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Biomedical subjects

S E Husted

Publications and source records attributed to S E Husted.

At least 91 records · Page 5Linked to original sources

The influence of intravenous furosemide on the renal excretion pattern of protein and protein degradation products.

To assist the attending physician who may have difficulties in deciding whether observed deviations from normal renal physiology are disease-induced or diuresis-induced we studied urinary excretion rate of proteins and protein degradation products in eight healthy male volunteers between 60 and 70 years. After a 24 hr control period in the ward the subjects received 80 mg furosemide intravenously. The 24 hr creatinine clearance was reduced from 95 +/- 9 to 83 +/- 6 ml/min. (P less than 0.05). The reduction in the 24 hr carbamide clearance from 35.8 +/- 9.4 to 33.1 +/- 6.2 ml/min. was not significant. The urinary pH was significantly increased during the first hour but after the pH showed a fall which was significant during 2-8 hours after the injection. Initially the urate excretion showed an apparent increase but from 1-8 hours after the injection significantly less urate was excreted. The 24 hr urate clearance was reduced by furosemide from 5.3 +/- 1.6 to 3.4 +/- 1.1 ml/min. (P less than 0.05) and the amount of urate excreted was reduced from 2.6 to 1.6 mmol per 24 hrs (p = 0.05). The excretion rate of beta 2-microglobulin was reduced (P less than 0.01) whereas the excretion rate of albumin was increased (P less than 0.05).

Aged↗

A new automated technique for platelet aggregation measurement.

A Multistat III Centrifugal Analyser (MCA) was used to measure platelet aggregation in vitro. It has a capacity of about 40 samples per h. In the analyser platelet-rich plasma and collagen-reagent were mixed, and the turbidity was measured as a function of time. The results were presented in arbitrary units ( arb . units), i.e. change in turbidity per min X 1000. The estimated 0.95 reference range was 50-95 arb . units, (n = 46) and the coefficient of correlation between MCA results and results obtained by conventional aggregometry ( Fibromat ) was 0.85 (P less than 0.001). The MCA method registered 50-75% reduction of platelet aggregation after intake of low dose acetylsalicylic acid (ASA) (1.2-4.0 mg/kg) during 3 days in 19 subjects. The MCA method is suitable to monitor ASA treatment routinely in order to establish an individual appropriate ASA dose during prophylactic treatment of arterial thromboembolic disease.

Autoanalysis↗

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

Adult↗

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.

Adult↗

The pharmacokinetics of frusemide are influenced by age.

After a 24 h control period 80 mg frusemide was given intravenously over 2 min to a group of young and a group of elderly healthy male volunteers. The serum concentration of frusemide and the excretion in urine of the drug and a glucuronidated metabolite were followed for 24 h. The elimination of the drug from serum was described by an open two compartment model. The serum clearance (CLs) was 170 +/- 19 ml min-1 in the young and 129 +/- 11 ml min-1 in the elderly (P less than 0.01) and the average renal clearance (CLr) was 67% of CLs in the young and 58% of CLs in the elderly (NS). The average amount of unchanged frusemide in the urine during the first 30 min was 30 +/- 6 mg in the young but only 20 +/- 4 mg in the elderly (P less than 0.01). The albumin concentration in serum was 15% lower in the elderly but on the average the protein bound fraction of frusemide was 98.6% in both groups. The Vd ss did not differ between the two age groups (0.130 1 kg-1) but the elimination half-life was 70 +/- 20 min in the young and 102 +/- 33 min in the elderly (P less than 0.05). In the young 11.4 +/- 5.0 mg frusemide was excreted as a glucuronidated compound whereas this figure was only 5.4 +/- 2.9 mg in the elderly (P less than 0.01). It is concluded that the age-related changes in the fate of unchanged frusemide in the organism mainly can be explained by a reduction in the tubular secretion of the drug which in turn may be caused by a reduction in renal plasma flow.

Adult↗

Topographic variations in alpha-adrenergic and cholinergic response in the pig renal pelvis.

The effect of alpha-adrenergic and cholinergic receptor stimulation is quantitatively analyzed in different regions of the pig pyeloureter. Smooth muscle strips from minor calyces, pelvis proper and ureter were investigated. Stimulation with potassium (127 mM) was used as reference. Both phenylephrine and carbachol caused a concentration-dependent increase in basal tone in the pelvis and the minor calyx. The maximum response obtained was significantly smaller in the pelvis than in the minor calyx. As compared to phenylephrine, the response to carbachol was negligible. The ureter showed a different behavior as compared to the minor calyx and pelvis. A constant basal tone could not be obtained and the tissue did not respond to potassium in a reproducible way.

Animals↗

Acute valproate intoxication: biochemical investigations and hemodialysis treatment.

A 20-year-old female was comatose for several days after intoxication with 75 g sodium valproate (VPA). She was successfully treated with hemodialysis, hemoperfusion, i.v. infusion of glucose, and given intensive care. Although a peak serum VPA of 2120 micrograms/ml (14720 microM) was registered 8 1/2 h after drug intake, no definite drug-related hepatotoxic or thrombocytopenic effects were seen. The only signs of organotoxicity were slight increases in serum amylase and a transient proteinuria. Further acute biochemical alterations were a decrease in serum calcium, an increase in plasma ammonia as well as in serum propionate, and elevated urinary excretions of adipic and suberic acid. Analysis of amino acids in serum revealed a stable increased level of glycine.

Adult↗

Long-term therapy of arterial hypertension with nifedipine given alone or in combination with a beta-adrenoceptor blocking agent.

The antihypertensive effect of nifedipine during long-term therapy was investigated in 5 patients receiving nifedipine as the sole drug and in 10 patients who had nifedipine in combination with a beta-adrenoceptor blocking drug. Nifedipine monotherapy was problematic because of side-effects and development of resistance to therapy after a few months. In patients who received the combined therapy significant and stable blood pressure reductions were maintained during the whole observation period (12-33 months). However, the occurrence of peripheral oedema in 4 of the patients necessitated the addition of a thiazide diuretic. It is concluded that nifedipine is not a first choice drug for the long-term treatment of arterial hypertension. When given in addition to a beta-blocker it is well tolerated and powerful but fluid retention may occur and if not counteracted by a diuretic it will limit the antihypertensive potential of the drug.

Adrenergic beta-Antagonists↗

Urinary retention during i.m. and extradural morphine analgesia.

In the postoperative period fifty-six healthy patients undergoing cholecystectomy or operations for duodenal ulcer, received, in a randomized order, i.m., "high-level" or "low-level" extradural morphine. Thirty-five per cent in the i.m. group, 33% in the high-level group and 50% in the low-level group suffered urinary retention, in all cases within the first 24 h. The mean cumulative dose of morphine necessary for pain relief was in the same range (13.4-16.5 mg) during the first 2 h of therapy for all groups, while the amounts after 24 and 48 h were twice to four times with the i.m. route compared with the extradural route. A peripheral effect of morphine on the urinary bladder is possible and the mechanism of action is discussed.

Adult↗

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.

Administration, Oral↗