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Biomedical subjects

O Stokke

Publications and source records attributed to O Stokke.

At least 37 records · Page 2Linked to original sources
PubMed1994

Muscle contraction increases the in vivo structural strength to the same degree in osteopenic and normal rat tibiae.

The increase in structural capacity due to muscle contraction in the lower leg was investigated in osteopenic and normal rats. Osteopenia was induced by ovariectomy combined with a low-calcium diet (0.01%). The control rats were sham operated and fed a diet containing 1.1% calcium. After 7 weeks the right lower leg of all animals were fractured in three-point ventral cantilever bending during muscle contraction induced by electrical stimulation of the ischiatic nerve. The left tibiae were resected and fractured as each animal's control. During muscle contraction in vivo, the ultimate bending moment, energy absorption, bending stiffness, and deflection were significantly lower in the osteopenic than in the sham-operated animals. However, the increase in mechanical parameters due to muscle contraction comparing the in vivo and resected tibiae in each animal were equally high in the osteopenic and sham-operated animals. Ultimate bending moment in the resected tibiae was 10% higher in the sham-operated animals compared with the ovariectomized, proving mechanically weaker tibiae in the osteopenic rats. In accordance with this, the medullary area of the osteopenic rats was 46% larger in the distal tibial diaphysis, and the ultimate stress the tibiae could withstand was 15% lower in the osteopenic compared with the sham-operated rats. The trabecular bone volume in the distal tibial metaphysis of the osteopenic rats was reduced by 70% compared with the sham operated. This study shows that muscle protection against fracture can be substantial in osteopenic tibia and that it is of the same magnitude as in rats with normal bone mass.

Animals↗
PubMed1994

Kinetics of mercaptopurine and thioguanine nucleotides in renal transplant recipients during azathioprine treatment.

The purpose of this study was to examine the pharmacokinetics of mercaptopurine (6-MP) and thioguanine nucleotides (6-TGN) during azathioprine treatment. Plasma profiles and urinary excretion of 6-MP and 6-TGN concentrations in red blood cells (RBCs) were measured repeatedly during the first 3 weeks following transplantation in 10 adults, who had received kidney grafts from living related donors. Mean maximal 6-MP plasma concentration (Cmax) was 340 nmol/L (SD = 290), mean time to Cmax (Tmax) was 2 h (SD = 1.8), and mean area under the plasma concentration-time curve (AUC) was 930 nmol/L/h (SD = 770). The mean fraction of azathioprine dose excreted as 6-MP in urine was 1.32% (SD = 1.11). Up to eightfold variability of Cmax and AUC was observed from day to day within each patient. The correlation between 6-MP AUC and amount excreted in the urine was weak (r = 0.37, 95% CI from 0.02 to 0.64). In this group of patients the observed 6-TGN levels in RBCs were low; maxima during the observation period ranged from undetectable to 250 pmol/8 x 10(8) RBCs. In individual patients, 6-TGN levels were relatively stable throughout the dosing interval ("within-dose-interval-CV" < 19%), even when sharp and high 6-MP peaks in plasma were observed.

Adult↗
PubMed1993

[Bone mineral density and occurrence of fractures in 66-year old women in Oslo].

During 1991 we examined 196 randomly chosen females born in 1925 and resident in Oslo. 40% had suffered fractures of the appendicular skeleton, most commonly of the forearm and the ankles, after the menopause. Results from bone mineral density measurements of the lumbar spine (L2-4) and the femoral neck were not significantly lower, while results from the distal 1/3 of the forearm site were significantly lower, among participants with fractures than among participants without fractures. The values for bone mineral density obtained from these three sites corresponded with the values reported from other countries. Biochemical indices of calcium metabolism were similar in fracture and non-fracture subjects. Age at menopause, weight, height and demographic characteristics were also similar in the two groups. We conclude that low bone mineral density cannot be the sole explanation of the very high prevalence of fractures among female residents of Oslo found in the present and previous studies.

Adult↗
PubMed1993

[Doxazosin (Carduran)--a research survey].

4,260 patients were included in an open surveillance study simultaneously with the introduction of doxazosin for treatment of essential hypertension in Norway. The main aim of the study was to systematically collect information on side effects and events in patients being treated with a new drug. The effect on blood pressure, heart rate and lipids was also recorded. The study lasted for one year. 21 deaths were reported. 53% of the patients reported side effects and/or events. The frequency of side effects was particularly high during the first month of treatment. No new types of side effects were found. The initial higher frequency of reported side effects referred to all organ systems, and was also of the same magnitude in the different systems. A relation was found between certain cardiac side effects and/or events and cessation of previous medication upon starting treatment with doxazosin. The study shows that certain safety precautions should be observed in patients with coronary heart disease and heart failure. In three patients, doxazosin should be used only in combination with more specific treatment. Special caution should be observed when changing the specific basic treatment. Doxazosin had a very favourable antihypertensive effect. A drop in cholesterol and triglycerides was observed, as expected. The HDL-cholesterol value declined, which was unexpected. The results are difficult to interpret, owing to lack of a control group. On the other hand, the study shows how high blood pressure is being treated with drugs in ordinary practice. The authors discuss the methodology of surveillance studies.

