The normal ranges of cardiovascular parameters measured using the ultrasonic cardiac output monitor

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18– 60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18–60 years; (2) combine these data with those for healthy children (aged 0–12), adolescents (aged 12–18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population- based cross-sectional observational study of healthy Chinese subjects aged 0.5–89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5–89; 52% male). From previous studies, 1197 children (aged 0–12, 55% male), 590 adolescents (aged 12–18, 49% male), and 77 elderly (aged 60–89, 55% male) were included. New data were collected from 354 adults aged 18–60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly

Early detection of acute myocardial infarction with the new marker Fatty Acid-Binding Protein : rapid testing and diagnostic value

There are several requirements for the early detection of AMI with biochemical markers: The biochemical marker should be: - Specific - Sensitive - Fast elevated after the clinical onset of the symptoms. The test should be: - Easy to perform - Give a fast result - Preferably bedside - Inexpensive Here, we demonstrate the biochemical characteristics of heart-type Fatty Acid-Binding Protein (FABP) in AMI and UAP patients. Also, we show some preliminary data on a new in-house made quantitative rapid test with simple test procedures. - Patients: 50 patients of the CCU of PWH are included in the study diagnosed with UAP or AMI. Eight blood samples per patient were taken at 0-72 hours after admission and analyzed with a laboratory ELISA test. - Rapid test procedure: 80 ml plasma or serum is added on the sample pad. Within 5 minutes, the strip can be read out with an optical reader (the PART from LRE, Munich, Germany). A release curve for AMI patients shows a significantly elevated FABP concentration already 1 hour after infarction, whereas for CPK, this is found after 3 hours. Comparing the ROC curve for patients arriving at the hospital and 1 hour later for FABP and CPK demonstrates the preference of FABP over CPK. The preliminary results of the rapid test show for selected plasma and serum samples a measuring range of 0-200 ng/ml FABP. The availability of a rapid bedside test for FABP enables faster diagnosis in patients with no clear ECG. This can be used for both inclusion or exclusion of AMI

Early exclusion of major adverse cardiac events in emergency department chest pain patients: A prospective observational study

Background The current evaluation of patients with chest pain presenting to an emergency department (ED) with suspected acute coronary syndrome (ACS) is a lengthy process involving serial measurements of troponin. Objective We aimed to validate the diagnostic accuracy of a Thrombolysis in Myocardial Infarction (TIMI) score with single high-sensitive cardiac troponin T (hs-cTnT) for early rule out of 30-day major adverse cardiac events (MACE), and to compare the TIMI score with combinations of heart-type fatty acid binding protein (H-FABP) and a modified HEART (history, electrocardiogram, age, risk factors, troponin) score. Methods We recruited 602 consecutive adult patients with chest pain and suspected ACS in the ED. Each patient had TIMI and HEART scores, and a point-of-care H-FABP test. Results MACE occurred in 42 (7.0%) patients within 30 days. A low risk for 30-day MACE was identified by a modified TIMI score of 0 in 65 (11%) patients, and by a HEART score ≤ 2 in 96 (16%) patients. No MACE occurred in these groups, giving both scores a sensitivity of 100% (95% confidence interval [CI] 91.6–100%), and specificity of 11.6% (95% CI 9.2–14.5%) and 17.1% (95% CI 14.2–20.5%), respectively. Use of combined TIMI and HEART scores improved the specificity further to 22.0% (95% CI 18.7–25.6%) without lowering sensitivity. Early H-FABP measurement > 7 μg/L had a sensitivity of 41.5% (95% CI 27.8–56.6%) and a specificity of 91.1% (95% CI 88.4–93.2%) for predicting 30-day MACE. Conclusions A modified TIMI score of 0 or a HEART score of ≤ 2, incorporating a single hs-cTnT level, will identify patients with low risk of 30-day MACE for early discharge within 2 h of ED arrival

A superior early myocardial infarction marker : human heart-type fatty acid-binding protein

