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H J Smith

Publications and source records attributed to H J Smith.

At least 55 records · Page 3Linked to original sources

Measurement of respiratory impedance by impulse oscillometry--effects of endotracheal tubes.

Impulse Oscillometry is a new, noninvasive method to measure respiratory impedance, i.e. airway resistance and reactance at different oscillation frequencies. These parameters are potentially useful for the monitoring of respiratory mechanics in the critically ill patent with respiratory dysfunction. The endotracheal tube, used to mechanically ventilate these patients, however, represents an additional nonlinear impedance that introduces artifacts into the measurements. The objective of this work was therefore to investigate the effects of clinically available endotracheal tubes on resistance and reactance of an in vitro analogue of the respiratory system. Additionally, the effects of decreasing the compressible gas volume in this experimental model, as a simulation of decreased lung capacity and compliance, was investigated. Impulse oscillometric measurements of the test analogue gave highly reproducible results with and without an endotracheal tube. The tubes had significant influence on the measurement of the test object at all frequencies investigated. Changes of low frequent reactance were negligible - at least if repetitive measurements of the same system are performed - for realistic measurement of airway resistance, a correction of the tube impedance or measurement of the pressure distal of the tube is required. Resistance increased and low frequent reactance decreased significantly with decreasing gas volume. These changes were of magnitudes higher than the variations due to the introduction of the endotracheal tubes. Our results suggest that changes of respiratory reactance measured with impulse oscillometry may be used as a monitoring parameter in intubated patients.

Airway Resistance↗

Effect of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts: modulation by eicosapentaenoic acid.

The effect of a proteolysis inducing factor (PIF) on protein synthesis and degradation and the modulation of this effect by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA), have been examined using a surrogate model system, C2C12 myoblasts in vitro. After 90 min of incubation, PIF produced a significant inhibition of protein synthesis in a dose-dependent manner, with maximal inhibition at a concentration of 4 nM. The effect was attenuated both by treatment with a monoclonal antibody to PIF and by treatment with insulin at physiological concentrations (1 nM) and below (0.1 nM), but not by EPA (50 microM). The inhibitory effect on protein synthesis was transitory and was not seen after prolonged incubation with PIF. An increased rate of protein degradation was observed in C2C12 myoblasts after addition of PIF, which was also maximal at a concentration of PIF of 4 nM. Higher concentrations of PIF did not produce an increase in protein degradation. Unlike the effect on protein synthesis, the enhanced protein degradation was completely abolished by pretreatment with 50 microM EPA, suggesting that the two effects are mediated by different mechanisms. PIF produced an increased release of [3H]arachidonic acid from prelabeled myoblasts with a dose-response curve parallel to that of protein degradation and with a maximum at 4 nM PIF. Release of [3H] arachidonic acid was completely blocked in cells pretreated with 50 microM EPA, suggesting that the effect was related to protein degradation. The [3H]arachidonic acid was rapidly metabolized to prostaglandins E2 and F2alpha and to 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs). Production of all eicosanoids was attenuated in cells pretreated with EPA. Of all of the metabolites, only 15-HETE produced a significant increase in protein degradation in C2C12 myoblasts with a maximal effect at 30 nM and with a bell-shaped dose-response curve similar to that produced by PIF. These results suggest that PIF enhances protein degradation as a result of an increased production of 15-HETE.

Animals↗

Dual modes of the carbon cycle since the Last Glacial Maximum.

The most conspicuous feature of the record of past climate contained in polar ice is the rapid warming which occurs after long intervals of gradual cooling. During the last four transitions from glacial to interglacial conditions, over which such abrupt warmings occur, ice records indicate that the CO2 concentration of the atmosphere increased by roughly 80 to 100 parts per million by volume. But the causes of the atmospheric CO2 concentration increases are unclear. Here we present the stable-carbon-isotope composition (delta 13 CO2) of CO2 extracted from air trapped in ice at Taylor Dome, Antarctica, from the Last Glacial Maximum to the onset of Holocene times. The global carbon cycle is shown to have operated in two distinct primary modes on the timescale of thousands of years, one when climate was changing relatively slowly and another when warming was rapid, each with a characteristic average stable-carbon-isotope composition of the net CO2 exchanged by the atmosphere with the land and oceans. delta 13 CO2 increased between 16.5 and 9 thousand years ago by slightly more than would be estimated to be caused by the physical effects of a 5 degrees C rise in global average sea surface temperature driving a CO2 efflux from the ocean, but our data do not allow specific causes to be constrained.

