Pirjo Hedberg

Determinants of Functional Recovery after Myocardial Infarction of Patients Treated with Bone Marrow Derived Stem Cells after Thrombolytic Therapy

Objective To assess the determinants of functional recovery in patients with ST-elevation myocardial infarction (STEMI) treated initially with thrombolysis, followed by percutaneous coronary intervention and intracoronary injection of bone marrow-derived stem cells (BMC). Design A randomised, placebo-controlled, double-blind study (substudy of FINCELL). Setting Two tertiary cardiac centres. Participants 78 patients with STEMI randomly assigned to receive either intracoronary BMC (n=39) or placebo (n=39) into the infarct-related artery. Interventions Thrombolysis a few hours after symptom onset, percutaneous coronary intervention and intracoronary injection of BMC 2–6 days later. Main outcome measures Efficacy of the BMC treatment was assessed by measurement of the change of global left ventricular ejection fraction (LVEF) from baseline to 6 months after STEMI. Various predefined variables (eg, the levels of certain natriuretic peptides and inflammatory cytokines) were analysed as determinants of improvement of LVEF. Results In the BMC group, the most powerful determinant of the change in LVEF was the baseline LVEF (r=−0.58, p<0.001). Patients with baseline LVEF at or below the median (≤62.5%) experienced a more marked improvement in LVEF (+12.7±12.5 %units, p<0.001) than those above the median (−0.8±6.3 %units, p=0.10). Elevated N-terminal probrain natriuretic peptide (p<0.001) and N-terminal proatrial natriuretic peptide (p=0.052) levels were also associated with improvement in LVEF in the BMC group but not in the placebo group. Conclusions The global LVEF recovers most significantly after intracoronary infusion of BMC in patients with the most severe impairment of LVEF on admission. The baseline levels of natriuretic peptides seem also to be associated with LVEF recovery after BMC treatment. Trial registration ClinicalTrials.gov number, NCT00363324.

Serum interleukin‐6 may modulate periodontal inflammation in type 1 diabetic subjects

AIMS To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators. MATERIAL AND METHODS Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models. RESULTS The level of serum IL-6 was associated with the extent of bleeding and PD≥4 mm at the baseline in non-smokers and in subjects with BMI≤26 kg/m(2). These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level. CONCLUSIONS The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

Serum IL-6 may modulate periodontal inflammation in type 1 diabetic subjects

AIMS To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators. MATERIAL AND METHODS Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models. RESULTS The level of serum IL-6 was associated with the extent of bleeding and PD≥4 mm at the baseline in non-smokers and in subjects with BMI≤26 kg/m(2). These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level. CONCLUSIONS The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

Association of abnormal glucose tolerance with self-reported sleep apnea among a 57-year-old urban population in Northern Finland

AIMS We examined the associations between glucose tolerance and sleep apnea in a 57-year-old unselected urban population in Northern Finland, taking into account some determinants of sleep apnea. METHODS A population-based health survey was conducted in a population of 555 women and 438 men born in 1945 and living in the city of Oulu in 2001. Glucose status was determined with a standard 2-h oral glucose tolerance test. Sleeping disorders were recorded on the Epworth Sleepiness Scale (ESS) and a questionnaire including 5 questions about sleeping and snoring. The Zung Self-rated Depression Scale (ZSDS) was used to assess depressive symptoms. Logistic regression was used in the estimation of odds ratios (OR) for the associations of sleep apnea with the covariates. RESULTS Sleep apnea was found to be associated with type 2 diabetes (OR 2.56, 95% CI 1.20-5.47) and newly diagnosed type 2 diabetes (OR 2.42 95% CI 1.01-5.82), but the estimated association with impaired glucose regulation (IGR) was coupled with a wide margin of error (OR 0.91, 95% CI 0.43-1.93) when adjusted for the following covariates: gender, current smoking, hypertension, hs-CRP, physical activity, waist circumference, and Zung depression scale. CONCLUSIONS There seems to be a positive association between sleep apnea and type 2 diabetes, and even with newly diagnosed type 2 diabetes, but we could not establish an association with IGR.

