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Insulin autoantibodies measured by radioimmunoassay methodology are more related to insulin-dependent diabetes mellitus than those measured by enzyme-linked immunosorbent assay: results of the Fourth International Workshop on the Standardization of Insulin Autoantibody Measurement.

Insulin autoantibodies (IAA) have been identified in newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients and in individuals at high risk of developing the disease. However, the literature is not in agreement regarding the prevalence, significance, and predictive value of IAA. Previous workshops have shown that certain sera give markedly different results depending upon assay methodology and, therefore, have suggested that these discrepancies may be due to variations in the assay methodologies used: either the fluid phase RIA or the solid phase enzyme-linked immunosorbent assay (ELISA). Sera from controls (n = 61), newly diagnosed IDDM patients (n = 30), healthy subjects who later became diabetic (n = 8), and first degree relatives of diabetic probands (n = 22) were randomly numbered and sent without category identification to 19 RIA and 10 ELISA laboratories. Each laboratory's raw data from the control sera were used to determine the cut-off point for positive (3 SD above the mean of control sera) in the disease relevant categories. RIA and ELISA methods were comparable in obtaining a low frequency of IAA in control sera. However, the laboratories using RIA methods found a much higher percentage of sera to be IAA positive among both newly diagnosed patients and healthy individuals who later developed diabetes than laboratories using ELISA methods (P less than 0.005). In contrast, there was considerable overlap in the percentage of sera from first degree relatives found positive by both assays. These data strongly suggest that IAA measured by RIA methodology are more disease related than those measured by ELISA methods. Consequently, RIA assays or assays proven to perform as well should be used to measure IAA associated with IDDM.

Autoantibodies

Magnetic resonance velocity measurements in small arteries. Comparison with Doppler ultrasonic measurements in the aortas of normal rabbits.

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) can be used to measure motion. This study compares MRI blood flow velocity measurements to Doppler ultrasound velocity measurements in an animal model. MATERIALS AND METHODS: Blood flow in the abdominal aortas of nine normal rabbits was measured using 16-frame, velocity-resolved MRI and Doppler ultrasound. The MRI data were processed into velocity spectra to aid in their interpretation. RESULTS: Maximum velocity measurements made by range-gated Doppler ultrasound were predicted by the maximum velocity values derived from MR velocity spectra with a slope of 0.861, an intercept of -2.78 cm/second, and an R-value of 0.935 in 70 measurements. CONCLUSIONS: Despite the longer time required for the MR measurement, the MR velocity measurement may be useful in the assessment of deep vessels or those obscured by other structures, which are difficult to measure with ultrasound.

Animals

Pulmonary artery pressure measurement in patients with elevated pressures: effect of backrest elevation and method of measurement.

OBJECTIVE: To determine whether pulmonary artery pressure measurement is accurate if the head of the bed is elevated; to compare the end-expiratory graphic recording and digital monitor methods for pulmonary artery pressure measurement; to determine whether either mean arterial pressure or mixed venous oxygen saturation changes during backrest elevation. DESIGN: Nonrandomized clinical trial. SETTING: A six-bed cardiac surgical intensive care unit of a 540-bed federal facility. POPULATION: Twenty-five postoperative cardiac surgical patients with elevated pulmonary artery pressures (systolic higher than 35 mm Hg). INTERVENTIONS: In supine patients pulmonary artery pressures were measured at each of the following backrest elevations: 0, 20, 30, 45 and again at 0 degrees. Measurements were obtained once during mechanical ventilation and once during normal breathing after extubation. MAIN OUTCOME MEASURES: End-expiratory graphic recording of pulmonary artery pressures; digital monitor values of pulmonary artery pressures; mean arterial pressure; and mixed venous oxygen saturation. RESULTS: No statistical difference was found in pulmonary artery pressures measured at each of the backrest elevations during mechanical ventilation or normal breathing after extubation. Pulmonary artery diastolic and pulmonary capillary wedge pressures obtained with the digital monitor method were significantly lower than the end expiratory graphic recording method during normal breathing after extubation but not during mechanical ventilation. No changes in mean arterial pressure or mixed venous oxygen saturation occurred during backrest elevation. CONCLUSIONS: These results show that pulmonary artery pressures can be measured accurately with the head of the bed in an elevated position. The data indicate that obtaining pulmonary artery pressure measurements from the digital display of the bedside monitor is accurate when respiratory wave form fluctuations are minimal but may lead to inaccurate values with prominent respiratory fluctuations. Further research is needed to validate this finding in different patient populations and with other models of monitoring equipment.