Antarctic Regions↗

Left atrial volumes assessed by three- and two-dimensional echocardiography compared to MRI estimates.

OBJECTIVES: The aim of the present study was to establish the accuracy and reproducibility of left atrial volume measurements by three-dimensional (3D) echocardiography compared to 2D biplane and monoplane measurements. BACKGROUND: No echocardiographic technique is generally accepted as optimal for estimation of left atrial size. METHODS: Left atrial volumes of 18 unselected cardiac patients were obtained with magnetic resonance imaging (MRI) (volumes 145 +/- 58 ml). These volumes were compared with those obtained with different echocardiographic methods: a multiplane 3D method based on 90 images acquired by apical probe rotation, a simplified 3D method using only the three standard apical views, and 2D biplane and monoplane methods based on area-length, disc summation and spherical formulas. RESULTS: The echocardiographic methods significantly underestimated maximum left atrial volumes as obtained by MRI by 14-37% (p < 0.001). Accuracy, expressed as 1 SD of individual estimates around this systematic underestimation, was 25 to 27% for all methods, except for the 2D 2-chamber monoplane method (37%). Interobserver coefficient of variation was between 14 and 20% for all methods (n.s.). CONCLUSION: All echocardiographic methods significantly underestimated left atrial volumes as obtained by MRI. A minor non-significant improvement in individual echocardiographic estimates by the 3D methods was obtained at the cost of more time consumption. In unselected patients ultrasound image quality precludes significant improvement of left atrial volume measurements by the applied 3D methods.

Aged↗

Cardiac MR imaging.

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Electrocardiography↗

Inhibition of aromatase (P450Arom) by some 1-(benzofuran-2-ylmethyl)imidazoles.

Studies of a series of 1-(benzofuran-2-ylmethyl)imidazoles, 1-5, previously proposed as potential agents for prostatic cancer by their inhibition of 17beta-hydroxylase:17,20-lyase (P450 17), have been extended to their selectivity against placental microsomal aromatase (P450(Arom)) in man. The compounds were 3-7-fold more potent than aminoglutethimide and had some selectivity for P450 17 as expressed by the ratio (IC50 P450(Arom))/(IC50 P450) 17)/17.0 (2), 10.3 (3), 34.6 (4) and 42.0 (5), where IC50 is the concentration resulting in 50% inhibition. The lower potency of 1-5 towards P450(Arom) compared with the racemic alpha-phenyl-substituted compounds (6, 80-1000 x aminoglutethimide) and some racemic alpha-methyl (8.5 and 12.2 x aminoglutethimide) and alpha-ethyl (12.1 and 32.9 x aminoglutethimide) analogues has been rationalized. This work selectively extends studies of the P450 17 inhibitor 5, a potential prostatic cancer agent, towards other cytochrome P450 enzymes in the steroidogenic pathway and provides a general method for determining the relative influence of chemical manipulation of a parent inhibitor towards two enzymes in the pathway using additional literature data.

Aromatase↗

Measurement of respiratory impedance in healthy calves using the impulse oscillation technique--physiological and methodological aspects.

The aim of the present study was to investigate methodological and physiological aspects of complex respiratory impedance measurements in calves using the impulse oscillation technique. To apply the system to animals, a tightly fitting face mask was used. The measuring system was modified by placing a flexible tube between the pneumotachograph and the loudspeaker. Complex respiratory impedance measurements were not significantly influenced by the modification. Linear correlations were found between body weight and respiratory impedance; as body weight increased, resistance decreased and reactance increased. The methodological variability of impedance measurements using the impulse technique was found to be extremely small. Diurnal variations of respiratory impedance were considered to be the main source of intra-individual variability. When comparing different animals (even when healthy and matched for age and body weight) our results suggest that inter-individual biological variability must be carefully considered.

Aging↗

Some 1-[(benzofuran-2-yl)methyl]imidazoles as inhibitors of 17 alpha-hydroxylase: 17, 20-lyase (P450 17) and their specificity patterns.

Four 1-[(benzofuran-2-yl)methyl]imidazoles (1-4) have been evaluated as in-vitro inhibitors of human testicular and bovine adrenal microsomal 17 alpha-hydroxylase: 17,20-lyase (P450 17) as potential anti-prostatic agents. Their specificity towards other steroidogenic and liver enzymes has been compared with that of ketoconazole. All four compounds were inhibitors of the testicular enzyme (2, IC50 (concentration resulting in 50% inhibition) 0.185 microM; 4, IC50 0.18 microM) but less potent than ketoconazole (IC50 0.03 microM). Towards bovine adrenal enzyme 2 and 4 were 35- and 31-fold more potent than ketoconazole (IC50 = 39.8 microM). Compound 2 is a useful lead compound but although less potent than ketoconazole towards P450SCC and P450 11 beta, but not P450C21, at the enhanced dose required for equivalent effects in-vivo on P450 17 it is likely that cortisol and aldosterone production will be affected to a greater extent than with ketoconazole.

