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Biomedical subjects

R E Vestal

Publications and source records attributed to R E Vestal.

At least 19 recordsLinked to original sources
PubMed1992

Impaired beta-adrenoceptor function, increased leukocyte respiratory burst, and bronchial hyperresponsiveness.

Inflammatory processes have potential importance in the pathogenesis of bronchial hyperresponsiveness and asthma. Because beta-adrenoceptor function may be impaired in asthma, we studied regulation of the leukocyte respiratory burst using blood samples from subjects with bronchial hyperresponsiveness to methacholine. Leukocytes from hyperresponsive subjects were less responsive to the beta-agonist isoproterenol than were leukocytes from healthy control subjects. The magnitude of the respiratory burst was increased in cells from hyperresponsive subjects and correlated with the degree of methacholine responsiveness. These results demonstrate that peripheral leukocytes reflect a functional impairment in beta-adrenergic responsiveness that parallels airway hyperresponsiveness. Because untreated subjects demonstrated a reduction in beta-adrenergic response, the impairment in beta-adrenoceptor function was not a result of drug therapy and may be associated with the pathogenesis of asthma.

Adult↗
PubMed1992

Comparison of the effects of adenosine and nifedipine in pulmonary hypertension.

The hemodynamic effects of intravenously administered adenosine, a potent vasodilator, were examined in 15 patients with pulmonary hypertension. All patients were given adenosine, 50 micrograms/kg per min, increased by 50 micrograms/kg per min at 2 min intervals to a maximum of 500 micrograms/kg per min or until the development of untoward side effects. The patients were then given oral nifedipine, 20 mg every hour, until a greater than or equal to 20% decrease in pulmonary vascular resistance or systemic hypotension occurred. The administration of maximal doses of adenosine, 256 +/- 46 micrograms/kg per min, produced a 2.4% reduction in pulmonary artery pressure (p = NS), a 37% decrease in pulmonary vascular resistance (p less than 0.001) and a 57% increase in cardiac index (p less than 0.001). The administration of maximally effective doses of nifedipine (91 +/- 36 mg) produced a 15% reduction in the mean pulmonary artery pressure (p less than 0.05), a 24% decrease in pulmonary vascular resistance (p less than 0.01) and an 8% increase in cardiac index (p = NS). There was a significant correlation (r = 0.714, p = 0.01) between the reduction in pulmonary vascular resistance that resulted from adenosine administration and that achieved with the administration of nifedipine. Six patients had substantial reductions in pulmonary vascular resistance with adenosine but not with nifedipine. Thus, adenosine is an effective vasodilator in patients with pulmonary hypertension and can be used for safe and rapid assessment of vasodilator reserve in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Clinical significance of crepitations in elderly patients following acute hospital admission: a prospective study.

Because of a clinical impression that lung crepitations are a common, non-specific sign in acutely ill elderly people, two investigators, blinded to each other's findings and to subject case notes, prospectively examined 207 consecutive elderly [aged 70-98 (mean 77) years] and 75 young patients [24-50 (41) years] acutely admitted to hospital. Crepitations and persistent crepitations (PCs) were commoner in the elderly patients (p less than 0.001) but agreement over their presence/absence was reduced (p less than 0.05). Both investigators agreed PCs were absent in 35% of elderly subjects suffering from conditions classically associated with their presence, and, conversely, were present in 29 elderly subjects in whom no cause for their presence was discovered (14% of the total elderly group or 42% of those with PCs). PCs without obvious cause were unrelated to smoking history and did not predict outcome, length of stay or development of cardiorespiratory complications. In view of poor sensitivity and specificity of crepitations in elderly patients undergoing acute hospital admission we caution against over-reliance on this sign in isolation in these circumstances.

Aged↗
PubMed1992

Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man.