Adult

Sensor-based measures of knee brace adherence have low agreement with self-report methods: A multi-measure study among knee osteoarthritis patients.

OBJECTIVE: To explore agreement between self-report and objectively measured adherence to brace wearing by patients with knee osteoarthritis. METHOD: A single-arm observational analysis nested within the PROP OA randomised controlled trial (ISRCTN28555470). Of 237 adults with symptomatic knee osteoarthritis randomised to brace treatment, 60 were included in this sub-study investigating three different methods of assessing knee brace wear time over 26 weeks: 1. Self-report questionnaires (SRQ) at 12 weeks and 26 weeks; 2. Short message service (SMS) questions (days worn in past week, typical hours per day when worn) administered from week 1 to week 24; 3. A skin temperature sensor embedded in the brace, sampling every 10 min for 26 weeks. The presence and reason for the sensor were concealed from participants. The estimated proportion of participants meeting "minimum brace use", defined a priori as ≥1 h on ≥2 days in past week, was described for each measurement method, overall and by brace type (unloader, neutral). For temperature sensor measurements, time spent above 24°C and time spent above 25°C were used. Agreement between the measures was summarised by percentage agreement and kappa (ĸ). RESULTS: The estimated proportions of participants meeting "minimum brace use" at 12 weeks were 83% (SRQ), 83% (SMS), 60% and 58% (temperature sensor, 24°C and 25°C thresholds, respectively). At 26 weeks, the corresponding estimates reduced to 72%, 71% (SMS at 24 weeks), 43% and 37%. Sensor data suggested the sharpest decline in brace use occurred within the first 12 weeks. Agreement between self-report measures was higher than between self-report measures and sensor (SRQ vs SMS at 12 weeks: 92% agreement, ĸ=0.67 (95%CI: 0.34, 1.00); SRQ vs Sensor at 12 weeks: 74%, 0.35 (0.10, 0.60); SMS vs Sens at 12 weeks: 76%, 0.36 (0.05, 0.66). Agreement between all measurement methods reduced at 26 weeks. CONCLUSIONS: This novel use of a temperature sensor to monitor brace adherence in knee osteoarthritis indicates that self-report adherence substantially overestimates knee brace wearing time, with implications for clinical trials and practice.

Humans

Effects of recording speed on precision of time-based polycardiographic measurements. Optimal paper speeds for measuring points and intervals.

Optimal paper speeds have not been established for all time-based measurements of the cardiac cycle by appropriately designed observer performance studies. In 10 subjects (5 normals and 5 cardiac patients) carotid pulse, phonocardiogram, and electrocardiogram were recorded on magnetic tape for measurement of all fiducial points for systolic time intervals, the systolic time intervals themselves, the pulse transmission time, cycle length (RR), qR time, and R-to-point versus q-to-point measurements at recording speeds of 25, 50, 75, 100, and 200 mm/s. Tracings were coded numerically and randomised. Three observers measured all points and calculated intervals in a sequence determined by individual tables of random numbers. Left ventricular ejection time was the only calculation that could be made at 25 mm/s statistically equally well as at all other speeds. The smallest numerical observer differences occurred uniformly at 100 mm/s paper speed when all recording speeds were considered. However, after excluding the 25 mm/s speed there were no significant differences among point measurements. Measurements of points from R (rather than q) reduced observer variability. We conclude that for point measurements, for systolic time intervals, pulse transmission time, and RR interval, recording speed between 50 and 200 mm/s showed no statistical differences, though smallest numerical differences occurred at 100 mm/s. For LVET, 25 mm/s was satisfactory.

Adult

Measurement of assertive behavior: construct and predictive validity of self-report, role-playing, and in-vivo measures.

Examined the predictive validity and construct equivalence of the three major procedures used to measure assertive behavior: Self-report, behavioral role-playing, and in-vivo assessment. Seventy-five Ss, who spanned the range of assertiveness, completed two self-report measures of assertiveness, the Rathus Assertiveness Scale (RAS) and the College Self-Expression Scale (CSES); two scales from the Endler S-R Inventory of General Trait Anxiousness, the interpersonal and general anxiety scales; eight role-playing situations that involved the expression of positive and negative assertiveness; and a telephone in-vivo task. In general, the study revealed the following: (1) assertiveness measures are task-dependent in that there was more overlap within task than between tasks; (2) there is a moderate degree of correspondence between self-report and role-playing measures, although this was true only for negative assertion; (3) positive and negative assertion do not appear to have the same topography of responding; and (4) there appears to be no consistent relationship between the in-vivo measure and any other type of assertiveness measure.

