Troponin T Identifies Patients With Unstable Coronary Artery Disease Who Benefit From Long-Term Antithrombotic Protection fn1fn1This study was supported by grants from the Swedish Heart and Lung Foundation, Stockholm, Sweden; the Selander’s Foundation, Uppsala, Sweden; the Uppsala County Association Against Heart and Lung Diseases, Uppsala, Sweden; Pharmacia Biosensor AB, Uppsala, Sweden; and Pharmacia AB, Stockholm, Sweden. Boehringer Mannheim Scandinavia AB, Bomma, Sweden provided the troponin T kits.

AbstractObjectives. We sought to evaluate whether troponin T might be used for identification of patients with unstable coronary artery disease in whom treatment with low molecular weight heparin is beneficial.Background. Early identification of subgroups with differences in response to a certain treatment is important to optimize the utilization of different therapeutic approaches.Methods. Nine-hundred seventy-one patients with unstable coronary artery disease who participated in a trial of the low molecular weight heparin dalteparin (Fragmin) and who provided blood samples were classified into subgroups according to troponin T level. In the short-term phase all patients received subcutaneous dalteparin/placebo twice daily for 6 days. During the long-term phase they continued with daltparin/placebo once daily for another 5 weeks.Results. In the short-term phase, dalteparin reduced the incidence of death or myocardial infarction from 2.4% to 0% (p = 0.12) and from 6.0% to 2.5% (p < 0.05) in 327 and 644 patients with troponin T levels <0.1 and ≥0.1 μg/liter, respectively. During long-term treatment there was an increasing difference between the placebo and dalteparin group in those with troponin T levels ≥0.1 μg/liter, in whom the incidences at 40 days were 14.2% and 7.4%, respectively (p < 0.01). In contrast, no beneficial effect of the long-term treatment could be demonstrated in those with troponin T levels <0.1 μg/liter (4.7% vs. 5.7%).Conclusions. Elevation of troponin T identifies a subgroup of patients in whom prolonged antithrombotic treatment (e.g., with dalteparin) is beneficial.(J Am Coll Cardiol 1997;29:43–8)

Serum concentrations of Thymidine kinase 1 measured using a novel antibody-based assay in patients with Hodgkin Lymphoma

Background: Thymidine kinase 1 (TK1) is an intracellular protein associated with DNA synthesis, expressed during the G1 phase and remained elevated through the M phase, with a potential as a biomarker for cell proliferation. In this study, we explore the possible use of TK1 in Hodgkin lymphoma (HL).Methods: Serum concentrations of TK1 (S-TK1) were measured in 46 newly diagnosed HL patients using prospectively collected biobanked serum samples. The samples were analyzed using a novel antibody-based TK1 immunosorbent assay (ELISA).Results: The concentrations of S-TK1 were elevated in HL patients compared with healthy controls (median 0.32 mu g/L vs. 0.24 mu g/L, P = 0.003). A further increase in S-TK1 was observed during the treatment. The S-TK1 concentrations were higher in patients with advanced stage disease, low B-Hb, elevated P-LD and in those with B-symptoms. A high ESR correlated with low S-TK1.Conclusions: The study results suggest that S-TK1, measured using a novel antibody-based assay, has the potential to be a biomarker in HL. However, while S-TK1 levels are elevated at baseline compared with healthy controls, a limited number of patients and comparatively short follow-up time render reliable -conclusions difficult

Novel sensitive cardiac troponin I immunoassay free from troponin I-specific autoantibody interference

BACKGROUND\nCardiac troponins (cTnI and cTnT) are the recommended biomarkers of myocardial infarction. As cTn-specific autoantibodies (cTnAAb) can interfere with the cTn detection by state-of-the-art cTnI assays, our objective was to develop a sensitive cTnI immunoassay free from this analytical interference.\nMETHODS\nThe assay used antibody-coated spots containing three capture Mabs/Fabs directed against the N-terminus, midfragment and C-terminus of cTnI and a europium chelate-labeled tracer Mab against the C-terminus. Following a 3-h sample incubation and washing, cTnI was quantified by time-resolved fluorometry.\nRESULTS\nThe limit of detection (LoD) was 2.9 ng/L and the assay was linear up to 50,000 ng/L. The total precision of 10% CV was not reached, but 20% CV was reached at 10 ng/L. Mean cTnI (10-50,000 ng/L) recoveries were 100% and 119% in three cTnAAb-positive and two cTnAAb-negative individuals, respectively, verifying the interference resistance of the antibody design used. On average, Architect hs-cTnI assay gave seven-fold higher cTnI concentrations than the new assay but the correlation between the assays was good (r=0.958). Of apparently healthy individuals (n=159), 18% had measurable cTnI values (&gt;LoD) and 10% were cTnAAb-positive. The proportion of measurable cTnI values, however, was significantly higher in cTnAAb-positive individuals (13/16, median cTnI 8.5 ng/L) than in cTnAAb-negative individuals (15/143, median cTnI</p