Aged↗
PubMed1993

Cyclosporine A monitoring in patients with renal, cardiac, and liver transplants: a comparison between fluorescence polarization immunoassay and two different RIA methods.

In the present study a new method for selectively determining parent cyclosporine (CsA) in whole blood, a fluorescence polarization immunoassay (FPIA; TDx Abbott), was compared with a RIA method (Sandimmun, Sandoz Ltd, Basle, Switzerland). A total of 974 samples were collected during the first 3 post-operative months from 63 renal, cardiac, and liver transplant recipients. The CsA concentrations measured with FPIA ranged from 14% to 19% above RIA (specific) in the middle ranges. Regression equations in renal transplants: FPIA = 1.001 x RIA + 28; in heart transplants: FPIA = 1.08 x RIA + 27 and in liver transplants: FPIA = 1.13 x RIA + 13. Considering the improved precision of the new method (inter-assay CV with FPIA: 3.8-9.5%; with RIA: 18.6%), the slightly lower specificity will usually be of minor importance in the therapeutic range for whole blood CsA concentrations following organ transplantations. The FPIA measurements which deviated most from the regression line compared with RIA-specific CsA values, tended to coincide with high CsA concentrations or rather extreme RIA specific to RIA non-specific ratios. In addition to analytical imprecision with the RIA-specific method, lower specificity of the FPIA vs. some of the metabolites may explain these deviations. The majority of these observations occurred as isolated episodes with normal relationship between RIA specific and FPIA on preceding and following days. Accordingly large dosage adjustments should await verification in repeated samples. Following these precautions the FPIA method may prove useful and safe in the monitoring of cyclosporine treatment.

Cyclosporine↗
PubMed1993

Peroxisomal beta-oxidation of polyunsaturated long chain fatty acids in human fibroblasts. The polyunsaturated and the saturated long chain fatty acids are retroconverted by the same acyl-CoA oxidase.

The metabolism of the C22 unsaturated fatty acids erucic acid (22:1(n-9)), adrenic acid (22:4(n-6)), docosapentaenoic acid (22:5(n-3)) and docosahexaenoic acid (22:6(n-3)) was studied in cultured fibroblasts from patients with acyl-CoA oxidase deficiency, the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. [3-14C] 22:4 (n-6) and [3-14C] 22:5 (n-3) were shortened (retroconverted) to [1-14C] 20:4 (n-6) and [1-14C] 20:5 (n-3), respectively, in normal and X-ALD fibroblasts. In Zellweger and acyl-CoA oxidase deficient fibroblasts these reactions were deficient. Since the retroconversion is normal in X-ALD fibroblasts peroxisomal very long chain (lignoceryl) CoA ligase is probably not required for the activation of C22 unsaturated fatty acids. The present work with fibroblasts from patients with a specific acyl-CoA oxidase deficiency, previously shown to have a deficient peroxisomal clofibrate-inducible acyl-CoA oxidase, and which accumulate 24:0 and 26:0 fatty acids, supports the view that this enzyme is responsible for the chain-shortening of docosahexaenoic acid (22:6(n-3)), erucic acid (22:1(n-9)), docosapentaenoic acid (22:5(n-3)), and adrenic acid (22:4(n-6)) as well.

Acyl-CoA Oxidase↗
PubMed1990

Pharmacokinetics of oral 6-mercaptopurine: relationship between plasma levels and urine excretion of parent drug.

Plasma levels and cumulative urine excretion of 6-mercaptopurine (6-MP) were measured using a specific and sensitive high-performance liquid chromatographic assay in seven children with acute lymphoblastic leukemia (ALL) as well as in one healthy volunteer. The dose of 6-MP varied in the range of 25-75 mg/m2 of body surface area and was administered with a standard breakfast. A 4- to 11-fold variation between individuals was found in the pharmacokinetic parameters: peak concentration, time to reach peak, area under the plasma concentration-time curve (AUC), and fraction of dose excreted in the urine. Three repeated determinations in one individual revealed that AUC also varied more than sixfold following an overnight fast. In three individuals, the reducing agents glutathione (10 mg/kg) and ascorbic acid (15 mg/kg) were coadministered with 6-MP to evaluate their possible role in the protection of 6-MP from oxidation and degradation in the intestinal lumen. No consistent effect was observed, however, on the AUCs of either of these agents. A clear relationship was found between AUCs and the 24-h urinary excretion of unchanged drug (r = 0.9381), indicating that determinations of 6-MP in the urine may replace the painful procedure of repeated blood sampling. Further studies are necessary to determine the factors contributing to the unpredictable plasma levels following oral doses of 6-MP and to determine the value of pharmacokinetic monitoring in ALL patients.

Administration, Oral↗
PubMed1989

Dehydroxylation of a 7 beta-hydroxy-C27 plant sterol in rat liver.

