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Ultraviolet B sensitivity of peripheral lymphocytes as an independent risk factor for cutaneous melanoma.

Susceptibility to solar ultraviolet is an important melanoma risk factor. We investigated the relationship between individual susceptibility to ultraviolet and risk of melanoma by measuring the apoptosis triggered in peripheral lymphocytes by a low-dose ultraviolet B irradiation (50 J/m(2)) in young and older melanoma patients and controls. Melanoma patients below the age of 40 are more sensitive to UVB-induced apoptosis than older melanoma patients and healthy controls. Analysis of data (adjusted for age and phototype) shows that UVB-induced apoptosis is an important risk factor for melanoma (OR 9.1, 95% CI [3-28], P=0.0001). UVB-induced apoptosis is independent of phototype (P=0.11, Wald test) and tumour thickness (P=0.88, Spearman correlation, for all cases and 0.26 for patients younger than 40 years), and may be used as a functional laboratory test for studying the genetic-environment interactions involved in melanoma occurrence.

Adolescent↗

Quality of life in long-term Hodgkin's disease survivors with chronic fatigue.

The prevalence of chronic fatigue (CF), elevated fatigue levels >six months, is 2.5-3 times higher in long-term Hodgkin disease survivors (HDSs) than in the general population (GP). This is the first study comparing the quality of life (QoL) of chronic fatigued survivors with that of chronic fatigued subjects in the GP. The fatigue questionnaire (FQ) and the SF-36 were mailed to 591 HDSs successfully treated at the Norwegian Radium Hospital from 1971 to 1997. Patient data were compared with nationally representative GP data, adjusted for age, gender and education. The response rate was 80% (N = 475), median follow-up 195 months (range 53-431), mean age 46 years (range 21-74), and 44% were females. HDSs reported significantly poorer QoL than the GP with lower scores on six of eight SF-36 scales (P < 0.001). The subgroup of HDSs with chronic fatigue however (N = 142/475, 30%) had better QoL on five of eight SF-36 scales than subjects with CF in the GP (N = 224/2141, 11%), particularly mental health and emotional role-functioning (P = 0.005 and <0.0001). No differences were found on the physical SF-36 domains. Overall, HDSs reported lower QoL than the GP, in particular the HDSs with CF. Their QoL was similar to that of GP subjects with CF, but with significantly better mental health status. This suggests that CF in long-term survivors may be associated with more physical than psychological aspects of long-term cancer survivorship.

Adult↗

An evaluation of the maximized survey-derived daily intake (MSDI) as a practical method to estimate intake of flavouring substances.

Realistic estimates of intake are essential for risk assessments of flavouring agents, since substantial over or underestimations introduce inaccuracies into such evaluations. The objectives of this study were to examine the relationship between intakes estimated using methods based on the reported volume of production [e.g., maximized survey-derived daily intake (MSDI)] versus use-level data [e.g., possible average daily intake (PADI) and modified theoretical added maximum daily intake (mTAMDI)]. The impact of volatility, self-limiting organoleptic properties and whether 10% of the population are eaters, an assumption in the MSDI calculation, on intake estimates were investigated. Analyses on 221 flavouring substances showed that intake estimates derived from MSDI correlated with values determined from detailed 14-day menu-census data, PADI, and mTAMDI. Comparisons of menu-census intake data adjusted to account for factors such as volatile losses showed that MSDI estimates are realistic and sufficiently conservative, whereas mTAMDI results in substantial overestimates of intake. Very few flavours have less than 10% eaters, and in the worst case, this assumption underestimates percent eaters by a factor of about 4. This investigation supports the use of MSDI as a conservative yet practical method to estimate intake of flavouring substances.

Consumer Product Safety↗

Pentachlorophenol removal from aqueous matrices by sorption with almond shell residues.

