A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS.

BACKGROUND: Micro-inflammation is considered an element in the pathogenesis of irritable bowel syndrome (IBS). High-sensitivity C reactive protein (hs-CRP) was previously shown to be higher in IBS compared to healthy controls, albeit within the normal range. Since probiotics may suppress micro-inflammation in the gut, we tested if they reduce symptoms and inflammatory markers (hs-CRP and fecal calprotectin (FC) in diarrhea-predominant IBS (IBS-D). The aim of this study was to assess the clinical and laboratory effects of BIO-25, a multispecies probiotic, in women with IBS-D. METHODS: A double-blind, placebo-controlled study. Following a 2-week run-in, eligible women were assigned at random to a probiotic capsule or an indistinguishable placebo, twice daily for 8 weeks. IBS symptoms and stool consistency were rated daily by Visual Analogue Scales (VAS) and the Bristol Stool Scale (BSS). High-sensitivity C reactive protein was tested at baseline, 4 and 8 weeks. FC was tested at baseline and 8 weeks. KEY RESULTS: One hundred and seventy-two IBS-D patients were recruited and 107 eligible patients were allocated to the intervention (n=54) or placebo (n=53) group. All symptoms improved in both groups with no significant difference between them in symptom improvement, hs-CRP or FC levels. CONCLUSIONS & INFERENCES: An 8-week treatment with BIO-25 improved symptoms in women with IBS-D, but was not superior to placebo. This rigorously designed and executed study supports the findings of other studies that did not demonstrate superiority of probiotics over placebo in IBS. High quality clinical studies are necessary to examine the efficacy of other specific probiotics in IBS-D patients since data are still conflicting.

Assessing fatigue in inflammatory bowel disease: comparison of three fatigue scales.

BACKGROUND: Fatigue is commonly reported by patients with inflammatory bowel disease (IBD), both in quiescent and active disease. Few fatigue scales have been tested in IBD. AIM: To assess three fatigue assessment scales in IBD and to determine correlates of fatigue. METHODS: Potential participants (n = 2131) were randomly selected from an IBD organisation's members' database; 605 volunteered and were posted three fatigue scales: Inflammatory Bowel Disease Fatigue scale, Multidimensional Fatigue Inventory and Multidimensional Assessment Fatigue scale and questionnaires assessing anxiety, depression, quality of life (QoL) and IBD activity. The questionnaires were tested for stability over time with another group (n = 70) of invited participants. Internal consistency was measured by Cronbach's alpha and test-retest reliability by the intraclass correlation coefficient (ICC). RESULTS: Four hundred and sixty-five of 605 (77%) questionnaires were returned; of 70 invited, 48/70 returned test (68.6%) and 41/70 (58.6%) returned retest. The three scales are highly correlated (P < 0.001). Test-retest suggests reasonable agreement with ICC values between 0.65 and 0.84. Lower age, female gender, IBD diagnosis, anxiety, depression and QoL were associated with fatigue (P < 0.001) on univariable analysis. However, on multivariable analysis only depression and low QoL were consistently associated with fatigue, while female gender was associated on most scales. IBD diagnosis, age and other factors were not consistently associated with severity or impact of fatigue once other variables were controlled for. CONCLUSIONS: All three fatigue scales are likely to measure IBD fatigue adequately. Responsiveness to change has not been tested. Depression, poorer QoL and probably female gender are the major associations of fatigue in IBD.

Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. METHOD: The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. RESULTS: The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001). CONCLUSIONS: Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities.

