Outcomes in Patients With Chest Pain Discharged After Evaluation Using a High-Sensitivity Troponin T Assay.

BACKGROUND: Most patients with chest pain are discharged from the emergency department (ED) with the diagnosis "unspecified chest pain." It is unknown if evaluation with a high-sensitivity troponin T (hsTnT) assay affects prognosis in this large population. OBJECTIVES: The aim was to investigate whether the introduction of an hsTnT assay is associated with reduced incidence of major adverse cardiac events (MACEs) and cardiovascular (CV) risk profile in patients with chest pain discharged from the ED. METHODS: The study included 65,696 patients with "unspecified chest pain" discharged from 16 Swedish hospital EDs between 2006 and 2013 in which an hsTnT assay was introduced as the clinical routine. Patients evaluated with a conventional and an hsTnT assay were compared regarding the occurrence of 30-day MACE and CV risk profile based on information from national registries. Patients directly discharged and those discharged after an initial admission were analyzed separately. RESULTS: Fewer directly discharged patients experienced a MACE when evaluated with an hsTnT compared with a conventional assay (0.6% vs. 0.9%; odds ratio [OR]: 0.7; 95% confidence interval [CI]: 0.57 to 0.83). In contrast, more patients discharged after an initial admission experienced a MACE when evaluated with an hsTnT (7.2% vs. 3.4%; OR: 2.18; 95% CI: 1.76 to 2.72). Admitted patients had a higher general CV risk profile when evaluated with hsTnT, whereas directly discharged patients had a lower general CV risk profile with the same test. CONCLUSIONS: Patients directly discharged from the ED with unspecified chest pain experienced fewer MACEs and had a better risk profile when evaluated with hsTnT. Our findings suggest that more true at-risk patients were identified and admitted. The implementation of hsTnT assays in Swedish hospitals has improved evaluations in the ED.

Reference values for clinical chemistry tests during normal pregnancy.

OBJECTIVE: Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. DESIGN: Longitudinal study of laboratory markers in normal pregnancies. SETTING: Uppsala University Hospital, Sweden. POPULATION: Healthy pregnant females. METHODS: We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24- 28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (> 6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. RESULTS: Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, gamma-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. CONCLUSIONS: Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.

Cystatin C--a marker of peripheral atherosclerotic disease?

UNLABELLED: It has been suggested that Cystatin C, besides its function as a marker of glomerular filtration, could be an independent marker of cardiovascular disease. However, studies on this topic are few and results have been indecisive. Our aim was to further investigate the subject of Cystatin C as an independent marker of peripheral atherosclerotic disease. METHOD: Blood samples were analysed for serum Cystatin C, IL6, CRP and creatinine in 103 males with peripheral arterial disease (PAD) and 96 controls matched for age and sex. Creatinine clearance (CCr) was calculated according to Cockcroft's formula and estimated glomerular filtration rate (eGFR) was calculated according to MDRD formula. RESULTS: Cystatin C-concentration was higher in PAD-patients compared to controls; 1.09+/-0.40 vs. 0.95+/-0.17 mg/L (p<0.01). There was no difference in CCr; 81+/-27 vs. 82+/-22 mL/min or eGFR; 76+/-21 vs. 79+/-14 mL/min. Cystatin C correlated to CCr, logIL-6 and logCRP in both patients (r=-0.60, p<0.001), (r=0.35, p<0.001) and (r=0.30, p<0.01) and controls (-0.44, p<0.001), (0.38, p<0.001) and (r=0.32, p<0.01), respectively. In an analysis of covariance, corrected for difference in eGFR, Cystatin C remained higher in PAD-patients compared to controls; 1.09 (C.I. 1.04-1.14) vs. 0.96 (C.I. 0.90-1.01). CONCLUSION: Cystatin C-concentration, corrected for differences in eGFR, IL-6 and CRP values, is higher in PAD-patients compared to controls. Our finding suggests that Cystatin C may be an independent marker of atherosclerotic disease apart from its relation to kidney function.

Estimated glomerular filtration rate (eGFRCystC) from serum cystatin C shows strong agreement with iohexol clearance in patients with low GFR.

