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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 271 records · Page 15Linked to original sources
PubMed1990

Evaluation of time-resolved fluoroimmunoassay for analysis of sex steroids in serum.

The performance characteristics of time-resolved fluoroimmunoassays (FIAs) for oestradiol and progesterone were evaluated in an in-vitro fertilization/embryo transfer (IVF/ET) programme and for use in differential diagnosis of early pregnancy. Comparisons were made with commercially available radioimmunoassays (RIAs) and the correlations between the results obtained were analysed. The possible clinical impact of the differences was assessed in 30 women undergoing ovarian stimulation for IVF/ET and also in 68 women presenting with suspected pathological gestation. There was good agreement between the performance characteristics observed in the present study and those claimed by the manufacturer. There was also a strong correlation between RIA and FIA within the working ranges of the assays. The differences in the results obtained with the two methods were within the normal limits of variation of the assays, and, consequently, the clinical relevance was minimal. In conclusion, for the clinical purposes in question, the FIAs perform at least as well as commercially available RIAs, and may, therefore, be regarded as an alternative to RIAs for many laboratories.

Embryo Transfer↗
PubMed1990

Studies on somatostatin with time-resolved spectroscopy and molecular dynamics simulations.

Somatostatin was studied by time-resolved fluorescence spectroscopy and by molecular dynamics simulations. The results obtained indicate the existence of mainly one conformation in DMSO, and the existence of several conformations in other solvents. Molecular dynamics simulations showed that the most important region for activity (residue 7-9) is also the most flexible region in the peptide.

Computer Simulation↗
PubMed1990

Heparin-coated equipment reduces complement activation during cardiopulmonary bypass in the pig.

Complement activation was studied during cardiopulmonary bypass (CPB) in the pig. One group of animals was perfused for 2 h using a standard extracorporeal circuit including a hollow fiber membrane oxygenator with full systemic heparinization. Another group was treated in the same way, except that bypass was performed through a heparin-coated CPB circuit (Carmeda Bio-Active Surface, CBAS) and systemic heparinization was reduced by 75%. It was found that complement activation during CPB, measured as changes in the ratio C3d/C3, was significantly less in the CBAS group, most probably reflecting a better biocompatibility.

Animals↗
PubMed1990

Tolerability and pharmacokinetics of remoxipride after intramuscular administration.

A study was undertaken in seven schizophrenic patients to evaluate the tolerability and examine the pharmacokinetics of intramuscularly administered remoxipride after a single 200 mg dose and at steady state following repeated doses of 200 mg twice daily for one week. Comparisons of AUC, t1/2 and tmax using the Wilcoxon's signed rank test showed no significant difference between single dose and steady state indicating that the pharmacokinetics of intramuscular remoxipride were linear. The steady-state Cmax was found to be significantly larger than that after single dose and the increase was accounted for by the predicted accumulation factor, assuming linear kinetics. Although the inter-individual variability in plasma concentrations was large, the intra-individual variability was low as shown by the reproducibility of the single-dose and steady-state plasma curves. Remoxipride, administered intramuscularly, was well tolerated.

Adolescent↗
PubMed1990

Pharmacokinetics of remoxipride in elderly psychotic patients.

The pharmacokinetics of remoxipride when given as single doses of 50 mg and repeated doses of 50 mg, 100 mg, and 200 mg twice daily to 10 elderly psychotic patients (71-89 years) were compared with the findings of two other studies to reveal any age-related differences. The three studies comprised a total of 38 patients in three distinct age groups: elderly (71-89 years), middle-aged (46-69 years) and young (19-36 years). AUC, Cmax and Cmin of both total and unbound remoxipride increased with increasing age. The unbound fraction was similar in the three age groups. The half-life was prolonged in the elderly, most probably caused by a decrease in intrinsic clearance. A two-fold increase in AUC of both total and unbound concentrations was observed in the elderly group compared to the young, suggesting that patients over 70 years in general require half the dose needed by young adult patients. In general, the pharmacokinetics of remoxipride in the elderly are linear.

Adult↗
PubMed1990

Long-term follow up of workers exposed to solvents.

