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Biomedical subjects

M Larsson

Publications and source records attributed to M Larsson.

At least 181 records · Page 10Linked to original sources
PubMed1988

Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants.

The disappearance of levonorgestrel from plasma after the removal of NORPLANT subdermal implants was studied in 12 women who had been treated from 5.5 to 78 months. The existence of one or two half-lives for the rate of disappearance was assessed. The influence of body weight, body fat and length of treatment upon levonorgestrel clearance was studied through stepwise regression analysis. It was found that the levonorgestrel decay rate after implant removal can be entirely accounted assuming one half-life of 42 +/- 16 h (mean +/- SD; range 13 to 62 h). Stepwise regression analysis showed that levonorgestrel half-life is positively correlated with body weight and not significantly correlated with the length of treatment or body fat. It is concluded that, after long-term administration of levonorgestrel via subdermal implants, the major part of the steroid is cleared from plasma within 96 h and that only trace amounts are detected in the following days.

Adult↗
PubMed1988

Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects.

The pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5 mg twice daily to steady-state. A single intravenous dose of 3H-felodipine (0.04mg) was given together with the oral dose on the study day. Cmax (17 nmol/L), Cmin (5 nmol/L) and AUC (82 nmol/L.h) were 3 times higher in the elderly than in the young subjects. Systemic availability was about 15% in both groups. Plasma clearance (CL) was reduced from 56.1 L/h in the young to 25.4 L/h in the elderly. There was no effect of age on the volume of distribution at steady-state (Vss). Reduced hepatic blood flow and enzyme activity or increased gut wall metabolism are possible reasons for the altered pharmacokinetics in the elderly. Blood pressure was reduced in the elderly from 190/99 to 177/91 mm Hg 12 hours after 5mg felodipine during twice daily dosage. The effect on blood pressure correlated with plasma concentrations of felodipine.

Adult↗
PubMed1988

HPLC assays of 5-HIAA and tryptophan in cerebrospinal fluid and 5-HT and tryptophan in blood: a methodological study with clinical applications.

HPLC methods were developed for the assay of 5-hydroxy-tryptamine (5-HT) and tryptophan in blood after a simple precipitation step, and 5-hydroxy-indolamine acetic acid (5-HIAA) and tryptophan in CSF by direct injection of CSF. Using these methods, CSF and blood contents were studied in drug-free volunteers and patients treated with tricyclic antidepressant (TCA) drugs. Previously reported variations in the CSF concentrations of 5-HIAA with sex and age were confirmed. No significant difference between patients and healthy subjects were seen in the concentrations of tryptophan in blood or CSF, which were significantly positively intercorrelated. There was no intercorrelation between the concentrations of tryptophan and 5-HIAA in CSF. Highly significant differences between patients and healthy subjects in the platelet-content of 5-HT could be ascribed to the TCA medication. Three TCA drugs, amitriptyline, clomipramine, and imipramine, were compared regarding influence on the platelet-content of 5-HT. Patients treated with clomipramine were found to have considerably lower 5-HT values than imipramine- and amitriptyline-treated patients. A logarithmic model indicated a positive correlation between the two serotonin markers studied, i.e., the amount of platelet-bound 5-HT and the CSF concentrations of 5-HIAA.

Adult↗
PubMed1988

Comparison between methylphenidate and placebo as adjuvant in care and rehabilitation of geriatric patients.

The aim of the present study was to establish to what extent a short-term treatment with methylphenidate would have such practical clinical effects that possibilities for medical rehabilitation would be improved. Other purposes of the investigation were to certify therapeutically acceptable plasma concentrations in the elderly, and to study possible mental and physical effects of the suddenly improved and greatly extended daily attention given to the patient during the course of the study. 24 fatigued, elderly patients (70-93 years) were treated with methylphenidate/placebo for 9 days. The study was carried out as a double-blind test. Although a significant effect on heart rate and blood pressure was recorded when the full dose (20 mg) had been reached, no difference in mental or physical performance was observed between the two groups.

Affect↗
PubMed1987

Purification and partial characterization of thyroid hormone binding proteins in canine serum.