BACKGROUND AND PURPOSE: Polymorphic paraoxonase (PON1) variants can variably prevent low- and high-density lipoprotein oxidation, but their role in provoking atherosclerosis remained unclear. We addressed this issue by profiling PON1 polymorphisms and enzymatic activities, and assessing atherosclerosis and cerebral arteriosclerosis severity in post-stroke patients. METHODS: Carotid artery intima-media-thickness (IMT), cerebral white matter lesions (WML), serum PON1 -108C/T, Q192R and L55M polymorphisms, and PON and acetylcholinesterase (AChE) enzyme activities were determined in 237 patients. RESULTS: Genetic variation at the PON1 locus showed a strong influence on PON1 activity in ischaemic stroke patients, but lacked direct influence on IMT. Stroke patients with PON1 QQ192 or MM55 genotypes demonstrated lower PON and arylesterase activities at both Day 1 and 12 months post-stroke than patients with either RQ/RR192 or LM/LL55 genotypes (P < 0.001). Furthermore, patients with carotid atherosclerosis and/or cerebral arteriosclerosis expressed as IMT, carotid plaques and WML had lower 12 months PON1 activity than patients without (P = 0.02, P = 0.027 and P = 0.001, respectively), and PON and AChE hydrolysis rates were more tightly correlated in patients carrying the PON1 192R compared with the 192QQ allele, in a gene dose-dependent manner (P < 0.001). CONCLUSION: Our findings show inverse PON1 activity-carotid atherosclerosis and -cerebral arteriosclerosis association in stroke patients: the lower the PON1 activity the more progressed is the atherosclerotic process and the weaker is the association with AChE activity. Extending previous PON1 genetic studies in stroke populations, our study emphasizes the PON1 activity as a potential anti-atherogenic element and proposes involvement of cholinesterase activities in its effects.

Post-traumatic anxiety associates with failure of the innate immune receptor TLR9 to evade the pro-inflammatory NFκB pathway.

Post-traumatic anxiety notably involves inflammation, but its causes and functional significance are yet unclear. Here, we report that failure of the innate immune system Toll-like receptor 9 (TLR9) to limit inflammation is causally involved with anxiety-associated inflammation and that peripheral administration of specific oligonucleotide activators of TLR9 may prevent post-traumatic consequences in stressed mice. Suggesting involvement of NFκB-mediated enhancement of inflammatory reactions in the post-traumatic phenotype, we found association of serum interleukin-1ß increases with symptoms severity and volumetric brain changes in post-traumatic stress disorder patients. In predator scent-stressed mice, the moderate NFκB-activating oligonucleotides mEN101 and its human ortholog BL-7040, but not the canonic NFκB activator oligonucleotide ODN1826, induced anxiolytic effects. In stressed mice, peripherally administered mEN101 prevented delayed stress-inducible serum interleukin-1ß increases while limiting stress-characteristic hippocampal transcript modifications and the anxiety-induced EGR1-mediated neuronal activation. Attesting to the TLR9 specificity of this response, BL-7040 suppressed NFκB-mediated luciferase in transfected cells co-expressing TLR9, but not other TLRs. Furthermore, TLR9-/- mice were mEN101 and BL-7040 resistant and presented unprovoked anxiety-like behavior and anxiety-characteristic hippocampal transcripts. Our findings demonstrate functional relevance of TLR9 in protecting stressed mammals from overreacting to traumatic experiences and suggest using oligonucleotide-mediated peripheral TLR9 activation to potentiate the innate immune system and prevent post-traumatic inflammation and anxiety.

Assessment of high-sensitivity CRP as a marker of micro-inflammation in irritable bowel syndrome.

BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is symptom-based. Although considered a functional disease, accumulating evidence supports a low-grade gut inflammation as an element of its pathophysiology. Thus, high-sensitivity C-reactive protein (hs-CRP), a marker of micro inflammation, may be elevated in IBS. Our aim was to assess whether hs-CRP is higher in IBS patients compared to healthy controls (HC) and does it differ among the IBS clinical subgroups and correlate with disease severity. METHODS: A diagnostic case control study was conducted in two gastroenterology departments. Eighty-eight IBS patients who were recruited prospectively answered the Rome III diagnostic questionnaire. They all completed the Functional Bowel Disorder Severity Index (FBDSI), dietary, and general health questionnaires. All patients underwent blood sampling for hs-CRP levels. Each IBS patient was matched to four HC by age, gender, and BMI. Blood samples were obtained from the HC at a periodic health survey. KEY RESULTS: The mean hs-CRP level in the IBS group was significantly higher than in HC (1.17±1.26mg L(-1) vs 0.72±0.91mg L(-1) respectively, P=0.001). Hs-CRP levels were highest in patients with diarrhea-predominant IBS and in patients with greater disease severity. A cut-off value of 1.08mg L(-1) had a sensitivity of 60.2% and a specificity of 68% for differentiating IBS from HC. CONCLUSIONS & INFERENCES: Hs-CRP levels are higher in IBS patients than HC, but still in the normal laboratory range. This may reflect the low-grade gut inflammation believed to occur in IBS and support its existence.

The association between the embolic load and atrial size in acute pulmonary embolism.

