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Diagnostic strategies in myocardial infarction using myoglobin measurement.

Determination of myoglobin, a low molecular weight haeme protein (17.8 kDa), present in both cardiac and skeletal muscle, is an old test with new perspectives. Advantages and disadvantages of myoglobin determination are well known; recent availability of rapid and accurate methods for the assay of this protein has greatly enhanced interest in the clinical utilization of the test. However, since myoglobin is present in both skeletal and cardiac muscle, any damage to these muscle types results in its release in blood and, consequently, high levels of the protein are observed in conditions unrelated to acute myocardial infarction (AMI). New strategies for myoglobin measurement may resolve this limitation. These strategies include both the combined measurement of myoglobin and a skeletal specific marker (carbonic anhydrase III) or a cardiac specific marker (troponin I or T), as well as myoglobin evaluation on serial samples. In particular. the diagnostic algorithm based on combined measurement of myoglobin and troponins significantly improves diagnostic efficiency in laboratory assessment of suspected AMI patients. However, further efforts are necessary to improve the standardization of present methods for myoglobin measurement: the significant disagreement demonstrated between some commercially available assays should be carefully considered in clinical practice.

Biomarkers↗

Kalman filter detection of blinks in video-oculography: applications for VVOR measurement during locomotion.

A Kalman filter algorithm was implemented for automatic detection of blink artifacts in video-oculography (VOG) data, and a cubic spline used to patch the eliminated data. The algorithm was tested by randomly introducing artificial blinks into eye movement data and computing the errors introduced by the patches. We also computed visual vestibulo-ocular reflex (VVOR) gain and phase in healthy and vestibulopathic subjects during a locomotor task, before and after blink removal, to demonstrate the interpretive importance of eliminating blink artifacts. The error introduced by the patched data was small (0.50+/-0.32 degrees ) and within the resolution of head angle measurements. Comparison of gain and phase shift before and after removing blinks revealed that even when calculated values are within expected limits, coherence of the VVOR signal was significantly (p=0.003) lower prior to blink removal (0.51+/-0.37) compared to that after blink removal (0.92+/-0.08). Comparison of VVOR calculations between healthy and vestibulopathic subjects (after removal of blinks) revealed that vestibulopathic subjects had significantly decreased gains (p=0.018) and increased phase shifts (p=0.009): these results agree with data reported in literature. We conclude that the Kalman filter detection and cubic spline patching algorithms are useful tools for VOG and should enable reliable VVOR measurements during unconstrained, ecologically meaningful locomotor activities.

Adult↗

Wideband external pulse recording during cuff deflation: a new technique for evaluation of the arterial pressure pulse and measurement of blood pressure.

Analysis of the external brachial pulse recorded during standard blood pressure cuff deflation with use of a transducer with a wide frequency response has revealed a reproducible pattern with three distinct components that we have labeled K1, K2, and K3. K1 is a low-amplitude, low-frequency signal that is present with cuff pressures above systolic pressure. K2 is a triphasic signal appearing at systolic pressure and disappearing at diastolic pressure, which approximately corresponds to the audible Korotkoff sound. K3 appears with cuff pressure between systolic and diastolic pressure and continues to be present below diastolic pressure. Intra-arterial pressure recordings made with a high-fidelity Millar catheter-tip manometer revealed K2 and K3 analogs. K3 resembles the intra-arterial pressure waveform and when calibrated according to the pulse pressure, noninvasive dK3/dt determinations correlated well with intra-arterial dP/dt measurements. The appearance/disappearance property of K2 was designated as the "K2 algorithm" and represents a new, objective noninvasive method for measurement of blood pressure. The K2 algorithm compares favorably with intra-arterial measurements, is more accurate than the auscultatory technique, and may be especially useful in clinical situations in which the auscultatory technique does not work well.

Adolescent↗

Age-dependent influence on heart rate variability in salt-sensitive hypertensive subjects.

