Effect of postural changes and isometric exercise on Doppler-derived measurements of diastolic function in normal subjects

To determine if simple maneuvers that occur in daily life, such as changes in body position and isometric handgrip exercise, affect Doppler-derived measurements of diastolic function, we studied 22 normal male subjects in the supine position at rest and during several postural manipulations and during handgrip exercise. Comparison of values obtained in the 80 degrees upright tilt position with those obtained in the standard supine position revealed significant decreases in early diastolic flow velocity (peak E) (-25 +/- 3 percent; p less than 0.001), late diastolic flow velocity (peak A) (-9 +/- 3 percent; p less than 0.01), and the ratio of early to late flow velocities (E/A ratio) (-17 +/- 4 percent; significant increases in deceleration time (+55 +/- 10 percent; p less than 0.001) and isovolumic relaxation time (+38 +/- 4 percent; p less than 0.001). Comparison of values obtained with supine isometric exercise with those obtained during the preceding supine resting state revealed significant decreases in peak E (-12 +/- 3 percent; p less than 0.001) and the E/A ratio (-21 +/- 4 percent; p less than 0.001) and significant increases in peak A (+15 +/- 4 percent; p less than 0.001) and isovolumic relaxation time (+16 +/- 3 percent; p less than 0.001). The response of Doppler-derived measurements of diastolic function to postural changes and isometric exercise is complex and multifactorial. Interpretation of these measurements must take into account changes in loading conditions.     

Face mask spirometry and respiratory pressures in normal subjects.

Spirometry and maximal respiratory pressures are pulmonary function parameters commonly used to evaluate respiratory function. Prediction values are available for conventional lung function devices using a standard tube or flanged type of mouthpiece connection. This equipment is not suitable for patients with facial or buccal muscle weakness, because of air leakage around the mouthpiece. A face mask was used for the portable lung function devices used in the neuromuscular department. The aim of this study was to compare the face mask and the conventional mouthpiece for the measurement of spirometry and of respiratory pressures in 22 healthy subjects. Values obtained with the conventional mouthpiece differed significantly from values obtained with the face mask. With the mask, forced vital capacity and forced expiratory volume in one second were 200 mL lower, and maximal expiratory pressure was 3.2 kPa lower than with the mouthpiece. Subsequently, new prediction values for face mask spirometry and maximal respiratory pressures were obtained from 252 other healthy subjects, from which new prediction equations were derived. It was concluded that the face mask connection to the lung function device is a valid alternative, is easy to use and is most useful to monitor changes in patients. This study confirms the importance of appropriate prediction equations, depending on subject-instrument interfaces.     

Effect of postural changes, nitroglycerin and verapamil on diastolic ventricular function as determined by radionuclide angiography in normal subjects

Whereas improvement in diastolic function indexes in response to therapeutic interventions has been attributed to a beneficial effect of the intervention, measurements of diastolic function appear to be influenced by changes in loading conditions, heart rate and sympathetic tone. To determine the effect of body position and short-term pharmacologic intervention on radionuclide angiographically determined left ventricular peak filling rate, high temporal resolution time-activity curves and absolute left ventricular volumes obtained by equilibrium-gated blood pool scans were evaluated in 12 normal subjects in the supine position at rest and in response to several postural and pharmacologic manipulations. This study confirmed the reproducibility of the technique and demonstrated that in normal subjects, peak filling rate varies in response to changes in body position and to short-term administration of sublingual nitroglycerin and intravenous verapamil. Peak filling rate ranged from 3.3 to 5.1 end-diastolic volumes (EDV)/s with a variability of 13.7% during five baseline supine measurements in the 12 subjects. Compared with values in the supine position (mean +/- SEM = 4.38 +/- 0.24 EDV/s), peak filling rate increased +16 +/- 6% to 4.75 +/- 0.27 EDV/s in the upright position (p less than 0.05) but did not change significantly with leg elevation. Peak filling rate at baseline and during postural changes correlated significantly with ejection fraction (r = +0.49), with stroke volume (r = +0.26) and inversely with end-systolic volume (r = -0.41), but did not correlate with heart rate or blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of volume expansion and contraction in normotensive whites, blacks, and subjects of different ages.

We studied the blood pressure, natriuretic, kaliuretic and humoral responses of 347 normal subjects after volume expansion and volume contraction to examine possible differences among whites, blacks and subjects of different ages. According to outpatient 24-hour urine collections, blacks excreted less sodium and potassium than whites. After similar states of sodium intake were achieved among all subjects, 2 liters normal saline were given i.v. Blacks and subjects greater than or equal to 40 years excreted less sodium than whites or subjects less than 40 years, over a 24-hour period. In addition, blacks excreted less potassium. The delay in sodium excretion occurred during the first 12 hours after the salt load. Blacks had a greater suppression of plasma renin activity than whites 24 hours after saline. Blacks also had higher blood pressures than whites after saline administration; their pressure remained elevated until furosemide was given. Furosemide, 120 mg over 24 hours, evoked greater natriuresis, but less kaliuresis in blacks than in whites. The greater prevalence of hypertension in both blacks and older subjects may be related to relatively blunted natriuretic responses when these groups engage in the high sodium-low potassium intake characteristic of our society.     