Long term occupational exposure to organic solvents may cause adverse effects to the central nervous system. This collaborative study between six Swedish departments of occupational medicine examines the overall prognosis in terms of working capacity, symptoms, and psychometric test performance for individuals occupationally exposed to organic solvents. After re-analyses of the data from an initial clinical investigation of 111 men, the subjects were divided into two subgroups: one group of 65 with symptoms but no impairment on the tests and one group of 46 with toxic encephalopathy (symptoms and test impairment). At least five years after the initial examination the subjects were asked to attend a re-examination that included a structured medical interview and a psychometric investigation. The results indicate that effects on the central nervous system persist even when exposure has ceased. In the group of 46 more men had stopped working and were receiving sickness or early retirement pensions. This group also had reduced activity levels with regard to everyday life, leisure activities, and education or training and more neuropsychiatric symptoms. There was no support for the view that a solvent induced toxic encephalopathy is a progressive disease comparable with presenile dementia such as Alzheimer's disease or Pick's disease. If a worker was removed from exposure when he presented symptoms without signs of impairment in intellectual function recovery was seen in most cases.

Aged↗
PubMed1990

Amikacin once daily: a new dosing regimen based on drug pharmacokinetics.

Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside therapy. In this study of 29 elderly patients with serious infections, amikacin 11 mg/kg or 15 mg/kg bw was administered as a short-term (30 min) intravenous infusion. The amikacin serum concentration-time profile was best described by a bi-exponential equation with a half-life of about 4.8 h. A triexponential equation was not applicable because the slow terminal elimination phase was not detected during the 24 h dosing interval. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. Amikacin clearance provides more direct information about elimination of amikacin than does serum half-life. Thus, there was a better correlation between the individual amikacin clearances and creatinine clearances (r = 0.89), than between the serum half-lives of amikacin and the creatinine clearances (r = 0.71). For elderly patients a smaller dose of amikacin than the regular daily dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is given once daily. From the data obtained it is also obvious that once-daily dosing of amikacin does not eliminate the need for checking serum concentrations of the drug.

Aged↗
PubMed1990

Inflammatory system activation during cardiopulmonary bypass as an indicator of biocompatibility: a randomized comparison of bubble and membrane oxygenators.

As the exposure of blood to foreign material during cardiopulmonary bypass (CPB) leads to triggering of inflammatory systems, the inflammatory response was used as an indicator of the biocompatibility of oxygenators. Activation of complement and neutrophil granulocytes during CPB was studied in 96 patients undergoing coronary bypass, with randomized comparisons between four different oxygenators, two of bubble and two of membrane type. Seven patients undergoing thoracotomy without CPB served as controls. During CPB there was significant complement activation, measured as changes in the ratio C3d/C3, with no demonstrable difference between the bubble and membrane oxygenator groups. Such change was not seen in the controls. Neutrophil granulocytes released significant amounts of the granule proteins lactoferrin and myeloperoxidase during CPB, but not during thoracotomy without CPB. The plasma concentrations of lactoferrin and myeloperoxidase were significantly lower in the membrane oxygenator groups, possibly indicating better biocompatibility. The strong inflammatory response with both oxygenator types, however, indicates that presently used CPB devices have unsatisfactory biocompatibility.

Adult↗
PubMed1990

Bubble and membrane oxygenators--comparison of postoperative organ dysfunction with special reference to inflammatory activity.

Bubble and membrane oxygenators (2 types of each) were compared in a randomized study of 96 patients undergoing coronary bypass grafting. Cardiac performance, assessed from postoperative need of inotropic support, was significantly better in the membrane oxygenator group. After perfusion lasting more than 2 hours, respiratory function, measured as alveolar-arterial oxygen pressure gradient, was less compromised in that group and renal function, quantified as postoperative rise of serum creatinine was less disturbed. Cerebral function, studied in terms of psychometric test results and concentration of adenylate kinase in cerebrospinal fluid, did not differ between the bubble and membrane oxygenator groups. In investigations concerning changes in inflammatory activity during bypass, complement activation could not be related to the mentioned clinical parameters. Release of the neutrophil granulocyte factors lactoferrin and myeloperoxidase was greater in the bubble oxygenator group and correlated to impaired cardiac and renal performance, but not to pulmonary or cerebral dysfunction.