Animals↗

Enantioselectivity of some 1-(benzofuran-2-yl)-1-(1-H-imidazol-1-yl) alkanes as inhibitors of P450Arom.

The low stereospecificity of the enantiomers of 1-[(benzofuran-2-yl)-4-chlorophenylmethyl]imidazole (6, R=H, R'=4'-Cl) and the corresponding 4-fluoro compound as inhibitors of aromatase (P450Arom) has been explored using 1-(5,7-dichlorobenzofuran-2-yl)-1-(1H-imidaz-1-yl)ethane (7, R1=R2=Cl, R=CH3), -propane (7, R1=R2=Cl, R=C2H5), and the corresponding 5,7-dibromo compounds resolved as their dibenzoyl-D (or -L) tartrates. Low enantioselectivity ratios of 4.8 (5,7-diCl) and 12.6 (5,7-diBr) were shown for the ethanes. The values for the corresponding propanes were 8.3 and 5.2, respectively, and for these compounds the stereoselectivity was reversed.

Alkanes↗

[Comparison of anterior rhinomanometry and impulse oscillometry in nasal provocation with histamine].

UNLABELLED: Anterior rhinomanometry (aR) is the standard method for measurement of nasal resistance, but it has some drawbacks because it requires full co-operation of the patient and the results are disturbed by forced ventilation due to stenosis. The patient must generate flow by active ventilation. Resistance results from the flow/pressure ratio. Forced oscillation technique (IOS) does not affect spontaneous breathing. Flow/pressure ratio is generated externally by a loudspeaker. IOS measures not only resistance but also reactance. Whereas former methods used only a single frequency IOS is capable of applying and analysing frequencies between 0 and 100 Hz. The range from 5 to 35 Hz is useful for diagnostic issues. We compared IOS with aR in nasal provocation tests with histamine and checked the sensitivity of resistance (R) and reactance (X) at different frequencies. METHOD: 20 patients (13 m, 7 f) underwent nasal challenge test using increasing doses of histamine (max. 3.2 mg). Resistance (aR, IOS) and reactance (IOS) were measured parallel. To compare the two methods, we calculated the dose of histamine which is required to double nasal resistance. RESULTS: 1. IOS demonstrates the increase of R at all frequencies. 2. The highest increase of R is measured at a frequency of 5 Hz (5 Hz: NaCl 0.41 +/- 0.25; Hist. 1.26 +/- 0.57; 35 Hz: NaCl 0.36 +/- 0.172; Hist. 0.60 +/- 0.1 kPa/l/s, p < 0.001). 3. The critical dose is significantly lower in IOS than in aR (2.29 +/- 2.59 vs. 1.06 +/- 1.16 mg/ml, p < 0.02). 4. Basal values of R do not differ significantly between aR and IOS (0.37 +/- 0.12 vs. 0.41 +/- 0.25 kPa/l/s, p < 0.001). CONCLUSIONS: We conclude from our results that IOS is at least equivalent to aR in measuring nasal resistance. R at 5 Hz is the most important parameter in IOS. IOS is less dependent on the cooperation of the patient. In case of stenosis it does not require forced ventilation to achieve the required flow-pressure ratio.

Adult↗

Outcome of bypass surgery in patients with chronic ischemic left ventricular dysfunction. Predictive value of MR imaging.

PURPOSE: To determine the preoperative findings of MR imaging of the left ventricle (LV) that could best predict the functional outcome of the LV after surgical revascularization. MATERIAL AND METHODS: Patients with angina pectoris, previous myocardial infarction, and dysfunction of the LV, and who had a preoperative cine MR, were re-evaluated after bypass surgery with MR in a study on the effects of revascularization after mean 22 months. RESULTS: Angina pectoris was relieved in all patients except one, but the maximum workload during the exercise test was increased in only 3 patients. Coronary angiography showed that 37 of 45 (82%) of the distal anastomoses were open. The LV ejection fraction was the same before and after operation both at angiography and MR imaging. MR showed LV end-diastolic volume to be increased from 190 +/- 50 ml to 250 +/- 70 ml. Compared to angiography, MR provided additional information regarding myocardial wall thickness and function, and the size of myocardial infarction. Improvement in systolic wall thickening was seen in 65% of the segments that had had an end-diastolic wall thickness (EDWT) greater than 15 mm before operation, while only 4% of the segments with EDWT < 6 mm improved. In the wall thickness range of 6-15 mm, MR was unable to predict the functional outcome of the LV. CONCLUSION: Preoperative MR findings of thick myocardial walls with poor function seem predictive of improved function after revascularization. When the LV wall thickness is less than 6 mm, no improvement should be expected.