Sorption with activated carbon has been the technique preferred for pentachlorophenol (PCP) removal from contaminated waters, but regeneration needs and high operation costs are supporting a renewed interest in the search for alternative sorbents. Among them, almond shell, an agricultural by-product, provides interesting economical advantages, once shells account for 50% (in mass) of the whole almond. In this work, the capacity of almond shells to remove PCP from waters without previous activation was studied in batch conditions. While PCP analysis was performed solid-phase microextraction (SPME) followed by gas chromatography with electron capture detection (GC-ECD), mercury porosimetry and Fourier transform infrared spectroscopy (FTIR) provided a preliminary physical and chemical characterization of the sorbent. Almond shells were essentially a macroporous material, with an average surface area of 12.9+/-2.8 m2/g. The efficiency of PCP removal was 93+/-14%, in 24 h, with an initial concentration of 100 microg/l PCP and 5 microg PCP/g shell. Isotherm data adjusted better to Freundlich equation, where K(F) and 1/n were 0.075+/-0.081 mg(1-1/n) l(1/n) and 1.882+/-0.289, respectively. Average desorption efficiency was 7%, indicating strong adsorption capacity. Results proved that almond shells may be an excellent low-cost alternative for PCP removal from contaminated waters.

Adsorption↗

Antibiotic use in two cohorts of German intensive care units.

Antibiotic use was evaluated in two cohorts of intensive care units (ICUs) in Germany. One cohort included ICUs participating in a surveillance programme (N=34) collecting antibiotic use and bacterial resistance data, with quarterly feedback. The second ICU cohort was from a cross-sectional study and represented a sample from hospitals in South-west Germany (N=58). Two dose definitions were used. These were the World Health Organization/Anatomical Therapeutic Chemical Classification (ATC) 2001 definition of defined daily dose (DDD), and a definition of recommended daily dose (RDD) that better reflected the currently prescribed dosages of parenteral drugs for hospitalized patients. Data were expressed as DDD or RDD per 100 patient-days. It was determined whether hospital size and affiliation, year of study and ICU type had an influence on overall use of antibiotics. Overall use differed between the two ICU cohorts irrespective of the dose definitions used. High use of antibiotics was primarily associated with hospital affiliation (university vs non-university) and hospital size. Mean overall use of antibiotics in non-university hospital ICUs ranged between 106 and 111 DDD/100 (59 and 67 RDD/100) for different hospital size categories, compared with 140 DDD/100 (87 RDD/100) in university hospital ICUs. In conclusion, in order to compare the use of antibiotics between ICU cohorts and to assess trends over time, data adjustment is required for hospital affiliation and size.

Anti-Bacterial Agents↗

Electromyogram-triggered neuromuscular stimulation and stroke motor recovery of arm/hand functions: a meta-analysis.

Debate persists about the effectiveness of poststroke behavioral interventions for progress toward motor recovery. The current meta-analysis assessed the effect of electromyogram (EMG)-triggered neuromuscular stimulation on arm and hand functions. Computer searches of PubMed and Cochran databases, as well as hand searches of reference lists identified seven EMG-triggered neuromuscular stimulation studies. Outcome measures focused on arm and hand motor capability functions. In addition, the quality of each study was rated on three guidelines: randomization, double blind, and dropouts. After adjusting data for consistency in the arm/hand outcome measures and to avoid bias, five active stimulation studies were included in the analysis. Rehabilitation treatment in each study focused on wrist extension. The total number of individuals in the treatment groups was 47 whereas the control groups had 39 subjects. The meta-analysis revealed a significant overall mean effect size (delta=0.82, S.D.=0.59). A homogeneity test indicated that the pooled standardized effect sizes estimated the same treatment effect. A fail-safe test for null effect findings revealed that 15 studies were required to reduce the large effect (0.82) to a small effect (0.20). These improved wrist extension motor capabilities findings support EMG-triggered neuromuscular stimulation as an effective poststroke protocol.

Arm↗

Hemisphere asymmetry for imitation of hand and finger movements, Goldenberg's hypothesis reworked.

