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The reproducibility of repeat measures of airway inflammation in stable atopic asthma.

Measures of airway inflammation are increasingly being used as outcome measures in asthma intervention studies. Meaningful interpretation of observed changes in bronchial mucosal cell numbers should depend, in part, on the reproducibility of repeat measures over time. We wanted to investigate the reproducibility of immunopathologic and physiologic parameters after short and long measurement intervals. We therefore performed spirometry, bronchial provocation challenge, and fiberoptic bronchoscopy with endobronchial biopsy (always right upper lobe second-generation bronchus) at baseline, after 2 wk, and again after 8 wk on nine subjects with stable atopic asthma (receiving inhaled placebo and beta-agonist therapy only). Numbers of T cells, memory T cells (CD45Ro(+)), macrophages (CD68(+)), and eosinophils (EG1(+) and EG2(+)) on immunohistochemical stains of bronchial biopsies were quantified by computerized image analysis. Intraclass correlation coefficients (ICCs) of reproducibility were calculated for repeat measures of each parameter and a high ICC (greater than 0.6) was interpreted as "highly reproducible." Repeat measures of FEV(1), FEF(25-75%), and PC(20) were highly reproducible after short (2-wk) and long (8-wk) intervals. Only repeat measures of EG2(+) had an ICC greater than 0.6 after 8 wk. Repeat measures of CD45Ro(+), EG2(+), and T cell numbers (but not CD68(+) and EG1(+) cells) are highly reproducible and reliable parameters of asthmatic airway inflammation after a 2 wk interval.

Adolescent↗

Back shape assessment in each of three positions in preoperative patients with adolescent idiopathic scoliosis: evaluation of a 10-level Scoliometer method interpolated to 18-levels.

A Scoliometer was used by one observer (RKP) to assess the reproducibility of angle of trunk inclinations (ATIs) in 13 preoperative patients with AIS (thoracic 7, thoracolumbar 6, mean Cobb angle 50 degrees, right 9, age 15.4 years, girls 10). Three positions were used namely standing forward-bending, (FB) sitting FB and prone. Readings of ATI on the back were obtained at each of 10 levels (T1-S1). The subject was repositioned after walking around the room and a second set of readings obtained (repeats). All readings were converted by a computer program to 18 levels and plotted. The readings from 18 levels were analysed by level, as well as summated and averaged both without and with correction for the side of the curve. Conclusions. Back surface asymmetry measured with a Scoliometer in these preoperative patients with AIS is less in the prone position than in each of the forward bending positions. The standing FB position has the best reproducibility which supports the practice of using this position to measure Scoliometer ATIs in preoperative patients with AIS.

Adolescent↗

Quantification of intracardiac shunts by gold-195m, a new radionuclide with a short half life.

Gold-195m, a radionuclide with a short half life (30.5 s) was used to quantify left to right intracardiac shunts. The results of this method were compared with those obtained with technetium-99m, a method that was validated against oximetry. In five patients the pulmonary to systemic flow ratio (greater than 3:1) obtained by both radionuclides indicated that the level of shunting was too high to be measured accurately. In one patient fragmentation of the bolus meant that no satisfactory gamma fit could be obtained. In the remaining 16 patients there was no significant difference between two successive 195mAu studies. The agreement between 99mTc results and 195mAu results was excellent. Oxygen administration, straight leg raising exercise, and the use of oblique projections did not affect the values of the pulmonary to systemic flow ratio. The technique of quantification of intracardiac shunts by 195mAu gives reproducible and accurate results and the low radiation dose means that it is suitable for use in children with suspected left to right shunts.

Adolescent↗

[Right accessory pathway simulating a nodo-ventricular pathway: an electrophysiologic study and intraoperative mapping].

We report a case of a patient with episodes of wide QRS tachycardia and syncope. During the electrophysiologic study, a wide QRS tachycardia (200 b/m) with left bundle branch block morphology was reproducibly induced by incremental atrial pacing with progressive shortening of the HV interval and lengthening of the AV interval, suggesting the presence of a nodoventricular accessory pathway (Mahaim fiber). The intraoperative mapping performed during tachycardia showed the earliest ventricular activation to be over the right antero-lateral AV groove, different from the usual epicardial activation previously described. According to the earliest epicardial breakthrough point, we performed an epicardial AV fat pad dissection which produced irreversible disappearance of preexcitation, confirmed at the postoperative electrophysiologic study. No recurrence of tachycardia was observed during a follow-up of 11 months. This case further confirms previous data that the "so-called" Mahaim fibers could be a right accessory pathway with decremental properties.