Thyroxine-binding prealbumin (TBPA) and thyroxine-binding globulin (TBG) were isolated from canine serum and partially characterized. TBPA was isolated by retinol-binding protein (RBP) affinity chromatography and further purified by preparative agarose gel electrophoresis or FPLC ion exchange chromatography. TBG was purified by thyroxine (T4)-Sepharose chromatography followed by gel filtration on Sephacryl S-300 and preparative electrofocusing in a granulated dextran gel. Molecular weights were estimated by SDS-polyacrylamide gradient gel electrophoresis. Canine TBPA had a tetramer molecular weight of 56,000, an extinction coefficient of 12.8 cm2cg.1, an isoelectric point of 5.26-5.70 and a microheterogeneity pattern similar to that of human TBPA. Partial immunochemical identity with human TBPA was also found. Plasma concentrations of TBPA were measured by rocket immunoelectrophoresis in 43 normal and 35 hypothyroid dogs. Reference levels for TBPA ranged between 205 and 474 mg/l. Hypothyroid dogs had a mean TBPA level of 315.0 mg/l (SD: 91.1 mg/l). TBG had a molecular weight of 75,000 and an isoelectric point of 5.0. No immunochemical identity with human TBG was found. Gel filtration of serum on Sephacryl S-200, identification of T4-binding proteins with 125I-T4, and protein- and lipoprotein staining of fractions was performed. Thyroxine-binding was found to TBG in the beta-globulin region, TBPA in the alpha 2-region, albumin, and to the high density lipoprotein (HDL2) in the alpha 1-region and the very low density lipoprotein (VLDL) in the pre-beta region. A corresponding band to the latter protein in serum was masked by TBG and TBPA, and T4-binding in the alpha 1-region was not always seen in serum. Many similarities were found between man and dog regarding TBPA, but not TBG. The differences in structure of TBG may in part be responsible for the low serum T4 levels and rapid T4 metabolism seen in dogs.

Animals↗
PubMed1987

Secondary aortoenteric fistulas--an analysis of 42 cases.

Secondary aortoenteric fistulas are seen with an increasing frequency which parallels the expansion of reconstructive vascular surgery. During a 12-year period 42 cases have been collected from the hospitals, which perform most of the vascular surgery in Sweden (0.7% of vascular operations). Twenty-five were seen after operation for aortic aneurysm, 15 for aortoiliac occlusive disease, one after renal artery ligation (as a part of reconstruction for renovascular hypertension) and one after operation for an iliac pseudoaneurysm. The frequency of complications during and after the primary operation was high. The interval between operation and onset of fistula symptoms was significantly shorter if there had been infectious complications, the median interval was 32 months, the longest being 10 years. The most important symptom was gastrointestinal haemorrhage, consisting of several small bleeds often combined with septic complications. A large number of negative investigations usually preceded the final diagnosis which was made at exploratory laparotomy. After surgery for the fistula the frequency of complications and mortality, were very high. Mortality was 58%, the most common cause of death being a blow out of the aortic stump. Of those leaving hospital, several further operations were performed with a high mortality. Recurrence of the fistula occurred in 16 out of 34 patients who survived surgery. At follow-up (12-74 months after fistula closure) seven patients were still alive.

Adolescent↗
PubMed1987

Ritanserin assessments in plasma and CSF by means of HPLC technique with fluorescence detection.

A specific HPLC-technique based on fluorescence detection was developed for assay of ritanserin, a serotonin receptor-blocking agent, in plasma and CSF. In 5 ml sample volumes, the limit of detection was 0.5 ng/ml, the recovery of ritanserin was 83 +/- 5%, and the inter-assay variability, expressed as the coefficient of variation, was 9.5% in the 2-788 ng/ml concentration range. When the values determined by this technique were compared with the results obtained by means of an independent HPLC-method with UV-detection, the coefficient of correlation was 0.995 (p less than 0.001). However, our technique proved to be more specific and less complicated.

Chromatography, High Pressure Liquid↗
PubMed1987

HPLC assays of noradrenaline and dopamine in CSF samples from drug-free subjects.