Goldenberg and co-workers put forward the hypothesis that coding of hand gestures with respect to body parts depends upon the functioning of the left hemisphere while the right hemisphere would be involved in imitation of finger postures. They supported this claim with experimental evidence from lesion studies, however, they failed to back it up with functional neuroimaging data. To verify Goldenberg's hypothesis on hemisphere asymmetries for hand/finger postures imitation, the performance of 35 patients with left hemisphere lesion (L/pts), of 24 patients with right hemisphere lesion (R/pts) and that of 41 matched controls was assessed in two imitation tasks, respectively, taxing hand or finger postures. The data, adjusted for the performance of the controls and for the effect of age were analysed using a multivariate, nonparametric approach. The outcome partly supports Goldenberg and colleagues' hypothesis: hand minus finger performance did differs between the R/pts and L/pts patients, even considering the pertinent hand-finger performances by control participants, however, in line with neuroimaging evidence, the left hemisphere's contribution is greater than that of the right for both finger and hand posture imitation.

Adult↗

Sexual activity as a trigger for cardiovascular events: what is the risk?

An important component in the rehabilitation program of patients with cardiac disease is assisting them in resuming sexual activity. In many cases, cardiac disease creates fear, particularly in the spouse, that sexual activity will trigger a cardiac event. Assessment of the possibility that sexual activity may lead to cardiac disease has been aided by advances in the study of triggers of cardiovascular disease. The acute onset of cardiovascular disease has, in many cases, proved to result from the exposures and activities of patients. Nonfatal myocardial infarction, sudden cardiac death, stroke, transient myocardial ischemia, and most arrhythmias have a marked peak during the period between 6:00 A.M. and noon. Wake-time-adjusted data indicate that peak occurrence follows waking and rising. In addition to this marked dependence of disease onset on time of day and awakening, it has been established that there are numerous other triggers of cardiovascular events. For nonfatal infarction, the triggers of heavy exertion, anger, sexual activity, and awakening account for approximately 17% of all cases. Other triggers are still being identified. A new epidemiologic method, the case-crossover method, has greatly enhanced identification of triggering. Regular exertion can reduce the incidence of triggering. It is possible, though unproved, that an acute event can be triggered by rupture of a vulnerable atherosclerotic plaque. With regard to sexual activity, the low absolute risk generated by a potential trigger is useful information with which to reassure patients.

Adult↗

Evidence against alterations in Lecithin:cholesterol acyltransferase (LCAT) activity in familial combined hyperlipidemia.

Elevated concentrations of plasma cholesterol and triglycerides are characteristic of familial combined hyperlipidemia (FCHL) which may also present with reduced high density lipoprotein (HDL) cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by converting unesterified cholesterol to cholesterol ester in the process of maturation of HDL in the presence of its activator, apolipoprotein (apo) A-I. We hypothesised that alterations in LCAT activity or plasma concentrations or gene sequence of apo A-I could influence HDL metabolism in these patients. We studied cholesterol concentrations of high density lipoprotein subfractions and LCAT activity in 25 FCHL subjects and 48 controls. Total HDL (p=0.018) and HDL2 (p=0.008) were significantly decreased in the FCHL group compared with controls. After analyses with adjusted data only HDL2 remained significantly decreased in the FCHL group (p=0.050). The LDLc/HDLc and A-I/HDLc ratios were significantly elevated in the FCHL group (p <0.0001), the latter suggesting the existence of compositional differences in the HDL particles of the FCHL individuals. LCAT activity assessed in the FCHL (19.94+/-3.95 nmol/ml per h) and control (20.13+/-6.86 nmol/ml per h) groups showed no statistically significant differences. A significant positive correlation of LCAT activity with total HDL (r=0.42), HDL3 cholesterol (r=0.46) and apolipoprotein A-I (r=0.47) was observed in affected subjects but not in controls. An association between a Ga(-75)-A variation in the promoter region of the apo A-I gene and elevated concentrations of apo A-I (p=0.009) and apo C-III (p=0.041) was observed. This association was strongly influenced by the status of the subject providing further evidence for a regulatory role of this genetic region in the expression of FCHL. Our data suggests that LCAT activity is normal in FCHL and, therefore, does not account for the abnormalities observed in these patients essentially with regard to the HDL2 subfraction.

Adult↗

Homocysteine and ischaemic heart disease in the Caerphilly cohort.