OBJECTIVE: The known association between systemic arterial hypertension in its initial stages and increased sympathetic nervous system drive prompted us to evaluate the influence of age on autonomic nervous system function in subjects with salt-sensitive arterial hypertension. DESIGN: In a randomized study, autonomic nervous system function was assessed by power spectral analysis of heart-rate variability calculated with an autoregressive algorithm in salt-sensitive hypertensives and controls at baseline and under sympathetic stress (passive head-up tilt). For 1 week before the study, all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary sodium intake of 20 mEq per day after a 7-day period on 220 mEq sodium/day. SETTING: Geriatric division at the I Medical Clinic of the University of Rome "La Sapienza". PARTICIPANTS: Sixty-five patients with salt-sensitive hypertension (age range 19 to 89 years) and 64 age-matched normotensive controls, divided for data comparison into three age-groups: < 44 years; 44 to 64 years; and > or = 65 years. MEASUREMENTS: With an autoregressive algorithm in a power spectral analysis of heart rate variability, we detected four spectral frequency-domains: total power (0.0033 to 0.40 Hz), high-frequency power (0.16 to 0.40 Hz), low-frequency power (0.04 to 0.15 HZ) and very-low-frequency power (0.0033 to 0.04 Hz). To determine sodium sensitivity, for 1 week before the study all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary intake of 20 mEq per day and after a 7-day period of 220 mEq sodium/day. RESULTS: Results were expressed as natural logarithms of power and normalized units. The hypertensive patients of all ages had significantly lower total power of heart rate variability than the normotensive controls (P < .05). At baseline, the youngest hypertensives had lower natural logarithms and low-frequency normalized units than controls (P < .001). After tilt, only their low-frequency normalized units exceeded those of controls (P < .001). The middle-aged hypertensive group had higher low-frequency normalized units than controls at baseline (P < .05) and after tilt (P < .001). At baseline and after tilt, the oldest hypertensives had lower low-frequency natural logarithms than controls (P < .05) and normalized units equal to those of controls. But the hypertensives of all ages were less able than controls (P < .001) to increase low-frequency power after head-up tilt. In the less than 44-year-old hypertensives, diastolic pressure correlated significantly with low-frequency power of heart rate variability, expressed in normalized units, at baseline (P < .05) and after head-tilt (P < .05). A significant inverse correlation was found between age and the natural logarithm of low-frequency power at baseline (r = -.682, P < .001) and after tilt (r = -.800; P < .001). Also, a significant inverse correlation was found to exist in normotensive subjects between the natural logarithm of low-frequency at baseline (r = -.595; P < .001) and after tilt (r = -.391; P < .001). The two regression line coefficients for age correlated significantly (P < .001) with the natural logarithm of low-power frequency after tilt. CONCLUSION: Whereas sodium chloride-sensitive hypertension appears to be associated with sympathetic hyperactivity in young and middle-aged subjects, in older people it is not. Sympathetic activity diminishes with age, declining faster in hypertensive subjects.

Adult↗

Resting membrane potentials: a student test of alternate hypotheses.

The frog sartorius muscle is a model tissue for demonstrating to physiology students the principles underlying both membrane phenomena and hypothesis testing. Myocytes can be impaled with conventional glass microelectrodes to measure membrane voltage (Vm). Further, Vm is observed as extracellular K+ is altered and a K+ channel blocker is added. After the experiment, students examine the underlying assumptions of the Nernst equilibrium and the Goldman-Hodgkin-Katz equation. They ultimately determine which of the two algorithms best predicts the measured Vm. In addition, students learn micromanipulation and impalement techniques. This experiment facilitates the student's understanding of membrane permeability, ionic gradients, and membrane voltage.

Algorithms↗

[A method for measuring QT and T duration and beat to beat variability].

The QT interval duration is an important non-invasive electrophysiological parameter that reflects ventricular depolarization and repolarization time. A knowledge of QT variability also provides specific information on the normal and pathological ventricular myocardium, and the influence of the autonomic nervous system. A numerical algorithm was developed for measuring QT interval and T-wave duration in the surface electrocardiogram. In comparison with numerous other approaches, this method calculates these durations without averaging of QRS complexes on a beat-to-beat basis. The main aim of this study was to assess the efficacy of this method for characterizing cardiac diseases. In 6 patients with hypertrophic cardiomyopathy and a control group of 5 healthy, age-matched subjects, different interval durations were calculated. In contrast to the mean QT interval duration, only the T-wave duration differed significantly between the two groups.

Algorithms↗

Computational waveform analysis and classification of auditory brainstem evoked potentials.

