Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.
Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ? 0.5 ?C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.
An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.
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The incidence of cardiovascular events remains high in patients with myocardial infarction (MI) despite advances in current therapies. New and better methods for identifying patients at high risk of recurrent cardiovascular (CV) events are needed. This study aimed to analyze the predictive value of an oral glucose tolerance test (OGTT) in patients with acute myocardial infarction without known diabetes mellitus (DM).
The prospective cohort study consisted of 123 men and women aged between 31-80 years who had suffered a previous MI 3-12 months before the examinations. The exclusion criteria were known diabetes mellitus. Patients were followed up over 6.03???1.36 years for CV death, recurrent MI, stroke and unstable angina pectoris. A standard OGTT was performed at baseline.
BACKGROUND: One hundred twenty women alcoholics recruited to a treatment program called EWA (Early Treatment for Women With Alcohol Addiction) were studied. The selected women were not previously treated for alcohol abuse. METHODS: The women were followed up by use of a structured personal interview, biomarkers sensitive for alcohol abuse (i.e., glutamyl transpeptidase), and questionnaires, by using defined criteria for abstinence, social drinking, satisfactory drinking outcome, and unsatisfactory drinking outcome. RESULTS: Drinking outcome was good (i.e., total abstinence, social drinking, or satisfactory drinking outcome) for 67% of the women during the total follow-up time, by use of strict criteria for relapse. The results were corroborated by the biomarkers. Similar results were reported from two previously studied groups of women from the same department. However, the frequency of abstinence was higher and social drinking was significantly lower among this sample of women. Daily drinking, the use of sedatives, and a long duration of pretreatment alcohol abuse predicted an unfavorable outcome. However, a long duration of outpatient treatment predicted a good outcome, whereas treatment dropout was related to an unsatisfactory drinking outcome. A majority of the women (96%) rated the treatment experience and the treatment program favorably. The overall good results might reflect the selection of the subjects studied. CONCLUSIONS: Improving treatment program adherence would probably improve outcome for the women with an unsatisfactory drinking outcome.
OBJECTIVES: Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases. To test this hypothesis, we conducted a 5-year follow-up study in middle-aged men. METHODS: A population-based cohort study conducted in 1995 amongst 141 Swedish men born in 1944, in whom a clinical examination supplemented by medical history aimed to disclose the presence of cardiovascular disease (CVD) (myocardial infarction, angina pectoris, stroke), type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000. In addition, salivary cortisol levels were measured repeatedly over the day. Serum testosterone concentrations were also determined. Using the baseline data, an algorithm was constructed, which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal. RESULTS: By the end of follow-up, men with an abnormal hormone secretion pattern (n = 73) had elevated mean arterial pressure (P = 0.003), fasting insulin (P = 0.009) and insulin : glucose ratio (P = 0.005) compared with men with a normal secretion pattern (n = 68). Body mass index, waist circumference, and waist : hip ratio were significantly elevated in both groups. However, the 5-year incidence of CVD, type 2 diabetes, and hypertension were significantly higher (P
To report the initial experience with combined 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) imaging for suspected recurrent papillary differentiated thyroid cancer (DTC) at Sunnybrook Health Sciences Centre (SHSC), Toronto.
Single institution retrospective study.
Consecutive patients from SHSC who underwent FDG PET/CT imaging for suspected recurrent DTC over a period of 2.5 years were identified and their charts reviewed.
Qualitative appraisal of FDG PET/CT imaging in suspected recurrent DTC.
Sixteen patients (14F, 2M) were identified accounting for 17 FDG PET/CT scans. Three scans (18%) in 3 different patients were reported as suspicious for recurrent disease in the neck (1-3 lesions) and were considered "positive". All were subsequently confirmed pathologically (4-13 positive lymph nodes post operatively). Prior conventional imaging was abnormal in two patients. Two patients had an elevated non-stimulated thyroglobulin (TG)
The objective of the study was to determine completeness of 24-hour urine collection in pregnancy.
This was a retrospective laboratory/chart review of 24-hour urine collections at British Columbia Women's Hospital. Completeness was assessed by 24-hour urinary creatinine excretion (UcreatV): expected according to maternal weight for single collections and between-measurement difference for serial collections.
For 198 randomly selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of 97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body weight resulted in more inaccurate collections (24-68%). The current weight was frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric) with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31] days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40 women (24.8%) had values 25% or greater, exceeding analytic and biologic variation.
Twenty-four hour urine collection is frequently inaccurate and not a precise measure of proteinuria or creatinine clearance.
