PubMed HealthSearch

Biomedical subjects

B Lindström

Publications and source records attributed to B Lindström.

At least 19 recordsLinked to original sources

Pharmacokinetics of ketotifen after oral administration to healthy male subjects.

The pharmacokinetics of 2 mg ketotifen from four different oral dosage forms were examined in two randomized, balanced cross-over studies. Forty healthy male subjects participated. Each of 20 subjects received two capsule formulations and each of the other 20 subjects received two syrup formulations. Ketotifen concentrations in plasma were determined by a modified GC-MS method. The limit of quantitation was 40 pg ml-1. Inter-day precision and accuracy calculated from quality control samples were 16.3 per cent (-1.9 per cent), 19.8 per cent (+4.5 per cent) and 23.6 per cent (+5.9 per cent) at plasma concentration levels of 86 (n = 18), 215 (n = 19) and 343 (n = 18) pg ml-1, respectively. Ketotifen was rapidly absorbed from all dosage forms reaching Cmax in the order of 400 pg ml-1 after the syrup formulations and 300 pg ml-1 after the capsule formulations within 2 to 4 h. The syrup formulations showed a significantly more rapid rate of absorption as assessed by Tmax. No significant differences in extent of absorption between dosage forms were observed. The terminal elimination half-life of ketotifen varied between subjects from 7 to 27 hours with a mean of about 12 h. The minor pharmacokinetic difference between dosage forms observed in this study is unlikely to be of clinical significance.

Administration, Oral

Quality of life: a model for evaluating health for all. Conceptual considerations and policy implications.

The potential of the quality of life (QoL) concept lies in its basically positive meaning and interdisciplinary acceptance. This can be used when the Public Health sector tries to develop health into a resource concept, as is the intention of the WHO Health For All Strategy. Out of different scientific views on QoL this paper synthesizes a theoretical framework of QoL and describes how this concept can be used in practice when evaluating the health resources of a population.

Health Policy

Cytochrome oxidase activity in rat retina after exposure to 404 nm blue light.

Cytochrome oxidase (CYO), a key enzyme in the respiratory chain, was observed as an indicator of retinal metabolism after an in vivo blue light exposure. Thirty Sprague-Dawley rats were exposed to optic radiation of 404 nm with a retinal dose of 110kJ/m2. Immediately after exposure, the CYO activity in the pigment epithelium, in the outer and inner segments of photoreceptors, and in the outer plexiform layer of the exposed retina, was reduced to one-third-to-half of the control level. However, there was an increase in CYO activity in the exposed retina one day after exposure. One week after exposure, the CYO activity in the inner segment and the outer plexiform layer was higher, while the activity in the other two layers was lower, than that at one day, although still higher than in the control. Two weeks after exposure, the CYO activity in the four retinal layers returned to the level of the control retina, as did the activity four weeks after. After exposure, no ophthalmoscopically visible retinal change and no light-microscopically evident morphological alterations were found. There was no retinal edema or loss of photoreceptor cells. The observed alteration in CYO activity after blue light exposure may represent an inhibition of retinal metabolism. The inhibition was reversible. If this compensation mechanism is overwhelmed, retinal damage may occur.

Animals

Fatal systemic poisoning after skin exposure to monochloroacetic acid.

Little information is available on the toxicity of monochloroacetic acid. We report the case of a 38 year-old man who was splashed with an 80% monochloroacetic acid solution on 25-30% of his body surface. In addition to epidermal and superficial dermal burns, features of systemic poisoning occurred within a few hours including disorientation, agitation, cardiac failure and coma. He later developed severe metabolic acidosis, rhabdomyolysis, renal insufficiency and cerebral edema, and died due to uncal herniation on d 8. The 4 h post exposure plasma monochloroacetic acid concentration was 33 mg/L confirming skin absorption. In addition to its corrosive action, monochloroacetic acid probably blocks the tricarboxylic acid cycle (Kreb's cycle) and may also react with sulfhydryl groups in enzymes, causing severe tissue damage in energy-rich organs.

Accidents

Endometrial carcinoma; ovarian dysfunction--a risk factor in young women.