Anxiety

Comparison of skull circumference and linear measurements with CSF volume MR measurements in hydrocephalus.

In children with hydrocephalus, accurate and reproducible estimation of the presence, severity, and course of the condition is of paramount importance for both clinical and scientific purposes. In this study, 30 hydrocephalic patients were assessed with a number of commonly used methods, such as occipitofrontal skull circumference (SC) measurements, Evans ratio (ER), and bicaudate index (BCI), as well as, for comparison, another ratio of linear measurements [ventricle-skull ratio (VSR)] and MR measurements of total intracranial CSF volume. In repeated CSF volume measurements in healthy volunteers, the MR method appeared to be accurate and reproducible. This technique was simpler and easier in application, requiring less interaction than comparable MR techniques described by others. The variation coefficients were within the same range. In increased CSF volumes, our technique can be recommended; in very small CSF volumes, another technique is more adequate. Direct assessment of CSF volume as a measure of hydrocephalus was preferable over derived estimations for scientific purposes and may function as a gold standard against which to evaluate other techniques that are easier to apply clinically. In comparison, SC measurements were poor; CSF volume changes were not reflected in SC changes. VSR was preferable over ER and BCI, because it correlated more closely with CSF volume.

Cerebrospinal Fluid

Measurement of thyroid-stimulating immunoglobulins by incorporation of tritiated-adenine into intact FRTL-5 cells: a viable alternative to radioimmunoassay for the measurement of cAMP.

OBJECTIVE: To evaluate the utility of 3H-adenine incorporation into intact rat thyroid epithelial cells (FRTL-5) as an alternative to radioimmunoassay for the measurement of cAMP following stimulation of these cells by serum thyroid-stimulating immunoglobulins from patients with Graves' disease. DESIGN: We determined the cAMP produced by FRTL-5 cells following incubation with serum from patients with a spectrum of autoimmune thyroid and other diseases using the 3H-adenine assay. PATIENTS: We studied 27 patients with untreated Graves' disease, 10 with Graves' disease complicated by ophthalmopathy (all on antithyroid medication), 11 with Hashimoto's thyroiditis, five with multinodular goitre, one with thyroid carcinoma, 23 with type 1 diabetes mellitus, 19 with other autoimmune diseases and 10 controls. MEASUREMENTS: The 3H-cAMP produced in cells incubated with either bovine TSH (bTSH) or polyethylene glycol-precipitated serum immunoglobulins, was separated by sequential chromatography on Dowex and alumina columns, and counted. The thyroid-stimulating immunoglobulins index (3H-cAMP patient immunoglobulins/3H-cAMP control immunoglobulins) was calculated for each serum and considered positive if greater than 1.5 (+ve thyroid-stimulating immunoglobulins index, i.e. > 2 standard deviations above control). The thyroid-stimulating immunoglobulins index was correlated with measurement of thyrotrophin binding inhibitory immunoglobulins (TBII) by radioreceptor assay. RESULTS: The 3H-adenine assay has a sensitivity of 10(-11) M bTSH with maximal stimulation at 10(-9) M bTSH (30-fold). Twenty-five of 27 patients (92%) with untreated Graves' disease and four of 10 patients with Graves' disease complicated by ophthalmopathy had +ve thyroid-stimulating immunoglobulin indices. The thyroid-stimulating immunoglobulins index in patients with untreated Graves' disease correlated with their TBII assay result (r = 0.63, P < 0.001). In addition, the index was negative in patients with Hashimoto's thyroiditis, multinodular goitre, thyroid carcinoma, and type 1 diabetes mellitus. Of the patients with other autoimmune diseases only one (a patient with systemic lupus erythematosis) had a +ve thyroid-stimulating immunoglobulin index. Direct comparison of cAMP measurement by 3H-adenine incorporation and commercial radioimmunoassay showed an equal sensitivity to both bTSH and Graves' immunoglobulins. After cell preparation, results are obtained more quickly with the 3H-adenine assay than with a cAMP radioimmunoassay (5 hours compared to 2 days), and far more cheaply than by commercial radioimmunoassays. CONCLUSIONS: Measurement of thyroid-stimulating immunoglobulins using the incorporation of 3H-adenine into cAMP in FRTL-5 cells is sensitive, reproducible, rapid and specific. These features make this assay a viable alternative to RIA for the measurement of thyroid-stimulating immunoglobulins in patients with Graves's disease.