BACKGROUND: Early identification by computed tomography pulmonary angiography (CTPA) of patients with acute pulmonary embolism (PE) who have signs associated with a high embolic burden would be highly desirable. OBJECTIVES: To investigate whether an increased obstruction of the pulmonary vasculature is associated with reduced left atrial (LA) and increased right atrial (RA) areas. METHODS: We retrospectively analyzed a consecutive series of CTPA studies of 137 patients with acute PE and 38 controls without PE between October 2004 and March 2006. Left and right atrial areas and longitudinal and short axis diameters were measured and correlated with the pulmonary arterial obstruction index (PAOI) divided into tertiles (obstruction of < 12.5%, 12.5%-42.5% and ≥ 42.5%). RESULTS: There was a significant negative age- and gender-adjusted correlation between the PAOI and LA measurements, particularly the LA area (r = -0.259) and the LA short axis diameter (r = -0.331). All RA measurements had positive correlations (RA area, r = 0.279; RA short axis diameter, r = 0.313). The LA/RA area ratio correlated negatively with the PAOI (r = -0.447). All above-mentioned correlations had P < 0.002. All the LA measurements were the largest in the controls and gradually decreased with higher PAOIs. A receiver operating characteristic curve analysis demonstrated that the RV/LV diameter, LA/RA area and LA/RA short axis diameter ratios had comparable discriminative ability for higher PAOI tertiles. CONCLUSIONS: The higher the clot load in the pulmonary arteries, the smaller the LA area and the larger the RA area. Atrial area measurements by CTPA may serve as a real-time parameter in assessing the severity of PE upon diagnosis.

Interleukin-6 as an early predictor for one-year survival following an ischaemic stroke/transient ischaemic attack.

BACKGROUND: Early biomarkers for survival in an acute ischaemic stroke/transient ischaemic attack might serve as a useful tool for the clinician. Several studies have highlighted the role of inflammatory biomarkers as an early signal for acute ischaemic stroke prognosis. AIMS: This study examines the potential advantage of using high-sensitivity interleukin-6 as a possible biomarker at the early stages of acute stroke for identifying patients at a high risk for 12-month mortality. METHODS: Inflammatory biomarkers and neurological scores were determined in 250 patients following mild to moderate acute ischaemic stroke within 24 h of hospital admission. Outcome data on mortality were collected after 12 months. The signal detection methodology was used to identify subgroups that were at a high risk for 12-month mortality. RESULTS: Twelve months following the event, 234 of the 250 stroke patients survived. Signal detection identified predictors that distinguished individuals likely to die from those with a better recovery prediction. Plasma interleukin-6 concentration emerged as the optimal predictor, with a cut point of 6.47 pg/ml, chi(2) (l, N=250)=20.5, P<0.001. Interleukin-6 above 6.47 pg/ml during the acute phase predicted subsequent non-survival (P=0.006, odds ratio 8.0). CONCLUSIONS: This study demonstrates the clinical potential of using high-sensitivity interleukin-6 as an early signal for acute ischaemic stroke survival and suggests a clear cut point for patients at a high risk who might benefit from closer clinical surveillance and/or administration of therapeutic interventions.

Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress?

BACKGROUND: The exact cause of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress is one of the factors implicated in the etiology of ALS as well as in that of other neurodegenerative diseases. Uric acid is an important natural antioxidant that may reduce oxidative stress. The objective of this study was to prospectively determine the serum uric acid levels in ALS patients and allegedly healthy individuals and to correlate those values with measures of ALS disease progression among the patients. METHODS: The ALS patients and well-matched controls underwent blood tests for serum uric acid levels which were then correlated with the patients' disability status, as expressed by the ALS Functional Rating Scale (ALSFRS-R). RESULTS: Eighty-six ALS patients and 86 well-matched controls participated. The ALS patients' mean+/-SD uric acid level was significantly lower (4.78+/-1.3 mg/dl) than that of the controls (5.76+/-1.26 mg/dl) (p<0.0001). The findings were similar for a second examination performed after an interval of at least 6 months. There was a correlation between the relative decrease of serum uric acid levels among patients (the difference between the patients' level and the controls' level) and the rate of disease progression (ALSFRS-R decline) (p<0.0001, r=0.624). CONCLUSIONS: ALS patients had lower serum uric acid levels than healthy individuals. The decreased uric acid levels were correlated to the rate of disease progression (ALSFRS-R decline), further demonstrating the possible role of oxidative stress in the induction and propagation of the disease.