OBJECTIVE: Estimation of glomerular filtration rate (eGFR) is essential in the diagnosis and monitoring of patients with kidney disease and for correct dosage of drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in estimating eGFR. However, there are few studies on the performance of cystatin C estimated eGFR (eGFRCystC) in patients with advanced kidney disease and low GFR. MATERIAL AND METHODS: We measured serum cystatin C, together with serum creatinine, during iohexol clearance in patients with iohexol clearance below 30 mL/min/1.73 m2. The cystatin C values were used to calculate eGFRCystC using the formula eGFR (mL/min/1.73 m2) = 79.901*(cystatin C value in mg/L)-1.4389. RESULTS: There was good correlation between eGFRCystC and iohexol clearance (r = 0.88) in patients with iohexol clearance <30 mL/min/1.73 m2 and none of the patients had a difference between eGFRCystC and iohexol clearance exceeding 50 %. The Modification of Diet in Renal Disease (MDRD) equation and corrected MDRD eGFR showed a positive bias and weaker correlations with iohexol eGFR (MDRD = 5.32+1.22*iohexol clearance; corrected MDRD = 4.76+1.10*iohexol clearance; r = 0.59). For MDRD eGFR, 42 of 94 (44.7%) samples showed more than 50% difference to iohexol clearance. CONCLUSIONS: eGFRCystC is an efficient, practical and cost-effective alternative to iohexol clearance in patients with reduced GFR.

Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L.

OBJECTIVE: Estimation of the glomerular filtration rate (GFR) is essential when evaluating patients with kidney disease and treating patients with drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in the estimation of GFR. At our hospitals, there is an increasing demand for cystatin C and at present we perform approximately 1500 cystatin C analyses a month. We thus need the assay available 24 h/day and to have it on our routine chemistry instrument to minimize handling time per test and time to reported test results. MATERIAL AND METHODS: We have evaluated a new cystatin C immunoassay from Gentian (Gentian, Moss, Norway) on Architect ci8200 (Abbott Laboratories, Abbott Park, Ill., USA). A prerequisite at our hospital is that cystatin C results are reported as a calculated GFR in mL/min/1.73 m(2), so we also made a comparison with iohexol clearance. RESULTS: The Gentian cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, Ill., USA) and good inter-laboratory concordance. The assay has very low total imprecision, good linearity and strong correlation with iohexol clearance (R (2) = 0.956). The equation for the correlation curve is: y = 79.901x(-1.4389). CONCLUSIONS: There was low inter-laboratory variation between the three laboratories involved in the cystatin C evaluation, and thus all three laboratories can use the same equation for calculating the estimated GFR.

Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response.

BACKGROUND: The role of inflammation in the pathogenesis of cardiovascular disease is well established. C-reactive protein (CRP) is the strongest independent predictor of myocardial infarction and stroke in women. Recent studies have indicated that CRP levels are raised during use of combined oral contraceptives (COCs). OBJECTIVES: The aim of the study was to investigate the effect of COCs on serum CRP levels and to indicate the underlying mechanisms of an expected increase. METHOD: In a prospective randomized cross over-study 35 women used two different preparations of COC, one second and one third generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two treatments. E-selectin, von Willebrand factor and factor VIII concentrations in plasma were also measured. RESULTS: A rise in serum CRP was observed during both treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The serum levels of SAA increased slightly during treatment with the third generation COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered IGF-I and raised IGFBP-1 and IGFBP-3 concentrations. CONCLUSION: The raised serum CRP concentration during treatment with COCs appears to be related to a direct effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated inflammation, endothelial activation or induction of insulin resistance.

Increased serum cystatin C is associated with increased mortality in elderly men.

Renal dysfunction measured by serum creatinine is associated with increased cardiovascular morbidity and mortality. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of glomerular filtration rate (GFR). The aim of the present study was to investigate the relationship between cystatin C and mortality in elderly men. Serum cystatin C was analyzed by nephelometry in a group of 77-year-old men (n=792) and correlated cystatin C levels with mortality during a follow-up period of 1-4 years. The cystatin C values were significantly correlated with overall mortality (p=0.013). Mortality was three times higher in the highest cystatin C quintile in relation to the lowest quintile.

Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L.

The Cockcroft Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p < 0.0001) was found between cystatin C and iohexol clearance (r2 = 0.91) than between creatinine and iohexol clearance (r2 = 0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y = 77.24x(-1.2623) (Dade Behring cystatin C calibration) or y = 99.43x(-1.5837) (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations.

Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy.

