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Biomedical subjects

A Arvidsson

Publications and source records attributed to A Arvidsson.

At least 37 records · Page 2Linked to original sources

Pharmacokinetic studies of cefoxitin in continuous ambulatory peritoneal dialysis.

The pharmacokinetics of cefoxitin was examined in 9 patients undergoing peritoneal dialysis for chronic renal failure. Cefoxitin was administered intraperitoneally in the dialysate fluid every 6 h for 24 h, in two different concentrations, 50 micrograms/ml and 100 micrograms/ml. The plasma half-life of cefoxitin was 20.2 h. The major route of elimination was non-renal, with a clearance of 8.0 ml/min. Peritoneal clearance was 4.1 ml/min. As expected, renal clearance was negligible. The peak plasma concentrations of cefoxitin at the two dose levels used were 7 micrograms/ml and 15 micrograms/ml, respectively, when assayed by HPLC, and 12 micrograms/ml and 24 micrograms/ml when determined by a microbiological assay. The cefoxitin concentration in the dialysate decreased from 50 micrograms/ml to 14 micrograms/ml and from 100 micrograms/ml to 37 micrograms/ml during the 6 h of its retention in the peritoneal cavity.

Adult↗

Automatic selection of uncontaminated electromyogram as applied to respiratory muscle fatigue.

An automatic procedure for detecting artifacts in the electromyogram (EMG) has been developed and applied to a study of respiratory muscle fatigue. Signal segments are characterized by a set of features, the normal variations of which have been estimated in a training session. From the features are calculated a classification variable, which expresses the degree of deviation from normal conditions. A deviation larger than a certain threshold value designates a segment as disturbed. The study deals with the choice of features, the selection of a suitable segment length, and the determination of an optimal classification threshold. The four features chosen include measures of amplitude symmetry, extreme excursions in the signal tracing, the signal-to-noise ratio, and the shape of the EMG power spectrum. Recordings from three subjects were used for the evaluation of the method. The results indicate that a segment length of 250 ms is appropriate. Accepting a 10% rate of false detections, the average rate of missed detections was 2.2%.

Diaphragm↗

Effect of cephapirin on tubular reabsorption of amino acids, uric acid and beta 2-microglobulin in man.

Cephapirin, a beta-lactam antibiotic, was administered intravenously to five healthy subjects in a dose of 1 g. Renal clearances of cephapirin, beta 2-microglobulin, uric acid and amino acids were measured during the experiment and compared to timed control data, i.e. when no cephapirin was given. Renal clearance of cephapirin decreased when plasma concentrations declined. As protein binding of cephapirin is constant over a wide plasma concentration range, this finding may indicate that cephapirin is reabsorbed in the kidney by a saturable process. Renal clearance of endogenous amino acids, particularly those belonging to the basic group increased after cephapirin. There was no change in renal clearance of beta 2-microglobulin which excludes a general toxic effect on tubular reabsorption of endogenous substances caused by cephapirin. A flow dependent increase of uric acid clearance was observed. Our results are suggestive of a competition between cephapirin and amino acids for some common step in the tubular reabsorption process.

Amino Acids↗

Evaluation of the effects of cephaloridine on urate excretion in the rat.

In female Sprague-Dawley rats, the renal clearance of cephaloridine decreased as the plasma concentration of the drug declined from above 10 micrograms/ml to below about 3 micrograms/ml, thus suggesting a saturable tubular reabsorption of cephaloridine similar to that shown previously in man. The effects of cephaloridine (250 mg/kg i.v.) were compared with those shown by a group of rats receiving saline and another group of rats receiving probenecid (250 mg/kg i.v.). Probenecid caused a sustained increase in the urate excretion rate. By contrast, cephaloridine produced a relatively small and transient increase in urate excretion, which may have been caused by its diuretic effect. Thus, it is unlikely that the reabsorption mechanism of urate is the principle mechanism by which cephaloridine is reabsorbed.

Animals↗

Optimal conditions for assay of cytochrome-c-oxidase activity in human skeletal muscle tissue.

Conditions for the assay of cytochrome-c-oxidase in human skeletal muscle tissue were studied, including an evaluation of the optimal conditions during the in vitro assay as well as the optimal conditions for storage and treatment of the tissue before the assay. The activity of cytochrome-c-oxidase was assayed polarographically with a Clark oxygen electrode. Optimal oxygen consumption rates were obtained at a cytochrome-c-concentration above 0.2 mmol/l, in the presence of TMPD, 2.2 mmol/l and ascorbic acid, 4.4 mmol/l as reducing agents. Enzyme proportionality was obtained after correction of the oxygen consumption rates for a blank reaction according to one of three alternatives presented. Variations in the homogenizing technique and the degree of dilution of the homogenate (1:11-1:88) had only moderate effects on the enzyme activity. Optimal storage conditions were evaluated by comparing the enzyme activities measured in fresh muscles, frozen muscles and homogenates prepared from fresh muscles. During all storage conditions significantly higher activities were obtained when sucrose buffer (0.25 mol/l) was used as homogenizing medium as compared to phosphate buffer (0.1 mol/l). Freezing and thawing of the muscle tissue before the assay caused an average decrease in the enzyme activity of 50% (P less than 0.005) as compared to the activity obtained in fresh tissue. This untoward effect of the freezing and thawing was reduced when the enzyme activity was analysed in frozen homogenates prepared from fresh muscles. Thus, an average decrease in the enzyme activity of 15% (P less than 0.05) was found in frozen homogenates prepared in sucrose buffer as compared to the activity obtained in the fresh tissue. These findings emphasize the importance of evaluating the effects of the tissue treatment for comparative studies of maximum enzyme activities in vitro.