Adenine

Measurement of oxygen concentrations in the intact beating heart using electron paramagnetic resonance spectroscopy: a technique for measuring oxygen concentrations in situ.

Electron paramagnetic resonance (EPR) spectroscopy can be applied to measure oxygen concentrations in cells and tissues. Oxygen is paramagnetic, and thus it interacts with a free radical label resulting in a broadening of the observed linewidth. Recently we have developed instrumentation in order to enable the performance of EPR spectroscopy and EPR oximetry in the intact beating heart. This spectrometer consists of 1-2-GHz microwave bridge with the source locked to the resonant frequency of a specially designed lumped circuit resonator. This technique is applied to measure the kinetics of the uptake and clearance of different free radical labels. It is demonstrated that this technique can be used to noninvasively measure tissue oxygen concentration. In addition, rapid scan EPR measurements can be performed enabling gated millisecond measurements of oxygen concentrations to be performed over the cardiac cycle. Thus, low-frequency EPR spectroscopy offers great promise in the study of tissue oxygen concentrations and the role of oxygen in metabolic control.

Animals

The application of generalizability theory to surface electromyographic measurements during psychophysiological stress testing: how many measurements are needed?

Generalizability theory is an extension of classical reliability theory that allows multiple sources of measurement error in an experimental design to be investigated simultaneously. In the present study, generalizability theory was used to evaluate measurement error in psychophysiological test procedures used to differentiate tension headache patients from normal controls based upon measures of electromyographic (EMG) responding. Thirty-three subjects who met diagnostic criteria for tension-type headache and 40 normal control subjects who rarely or never experienced headache participated in two laboratory sessions. EMG activity of head and neck muscles was recorded while subjects performed baseline, relaxation, choice reaction time, psychomotor tracking, and cold pressor tasks. Variance components were computed for an experimental design having subjects nested within experimenters and crossed with sessions and replications. Generalizability coefficients were computed for combinations of various numbers of sessions and replications. The generalizability of EMG measures was highly variable, depending on the experimental conditions in force. The largest sources of measurement error were attributed to the unique responsiveness of individual subjects under a particular set of treatment conditions. For some stress tests currently in use, data from several testing sessions may need to be averaged in order to achieve acceptable levels of generalizability. Generalizability greater than 0.80 can be expected only rarely when data are collected during a single session. In the research setting, low generalizability may account for the failure of EMG-based stress tests to differentiate tension headache patients from controls during stressful task performance. In the clinical setting, the generalizability of information derived from "stress profiling" or muscle "scanning" techniques, which depend on results obtained during a single testing session, is doubtful.

Adult

Use of the pigmentometer, a new device for measuring skin albedo: relating skin color with a series of physiological measures.

Use of the Pigmentometer, a new device for measuring skin albedo: Relating skin color with a series of physiological measures. An apparatus has been described for the indirect measurement of skin albedo in human subjects. This device operates on the principle of the reflectance of light as influenced by the lightness or darkness of the skin. This new equipment was used to examine the relationship between lightness or darkness of the skin and the basal level and responsivity of some autonomic nervous system physiological variables in a series of 46 black and 47 white male and female subjects. It was observed that blacks had significantly lower (darker) skin albedo (PI), a significantly higher skin resistance (SR) and amplitude of the galvanic skin response (GSR), and an insignificant higher basal heart rate (HR). Pearson Product-Movement correlations between all measures from the total population showed significant relationships between PI and SR, SR and GSR and HR and HRR (heart rate response). The further separation of the total population into subgroups of blacks, whites, males, females, and black and white male and female goups, respectively, altered some of these differences and relationships previously observed. These results appeared to support the premise that race is more responsible for influencing the measured physiological responses, particularly SR, than is the lightness or darkness of the skin.

Age Factors

Repeated measurement variation and precision of laser Doppler flowmetry measurements.

The repeated measurement variation of laser Doppler flowmetry (LDF) recordings is essential for the precision level of the method in the assessment of tissue perfusion. The objective of this paper was to discuss the practical consequences of this problem by presenting a statistical method which can be used to estimate the number of replicates needed to reach a certain precision standard. By a repeated measures analysis of variance with a single-factor design, the mean variation of repeated measurements and its standard deviation were estimated. This estimate was used for simulation of a 95% confidence interval with length defined as a percentage of the mean of repeated measurements. The analyses were made in LDF samples performed in skin, gastric mucosa, and pig kidney in order to exemplify the use of the method. Paired values gave an unacceptable precision estimate in all tissues, but by increasing the number of replicates, the estimated precision was greatly enhanced. A preliminary recommendation for the practical use of LDF in the assessment of tissue perfusion is to perform at least four to six repeated measurements. Further studies are needed in order to establish methodological standards. The presented statistical considerations could also be relevant for other procedures used in microvascular research.