Elevated circulating total homocyst(e)ine concentrations are associated with a higher prevalence of ischaemic heart disease (IHD). We utilized data from the Caerphilly Prospective Cohort Study to assess the predictive power of the serum total homocyst(e)ine concentration for future IHD. Serum total homocyst(e)ine concentrations were measured in 2290 men in the Caerphilly cohort, a representative population sample of men aged 50-64 years. During a 5-year follow-up period, 56 men suffered fatal IHD, 77 had a non-fatal myocardial infarction, while 21 were found to have ECG evidence of myocardial infarction (MI) when examined at follow-up. The mean serum total homocyst(e)ine concentration in the total of 154 men who experienced an incident IHD event was 12.4 micromol/l, whereas the 2136 men who experienced no such event had a mean level of 11.7 micromol/l. The difference between these means, examined by logistic regression and standardising for the effects of differences in age, social class, smoking, BMI, diabetes, HDL-cholesterol and prevalent IHD is 0.47 micromol/l (95% CI = -0.13 to 1.11 micromol/l). The mean difference for the 56 men who died, and whose death was attributed to IHD, is 0.81 micromol/l (95% CI= -0.17 to 1.88 micromol/l) after correction for confounding factors. Vitamin nutritional status and alcohol intake were significant negative determinants of serum total homocyst(e)ine concentrations; the effect of alcohol is explained by the folic acid content of beer, which is the preferred alcoholic beverage in Caerphilly. It is concluded that the serum total homocyst(e)ine concentration is weakly predictive of IHD events, though in the present data adjustments for other factors attenuated the relationship and it became not statistically significant (P > 0.05).

Biomarkers↗

Influence of Holter monitor and electrophysiologic study methods and efficacy criteria on the outcome of patients with ventricular tachycardia and ventricular fibrillation in the ESVEM trial.

Because not all laboratories use the monitoring and stimulation protocols used in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, we reanalyzed the ESVEM patients' data using alternative, commonly used Holter monitor (HM) and programmed stimulation efficacy criteria to determine if different criteria would have changed the trial's conclusions. Also, because beta-blocker use and coronary artery disease frequency were not equally distributed between the two limbs in ESVEM, we reanalyzed the ESVEM data adjusting for the possible effect of these variables. In the HM limb, drug efficacy in the original ESVEM analysis was declared by reduction of total premature ventricular complexes (PVCs) by 70%, pairs by 80%, runs of 3 to 15 beats by 90%, and all ventricular tachycardia (VT) more than 15 beats by 100%. In this analysis, we examine outcome in subjects meeting two more stringent sets of criteria, (1) reduction of total PVCs by 70%, of pairs by 80%, and of all VT by 100% (new criteria set 1) and (2) reduction of total PVCs by 80%, of pairs by 90%, and of all VT by 100% (new criteria set 2). In electrophysiology (EPS) limb patients, we compared arrhythmia recurrence when efficacy was declared with triple extrastimuli as compared with maximally testing with double extrastimuli, and arrhythmia recurrence was compared in patients tested with identical versus any more aggressive protocol on drug than was used before drug. We also compared the predictive accuracy of zero versus 3 to 15, and 0 to 5, 6 to 10, and more than 10 induced beats on drug. Additionally, we compared predictive accuracy of the HM- and EP-guided limbs excluding patients on beta blockers and those with noncoronary disease. Lastly, to determine whether concordant results on HM and EPS testing would provide more accurate efficacy predictions than EP testing alone, HM recordings obtained in EPS-limb patients but not processed or used during the course of the EVSEM study were analyzed. The original ESVEM HM criteria, new set 1, and new set 2 yielded predicted drug efficacy rates of 77%, 68%, and 58%, respectively; however, arrhythmia recurrence rates were unchanged. Similarly, arrhythmia recurrence rates for patients tested with triple versus less than triple extrastimuli (p=.238), more aggressive versus identical protocols (p=.955), and 0 to 5 v 6 to 10 v more than 10 induced beats (p=.263) or 0 v 3 to 15 induced beats (p=.106) were unchanged. in the 215 (of 286) patients with coronary disease and not receiving beta blockers, there was still no difference in arrhythmia recurrence or mortality between the noninvasive and invasive limbs in ESVEM. Lastly, in patients with drug efficacy predictions by EPS testing, there was no difference in outcome in patients who had concordant versus discordant efficacy prediction by simultaneously obtained HMs. The use of more stringent testing methods and efficacy criteria would not have significantly improved the predictive accuracy of drug assessment by HM or EPS in the ESVEM trial. Additionally, excess noncoronary disease in EP-guided patients and excess beta-blocker used in HM-guided patients did not influence the results in the ESVEM trial.