Adult↗

Quantitative echocardiographic analysis of the right ventricle in healthy individuals.

INTRODUCTION: Three-dimensional echocardiography and Doppler tissue imaging (DTI) are new technologies for evaluation of right ventricular (RV) size and function, but little is known about the differences of these measurements in men and women of different age groups, and how these differences can be adjusted. METHODS: In all, 54 healthy participants, mean age 59 years (range: 21-86), underwent resting echocardiography, including 3-dimensional echocardiography and DTI. RESULTS: There were significant differences in RV end-diastolic volume between men and women (129 +/- 25 vs 102 +/- 33 mL, P < .01). Adjusting to lean body mass, but not the body surface area or height, eliminated this difference (2.1 +/- 0.5 vs 2.2 +/- 0.4 mL/kg, P = not significant). DTI demonstrated that RV time to peak systolic velocity, late diastolic basal velocity, and peak systolic strain were significantly affected by increasing age (r = -0.53, P < .0001; r = 0.58, P < .0001; and r = -0.35, P < .05, respectively). CONCLUSION: Echocardiographic measures of RV size are significantly different in men and women, and indexing to lean body mass appears to be more effective than indexing to body surface area. DTI is feasible, but the amount of variation found in the measurements may be a limiting factor in the clinical application of the technology.

Echocardiography, Doppler↗

Reproducibility of leukotriene D4 inhalation challenge in asthmatics. Effect of a novel leukotriene D4/E4-antagonist (SR 2640) on leukotriene D4-induced bronchoconstriction.

We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics.

Adult↗

Variability of flow rate when collecting stimulated human parotid saliva.

The aim of this study was to estimate the accuracy and reproducibility of citric-acid-stimulated parotid saliva sampling. In healthy volunteers a strong correlation (r2 = 0.79) between flow rates from the left and right parotid gland was observed. In patients with Sjögren's syndrome this correlation (r2 = 0.90) was even stronger. The intraindividual variation in healthy volunteers was 23.3 +/- 5.9%. Increasing the number of collections did not reduce this variation significantly. In head and neck cancer patients, to estimate whether repeated measurements result in more reliable baseline values for use in clinical studies, repeated collections did not result in a significant reduction of intrapatient variation, similar to the results with the healthy volunteers. Thus, notwithstanding the good agreement between left and right flow rates, a high variation in parotid flow rates has to be considered when planning clinical trials evaluating the effects of treatment on salivary gland functioning.

Adult↗

Osteoarthritis of the knee in the rabbit produced by immobilization. Attempts to achieve a reproducible model for studies on pathogenesis and therapy.

In order to obtain a reproducible experimental model of osteoarthritis a method of immobilizing the rabbit's knee in extension by means of plastic splint was developed. The right knees of the rabbits were immobilized for periods varying from 4 days to 24 weeks. With the left knees as controls the knees were studied in a variety of ways among these being radiography (126 rabbits), histological sections stained with Alcian Blue (88 rabbits), analysis of 35S-sulphate uptake (22 rabbits) and 35S-autoradiography (6 rabbits). In 27 rabbits the regaining of mobility after immobilization was studied. After 5-6 weeks of immobilization most of the knees showed moderate or severe changes including loss of articular cartlilage and osteophyte formation. Immobilization of the rabbit's knee by this method provokes a fairly easily reproducible type of degenerative joint disease showing similarities to advanced osteoarthritis as seen in humans.

Animals↗

Right and left lung perfusion: in vitro and in vivo validation with oblique-angle, velocity-encoded cine MR imaging.

Quantification of pulmonary flow is clinically important in the evaluation of both congenital and acquired heart disease. Velocity-encoded cine magnetic resonance (MR) is a promising technique for measuring velocity and volume of blood flow. The authors report validation of the accuracy of velocity-encoded cine MR for measurement of oblique-angle flow in vitro, with use of a constant-flow phantom, and in vivo, with nine healthy volunteers in whom velocities were measured separately in the main, right, and left pulmonary arteries. Findings at MR were compared with findings at Doppler echocardiography. Velocity measurements in a flow phantom with cine MR correlated well with direct measurements at Doppler echocardiography. Velocity-encoded cine MR enabled accurate and reproducible measurement of absolute blood flow in healthy subjects. Oblique-gradient flow encoding (ie, flow-encoding direction coinciding with the true direction of flow) was the method of choice for velocity measurements in the right and left pulmonary arteries.

