity and risk assessment of a mixture. Comprehensive time course and dose-response studies with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), non-dioxin-like 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and their mixture were performed in immature, ovariectomized C57BL/6 mice. Mice were gavaged once with 30 μg/kg TCDD, 300 mg/kg PCB153, a mixture of 30 μg/kg TCDD with 300 mg/kg PCB153 (MIX) or sesame oil vehicle for 4,12, 24,72 or 168 h. In the 24h dose-response study, animals were gavaged with TCDD (0.3,1, 3, 6, 10, 15, 30, 45 μg/kg), PCB153 (3,10, 30, 60, 100, 150, 300, 450 mg/kg), MIX (0.3+3, 1+10, 3+30, 6+60, 10+100, 15+150, 30+300, 45 μg/kg TCDD+450 mg/kg PCB153, respectively) or vehicle. All three treatments significantly increased relative liver weights (RLW), with MIX eliciting significantly greater increases compared to TCDD and PCB153 alone. Histologically, MIX induced hepatocellular hypertrophy, vacuolization, inflammation, hyperplasia and necrosis, a combination of TCDD and PCB153 responses. Complementary lipid analyses identified significant increases in hepatic triglycerides in MIX and TCDD samples, while PCB153 had no effect on lipids. Hepatic PCB153 levels were also significantly increased with TCDD co-treatment. Microarray analysis identified 167 TCDD, 185 PCB153 and 388 MIX unique differentially expressed genes. Statistical modeling of quantitative real-time PCR analysis of Pla2g12a, Serpinb6a, Nqo1, Srxn1, and Dysf verified non-additive expression following MIX treatment compared to TCDD and PCB153 alone. In summary, TCDD and PCB153 co-treatment elicited specific non-additive gene expression effects that are consistent with RLW increases, histopathology, and hepatic lipid accumulation.

Bilateral Diffuse Uveal Melanocytic Proliferation with a Positive Ophthalmoscopic and Visual Response to Plasmapheresis

Archives of Ophthalmology. Sep, 2011  |  Pubmed ID: 21911680

Next-day Effects of Ramelteon (8 Mg), Zopiclone (7.5 Mg), and Placebo on Highway Driving Performance, Memory Functioning, Psychomotor Performance, and Mood in Healthy Adult Subjects

Sleep. Oct, 2011  |  Pubmed ID: 21966064

To evaluate the next-morning residual effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects following bedtime dosing and a middle of the night awakening.

Grip Work Estimation During Sustained Maximal Contraction: Validity and Relationship with Dependency and Inflammation in Elderly Persons

The Journal of Nutrition, Health & Aging. Aug, 2011  |  Pubmed ID: 21968873

To validate muscle endurance estimation and to examine relationships with dependency and inflammation in elderly persons.

Occupational Hazard of Rubber Tapping

Occupational Medicine (Oxford, England). Oct, 2011  |  Pubmed ID: 21976220

Identification of Chronic Obstructive Pulmonary Disease in Lung Cancer Screening Computed Tomographic Scans

JAMA : the Journal of the American Medical Association. Oct, 2011  |  Pubmed ID: 22028353

Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage.

Conversion of the Mini-Mental State Examination to the International Classification of Functioning, Disability and Health Terminology and Scoring System

Gerontology. Nov, 2011  |  Pubmed ID: 22067433

Background: In older patients, evaluation of the cognitive status is crucial. The Mini-Mental State Examination (MMSE) is widely used for screening of cognition, providing fairly high sensitivity, specificity and reproducibility. Recently, a consensus emerged on the necessity of an international and transparent language, as provided by the WHO's International Classification of Functioning, Disability and Health (ICF). Most assessment tools however are not in accordance with the ICF. Objective: To reformulate the MMSE according to the ICF, both for the individual items and for the scoring system. Method: MMSE data (scores varying from 3 to 30/30) of (1) 217 cognitively healthy elderly, (2) 60 persons with mild cognitive impairment, (3) 60 patients with mild Alzheimer's disease (AD), and (4) 60 patients with moderate/severe AD were obtained from studies at a university hospital setting. Subjects were aged 65 years or more and recruited either through advertisement (group 1), from the geriatric day hospital (groups 2 and 3), or the geriatric ward (group 4). The allocation to the groups was done after multidisciplinary evaluation. The conversion of the MMSE to ICF-MMSE was done by content comparison and by subsequent translation of the scoring system using automatic algorithms. Results: All MMSE items were converted to the corresponding ICF categories. Three ICF domains were addressed: global and specific mental functions, general tasks and demands, divided over 6 ICF categories (orientation time/place, sustaining attention, memory functions, mental functions of language, undertaking a simple task). Scores on individual items were transformed according to their relative weight on the original MMSE scale, and a total ICF-MMSE score from 0 (no problem) to 100 (complete problem) was generated. Translation was satisfying, as illustrated by a good correlation between MMSE and ICF-MMSE. The diagnostic groups were distributed over the ICF-MMSE scores as expected. For each ICF domain, ICF-MMSE subscores were higher with increasing severity in cognitive decline. There was a higher dispersion, in accordance with the more detailed scoring possibilities of the ICF-MMSE. Conclusions: It is possible to adapt the MMSE to the ICF concept. This adaptation enhances interdisciplinary communication since it provides more clarity in assessment, with better visibility of the areas covered by the instrument.