Aged↗

The diagnostic capacity of forced oscillation and forced expiration techniques in identifying asthma by isocapnic hyperpnoea of cold air.

The measurement of forced expiratory volume in one second (FEV1) is often used to assess the effect of bronchial provocations, and deep inspiration is required beforehand. This may briefly alter the bronchial tone in a variable way in some subjects. The forced oscillation technique (FOT) is a test used to characterize the mechanical impedance of the respiratory system, and prior deep inspiration is not required. We tested the hypothesis that measurable bronchoconstriction would occur in all asthmatic subjects stimulated with isocapnic hyperventilation of dry cold air (IHCA). Twenty patients with mild asthma and nine healthy controls were exposed to IHCA, at 70% of their maximal voluntary ventilatory capacity for 4 min and the results were assessed both by applying the FOT and by measuring FEV1. Optimal cut-off levels were defined by receiver operating characteristic (ROC) curve analyses of the changes in respiratory resistance and reactance at 5-35 Hz, resonant frequency (fres) and FEV1. A positive result was present in the asthmatics when measured by FOT, and using ROC analyses the discriminative capacity to correctly diagnose asthma was greatest for responses in fres; the sensitivity was 89% and the specificity 100%. The sensitivity of FEV1 to correctly diagnose asthma was only 73%, and the specificity 88%. In conclusion, the results of this study suggest that the use of forced expiratory volume in one second for bronchial provocation tests by isocapnic hyperventilation of dry cold air may be misleading and that the bronchoconstriction thus elicited is measured with greater sensitivity and specificity by the forced oscillation technique than by forced expiratory volume in one second.

Adult↗

[Technical adaptation of impulse oscillometry to special research conditions].

The technical adaptation of the Impulse-Oscillometry (IOS) to different conditions of measurement allows a wide range of applications so that even questions of peripheral user groups using lung function tests can be answered. Thus, the variable connection of the IOS head via fold hose opens the field of bedside measurements and additional applications in pediatrics, intensive care and veterinary medicine. Rhinomanometric examinations are possible with little expenditure and high practicability using nasal tips.

Adult↗

[Impulse oscillometry and body position].

To assess diurnal profiles of impulse-oscillometry (IOS) changes of IOS-parameters between different body positions have been studied using a special set IOS-Bedside for individual home care. IOS has been applied in lateral lying and in sitting position in 20 healthy female and male probands, aged 10-67, during 24 hours in intervals of 3 hours. In each test during normal breathing for approximately 30 sec about 130 spectral and structural analyses have been performed at an impulse distance of 0.2 sec. The global means of resistance at 5 Hz (R5) in lying position are in men about 0.6 and in women about 0.3 hPa/l/s higher than in sitting position, those of reactance in men and women are only about 0.2 hPa/l/s lower. There is a distinct diurnal periodicity of the differences. The maxima of them may occur at different hours of the day in single probands; but at the average mean the maxima are found at the end of night. The differences of oscillation parameters between lying and sitting position are bigger at end-expiration than at end-inspiration. The resistance-flow-gradients, representing the component of turbulent flow, are enlarged in lying position especially at night.

Adolescent↗

[Diurnal profile of impulse oscillometric impedance in healthy subjects].

Diurnal profiles of impulse oscillometry during 24 hours in 3 hour intervals in sitting and lateral lying position have been studied in 20 healthy female and male probands 10-67 years of age. Approximating the profiles by a sine-cosine-function the amplitude of resistance was found up to 3, that of reactance up to 1 hPa/l/s in single cases, preferably for end-expiratory values and for the resistance-flow- and the resistance-volume-gradients, more pronounced in lying than in sitting position. The daytime reaching maxima of resistance and minima of reactance is different in single individuals. Single persons with obviously high vitality or sensibility showed very high amplitudes reproducible within IOS measuring limits of 0.2 hPa/l/s after 6 months.

Adolescent↗