1. Ageing is associated with a decline in beta-adrenergic responsiveness in several tissues. Reduced beta-adrenoceptor mediated smooth muscle relaxation in aged man has been demonstrated using the dorsal hand vein technique. Isoprenaline and adenosine activate adenylate cyclase through separate membrane bound receptors to induce vasodilatation. 2. To determine the specificity of reduced beta-adrenergic responsiveness in smooth muscle of aged man, and possible sites of the defect responsible, venodilatory responses to isoprenaline, a beta-adrenoceptor agonist and adenosine were determined in nine young (age 26 +/- 3 years: mean +/- s.d.) and eight elderly (age 70 +/- 5 years), healthy male volunteers. Veins were partially constricted with the alpha 1-adrenoceptor agonist phenylephrine and increasing doses of adenosine (5 to 1220 micrograms min-1) or isoprenaline (271 ng min-1) were infused. 3. Maximal dilatation induced by isoprenaline was 83 +/- 26% in the young and 51 +/- 34% in the elderly, P = 0.02. Maximal dilatation induced at the highest dose of adenosine (1220 micrograms min-1) was similar in young and elderly: 79 +/- 25% vs 88 +/- 28%, P = 0.26. 4. Adenosine venodilatation was measured before and after infusions of theophylline (6.8 to 135 micrograms min-1) for 30 min in six subjects. Adenosine responsiveness was unchanged following theophylline: 48 +/- 16% to 49 +/- 40%, P = 0.44. 5. The results suggest that the age-associated reduced responsiveness of the beta-adrenergic system in human vascular smooth muscle is not shared by venodilatation mediated by adenosine.

Adenosine↗
PubMed1992

Reduced subjective awareness of bronchoconstriction provoked by methacholine in elderly asthmatic and normal subjects as measured on a simple awareness scale.

BACKGROUND: Asthma death rates are rising, with the greatest rise and highest death rates in old age. A reduced cardiovascular response in the elderly may lead to the underestimation by physicians of the severity of acute asthma attacks. This would be compounded if elderly patients had reduced awareness of bronchoconstriction. METHODS: Methacholine provoked bronchoconstriction was compared in 34 elderly (17 asthmatic, 17 normal; age 60-83, mean 68 years) and 33 young subjects (16 asthmatic, 17 normal; 20-46, mean 30 years). None were smokers. All underwent inhaled methacholine challenge by the Newcastle dosimeter method, monitored by maximal expiratory flow-volume loops (MEFVL). The endpoints were a 35% fall in forced expiratory flow at 50% vital capacity or cumulative inhalation of 6.4 mg methacholine. The one second forced expiratory volume (FEV1) was derived from MEFVL. After challenge and before bronchodilatation subjects graded awareness of respiratory discomfort from 1 (no symptoms) to 4 (pronounced symptoms needing immediate treatment). RESULTS: Despite a greater fall in FEV1 in elderly asthmatic patients (mean (SE) 27.4% (2.2%)) than in young asthmatic patients (21.5% (1.7%)) elderly patients were less aware of bronchoconstriction (awareness score 2.00 (SE 0.15) than young patients (3.06 (0.11)). Similar differences in awareness score were seen between elderly normal subjects (1.53 (0.17)) and young normal subjects (2.76 (0.22)), despite no difference in degree of bronchoconstriction. CONCLUSIONS: Reduced awareness of moderate acute bronchoconstriction in old age may delay self referral in acute asthma and contribute to higher asthma mortality in the elderly.

Adolescent↗
PubMed1992

Relationship between nonspecific bronchial responsiveness to methacholine and peripheral mononuclear leukocyte beta-adrenergic receptor function in young drug-naive subjects.

Asthma is associated with dysfunction of the beta-adrenergic receptor adenylyl cyclase signal transduction pathway. It has been argued that this results from receptor down-regulation by beta-agonist therapy. This study examined the relationship between nonspecific bronchial responsiveness (NSBR) to methacholine (Newcastle dosimeter method) and beta-adrenergic receptor density (Bmax) and affinity (%KH) in membranes from peripheral blood mononuclear leukocytes (MNL) in 12 male (27.3 +/- 1.7 yr old) and 14 female (31.4 +/- 1.7 yr old) drug-naive subjects with and without symptoms of mild intermittent wheezing. None had ever smoked or received any antiasthma medication. "Hyperresponsive" subjects were defined as those (n = 11) whose simplified slope of FEF50 (calculated as the percent fall in FEF50 divided by the dose of methacholine) was more than one SD above the mean for asymptomatic subjects. The log of the slope was reproducible (repeatability coefficient = 0.43) on two nonconsecutive days. Multiple regression analysis (overall R2 = 0.57) revealed negative relationships between the log of the slope and both Bmax (p = 0.016) and %KH (p = 0.011). Analysis of variance confirmed a lower mean (+/- SEM) value of %KH in "hyperresponsives" (45.7 +/- 5.5%) than in "normoresponsives" (60.4 +/- 4.1%, p = 0.04) with a similar trend for Bmax (hyperresponsives = 33.5 +/- 4.1 fmol/mg, normoresponsives = 45.9 +/- 7.1 fmol/mg, p = 0.18). These relationships between bronchial responsiveness, Bmax, and %KH cannot be explained by drug therapy, and they provide further evidence that there is an intrinsic impairment in the function of beta-adrenergic receptors on peripheral MNLs from subjects with high levels of nonspecific bronchial responsiveness.

Adolescent↗
PubMed1992

Increased ventricular response rate during exercise in patients with atrial fibrillation treated with theophylline.

The effect of theophylline on atrioventricular conduction in atrial fibrillation was investigated by determining ventricular response rates at rest and during exercise treadmill tests in eight patients (mean [+/- SEM] age, 64.2 +/- 2.0 years) with chronic atrial fibrillation. Tests were performed before and after 7 days of oral theophylline treatment (plasma level, 87.7 +/- 7.8 mumol/L). There was no significant change in baseline ventricular rate or duration of exercise, but the maximum ventricular rate with theophylline treatment was 12.3% +/- 2.4% higher than that with placebo (176.3 +/- 7.5 vs 158.1 +/- 8.8 beats per minute), and, during each stage of exercise, the ventricular rate with theophylline exceeded that with placebo. The increased heart rate during theophylline administration occurred without a significant difference in the exercise-induced increase in circulating plasma catecholamine levels. We conclude that treatment with theophylline may contribute to difficulties with rate control in acutely ill patients with coexisting atrial fibrillation.

Aged↗
PubMed1990

Effects of selective phosphodiesterase inhibitors on the polymorphonuclear leukocyte respiratory burst.

Modulation of the human polymorphonuclear leukocyte (PMN) respiratory burst by selective cyclic 3',5' adenosine monophosphate (cAMP) phosphodiesterase (PDE) inhibitors was studied with respect to PDE isozyme characteristics. Zaprinast, an inhibitor of a cyclic guanosine monophosphate (cGMP)-specific PDE (PDE I), at concentrations up to 100 mumol/L, had no significant effect on the respiratory burst. Milrinone and imazodan, inhibitors of cAMP-metabolizing, cGMP-sensitive PDE (PDE III), reduced the respiratory burst to 60% of control magnitude but only had significant effects when they were introduced at high (100 mumol/L) concentrations. In contrast, rolipram and RO 20-1724, inhibitors of a cAMP-metabolizing, cGMP-insensitive PDE (PDE IV), had significant effects at low concentrations (0.1 mumol/L) and caused marked reduction of the respiratory burst at higher concentrations (25% of control at 10 mumol/L). The selective PDE IV inhibitors significantly potentiated PMN inhibition by isoproterenol. Diethylaminoethyl (DEAE)-Sepharose chromatography demonstrated a predominant PDE isozyme with high affinity and selectivity for cAMP that was insensitive to cGMP and was completely inhibited by rolipram, a PDE IV inhibitor. These results are consistent with the conclusion that the PMN respiratory burst is inhibited by an elevation of cAMP induced by PDE IV inhibition.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1979

Effect of aging and cigarette smoking on antipyrine and indocyanine green elimination.

The plasma clearances of antipyrine (AP) and indocyanine green (ICG) have been measured after intravenous administration in each of 20 normal male subjects aged 22 to 72 yr. An additional 4 subjects aged 65 to 73 yr received only ICG. AP clearance fell with age in the group as a whole (r = 0.56; p less than 0.01), but when cigarette smoking habits were considered the relationship was apparent only in smokers (r = 0.68; p less than 0.02). In the under 40 yr group. AP clearance was higher in smokers than nonsmokers (p less than 0.02). There was no such difference in men over 40 yr of age. These observations suggest that the enzyme-inducing effect of smoking diminishes with advancing years. In contrast, and consistent with a reduction in liver blood flow, the clearance of the highly extracted ICG fell with age, irrespective of smoking habits (r = 0.57; p less than 0.004). These findings suggest that while hepatic drug clearance may be impaired in elderly people, the outcome depends not only on the effects of the aging process on the physiologic determinants of hepatic clearance (liver blood flow and the activity of the drug-metabolizing enzymes) but also on the effects of environmental factors, such as smoking.

Adult↗
PubMed1979

Reduced beta-adrenoceptor sensitivity in the elderly.

The effect of age on sensitivity to both isoproterenol and propranolol has been investigated in 27 male volunteers aged 21 to 73 yr. The dose of isoproterenol (given as a rapid intravenous injection) required to increase the resting heart rate by 25 bpm (I25) increased with age. The I25 was repeated during an intravenous infusion of propranolol and the dose ratio (I25 after propranolol divided by the control I25) determined. This was related to the concentration of free propranolol in plasma. It was found that the effectiveness of any given free concentration diminished progressively with age. These data are consistent with a diminished responsiveness of the beta-adrenoceptor to both agonist and antagonist drugs with advancing years.

Adrenergic beta-Agonists↗
PubMed1979

Influence of the emetic reflex on vasopressin release in man.

The mechanisms underlying the frequent association of nausea and vomiting with elevations of plasma vasopressin(PAVP) were studied in man and rat. After oral water loads (N = 16), plasma osmolality fell in all human subjects and was associated with a decline in PAVP in 14 asymptomatic human subjects. In 2 human subjects, nausea occurred and was associated with increases in PAVP, without changes in blood pressure. During ethanol infusion (N = 28), PAVP was suppressed unless nausea supervened. In 4 nauseated human subjects, PAVP escaped from ethanol inhibition and rose to levels 10 times basal, despite the absence of hemodynamic changes. Apomorphine, a potent dopamine agonist and emetic agent, was administered to human volunteers in doses of 7 to 24 microgram/kg. There was no increase in PAVP in 3 human subjects who remained asymptomatic (7 to 16 microgram/kg). Ten human subjects experienced nausea after 16 microgram/kg, which was followed shortly by marked increases in PAVP. Emesis occurred in 5 human subjects given 16 to 24 microgram/kg, and was followed by PAVP levels similar to those seen with nausea alone. In 7 human subjects from the nausea group, the repeat study (16 microgram/kg) after pretreatment with dopamine antagonist (haloperidol, N = 4; fluphenazine, N = 3) resulted in complete blockage of apomorphine-induced AVP release. In rats, which lack an emetic reflex, apomorphine doses of 200 microgram/kg induced only slight increases in PAVP when compared to the response to 16 microgram/kg in man. These studies indicate that stimulation of the emetic reflex results in AVP-release in man. Nausea-mediated AVP release supervenes over concomitant osmolar or pharmacologic (ethanol) inhibition.

Alcohols↗