Acute effects of acetylsalicylic acid on renal and hepatic function in normal humans.

The effect of a single oral dose (1 g) of acetylsalicylic acid (ASA) on renal function and hepatic enzymes as well as prothrombin time was studied in two series of experiments on normal human volunteers. Radioimmunoassay of albumin and beta 2-microglobulin excretion rates in urine revealed a statistically significant increase in both beta 2-microglobulin and albumin excretion rates within 2 h after dosage. Hepatic enzymes were not influenced by a single dose of ASA, while a statistically significant reduction in prothrombin time was registered. High-pressure liquid chromatography was used for measuring serum levels of ASA and salicylic acid (SA). Peak levels of 500 mumol/l and 150 mumol/l for SA and ASA, respectively, were found.

Renal effects of acute exposure to toluene. A controlled clinical trial.

Urinary excretion rates of beta 2-microglobulin and albumin were measured in 43 male printing trade workers and 43 age-matched male controls before and during exposure to toluene, 382 mg/m3, for 6 1/2 hours in a climate chamber. There were no significant changes in renal excretion rates of albumin and beta 2-microglobulin during toluene exposure indicating that no causal relationship exists between moderate exposure to organic solvents and renal injury.

Renal effects of chronic exposure to organic solvents. A clinical controlled trial.

Chronic effects of organic solvents on renal function were measured by creatinine clearances and urinary excretion rates of beta 2-microglobulin and albumin. Forty-three male printing trade workers occupationally exposed to different organic solvents for 9-25 years were compared with 43 age-matched male controls. No differences were found either in creatinine clearances or average basal levels of beta 2-microglobulin and albumin excretion rates, whereas a positive relation could be demonstrated between alcohol consumption on the day before the trial and urinary excretion rate of albumin. This investigation did not reveal any adverse renal effects of moderate chronic exposure to organic solvents in a group of active trade workers.

Systemic availability of acetylsalicylic acid in normal men and women and its effect on in vitro platelet aggregability.

The systemic availability of acetylsalicylic acid (ASA) after oral ingestion of 1 g in an effervescent formulation was 16.3 +/- 2.0% and 16.9 +/- 3.2% of the ingested dose in normal women and men, respectively. The average plasma half-life of ASA in each sex was also identical at 18.5 +/- 1.4 and 18.1 +/- 1.2 min, respectively. The inhibitory effect of ASA on collagen-induced platelet aggregation in vitro on blood from both sexes was studied. The IC50 was 23.9 +/- 2.9 micrograms/ml in females and 22.5 +/- 2.7 micrograms/ml in males, which did not differ significantly. The inhibition by salicylic acid (SA) of the antiaggregatory effect of ASA was similar in both sexes with increases in IC50 to 33.5 +/- 5.1 micrograms/ml in females (p less than 0.02) and to 29.5 +/- 3.8 micrograms/ml in males (p less than 0.05). It is concluded that the observed sex-difference in the antithrombotic effect of ASA cannot be explained neither by differences between females and males in the pharmacokinetic properties of ASA after oral ingestion, nor by differences in the in vitro effect of ASA on the platelet aggregation induced by collagen.

Systemic availability of acetylsalicylic acid in human subjects after oral ingestion of three different formulations.

Systemic availability of acetylsalicylic acid (ASA) in normal human subjects after oral ingestion of 1 g in three different formulations was determined by using high-pressure liquid chromatography for ASA assay. For an effervescent, a plain and a sustained release preparation systemic availabilities expressed in percent of the ingested dose were 16.9 +/- 3.2, 8.6 +/- 1.2 and 2.6 +/- 0.4%, respectively. All subjects had clearly measureable amounts of ASA in plasma after oral intake of a sustained release preparation with an average peak concentration of 15 mumol/l. Peak concentration after an effervescent and plain formulation was on the average 80 and 40 mumol/l, respectively. Half-life of ASA in plasma was 18.1 +/- 1.2 min. for the effervescent and 28.7 +/- 5.3 min. for the plain preparation, while the elimination phase was too ill defined for the sustained release formulation. Average plasma half-life of salicylic acid (SA) was similar after the three different administration forms with values between 3.0 and 3.7 hrs. Further, no difference in SA distribution volumes or amounts of SA absorbed was found. The present study demonstrates that oral ingestion of ASA in effervescent, plain and sustained release formulations gives rise to significant amounts of ASA in plasma. Concentrations found indicate that long-term antithrombotic therapy with ASA in a sustained release formulation may be possible.

Antihypertensive effect of atenolol (100 mg once a day) and methyldopa (250 mg thrice a day). A double-blind cross-over multicentre study.

In a double-blind cross-over multicentre study lasting for 16 weeks, the antihypertensive effect of atenolol (100 mg once a day) was compared with that of methyldopa (250 mg thrice a day) in 48 patients with mild to moderately severe hypertension. At the end of the trial, atenolol was superior to methyldopa in achieving clinically relevant BP levels, less than 150/95 mmHg (p less than 0.001), and in respect to patients' drug preference (p less than 0.04). The BP levels after the first 2 weeks of treatment with either drug were identical but, in contrast to methyldopa, atenolol caused further significant reduction in BP during the following 4 weeks. This finding implies that one should hesitate to start additional therapy until after at least six weeks of atenolol treatment, whereas no further reduction in BP can be expected after the first 2 weeks of treatment with methyldopa. Two patients had to be withdrawn from the study during treatment with atenolol, as they developed severe bradycardia and dyspnoea, respectively. Other side-effects were few and of minor clinical importance.

178 fatal cases of pulmonary embolism in a medical department.

The diagnosis of pulmonary embolism was established during a 6-year period in 284 patients hospitalized in medical departments of a general hospital. Of the 183 patients who died, 178 were autopsied. A retrospective study was performed on the autopsy-verified fatal cases to correlate their clinical state to relevant postmortem findings. Two groups made thorough, independent evaluations of data from the medical and pathological records. In 95% of the patients a confirmed fatal pulmonary embolism constituted only a slight modification of life expectancy, because of concomitant complicating, severe, terminal disease. Reflecting this poor clinical state, only 26 patients (15%) had a diagnosis of pulmonary embolism premortally and of these patient, 13 died within 5 hours after onset of symptoms and 10 were treated with antithrombotic drugs. Our results seem to indicate an increase in the incidence of terminal diseases in the population of elderly, hospitalized patients and change the concept of fatal pulmonary embolism into an agonal incident in a terminal-care medical patient.