Adult↗

Comparison of in vitro velocity measurements in a scaled total cavopulmonary connection with computational predictions.

Minimizing pressure drop through the total cavopulmonary surgical connection (TCPC), where the superior and inferior vena cavae (SVC), (IVC) are connected directly to the right and left pulmonary arteries, is an important clinical consideration. Computational fluid dynamics (CFD) models have been used to examine the impact of connection configuration on TCPC pressure drop. However, few studies have validated CFD results with experimental data. This study compares flow field measurements on two different TCPC models at varying SVC:IVC flow rate ratios using CFD and digital particle image velocimetry (DPIV). Although the primary flow fields generated by CFD and DPIV methods were similar for the majority of flow conditions, three key differences were found: (1) the CFD model did not reproduce the 3D complexity of flow interactions in the no-offset model with 50:50 flow ratio; (2) in vitro results showed consistently higher secondary flow components within the pulmonary artery segments, especially for the no-offset model; (3) recirculation areas for the 1/2 diameter offset model were consistently higher for in vitro versus CFD results. We conclude that this numerical model is a reasonable means of studying TCPC flow, although modifications need to be addressed to ensure that numerical results reproduce secondary flow characteristics.

Blood Flow Velocity↗

Synthesis and biological evaluation of novel NK-1 tachykinin receptor antagonists: the use of cycloalkyl amino acids as a template.

In the course of a program aimed at synthesizing novel, potent NK-1 tachykinin receptor antagonists, we developed upon a bioactive model by comparing the low energy structures of a series of peptide and nonpeptide Substance P antagonists. The comparison was based on the superimposition of the aromatic rings, assuming that the rest of the molecule behaves predominantly as a template to arrange the key aromatic groups in the right spatial position. A series of 2-aminocyclohexane carboxylic acid analogues were then selected as the best templates for reproducing the postulated bioactive structure, leading to several pseudo-peptides with interesting biological activity. According to the molecular modeling, these compounds exhibit a neat parallel facing of the indolyl and naphthyl groups at about 3 A distance. Ultraviolet absorption and steady state fluorescence measurements support this conclusion, showing a linear correlation between the spectral properties and the binding affinity of these analogues. Stacking of the indole ring with naphthalene gives rise to a complex characterized by a well-defined molar extinction coefficient. Consistently, steady state and lifetime fluorescence measurements suggest that the quenching process is ascribable to ground-state interactions between the chromophores. Implications of the pi stacking propensity of aromatic groups in the biological activity of the compounds examined are briefly discussed.

Amino Acids↗

[Unusual intimal and endocardial damage following suicidal infusion of thiobutabarbital].

A suicide is reported that was carried out by i.v. infusion of thiobutabarbital. The most impressive findings were macroscopical alterations in the venous endothelium, the endocardium of the right atrium and ventricle, and the endothelium of the pulmonary artery. The same local cytotoxic side effects could be reproduced in animal experiments. The lesions are most striking after circulatory stagnation in the agonal and supravital period when highly concentrated thiobarbiturates come into contact with the endothelium.

Adult↗

The assessment of the beta-blocking activity of urapidil: a new method.

Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined.

Adrenergic beta-Antagonists↗

Somatosensory evoked potentials elicited by air-puff stimuli generated by a new high-speed air control system.

Sharp-fronted air-puffs (a rise-time of 1 msec) generated by the new high-speed air control system were used for eliciting SEPs. This system employs a rotating disk driven by a synchronous electric motor for high-speed control of air flow from a compressed air source. The air-puff is reproducible and its pressure wave form can be varied. SEPs to air-puffs or electrical stimulations of the right hand recorded from the contralateral parietal scalp had similar wave forms, but SEPs to air-puffs showed longer latencies (1-4 msec) and smaller amplitudes than those to electrical stimuli. The amplitude of early components in air-puff SEPs was on average 30% of that in electrical SEPs, but later components reached up to about 90%.

