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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 163 records · Page 9Linked to original sources
PubMed1981

Acetylator phenotyping: a comparison of the isoniazid and dapsone tests.

A comparison was made between the results of acetylator phenotyping by isoniazid (INH) half-life measurements based on 5 samples (0-6 h), and by determination of the ratio of monoacetylated (MAD) to unchanged dapsone (DDS) in a single sample obtained 3 h after dapsone intake. In each of 44 subjects examined, there was unequivocal agreement about classification of the subject as a rapid (INH t1/2 less than 2 h; MAD/DDS greater than 0.3) or slow (INH t1/2 greater than 2 h; MAD/DDS less than 0.3) acetylator. It appears that the single-sample (3 h) dapsone test is as reliable as the more laborious and time-consuming INH test for acetylator phenotyping.

Acetylation↗
PubMed1981

Excretion of paracetamol in human breast milk.

Breast milk and plasma levels of paracetamol were monitored in 3 lactating women after ingestion of a single 500 mg dose of paracetamol. The paracetamol concentrations were consistently lower in milk, with a mean milk/plasma AUC ratio of 0.76. This value was in close agreement with the milk/plasma partition ratio of 0.81 found in vitro, and could be related to quantitative binding differences between the two fluids. The half-lives of paracetamol in plasma and breast milk were almost identical, with an overall mean of 2.7 h. As less than 0.1% of the maternal dose would be present in 100 ml milk, breast feeding need not be discontinued due to paracetamol treatment in conventional dosage.

Acetaminophen↗
PubMed1981

High-pressure liquid chromatographic determination of acetylsalicylic acid, salicylic acid, diflunisal, indomethacin, indoprofen and indobufen.

A high-pressure liquid chromatographic technique was developed which allowed concurrent measurement of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma. ASA was extensively deacetylated to SA not only in vivo but also in vitro, even in frozen plasma. The in vitro conversion could be prevented by physostigmine. In vivo, ASA was eliminated within few hours, whereas SA was continuously present following daily administration of conventional doses of ASA. A slight modification of a similar method, originally developed for naproxen determination [9], was found appropriate for measurement of the SA derivative diflunisal, of two non-SA antiinflammatory agents, indomethacin and indoprofen, and of a related anti-platelet agent, indobufen.

Anti-Inflammatory Agents↗
PubMed1981

Influence of smoking on thyroid activity.

Serum concentrations of T4, T3, rT3 and TSH were determined before and after cessation of chronic smoking in healthy subjects. Their body weights were measured at the same intervals. Abstention from smoking was monitored through determination of CO content in blood. Cessation of smoking was accompanied by small reductions in serum T4 and rT3 and by a small rise in serum TSH. Serum T3 was not significantly altered. A minor rise in body weight was noticed. It is suggested that smoking promotes a modestly increased secretion of thyroid hormone, which is readjusted to normal following cessation of smoking. The assumed smoking-induced increase in thyroid hormone secretion is apparently not mediated by enhanced TSH secretion but by some other factor, e.g. the sympathetic nervous system. The hormonal changes might contribute to the increase in body weight frequently seen after cessation of smoking.

Adult↗
PubMed1981

Effects of sulfonylurea on the secretion and disposition of insulin and C-peptide.

In an attempt to examine the influence of sulfonylurea on the secretion, disposition and effect of insulin, 9 diabetic patients were studied during three one-month medications with (a) chlorpropamide (t1/2 greater than 24 h) once daily, (b) glipizide (t1/2 2-4 h) once daily, and (c) glipizide in divided dosage. The food intake of each patient was identical during each examination period. Blood concentrations of C-peptide, insulin, glucose, and drugs were determined before and after breakfast and lunch on the 4th day of each examination period. As expected, once-daily administration of glipizide led to higher after-breakfast concentrations of the drug than when the dose was divided. However, the C-peptide changes following breakfast were similar both during these two treatments and also during chlorpropamide, indicating that the amounts of insulin released from the pancreas were equivalent. In spite of this, glipizide once daily yielded 60-70% more insulin in systemic blood following breakfast than did the two other treatments. Reasonably, this signifies that the hepatic extraction of insulin was reduced during once-daily glipizide, allowing more insulin to reach systemic circulation. In addition, this was found to promote a more effective utilization of glucose following breakfast. Following lunch, the C-peptide release, the plasma insulin increase and the blood glucose reduction were greater when glipizide was given in divided dosage than when once-daily glipizide or chlorpropamide was employed. This occurred even though the after-lunch concentration of glipizide in systemic blood was lower rather than higher during divided than during once-daily administration. This supports the notion that the effect of orally administered sulfonylurea is determined not only by its concentration in systemic blood but also by its gastroenterohepatic appearance. Glipizide may offer greater therapeutic flexibility than chlorpropamide, but further studies are required to define the optimum choice and use of sulfonylureas.

Aged↗
PubMed1981

Varying distribution of acetylation phenotypes in RA patients with and without Sjögren's syndrome.

The acetylator phenotype status was studied in 61 patients with rheumatoid arthritis (RA), of whom 27 had associated Sjögren's syndrome (SS). The acetylation tests were carried out by means of isoniazid and in 24 patients also with the use of dapsone; there was complete agreement between the outcome of the two tests. The results showed that the frequency of slow acetylators in the whole material was 59%. In RA patients with SS, however, the frequency of slow acetylators was as great as 78%, while it was only 44% among patients without SS (p less than 0.02). Thus, there appears to exist a (pharmaco) genetic difference between RA patients with and without SS. In addition, toxicodermias were found to be more frequent in RA patients with than without SS (P less than 0.01). However, this could not be systematically correlated to slow acetylation.