The widely used quantitative descriptors of amplitude and latency of evoked potentials, for peaks and troughs along the waveform, relate to only a limited number of points along the waveform, ignoring the interposed data. Moreover, these descriptors are typically determined manually, rendering them susceptible to user bias. We propose and demonstrate a machine-scoring algorithm for the identification and measurement of Auditory Brainstem Evoked Potentials (ABEP) peaks I, III and V. We further introduce an algorithm for the quantitative analysis of ABEP by waveform, and for clustering records according to waveform characteristics. The results of computerized peak identification and measurement, without user intervention, were correlated with manual measurements of the same peaks in a large number of waveforms. The waveform analysis and classification procedure differentiated waveforms to monaural left, monaural right and binaural stimulation, as well as according to the recording montage. These results underscore the advantages of using information in the waveform of ABEP, which has so far been overlooked. The automated algorithms for evaluation of ABEP by waveform hold the promise of a more comprehensive and consistent evaluation, and hence improved sensitivity.

Adult↗

Assessment of telomere length in hematopoietic interphase cells using in situ hybridization and digital fluorescence microscopy.

Telomeres are G/C-rich repetitive DNA sequences at the end of all eukaryotic chromosomes. The loss of telomeric repeat sequences during cell divisions has been proposed as a possible mechanism for cell senescence. The standard procedure for measurement of telomere length is Southern blot (SB) hybridization with a telomere-specific probe. However, in using this technique no information can be obtained on variation in telomeric fragments due to interchromosomal, intrachromosomal, and intercellular differences. Lansdorp et al. (Hum Mol Genet 5:685-691, 1996) developed a method to measure individual telomeres, using in situ hybridization on metaphase chromosomes, employing peptide nucleic acid (PNA) probes and digital fluorescence microscopy. In this paper we describe a method that can be used to assess telomeric length in interphase cells. An algorithm was developed to measure the total intranuclear fluorescence in situ hybridization (FISH) signal, which features accurate correction for the local autofluorescence. Application of this methodology to samples of fetal liver, umbilical cord blood, and adult bone marrow cells showed a gradual decrease of average telomeric length. Southern blot analysis and PNA FISH measurements on chromosomes in the same samples showed similar results. Advantages of interphase measurements include the possibility of studying nonproliferating cells, thus avoiding selection and cell culturing.

Adult↗

Acoustic pattern recognition of /s/ misarticulation by the self-organizing map.

The [s] samples of 11 women, psychoacoustically classified as acceptable/unacceptable, were studied with the self-organizing map, the neural network algorithm of Kohonen. The measurement map had been previously computed with nondisordered speech samples. Fifteen-component spectral vectors, analyzed with the map, were calculated from short-time FFT spectra at 10-ms intervals. The degree of audible acceptability correlated with the location of the sample on the map. Spectral model vectors in different map locations depicted distinguishing spectral features in the [s] samples analyzed. The results demonstrate that self-organized maps are suitable for the extraction and measurement of acoustic features underlying psychoacoustic classifications, and for on-line visual imaging of speech.

Adolescent↗

Can the same edge-detection algorithm be applied to on-line and off-line analysis systems? Validation of a new cinefilm-based geometric coronary measurement software.

In the Cardiovascular Measurement System (CMS) the edge-detection algorithm, which was primarily designed for the Philips digital cardiac imaging system (DCI), is applied to cinefilms. Comparative validation of CMS and DCI was performed in vitro and in vivo with intracoronary insertion of stenosis phantoms in anesthetized pigs. The "obstruction diameter" (OD) was measured at the artificial stenoses visualized by angiography with calibration at the isocenter (ISO) and catheter calibration (CATH) and compared with the true phantom diameters. A clinical comparison of OD, reference diameter (RD), and percentage diameter stenosis (DS) was performed on 70 corresponding images from post-PTCA angiograms. In vitro, OD (CMS) yielded an accuracy of 0.18 +/- 0.14 mm with 100% (correlation coefficient: r = 0.97, y = 0.06 + 0.75x, standard error of estimate [SEE] = 0.09) and 0.19 +/- 0.15 mm with 50% contrast (r = 0.94, y = 0.02 + 0.81 x). OD (DCI) yielded an accuracy of 0.11 +/- 0.06 mm with 100% (r = 0.99, y = -0.03 + 0.91 x, SEE = 0.05) and 0.24 +/- 0.13 mm with 50% contrast (r = 0.94, y = 0.29 + 6.69 x, SEE = 0.12). In vivo, OD (CMS) yielded an accuracy of 0.18 +/- 0.23 mm with ISO (r = 0.89, y = 0.02 + 0.83 x, SEE = 0.22) and 0.26 +/- 0.24 mm with CATH (r = 0.89, y = 0.06 + 0.72 x, SEE = 0.19). OD (DCI) yielded an accuracy of 0.08 +/- 0.15 mm with ISO (r = 0.96, y = 0.08 + 0.86 x, SEE = 0.14) and 0.18 +/- 0.21 mm with CATH (r = 0.92, y = 0.09 + 0.76 x, SEE = 0.17). The clinical comparison showed reasonable agreement for OD only (r = 0.81, y = 0.26 + 0.81 x, SEE = 0.29). Transformation of an edge-detection algorithm from a digital to a cinefilm-based system can lead to impairment of measurement reliability.

