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Biomedical subjects

H Olsen

Publications and source records attributed to H Olsen.

At least 55 records · Page 3Linked to original sources

Carisoprodol elimination in humans.

The elimination of the muscle relaxant drug, carisoprodol, was examined in 10 healthy volunteers after an oral dose of 700 mg. In nine subjects, carisoprodol was rapidly eliminated, with a mean half-life of 99 +/- 46 min, and extensively converted to meprobamate. Within 2.5 h after carisoprodol intake, meprobamate serum concentrations exceeded those of carisoprodol. Serum levels of meprobamate recorded (15-25 mumol/L) indicate that meprobamate might contribute to the effect(s) of carisoprodol. One subject eliminated carisoprodol with an overall half-life of 376 min, and only small amounts of meprobamate were recorded. This subject was found to be a poor metabolizer of mephenytoin. In spiked human sera, protein binding of carisoprodol was in the range of 41-67%, whereas meprobamate was bound to a lesser extent, 14-24%.

Adult↗

Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD.

This study examined the changes in cellular glucose uptake induced by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) as measured by quantification of intracellular radioactivity in the NIH 3T3 L1 preadipocyte cell line after a 30-minute incubation with the non-metabolizable radioactive analogue of glucose, 3-O-methyl-D-[1-3H] glucose. Treatment of differentiated NIH 3T3 L1 cells with TCDD produced a time- and dose-dependent decrease in the cellular uptake of glucose. Treatment of cells for 3 hr with 10(-8) M TCDD significantly reduced glucose uptake to about 10% of control values (p </= 0.05). Furthermore, cytochalasin B, a specific inhibitor of facilitative glucose transporter proteins totally abolished the portion of glucose transport activity that is sensitive to TCDD. The role of the Ah receptor in TCDD-mediated reduction in glucose uptake was investigated. Pretreatment of 3T3 L1 cells with the Ah receptor blocker 4,7-phenanthroline antagonized the effect of TCDD on glucose uptake. Structure-activity relationship studies with TCDD and two polychlorinated biphenyl (PCB) congeners revealed a rank order for their potency in the inhibition of glucose transport as follows: TCDD <<3,3',4,4' tetrachlorobiphenyl <2,2',5,5' tetrachlorobiphenyl (TCB). Such a rank order correlates both with previously determined biological activity of TCDD and the more active 3,3',4,4'- and less active 2,2',5,5'-TCB and with affinity for binding to the Ah receptor. The thyroid hormone T4, like TCDD, reduced glucose uptake and blocked the action of TCDD to further reduce glucose uptake. Experimental evidence is consistent with a proposed mechanism for TCDD to reduce the titer of functional glucose transporter proteins through its interaction with the Ah receptor.

3T3 Cells↗

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters pancreatic membrane tyrosine phosphorylation following acute treatment.

To understand the basic mechanisms of TCDD's action to cause hypoinsulinemia in several experimental animals, we have studied TCDD-induced changes in various protein kinase activities in membrane preparations of guinea pig pancreas. For this purpose, young male guinea pigs were treated through a single intraperitoneal injection with 1 or 3 micrograms/kg of TCDD in vivo, and, after given time periods, pancreas samples were obtained and membranes were isolated through homogenization and centrifugation procedures. Several sets of incubation conditions were selected for protein kinase activity assay, each favoring a specific type of protein kinase. It was found that overall protein phosphorylation activities were higher in the preparation from TCDD-treated animals as compared to those found in pair-fed controls and that this trend was more pronounced when the assay medium contained Mn2+ in place of Mg2+ and EGTA. These are the conditions that are known to favor protein tyrosine kinases. Other types of protein kinases from the treated animals did not show any significant differences from the pair-fed control animals, though that of protein kinase C in the treated preparation showed a modest increase. To establish that the type of protein kinases stimulated by TCDD are protein tyrosine kinases, we have carried out phosphoamino acid analyses, KOH digestion, and western blot analyses using an antibody to phosphotyrosine. All the results were consistent in supporting the idea that TCDD causes a rise in protein-tyrosine kinases in pancreas at early stages of poisoning.

Animals↗

Influence of ethanol ingestion on the cornea.

The corneal thickness variations on both eyes of thirteen healthy volunteers were measured in absence and presence of ethanol with ultrasound pachymetry. During ethanol ingestion, to a serum ethanol concentration of 0.98 +/- 0.22 g/l, a small and transient, but statistically significant increase of the corneal thickness appeared (3.0 +/- 3.4% right eye - 4.3 +/- 2.9% left eye, p < 0.05). We suggest that ethanol causes a transient depression of the endothelial pump activity. The measured effect on the cornea is too small to cause reduced visual acuity on Snellen chart. However, a resulting loss of contrast sensitivity may have consequences for car driving and safety work.