Low-grade systemic inflammation in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To prospectively determine the intensity of systemic low-grade inflammation in patients with amyotrophic lateral sclerosis (ALS). PATIENTS AND METHODS: Patients with ALS and matched healthy controls underwent blood tests for inflammation-sensitive biomarkers: erythrocyte sedimentation rate (ESR), quantitative fibrinogen, wide-range C-reactive protein (wrCRP) concentrations, leukocyte count and neutrophil-to-lymphocyte ratio (NLR). The correlation between these inflammatory biomarkers and disability status of the patients, expressed by the ALS Functional Rating Scale (ALSFRS-R), was evaluated. RESULTS: Eighty patients with ALS and 80 matched controls were included. wrCRP, fibrinogen, ESR and NLR values were significantly elevated in patients compared with controls. There was a significant correlation between the ALSFRS-R score and wrCRP, ESR and fibrinogen levels. This correlation persisted on sequential examinations. CONCLUSIONS: A systemic low-grade inflammation was detected in patients with ALS and correlated with their degree of disability. A heightened systemic inflammatory state is apparently associated with a negative prognosis in ALS.

Increased red blood cell aggregation in patients with Gaucher disease is non-inflammatory.

Red blood cell (RBC) aggregation is enhanced in the presence of ongoing inflammation, because of plasma protein effects, especially fibrinogen. Large RBC aggregates, in addition to being a marker of systemic inflammation, may hinder tissue perfusion and oxygenation. Gaucher disease, the most common lysosomal storage disorder, evinces many of the hallmarks of chronic inflammation. Manifestations of Gaucher disease which may be related to microvascular occlusion include avascular necrosis (AVN), bone crisis, and pulmonary hypertension. This study aims to determine whether increased RBC aggregation in non-splenectomized patients with Gaucher disease is due to Gaucher-related inflammation. The Cell Flow Properties Analyzer (CFA) monitors blood under conditions of different shear stress by creating varying pressure gradients. Blood from non-splenectomized patients with Gaucher disease showed only a slight correlation between aggregation parameters and fibrinogen levels, whereas blood from non-splenectomized patients treated with enzyme replacement therapy (ERT) showed marked correlation between aggregation parameters and fibrinogen, as in the control group. These results underscore the hypothesis that RBC aggregation in Gaucher disease is increased by (at least) two mechanisms: a fibrinogen-mediated inflammatory process and another non-inflammatory process that may be induced by elevated glucocerebroside levels in the RBC and/or inhibited by elevated plasma cerebroside levels.

Real-time risk stratification of patients with acute pulmonary embolism by grading the reflux of contrast into the inferior vena cava on computerized tomographic pulmonary angiography.

OBJECTIVE: To investigate whether fast grading of reflux of contrast to the inferior vena cava (IVC) on computerized tomographic pulmonary angiography (CTPA) is a potential biomarker for real-time risk stratification. METHODS: We retrospectively identified 343 patients investigated for possible pulmonary embolism (PE) by CTPA at our medical center between September 2004 and March 2006. A total of 145 consecutive patients with PE (age 67 +/- 19 years) and 168 consecutive ones with negative CTPAs (age 64 +/- 20 years) fulfilled entry criteria. CTPAs were evaluated for retrograde reflux of contrast to the IVC by fast visual grading from 1 to 6 using the original axial images. Pulmonary obstruction index, the diameters of right and left ventricles and pulmonary artery, and patient survival data were recorded as well. RESULTS: Twenty-nine (20.0%) patients with positive CTs and 23 (13.7%) patients with negative CTs had substantial degrees (>or=4) of reflux of contrast to the IVC (P = 0.14). The Kaplan-Meier 30-day survival curves demonstrated significant reduction in survival in individuals with PE and grade >or=4 reflux of contrast to the IVC compared with lower grades (P = 0.008), but not in patients with grade >or=4 and no PE on CTPA (P = 0.26). The other cardiovascular parameters showed no significant correlation with survival in patients with and without PE. CONCLUSION: Substantial grades of reflux of contrast to the IVC during CTPA could predict early mortality in patients with acute PE. Rapid grading of reflux of contrast from the original axial CTPA images can be used for real-time risk stratification in patients with acute PE.

