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Biomedical subjects

B J Sproule

Publications and source records attributed to B J Sproule.

At least 19 recordsLinked to original sources

Adrenocortical function in patients investigated for active tuberculosis.

Previous reports have identified adrenal insufficiency in groups of patients with active pulmonary tuberculosis. To investigate this possibility, serum cortisol levels were measured in consecutive patients admitted to the hospital for investigation of active tuberculosis. Blood was drawn for cortisol determination promptly at the time of hospital admission, in the morning and afternoon before commencing chemotherapy for the suspected tuberculosis, and before the diagnosis was confirmed. Thirty-seven patients were assessed; 19 of these patients were subsequently proven to have active pulmonary tuberculosis, six had pulmonary disease caused by mycobacteria other than tuberculosis, and 12 had radiologic appearance indicating tuberculosis, accompanied by a significant tuberculin skin reaction but with negative sputum cultures and no change in roentgenographic appearance during the course of treatment. In evaluating the adrenocortical function, the morning and afternoon serum cortisol level was measured and the diurnal change in serum cortisol level (the difference between afternoon and morning levels) was calculated. There was no association of either morning cortisol levels or diurnal change in cortisol levels with age, gender, or race. There was no difference among the three groups in either cortisol determination. Although difference in morning cortisol levels between those with extensive as compared with limited disease was not statistically significant (p = 0.349 from analysis of variance), there was a significantly decreased diurnal change in cortisol levels in those with extensive disease as compared with those with limited disease (+2.7 +/- 188.3 vs -259.1 +/- 177.1). We conclude that patients in our hospital with active pulmonary tuberculosis do not exhibit decreased adrenocortical function as compared with groups of patients without active pulmonary tuberculosis.

Adrenal Cortex↗

Cyclosporine and chronic sarcoidosis.

Two patients with progressive sarcoidosis who had poor responses and side effects from corticosteroid therapy were treated with cyclosporine. Cyclosporine suppressed conventional markers of inflammation and there was clinical improvement in one patient, but the disease recurred when therapy was discontinued. The second patient who had diabetes mellitus developed unstable glucose metabolism when given cyclosporine. This unstable diabetes mellitus together with side effects of nausea and vomiting resulted in weight loss and inadequate serum therapeutic levels that was associated with a poor therapeutic response to the cyclosporine. The major side effects in both patients were headache and gastrointestinal symptoms, but there was no renal dysfunction. We conclude that while corticosteroids remain the mainstay of sarcoid therapy, when these drugs have not been successful for the skin manifestations of the disease, a trial of cyclosporine may be justified.

Adult↗

Endobronchial tuberculosis presenting as asthma.

Clinical deterioration with features suggestive of asthma was seen in three patients following two to six months of drug therapy of primary tuberculosis. There was a poor clinical response to administered bronchodilators. Bronchoscopy in all three revealed culture-negative mycobacterial caseating granulomas. Corticosteroid therapy resulted in good clinical response, with resolution of the asthmatic symptoms and improvement in the expiratory flow rates. In our opinion these patients are clinically compatible with a hypersensitivity response to mycobacteria following antituberculosis therapy and release of tuberculosis antigens. Corticosteroid therapy is appropriate in this form of tuberculous disease.

Adult↗

Control of breathing in patients with chronic obstructive lung diseases and secondary polycythemia after venesection.

Using the mouth occlusion pressure technique, we have studied the control of breathing in 10 hypercapnic patients with chronic obstructive pulmonary diseases and polycythemia before and after venesection. The mean hematocrit value was 59.9 +/- 5.5% which, following venesection (approximately 1,200-1,600 cm3 of blood was removed from each patient over three consecutive days), fell to 44.4 +/- 2.2%. Respiratory drive, expressed as P0.1 (mouth occlusion pressure 0.1 s after the onset of occluded inspiration at functional residual capacity) and as mean inspired flow (VT/TI), was diminished after venesection (p less than 0.001 and p less than 0.05); in contrast to that, we found no changes in respiratory timing (TI and TI/Ttot). The arterial PCO2 was decreased (p less than 0.001) and arterial PO2 was increased after venesection, these improvements are mainly attributed to decreased dead space ventilation (p less than 0.05). It seems that the improvements of blood gases after venesection is probably responsible for the decrease in respiratory drive.