From a referral area comprising one-fifth of the Swedish female population we investigated possible risk factors for endometrial cancer (EC) in different age groups. Seventy-seven women aged 31-45 with EC were collected retrospectively, and 99 women aged 46-65 were consecutively collected. Both groups were compared to referents randomly selected from a population based study from the city of Göteborg. The referents consisted of 1746 women aged 39-65 years. All cases were studied by hospital record and 82% of the women aged 31-45 years and 85% of those aged 46-65 years were studied by an extensive questionnaire. Among the referents 1409 (81%) were investigated by the above-mentioned questionnaire. Hirsutism, increased body mass index (BMI) and hypertension were significantly more common in both EC groups compared to referents. Nulliparity and infertility were significantly more common in the young EC group. Referents used combined oral contraceptives significantly more often than women developing EC. There was, however, no difference between the groups with respect to the duration of medication with combined oral contraceptives. There was a significant negative correlation between cigarette smoking and the development of EC. These findings indicate that untreated ovarian dysfunction like that present in polycystic ovarian disease (PCO) with unopposed estrogen action on the endometrium is associated with EC in younger women, and that smoking may protect against EC by an 'anti-estrogenic' effect.

Adult

Differential foetal development of the O- and N-demethylation of codeine and dextromethorphan in man.

1. Codeine and dextromethorphan were N-demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O-demethylation of these drugs at mid-gestation. 2. The metabolic data were in accordance with the absence of P450IID6 and the presence of P450 IIIA as determined by Western blotting with anti-human P450 IID6 (MAb 114/2) and anti-rat P450 IIIA (PCN 2-13-1/C2) monoclonal antibodies, respectively. 3. The inhibitory effects of midazolam and dehydroepiandrosterone support the contention that the N-demethylase is a human foetal form of the cytochrome P450 IIIA family. Consistent with this we found that blotting with the MAb PCN 2-13-1/C2, which recognizes an epitope specific for the P450 III family, correlated well with the N-demethylase activities.

Antibodies, Monoclonal

Microradiographical determination of the dry mass density in the rat retina.

A method for the quantitative measurement of the dry mass density in retinal tissue is presented. Cryosections of rat retinas were freeze-dried and exposed to soft X-rays together with a reference system. The section thickness was measured optically. The X-ray energy absorbed by the retinal tissue was recorded photographically and the microradiographs were evaluated photometrically. These measurements were used to estimate the dry mass density for each retinal layer. Sources of variation were evaluated. The precision was found adequate. The present method allows a localized determination of the dry mass density and of the hydration in the retina at a microscopic resolution.

Analysis of Variance

Lipid and protein density in the rat retina: a microradiographical study.

Lipid and protein density in each retinal layer were determined microradiographically in retinal sections of 10 rats. Lipid in retinal sections was extracted with chloroform. The fraction of dry mass remaining after lipid extraction is mainly protein. The dry mass lost in chloroform processing was calculated to obtain the lipid density, which accounts for about 30% of the total dry mass density. The total dry mass density in each retinal layer is the sum of the lipid and protein density. Lipid should be regarded as an important X-ray absorber when determining the dry mass density in the rat retina with microradiography.

Animals

Measurement of human cochlear blood flow.

Cochlear blood flow (CBF) was measured with a laser-Doppler (L-D) flowmeter (Periflux PR2-B) in four unanesthetized human subjects with chronic tympanic membrane perforations and nine anesthetized human subjects undergoing middle ear operations. The L-D recordings were made over the promontory and/or the round window membrane during carbogen breathing and direct electrical stimulation of the cochlea in both groups and with warm water irrigation of the external ear canal in the anesthetized subjects. Carbogen led to little or no change in CBF as monitored with either measurement approach in either subject group. Electrical stimulation yielded an increase (15% to 25%) in CBF as recorded from the promontory in seven of the nine subjects tested. Warm (44 degrees C to 49 degrees C) water irrigation produced changes of 20% to 60% in CBF that were partially recoverable in the 10 minutes available for study. This study demonstrated the feasibility of direct CBF measurement in humans with the L-D method. Moreover, the data indicate that carbogen has little influence on CBF and that electrical stimulation at relatively safe levels and warm water irrigation of the ear canal produce increases in human CBF.

