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Biomedical subjects

S Waldorff

Publications and source records attributed to S Waldorff.

At least 19 recordsLinked to original sources
PubMed1992

Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis. A double-blind, placebo-controlled multicentre study in general practice.

The aim of the study was to evaluate whether a broad-spectrum penicillin, amoxicillin, was superior to placebo in resolving symptoms of acute exacerbations of chronic bronchitis in patients from general practice. 131 general practitioners included 278 patients over a period of 30 months. The patients were randomly assigned to treatment with amoxicillin 750 mg b.i.d. or corresponding placebo for 7 days. Patients with pneumonia, a temperature above 38.5 degrees C or heart rate over 100 were excluded for safety reasons. The main effect parameter--the doctors' overall evaluation of the treatment--did not demonstrate any statistically significant difference between amoxicillin or placebo, 63% versus 64% of the patients. Resolution of symptoms was obtained by 19% (25/132) of the patients in the amoxicillin group compared with 10% (13/136) of the patients in the placebo group, P = 0.03. The present findings do not favour routine use of antibiotics in an attempt to improve the course of acute exacerbations as defined in this study in patients with chronic bronchitis.

Acute Disease↗
PubMed1989

N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing.

Nitrates are well established in the treatment of angina pectoris and the presence of sulfhydryl groups seems to be fundamental to nitrate-induced vasodilatation. The present study was performed to elucidate if large oral doses of N-acetylcysteine (NAC, 2,400 mg X 2), a donor of sulfhydryl groups, given together with a single oral dose of the long-acting nitrate, isosorbide-5-mononitrate (5-ISMN, 60 mg), would modify the nitrate effect evaluated by exercise testing before and after additional sublingual doses of nitroglycerin (NTG). Ten patients with angina pectoris and angiographically proven significant coronary artery disease were included. All patients received a baseline therapy with beta blockers. None of the patients had developed nitrate tolerance at inclusion. NAC/5-ISMN treatment significantly prolonged the total exercise time as compared with placebo/5-ISMN (7.7 +/- 2.1 min vs. 6.8 +/- 1.7 min, p less than 0.05). This increase was of such magnitude that no further effect was obtained after additional NTG doses. This study demonstrated that increased availability of sulfhydryl groups can increase the exercise capacity in angina pectoris patients treated with 5-ISMN without nitrate tolerance.

Acetylcysteine↗
PubMed1988

Beta 2-mediated changes in central haemodynamics, coronary circulation and myocardial metabolism in canine.

The combined effect of terbutaline on systemic and coronary circulation was investigated in dogs to clarify its influence on myocardial oxygen supply and lactate balance. The dogs were anaesthetized and the chest opened. Coronary sinus blood flow and cardiac output were monitored by thermodilution, aortic pressure was measured by tip-transducer and heart rate by RR-interval on ECG, coronary sinus blood were analyzed for lactate, oxygen and carbon dioxide. Terbutaline caused a substantial systemic vasodilation and an increased heart rate, the total external cardiac work increased to a minor degree. Terbutaline increased arterial lactate concentration. Coronary vascular resistance was reduced after terbutaline. Even if myocardial perfusion pressure was reduced and an increased external cardiac work was present, no signs of myocardial distress was observed in lactate metabolism or coronary sinus oxygen content. In fact a tendency to increased myocardial aerobic metabolism was observed, as myocardial lactate consumption increased after terbutaline. Terbutaline seems to be a coronary vasodilator in dogs. However, the demand for oxygen secondary to both an increase in cardiac work and aerobic metabolism can be hazardous to the potentially ischaemic myocardium.

Animals↗
PubMed1987

Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress.

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.

Adult↗
PubMed1987

Evaluation of increased serum creatine kinase as an indicator of irreversible myocardial damage in dogs.

To evaluate the relationship between creatine kinase (CK) elevation and irreversible myocardial damage, a coronary artery branch was occluded for periods of 5 to 40 min in ten dogs. In five other dogs the coronary vessel was occluded for 480 min, and five dogs underwent the same operative procedure but without occlusion of the artery. The serum CK was monitored for 8 hours postoperatively in all dogs. Elevation of the CK levels occurred in all groups, but the area under the time-enzyme activity curve showed no statistically significant difference between the group with 480-min occlusion, in which transmural myocardial infarction occurred in all dogs, and the group with temporary occlusion, in which no infarction could be histologically or histochemically demonstrated. Contrastingly, a statistically significant difference was found between the group with temporary occlusion and the control group with no occlusion. The results suggest that CK elevation is of no value as an indicator of irreversible myocardial damage during heart surgery that involves temporary myocardial ischaemia.

Animals↗
PubMed1986

Aprotinin does not add protective effect to cold cardioplegia during coronary artery bypass surgery.