Dissociated effects of physical activity and weight loss on fibrinogen concentrations and markers of red blood cell aggregation. Relevance for life style modification in atherothrombosis.

It has been shown that weight loss and physical activity contribute to a better biorheological profile. Yet, the concentrations of fibrinogen are not always reduced following life style modification. We evaluated the inter-relations between fibrinogen's pro red cell aggregation potential and reduced inflammation and improved lipid profile as anti-aggregating forces in a group of 20 apparently healthy obese volunteers following 4 and 8 months of intensive life modification program which included diet and strenuous physical activity. A significant (p=0.005) weight loss (from a mean+/-SD of 121.4+/-20.9 to 98.0+/-21.3 kg) and decrease in body mass index (from 40.8+/-4.3 to 32.9+/-5.3 kg/m(2), p=0.005) was noted in fourteen individuals who completed the 8-month program. The concentrations of clottable fibrinogen rose from 318+/-96 to 387+/-72 mg/dl (p=0.012) while there was a significant reduction in the erythrocyte sedimentation rate (ESR) (from 19.0+/-12.6 to 10.8+/-7.5 mm/h, p=0.018), triglycerides (from 143+/-80 to 80+/-44 mg/dl, p=0.005), LDL cholesterol (from 128+/-34 to 103+/-17 mg/dl, p=0.005) and total cholesterol (from 211+/-40 to 171+/-17 mg/dl, p=0.007), as well as decrease in insulin concentration (from 36.1+/-21.3 to 20.6+/-8.0 microu/ml, p=0.01) and the insulin resistance index (HOMA-R, from 9.1+/-6.4 to 4.9+/-2.1 glu*ins/405, p=0.008). Despite a significant increment in the concentrations of clottable fibrinogen, a significant reduction was noted in the degree of red cell aggregation as measured by using a slide test and direct visualization of the aggregates. Our conclusion is that the pro-aggregating properties of fibrinogen following intense physical activity are probable counterbalanced by the anti-aggregatory properties of an improved lipid profile and an attenuated acute phase response.

Lack of difference in the intimal medial thickness between the left and right carotid arteries in the young.

BACKGROUND: Carotid intimal medial thickening (c-IMT) is an established surrogate marker for atherosclerosis. There have been sporadic reports about an increase of c-IMT on the left carotid artery among populations with a mean age of +/-50 years. OBJECTIVE: The purpose of this study was to evaluate whether there is a difference in c-IMT between the two carotid arteries in a group of young healthy adults. METHODS: Ninety-eight healthy adults with a mean age of 28 years underwent blood tests to evaluate various cardiovascular risk factors as well as automated ultrasonic measurements of their c-IMT on both carotid arteries. RESULTS: No significant difference was noted between c-IMT on both sides. In fact, the c-IMT on left carotid artery in men (n = 52) was 0.625 +/- 0.078 mm while on the right carotid it was 0.626 +/- 0.075 mm (P = 0.884). The values for women (n = 46) were 0.615 +/- 0.059 mm and for men 0.622 +/- 0.0618 mm (P = 0.582), respectively. CONCLUSION: As opposed to a noted increase of c-IMT on the left carotid artery in older individuals, we did not find this difference in a group of young and relatively healthy adults. It is possible that if mechanical stress forces contribute to an enhanced left c-IMT, it takes a relatively long time to become evident.

Triggered C-reactive protein (CRP) concentrations and the CRP gene -717A>G polymorphism in acute stroke or transient ischemic attack.

C-reactive protein (CRP) increases following an acute stroke/transient ischemic attack (TIA), but the increment level varies among patients. We analyzed CRP concentrations during an acute stroke/TIA in relation to the CRP gene -717A>G polymorphism. Six months following an acute ischemic stroke/TIA, basal concentrations of CRP were measured in 507 controls and 219 patients and were found to be unassociated with the CRP -717A>G polymorphism. However, during the acute phase of stroke/TIA, individuals with the AG/GG genotype had significantly elevated CRP concentrations as opposed to those with the AA genotype (2.02 +/- 1.59 vs. 1.73 +/- 1.69 mg/l, P = 0.027). In addition, significant 3.22-fold increments in CRP concentrations was noted in individuals carrying the -717G allele when comparing the acute phase with the basal state of each patient and averaging the results. CRP -717A>G polymorphism is associated with triggered CRP concentrations during acute stroke/TIA. These findings might shed more light on the mechanisms of CRP elevation in acute ischemic stroke/TIA.