Various biochemical markers are available to detect cardiac tissue injury after an acute myocardial infarction (AMI) and to estimate the extent of this injury. One of the markers used to detect AMI early after onset of symptoms is heart-type fatty acid-binding protein (H-FABP). To make it clinically applicable it is important to develop rapid diagnostic tests to assess its concentration in whole blood. For this purpose, a one-step quantitative lateral-flow assay for rapid detection of H-FABP has been developed. To have sufficient amount of H-FABP for in vitro studies, a high-level expression of human H-FABP in Escherichia coil was achieved with a yield of the recombinant protein of 112 mg/L culture. This was the first time in Asia to produce recombinant H-FABP. Moreover, time-consuming procedures for purifying the recombinant protein were eliminated by the one-step purification method. Among 218 patients presenting with chest pain and suspected myocardial infarction at the Prince of Wales Hospital in Hong Kong, increased H-FABP was found in those with confirmed MI. The area under the receiver operating characteristic (ROC) curve indicating diagnostic performance for H-FABP was 0.995 one hour after admission (1.00 corresponding to 100% sensitivity and 100% specificity). Similar values were reached for CK (0.998) and the “gold-standard” in cardiology, cTnI (0.995), only 8 hours after admission. Therefore, H-FABP reveals the same information 7 hours earlier compared to cTnI and CK. Sensitivity and negative predictive value for H-FABP reached 100% 1 hour after admission. Thus, H-FABP is a promising marker for AMI as it can reliably confirm or exclude myocardial infarction with two tests only, one at admission and one 1 hour post admission. A rapid and quantitative lateral-flow assay for the detection of H-FABP in serum samples has been successfully developed with a performance time of 5 minutes. 51 serum samples from patients were evaluated using a conventional ELISA and the newly developed lateral-flow assay. A good agreement between the two methods was found according to the Bland and Altman plot. The correlation found was y = 0.9685x - 0.6270 (r2 = 0.9585). With the successful development of the H-FABP lateral-flow assay, we have been the first to develop a novel FABP test designed for quantitative detection of H-FABP in whole blood samples. It requires no sample pretreatment and gives result within 15 minutes. With this rapid and sensitive immunoassay, H-FABP will be soon introduced in clinical practice. Furthermore, H-FABP also presents in skeletal muscle but with much lower content than in cardiac muscle. This feature makes it possible to use H-FABP in monitoring skeletal muscle injury induced by exercise and physical training. The timely feedback based on the monitoring system will allow coaches to modify the training program as appropriate and thus will prevent athletes from excessive muscle damage and overtraining

Pathophysiological roles and clinical importance of biomarkers in acute coronary syndrome

Early diagnosis of acute coronary syndrome (ACS) is important to guide appropriate therapy at a time when it is most likely to be of value. Accurate prognostic and risk stratification will facilitate high-risk patients to have early advanced diagnostic investigations and early appropriate interventions in a cost-effective and efficient manner, while those patients at low risk of ACS complications do not need such costly diagnostic tests and unnecessary hospital admission. Recent investigations have demonstrated that elevation of biomarkers upstream from acute-phase biomarkers, biomarkers of plaque destabilization and rupture, biomarkers of myocardial ischemia, necrosis, and dysfunction may provide an earlier assessment of patient risk and identify patients with higher risk of having an adverse event. This review provides an overview of the pathophysiology and clinical characteristics of several well-established biomarkers as well as emerging biomarkers that may have potential clinical utility in patients with ACS. Such emerging biomarkers hold promise and need to be more thoroughly evaluated before utilization in routine clinical practice

Development of enzyme-based bar code-style lateral-flow assay for hydrogen peroxide determination