During pregnancy, significant changes occur in the hemostatic system and in the plasma levels for several plasma proteins, especially towards term. In this study changes occurring during normal pregnancy and immediately postpartum were investigated to establish adequate reference intervals for important hemostatic parameters. Blood samples were collected during pregnancy weeks 33, 36, 39 and 1-3 h after delivery from 153 healthy pregnant women with at least one previous normal pregnancy. The plasma samples were analyzed for antithrombin, von Willebrand factor (vWf), free protein S and fibronectin. Fibronectin and vWf are contact-promoting proteins responsible for adhesion and aggregation during primary hemostasis, but are also released from thrombocytes during activation of the coagulation process. Antithrombin is the most important primary physiological inhibitor of activated serine proteases related to the coagulation cascade. Protein S is a co-factor to protein C and in cooperation is also an important inhibitor of the coagulation cascade. During third-trimester pregnancy, vWf was higher than in non-pregnant women, and continued to increase postpartum. The fibronectin plasma level was mostly unchanged in comparison with non-pregnant values. Within this reference interval it gradually increased during the third trimester, but fell slightly postpartum. Antithrombin decreased slightly during the third trimester and even further, postpartum. Free protein S decreased markedly but to a stable level from week 33 to 39, decreasing even more postpartum. The present results are concordant with clinical knowledge of increased risk of thrombosis during pregnancy and early puerperium, with increased levels of vWf and fibronectin and decreased levels of antithrombin and free protein S. Clearly, current reference values based on healthy non-pregnant subjects are not usable during late pregnancy and immediately postpartum.

C-reactive protein and myocardial infarction during percutaneous coronary intervention.

OBJECTIVE: To evaluate the prognostic information of preprocedural C-reactive protein (CRP) levels in serum to predict myocardial infarction during percutaneous coronary interventions (PCI). DESIGN: Prospective study. SETTING: University hospital. PATIENTS: A total of 400 consecutive patients with normal serum troponin T levels (0.05 microg L-1. RESULTS: Eighty-three patients (21%) experienced a myocardial infarction during PCI. The median value of CRP before the procedure was 1.83 (0.12-99.7) mg L-1. No difference was seen in CRP levels before PCI between patients without or with myocardial infarction during PCI. Multivariate analysis identified stent implantation (OR 2.68, 95% CI 1.18-7.28, P = 0.03), procedure time (OR 2.15, 95% CI 1.28-3.67, P < 0.005) and complications during the procedure (OR 3.62, 95% CI 1.72-7.58, P < 0.001) as independent predictors of myocardial infarction during PCI. CONCLUSION: Increased CRP levels in serum before PCI were not associated with myocardial infarction during the procedure. Furthermore, patients with an expected long procedure and a high probability of stent implantation have an increased risk of developing myocardial infarction during PCI. This finding may be useful to help the operator to decide the antithrombotic regime before, during and after the procedure and the need for observation after the procedure.

Prognostic value of plasma C-reactive protein and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis.

OBJECTIVES: To investigate the prognostic value of plasma C-reactive protein (CRP) and fibrinogen determinations in patients with acute myocardial infarction treated with thrombolysis. DESIGN: Longitudinal study of morbidity and mortality. SETTING: Coronary care unit at Danderyd Hospital, Stockholm, Sweden. SUBJECTS: A total of 222 patients aged 75 years or below, treated with thrombolysis because of typical symptoms of myocardial infarction and electrocardiogram showing ST-segment elevation or bundle branch block were included in the study. The patients were followed for 24-60 months (mean 40 +/- 16 months). MAIN OUTCOME MEASURES: Cardiovascular death or new myocardial infarction. RESULTS: Concentrations of CRP were significantly higher at 48 h than at 3 months, whilst the levels of fibrinogen were similar. CRP and fibrinogen concentrations measured during the acute phase of myocardial infarction were associated with cardiovascular death or a new myocardial infarction during follow-up in univariate analysis. CRP levels measured 3 months after the acute event were not associated with subsequent events whereas fibrinogen concentrations showed a borderline prognostic significance (P = 0.05). When CRP and fibrinogen were entered into multivariate analysis together with the previously established prognostic factors in the patient group (age, diabetes mellitus and left ventricular function), these markers of inflammation did not add further prognostic information. CONCLUSION: C-reactive protein and fibrinogen do not carry the same independent prognostic information after acute myocardial infarction treated with thrombolysis as in studies previously reported for patients with unstable angina or non-Q-wave myocardial infarction.

High sensitivity CRP and serum amyloid A as expressions of low grade inflammation do not correlate with bFGF or VEGF.