The effect of aprotinin on intraoperative and postoperative CK-MB and left ventricular contractility in terms of dp/dt response to atrial pacing up to 150 beats/min was studied in 20 patients randomized before aortocoronary bypass surgery to either aprotinin or placebo administration. Cold cardioplegia and topical deep hypothermia were used in both groups. No difference could be demonstrated between the aprotinin and the placebo group, and the authors therefore concluded that aprotinin does not add substantially to the protective effect of cold cardioplegia and deep topical hypothermia during aortocoronary bypass surgery.

Aprotinin↗
PubMed1984

Influence of atenolol and nifedipine on digoxin-induced inotropism in humans.

Short term effect of digoxin on left ventricular performance was studied in six healthy volunteers before and during atenolol or nifedipine administration. Left ventricular function was evaluated by systolic time intervals and echocardiography. No changes in left ventricular end diastolic or systolic dimensions occurred throughout the study, indicating unchanged ventricular pre- and afterload. Thus, changes in the systolic time intervals must be attributed to changes in cardiac contractility. Changes in the pre-ejection period index (PEPI) obtained from the systolic time intervals were used as a measure of digoxin-induced inotropism. A concentration-response relationship between plasma digoxin level and changes in PEPI was revealed when digoxin was given alone. Atenolol did not influence the digoxin-induced inotropism at a given serum digoxin level. During nifedipine administration no inotropic effect of digoxin could be demonstrated. Thus, it is concluded that nifedipine attenuates digoxin-induced inotropism, while atenolol seems without this effect. These results are in accordance with previous experiments and reflect the different pharmacological sites of action of beta-adrenoceptor antagonists and calcium channel blocking agents. Plasma digoxin concentration, renal digoxin clearance and creatinine clearance did not change during atenolol or nifedipine.

Adult↗
PubMed1984

Pharmacokinetics and bronchodilatory effect of proxyphylline and theophylline.

In a double-blind cross-over study, including double-dummy placebo, 8 adult asthmatics received oral sustained-release proxyphylline 900 mg (Neofyllin retard) twice daily, or 250 mg microcrystalline theophylline (Nuelin) 4 times daily for 6 days. It was found that there was a reduction in the number of bronchodilatory aerosol dosages used with both proxyphylline treatment (139 dosages) and theophylline treatment (165) dosages, but only with proxyphylline was the difference in number statistically significant when compared with the placebo period (236 dosages, p less than 0.05). Subjective side-effects occurred significantly more often during theophylline treatment than during proxyphylline treatment (p less than 0.05). Changes in lung function after intravenous infusion of proxyphylline 1400 mg and aminophylline 400 mg confirmed the potency difference between the drugs. Volume of distribution and total body clearance were comparable for the two drugs. In 2 subjects, calculations of the fraction of drug absorbed and plasma-concentration versus time curves after oral and intravenous administration, suggested saturation kinetics of theophylline.

Administration, Oral↗
PubMed1983

Interactions between digoxin and potassium-sparing diuretics.

A kinetic and hemodynamic study of digoxin was performed in six healthy subjects and similar studies were performed during digoxin with spironolactone and with triamterene. Spironolactone reduced renal tubular secretion of digoxin and attenuated its positive inotropic effect (evaluated by systolic time intervals and echocardiography) and triamterene reduced the extrarenal elimination of digoxin, but induced no changes in digoxin-elicited inotrophy. It is suggested that the renal handling of digoxin is influenced by the intracellular potassium concentration in the renal tubular cell. The results indicate a drug-receptor interaction between spironolactone metabolites and digoxin at the hypothetical inotropic digitalis receptor. Amiloride has been reported to suppress digoxin inotropism, whereas spironolactone induces minor inhibition and triamterene does not affect digoxin inotropism.

Adult↗
PubMed1983

Non-invasive measuring of the circulatory effect of afterload reduction in order to monitor the pharmacodynamic effect of drugs in normal volunteers.

In order to measure the effect of a decrease in afterload on systolic time intervals, left ventricular end-systolic diameter, and left ventricular wall stress, eight healthy young persons underwent a randomised placebo controlled trial of terbutaline before and during atenolol treatment. Pre-ejection period index, left ventricular end-systolic diameter, and wall stress all decreased after terbutaline, the decrease being clearly dose dependent. This was identical before and during atenolol administration. Consequently the observed changes were induced by beta-2 elicited vasodilatation, possibly combined with some decrease of parasympathetic tone. A close correlation between changes in pre-ejection period index (PEPI) and changes in left ventricular end-systolic diameter (LVESD) and wall stress was shown both before and during atenolol treatment. When using non-invasive methods in the evaluation of changes in contractility, it is important to correct for changes in preload and afterload. For normal subjects it is suggested that the relation between delta PEPI and delta LVESD as a percentage of the mean values should be used for evaluation of afterload changes. A method is suggested for estimating changes in pre-ejection period index induced by changes in left ventricular end-systolic diameter or wall stress.

Adult↗