Is thoron a problem in Swedish dwellings? Results of measurements of concentrations of thoron and its progeny.

Long-term measurements of thoron progeny concentrations (equilibrium-equivalent thoron concentration) have been carried out in Swedish dwellings with the aim of investigating if thoron and its progeny pose a health risk. Measurements were performed in 93 houses and 25 apartments. In addition to thoron progeny concentration, thoron gas concentration near the wall surface, ambient dose equivalent rate of gamma radiation and radon gas concentration were also measured. The results show that the mean value of thoron progeny was 2.2 Bq m(-3) in houses and 1.6 Bq m(-3) in apartments. Ten per cent of the dwellings (both houses and apartments) had thoron progeny concentrations exceeding 10 Bq m(-3). Thoron progeny concentration is not significantly different in dwellings built of alum shale-based aerated concrete ('blue concrete') than dwellings built of other construction materials. For the dwellings in this study (not representative of the Swedish population), the mean dose estimated due to exposure to thoron was found to be 0.4 mSv y(-1).

A simple double-focusing electrostatic ion beam deflector.

We have developed an electrostatic, double-focusing 90 degrees deflector for fast ion beams consisting of concentric cylindrical plates of differing heights. In contrast to standard cylindrical deflectors, our design allows for focusing of an incoming parallel beam not only in the plane of deflection but also in the orthogonal direction. The optical properties of our design resemble those of a spherical capacitor deflector while it is much easier and more cost effective to manufacture.

Enhancement of dicoumarol bioavailability by concomitant food intake.

The influence of food intake on the bioavailability of dicoumarol from a non-micronized formulation was examined in ten healthy volunteers, by examination of its single-dose kinetics after ingestion of dicoumarol 250 mg with a standardized breakfast and on an empty stomach. Blood samples were collected at regular intervals from 0 to 72 h, and the serum concentration of unmetabolized dicoumarol was determinded by spectrophotometry. Postprandial AUC (area under the curve) values were significantly (p less than 0.01) greater than the preprandial figures, the mean increase being 85 per cent. The results suggest that dicoumarol should always be taken with food.

Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus.

A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0.5-3.9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 mumol/l (244 mug/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs.Only 2 (5.4%) of the tolbutamide-treated patients and 10 (16.7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5.5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8.0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient.There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug.We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.

Enhancement by food of canrenone bioavailability from spironolactone.

The influence of food intake on the bioavailability of canrenone, the major and active metabolite of spironolactone, was explored in 8 healthy male volunteers. Spironolactone was administered as a single oral dose of 100 mg, both in the fasting state and together with a standardized breakfast. Numerous venous blood samples were taken from 30 min to 96 hr after ingestion of the drug, and the plasma concentrations of canrenone were determined by spectrofluorometry. The results indicate that more canrenone enters the general circulation when spironolactone in ingested together with a meal.

Enhancement of hydralazine bioavailability by food.

The influence of food on the bioavailability of hydralazine in noncoated and coated tablets was examined in 5 healthy males. Each subject received an oral 50-mg dose on four different occasions: two 25-mg noncoated tablets with and without food and one 50-mg coated tablet with and without food. The meal was a standardized breakfast of 440 calories. Venous blood samples were obtained during a 6-hr period, and the plasma concentrations of unmetabolized hydralazine were assessed by a selective and sensitive gas chromatographic method. The results indicate that food enhances the bioavailability of hydralazine 2- to 3-fold both when noncoated and coated tablets are used.

Enhancement of the bioavailability of propranolol and metoprolol by food.

The possible influence of food intake on the bioavailability of one nonselective and one cardioselective beta adrenoceptor antagonist, propranolol and metoprolol, was examined by serial determinations of the drug concentrations in blood of healthy subjects, taking single doses of the drugs both on an empty stomach and together with a standardized breakfast. The results indicate that food enhances the bioavailability of both propranolol and metoprolol. They also confirm that there is extensive interindividual variation in the bioavailability of these drugs.

Divergent effects of 6-propylthiouracil on 3,3',5'-triiodothyronine (RT3) serum levels and in man.

The effect of 6-propylthiouracil (PTU) on the peripheral conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (reverse T3 rT3) was investigated by assessments of the concentrations of T4 T3 and rT3 in peripheral venous blood from T4-treated healthy volunteers given PTU, 4 X 150 mg daily. Within on day of PTU administration, serum T3 concentrations were reduced, and those of rT3 enhanced. These deviations lasted as long as PTU was given (five days), and there was a rapid return towards normal within one day after PTU administration ceased. It seems probable that, in man, PTU can evoke a diversion of T4 monodeiodination, less being converted to the metabolically active T3 and more to the metabolically inactive rT3. It is ppossible that the rapidity whereby PTU can reduce T3 levels can offer an advantage in the treatment of hyperthyroidism.

Bioavailability of oxazepam: absence of influence of food intake.

