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Biomedical subjects

T Wessel-Aas

Publications and source records attributed to T Wessel-Aas.

At least 19 recordsLinked to original sources

Relation between low dose of hydrochlorothiazide, antihypertensive effect and adverse effects.

Thiazide diuretics are widely used in the drug treatment of hypertension but their dose-response curves for the antihypertensive and adverse metabolic effects differ. To characterize the lower end of the dose-response curve a double-blind, parallel group trial was performed as multicentre study in Scandinavia. One hundred and eleven patients with newly diagnosed or previously treated mild to moderate hypertension (untreated diastolic blood pressure of 95-115 mmHg after 4 weeks placebo) were randomly allocated to various doses of hydrochlorothiazide (3, 6, 12.5 or 25 mg) or placebo for 6 weeks. Blood pressure and biochemical variables (plasma renin activity, serum potassium, magnesium, urate, fasting glucose, total cholesterol, HDL-cholesterol, triglycerides and apolipoproteins A1 and B were measured. 12.5 mg hydrochlorothiazide had a borderline effect on blood pressure whilst 25 mg had a definite antihypertensive effect. Biochemical changes were seen in plasma renin activity, serum potassium and urate after the 12.5 and 25 mg dose. Three and 6 mg had no effect on blood pressure or metabolic parameters.

Adolescent↗

The influence of sustained release theophylline therapy on free fatty acids in serum.

The serum concentrations of theophylline, total free fatty acids (FFA) and subgroups were studied in ten healthy volunteers treated with sustained release theophylline twice daily during 9 days. Analyses were performed before and on day 1, 4 and 9 of treatment. Mean theophylline serum levels within the therapeutic range were obtained during the study, ranging from 62 +/- 7 to 82 +/- 10 mumol/l. The mean serum concentrations of total FFA and subgroups increased significantly during treatment, showing the highest levels on day 4. Comparing fasting total FFA concentrations, an increase of 123% and 48% from pretreatment levels were found on day 4 and 9, respectively. The subgroups were influenced to a different degree by theophylline intake. Arachidonic acid (20:4) was not increased, while among the others, saturated FFA increased less than the unsaturated.

Adult↗

Single dose pharmacokinetics of tiaprofenic acid. Effects of food and severe renal insufficiency.

The single oral dose pharmacokinetics of tiaprofenic acid (Surgam) has been investigated in fasting and non-fasting healthy volunteers (200 and 300 mg) and in fasting patients with severe renal insufficiency (200 mg). A dose independent pharmacokinetics of tiaprofenic acid was shown in fasting healthy volunteers and the following parameters were calculated after administration of 200 mg: tl = 0.53 +/- 0.15 h, tm = 1.28 +/- 0.19 h, cm = 27.1 micrograms/ml, ka = 2.79 +/- 0.93 h-1, lambda 2 = 1.06 +/- 0.14 h-1, t1/2 = 3.0 +/- 0.2 h, AUCl-infinity = 80 +/- 7 mg X h/l, Clt = 43.8 +/- 3.7 ml/min and V beta = 11.1 +/- 0.8 l. A small, but significant positive deviation from linearity was observed with increasing dose for cm and AUCl-infinity in non-fasting healthy volunteers, probably due to a slightly higher bioavailability of the 300 mg formulation in the non-fasting state as compared with the 200 mg formulation. Intake of food decreased cm significantly at both dosage levels from 27.1 to 19.1 micrograms/ml and from 47.9 to 39.1 micrograms/ml for 200 and 300 mg, respectively. The absorption kinetics of tiaprofenic acid was not significantly different in fasting healthy volunteers and in fasting patients with severe renal insufficiency. However, a significant increase in t1/2 and AUCl-infinity to 5.8 +/- 0.9 h and 173 +/- 34 mg X h/l, respectively, and a significant decrease in total body clearance to 25.5 +/- 5.3 ml/min were observed in this category of patients. No correlation was found between creatinine clearance and tiaprofenic acid clearance.

Aged↗

Hemodialysis and cell toxicity in vitro related to plasma triglycerides, post-heparin lipolytic activity and free fatty acids.

