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Biomedical subjects

N K Burki

Publications and source records attributed to N K Burki.

At least 19 recordsLinked to original sources

The effects of acetazolamide on the ventilatory response to high altitude hypoxia.

Acetazolamide treatment ameliorates the symptoms of AMS; however, the mechanism by which this occurs is unclear. To examine the effects of acetazolamide on oxygenation, CO2 responsiveness and ventilatory pattern during acute exposure to HA, we studied two groups of subjects at SL and following rapid (less than 8 h) transport to HA. Acetazolamide or placebo tablets were given to groups 1 and 2, respectively, in a double-blind manner after baseline SL measurements; treatment was continued during HA exposure. There was no difference in the ventilatory pattern at HA, between the two groups. While the Ve achieved in response to CO2 at HA vs SL was much greater in each group the percent change from baseline at HA versus that at SL was not significantly different. The beneficial effects of acetazolamide in AMS are associated with a higher level of ventilation at HA and better oxygenation: CO2 chemosensitivity is not affected by acetazolamide at HA.

Acetazolamide

Pulmonary function in the elderly: response to theophylline bronchodilation.

This clinical investigation was designed to characterize the pharmacologic response to theophylline in elderly individuals. Incremental theophylline plasma concentrations (0, 5, 10, 15, and 20 mcg/mL), achieved through dose escalation of intravenous aminophylline, were correlated with pulmonary airway responses in ten young and ten elderly male asthmatic volunteers. The older group had lower baseline pulmonary function values, suggestive of a greater degree of baseline airways obstruction. Despite wide intersubject variability, the elderly subjects demonstrated a lower absolute change in bronchodilator response to equal concentrations of theophylline than did their younger counterparts (P less than .05). A progressive increase in heart rate was noted with increasing theophylline concentrations, but no significant difference in heart rate change between groups was detected (P greater than .05). Whether the difference in theophylline induced bronchodilator response observed in the young and elderly groups is due to a difference in age or in severity of airway obstruction is yet unknown.

Adult

Effects of sequential doses of parenteral terbutaline on plasma levels of potassium and related cardiopulmonary responses.

beta-agonist bronchodilator drugs are known to cause hypokalemia; nevertheless, successive parenteral doses are recommended for the treatment of status asthmaticus. The metabolic and cardiopulmonary effects of sequential, subcutaneous doses of terbutaline were studied in eight stable adult asthmatic patients. Each subject received terbutaline, 0.25 mg subcutaneously, followed 30 min later either by a second subcutaneous dose of terbutaline (sequential) or normal saline (single) in a randomized, double-blind, crossover fashion. Maximum reductions in plasma potassium from baseline were significantly greater (p less than 0.05) following sequential treatment compared to single treatment (-1.1 versus -0.6 mEq/L, respectively). Improvements in forced expiratory volume in 1 s were temporally related to changes in serum potassium and were significantly greater (p less than 0.01) following sequential terbutaline treatment. Prolongation of the QTc interval occurred following both treatment regimens. The change in QTc was statistically significant only following sequential treatment, increasing from 377 +/- 21 to 441 +/- 39 ms (p less than 0.05). Sequential doses of parenterally administered terbutaline result in clinically significant reductions in plasma potassium that are temporally related to changes in pulmonary function and associated with important electrocardiographic alterations.

Adult

The relationship of resting ventilation to mouth occlusion pressure. An index of resting respiratory function.

In order to examine the relationship of mouth occlusion pressure (MOP), an index of central inspiratory neuromuscular drive, to age and sex and to resting ventilation (VE), measurements were made in the seated posture in 84 healthy, normal subjects (38 men, 46 women; ages 18-72 years, mean +/- SD = 39.8 +/- 14.5 years) and in 79 patients with either airways obstruction (n = 63) or restrictive lung disease (n = 16). In the normal subjects, there was no significant relationship between age or sex and MOP (expressed as P0.1), which is the mouth pressure developed against a complete occlusion at 0.1 s after the beginning of inspiration, and dP/dtmax, the maximal rate of rise of this pressure; mean +/- SD for P0.1 = 0.75 +/- 0.32 cmH2O, and dP/dtmax = 19.41 +/- 10.10 cmH2O/s. Similarly, there was no significant relationship between age or sex and VE/P0.1 or VE/dP/dtmax. In 99 percent of normal subjects (83 of 84), VE/P0.1 was greater than 8.0 L/min/cmH2O, whereas in only 1 of the 79 patients was the value greater than 7.9 L/min/cmH2O. While the mean values of P0.1 and dP/dtmax were significantly different between normal subjects and patients, there was considerable overlap, whereas the ratio VE/P0.1 or VE/dP/dtmax provided excellent differentiation between normal subjects and patients with lung disease. This index, which is easily measured and requires minimal patient cooperation, provides valuable information in the clinical assessment of ventilatory drive and lung mechanics.

Adult

Airways responsiveness determined by consecutive histamine challenges in asymptomatic asthmatics.