Adult

Hepatic blood flow measurement III. Total hepatic blood flow measured by ICG clearance and electromagnetic flowmeters in a canine septic shock model.

The validity of the ICG clearance method for the measurement of THBF in abnormal circulatory states remains questionable. In this study THBF measured by this method is compared with the electromagnetic flow technique in a canine spetic model. Good correlation is demonstrated between the two in normal control animals. However, in the septic animals the ICG underestimated the electromagnetic flow result by 20%. This is true in both the high and the low cardiac output septic shock pictures that emerge. In the septic animals, the total hepatic blood flow as measured by the ICG was almost equal to the portal vein flow alone measured by the electromagnetic flowmeters suggesting that this was the quantity it was measuring in this abnormal state. Pathophysiologic mechanisms that may explain the discrepancy are given.

Animals

Measurement of 42K concentration in the mucosal portion of the intestine without tissue samples: an approach to the measurement of mucosal blood flow in the dog.

1. The concentration of 42K within the jejunal mucosa was measured by intraluminal miniatrue Geiger-Müller tubes shieleded with platinum foil. 2. Isotope concentration measured by tissue assay of jejunal mucosa gave similar results to that obtained by the Geiger-Müller tubes. 3. Isotope measurement by shielded Geiger-Müller tubes obviates the need for tissue samples and permits repeat measurement in the same animal. This should find physiological application in measuring the mucosal portion of total intestinal blood flow by the indicator fractionation technique.

Animals

Dependence of measured ionized calcium on protein concentration as measured by three ion-selective electrodes.

A positive effect of protein on the measurement of ionized calcium in serum by ion-selective electrodes (ISEs) has been previously reported and the present study confirms this finding. Ionized calcium in serum was measured in the presence of increasing protein concentrations induced by venous stasis in 17 healthy volunteer subjects. Ionized calcium was measured using two commercial analysers, a Radiometer ICA2 analyser and a Baker Analyte+2 analyser, and a calcium cell devised by Covington for the calcium reference method (CRM). Both commercial analysers used charged ionophores and the CRM used a neutral carrier ionophore in the selective membrane. A small but significant rise in ionized calcium with increasing protein was measured on all analysers. Substitution of isotonic KCl for saturated KCl in the reference electrode of the CRM resulted in significantly reduced values for ionized calcium in paired serum samples when measured using the isotonic salt bridge. This study supports the premise that the positive effect of protein is related to the salt bridge concentration of the reference electrode rather than the ISE membrane composition.

Adult

Measurement of health status in diabetic patients. Diabetes impact measurement scales.

OBJECTIVE: To develop an instrument to measure health status in adult insulin-dependent (type I) and non-insulin-dependent (type II) diabetic patients. RESEARCH DESIGN AND METHODS: Correlative study to examine psychometric properties of the questionnaire. Test-retest reliability, item-scale correlations, principal-components analysis, correlations with global clinical ratings, and correlations with clinical data extracted from medical records were examined at the diabetes clinics at the University of California, Davis, Medical Center. Patients were volunteer clinic patients able to complete the questionnaire. One hundred thirty patients completed a first administration of the questionnaire, and 52 completed a second administration. RESULTS: Test-retest reliability was satisfactory. Item-scale correlations showed that 40 of 44 questionnaire items were highly correlated with subscale and total scale scores. Principal-components analysis identified one major factor measured by the questionnaire. Cronbach's alpha, a measure of the scales' internal consistency, was of satisfactory magnitude. Global ratings of clinical status by patients and clinicians were highly correlated with scale scores. Correlations of scale scores with clinical data were generally of low magnitude but, where significant, were consistently in the direction hypothesized if the scale truly measures health status or disease impact. CONCLUSIONS: The Diabetes Impact Management Scales (DIMS) is an easily administered questionnaire with internal consistency and test-retest reliability. Preliminary correlative analyses support the validity of the instrument as a measure of health status in adult type I and type II diabetic patients. Further work will be necessary to firmly establish the validity of the DIMS and its usefulness in clinical outcomes research.

Adult