Acetylation↗
PubMed1981

Comparison of diflunisal and acetylsalicylic acid in patients with rheumatoid arthritis.

A double-blind comparison of the clinical efficacy and tolerance of varying doses of diflunisal (DFS) and acetylsalicylic acid (ASA) was carried out in 15 patients with rheumatoid arthritis who were given no other antirheumatic medication. An effort was made to select appropriate anamnestic, functional and sociofunctional tests and to optimize their validity by careful measurements performed by the same specialized physiotherapist and occupational therapist. In addition, the serum concentration of DFS and salicylic acid were monitored by high-pressure liquid chromatography. The therapeutic effects of DFS was at least as good as that of ASA. Moreover, DFS was better tolerated; all 7 patients on DFS could sustain the maximum dose (1g) of this drug, while that of ASA (4g) was tolerated by only one of 8 patients. All these experienced side effects, necessitating drug withdrawal in 3 cases, one being a serious hepatotoxic reaction. DFS treatment, on the other hand, was associated with only one minor side effect. The side effect difference was statistically significant (p less than 0.01). The analyses of drug concentrations in serum verified that all patients were exposed to DFS and ASA as planned, adding safety to the judgement of the therapeutic effects. The findings support the view that the novel salicylic acid derivative DFS may offer a therapeutic advantage in the treatment of rheumatoid arthritis; it seems to have at least the same therapeutic effect as ASA an may be better tolerated.

Adult↗
PubMed1981

Interaction of glipizide and indoprofen.

The possible kinetic and dynamic interactions of indoprofen and glipizide were investigated in 6 healthy volunteers, taking indoprofen 200 mg t.i.d. for 7 days and a single dose of glipizide 5 mg before and during indoprofen medication. Series of blood samples were obtained for measurements of indoprofen, glipizide and glucose concentrations in blood. In addition urine concentrations of indoprofen were determined. The concentrations of indoprofen and glipizide were examined by HPLC and that of glucose enzymatically. Results suggest that indoprofen may reduce glipizide concentrations in plasma, but this does not seem to influence the blood glucose response to glipizide.

Administration, Oral↗
PubMed1980

VIP occurs in intrathyroidal nerves and stimulates thyroid hormone secretion.

Vasoactive intestinal polypeptide (VIP) is known to have powerful effects on the secretion from several endocrine and exocrine glands, and occurs in nerves with a ubiquitous distribution in the body. This infers that neuronal VIP may be a regulator of such secretion, and there is evidence that it is involved in the regulation of exocrine pancreatic function. Previous studies have shown that adrenergic and cholinergic nerves participate in the regulation of thyroid hormone secretion. We describe here combined immunohistochemical and immunochemical studies which show that the thyroid of several species is supplied with VIP-containing nerve fibres that surround blood vessels and run between and along thyroid follicles and that in the mouse neuronal VIP participates in the regulation of thyroid hormone secretion through a mechanism that is mediated by cyclic AMP.

Animals↗
PubMed1980

Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients.

The effects and plasma concentrations of different doses of propranolol and metoprolol were studied in 34 hyperthyroid patients. The initial daily doses were propranolol 160 mg or metoprolol 200 mg. If the resting heart rate remained above 75 beats per min after treatment for 4-7 days, the dose was increased and the patient re-examined after a further 4-7 days. Propranolol (n = 17) caused a reduced heart rate, a decrease in serum 3,3',5-triiodothyronine (T3) and an increase in serum 3,3',5'-triiodothyronine (reverse T3, rT3). In 10 patients, there was no change in T3 or rT3 until the daily dose of propranolol had been increased to 240 or 320 mg. The plasma level of propranolol was significantly correlated with the decrease in T3 and the increase in rT3. Metoprolol (n = 17) caused a reduction in heart rate similar to that following propranolol. However, serum T3 was only slightly reduced even after an increase in dose to 300 or 400 mg, and serum rT3 was not altered. Metoprolol concentrations were not significantly correlated with the fall in T3. It appears that the influence of beta-blockers on T4 conversion is of little importance for the clinical improvement in hyperthyroid patients, and rather it is a consequence of beta 1-adrenergic blockade interfering with the effect of T3. In addition, the findings support the assumption that therapeutic failure with beta-blockers in hyperthyroidism may be due to suboptimal treatment, and that individualized dosage is necessary.

Adult↗
PubMed1980

Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects.

The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients. glipizide produced a significant increase in plasma glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.

Adult↗
PubMed1980

Serum glibenclamide in diabetic patients, and influence of food on the kinetics and effects of glibenclamide.

The steady state concentrations of glibenclamide in serum were measured radioimmunologically in 37 diabetic patients after administration for at least a year. No other antidiabetic drugs had been given. The interindividual variation in glibenclamide concentrations was extremely large (0 to 1520 nmol/l), greatly exceeding the variation in dosage (2.5--25 mg daily). There was no relation between dose and serum concentration of glibenclamide. Only four (9%) patients had fasting blood glucose concentrations below 5.5 mmol/l, and fewer than half had values below 8 mmol/l. In most cases, therefore, the therapy was inadequate. Single-dose kinetics of glibenclamide was assessed in healthy volunteers. Food intake did not influence the bioavailability of a 5 mg dose of glibenclamide. There was no insulin increase in response to glibenclamide unless a meal was also given, and this increase was not significant until 1 h after administration of drug and meal, when the mean serum concentration of glibenclamide had reached 100 nmol/l. Even in the fasting state, however, there was a progressive fall in blood glucose after glibenclamide administration, significant within 45 min and with a nadir at 2--2 1/2 h.

Adult↗