Algorithms↗

Beam profiles along the nonwedged direction for large wedged fields.

Beam profiles along the nonwedged direction of a wedged field produced by a linear accelerator exhibit more "sagging" than that of an open field at the same depth. For large fields, the profiles of open and wedged fields can differ by as much as 7%. The extra "sagging" of wedged profiles is mainly due to the difference in penetration between on- and off-axis rays caused by the variation of beam quality across the field. An algorithm was developed to estimate an "effective" depth such that the profile of a wedged field can be approximated by the open-field profile at the effective depth. The algorithm was verified by measured beam profiles for 6- and 15-MV x-ray beams for 15 degree, 30 degree, 45 degree, and 60 degree wedges.

Algorithms↗

Use of Monte Carlo computation in benchmarking radiotherapy treatment planning system algorithms.

Radiotherapy treatments are becoming more complex, often requiring the dose to be calculated in three dimensions and sometimes involving the application of non-coplanar beams. The ability of treatment planning systems to accurately calculate dose under a range of these and other irradiation conditions requires evaluation. Practical assessment of such arrangements can be problematical, especially when a heterogeneous medium is used. This work describes the use of Monte Carlo computation as a benchmarking tool to assess the dose distribution of external photon beam plans obtained in a simple heterogeneous phantom by several commercially available 3D and 2D treatment planning system algorithms. For comparison, practical measurements were undertaken using film dosimetry. The dose distributions were calculated for a variety of irradiation conditions designed to show the effects of surface obliquity, inhomogeneities and missing tissue above tangential beams. The results show maximum dose differences of 47% between some planning algorithms and film at a point 1 mm below a tangentially irradiated surface. Overall, the dose distribution obtained from film was most faithfully reproduced by the Monte Carlo N-Particle results illustrating the potential of Monte Carlo computation in evaluating treatment planning system algorithms.

Algorithms↗

Estimation of peripheral dose from two linacs: Mevatron MX6700 and Mevatron KDS.

An empirical calculation method for high-energy beam peripheral dose estimation is described. The peripheral dose has been measured for a Siemens Mevatron MX6700 (6 MV) and a Siemens Mevatron KDS (6 and 18 MV) linear accelerators. The dose distribution is parameterized for each beam energy as a function of depth, distance from the edge of the field, and field size. A simple algorithm has been developed for dose calculation up to 100 cm from the field central axes. Predictions by this algorithm are compared with measurements in an Alderson phantom.

Particle Accelerators↗

The use of urinary hormonal assessments in human studies.

The collection and analysis of urine samples provides a practical method for monitoring female reproductive events in non-laboratory and non-clinic populations. Collection of biologic samples permits objective assessment of reproductive health endpoints in epidemiologic studies and for epidemiologic research purposes can provide validation of information provided by the subjects, especially outcomes which are usually concealed and thus unknown to the participant. Urine sampling has several advantages over the collection of blood samples, such as simplicity, non-invasiveness, and cost efficiency. Several studies have shown that endocrine information similar to that obtained in blood samples can be obtained from assays of daily urine samples. The measurement of human chorionic gonadotropin in daily and selected urine samples has been incorporated into several recent epidemiologic studies focusing on early fetal loss, and ovarian and pituitary hormone metabolites have been measured in daily urine samples to evaluate ovarian function in studies focusing on women's reproductive health. As the strategy of urinary monitoring becomes more accepted as a legitimate research tool, laboratory methods are being modified to improve performance, reduce costs and adapted to sophisticated algorithms using multiple hormonal measurements to identify a number of end-points.

Biomarkers↗