Adult↗
PubMed1990

Blood cell trauma and postoperative bleeding: comparison of bubble and membrane oxygenators and observations on coronary suction.

Blood cell trauma and postoperative bleeding were studied in 96 patients following coronary artery bypass grafting, with bubble oxygenator used in 47 cases and membrane oxygenator in 49. The haemocompatibility of membrane oxygenators was superior to that of the bubble type, as reflected by less haemolysis, better preservation of platelet function, less release of betathromboglobulin and less degranulation of neutrophil granulocytes. Coronary suction contributed to haemolysis, but did not affect platelet or granulocyte function. Fibrinolysis, postoperative blood loss and need for blood transfusion did not differ between the bubble and membrane oxygenator groups.

Adult↗
PubMed1990

Short-term cefotaxime prophylaxis reduces the failure rate in lower limb amputations.

The effect of prophylaxis with a broad-spectrum antibiotic agent in lower limb amputations was studied in a prospective, randomized investigation of 38 patients. Nineteen received cefotaxime (Claforan) and 19 served as controls. Three patients died in the immediate post-operative period. In the treatment group, 15/18 healed compared with 10/17 controls (P less than 0.001). We concluded that short-term cefotaxime prophylaxis increases the chances to achieve good stump healing.

Aged↗
PubMed1990

Endotoxins in cardiopulmonary bypass.

Endotoxins are biologically active substances derived from the cell wall of degraded gram-negative bacteria. Since sterile water may also contain large amounts of endotoxins, these are easily introduced into the manufacturing processes of technical medical material, such as the extracorporeal components used in cardiopulmonary bypass. In hemodialysis, the presence of endotoxins has been related to untoward effects in patients. Using the limulus amebocyte lysate test, we determined the serum concentration of endotoxin in 42 patients undergoing coronary bypass operations. The values increased during cardiopulmonary bypass, exceeding the normal range of 0 to 20 ng/L in 10 patients with a maximum of 82 ng/L, which probably indicates endotoxin release from the extracorporeal equipment. We found no obvious relation to postoperative morbidity. The endotoxin levels of this study are considerably lower than those reported in two other studies of patients having cardiopulmonary bypass. This might be due to less intraoperative contamination but possibly also to differences in analytic methods.

Adult↗
PubMed1989

Structure and dynamics of a fluorescent DNA oligomer containing the EcoRI recognition sequence: fluorescence, molecular dynamics, and NMR studies.

The self-complementary DNA decamer duplex d(CTGAATTCAG)2 and its modified counterpart d(CTGA[2AP]TTCAG)2, where the innermost adenine (6-aminopurine) has been replaced with the fluorescent analogue 2-aminopurine (2AP), have been studied by fluorescence and NMR spectroscopy and simulated by molecular dynamics. Both decamers are recognized and cleaved by the EcoRI restriction endonuclease. 2D NMR results show that both decamers have a standard B-type conformation below 20 degrees C, though a disturbance exists to the 5' side of the 2AP site which may originate from increased local mobility. The fluorescence and fluorescence anisotropy decays of both decamers, as well as the one containing 2AP in only one chain, were studied as a function of temperature. The data show that the 2AP base exists in a temperature-dependent distribution of states and shows rapid motions, suggesting interconversion among these states on a time scale of about 10(-10) s. The integrated fluorescence of the decamer with 2AP in both chains shows a large increase around the helix melting temperature whereas the decamer with one 2AP shows only a mild increase, showing that the mixed helix has a different structural transition as sensed by the 2AP base. The data suggest a model of conformational states which have distinct fluorescence decay times. The various states may differ in the degree of base stacking. Fluctuations in the degree of stacking of the A or 2AP base are supported by molecular dynamics simulations, which additionally show that the 2AP-T or A-T base pair hydrogen bonds remain intact during these large motions.

DNA↗
PubMed1989

Characterization of the ribosomal properties required for formation of a GTPase active complex with the eukaryotic elongation factor 2.