Adult↗

Significant decrease of gram-negative anaerobic bacteremia in a major hospital from 1967-73 to 1981-89: an effect of the introduction of metronidazole?

Declining rates of anaerobic bacteremia are reported from medical centres all over the world. At Odense University Hospital the frequency of Gram-negative anaerobic bacteremia decreased from 1.62% in 1967-73 to 0.83% in 1981-89 (p < 0.001). Metronidazole prophylaxis prior to bowel surgery seems to be the most important explanation, as the association of Bacteroides bacteremia with surgery decreased from 80% to 48% (p < 0.01) and no cases of Bacteroides bacteremia occurred during metronidazole treatment without the presence of abscess or gangrene. A contributory factor may be improved methods for abscess localization and drainage. Other drugs having an effect on anaerobes seem of minor importance. A new category of patients seems to be those who have undergone aorto-femoral bypass operation for aneurysm of the aorta. They contract anaerobic Gram-negative bacteremia from infected hematomas or intestinal gangrene.

Adolescent↗

Cataracts in Morquio syndrome (mucopolysaccharidosis IV A).

Three siblings with Morquio syndrome (mucopolysaccharidosis IV A) are described. In addition to the characteristic dwarfism with skeletal deformities, odontoid anomalies, hearing loss and corneal clouding, the authors found almost identical lens opacities in all three patients. Lenticular opacities have not previously been described in patients with Morquio's syndrome IV A.

Adolescent↗

TCDD causes stimulation of c-ras expression in the hepatic plasma membranes in vivo and in vitro.

A series of in vivo and in vitro experiments were conducted to determine the effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) administered on the expression of c-ras. Differences in c-ras expression between control and TCDD treated groups were determined by immunoassay of p21ras protein, or indirectly measured by the specific binding of 3H-GTP to hepatic plasma membrane preparations. Intraperitoneal injection of sublethal doses of TCDD significantly elevated (P less than 0.05, Student t test) levels of hepatic p21ras protein in Sprague-Dawley rats and TCDD sensitive C57BL/6J mice. Such an increase occurred at an early stage of poisoning in the C57BL/6J mice. The earliest increase was detectable 6 hr after dosing, and the difference became statistically significant by 12 and 24 hr after dosing. In contrast, TCDD tolerant DBA/2J mice had only a marginal increase in hepatic p21ras protein which did not become statistically significant even at 24 hr host-dosing. TCDD evoked increases in hepatic p21ras protein of C57BL/6J mice were accompanied by the increase in the specific binding of GTP to hepatic plasma membranes. Column chromatography of solubilized rat hepatic membrane proteins on sephadex G-50 showed TCDD administration increased levels of a 3H-GTP binding protein with MW of approximately 21 Kd. 3H-GTP binding in total hepatic membranes was also elevated (P less than 0.05, Fisher PLSD multiple comparison test) 6 hr and 24 hr after dosing of C57BL/6J mice, but as expected the effect of TCDD was not as conspicuous as that found in the plasma membrane. TCDD treatment increased levels of a 21 Kd protein found in the in vitro translation products of RNA purified from guinea pig liver. This protein was identified as a c-ras protein based upon its ability to bind GTP, precipitation by a polyclonal antibody against the rasHa and Ki proteins and subsequent SDS-PAGE which showed a single protein band of approximately 21 Kd.

3T3 Cells↗

Therapeutic lidocaine concentrations have no effect on blood platelet function and plasma catecholamine levels.

The effects of therapeutic plasma concentrations of lidocaine on blood platelet function and plasma catecholamine levels were assessed in 9 healthy subjects. There were no significant effects on plasma levels of beta-thromboglobulin, collagen and adenosine diphosphate-stimulated platelet aggregation, thromboxane-B2-concentration in plasma after collagen and ADP stimulated platelet aggregation, or on plasma nor-adrenaline and adrenaline. No significant correlation could be demonstrated between any of the variables tested. Thus, it appeared that lidocaine had no effect on platelets that could be of benefit in acute myocardial infarction. It should be possible to use lidocaine, in combination with thrombolytic therapies without increasing the risk of bleeding complications.

Adult↗

[Costs and prices of laboratory services].

Cost accounting is performed in private and public laboratories. Guidelines for these activities are required and with this objective in mind, the Board of the Danish Society of Clinical Chemistry commissioned a working group to produce a position paper which is presented now in this report. The report discusses the objectives, the principles and the general requirements for cost accounting. The significance of information on costs for the clinicians' rational use of the laboratory is also illustrated. The working group points out that prerequisites for lucid and appropriate costing guidelines are clarification of which purposes information on costs are meant to serve, identification of the relevant cost centers and quality assurance of laboratory services to a defined extent. It is common practice to express laboratory costs as costs per test. The report advocates calculation of the cost per patient contact, i.e. the overall costs for laboratory service in a given investigative situation.

Accounting↗

Contrast sensitivity in radial keratotomy.

In a prospective study, contrast sensitivity function was determined before and one month postsurgery in 15 consecutive cases of radial keratotomy. The results obtained pre-operatively were compared to those of an age-matched, emmetropic reference group also comprising 15 persons. Three different test conditions were employed. High luminance background levels of 130 cd/m2, low luminance levels of 3.5 cd/m2 and low luminance levels completed with a central glare source of 7.5 lux. Using an eight-incisional radial keratotomy technique with a 3 mm optical zone, a median reduction in myopia of 3.5 diopters was observed. Corrected visual acuity was not affected by the surgery. The contrast sensitivity functions of the myopic group pre-operatively compared to the post-operative values showed no significant difference for any of the three test conditions. Compared to the reference group, the myopic group pre-operatively demonstrated a statistically significant reduced contrast sensitivity for all test conditions.

Adult↗

Ethanol elimination-rates determined by breath analysis as a marker of recent excessive ethanol consumption.

The rate of ethanol elimination was studied in two groups of men by means of an Alcotest 7010 breath analyser. The experimental group consisted of 15 skid-row alcoholics undergoing detoxification. Their median daily ethanol consumption was 211 (range 26-476) g pure ethanol during the last year. The control group was made up of 12 age-matched healthy social drinkers consuming 9 (range 4-23) g day-1 pure ethanol during the last year. The median ethanol elimination-rate in the elimination phase was 0.25 (range 0.13-0.31) g 1-1 h-1 during the detoxification period in the experimental group. This value was approximately 70% higher than in the control group (0.14(0.12-0.17) g 1-1 h-1). Some correlation was found between reported ethanol intake, and the calculated ethanol elimination-rate, as well as gamma glutamyl transferase (GGT), alanine amino transferase (ALAT), aspartate amino transferase (ASAT), glutamate dehydrogenase (GLDH), mean corpuscular volume (MCV) and HDL-cholesterol. Of these measures, ethanol elimination-rate showed highest sensitivity and efficiency for detection of ethanol consumption above the limit of 50 g per day.

Adult↗

Outbreak of infection with Achromobacter xylosoxidans from contaminated intravascular pressure transducers.

Achromobacter xylosoxidans contaminating transducers caused 15 cases of hospital infection. In the eight patients with bacteraemia the interval from inoculation to fever was an average of 6.6 days. All the infected patients recovered. Computerization of laboratory records allowed retrieval of previous isolates, and review of clinical records focused the problem on patients with cardiac and aortic diseases. The problem arose from the re-use of disposable equipment after disinfection with a benzalcone.

Aged↗

An experimental study on ethanol elimination at subphysiological temperatures.

Hepatocytes isolated from fed and fasted rats have been used to study the rate of ethanol elimination at different incubation temperatures. In the presence of exogenous pyruvate, hepatocytes from fed and 42 hr fasted rats, eliminated ethanol at 37 degrees by a rate of 11.6 +/- 3.4 and 6.4 +/- 0.8 nmol/min./mg of cell protein (+/- S.D.; n = 5), respectively, which are comparable to the rates obtained in vivo. The ethanol oxidation rate in cells from rats of both nutritional states correlated linearily to the incubation temperature (t = 24-37 degrees) with a temperature coefficient (Q10) of 1.8-2.3. (Q10, (= temperature coefficient) is the factor by which the enzyme activity is increased on raising the temperature 10 degrees). These findings indicate that the oxidation is not controlled by processes which involve membrane transitions in the temperature range 24-37 degrees. Our results indicate that a hypothermic individual with a body temperature of 27 degrees would have a 40-50 per cent inhibition of the ethanol elimination rate. Thus, the observed dependency of the ethanol oxidation on the body temperature has to be regarded in back-calculations of blood ethanol concentrations in forensic toxicology.

Animals↗

Bacterial urinary tract infection in cyclosporine-A immunosuppressed renal transplant recipients.

Urinary tract infection and rejection in 48 renal transplant patients immunosuppressed with cyclosporine-A monotherapy were analysed. Urinary tract infection was diagnosed in 52% of the cases with Escherichia coli dominating. Urinary tract infection took a mild and relatively uncomplicated course as only one case of graft pyelonephritis caused graft nephrectomy and no influence on graft survival was observed (p greater than 0.05) in the infected cases in contrast to rejection episodes which caused a significantly reduced graft survival (p less than 0.01).

Aged↗