Adolescent↗

Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage--immunohistochemical investigation of dendritic damage.

We investigated the neuronal distribution of microtubule-associated protein 2 in gerbil brain and monitored the progression of ischemic damage immunohistochemically by using this protein as a dendritic marker. The reaction for microtubule-associated protein 2 in normal gerbil brain clearly visualized neuronal soma and dendrites but other structures such as axonal bundles, glia and endothelial cells exhibited little immunoreactivity. In a reproducible gerbil model of unilateral cerebral ischemia, we could detect the ischemic lesions as early as 3 min after right common carotid occlusion at the subiculum-CA1 region of the ipsilateral hippocampus as faint loss of the reaction in the dendrites. After ischemia for 30 min, the ischemic lesions were clearly detected as loss of the reaction in the nerve cell bodies, dendrites and the neuropil in the hippocampus, cerebral cortex, thalamus and the caudoputamen. Although the mechanism for prompt disappearance of the immunohistochemical reaction for microtubule-associated protein 2 is not clear, the present investigation suggests that dendrites in the vulnerable regions may be quite susceptible to ischemic stress and that the immunohistochemical procedure for microtubule-associated protein 2 may be very useful for demonstration of dendritic damage in various pathophysiological states of the central nervous system.

Animals↗

Reference values for metacarpophalangeal joint stiffness in normals.

A new form of microprocessor-controlled arthrograph is described which measures stiffness parameters of the metacarpophalangeal joints of the index, middle, and ring fingers of both hands. The apparatus is simple and quick to use and gives reproducible results. The arthrograph is used to determine the reference limits for stiffness at the middle finger of the right hand in 128 normal subjects. It is found that incorporating information on the subject's finger circumference allows a much improved precision to be achieved, but the precision is not further enhanced by including details of age and sex.

Adolescent↗

Inhibition of the bronchial response to respiratory heat exchange by increasing doses of terbutaline sulphate.

Ten asthmatic patients inhaled terbutaline sulphate (250, 500, or 1000 micrograms) or placebo on separate days, double blind and in random order, 30 minutes before isocapnic hyperventilation induced by cold air inhaled in doses that increased in a precisely controlled manner. The respiratory heat exchange (RHE) was calculated for each level of ventilation and the results were expressed as the RHE causing a fall in FEV1 of 10% (PD10RHE). The PD10RHE after placebo was highly reproducible. After terbutaline inhalation there was a highly significant shift in the RHE dose-response curves to the right and a trend towards a linear increase in PD10RHE with increasing doses of terbutaline. The subjects who were most responsive to the RHE required more terbutaline to inhibit the response completely. The results indicate that RHE dose-response curves are a precise method to examine the effects of drugs on hyperventilation-induced asthma, that increasing doses of terbutaline can produce increasing protection, and that the degree of protection is dependent on the level of increased bronchial responsiveness to RHE.

Adult↗

System 8000: computerized antenatal FHR analysis.

SYSTEM 8000 is a computerized system for antenatal fetal heart rate (FHR) analysis, with interaction online to ensure good quality recording and to minimize the time required to obtain the necessary information (based on fetal movements and tocodynamometer readings as well as FHR). The equipment consists of a Personal Computer with hard disk, interfaced to a fetal monitor. Software is written in C. An extensive definition is given on most of the functions and parameters as calculated by the system, e.g. record quality, uterine contraction peaks, basal heart rate, variation, decelerations and accelerations. System 8000 is designed to take account of the episodic changes in FHR and fetal movements characteristic of sleep states. Their presence naturally affects the mean FHR variation calculated over, say 20-30 mins. But, as the amplitude of these episodes is attenuated in association with growth retardation and hypoxaemia, the measurements of variation decline. In practice inter- and intra-observer variation is greatest in assessing FHR variation. Yet a decrease in variation is the most reliable index of fetal deterioration. The system measures FHR variation accurately and reproducibly, as well as fetal movements. In the synoptic display these two equally important fetal variables are given their rightful prominence. It has been interesting to observe how rarely the basal FHR changes in fetuses suffering progressive respiratory insufficiency, and how extreme tachycardia (a basal rate greater than 170/min) tends to reflect other fetal problems such as infection or maternal pyrexia.

Cardiotocography↗