The effect of two consecutive histamine inhalation challenges on airways responsiveness was assessed in a group of eight nonsmoking nonmedicated asthmatics aged 19-27 yr. All subjects had a base-line forced expiratory volume in 1 s (FEV1) of greater than 80% of their predicted normal value before the initial challenge and were allowed to recover to greater than 95% of the initial base-line FEV1 value before the second challenge was initiated. The average airways recovery time after the first challenge was 44 min but ranged between 30 and 90 min. The mean +/- SD values of cumulative histamine dose units provoking a 20% decrease of the FEV1 from the buffer control value (PD20FEV1) were 10.79 +/- 5.95 determined with the first and 30.50 +/- 46.36 with the second challenge (P greater than 0.05). We conclude that sequential histamine challenges performed in mild asthmatics with closely controlled prechallenge airways function are well tolerated. Although some variance does exist in intersubject airways recovery time and in intra-subject histamine airways responsiveness determined by sequential challenges, our data do not support recent observations (J. Appl. Physiol. 63: 1572-1577, 1987) that histamine tolerance is a characteristic finding associated with bronchial asthma.

Adult

Pulmonary gas exchange during histamine-induced bronchoconstriction in asthmatic subjects.

Bronchial provocation for testing airway hyperreactivity is now well-established. However, the effects of histamine-induced bronchoconstriction on pulmonary gas exchange in man have not been systematically studied. We empirically noted marked decreases in PaO2 in some asthmatic subjects following induced bronchoconstriction. Nine subjects with mild, stable asthma were studied, each on two separate days. The first determined the dose of inhaled histamine necessary to decrease FEV1 by 20 percent and the relationship to lung volume and to pulmonary resistance by the interrupter technique (Rint). On the second day arterial blood gases, ventilation, Rint, and the anatomic (VDan) and physiologic (VDphys) dead spaces were measured simultaneously. There was a significant (p less than 0.05), profound fall in PaO2 (mean, -21.8 mm Hg) and in P(A-a)O2 (mean +14.7 mm Hg) within 5 min after bronchoconstriction, associated with a significant (p less than 0.05) increase in respiratory frequency (mean +5.1 min-1); and decrease in tidal volume (mean, -0.3 L). The ratio VDphys/VT increased significantly (p less than 0.05; mean change, +0.08) even though VDan and VDphys did not. Bronchoconstriction induced the broadening of ventilation (V)/perfusion (Q) ratios, with, most likely, an increase in areas of high V/Q. Histamine-induced bronchoconstriction in mild asthma results in a marked fall in PaO2 due to induced V/Q inequality. Therefore, histamine airway challenge should be used with caution in patients with any preexisting hypoxemia.

Adult

Measurements of ventilatory regulation.

The ventilatory control system, although not yet fully understood, is a complex interaction of volitional and reflex mechanisms extending from the cerebral cortex to receptors in the lungs and chest wall. Measurements of ventilatory control mechanisms can be made at rest, during exercise, during sleep, and during hypercapnic or hypoxic stimuli. Measurements of ventilation, ventilatory pattern, and mouth occlusion pressure at rest provide valuable information on ventilatory control mechanisms; these measurements can be extended by measurements of diaphragmatic EMG (indicating central neural output) and measurements of ventilation and mouth occlusion pressure during CO2 or hypoxic stimulation. Clinical assessment of ventilatory control abnormalities requires an understanding of the basic features of the control system and a logical application of the available tests.

Humans

Dyspnea.

Dyspnea, an unpleasant sensation of difficulty in breathing, is a common accompaniment of cardiopulmonary disease. The underlying mechanisms generating this sensation are not clearly understood. There does not appear to be any one specific site or specific receptor(s) involved in this sensation; however, reflex increase in central respiratory motor "command," as well as activity of the respiratory muscles, appear to be necessary for the genesis of the sensation. Whether there is a direct dyspnogenic effect of changes in chemical drive (increased arterial PCO2 or decreased arterial PO2) is unclear. Several methods to quantify dyspnea for clinical purposes have been described; techniques using exercise as the stimulus and expressing the response on a visual analogue or Borg category scale appear to be clinically applicable. The specific treatment of dyspnea remains in the experimental stage. The direct effects of exercise conditioning are unclear. A number of drugs (mainly central nervous system depressants) have been examined; preliminary work holds promise, but no particular drug can as yet be recommended for routine clinical use.

Dyspnea

Spirometry and flow-volume curves in healthy, normal Pakistanis.