Actuarial Analysis↗

Cerebral hypoperfusion in medication resistant, depressed patients assessed by Tc99m HMPAO SPECT.

Functional imaging studies generally show decreased cerebral metabolism and perfusion in depressed patients relative to normal controls, although the location of the deficits varies. We used Tc99m HMPAO SPECT to compare cerebral blood flow in medication resistant, depressed patients and a normal control group. HMPAO uptake ratios (adjusted for age) were significantly lower in the depressed patients in the transaxial slices 4 cm and 6 cm above the orbitomeatal line (OML) on the left side. Examining individual regions of interest (corrected for age and multiple testing), we found significantly lower perfusion in the left superior temporal, right parietal and bilateral occipital regions in the patient group. These findings are in limited agreement with previous HMPAO SPECT studies. Methodological differences between studies, particularly variability in adjusting data for age, lead to a divergence in findings. Future research should seek to standardize protocols and data analysis in order to generate comparable results.

Adult↗

Influence of agitation, inoculum density, pH, and strain on the growth parameters of Escherichia coli O157:H7--relevance to risk assessment.

Foods may differ in at least two key variables from broth culture systems typically used to measure growth kinetics of enteropathogens: initial population density of the pathogen and agitation of the culture. The present study used nine Escherichia coli O157:H7 strains isolated from beef and associated with human illness. Initial kinetic experiments with one E. coli O157:H7 strain in brain-heart infusion (BHI) broth at pH 5.5 were performed in a 2 x 2 x 3 factorial design, testing the effects of a low (ca. 1-10 colony-forming units [CFU]/ml) or high (ca. 1000 CFU/ml) initial population density, culture agitation or no culture agitation, and incubation temperatures of 10, 19, and 37 degrees C. Kinetic data were modeled using simple linear regression and the Baranyi model. Both model forms provided good statistical fit to the data (adjusted r(2)>0.95). Significant effects of agitation and initial population density were identified at 10 degrees C but not at 19 or 37 degrees C. Similar growth patterns were observed for two additional strains tested under the same experimental design. The lag, slope, and maximum population density (MPD) parameters were significantly different by treatment. Further tests were conducted in a 96-well microtiter plate system to determine the effect of initial population density and low pH (4.6-5.5) on the growth of E. coli O157:H7 strains in BHI at 10, 19, and 37 degrees C. Strain variability was more apparent at the boundary conditions of growth of low pH and low temperature. This study demonstrates the need for growth models that are specific to food products and environments for plausible extrapolation to risk assessment models.

Animals↗

Rapid mass spectrometric analysis for ascorbate and related organic acids in small volumes of plasma for use in pediatric subjects.

A gas chromatographic-mass spectrometric isotope dilution method was developed for analysis of ascorbate on 10 microl samples of plasma. This assay was reproducible (standard deviation of less than 4%) and gave values for plasma ascorbate content within 8% of our previously published gas chromatographic-mass spectrometric method. Non-specific sample preparation allowed other analytes to be determined on the same sample by adjusting data acquisition parameters and adding the appropriate internal standard. Analysis on 28 subjects fell within the expected range for plasma ascorbate 68+/-29 microm (11.9+/-5.0 microg/ml) and established a normal range for plasma threonate of 28.1+/-2.4 microm (3.8+/-0.4 microg/ml).

Ascorbic Acid↗

Some carcass characteristics of Alpine kids under intensive versus semi-intensive systems of production in France.

The effect of system of production (intensive versus semi-intensive) on some slaughter and carcass traits of Alpine male kids was evaluated. Data adjusted to a common age, indicated that management system had no significant effect (P>0.05) on carcass shape (carcass conformation and compactness and gigot conformation) and external fat score. Kids raised under the intensive management (IM) had heavier slaughter and carcass weights and large carcass width (P<0.01). Their dressing percentage and internal fat score were higher (P<0.05).