An analytical technique based on HPLC and electrochemical detection was developed for assay of free catecholamines in CSF. The mean CSF concentrations of noradrenaline and dopamine were found to be 123 +/- 48 pg/ml and 10 +/- 6 pg/ml, respectively, in 14 drug-free subjects. The monoamine concentrations did not vary with sex or age. No correlation was seen between the noradrenaline and dopamine values. As a preliminary investigation, signs of seasonal variation in the CSF concentration of noradrenaline and dopamine were registered in 4 female subjects.

Adult↗
PubMed1987

Anaphylatoxin release in association with methylmethacrylate fixation of hip prostheses.

In a prospective study, thirty patients in whom a Charnley hip prosthesis was implanted with cement (methylmethacrylate) and fifteen who received a prosthesis without cement were studied. The activation of complement, as indicated by the release of anaphylatoxins (C3a and C5a), reduced activity of whole complement, and decreased levels of C3, C4, and C5 in plasma, was evaluated. Activation of complement was found when methylmethacrylate was used. In patients in whom components were fixed without cement, no formation of anaphylatoxins occurred, and only slightly reduced whole-complement activity and concentrations of C3, C4, and C5 in plasma were found. A dose-correlated release of the anaphylatoxins was found when monomethylmethacrylate was incubated in fresh serum. One explanation for the hemodynamic instability in these patients might be the biological effects of anaphylatoxins that are released in association with fixation by cement.

Adult↗
PubMed1986

Renal function in an elderly population. A study of S-creatinine, 51Cr-EDTA clearance, endogenous creatinine clearance and maximal tubular water reabsorption.

There has been reported a decline in renal function with age, a decline that seems to accelerate after the age of 50. A systemically chosen sample of 70- and 75-year-old probands from the study '70-year-olds in Göteborg' have previously been examined with respect to GFR. The present study is a longitudinal follow-up of GFR in the previously examined 75-year-old probands at age 79. Renal tubular water absorption was also determined. In order to make a longitudinal comparison, S-creatinine was determined in a subsample of 166 probands, who had attended the study at 70, 75 and 79 years of age, by using frozen sera from these three examinations. S-creatinine increased slightly but statistically significant in both sexes between 70 years and 79 years of age. The reference values for EDTA clearance at age 79 calculated as M +/- 2 SD were 46-94 ml/min X 1.73 m2 BSA without any difference between the sexes. There was no change in GFR between 75 years and 79 years of age. We did not find any correlation between EDTA clearance and creatinine clearance. The tubular water reabsorption for probands without disorders was 843 +/- 92.6 (range 709-982). The results suggest that the renal filtration rate at age 79 is still good and that the ageing of the tubular function is not as pronounced as that of the GFR.

Age Factors↗
PubMed1985

Thyroid hormone binding in serum of 15 vertebrate species: isolation of thyroxine-binding globulin and prealbumin analogs.

The binding of [125I]T4 to serum proteins was studied in human, monkey, cattle, sheep, goat, water buffalo, horse, swine, dog, cat, rabbit, rat, chicken, frog, and salmon. Attempts were made to isolate thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) from serum of all species, utilizing purification methods based on the specific properties of these proteins. TBPA was found to exist in all species examined. The protein was found anodal to albumin only in human, monkey, horse, and chicken. In cattle, swine, dog, cat, rabbit, frog, and salmon, TBPA was found cathodal to albumin, while sheep, goat, water buffalo, and rat had identical mobility of albumin and TBPA. The presence of TBG was demonstrated in larger mammals. In cat, rabbit, rat, chicken, frog, and salmon, TBG could not be demonstrated. The thyroxine-binding capacity of TBPA in serum varied from 1000 to greater than 6000 nmol/l and that of TBG between 150 and 600 nmol/l. TBPA from all species except salmon showed affinity to human retinol-binding protein. The presence of TBPA in all vertebrates suggests prealbumin to be a far more important thyroxine carrier than earlier anticipated.

Animals↗
PubMed1984

Pharmacokinetics of metoprolol in healthy, elderly, non-smoking individuals after a single dose and two weeks of treatment.