High sensitivity CRP (hsCRP) and serum amyloid component A (SAA) are two acute phase proteins that have been shown to be prognostic markers in cardiovascular diseases. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two angiogenic growth factors involved in the growth and invasion of solid tumors and hematological malignancies. They also play an important role in cardiovascular and inflammatory diseases. The acute phase response induces the production of angiogenic peptides and angiogenic peptides have also been shown to induce the synthesis of inflammatory cytokines. HsCRP and SAA, bFGF and VEGF in serum and EDTA plasma were measured in samples from 80 human blood donors. There were strong correlations between hsCRP and SAA but there were no significant correlation between hsCRP or SAA and any of the angiogenic peptides. Low-grade inflammation did not induce bFGF or VEGF production.

Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusion.

BACKGROUND: Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). OBJECTIVES: The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. PATIENTS AND METHODS: Twenty-eight patients were investigated before and after 4-6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. P-fibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. RESULTS: Eighteen patients showed improved and 10 patients unchanged HbA1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass-length ratio ( micro ) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA(1c) (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r = 0.50; P < 0.01) and in LDL-cholesterol (r = 0.46; P < 0.05). CONCLUSIONS: Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity.

Risk factors for coronary heart disease in 55- and 35-year-old men and women in Sweden and Estonia.

OBJECTIVE: To illustrate the geographical West-to-East division of coronary heart disease (CHD) by comparing a population from Sweden, that represents a Western country to a population from Estonia, that represents an Eastern country. Estonia has an approximately 2-4-fold higher CHD prevalence for 55-year-old women and men, respectively, than Sweden. DESIGN: Randomized screening of 35- and 55-year-old men and women in Sollentuna county, Sweden and Tartu county, Estonia. Eight hundred subjects, 100 from each cohort, were invited to participate in the study, 272 Swedes and 277 Estonians participated. SETTING: Preventive cardiology, administered by a primary health care centre at the Karolinska Hospital, Sweden and a cardiology centre at Tartu University Hospital, Estonia. MAIN OUTCOME MEASURES: The CHD risk factors (smoking, blood pressure, concentrations of lipoproteins, fibrinogen, and glucose) and certain environmental factors and attitudes related to CHD risk by questionnaires (fat-type and alcohol ingestion, self-assessed rating of CHD susceptibility). RESULTS: Of the 55-year-old men, 57% smoked in Estonia and 20% smoked in Sweden. Similar, although less pronounced differences showing higher smoking prevalence, were seen for 35-year-old Estonian men and women, whilst for 55-year-old women, less than 20% smoked in either country. Estonian 55-year-old women had lower HDL cholesterol and higher LDL cholesterol serum concentrations than Swedish 55-year-old women. Estonians reportedly ate food containing more saturated fats than Swedes, as indicated by the scale-score questionnaire. Estonians, relative to Swedes, rated their chance of developing CHD higher, and paradoxically, Estonians did to a much lesser degree believe that life style influences the risk of developing CHD. CONCLUSIONS: Elevated smoking prevalence is a striking difference between the Estonian and Swedish populations likely to explain the much higher CHD prevalence in Estonian men. The lower HDL cholesterol and higher LDL cholesterol in Estonian 55-year-old women may explain the higher CHD prevalence in Estonian women. Furthermore, the SWESTONIA CHD study (i.e. comparison between Sweden and Estonia) shows several environmental differences between the countries populations related to fat content in food, alcohol drinking patterns, and views on CHD risk and the importance of lifestyle intervention, that could contribute to the higher CHD prevalence in Estonia.

Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Strictures of the bile ducts due to malignant changes are difficult to distinguish from benign changes, particularly in patients with primary sclerosing cholangitis (PSC). The aim of this study was to evaluate diagnostic methods for malignancy in biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography (ERCP). PATIENTS AND METHODS: Bile duct strictures were identified during ERCP in 57 patients, who were thus included in the present study. Brush samples from the strictures were taken for cytology and for evaluation of DNA content by flow cytometry. The tumor markers CA 19-9 and CEA were determined both in serum and bile fluid. Two independent radiologists evaluated all cholangiograms. The diagnostic sensitivity, specificity, and accuracy of each diagnostic method were evaluated separately and in combination. RESULTS: 32 patients were found to have malignant strictures and when the four methods: brush cytology, DNA analysis, serum CA 19-9 and serum CEA were combined, a diagnostic sensitivity of 88 % and specificity of 80 % were reached. Seven of the 20 patients with PSC were found also to suffer from cholangiocarcinoma, yielding a sensitivity and specificity of 100 % and 85 %, respectively. Analyses of CA 19-9 and CEA in bile fluid had no diagnostic significance. CONCLUSION: An ERCP procedure with brush cytology, a DNA analysis, combined with serum analysis of CA 19-9 and CEA, can increase the possibility of distinguishing between malignant and benign biliary strictures, especially in PSC patients.

Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.

OBJECTIVE: To compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes. STUDY DESIGN: Open randomised multicentre study. Women were treated with multiple insulin injections aiming at normoglycaemia. Blood glucose was determined six times daily, HbA(1c) every 4 weeks. Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21, 28 and 34. PARTICIPANTS: 33 pregnant women with type 1 DM were randomised to treatment with lispro insulin (n=16) or regular insulin (n=17). RESULTS: Blood glucose was significantly lower (P<0.01) after breakfast in the lispro group, while there were no significant group differences in glycemic control during the rest of the day. Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA(1c) values at inclusion were 6.5 and 6.6% in the lispro and regular group respectively. HbA(1c) values declined during the study period and were similar in both groups. There was no perinatal mortality. Complications during pregnancy, route of delivery and foetal outcome did not differ between the groups. Retinopathy progressed in both groups, one patient in the regular group developed proliferative retinopathy. CONCLUSION: The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies.

High serum S100B levels for trauma patients without head injuries.

OBJECTIVE: Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS: A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS: The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION: Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources.

BACKGROUND: Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS: Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS: Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS: Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.

Serum S-100b protein as a prognostic marker in malignant cutaneous melanoma.

PURPOSE: To evaluate whether S-100B protein in serum is an independent prognostic marker in malignant melanoma. MATERIALS AND METHODS: S-100B protein in serum was analyzed in 1,007 consecutive patients with histologically verified cutaneous malignant melanoma. At the time of blood sampling, 876 patients were in clinical stage I, 35 were in stage II, and 96 were in stage III. The serum concentrations of S-100B protein were measured by a luminescence immunoassay (LIA). RESULTS: The mean serum concentration of S-100B protein was significantly related to clinical stage, with the lowest level in stage I and the highest in stage III. In a multivariate analysis, S-100B protein levels in serum showed the strongest prognostic impact of the factors analyzed with respect to disease-specific survival in clinical stages II to III, followed by clinical stage. Serum S-100B protein was not a significant independent prognostic factor in clinical stage I, where tumor thickness showed the strongest relation to melanoma-specific survival, followed by ulceration and satellites. CONCLUSION: This investigation contains the largest material of patients so far analyzed with the new LIA assay of S-100B protein in serum and confirms that S-100B protein in serum is correlated with clinical stage and is an independent prognostic marker in clinical stages II and III.

Fibronectin is a marker for organ involvement and may reflect the severity of preeclampsia.

OBJECTIVE: We have studied whether plasma fibronectin is related to a rise in blood pressure during normal pregnancy, whether it can be used for the early prediction of preeclampsia, and whether plasma fibronectin is a marker for organ involvement in preeclampsia. STUDY DESIGN: Two hundred twenty-eight healthy pregnant nullipara women were examined prospectively during pregnancy. Analyses of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and 36. During the same period, 177 patients with suspected preeclampsia and/or intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly in the third trimester. RESULTS: In the normal population of pregnant women (n=222/228), fibronectin levels were 0.35 +/- 0.06 g/L in pregnancy week 16 and 0.43 +/- 0.12 g/L in week 36. These levels showed a positive correlation to blood pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this group (n=6/228) who later developed preeclampsia had higher fibronectin values 0.42 +/- 0.07 g/L already in week 16 (p=0.023). In the population of women with suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or proteinuria during pregnancy, n=31), fibronectin values were significantly higher, 0.75 +/- 0.27 g/L than in the normal population. Patients with preeclampsia and laboratory signs of organ involvement (n=56) showed significantly higher fibronectin values (0.85 +/- 0.27 g/L) compared to preeclampsia without organ involvement (n=73) [0.76 +/- 0.22 g/L (p=0.03)]. CONCLUSION: Our data show that fibronectin is related to blood pressure in pregnancy. Fibronectin values in women who develop preeclampsia are elevated already in pregnancy week 16 and were higher in those with laboratory signs of organ involvement.