The binding stability of the different nucleotide-dependent and -independent interactions between elongation factor 2 (EF-2) and 80S ribosomes, as well as 60S subunits, was studied and correlated to the kinetics of the EF-2- and ribosome-dependent hydrolysis of GTP. Empty reconstituted 80S ribosomes were found to contain two subpopulations of ribosomes, with approximately 80% capable of binding EF-2.GuoPP[CH2]P with high affinity (Kd less than 10(-9) M) and the rest only capable of binding the factor-nucleotide complex with low affinity (Kd = 3.7 x 10(-7) M). The activity of the EF-2- and 80S-ribosome dependent GTPase did not respond linearly to increasing factor concentrations. At low EF-2/ribosome ratios the number of GTP molecules hydrolyzed/factor molecule was considerably lower than at higher ratios. The low response coincided with the formation of the high-affinity complex. At increasing EF-2/ribosome ratios, the ribosomes capable of forming the high-affinity complex was saturated with EF-2, thus allowing formation of the low-affinity ribosome.EF-2 complex. Simultaneously, the GTPase activity/factor molecule increased, indicating that the low-affinity complex was responsible for activating the GTP hydrolysis. The large ribosomal subunits constituted a homogeneous population that interacted with EF-2 in a low-affinity (Kd = 1.3 x 10(-6) M) GTPase active complex, suggesting that the ribosomal domain responsible for activating the GTPase was located on the 60S subunit. Ricin treatment converted the 80S particles to the type of conformation only capable of interacting with EF-2 in a low-affinity complex. The structural alteration was accompanied by a dramatic increase in the EF-2-dependent GTPase activity. Surprisingly, ricin had no effect on the factor-catalyzed GTP hydrolysis in the presence of 60S subunits alone.

Animals↗
PubMed1989

Molecular dynamics simulations of ribonuclease T1: comparison of the free enzyme and the 2' GMP-enzyme complex.

Molecular dynamics simulations were performed on free RNase T1 and the 2'GMP-RNase T1 complex in vacuum and with water in the active site along with crystallographically identified waters, allowing analysis of both active site and overall structural and dynamics changes due to the presence of 2'GMP. Differences in the active site include a closing in the presence of 2'GMP, which is accompanied by a decrease in mobility of active site residues. The functional relevance of the active site fluctuations is discussed. 2'GMP alters the motion of Tyr-45, suggesting a role for that residue in providing a hydrophobic environment for the protein-nucleic acid interactions responsible for the specificity of RNase T1. The presence of 2'GMP causes a structural change of the C-terminus of the alpha-helix, indicating the transmission of structural changes from the active site through the protein matrix. Overall fluctuations of both the free and 2'GMP enzyme forms are in good agreement with X-ray temperature factors. The motion of Trp-59 is influenced by 2'GMP, indicating differences in enzyme dynamics away from the active site, with the calculated changes following those previously seen in time-resolved fluorescence experiments.

Binding Sites↗
PubMed1989

Remoxipride--a new potential antipsychotic compound. Tolerability and pharmacokinetics after single oral and intravenous administration in healthy male volunteers.

The tolerability and pharmacokinetics of remoxipride were studied in 18 healthy normal male volunteers. Increasing oral doses of 0.5-100 mg were given to eight male volunteers in one study (study I). In addition, an intravenous (IV) infusion of 20 mg remoxipride and a 20 mg oral dose were given in an open crossover study to ten males (study II). Remoxipride was well tolerated with respect to cardiovascular effects, clinical chemistry, body temperature and adverse effects in all subjects. Following IV administration, remoxipride plasma concentrations declined exponentially in five subjects and biexponentially in the remaining five. The mean apparent volume of distribution was 0.5 l/kg (SD = 0.10) and the mean half-life 4.1 h (range 2.6-6.6). The recovery of unchanged remoxipride in urine was 10-36%, and the mean renal clearance was 32 ml/min (SD = 13). Remoxipride was a low clearance drug with a total plasma clearance of about 120 ml/min (SD = 41). The mean oral bioavailability was 96%. There was a linear relationship between the peak plasma concentration as well as the area under the concentration versus time curve and the administered dose. A transient increase in plasma prolactin concentrations occurred but there were no effects on plasma growth hormone levels.

Administration, Oral↗