The effect of long-term treatment on the absorption and disposition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 mg dose of cold metoprolol, and second, with the morning dose after 2 weeks of treatment with 50 mg b.d. In the elderly, the mean AUC increased by about 45% (p less than 0.05) over the treatment period, while in the control group the mean AUC was 18% greater (p less than 0.05) on Day 14 than on Day 1. In the elderly, changes both in pre-systemic elimination and in total body clearance accounted for the elevation of the AUC, whereas reduced first-pass effect appeared to be the major cause of the increased steady-state plasma level in the control group. With the exception of the volume term, V beta, the pharmacokinetic parameters were not significantly different between the elderly and the young individuals. For this reason, almost identical steady-state plasma levels were attained in the two groups. The results suggest that age-related physiological changes may have some minor effects on the pharmacokinetics of metoprolol, and also that the changes do not lead to significantly altered plasma concentrations compared to those in young individuals.

Administration, Oral↗
PubMed1984

Antipsychotic treatment with alpha-methyltyrosine in combination with thioridazine: prolactin response and interaction with dopaminergic precursor pools.

The antipsychotic effect of alpha-methyltyrosine (alpha-MT) in combination with thioridazine was investigated by means of rating scales for "social behaviour" and "mental symptoms". The clinical effect was also evaluated in relation to the serum concentrations of alpha-MT and thioridazine and to the increase in prolactin secretion in response to the interaction with hypothalamic dopaminergic mechanisms. The interactions between the serum levels of alpha-MT and those of the transmitter precursors phenylalanine and tyrosine were analysed. The results confirmed the ability of alpha-MT (2 g/day) to potentiate the antipsychotic effect of thioridazine, whereby the dose of neuroleptic drug required to control psychotic symptoms may be markedly reduced. None of the four patients who completed the trial showed side effects that could be ascribed to alpha-MT. The antipsychotic effect of thioridazine, alone or in combination with alpha-MT, correlated well with the prolactin response in the individual patient. No important interference with serum phenylalanine or tyrosine levels was noted during treatment with alpha-MT.

Aged↗
PubMed1984

Comparison of isotope dilution technique and haematocrit determination for blood volume estimation in rats subjected to haemorrhage.

The method of posthaemorrhagic blood volume (BV) determination by simple haematocrit measurement has been compared with the conventional isotope dilution technique. 51Cr tagged erythrocytes and 125IHSA were used to estimate RBC volume and plasma volume in non-starved male Sprague-Dawley rats. Two series of experiments were carried out by two different investigatory groups. Haemorrhage was inflicted by 60 or 90 min of haemorrhagic hypotension at 70 mm Hg, causing 41% and 56% loss of the initial estimated BVs, respectively. There was agreement in both series for the initial blood volume indices; RBC volume, 2.82 ml x 100 g-1 b.wt.; plasma volume 3.33 ml x 100 g-1 b.wt. and F cells, 0.91. Using the RBC volume data, the calculated residual BVs after haemorrhage corresponded accurately to the isotope measurements in both series. It is concluded that non-splenectomized rats may be used for accurate BV analysis after haemorrhage if the basal data for the strain used are known.

Animals↗
PubMed1983

Pharmacokinetics of metoprolol and its metabolite alpha-OH-metoprolol in healthy, non-smoking, elderly individuals.

The absorption and disposition of metoprolol have been evaluated in 10 healthy, non-smoking, elderly individuals (mean age 73.1 years) by simultaneous determination of [3H]-metoprolol and unlabelled metoprolol. The labelled drug was given as an intravenous tracer dose, immediately followed by oral metoprolol 25 mg. The experiment was preceded by administration of metoprolol 25 mg b.i.d. for 3 days. The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects. The mean systemic availability was about 39% in the elderly, which is lower than the mean of 55% observed in a control group of young volunteers who received 50 mg b.i.d. In the elderly, the mean plasma concentration of alpha-OH-metoprolol was about twice as high as that of the parent drug, whereas the opposite was true of the control group. The results indicate that age-related physiological changes have a negligible effect on the pharmacokinetics of metoprolol.

Adult↗