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.
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
18F-fluorodeoxyglucose positron emission tomography-computed tomography for suspected recurrent papillary thyroid cancer: early experience at Sunnybrook Health Sciences Centre.
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)
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.
25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies.
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.
A 52-week prospective, cohort study of the effects of losartan with or without hydrochlorothiazide (HCTZ) in hypertensive patients with metabolic syndrome.
The impact of an ARB, with or without hydrochlorothiazide (HCTZ), on glycaemic factors and the risk for developing diabetes in hypertensive patients with the metabolic syndrome have not been fully assessed. This was a 52-week multicentre, prospective, phase-IV, open-label, cohort study of losartan or losartan/HCTZ in hypertensive patients with metabolic syndrome. All subjects were treated initially with losartan 50?mg?day(-1). Those not achieving target blood pressure (BP
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.
We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.
We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).
We found differential DNA methylation at epigenome-wide statistical significance (p-value
Recent data from the Diabetes Control and Complications Trial (DCCT) indicated that A1C variability is associated with the risk of diabetes microvascular complications. However, these results might have been influenced by the interventional study design. Therefore, we investigated the longitudinal associations between A1C variability and diabetes complications in patients with type 1 diabetes in the observational Finnish Diabetic Nephropathy (FinnDiane) Study.
A total of 2,107 patients in the FinnDiane Study had complete data on renal status and serial measurements of A1C from baseline to follow-up (median 5.7 years), and 1,845 patients had similar data on cardiovascular disease (CVD) events. Intrapersonal SD of serially measured A1C was considered a measure of variability.
During follow-up, 10.2% progressed to a higher albuminuria level or to end-stage renal disease, whereas 8.6% had a CVD event. The SD of serial A1C was 1.01 versus 0.75 (P
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Cites: N Engl J Med. 2005 Dec 22;353(25):2643-5316371630