We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population.
We measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events.
Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend = 2 × 10(-3)). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (
Vitamin D has potential antithrombotic effects, suggesting that vitamin D analogs could be used as adjunctive antithrombotic agents. However, epidemiologic evidence of an association between reduced 25-hydroxyvitamin D concentrations and the risk of venous thromboembolism is lacking.
To test the hypothesis that reduced plasma 25-hydroxyvitamin D concentrations are associated with an increased risk of venous thromboembolism in the general population.
We prospectively studied 18 791 participants from the Copenhagen City Heart Study and the Copenhagen General Population Study. During up to 30 years of follow-up, 950 participants were diagnosed with venous thromboembolism. Plasma 25-hydroxyvitamin D concentrations were adjusted for seasonal variation.
The cumulative incidence of venous thromboembolism as a function of age increased with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D (log-rank trend: P = 4 × 10(-4) ). On comparison of participants in the lowest and the highest tertile of plasma 25-hydroxyvitamin D concentrations, the crude risk estimate in a model adjusted for age and sex was a 37% (95% confidence interval [CI] 15-64%) increased risk of venous thromboembolism. The corresponding risk increase in a model adjusted for age, sex, body mass index, smoking and cancer was 26% (95% CI 5-51%), and in a multivariable-adjusted model also including physical activity, hormone replacement therapy, menopausal status, oral contraception use and lipid-lowering therapy it was 28% (95% CI 6-53%). Furthermore, corresponding risk increases with attempts to correct for regression dilution bias were 103% (95% CI 37-202%), 70% (95% CI 14-155%) and 73% (95% CI 15-160%) in the three models, respectively.
In these large general population studies, we observed a stepwise increasing risk of venous thromboembolism with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D concentrations.
We tested the hypothesis that reduced plasma 25-hydroxyvitamin D associates with increased risk of ischemic heart disease, myocardial infarction, and early death.
We measured baseline plasma 25-hydroxyvitamin D in 10 170 women and men from the Danish general population without vitamin D-fortified food. During 29 years of follow-up, 3100 persons developed ischemic heart disease, 1625 myocardial infarction, and 6747 died. Decreasing plasma 25-hydroxyvitamin D levels were associated with increasing risk of ischemic heart disease, myocardial infarction, and early death as a function of seasonally adjusted percentile categories (P for trend, 2×10(-4)-3×10(-53)). Comparing individuals with plasma 25-hydroxyvitamin D levels at the 1st to 4th percentile with individuals with levels at the 50th to 100th percentile, the multivariable adjusted risk was increased by 40% (95% CI, 14%-72%) for ischemic heart disease, by 64% (25%-114%) for myocardial infarction, by 57% (38%-78%) for early death, and by 81% (40%-135%) for fatal ischemic heart disease/myocardial infarction. In the meta-analyses of 18 and 17 studies, risk of ischemic heart disease and early death were increased by 39% (25%-54%) and 46% (31%-64%) for lowest versus highest quartile of 25-hydroxyvitamin D level.
We observed increasing risk of ischemic heart disease, myocardial infarction, and early death with decreasing plasma 25-hydroxyvitamin D levels. These findings were substantiated in meta-analyses.
Center for Nutrition and Toxicology, Department of Biosciences, Karolinska Institute, Novum, S-141 57 Huddinge and Department of Molecular Genome Research, Stockholm University, S-106 91 Stockholm, Sweden. kamila.plna2cnt.ki.se
Epichlorohydrin (ECH) is a simple 3-carbon epoxide of industrial importance. It has been shown to be genotoxic in several systems and carcinogenic in experimental animals. The aim of the present investigation was to study DNA adducts of ECH as a biomarker of occupational exposure to this chemical. 7-(3-Chloro-2-hydroxypropyl)guanine (7-CHP-guanine) was analysed in DNA from white blood cells using an anion exchange-based adduct enrichment protocol of the (32)P-post-labelling/HPLC-based assay. Blood samples were collected from seven workers handling ECH (exposed), nine workers not handling ECH but normally present in the premises where this chemical is used (potentially exposed) and 13 office and factory workers from locations in the plant where ECH is not handled (controls). 7-CHP-guanine was detected in five of the seven workers exposed to ECH (1.6-7.1 mol/10(9) mol nucleotides) and in two of the nine workers potentially exposed to ECH (0.8-1.5 mol/10(9) mol nucleotides). This adduct was not detected in any of the 13 controls. The difference in adduct levels between exposed workers and controls was statistically significant (Mann-Whitney test, P