Low molecular weight heparin (dalteparin) as adjuvant treatment to thrombolysis in acute myocardial infarction—a pilot study: Biochemical Markers in Acute Coronary Syndromes (BIOMACS II)

AbstractOBJECTIVESThis randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h.BACKGROUNDLow-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction.METHODSIn 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20–28 h to evaluate TIMI-flow in the infarct-related artery.RESULTSDalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6–24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04).CONCLUSIONSWhen dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study

Acute Effects of a Fungal Volatile Compound

Objective: 3-Methylfuran (3-MF) is a common fungal volatile product with active biologic properties, and previous studies have indicated a contribution to airway disease. The aim of the present study was to assess the acute health effects of this compound in humans. Design: Acute effects were assessed via chamber exposure to (1 mg/m(3)) 3-MF. Participants and measurements: Twenty-nine volunteers provided symptom reports, ocular electromyograms, measurement of eye tear film break-up time, vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests, and dynamic spirometry. Results: No subjective ratings were significantly increased during exposure. Blinking frequency and the lavage biomarkers myeloperoxidase and lysozyme were significantly increased, and forced vital capacity was significantly decreased during exposure to 3-MF compared with air control. Conclusions and relevance to clinical practice: Acute effects in the eyes, nose, and airways were detected and might be the result of the biologically active properties of 3-MF. Thus, 3-MF may contribute to building-related illness

Randomised clinical trial and meta-analysis: mesalazine treatment in irritable bowel syndrome—effects on gastrointestinal symptoms and rectal biomarkers of immune activity

Background Low-grade immune activation in the gut is a potential treatment target in irritable bowel syndrome (IBS). Aims To determine improvement in IBS symptoms after mesalazine treatment, and the utility of measures of immune activity in the rectal mucosa Methods This was a randomised, double-blind, placebo-controlled, parallel-arm, multicentre trial in subjects with IBS (Rome III criteria), with an eight-week treatment period of mesalazine 2400 mg or plcebo once-daily. The primary endpoint was the global assessment of satisfactory relief of IBS symptoms in ≥50% of weeks during intervention. IBS symptoms were also measured with the IBS severity scoring system; immune activity was measured by mucosal patch technology. A post hoc meta-analysis of randomised placebo-controlled trials of mesalazine in IBS was added. Results Of 181 included patients, 91 received mesalazine and 90 received placebo. The primary endpoint was met by 32 (36%) patients after mesalazine and 27 (30%) after placebo (p = 0.40). There were no differences in response rates related to IBS subtype or post-infection symptom onset. More reduction of abdominal bloating was noted in the mesalazine group (p = 0.02). The meta-analysis showed no effect of mesalazine on IBS symptoms. No mucosal patch technology measure could predict response to mesalazine, and found no differences in the effects of intervention on levels of immune markers. Conclusions Mesalazine is ineffective in reducing IBS symptoms. Rectal measures of immune activity by the mucosal patch technology cannot predict a higher chance of response to mesalazine.publishedVersio

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7

Human neutrophil lipocalin (HNL) as a biomarker of acute infections

The early and accurate discrimination between bacterial and viral causes of acute infections is the key to a better use of antibiotics and will help slow down the fast-growing resistance to commonly used antibiotics. This discrimination is in the vast majority of cases possible to achieve by blood assay of the biomarker human neutrophil lipocalin (HNL), which we showed to be uniquely increased in patients suffering from bacterial infections. In serum, sensitivities and specificities of &gt;90% are achieved in both adults and children. In order to eliminate the need to produce serum, a whole-blood assay with an assay time of &lt;10 min was developed in which blood neutrophils are activated to release HNL. The diagnostic accuracy of this assay also showed sensitivities and specificities of &gt;90% in most infectious diseases and was clearly superior to contemporary assays such as blood neutrophil counts, C-reactive protein, procalcitonin, and expression of CD64 on blood neutrophils. This format lends itself to the development of a point-of-care HNL assay and will be a major step forward to accomplish the goal of accurately diagnosing patients with symptoms of acute infections within 10 min at the emergency room or at the doctor's office