Association Between High-Sensitive Measurement of C-Reactive Protein and Metabolic Syndrome as Defined by International Diabetes Federation, National Cholesterol Education Program, and World Health Organization Criteria in a Population-Based Cohort of 55-Year-Old Finnish Individuals

Recently, the International Diabetes Federation (IDF) consensus group published a new definition of metabolic syndrome for identifying individuals at high risk for cardiovascular disease (CVD) (1). The high-sensitive measurement of C-reactive protein (hs-CRP), a marker of chronic low-grade inflammation, can also be used in the risk assessment of CVD (2). We investigated whether the new IDF (1), National Cholesterol Education Program (NCEP) (3), and World Health Organization (WHO) (without microalbuminuria) (4) definitions differ at the epidemiological level regarding the strength of their association with elevated hs-CRP (>3 mg/l) (2) among a population of 992 subjects (438 men) born in 1945 and living in the City …

Skeletal troponin I cross-reactivity in different cardiac troponin I assay versions.

OBJECTIVES To study the skeletal troponin I (skTnI) cross-reactivity of four different commercially available antibodies in four cardiac troponin I (cTnI) research assay versions having the same epitope specificity as evidenced by peptide mapping. DESIGN AND METHODS The four research assays all use two solid phase antibodies and one detection antibody attached to intrinsically fluorescent nanoparticles. Two alternative antibodies were used for one capture antibody and two for the detector antibody. The assays were evaluated in terms of analytical sensitivity and by determining assay cross-reactivity to skTnI. Additionally, regression analysis was performed by measuring a sample panel (n=101) with all of the four assay versions. RESULTS A false-positive cTnI concentration of >7000ng/L was measured with one of the assay versions, when serum was spiked with 500,000ng/L skTnI. The corresponding observed cTnI values for the other three assay versions varied from 616ng/L to 727ng/L. Out of the 101 clinical samples assayed, five showed spuriously (3- to 148-fold) elevated cTnI values with the skTnI interference prone assay setup, but not with the other assay versions. According to our investigational skTnI assay, all five samples contained measurable amounts of skTnI (range: 5500-702,000ng/L). CONCLUSIONS Two out of four cTnI antibodies tested cross-reacted vastly with skTnI but did not cause any notable interference unless paired together. Therefore, skTnI cross-reactivity should be carefully assessed when cTnI assay antibodies claimed to be cTnI specific are selected.

Chimeric recombinant antibody fragments in cardiac troponin I immunoassay.

OBJECTIVES To introduce a novel nanoparticle-based immunoassay for cardiac troponin I (cTnI) utilizing chimeric antibody fragments and to demonstrate that removal of antibody Fc-part and antibody chimerization decrease matrix related interferences. DESIGN AND METHODS A sandwich-type immunoassay for cTnI based on recombinant chimeric (mouse variable/human constant) antigen binding (cFab) antibodies and intrinsically fluorescent nanoparticles was developed. To test whether using chimeric antibody fragments helps to avoid matrix related interferences, samples (n=39) with known amounts of triglycerides, bilirubin, rheumatoid factor (RF) or human anti-mouse antibodies (HAMAs) were measured with the novel assay, along with a previously published nanoparticle-based research assay with the same antibody epitopes. RESULTS The limit of detection (LoD) was 3.30ng/L. Within-laboratory precision for 29ng/L and 2819ng/L cTnI were 13.7% and 15.9%, respectively. Regression analysis with Siemens ADVIA Centaur® yielded a slope (95% confidence intervals) of 0.18 (0.17-1.19) and a y-intercept of 1.94 (-1.28-3.91) ng/L. When compared to a previously published nanoparticle-based assay, the novel assay showed substantially reduced interference in the tested interference prone samples, 15.4 vs. 51.3%. A rheumatoid factor containing sample was decreased from 241ng/L to <LoD. CONCLUSIONS Utilization of cFab-fragments enabled the development of a sensitive (LoD=3.3ng/L) immunoassay for the detection of cTnI and decreased matrix related interferences, thus resulting in a lower number of falsely elevated cTnI-values.