Plasma triglyceride (TG) concentrations, post-heparin lipolytic activities and the free fatty acid (FFA) pattern of uremic and normal plasma were compared and correlated to plasma toxicity as measured by the effect on human mononuclear phagocytes cultured in vitro. Plasma TG concentration and FFA: albumin molar ratios were significantly higher in uremic plasma, and a correlation was found between TG concentrations prior to heparinization and post-heparin FFA concentrations. Uremic plasma toxicity was significantly correlated to increased post-heparin FFA: albumin molar ratio. The post-heparin lipoprotein lipase activity in uremic plasma collected 120 min after heparinization was higher than in normal plasma. Qualitative and quantitative experiments in vitro showed increased plasma toxicity with increasing FFA: albumin molar ratios. The proportion of unsaturated FFA in uremic post-heparin plasma increased compared to saturated FFA during incubation for 96 hours. Altered lipid metabolism after systemic heparinization thus seems to be important for the cell toxicity of uremic plasma in vitro.

Adolescent↗

The effect of systemic heparinization on plasma lipoproteins and toxicity in patients on hemodialysis and continuous ambulatory peritoneal dialysis.

The lipid patterns of plasma from 6 patients on hemodialysis (HD) and 6 patients on continuous ambulatory peritoneal dialysis (CAPD) were compared and correlated to plasma toxicity as measured by the survival of human macrophages cultured in vitro. The median values for plasma triglycerides (TG), cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipolytic activities (lipoprotein lipase and hepatic lipase) were insignificantly higher in CAPD plasma than in HD plasma. The median high density lipoprotein (HDL) cholesterol/LDL cholesterol ratio was significantly higher in HD plasma than in CAPD plasma. In both groups systemic heparinization was followed by a significant increase in free fatty acids and in plasma toxicity. The difference in plasma toxicity was insignificant. In the whole group of patients (n = 12) toxicity in post-heparin plasma was correlated to pre-heparin very low density lipoprotein (VLDL) TG, but not to LDL TG. Separately post-heparin toxicity in CAPD plasma was correlated to pre-heparin total TG, VLDL TG and post-heparin LDL TG.

Adolescent↗

Toxicity of plasma from hemodialysis patients treated with heparin or prostacyclin.

Hemodialysis was performed in 6 uremic patients with either a bolus dose of 5 000 IU heparin or prostacyclin at a constant infusion rate of 5 ng/kg/min. Clinical data, plasma triglycerides (TG), free fatty acids (FFA), platelet aggregation, white blood cell count and plasma toxicity were measured prior to and during both procedures. No serious side-effects were recorded. Heparin induced a fall in plasma TG, a rise in FFA and increased plasma toxicity. Prostacyclin infusion had no effect on these parameters. During both tests a marked drop in white blood cell count was found 15 min after the start of hemodialysis. During heparin dialysis no clotting was observed in the extracorporeal circuit. During prostacyclin dialysis clotting was observed at the venous line in three cases.

Adult↗

Glucose, insulin and C-peptide kinetics during continuous ambulatory peritoneal dialysis.

The insulin and C-peptide kinetics due to glucose (50 g), given intraperitoneally or enterally has been compared in five non-diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The fasting C-peptide concentrations were three to ten times the normal values whereas the fasting plasma insulin concentrations were within normal limits. After intraperitoneal glucose administration a more marked hyperglycaemia (p less than 0.05) and a more long lasting hyperinsulinaemia (p less than 0.05) was found than after the enteral glucose load. The relative change in plasma C-peptide was slower and less pronounced in both experiments. C-peptide concentration in plasma did not differ significantly between the two experiments. Estimated total body clearance (Kt) for insulin was higher than for C-peptide (p less than 0.01), but dialysis clearance (Kd) for C-peptide was higher than for insulin in both experiments (p less than 0.01).

Adult↗

Labetalol in the treatment of hypertension in patients with normal and impaired renal function.