(22R)-Cholest-5-ene-3 beta,7 alpha,22-triol and the isomeric (22R)-cholest-5-ene-3 beta,7 beta,2-triol were 7-dehydroxylated by rat liver microsomes, after addition of NAD+ to the incubations. The product from both sterols was identified as (22R)-22-hydroxycholesta-4,6-dien-3-one by gas chromatography-mass spectrometry. The overall conversion of the 7 alpha-compound had an apparent Vmax of 5 nmol/mg protein per h, about 3-times higher than that of the 7 beta-isomer. Km was about 0.018 mmol/l in both reactions. NAD+ was required for the 7-dehydroxylation to proceed, conceivably by serving as cofactor in formation of the intermediate 7 beta,2-dihydroxy-4-cholesten-3-one. EDTA had a stimulatory effect upon the product formation. 7 alpha-Dehydroxylation of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one has been demonstrated in liver tissue, but a 7 beta-hydroxy-C27-steroid dehydroxylating enzyme has previously not been identified. The results are discussed in relation to the marked differences in effect on neoplastic growth by the two isomeric hydroxysterols.

Animals↗
PubMed1989

Advances in the use of computerized gas chromatography-mass spectrometry and high-performance liquid chromatography with rapid scanning detection for clinical diagnosis.

A multi-component analytical system designed for the diagnosis of metabolic disorders is described. The urinary components are separated by a variety of chromatographic techniques, including automated amino acid analysis, high-performance liquid chromatography with diode-array detection and gas chromatography-mass spectrometry with a computerized mass spectral library search for identification of organic acids. The complete system can be used to diagnose over 100 different metabolic diseases. The usefulness of the chromatographic system is exemplified by the pre- and postnatal diagnosis of glutaric aciduria type I, the diagnosis of lysinuric protein intolerance and of alkaptonuria. Drugs and diet may cause interfering metabolites, as exemplified by glycofurol, used as a solvent for intravenous drugs, and saccharin. It is predicted that chromatography and mass spectrometry will continue to be important diagnostic tools for many years ahead.

Acids↗
PubMed1989

Phytanic acid alpha-oxidation and complementation analysis of classical Refsum and peroxisomal disorders.

We have measured the production of 14CO2 from exogenous [1-14C] phytanic acid in fibroblast monolayers from patients with classical Refsum's disease and peroxisomal disorders. Activities in the different disorders were (percentage of control): classical Refsum's disease (5%), isolated peroxisomal acyl-CoA oxidase deficiency (75%), Zellweger syndrome (4%), neonatal adrenoleukodystrophy (5%), and rhizomelic chondrodysplasia punctate (3%). Absence of complementation was demonstrated between Zellweger syndrome and infantile Refsum's disease lines after polyethylene glycol fusion, with decreases of average activity of 11% relative to unfused cell mixtures. Classical Refsum's disease, rhizomelic chondrodysplasia punctata, and neonatal adrenoleukodystrophy lines all complemented one another, and Zellweger syndrome or infantile Refsum's disease lines, with average activity increases of 522%-772%. No intragenic complementation was observed within either group. Four complementation groups were detected suggesting that at least four genes are involved in phytanic acid alpha-oxidation: one gene for the enzyme phytanic acid alpha-hydroxylase (probably mitochondrial); one gene for a regulatory factor for the expression of phytanic acid alpha-decarboxylation activity and two membrane-bound peroxisomal enzymes involved in the synthesis of plasmalogens; two genes for the assembly of functional peroxisomes and/or import of proteins into peroxisomes.

Adrenoleukodystrophy↗
PubMed1989

Double-blind comparison of tiapamil and atenolol in patients with mild to moderate hypertension: a multicenter trial.

The efficacy and safety of tiapamil, a new calcium-channel blocker, was compared with the cardio-selective beta-blocker atenolol in a 16-week double-blind, multicenter trial with an initial 4-week placebo run-in period. Eighty-one outpatients with WHO stage I or II hypertension, 55 men and 26 women, entered the study. There was a total of nine drop-outs, six in the tiapamil group and three in the atenolol group. Five were due to side effects (four in the tiapamil group and one in the atenolol group). Sixty-one patients performed a graded exercise test sitting on a ergometer bicycle before and after completion of the therapy. Patients eligible for the study after the placebo period received either tiapamil 450 mg b.i.d. or atenolol 100 mg daily. Both drugs lowered systolic and diastolic blood pressure significantly. After 12 weeks of therapy, supine blood pressure in the tiapamil group fell from 167/104 mmHg to 154/91 mmHg (p less than 0.005), and in the atenolol group from 166/102 mmHg to 151/89 mmHg (p less than 0.005). A satisfactory reduction in diastolic blood pressure, defined as a reduction of more than 10 mmHg and/or values below or equal to 90 mmHg at the end of the study, was achieved in 29 of 35 patients in the tiapamil group and in 27 of 37 in the atenolol group. No changes in heart rate were observed in the tiapamil group, whereas there was a significant fall in heart rate in the atenolol group. The maximal exercise workload tolerated increased equally in both groups, from 135 to 147 watts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