Rheological consequences of acute infections: the rheodifference between viral and bacterial infections.

The aim of the present study was to explore the difference between viral and bacterial infections regarding the intensity of erythrocyte aggregation in the peripheral venous blood. Although a rheodifference in terms of erythrocyte aggregation between viral and bacterial infections has been shown by us in the past, the time from onset of disease was not included. We have presently included the time from the onset of disease in a group of 133 patients with an acute bacterial infection who showed a significantly enhanced erythrocyte aggregation as opposed to a group of 23 with viral ones and no increased erythrocyte aggregation despite of there being no significant difference in the time from onset of disease (55.7+/-55.6 hours in the bacterial group versus 50+/-35.2 in the viral one). In addition, we could match 22 patients with viral infections who presented the same fibrinogen concentrations (338+/-78 mg/dl) as those with acute bacterial ones (338+/-79 mg/dl). Although of borderline (p=0.06) significance, patients with an acute bacterial infection presented enhanced (vacuum radius=12.6+/-6.4 microns) erythrocyte aggregation as opposed to their isofibrinogenemic counterparts (vacuum radius=9.4+/-6.5 microns). Again, both groups presented no difference regarding the time from onset of disease. We conclude therefore that patients with acute bacterial infections present higher levels of erythrocyte aggregation. This is not a result of a shorter time interval from disease onset of the viral group. The known detrimental effects of increased erythrocyte aggregation regarding capillary slow flow, endothelial dysfunction and reduced tissue oxygenation might be therefore relevant in the context of patients with an acute infection, especially the bacterial ones.

Heart rate and microinflammation in men: a relevant atherothrombotic link.

OBJECTIVE AND BACKGROUND: To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR. METHODS: Concentrations of fibrinogen and high-sensitivity C-reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors. RESULTS: Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001) difference was noted between individuals in the first quintile of HR (< or =58 beats/min) and those in the fifth quintile (> or =79 beats/min) regarding all the above-mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 micromol/l, 1.12 and 1.61 mg/l, and 4.23 and 4.74 x 10(9)/l. CONCLUSIONS: Resting HR is associated with a microinflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association. If confirmed in additional studies, this association might be a relevant target for therapeutic manipulations.

Wide-range C-reactive protein efficacy in acute ischemic stroke patients.

OBJECTIVE: To compare the recently introduced wide-range C-reactive protein (wr-CRP) with the widely used high-sensitivity Behring Dade method (hs-CRP) in acute stroke/transient ischemic attack (TIA) patients. MATERIALS AND METHODS: A total of 119 consecutive patients admitted to a tertiary medical center with acute ischemic stroke/TIA were included in the study. Venous blood was obtained for both assays during the first 24 h, 3-5 days, as well as 3-6 months thereafter. RESULTS: A highly significant correlation (r=0.994, P<0.0001) was found between the two methods even when analyzed at three different time points. In addition, a similar correlation was noted between these two assays and other commonly used biomarkers, including white blood cell count, Westergren's sedimentation rate and quantitative fibrinogen. CONCLUSION: Real-time, on-line and low-cost wr-CRP assay is a reasonable alternative to the Behring Dade hs-CRP method in acute stroke/TIA patients.

Increased erythropoiesis and subclinical inflammation as part of the metabolic syndrome.

Recent studies have suggested the insulin resistance might be accompanied by enhanced erythropoiesis. We have examined this association in individuals with the metabolic syndrome (MS) who in addition to insulin resistance harbor a chronic low grade inflammation. This study is relevant because chronic inflammation might have a suppressive effect on erythropoiesis. 280 and 554 non-smoking women and men with respective age of 46.4+/-9.3 (mean+/-S.D.) and 44.0+/-11.0 years are included. A significant correlation was noted between the numbers of the components of the MS and the inflammatory biomarkers including the white blood cell count, high sensitivity C-reactive protein, fibrinogen concentrations and the erythrocyte sedimentation rate. In addition, a significant correlation (r=0.157, p=0.008) was noted between the number of components of the MS and the number of red blood cells in the peripheral blood in women. The same was true for men (r=0.192, p<0.0005). We conclude that enhanced erythropoiesis could be a new, hitherto unrecognized component of the MS. The enhanced erythropoiesis could give an erroneous impression of general "good" health in these individuals.