Aged

Youth, disability and quality of life.

When broader aspects of health are considered especially when assessing the life of the disabled it becomes necessary to reach beyond physical measurements to more dynamic aspects including the individual's other resources and demands. In such a context issues of quality of life are important. Quality of life is here defined as a term describing the total existence of an individual or a group and is operationalized in three life spheres: external conditions, interpersonal conditions and personal psychological conditions. National samples of youths aged 12-18 years with cystic fibrosis and myelomeningocele are compared to a reference group of normal youths in the five Nordic countries. The study was based on a mailed questionnaire. The results show that the disabled groups had equal external conditions as their peers while they rated lower on the interpersonal and personal levels. This indicates that the Nordic countries have succeeded in providing a good material support for families with handicapped youths. The fact that these families are also more satisfied with the different life spheres means that both objective and subjective needs are met. The social networks and personal psychological conditions, though, proved to be less sufficient and there is still a lot to be done to give handicapped youngsters a full life.

Adolescent

Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine.

The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l.h-1. Volume of distribution, V alpha varied 100-680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6-36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.

Administration, Oral

Liquid scintillation counting of 3H-thymidine incorporated into rat lens DNA.

DNA synthesis in the lens has previously been localized by autoradiography following incorporation of 3H-thymidine. For the quantification of DNA synthesis in the lens, pooling of lenses and extraction of the DNA for liquid scintillation counting, has formerly been adapted. In the present investigation a method has been developed for the extraction of the unincorporated tracer from whole lenses after short time incubation in a medium containing 3H-thymidine. The 3H-thymidine incorporated into individual lenses was then detected by liquid scintillation counting after dissolution of the lenses. The sources of the variation in the method are evaluated.

Animals

Morphine sulphation in children.

The metabolism of morphine was studied in nine children and seven preterm neonates receiving a continuous infusion of morphine. All the neonates and three children had detectable concentrations of morphine-3-sulphate (M3S) in urine. None of the neonates or the children had detectable concentrations of morphine-6-sulphate (M6S) in urine. None of the children had detectable concentrations of M3S in plasma. The M3S/morphine ratios were significantly higher in neonates than children (P less than 0.01), suggesting that morphine sulphation decreases after the neonatal period. The amount of M3S formed, even in neonates, is low suggesting that this is a minor metabolic pathway.

Humans

Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.

Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.

Administration, Oral

An objective and rapid method for the determination of light dissemination in the lens.

A method for the objective measurement of light dissemination in the lens was developed. There is an exponential relationship between the concentration of standard solutions and the intensity of light disseminated forwards. The light disseminated in non-pathological lenses from Sprague Dawley rats was registered as the equivalent standard concentration, C, and then transformed to log10 (C + 1) and was found not to deviate from the normal distribution. The tolerance limit for light dissemination was derived by setting the probability to classify a non-pathological lens as pathological. An analysis of variance demonstrated that the inter-animal variation was the dominating source of imprecision. It is anticipated that the developed system will be useful in experimental toxicological risk assessment.

Analysis of Variance

Electrophonic hearing and cochlear implants.

It has been difficult to explain the good speech understanding obtained by some cochlear implant patients fitted with a single-channel electrode and analog transmissions of the speech signal (Vienna/3M implant). It has also been difficult to explain the variation in results reported by different groups using the same implant. One hypothesis asserts that the above differences can be explained by the observation that electric stimulation with an implanted electrode might result in two different auditory sensations, the first resulting from the stimulation of the remaining hair cells (electrophonic component) and the second from the electric stimulation of the auditory nerve (electro-neural component). The two sensations are very different. As a result of different definitions of total deafness (functional or threshold definition), patients with remaining hair cells are operated on by some groups, but not by other groups. Some published results from different studies are discussed with reference to the above hypothesis and the possible consequences for the selection of the patients, the use of extra- or intracochlear electrodes, and the selection of the speech coding strategy are discussed.

Audiometry, Pure-Tone