Labetalol (Trandate) is a new antihypertensive agent with both alpha- and beta-adrenoceptor blocking properties. In a double-blind cross-over study the antihypertensive action and side-effects of labetalol and propranolol were compared in 18 previously untreated outpatients with hypertension, WHO stage I--III. Mean daily dose of labetalol was 667 mg and of propranolol 129 mg. Labetalol reduced systolic and diastolic blood pressure in the seated and upright position significantly more than propranolol. The pulse rate reduction was greater with propranolol. Side-effects were more pronounced with propranolol. The antihypertensive effect, effect on pulse rate and pharmacokinetics of a single oral dose of 400 mg labetalol were studied in 6 patients with normal and 6 patients with impaired renal function (creatinine clearance less than 20 ml/min), all belonging to WHO stage I--II. A significant fall in pulse rate and systolic and diastolic blood pressure was observed in both groups, the duration being more than 25 h. No difference was found between the two groups. From the serum concentration-time curves the elimination rate constant, elimination half-life and area under the curve were calculated. The mean values of the two groups did not differ significantly. A pronounced interindividual variation was found in both groups.

Adult↗

Systemic heparinization of uremic patients and its effects on blood lipids and on in vitro toxicity of the plasma.

The effect of heparin on plasma lipids was investigated in uremic patients prior to and during hemodialysis, and in healthy individuals receiving equal heparin doses. The effects of heparin on plasma lipids were correlated with the effects of plasma on phytohemagglutinin (PHA)-stimulated lymphocytes, and on the function of human mononuclear phagocytes cultured in vitro. The plasma concentrations of high density lipoproteins, cholesterol and albumin were not influenced by systemic heparinization or hemodialysis. Plasma triglycerides showed a significant fall in both groups tested, and remained almost unchanged during hemodialysis. The ratio between the molar concentration of free fatty acids and albumin increased in both groups following systemic heparinization and was significantly correlated with a rise in plasma toxicity.

Adult↗

The effect of serum and plasma from haemodialysis patients on human mononuclear phagocytes cultured in vitro.

Human mononuclear phagocytes from healthy individuals were cultured in plasma and sera from normal persons and patients with chronic renal failure receiving haemodialysis. There was a marked detachment of macrophages from the glass coverslips when the cells were grown for 4 days in uraemic serum or plasma compared to normal serum. The ability of the macrophages to adhere to the glass coverslips was reduced when the cells were cultured in plasma from normal persons and uraemics subjected to systemic heparinization. However, the toxic effect of in vivo heparinization was much higher in the uraemics than in normal persons. Heparin added to normal and uraemic blood samples in vitro far in excess of in vivo heparinization did not influence the macrophage function to the same extent. Cell toxic substances seem to be produced as a consequence of systemic heparinization. These substances were not removed during 100 minutes of haemodialysis. Heparin added to pooled A Rh+ serum in concentrations far above those present in plasma following in vivo heparinization had little adverse effect on the macrophage function.

Adolescent↗

The effect of uraemic serum and plasma on proliferating cells in vitro.

Phytohaemagglutinin (PHA)-stimulated lymphocytes from healthy individuals and a malignant cell-line (K-562 cells) were cultured in a growth medium of 75 per cent RPMI 1640 (Gibco) supplemented with 25 per cent of uraemic serum or plasma obtained after systemic heparinization. Pooled human A Rh+ serum from 3 different donors served as controls. There was a depression of the DNA synthesis in both cell systems measured as uptake of methyl-3H-thymidine when the cells were cultured in uraemic milieu. Systemic heparinization markedly increased the depressive effect of uraemic plasma compared with controls. Heparin added to the growth media in concentrations much higher than those usually present in plasma after systemic heparinization had little effect on the cell proliferation. Systemic heparinization thus appears to induce production of toxic substances in plasma acting on proliferating cells.

Cell Division↗

Serum levels of mecillinam in patients with severely impaired renal function.

12 patients with severe renal insufficiency were treated for urinary tract infection with 400 mg of mecillinam intravenously every 6 h. High serum concentrations of mecillinam were found 6 h after the first morning dose on day 2 and day 5 of the treatment period (mean values 11.4 and 14.5 microgram/ml respectively), and a serum half-life of 334 min. In spite of reduced elimination of the drug, a nearly steady state was achieved within the first few days of treatment. Side effects were not observed.

Amdinocillin↗

[Lung physiology].

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Auscultation↗