Previous studies have indicated that lung volumes in healthy, normal Pakistani adults are smaller than measurements reported in comparable healthy European populations; in order to confirm these findings and to examine the relationship of maximal expiratory flow rates to lung volumes, we studied 250 non-smoking healthy subjects (116 men and 114 women) between the ages of 18 and 65 years. The population sample was drawn from urban and rural areas of Pakistan, with low levels of air pollution. The results indicate that the forced vital capacity (FVC) and forced expired volume in 1 second (FEV1) were lower in the Pakistani population compared to European populations and North American populations of European descent. These data are in conformity with previous studies; however, in Pakistani men the effects of age on FVC and FEV1 were slight so that, after the fourth decade, the FVC and FEV1 values are very comparable between the European and Pakistani populations. Amongst Pakistani women, on the other hand, FVC and FEV1 remained lower than in their European counterparts throughout adult life. Maximal expiratory flow rates amongst the men did not correlate with age, and these values were very similar to those reported in age-matched European populations. In women, however, there was a significant correlation of maximal flow rates with age and height, and the maximal expiratory flows were decreased compared to European populations. These data indicate that in Pakistani men pulmonary mechanics may be different to their European counterparts, allowing for higher maximal expiratory flows at any given lung volume.

Adolescent

The relationship between exercise-induced asthma and plasma catecholamines.

In asthmatics, exercise (E1) is known to induce bronchoconstriction; a second period of exercise (E2) within 30 to 90 min induces a lesser degree of bronchoconstriction. The reason for the "refractory" bronchoconstrictor response to E2 is unclear. We studied 6 normal subjects (Group 1) and 12 stable asthmatics to examine the possible relationship between the refractory period and sympathoadrenal function. The asthmatics were further divided into 2 groups, based on the absence (Group 2, n = 5) or presence (Group 3) of an exercise-induced bronchoconstrictor response. In each subject/patient, after control measurements of spirometry and venous blood sampling, a standard level of treadmill exercise was performed, and blood and spirometry were obtained at 1, 5, 15, and 25 min after the end of exercise. A second period of treadmill exercise, of the same level and duration, was then performed, and blood sampling and spirometry were repeated at the same time intervals after the end of exercise. There was no significant (p less than 0.1) difference in baseline plasma epinephrine (Ep), or norepinephrine (Np) levels; however, plasma dopamine (Dp) levels were significantly (p less than 0.05) higher in Group 3. In Groups 1 and 2, FEV1 did not change significantly after the first (E1) or second (E2) exercise periods, but there were significant (p less than 0.01) changes in Group 3 (maximal percent changes in FEV1, delta FEV1%, E1 = -14.4%, E2 = -8.8%), and the delta FEV1% after E2 was significantly (p less than 0.01) less than after E1.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma

Alterations in ventilatory pattern and ratio of dead-space to tidal volume.

The effects of alterations in ventilatory pattern on the simultaneously measured physiologic and anatomic dead-spaces (VDphys and VDan, respectively) and the dead-space to tidal volume ratio (VD-VT) were studied in 17 healthy normal subjects (13 men, four women, ages 21 to 36 years). There were no significant changes in VDan with increases in respiratory frequency (f) or tidal volume (VT). The VDphys increased (mean change +0.153 L, p less than 0.05) with increase in VT (mean increase +0.84 L, p less than 0.01), but did not alter significantly with a twofold increase in f, at control VT. Increase in VT significantly reduced VD/VT (mean change -10.4 percent, p less than 0.05), but increase in f, at control VT, did not significantly alter VD/VT. These results indicate that in normal subjects, increase in VT alters ventilation/perfusion matching in the lungs, whereas an increase in f, at constant VT, has no effect on ventilation/perfusion matching. Increases in VD/VT cannot, therefore, be ascribed to alterations in ventilatory pattern where either VT, or f, or both are increased.

Adult

The dead space to tidal volume ratio in the diagnosis of pulmonary embolism.

In order to assess the value of the measurement of the physiologic dead space (VD) to tidal volume (VT) ratio in pulmonary embolism (PE), a prospective study was performed in hospital inpatients suspected to have PE (n = 110; mean age +/- SD, 52.2 +/- 15.5 yr). In 16 of 29 patients in whom the diagnosis of PE was excluded on the basis of a normal radioisotope perfusion scan and/or normal pulmonary angiogram, VD/VT was less than 40%; in the other 13 patients, a VD/VT greater than 40% was associated with an abnormal spirogram. In all patients in whom PE was angiographically diagnosed (n = 16), VD/VT was greater than 40%. In the remaining 65 patients, a high probability of PE was rarely (6%) associated with a normal VD/VT, whereas in patients with a low probability of PE, 71% had normal VD/VT values. These data indicate that a VD/VT value of less than 40% makes the diagnosis of PE extremely unlikely, whereas VD/VT value greater than 40% in the presence of a normal spirogram is highly suggestive of PE. The diagnostic sensitivity of a VD/VT greater than 0.4 with a normal spirogram as a positive test of PE, and a VD/VT less than 0.4 excluding the diagnosis of PE was 100%, whereas the specificity was 94%; applying Bayesian analysis, the probability of a correct diagnosis of PE using these criteria in a similar population would be 90.5%, and of excluding PE, 96.7%. Thus, as a diagnostic test in PE, VD/VT measurement is comparable, in terms of sensitivity and specificity, to radioisotope lung scanning.

Adult