Cellular Aging and Senescence Characteristics of Human T-lymphocytes

Biogerontology. Nov, 2011  |  Pubmed ID: 22102004

CD28-, CD57+ and KLRG1+ are cell surface markers that have been used to describe senescent T-lymphocytes in humans. However, the relationship among these phenotypes during aging, and their relationship with the concept of in vitro cellular aging have not been well established. Using five-colour flow cytometry, we analyzed peripheral blood T-lymphocytes for their expression of CD28, CD57 and KLRG1 in 11 young (Y) and 11 old (O) apparently healthy human subjects. The proportions of CD28- and CD57+ cells were significantly higher among the T-cell populations of O compared to Y subjects; the proportion of KLRG1+ cells was significantly higher only among CD8+ cells. Populations that were more frequent in the elderly participants were characterised as CD28+ CD57+, CD28- CD57+ or CD28- CD57-. The expression of p16 and p21, considered as markers for in vitro senescence, was higher in CD28+ CD57+ cells than in other subpopulations in both age groups. The expression of p21 was age-related, which was not the case for p16. Thus, although both p16 and p21 are involved in T-cell senescence, they appear to behave differently. CMV infection and shifts in subpopulations are unlikely as explanations of the observed differences. Their higher levels of p16 and p21 expression, coupled with their higher prevalence in the elderly participants make CD28+ CD57+ cells the subpopulation of T-cells most closely corresponding to the concept of senescent cells.

The Use of Acetyl Cholinesterase Inhibitors and Memantine in Nursing Home Residents

Acta Clinica Belgica. Sep-Oct, 2011  |  Pubmed ID: 22145270

Although a high proportion of elderly nursing home residents suffer from Alzheimer's disease (AD), data from the literature indicate that they are only rarely treated with Acetyl Cholinesterase Inhibitors (ChEls) or memantine. The aim of this study was to describe the use of ChEls or memantine by elderly residents in nursing homes, suffering from AD and to document who might qualify for pharmacological treatment according to the Belgian reimbursement rules.

Quantitative Computed Tomography in COPD: Possibilities and Limitations

Lung. Dec, 2011  |  Pubmed ID: 22179694

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD.

Effects on Muscle Performance of NSAID Treatment with Piroxicam Versus Placebo in Geriatric Patients with Acute Infection-induced Inflammation. a Double Blind Randomized Controlled Trial

BMC Musculoskeletal Disorders. 2011  |  Pubmed ID: 22208783

ABSTRACT:

The Process of Decline in Advanced Activities of Daily Living: a Qualitative Explorative Study in Mild Cognitive Impairment

International Psychogeriatrics / IPA. Feb, 2012  |  Pubmed ID: 22301014

ABSTRACTBackground: The notion of "minimal impairment in instrumental activities of daily living (i-ADL)" is important in the diagnosis of mild cognitive impairment (MCI), but is presently not adequately operationalized. ADL is stratified according to difficulty, complexity, and also to vulnerability to early cognitive changes in a threefold hierarchy: basic activities of daily living (b-ADL), i-ADL, and advanced activities of daily living (a-ADL). This study aims to gain a deeper understanding of the functional decline in the process of MCI.Methods: In a qualitative design, 37 consecutive patients diagnosed with amnestic (a)-MCI and their proxies were interviewed at two geriatric day hospitals. Constant comparative analysis was used for the analysis.Results: The a-ADL-concept emerged as important in the diagnosis of MCI. All participants were engaged in a wide range of activities, which could be clustered according to the International Classification of Functioning, Disability and Health (ICF). Participants reported subtle difficulties in performance. A process of functional decline was identified in which adaptation and coping mechanisms interacted with the process of reduced skills, leading to an activity disruption and an insufficiency in functioning.Conclusion: This study asserts the inclusion of an evaluation of a-ADL in the assessment of older persons. When evaluating ADL at three levels (b-ADL, i-ADL, and a-ADL), all the activities one can perform in daily living are covered.