Journal Article↗

Maintenance of lightweight correlates with decreased cardiovascular risk factors in early adolescence.

PURPOSE: To describe predictors of lightweight in 11-year-olds and how weight changes between ages 9-11 years affected selected cardiovascular risk factors. METHODS: Cohort study among an ethnically and geographically diverse group of 5098 nine-year-olds who participated in the Child and Adolescent Trial for Cardiovascular Health (CATCH) and were followed from 1991 to 1994 until age 11 years. Lightweight (body mass index [BMI] <15th percentile) was defined from gender- and age-adjusted data on the total population in the National Health and Nutrition Examination Survey I of 1971 to 1973. Weight (BMI) category at follow-up (age 11 years) was the dependent variable in the logistic regression. Gender, race/ethnicity, school site, weight category at baseline, and participation in the CATCH (intervention or control group) were examined for possible predictors. RESULTS: The prevalence of lightweight was much lower than the 15% expected at both ages 9 and 11 years; 4.7% for males (M) and 7.4% for females (F) and at age 11 years; 5.9% for M and 8.3% for F. Lightweight at age 9 years was the best predictor of lightweight at age 11 years (OR = 56.8; CI 41.3, 78.2). Normal-weight children who entered the overweight category exhibited striking adverse percent changes in serum cholesterol and in both serum high-density cholesterol and apolipoprotein B cholesterol levels. Among children in each weight group at age 9 years, the heavier children at age 11 years had higher percent changes in systolic blood pressure, and lower times on the 9-min run. Maintenance of lightweight was associated with the most favorable pattern of cardiovascular risk factors. Differences between groups were not found for percent change in total calorie intake or percentage of calories from fat. Normal-weight children who became overweight exhibited striking percentage increases in levels of serum cholesterol and in serum apolipoprotein B cholesterols. CONCLUSIONS: Population-based anticipatory guidance about weight should focus on all children in mid-childhood, not only those at the upper extremes of weight. These who are genetically lean and healthy should be encouraged to remain so. Maintenance or achievement of lightweight was associated with favorable changes in systolic blood pressure in CATCH children during early adolescence. Those below the 5th percentile should be assessed and treated if eating disorders, undernutrition, or chronic illness are present. Optimal weight and optimal health should not be confused.

Blood Pressure↗

Is antioxidant use protective of cognitive function in the community-dwelling elderly?

BACKGROUND: The role of oxidative stress in the pathogenesis of diseases such as macular degeneration, certain types of cancer, and Alzheimer's disease has received much attention. Thus, there is considerable interest in the potential contribution of antioxidants to the prevention of these diseases. OBJECTIVE: The objective of this study was to determine whether use of supplemental antioxidants (vitamins A, C, or E, plus selenium or zinc) was associated with a reduced risk of development of cognitive impairment or cognitive decline in a representative sample of the community-dwelling elderly. METHODS: The sample consisted of 2082 nonproxy subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly who were not cognitively impaired at the 1989-1990 interview (baseline for the present analysis). Medication use was determined during in-home interviews. Cognitive function was assessed 3 and 7 years from baseline in terms of incident cognitive impairment, as measured on the Short Portable Mental Status Questionnaire (SPMSQ) using specific cut points (number of errors) based on race and education, and cognitive decline, defined as an increase of > or = 2 errors on the SPMSQ. Multivariate analyses were performed using weighted data adjusted for sampling design and controlled for sociodemographic characteristics, health-related behaviors, and health status. RESULTS: At baseline, 224 (10.8%) subjects were currently taking a supplement containing an antioxidant. During the follow-up period, 24.0% of subjects developed cognitive impairment and 34.5% experienced cognitive decline. Current antioxidant users had a 34.0% lower risk of developing cognitive impairment compared with non-antioxidant users (adjusted relative risk [RR], 0.66; 95% CI, 0.44-1.00) and a 29.0% lower risk of experiencing cognitive decline (adjusted RR, 0.71; 95% CI, 0.49-1.01). CONCLUSION: The results of this analysis suggest a possible beneficial effect of antioxidant use in terms of reducing cognitive decline among the community-dwelling elderly.

Age Factors↗