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Biomedical subjects

B Lindström

Publications and source records attributed to B Lindström.

At least 109 records · Page 6Linked to original sources

Transfer of terbutaline into breast milk.

Terbutaline has been determined in milk and plasma from 4 nursing mothers treated with Bricanyl tablets (2.5 or 5 mg, 3 times daily) because of obstructive lung disease. Both doses produced milk concentrations of terbutaline in the range 2.5-4.6 ng/mL, which were similar to or higher than the concentrations found in plasma. The highest milk:plasma concentration ratios (up to 2.9) were observed at the beginning and end of the dosage interval. The infants in this study were estimated to have ingested about 0.4-0.6 micrograms/kg/day of terbutaline base, which corresponds to 0.2-0.7% of the daily dose per kg taken by the mothers. Terbutaline was not detectable in plasma when samples were taken from one of the infants and no symptoms of beta-adrenoceptor stimulation could be found in any of the babies.

Biological Transport↗

Steady-state kinetics of sustained-release phenylpropanolamine.

The plasma concentrations and the urinary excretion of phenylpropanolamine were studied in eight healthy volunteers during a dose interval in steady state after intake of a sustained-release preparation of the drug (Rinexin, AB Leo). The plasma and urine levels were determined by a gas chromatographic method using electron capture detection, with a detection limit of about 10 ng/ml. The sustained-release action of the dosage form was consistent in all subjects, with a flat plasma concentration-time profile between 2 and 8 h after dose intake. Cmax was 167 +/- 28 ng/ml (mean +/- SD) and Cmin 59 +/- 19 ng/ml. The terminal plasma half-life was 5.6 +/- 1.0 h, total body clearance 0.57 +/- 0.14 l/kg/h, Vdarea 4.4 +/- 1.2 l/kg, and the fraction excreted unchanged in the urine 86 +/- 13%. In conclusion, phenylpropanolamine was found to be a high clearance drug characterized by extensive renal elimination of unchanged drug. The plasma levels showed only small interindividual variations in our healthy volunteers. Caution should be taken in treating patients with impaired renal function.

Adult↗

[Effects of antiandrogenic treatment with cyproterone acetate on the sexual tonus in virilized women].

Sexual responsiveness was assessed in 46 virilized women during cyproterone acetate treatment over a period of several years according to a sexual score previously described. In general, sexual tonus was depressed by intensive cyproterone acetate medication of several months' duration without concurrent oestrogen. By changing to sequential therapy according to Hammerstein, however, sexual tonus returned to initial levels in the group with normal pre-medication responsiveness. Furthermore, in another group with diminished sexual tonus before treatment, sexual responsiveness, in particular the capacity for orgasm, was stimulated to the level of the first group. The endocrinological basis for this observation is discussed with aid of results of the plasma testosterone/sex hormone binding globulin complex.

Adult↗

Plasma theophylline and caffeine and plasma clearance of theophylline during theophylline treatment in the first year of life.

Plasma concentrations of caffeine and theophylline were simultaneously determined in 17 preterm infants after oral administration of aminophylline for treatment of apnoea. The ratio of caffeine/theophylline concentration in plasma increased during the first 2 weeks of treatment, owing to the longer time required for caffeine than for theophylline to reach steady state. The caffeine/theophylline ratio at steady state was 0.57 +/- 0.03 (mean +/- SE). Thus, caffeine contributed significantly to the total methylxanthine load in the infants. The plasma clearance of theophylline was calculated from the plasma steady state concentrations. In 3 preterm infants treated with oral aminophylline, repeated sampling showed an approximately linear increase in clearance with time from 16.8 +/- 0.4 (mean +/- SE) at a postnatal age of 6-11 days to 30.9 +/- 2.5 ml/kg/h at 64-69 days. In 1 full-term infant treated with oral theophylline from 3.5 to 11.5 months of age, the plasma clearance of theophylline increased in a roughly linear manner, reaching a plateau of about 100 ml/kg/h at 6-7 months of age. This corresponds to the clearance found in 1-4 year old infants.

Apnea↗

Coupling between renal tubular secretion and effect of bumetanide.

The relationship between renal tubular secretion of bumetanide and its saluretic effect was studied in six healthy subjects before and after probenecid (1 gm IV). Bumetanide was determined in serum and urine by HPLC. Continuous intravenous infusion of bumetanide (200 micrograms/hr) gave an average diuresis at steady state of 15 +/- 3 ml/min. Corresponding plasma concentration, urinary excretion rate, and renal clearance of bumetanide averaged 14.3 +/- 2.3 ng/ml, 64 +/- 31 micrograms/30 min, and 145 +/- 59 ml/min. After probenecid there was a marked change in bumetanide kinetics. Average plasma concentration rose to 41.7 +/- 8.1 ng/ml, whereas renal clearance and urinary excretion rate fell to 15.1% and 29.5% of control. There was also a concomitant decrease in diuresis and saluresis to 47% and about 40% of control. Probenecid also reduced the renal clearance of para-aminohippurate and inulin to 67% and 75% of control. Since the fractional water and sodium chloride excretion was also reduced about 33% and 42%, it is concluded that a large part of the diuretic effect of bumetanide depends on its active tubular secretion. As with furosemide and piretanide, bumetanide diuresis is elicited from the luminal side of the human nephron.