Effects of Coffee on Driving Performance During Prolonged Simulated Highway Driving

Psychopharmacology. Feb, 2012  |  Pubmed ID: 22315048

RATIONALE: Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals. OBJECTIVES: The aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance. METHODS: Non-sleep deprived healthy volunteers (n = 24) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance. RESULTS: The results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p = 0.024) and second hour (p = 0.019) after the break. Similarly, the standard deviation of speed (p = 0.024; p = 0.001), mental effort (p = 0.003; p = 0.023), and subjective sleepiness (p = 0.001; p = 0.002) were reduced in both the first and second hour after consuming caffeinated coffee. Subjective driving quality was significantly improved in the first hour after consuming caffeinated coffee (p = 0.004). CONCLUSIONS: These findings demonstrate a positive effect of one cup of caffeinated coffee on driving performance and subjective sleepiness during monotonous simulated highway driving.

Chronic Low-grade Inflammation and Age-related Sarcopenia

Current Opinion in Clinical Nutrition and Metabolic Care. Jan, 2012  |  Pubmed ID: 22108098

Age-related chronic low-grade inflammatory profile (CLIP) has been recognized as an important causative factor for sarcopenia. Here, we report the recent evidence concerning CLIP and sarcopenia.

Antimalarial Efficacy of a Quantified Extract of Nauclea Pobeguinii Stem Bark in Human Adult Volunteers with Diagnosed Uncomplicated Falciparum Malaria. Part 1: A Clinical Phase IIA Trial

Planta Medica. Feb, 2012  |  Pubmed ID: 22095262

The aim of this phase IIA clinical trial was to assess the efficacy of an 80 % ethanolic quantified extract (containing 5.6 % strictosamide as the putative active constituent) from NAUCLEA POBEGUINII stem bark denoted as PR 259 CT1 in a small group of adult patients diagnosed with uncomplicated falciparum malaria. Results obtained from a phase I clinical trial on healthy male volunteers indicated that the oral administration during meals of two 500 mg capsules three times daily (each eight hours) during seven days was well tolerated and showed only mild and self-resolving adverse effects. This PR 259 CT1 drug regimen was obtained by mathematical conversion of animal doses obtained in several IN VIVO studies in mice to human equivalent doses as in falciparum malaria patients. The phase IIA study was an open cohort study in eleven appraisable adult patients suffering from proven PLASMODIUM FALCIPARUM malaria. The study was specifically designed to assess the efficacy of PR 259 CT1 administered with a dose regimen of two 500 mg capsules three times daily for three days, followed by outpatient treatment of one 500 mg capsule three times daily for the next four days, in order to prove that this therapeutic dose, which was calculated from animal doses, was effective to treat adult malaria patients and consequently useful for a future Phase IIB clinical trial. This study would then substitute a dose-escalating trial, which in general is used to find the appropriate dose for clinical studies. The phase IIA clinical trial was carried out according to the WHO 2003 14-day test, and the results revealed that all eleven patients were completely cleared of parasitemia and fever on days 3, 7, and 14 except for one patient, who experienced a recurrence of parasitemia at days 7 until 14. Besides this adequate clinical and parasitological response (ACPR), this trial also demonstrated that PR 259 CT1 was well tolerated with only mild and self-resolving adverse effects including fatigue and headache, which were in accordance with those found in the phase I clinical trial. Moreover, all symptoms progressively disappeared, and no symptoms were observed on day 14. Although the number of patients included in this study was rather limited, the statistical analysis nevertheless suggested the efficacy and tolerability of PR 259 CT1, which indicated that this herbal medicinal product might be considered as a putative candidate for a large scale clinical trial.