Aged↗

Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease.

To evaluate the efficacy of a mild anxiolytic, alprazolam, in relieving dyspnea, we conducted a randomized, placebo-controlled double-blind study on patients with chronic obstructive lung disease. Twenty-four patients had alprazolam (0.5 mg bid) or placebo administered for one week, followed by placebo for one week, then either placebo or alprazolam for the third week. Assessment tests were performed at the outset, end of the first and second weeks, and finally end of the third week. The parameters measured were: pulmonary function, exercise testing on a bicycle ergometer, and the distance covered in a 12 minute walk. Subjective sensations of dyspnea at rest and during guarded exercise, as well as subjective feelings of calmness or anxiety were also recorded. There was no difference in mechanical lung function, but the PO2 tended to decrease and PCO2 to increase after alprazolam administration. The maximum exercise level attained and the distance covered in the 12 minute walk was unchanged. The subjective perception of dyspnea was the same before and after alprazolam, at rest and during exercise. We conclude that alprazolam is not effective in relieving exercise dyspnea in patients with obstructive lung disease.

Aged↗

The effect of methacholine inhalation challenge on regional residual volume in patients with subclinical asthma.

Regional residual volume to total lung capacity (RVr/TLCr) was measured with xenon 133 before and after methacholine challenge in 26 nonsmoking subjects (mean age 34 years). Eleven were normal control subjects and 15 were patients referred for methacholine challenge because of previous asthma-like symptoms. All had normal pulmonary function and normal RVr/TLCr distribution. Following methacholine challenge, RVr/TLCr increased in two control subjects and ten patients who also had decreases in FEV1 of greater than 20 percent. The RVr/TLCr changes were patchy, suggesting that the degree of bronchospasm varied between individual lung regions. The other 14 subjects did not have a 20 percent decrease in FEV1, but two controls and four patients had generalized increases in RVr/TLCr, while seven controls and one patient had no significant changes in RVr/TLCr. In all subjects, FEV1 and RVr/TLCr returned to the baseline level after salbutamol administration. The results indicate that methacholine can cause localized or diffuse effects on lung emptying and that bronchodilator completely reverses the bronchoconstriction induced by methacholine.

Adult↗

The influence of orally administered cimetidine and theophylline on the elimination of each drug in patients with chronic airways obstruction.

We studied the effect of cimetidine and theophylline on the metabolism of each drug in 19 elderly patients with stable chronic obstructive pulmonary disease. Each patient received either regular release or sustained release oxtriphylline. Cimetidine was given to some patients in both groups after steady state for theophylline was achieved. Multiple serum theophylline and cimetidine measurements were performed. Cimetidine decreased theophylline clearance by an average of 37.8% (26.2 to 46.7) for regular release and 33.4% (22.2 to 45.0) for sustained release oxtriphylline. The apparent volume of distribution was not changed; however, the half-life for theophylline was increased. As there is a linear relationship between the theophylline clearance before and after the addition of cimetidine and a linear relationship between trough and peak values before and after cimetidine, these 2 relationships may be used to predict clearance values and serum levels after cimetidine treatment when the initial values are known.

Age Factors↗

Pulmonary function associated with the Mmalton deficient variant of alpha 1-antitrypsin.

We have studied 78 members of a large family in which the Mmalton deficiency allele of alpha 1-antitrypsin (alpha 1AT) is present. Four patients of PI type MmaltonZ (alpha 1AT concentration, 16.4% of normal) had severe emphysema and marked depression in all flow and gas exchange parameters, significantly different from other members of the same family who were normal or had intermediate concentrations of alpha 1AT. Fourteen subjects with PI type MMmalton (alpha 1AT concentration, 63.3% of normal) were compared with 46 PI MM relatives (alpha 1AT, 103.8% of normal) and 14 relatives of PI type MZ (alpha 1AT concentration, 66.5% of normal). Spirometry, flow-volume loops, plethysmography, gas exchange at rest and exercise, and xenon 133 regional lung function were similar in those partially deficient when compared with the normal subjects. There was a trend for impairment of tests of lung function between smoking partially deficient (PI MZ, PI Mmalton) and normal (PI MM) relatives.