A unique approach of developing a bar code version of lateral-flow enzymatic-based assay for the semiquantification of hydrogen peroxide is described. The proposed assay system is mainly composed of a goat anti-mouse IgG-horseradish peroxidase conjugate (Gt anti-M IgG-HRP)-coated nitrocellulose (NC) membrane and a peroxidase substrate pad. Unlike the bar code immunochromatographic assay which depends on the stepwise capture of analyte, the principle of enzyme-based bar code lateral-flow assay is based on the different reaction time on successive lines due to the delay in 3,3',5,5'-tetramethylbenzidine (TMB) release. Hydrogen peroxide (H2O2) acts as a limiting factor which controls the rate of the enzymatic conversion of TMB to blue color complex. The system expresses the concentration of H2O2 in micromole range as three distinct ladder bars in 9 min therefore without the need of any reading device. The major advantages of this assay are its easily readable result, and also its simplicity and low-cost in production offers a cheaper alternative for testing those expensive biosensors might not be available to the third world countries. By incorporating with H2O2-generating oxidoreductases, the assay can be further extended to detect a variety of analytes with clinical and environmental importance. Glucose was chosen to be the model analyte where the proposed system gave signal response at between 5 mu M and 100 mu M. (C) 2008 Elsevier B.V. All rights reserved

Development of a creatinine enzyme-based bar-code-style lateral-flow assay

A lateral-flow, enzyme-based, bar-code assay for creatinine employing the concept of combination of diffusion and kinetics controlled has been developed. Unlike the traditional bar-code version of immunochromatographic assay, which depends on the stepwise capture of colorimetric tracer-labeled antibody-antigen complex by the immobilized antibody on each successive line, the principle of our proposed assay is based on the delay in TMB release and its diffusion in combination with horseradish peroxidase kinetics. Hydrogen peroxide (H2O2) produced from enzymatic reactions acts as a limiting factor, which controls the rate of conversion of TMB to blue color complex. The assay takes advantage of giving ladder bar result therefore without the need of any reading device. Depending on the amount of enzymes used, the assay can be one (9 min) or two steps (19 min). The strip assay semiquantitatively measures creatinine concentrations ranging from 0 to 400 mu M. Thirty urine samples and thirty serum samples were tested, and the assay showed 90.0\% and 86.7\% agreement compared with conventional Jaffe method, respectively. This assay provides a tool for quick identification of creatinine for patients without the requirement of any instrument

Matrix metalloproteinase 9 mRNA: An early prognostic marker for patients with acute stroke

To investigate matrix metalloproteinase 9 (MMP9) mRNA as a prognostic marker in stroke. Design and methods MMP9 mRNA concentrations in 126 stroke patients were analyzed using quantitative reverse transcription-polymerase chain reaction. Results The normalized MMP9 mRNA concentration was almost 3 times higher in non-survival patients compared to survival patients (P = 0.0002); and 1.9-fold higher in patients with post-stroke modified Rankin score (mRS) > 2 than patients with mRS ≤ 2 (P < 0.05). Conclusions MMP9 mRNA was a predictor of poor outcome and mortality in stroke

Prospective validation of Thrombolysis in Myocardial Infarction and front door Thrombolysis in Myocardial Infarction risk scores in Chinese patients presenting to the ED with chest pain

Chest pain is a common complaint among emergency department (ED) patients. The Thrombolysis in Myocardial Infarction (TIMI) and front door TIMI (FDTIMI) scores are used to risk stratify chest pain patients in many Western countries; they have not been validated in patients with undifferentiated chest pain in Asia. Our objective was to establish the relationship between the TIMI and FDTIMI scores and the 30 day rate of major adverse cardiac outcomes (MACE) in Chinese patients presenting to the ED with chest pain. Methods Prospective, single-center, observational cohort study of consecutive patients presenting with chest pain from July 2009 until March 2010 to a Hong Kong university hospital ED. Data collected included patient characteristics, TIMI items and past medical and medication history. Primary outcome was MACE within 30 days of presentation. MACE was a composite outcome of any of the following: death (all causes), readmission with myocardial infarction, acute coronary syndrome not diagnosed at initial ED presentation and coronary revascularization. Results One thousand patients recruited with complete 30-day follow-up. STEMI patients (n = 75) were excluded. Mean patient age 66.8 ± 13.9 years; 51.7% male. 119 (12.9%) patients had MACE within 30 days of presentation. The incidence of MACE ranged from 0 for TIMI0 to 37.5% for patients with TIMI6/7. Increasing TIMI and FDTIMI scores were associated with a higher incidence of MACE. Conclusions This validation suggests that the TIMI/FDTIMI scores can be employed in Hong Kong Chinese; they may be useful for risk stratificatio