Adult↗

Disposition of chloroquine in man after single intravenous and oral doses.

1 Chloroquine was given in 300 mg single doses as an i.v. infusion, an oral solution and as tablets at intervals of at least 56 days to 11 healthy volunteers. Concentrations of chloroquine and its metabolite desethylchloroquine were measured in plasma, erythrocytes and urine using h.p.l.c. 2 Chloroquine was detectable in all plasma samples up to 23 days and occasionally up to 52 days after dosage. Urinary concentrations were monitored up to 119 days. The disposition pattern was multiexponential reflecting extensive tissue binding of the drug. 3 After i.v. dosing the volume of distribution ranged from 116 to 285 l/kg and the apparent terminal half-life from 146 to 333 h. Total plasma clearance +/- s.d. was 712 +/- 166 ml/min and renal clearance 412 +/- 139 ml/min. The mean estimated urinary recovery of chloroquine was 47%, 42% and 46% after i.v., oral solution and tablets indicating nearly complete bioavailability. The corresponding figures for the metabolite were 7%, 10% and 12%. 4 The disposition of chloroquine in erythrocytes was parallel to that in plasma. The concentrations in erythrocytes were consistently 2 to 5 times higher than in plasma. 5 Subjective side effects like difficulties with swallowing and accommodation, diplopia and fatigue occurred during intravenous infusion and were closely related to plasma concentrations. No effect was seen on the electrocardiogram, mean arterial blood pressure and pulse rate. No adverse reactions were observed after the oral doses. High frequency audiometry did not reveal any significant hearing impairment for the group as a whole.

Administration, Oral↗

Clinical pharmacology of pyridostigmine and neostigmine in patients with myasthenia gravis.

Determination of plasma concentration of pyridostigmine in 20 myasthenic patients on maintenance therapy revealed rather small intraindividual variations within a dose interval. The predose concentration varied considerably between different patients and up to seven fold in patients on the same daily dose. No pharmacokinetic interaction between pyridostigmine and neostigmine was found in five patients studied. In six patients the decrement in the deltoid muscle was studied in parallel with determination of the plasma concentrations following administration of pyridostigmine or neostigmine. In these patients the existence of a "bell-shaped" dose response curve is suggested with the maximal effect at a concentration of 30-60 ng/ml for pyridostigmine and 5-15 ng/ml for neostigmine.

Adult↗

Intrathyroidal concentrations of methimazole in patients with Graves' disease.

A sensitive gas chromatographic-mass spectrometric method enabled us to study intrathyroidal concentrations of methimazole in 20 euthyroid patients with Graves' disease on treatment with carbimazole and T4. There was no difference between patients receiving a final dose of carbimazole (10 mg), known to be totally bioactivated to methimazole (6.1 mg), 3-6 h before thyroid excision (518 ng/g thyroid tissue +/- 90 SEM) and patients who received the same dose 17-20 h before excision (727 ng/g thyroid tissue +/- 157 SEM), indicating a slow intrathyroidal turnover of the drug. On the other hand, the serum concentrations were much higher in the first group (102 ng/ml +/- 5 SEM vs. 16 ng/ml +/- 3 SEM), reflecting a short plasma half-life of the drug. The intrathyroidal concentrations of methimazole ranged from 230-1895 ng/g among individual glands but were similar in pieces from different parts of a single gland. These methimazole concentrations are lower than the concentrations reported by others to have an immunosuppressive action on lymphocytes in vitro.

Adult↗

A case material with post lingual severe hearing loss and communication handicap.

The analyses have given some general clues to the therapeutic handling of these patient categories: 1. The A and B groups can be labelled "hearing" with clearly useful residual hearing. 2. The patients in the C group, as a rule, are utilizing very little from acoustic speech stimulation, mostly the prosodic information. Several patients in this group are possible implant candidates, and it is reasonable to expect that (with a suitable stimulus device and a suitable application of this) the patients could get an additional support during speech reading, so that they function as the B group. Tactile devices are also an alternative or a supplement for this group, and a pilot study on six patients is in progress in the department in cooperation with the Department of Speech Communication at the Royal Institute of Technology. 3. The patients within the A and B groups will in the first place be offered additional functional training programmes (prosodic training, audio-visual training and possibly vibration training) and, as an ultimate alternative a social activation in group therapy may be considered. Some patients in these groups might also be candidates in the future for an extra cochlear implant.

Hearing Aids↗

Comparative bioavailability of carbimazole and methimazole.

