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Biomedical subjects

B Lindström

Publications and source records attributed to B Lindström.

206 records · Page 12Linked to original sources

Pharmacokinetics and effects of 9-amino-1,2,3,4-tetrahydroacridine in the immediate postoperative period in neurosurgical patients.

STUDY OBJECTIVE: To determine the effects of intravenous (IV) 9-amino-1,2,3,4-tetrahydroacridine (THA) on postoperative somnolence in comparison to its pharmacokinetics. DESIGN: Open-label study of the pharmacokinetics and effects of THA. SETTING: Postoperative intensive care ward at the Department of Neurosurgery, Uppsala University Hospital, Sweden. PATIENTS: Ten neurosurgical patients immediately after their operations were given 30 mg of THA for reversal of postoperative somnolence. INTERVENTIONS: Plasma concentrations of THA and, in seven cases, the metabolite 1-hydroxy-THA were assayed using high-performance liquid chromatography. The pharmacokinetic data were compared to the degree of sedation and pain relief. After an IV dose of 30 mg THA, plasma concentrations were fit to an open two- or three-compartment model. MEASUREMENTS AND MAIN RESULTS: The antagonistic effect of THA on sedation occurred immediately following IV administration and lasted 60 to 90 minutes. At a mean plasma THA concentration of 44 +/- 18 ng/ml, patients were resedated. There was no obvious relation between analgesia and plasma THA concentrations. Side effects such as nausea, salivation, and lower heart rate (HR) were observed in several patients. Plasma clearance (C1) was high and showed a twofold inter-individual variation, with a mean of 2.64 +/- 1.17 L/h. Volume of distribution (Vd gamma) varied between 300 and 850 liters, with a mean of 477 +/- 185 liters. The plasma half-lives of rapid and slow distribution, and elimination were 2.1 +/- 0.7 minutes, 26 +/- 18 minutes, and 133 +/- 48 minutes, respectively. Maximum plasma concentrations of 1-hydroxy-THA were 27 to 90 ng/ml in five patients; the concentration was below 1 ng/ml in two other patients. CONCLUSIONS: The duration of the effects of THA as an antagonist of postoperative sedation was only about double that seen previously after the IV administration of physostigmine in a similar group of patients, although the elimination half-life of THA was six times longer than that of physostigmine. A larger dose of THA possibly could have been given to prolong the period of antagonism of sedation, but the profile of adverse effects seen even at the doses used precluded that option.

Adult↗

Effects of fructose on D-[6-3H]-glucose uptake and sorbitol metabolism of bovine retina in vitro.

In order to study the influence of fructose on sorbitol formation, bovine retinal tissue was incubated with different concentrations of glucose and fructose, and supplemented with tracer amounts of D-[6-3H]-glucose. Combining high-performance liquid chromatography (HPLC) with radioactivity determinations allowed detection of sorbitol and fructose derived from glucose in the incubation medium. In addition, the total amount of sorbitol was measured with a sensitive bioluminescence method. In this way, it was possible to distinguish between sorbitol formation from glucose and fructose. High concentrations of glucose in the medium increased the formation of sorbitol and fructose from glucose. Addition of fructose to the incubation medium diminished the sorbitol and fructose formation from glucose although the total amount of sorbitol increased significantly. Incubating retinal tissue with an aldose reductase inhibitor decreased sorbitol formation from glucose but did not influence the formation of sorbitol from fructose. Thus, the present findings clearly demonstrate the important influence exerted by fructose on sorbitol formation. The possible significance of the present finding is discussed with respect to diabetes retinopathy and retinal osmoregulation.

Animals↗

Factors affecting auditory performance of postlinguistically deaf adults using cochlear implants.

A model of auditory performance and a model of ganglion cell survival in postlinguistically deafened adult cochlear implant users are suggested to describe the effects of aetiology, duration of deafness, age at implantation, age at onset of deafness, and duration of implant use. The models were compared with published data and a composite data set including 808 implant users. Qualitative agreement with the model of auditory performance was found. Duration of deafness had a strong negative effect on performance. Age at implantation had a slight negative effect on performance, increasing after age 60 years. Age at onset of deafness had little effect on performance up to age 60. Duration of implant use had a positive effect on performance. Aetiology had a relatively weak effect on performance.

Adolescent↗

Pharmacokinetic properties and bioavailability of methimazole.

The pharmacokinetics of methimazole following therapeutic doses were studied in healthy subjects, in thyrotoxic and hypothyroid patients before and after treatment to euthyroidism, and in patients with renal or hepatic insufficiency, using a highly sensitive gas chromatographic-mass spectrometric assay. Following intravenous administration of 10mg to healthy subjects, methimazole had an initial distribution half-life (t1/2 alpha) of 0.10 to 0.23 hours and an elimination half-life (t1/2 beta) of 4.9 to 5.7 hours. The absolute bioavailability after oral administration of 10mg methimazole in the fasting state was high, with a mean of 93%. The pharmacokinetic profiles showed small interindividual variations, although one of the hypothyroid patients had a rapid elimination half-life, in both the hypothyroid and euthyroid state (2.6 and 2.4 hours, respectively). The elimination rate was not enhanced in the thyrotoxic patients but was slightly prolonged in the hypothyroid patients. There was no influence of renal insufficiency, but a prolonged elimination half-life was observed in patients with hepatic failure, the prolongation being proportional to the degree of impairment. Thus, the pharmacokinetics of methimazole are relatively simple with small interindividual variations. In general, there are no pharmacokinetic reasons to adjust dosage in the treatment of thyrotoxicosis, except in the rare case of concomitant advanced hepatic insufficiency.

Adult↗

Topical chloroquine applied before irradiation protects against ultraviolet B (UVB)- and UVA-induced erythema but not against immediate pigment darkening.

Seventeen healthy volunteers were phototested with ultraviolet B (UVB) and UVA before and after topical treatment with chloroquine phosphate. The skin areas treated before but not after irradiation showed higher minimal erythema dose values for UVB and UVA than control skin. The effect was clearly spectral with greater protection afforded against UVB than UVA. The immediate pigment darkening after irradiation with UVA, however, was not affected by pretreatment with the drug. The mechanism of action for this protective effect did not seem to be related to merely absorption and screening, inhibition of the inflammatory reaction or a UV-induced effect on the stereo-isomerization of the drug.

Administration, Cutaneous↗