Adult↗

Reversible ventilation and perfusion abnormalities in unilateral obstructed lung.

An intraluminal carcinoid tumor obstructing the left mainstem bronchus produced hypoxemia through alteration in ventilation/perfusion matching. Studies of regional lung function using 133-xenon (133Xe) and a multiprobe computerized instrumentation system documented a reduction of perfusion to 22 percent and ventilation to 6 percent of the total. There was negligible washout of intravenously injected 133Xe from the left lung consistent with air trapping. Four days after left mainstem bronchial sleeve resection, perfusion, ventilation and washout of injected xenon had significantly improved and by four months postresection, all measurements were virtually normal, although complete restoration of perfusion in relation to ventilation was delayed. Regional lung function studied with a multiprobe system in this patient provided a clinical model for the study of ventilation and perfusion inter-relationships in large airway obstruction and demonstrated that a prolonged time may be required for return of perfusion to normal.

Adult↗

Effects of secondary polycythemia on cerebral blood flow in chronic obstructive pulmonary disease.

Cerebral blood flow was measured before and after venesection in 6 patients with chronic obstructive pulmonary disease and secondary polycythemia. The hematocrit was decreased from a mean of 59.6 to 43.9%, and whole blood viscosity was decreased by 35%. The supratentorial blood flow increased 78.2% (p < 0.005) after venesection; subtentorial flow also increased, but not significantly. The improvement in cerebral blood flow appeared to be related to a decrease in blood viscosity, because pulmonary function and arterial blood gases did not change significantly. There was subjective improvement in all patients, and this improvement might have been due to the increased supratentorial blood flow.

Aged↗

Rapid onset of emphysema associated with diffuse parenchymal disease.

In experimental models pulmonary emphysema may be produced in hours to days; however, in human subjects emphysema commonly develops over a period of many years. In this report we document a case of severe emphysema which developed in less than six months in association with an unexplained illness characterized by dyspnea, hypoxemia and bilateral lung parenchymal disease. There was no hereditary predisposition. The diffuse alveolar injury syndrome must be considered as a potential cause of alveolar disruption.

Adult↗

A single-breath method of alveolar O2 determination.

We designed a single-breath method of alveolar O2 determination, requiring only a single tidal breath expirate and concomitant arterial blood sample. The PAO2 equation used in our method was derived by applying the Bohr equation to both O2 and CO2 and independant of VO2, VCO2 and RQ. In 35 patients with different degrees of airway obstruction, at rest and during exercise, the single-breath method agreed well with the classic method of PAO2 determination which required 3 min of expired gas collection and derivation of VO2, VCO2 and RQ. The mean difference between the PAO2 estimates by the two methods was 0.36 mm Hg as calculated for all patients, both at rest and during exercise. At rest, in 2 out of 35 cases the difference was greater than 2 mm Hg and such difference happened only in 1 case during exercise. A good correlation existed between the two PAO2 estimates by the two methods (r ranging from 0.977 to 0.996). The data indicated that single-breath method of PAO2 determination was reliable. Its extreme simplicity would facilitate greatly the assessment of gas exchange efficiency in situations where both patient's cooperation and laborator equipment are less than optimum.

Adult↗

Hypothalamic-pituitary-adrenal function in extrinsic asthma.

Hypothalamic-pituitary-adrenal function in a well-defined, carefully selected group of 25 patients with extrinsic asthma was assessed by measuring plasma levels of adrenocorticotropic hormone (ACTH) and of 11-deoxycorticol after administration of metyrapone and by measuring the level of cortisol following stimulation with cosyntropin. No difference was demonstrated between asthmatic subjects and 20 normal age-matched controls. In addition, neither the response of the level of ACTH nor of 11-deoxycortisol correlated with the duration of asthma or the severity as assessed in 23 patients by tests of pulmonary function. We conclude that there is no abnormality in hypothalamic-pituitary-adrenal function in patients with extrinsic asthma, and we suggest that previous data suggesting such an abnormality may reflect heterogeneous groups of patients, inaccurate methods, and the variability of normal responses to ACTH and stimulation with metyrapone.

17-Hydroxycorticosteroids↗