Total folate binding capacity of normal human plasma, and variations in uremia, cirrhosis, and pregnancy.

The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325 pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements.     

Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages.

Serum and granulocyte elastase-type protease activities were determined simultaneously with their main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic (ATS) subjects. The age-related associations of these parameters were also investigated. Serum elastase-type protease activity increased, but not statistically significantly, with aging in both control and ATS subjects. The enhancement of elastase-type protease activity in sera of ATS patients was significantly (p less than .02) greater than control subjects only in the case of the elderly. The granulocytes' elastase activity was significantly greater in granulocytes derived from both middle-aged and elderly ATS patients (p less than .03 and p less than .06) compared to age-matched control subjects. Alpha-1-antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was significantly lower in sera of ATS subjects compared to age-matched control subjects (p less than .01). The conclusion is that increased elastase-type activity and decreased antiproteinase activity should be considered as potential factors in atherosclerotic arterial wall damage. The similarity of the results in the elderly and the ATS subjects suggest that atherosclerosis is an early aging process.     

Fasting-induced changes in thyroid hormone economy in normal and acromegalic subjects.

To study whether high growth hormone (GH) milieu may counteract fasting-induced changes in thyroid hormone economy, we measured basal and TRH-stimulated TSH concentrations as well as thyroxine (total, TT4 and free, FT4), total triiodothyronine (TT3) and total reverse T3 (TrT3) before and after a 6-day fast in 6 healthy men and in 8 patients with acromegaly. Baseline values for all parameters were similar in both groups. Fasting induced similar increases in TT4 and TrT3 concentrations and a similar decline in TT3 concentrations in both groups. The TT3/TT4 and TrT3/TT4 ratios changed identically in both groups. We conclude that high GH is incapable of altering fasting-induced changes in thyroid hormone economy.     

Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases

In an attempt to establish the relevance of ciliary ultrastructure to the pathophysiologic aspects of respiratory tract disease, we compared quantitatively the ultrastructure and function of cilia from healthy subjects (atopic and nonatopic nonsmokers, asymptomatic smokers) and patients with a variety of respiratory diseases (cystic fibrosis, chronic rhinitis, bronchiectasis associated with hypogammaglobulinemia, chronic bronchitis) with cilia from patients with primary ciliary dyskinesia (PCD). In healthy subjects and patients with non-PCD respiratory disease, approximately 5% of the cilia evaluated had ultrastructural abnormalities. Ciliary beat frequency was significantly higher in the chronic rhinitis group (15.3 +/- 1.2 Hz) than in the other non-PCD groups, which were within the normal range (12.5 +/- 1.7 Hz), and in all non-PCD cases ciliary wave form was normal. In each of these groups, normal mucociliary transport had been previously demonstrated. By contrast, in patients with PCD, the proportion of cilia with ultrastructural abnormalities was significantly greater than in the normal subjects and those with non-PCD respiratory disease (p less than 0.0001). In addition, beat frequency was significantly reduced, ciliary wave form was grossly abnormal, and pulmonary and nasal mucociliary transport were virtually absent. These findings demonstrate the relevance of ciliary ultrastructural abnormalities to altered ciliary function and lend support to the primary role of the demonstrated abnormalities in the respiratory tract disease of PCD.     

Relationship between inspiratory mouth pressure and respiratory muscle activity in normal subjects.

The relationship between inspiratory mouth pressure and respiratory muscle activation was investigated in 20 normal non-smoking subjects (13 males). Surface electromyography (EMG) was recorded from the seventh intercostal space bilaterally during different levels of inspiratory effort monitored by a respiratory mouth pressure gauge. The mouth pressure and EMG relationship was non-linear between 20 and 100% of inspiratory effort. Quadratic regression analysis was performed between percent inspiration and percent EMG on each side of the chest. The regression equation and coefficient of determination (r2) for the right side were y = 9.73 (e0.024x-1), r2 = 0.91, and for left side were y = 10.79 (e0.023x-1), r2 = 0.88. An independent t-test did not reveal significant difference (P > 0.05) between the slopes of the regression lines from the two sides of the chest. Therefore, results of the two sides were pooled and the predictive regression equation for the combined results was y = 10.05 (e0.0236x-1). Reasons for such a non-linear relationship may include the loading mechanism of respiratory muscles, inefficiency of intercostal muscles at high levels of inspiration, their recruitment pattern and the histochemical characteristics of respiratory muscles. Since absolute EMG values cannot be used to assess changes in activation on different days, further work is required to establish the between-day repeatability of the technique described which is potentially useful for assessing respiratory muscle function pre- and post-operatively in chest surgery patients.     

Physiological changes in circulating mannose levels in normal,glucose-intolerant,and diabetic subjects

Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM.