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Biomedical subjects

B Farrell

Publications and source records attributed to B Farrell.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of diuretic therapy on the development of tolerance during continuous therapy with nitroglycerin.

OBJECTIVES: This study examined the effects of concurrent diuretic therapy on the hemodynamic responses to short-term and sustained therapy with transdermal nitroglycerin. BACKGROUND: Sodium retention and plasma volume expansion occur during therapy with nitroglycerin and may play a role in the loss of nitroglycerin effects during sustained therapy. METHODS: Twenty-two normal male volunteers were treated for 1 week with either hydrochlorothiazide and amiloride (50 + 5 mg) (n = 11) or placebo (n = 11) in a randomized, double-blind fashion. All 22 subjects then received continuous transdermal nitroglycerin (19 +/- 1 mg/24 h) for 5 to 7 days. RESULTS: On the first and last day of transdermal nitroglycerin therapy, standing heart rate, systolic blood pressure and hematocrit values were assessed at 8, 9 and 10 AM and 12 noon. Heart rate and blood pressure responses to sublingual nitroglycerin (0.6 mg) were also evaluated before and after sustained transdermal nitroglycerin therapy. A significant loss of the hemodynamic effects of transdermal and sublingual nitroglycerin occurred during sustained therapy in both the diuretic and placebo therapy groups. In both groups, transdermal nitroglycerin therapy was associated with a significant decrease in hematocrit that persisted for the entire treatment period. CONCLUSIONS: These results suggest that diuretic therapy does not prevent plasma volume expansion or the loss of hemodynamic effects during sustained transdermal nitroglycerin therapy. The persistent decrease in hematocrit suggests that plasma volume expansion plays a role in the attenuation of nitrate effects. It also provides evidence of continued vascular activity of nitroglycerin despite loss of systemic hemodynamic effects.

Administration, Cutaneous↗
PubMed1991

Paraesophageal hernia causing colonic obstruction.

In a paraesophageal hernia, the esophagogastric junction remains below the hiatus while portions of the fundus or other parts of the stomach herniate in front and to the left of the esophagogastric junction through the hiatus into the thorax. We describe an unusual presentation of a paraesophageal hernia, in which herniation of the splenic flexure of the colon led to colonic obstruction.

Aged↗
PubMed1991

The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.

From 1979-85, 2435 patients with a transient ischaemic attack or minor ischaemic stroke were randomly allocated to receive long term "blind" treatment with aspirin 600 mg twice daily (n = 815), aspirin 300 mg once daily (n = 806) or placebo (n = 814). No patient was lost to follow up. The "intention to treat" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986. There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin, but the lower dose was undoubtedly less gastrotoxic. Also, there was no definite difference in the response of males and females to aspirin. The odds of suffering a major stroke, myocardial infarction or vascular death were 15% less in the combined aspirin groups compared with the placebo group (95% confidence interval 29% reduction to 3% increase in odds) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25%. There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring.

Aged↗
PubMed1991

Counter-regulatory responses to continuous and intermittent therapy with nitroglycerin.

BACKGROUND: Vasodilator therapy may be associated with reflex counter-regulatory responses, and these responses may play a role in the development of tolerance to nitroglycerin (GTN). METHODS AND RESULTS: Standing systolic blood pressure, body weight, urinary sodium, and hormonal responses to continuous (n = 10) and intermittent (n = 10) transdermal GTN administration were studied in normal volunteers. There was rapid attenuation of the hypotensive response to transdermal GTN therapy in the continuous but not in the intermittent therapy group. Significant weight gain and sodium retention occurred during continuous but not during intermittent GTN therapy. This was accompanied by a greater decrease in hematocrit in the continuous group, a finding that suggests that plasma volume expansion occurred during continuous GTN therapy. Continuous GTN therapy was associated with increases in plasma norepinephrine, atrial natriuretic peptide, arginine, vasopressin, and plasma renin activity. A different pattern of neurohormonal response was seen during intermittent therapy, with values tending to return to baseline levels after the nitrate-free interval. CONCLUSIONS: Continuous transdermal GTN therapy leads to counter-regulatory responses associated with sodium retention and probable plasma volume expansion. By contrast, intermittent transdermal GTN therapy is associated with a different pattern of hormonal response, the lack of sodium retention and no evidence of plasma volume expansion. It is likely that these counter-regulatory responses play an important role in the attenuation of nitrate effects.

Administration, Cutaneous↗
PubMed1987

Effect of intervals between doses on the development of tolerance to isosorbide dinitrate.

We studied the development of tolerance to isosorbide dinitrate in 12 patients with chronic stable angina pectoris. The effect of 30 mg of isosorbide dinitrate on treadmill exercise performance was assessed before and at one, three, and five hours after a single dose. As compared with placebo, the drug increased treadmill walking time until the onset of angina and until the development of moderate angina over the five-hour observation period (P less than 0.05). The patients then received 30 mg of isosorbide dinitrate twice, three times, and four times daily for a period of one week, and exercise performance was assessed before and at one, three, and five hours after the final morning dose. During sustained treatment two and three times daily, treadmill walking time was longer throughout the five-hour testing period than during the placebo phase (P less than 0.05). In contrast, during treatment four times daily, treadmill walking time was prolonged at one hour (P less than 0.05) but not at three and five hours after the last dose. We conclude that tolerance to the clinical effects of isosorbide dinitrate develops with a sustained dosage of 30 mg four times daily, but not when the drug is given two or three times daily.

Adult↗
PubMed1987

Nitrate tolerance: the lack of effect of N-acetylcysteine.

The hemodynamic and antianginal effects of 30 mg of isosorbide dinitrate (ISDN) were assessed in 12 patients with chronic stable angina after initial dosing and after 7 to 10 days of therapy four times daily. During early therapy, ISDN produced significant hemodynamic and antianginal effects that persisted over a 3 hr observation period. During sustained therapy there was attenuation of the hemodynamic effects at rest, and treadmill exercise time to the onset of angina and to the development of moderate angina was increased 1 hr after dosing; no effect was apparent at 3 hr. During this state of nitrate tolerance, patients were treated with an infusion of normal saline or 100 mg/kg N-acetylcysteine and exercise testing was repeated. N-Acetylcysteine did not change the hemodynamic findings at rest or during exercise and there was no improvement in exercise tolerance. It is apparent that the short-term administration of reduced sulfhydryl groups does not reverse tolerance to the hemodynamic and antianginal effects of isosorbide dinitrate in an exercise test model.

Acetylcysteine↗
PubMed1986

Comparative antianginal effects of bepridil and propranolol in angina pectoris.

Eighteen patients with chronic, stable angina were studied in a double-blind, placebo-controlled, 3-way, crossover study in which they received 4 weeks of treatment with a once-daily dose of bepridil, 300 mg, a once-daily dose of long-acting propranolol, 160 mg, and placebo. Heart rate at rest during bepridil treatment was less than that during placebo (p less than 0.01), whereas propranolol reduced heart rate compared with placebo (p less than 0.001) and bepridil (p less than 0.01). Systolic blood pressure at rest did not change during the 3 treatment phases. Exercise time to onset of angina and to development of moderate angina were reproducible over the 24-hour period during each treatment phase. Treadmill walking time to onset of angina and to development of moderate angina was significantly prolonged during bepridil (p less than 0.01) and during propranolol treatment (p less than 0.05). Heart rate at peak exercise was similar during bepridil and during placebo, but was markedly reduced with propranolol treatment (p less than 0.001). Systolic blood pressure during exercise was similar during placebo and bepridil, but was substantially lower during propranolol treatment (p less than 0.01).

Aged↗
PubMed1986

Nitroglycerin lingual spray: clinical efficacy and dose-response relation.

Twenty patients with chronic, stable, exercise-induced angina pectoris were studied after receiving lingual sprays that delivered 0.2, 0.4 and 0.8 mg of nitroglycerin (GTN). The hemodynamic effects and changes in exercise time to the onset of angina and to the development of moderate angina were compared with those of placebo spray and 0.4 mg of sublingual GTN. A dose-response relation was apparent with the 3 doses of active spray for heart rate at rest but not for standing systolic blood pressure. Sublingual GTN produced effects similar to those with 0.4 and 0.8 mg of GTN spray, but exceeded the response to 0.2 mg of GTN spray. Treadmill walking time to the onset of angina and to the development of moderate angina was prolonged with each dose of GTN spray and showed a dose-response relation with significantly greater effects with increasing doses of GTN spray. This study indicates that GTN lingual spray is effective in the prophylaxis of angina and should be effective in the therapy of exercise-induced or spontaneous episodes of angina pectoris. The dose of 0.4 or 0.8 mg would appear to be most effective and similar to 0.4 mg of sublingual GTN.

Aerosols↗
PubMed1985

Comparison of buccal nitroglycerin and oral isosorbide dinitrate for nitrate tolerance in stable angina pectoris.

Sixteen patients with chronic stable angina pectoris were studied to compare the hemodynamic and antianginal effects of buccal nitroglycerin (GTN) in a dose of 3 mg administered 3 times daily and oral isosorbide dinitrate (ISDN) in a dose of 30 mg administered 4 times daily. Compared with placebo, both oral ISDN and buccal GTN treatment induced a decrease in systolic blood pressure at rest over a 5-hour period during acute but not during sustained therapy. Neither buccal GTN nor oral ISDN modified the changes in systolic blood pressure during exercise. Both treatment programs were associated with a higher exercise heart rate during acute therapy. During sustained treatment with buccal GTN, the heart rate during exercise remained greater than that during placebo throughout the 5-hour test period, but during treatment with oral ISDN, only the exercise heart rate at 1 hour was greater than that seen with placebo. Treadmill walking time to the onset of angina and to the development of moderate angina increased significantly during acute therapy with both buccal GTN and oral ISDN. The clinical efficacy of buccal GTN was maintained after 2 weeks of 3-times-daily therapy. In contrast, during 4-times-daily therapy with oral ISDN, treadmill walking time was prolonged for only 1 hour after drug administration. This investigation indicates that tolerance develops during 4-times-daily therapy with oral ISDN, but 3 times daily therapy with buccal GTN is not associated with diminished antianginal effects.

Aged↗
PubMed1984

Alcohol and aggression in men: a comparison of brewed and distilled beverages.

The effects of distilled and brewed alcoholic beverages on aggressive behavior were compared in a 2 x 2 factorial design with 16 subjects per cell (N = 64 men social drinkers). One-half of the sample population was told that they would be consuming an alcohol (distilled spirits) beverage and the other half that they would be consuming beer. Within each of these conditions, one-half of the subjects received the expected drug (alcohol) and one-half was given a corresponding placebo beverage. Aggression was measured using a modified version of the Buss aggression machine. Subjects who consumed beer or believed that they were consuming beer were significantly less aggressive than subjects who consumed distilled spirits or believed that they were consuming distilled spirits. Differences between subjects receiving the drug (alcohol) and the placebo were not significant.

Adolescent↗
PubMed1984

Individual characteristics of aggressive beer and distilled beverage drinkers.

Sixty male social drinkers completed the MMPI and a drinking history and attitude questionnaire. These individuals were then randomly divided into four groups, receiving either a distilled or brewed beverage, or two comparable placebos. Subjects in the alcohol groups became equally intoxicated (BAC = .71) and rated themselves as significantly more intoxicated than placebo subjects. All subjects then participated in a Buss aggression task. Aggression scales were related to the pretask personality, history, and attitude measures. Differences were found between factors descriptive of subjects who became aggressive after consuming or believing they had consumed a distilled versus a brewed beverage. In particular, a history of lack of positive alcohol effects and social maladjustment were typical of high-aggressive distilled alcohol and alcohol-placebo subjects, while the presence of family problems and anxiety typified high-aggressive beer and placebo-beer subjects.

Adult↗
PubMed1982

Preoperative and postoperative renin levels in coarctation of the aorta.

We studied plasma renin activity (PRA) in eight children before and after surgical correction of aortic coarctation. These eight children underwent a combination of low-sodium diet and diuresis before surgery, and PRA was measured shortly thereafter. Thirty-two to 51 months after successful surgical correction, PRA was measured again. The mean PRA was 21.4 +/- 1.3 ng/ml/hour (+/- SD) preoperatively and 5.5 +/- 1.5 ng/ml/hour postoperatively. These findings provide further evidence of the significance of increased renin-angiotensin activity in patients with aortic coarctation.

Adolescent↗
PubMed1980

Hypertensive mechanisms in coarctation of the aorta. Further studies of the renin-angiotensin system.

The mechanisms of hypertension in coarctation remain to be clearly defined. In other hypertensive states, abnormal plasma renin activity (PRA) has been unmasked by the depletion of extracellular volume and the use of angiotensin antagonists. In a group of patients with coarctation, preoperative and postoperative evaluations of the renin-angiotensin system have been performed. Before operation, a group of patients with coarctation and a group of normal control subjects both underwent salt restriction followed by diuresis. A standard angiotensin antagonist (saralasin) test was performed on the patients with coarctation, and they demonstrated excessive renin-angiotensin activity compared to the control subjects. Following operation, paradoxical hypertension developed in all of the patients. Repeat saralasin test in these patients again revealed excessive angiotensin activity in the same patients as preoperatively. It appears that the renin-angiotensin system plays a more active role in coarctation than previously believed.

Adolescent↗