The possible influence of food intake on the bioavailability of the anxiolytic drug oxazepam was assessed in eight healthy volunteers taking a single dose of the drug both on an empty stomach and together with a standardized breakfast meal. The serum concentrations of oxazepam were determined by gas chromatography on samples obtained before, and at numerous occasions up to 48 hours after drug administration. The results indicate that concomitant food intake has no essential influence on the bioavailability of oxazepam.

Secretion of thyroxine, 3,5,3'-triiodothyronine and 3,3'5'-triiodothyronine in euthyroid man.

The secretion of iodothyronines from the normal human thyroid gland was assessed by radioimmunoassay analyses of the concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (reverse T3, rT3) in thyroid venous and peripheral venous blood. The subjects studied were euthyroid patients undergoing parathyroid surgery. Measurements were carried out both under apparently normal conditions, following peroral T3 pre-treatment, and before and after acute administration of TSH into a thyroid artery. In the control subjects, significant gradients between thyroid venous and peripheral venous concentrations were recorded both for T4, T3 and rT3, suggesting that all three iodothyronines are secreted by the normal human thyroid. T3 pre-treatment seemed to reduce this secretion, and acute administration of TSH promoted rapid, marked, and concomitant increments in the thyroid venous concentrations of all three iodothyronines. Hence, it appears that not only T4 but also T3 and rT3 are secreted by the normal human thyroid gland, and that TSH stimulates the secretion of all three iodothyronines. On the other hand, calculations of the relative secretion rates uielded the relation T4:T3:rT3 as 85:9:1. This indicates that, in euthyroid subjects, most of T3, and almost all of rT3, is produced by extrathyroidal conversion of T4 and not by direct thyroidal secretion.

Bioavailability of propylthiouracil: Interindividual variation and influence of food intake.

The bioavailability of 6-propylthiouracil (PTU) has been examined in eight healthy volunteers, with respect to interindividual variation and influence of food intake. PTU was given as a single oral dose, both in a fasting state and together with a standardized breakfast. Numerous venous blood samples were taken during 5 hours after PTU ingestion, and the concentration of unmetabolized PTU in serum was determined by a specific gas-chromatographic technique. The observations indicate that the amount of PTU absorbed is subject to a large interindividual variation, and that concomitant food intake may exert a minor and non-systematic influence on PTU absorption. Hence, the major issue in PTU therapy is the individualization of the size and interval of dosage. Testing of single-dose PTU kinetics in patients would apparently be helpful.

Blood levels of 3,5,3'-triiodothyronine and thyroxine: differences between children, adults, and elderly subjects.

The serum levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) in children, adolescents, adults, and elderly subjects have been measured by radioimmunoassays. It was found that while the T4 levels were essentially equal in all age groups examined, the T3 levels were markedly different. In children and adolescents (1-15 years), high values were recorded; indeed, they exceeded the upper normal limit in adults (20-80 years). From the age of 20, the T3 levels remained unaltered until the age of 80, after which there was a further reduction, to values approaching the lower normal limit for T3 in middle-aged subjects. The findings emphasize that separate normal values must be established for different age groups, in order to avoid diagnostic misinterpretations and therapeutic failures.

On the influence of concomitant food intake on sulfonamide bioavailability.

The influence of food intake on the bioavailability of a frequently used short-acting sulfonamide, sulfaisomidine (Elkosin), has been examined in eight healthy volunteers. The drug was administered as a single oral dose, both on an empty stomach and together with a standardized breakfast. Numerous venous blood samples were drawn for the first eight hours after ingestion of the drug, and the concentration of unmetabolized sulfonamide in serum was assessed by spectrophotometry. The observations indicate that concomitant food intake alters neither absorption rate, peak concentration, time to reach peak concentration, elimination rate, nor total amount of sulfonamide reaching the general circulation. Thus, the absorption of orally administered sulfaisodimidine is not at all affected by concomitant intake of food. This finding contrasts with previous observations on some other sulfonamides, and it may signify a therapeutic advantage of sulfaisodimidine. In addition, the amount absorbed showed only a little interindividual variation. This suggests that the use of standardized size and interval of sulfaisodimidine dosage can be recommended. The present findings emphasize that conclusions about the absorption of a certain drug should not be derived from studies with other, albeit chemically related, compounds.

Reduction of isoniazid bioavailability in normal men by concomitant intake of food.

The influence of food intake on the bioavailability of isoniazid (INH) has been examined in nine healthy male volunteers. INH was administered as a single oral dose, both in fasting state and together with a standardized breakfast. Numerous venous blood samples were obtained 5 min-6 hours after the INH ingestion, and the concentrations of unmetabolized INH in serum were assessed by spectrophotometry. The observations indicate that both the peak concentration and the total amount of INH absorbed are greatly reduced when the drug is ingested together with food. Hence it is recommended that, in the treatment of tuberculosis with INH, the drug should be given on an empty stomach. The data may also have some bearing on the use of INH for assessing acetylation rates and estimating dosages of hydralazine and related drugs.