In this study we investigated the oral bioavailability of therapeutic doses of two antithyroid drugs, methimazole and carbimazole, in seven euthyroid subjects. To increase the statistical power deuterium-labeled methimazole was given orally as an internal standard together with the tested drugs. Using a recently described highly sensitive gas chromatographic-mass spectrometric assay for methimazole we found that intake of 15 mg carbimazole resulted in plasma concentrations of methimazole and pharmacokinetic data comparable to intake of an equimolar amount of methimazole, i. e., 9.2 mg. Maximum concentrations of 163 and 149 ng/ml, respectively, were reached in both instances at 0.9 h after intake of 15 mg carbimazole and 10 mg methimazole. The plasma half-life was 5.7 and 5.4 h, respectively. In contrast to previous suggestions the interindividual differences in pharmacokinetics were small. In conclusion, carbimazole was rapidly and totally bioactivated to methimazole, and the drugs should be regarded as equipotent when compared on a molar basis.

Administration, Oral↗

Electrically induced short-lasting tetanus of the calf muscles for prevention of deep vein thrombosis.

Electrical calf muscle stimulation during surgery has been used for the prevention of deep vein thrombosis (DVT) with varied results in several studies. This effect is mainly achieved by the reduction of venous stasis in the legs. Another possible beneficial effect might be an increased fibrinolytic activity of the blood secondary to the muscle contractions. Previously, single electrical impulses have been used for stimulation, giving rise to 'single twitches' in the muscles. In the present study the effect on calf volume of muscle stimulation with groups of impulses giving a short-lasting tetanus was investigated. Changes in calf volume were recorded by strain gauge plethysmography. Optimal values for duration, number and frequency of the impulses within the groups were determined. Stimulation with groups of impulses reduced calf venous volume approximately three times more efficiently than stimulation with single impulses. Calf muscle stimulation did not enhance the increase in fibrinolytic activity of venous blood observed after oesophago- or laryngoscopies under general anaesthesia.

Adult↗

Prediction and prophylaxis of postoperative thromboembolism--a comparison between peroperative calf muscle stimulation with groups of impulses and dextran 40.

The effects of peroperative electrical calf muscle stimulation with groups of impulses giving a short lasting tetanus of the calf muscles on postoperative deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared with that of dextran 40 given per and postoperatively. The incidence of DVT and PE during the first 4-6 postoperative days was recorded. The diagnosis of DVT was based on the 125I-fibrinogen uptake test and phlebography and of PE on pre- and postoperative perfusion pulmonary scintigram and chest X-ray examination. Both methods reduced the incidence of PE. Calf muscle stimulation reduced the DVT incidence in patients with malignant disease while the reduction in DVT incidence for the whole group only was significant in the stimulation as well as the dextran 40 group. Mean values for preoperatively determined levels of antithrombin III, beta-thromboglobulin, fibrinopeptide A, plasminogen and ability to release fibrinolytic activity during venous stasis did not differ between those patients who developed or those who did not develop postoperative DVT or PE. However, antithrombin III levels below 80 per cent appeared to predispose to postoperative thromboembolism. The two prophylactic methods have similar effects on the incidence of postoperative thromboembolism. The stimulation method has certain advantages due to its safety and simplicity.

Adult↗

Alpha-receptor function changes after the first dose of prazosin.

The effect of oral prazosin on blood pressure and antagonism of phenylephrine-induce blood pressure increase was investigated in six healthy subjects during a dosing interval after the first dose and 3 days after the first dose of the drug. Prazosin lowered standing blood pressure more after the first dose than after the same dose 3 days later, despite similar plasma levels. Blood pressure decrease correlated with plasma prazosin levels during the elimination phase at the first dose, but not after 3 days of therapy. The phenylephrine log dose-response curves shifted to the right after prazosin, which indicates alpha-receptor antagonism of the drug. On day 4, the phenylephrine curve before prazosin dose shifted to the right of the pretreatment curve on day 1, despite very low prazosin plasma levels. On day 4 after after prazosin dosing the phenylephrine dose-response curves were shifted to the left of that on day 1. Our data indicated tolerance to prazosin effect on blood pressure and to phenylephrine agonism after 3 days dosing. Our data suggest that this might be due to desensitization of alpha-adrenoceptors with differential effects of agonists and antagonists.

Adult↗

Prazosin first dose phenomenon during combined treatment with a beta-adrenoceptor blocker in hypertensive patients.

1 The antihypertensive effect of prazosin has been studied in three groups of hypertensive patients. 2 The drug caused a significant reduction of blood pressure both as monotherapy and combined with alprenolol. 3 The effect of prazosin on blood pressure was more marked at the first dose and especially in combination with alprenolol. 4 No pharmacokinetic interaction between prazosin and alprenolol was observed. 5 Prazosin exhibits an exaggerated first dose effect together with alprenolol. Smaller starting doses of prazosin in combination therapy with beta-adrenoceptor blockers are warranted.

Adult↗

Oral leukoplakias. A microradiographic and lipid-histochemical study.

Biopsies from 13 oral leukoplakias and from normal tissue specimens in the contralateral region of each patient were examined microradiographically and lipid-histochemically using freeze-sectioned and freeze-dried sections. The investigation showed that an epithelial zone of cell layers with different degrees of keratinization and varying dry mass concentrations occurred in oral leukoplakias. A concentrated localization of phospholipids, free fatty acids and cholesterols was found in the zones with a high dry mass content and, consequently, high keratin content, while a negative lipid reaction was obtained in the zones where the dry mass concentration was low.

Adult↗