Electron Transport Complex IV↗

The distribution of amino acids between plasma and erythrocytes.

Amino acid concentrations were determined in whole blood, plasma and washed erythrocytes from a group of healthy subjects. A comparison between the erythrocyte concentrations calculated from whole blood and plasma concentrations and those measured in washed erythrocytes showed that several amino acids (especially methionine, valine, isoleucine, leucine, tyrosine and phenylalanine) can easily be washed out of the erythrocytes. Statistical analysis of the data indicates that at least three different amino acid transport systems are operative in erythrocytes: (1) a system for anionic amino acids (aspartate and glutamate), which concentrates these amino acids intracellularly, reaching high erythrocyte/plasma (E/P) concentration ratios; (2) a concentrating system of A type, transporting serine, glycine and alanine and maintaining E/P ratios less than two; these amino acids show positive corelations between plasma and erythrocyte concentrations and are retained in the erythrocytes when they are washed; (3) a system of L type, with reactivity to the branched chain amino acids, methionine, phenylalanine, lysine and glutamine, which is not concentrating. The erythrocyte concentrations of these amino acids are independent of those in plasma and they can easily be washed out of the cells. Threonine and tyrosine seem to be transported by both the A and L system.

Adult↗

Renal excretion of cephapirin and cephaloridine: evidence for saturable tubular reabsorption.

Drug concentrations in plasma and urine were determined in 5 healthy subjects after intravenous infusion of 1 gm cephapirin and cephaloridine. Sampling of blood and urine was frequent and prolonged. Specimens were analyzed by high-pressure liquid chromatography (HPLC). Renal clearance of cephapirin decreased to less than 5% of control in all subjects when drug concentrations in plasma and urine declined. Cephaloridine clearance decreased to a lesser extent. Our findings suggest that, besides tubular secretion and glomerular filtration, a saturable and probably active tubular reabsorption is also involved in the renal handling of these two cephalosporins. The saturable reabsorption process was characterized by its Michaelis-Menten constant Km and its maximum transport capacity Tm.

Absorption↗

Serial quantitative electroencephalography.

Repeated EEG examinations are often used in diagnostically difficult cases to assess whether an EEG abnormality is progressive, regressive, or stationary. The conventional visual method is, however, poorly adapted to consider the variability when consecutive EEG recordings are compared. Using computer analysis of EEGs, the feature of the recordings as well as their variances can be measured, and the differences between the recordings can be tested statistically. The aim of the present study was to develop a practicable method for quantitative serial EEG examinations. Twenty EEGs from 5 volunteers were recorded to obtain reference data. The data acquisition was automated to obtain data without visual bias. The previously developed method using age ratios was employed for the primary analysis. The changes of the EEG activity during the observation period were evaluated statistically. Differences between consecutive EEGs could be observed even in normal subjects but the number of 'false positive' findings was reduced by the automatic data selection, by the choice of proper measures, and by adequate statistical treatment. The diagnostic value of the method was tested in 59 EEGs from 13 patients with well-defined brain disorders. Most EEG changes which could be attributed to the development of the disease were discovered and labelled as statistically significant.

Adult↗

Glutathione and gamma-glutamylcysteine in whole blood, plasma and erythrocytes.

A method for the simultaneous determination of glutathione and gamma-glutamylcysteine in capillary blood samples is described. The whole blood levels of glutathione and gamma-glutamylcysteine are t.09 +/- 0.20 mmol/l and 25 +/- 8 mumol/l (M +/- S.D.), respectively. The plasma concentration is approximately 4 mumol/l for both compounds. It is important to treat the blood samples with a reducing agent before protein precipitation to release glutathione and gamma-glutamylcysteine from disulfide linkages since, otherwise, 30--40% of the glutathione and 80% of the gamma-glutamylcysteine is lost with the protein precipitate. Whole blood is preferable to washed erythrocytes for the analysis since the washing procedure involves losses of, especially, gamma-glutamylcysteine.

Adult↗

A controlled long-term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects.

The hypnotic effect of flunitrazepam (Ro 5-4200), nitrazepam and a placebo was studied in 117 outpatients using hypnotics for at least 3 months prior to the study. They obtained various neurotropic drugs and this and other treatments were unchanged throughout the trial period of 13 weeks. This consisted of 3 weeks on the previously used hypnotic, 3 weeks on a test drug (during the first of these a doubling of the dose was permitted if the initial dose of 1 mg flunitrazepam, 5 mg nitrazepam or one tablet of placebo was not satisfactory) and 4 weeks' observation after a request to stop medication with the test drug. The effects were evaluated every week by self-ratings. Also noted were: the frequency of dose increase after 1 week of the test period, number of drop-outs in the test period, and failure in the attempt to stop taking the test drug. A "psychological concentration test" was done, as was a follow-up interview. The self-ratings had a good reliability and showed that more patients experienced shorter sleep induction, longer sleep time, better sleep quality and a subjective feeling of having had a better rest with flunitrazepam than with either nitrazepam or placebo. There were no differences between the nitrazepam and the placebo groups. Tiredness was the most common side effect and appeared in the same frequency in all groups. The number of patients who increased the dose after 1 week's medication, as well as the number of drop-outs, was significantly higher in the nitrazepam and placebo groups than in the flunitrazepam group. There was no difference in the ability to discontinue the medication between the test groups or between groups having previously used different hypnotics. The "psychological concentration test" did not reveal any differences between groups. It was concluded that withdrawal of a hypnotic in chronic users was not facilitated by the use of a placebo. This was interpreted as due to a strong psychological dependence upon the hypnotics and their lack of pharmacological effects during long-term treatment.

Adult↗