Inflammation-related Muscle Weakness and Fatigue in Geriatric Patients

Experimental Gerontology. Jan, 2012  |  Pubmed ID: 22032874

Inflammation in older persons is associated with muscle wasting, leading to frailty and functional decline. Most studies have focused on IL-6 and TNF-α. In order to further elucidate the underlying mechanisms of muscle wasting and reduced muscle mass and strength we investigated a large panel of cytokines and chemokines, as well as cytoprotective heat shock proteins (Hsp), and measured lean body mass (LBM) and grip strength (GS), fatigue resistance (FR), and grip work (GW) in 33 geriatric patients (median age 84 years) admitted with acute infection-induced inflammation. Higher expression of Hsp27 without heat challenge (WHC) in circulating monocytes and lymphocytes correlated with better FR (r=0.363, p<0.05 and r=0.602, p<0.001 respectively) suggesting a protective effect, as Hsp27 is abundant in muscle. On the other hand, higher serum levels of the inflammatory chemokines CCL11/Eotaxin and CCL2/MCP-1 were related to lower GS and lower LBM (r=-0.393, p<0.05; r=-0.431, p<0.05) respectively. Our results point to a complex pattern of pro-and anti-inflammatory substances that interact with skeletal muscle performance during acute inflammation.

Immunomodulatory Effect of NSAID in Geriatric Patients with Acute Infection: Effects of Piroxicam on Chemokine/cytokine Secretion Patterns and Levels of Heat Shock Proteins. A Double-blind Randomized Controlled Trial. (ISRCTN58517443)

Cell Stress & Chaperones. Mar, 2012  |  Pubmed ID: 22057579

Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection. Patients were randomized to receive either 10 mg piroxicam or placebo. Patients ≥70 years with CRP levels >10 mg/L of acute infectious origin were eligible. Twenty-five cyto-/chemokines as well as heat shock proteins Hsp27 (HSPB1) and Hsp70 (HSPA1A) were measured the first 4 days and then weekly until discharge, with a maximum of 3 weeks. Thirty Caucasian patients were included (median age 84.5 years, 67% female, median CRP 87.5 mg/L). In the piroxicam group, IL-6 and IP-10/CXCL10 decreased significantly during the study period. Relationships between cytokines were disrupted in the piroxicam group: for 12 out of 20 cytokines the number of correlations between changes in serum levels was significantly lower compared to placebo. Serum Hsp70 levels decreased significantly in the piroxicam group, but not in the placebo group. Without heat challenge, intracellular levels of Hsp70 in monocytes decreased in both groups, whereas HsP27 in monocytes increased with piroxicam with a significant difference compared to placebo at 3 weeks. Piroxicam in this setting cannot be considered merely as an anti-inflammatory drug, but rather as an immunomodulator. Further studies are needed to establish whether these effects can change functional outcomes in geriatric patients.

Comparative Metabolomic and Genomic Analyses of TCDD-elicited Metabolic Disruption in Mouse and Rat Liver

Toxicological Sciences : an Official Journal of the Society of Toxicology. Jan, 2012  |  Pubmed ID: 21964420

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) elicits a broad spectrum of species-specific effects that have not yet been fully characterized. This study compares the temporal effects of TCDD on hepatic aqueous and lipid metabolite extracts from immature ovariectomized C57BL/6 mice and Sprague-Dawley rats using gas chromatography-mass spectrometry and nuclear magnetic resonance-based metabolomic approaches and integrates published gene expression data to identify species-specific pathways affected by treatment. TCDD elicited metabolite and gene expression changes associated with lipid metabolism and transport, choline metabolism, bile acid metabolism, glycolysis, and glycerophospholipid metabolism. Lipid metabolism is altered in mice resulting in increased hepatic triacylglycerol as well as mono- and polyunsaturated fatty acid (FA) levels. Mouse-specific changes included the induction of CD36 and other cell surface receptors as well as lipases- and FA-binding proteins consistent with hepatic triglyceride and FA accumulation. In contrast, there was minimal hepatic fat accumulation in rats and decreased CD36 expression. However, choline metabolism was altered in rats, as indicated by decreases in betaine and increases in phosphocholine with the concomitant induction of betaine-homocysteine methyltransferase and choline kinase gene expression. Results from these studies show that aryl hydrocarbon receptor-mediated differential gene expression could be linked to metabolite changes and species-specific alterations of biochemical pathways.

The Relationship Between Lung Function Impairment and Quantitative Computed Tomography in Chronic Obstructive Pulmonary Disease

European Radiology. Jan, 2012  |  Pubmed ID: 21837396

To determine the relationship between lung function impairment and quantitative computed tomography (CT) measurements of air trapping and emphysema in a population of current and former heavy smokers with and without airflow limitation.