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Biomedical subjects

P Olsson

Publications and source records attributed to P Olsson.

At least 91 records · Page 5Linked to original sources

Absolute bioavailability of nicotine applied to different nasal regions.

The absolute bioavailability of nicotine administered nasally, as drops to the nasal conchae and nasal septum, and as a nasal spray, has been studied in eight healthy volunteers. Single nasal doses of 1 mg nicotine were given and plasma concentrations of nicotine were followed for 6 h. Compared to an intravenous infusion of nicotine, the bioavailability of the nasal administrations was 60 to 75%. The rate of absorption was fast, the maximum concentration being reached after about 10 min. In the present study, there was no significant difference in the rate or extent of absorption between the different nasal treatments.

Absorption↗

Dermal blood flow after local challenges with allergen, histamine, bradykinin and compound 48/80.

Blood flow was determined in weal and flare reactions and in late dermal reactions after skin-prick tests with allergen, histamine, bradykinin and compound 48/80 in pollen-allergic subjects. Local blood flow was measured with laser Doppler flowmetry intermittently for up to 48 hr at three distances from the prick centre (2 mm; weal, 15 mm; flare and 30 mm). Continuous recordings were also made in the weal area after challenge with bradykinn and compound 48/80. The size of the induced weal and flare area of all the substances and the late phase after allergen was determined using digitized planimetry. Furthermore, simultaneous determinations of local dermal temperature and blood flow in the weal and flare site were performed intermittently for 6 hr after allergen and histamine challenges. There was a dose-dependent and distance-related increase in blood flow for all the substances tested. The blood flow in the 2-mm registrations had normalized 20 min after bradykinin, 1.5-2 hr after histamine and 3 hr after compound 48/80, while allergen induced a continuous increase in blood flow for more than 24 hr. The area of the weal and flare reaction was dose related for all substances, and a similar dose-dependent increase was noted for the observed dermal late-phase reactions present after allergen. The local temperature after challenge with allergen and histamine was also increased in a distance-dependent manner. These studies suggest that laser Doppler flowmetry is a sensitive and reproducible method to quantify blood flow changes occurring after skin-prick tests. Different putative mediators or mast cell stimulating substances produce various response profiles, all of which differ from those observed after allergen. Temperature measurements after skin-prick tests seem to follow the observed changes in blood flow as measured with laser Doppler flowmetry, which may be why both techniques might reflect changes in capillary blood flow.

Adult↗

Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS.

To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects.

Adult↗

Increased erythrocyte volume in car repair painters and car mechanics.

The biological effect of occupational long term low level exposure to organic solvents was studied in 17 car repair painters and 28 car mechanics, and compared with a control group consisting of 46 healthy men not exposed to organic solvents. The erythrocyte count (RBC) was significantly decreased for both the painters and the mechanics compared with the control group, and a significant increase in the mean erythrocyte volume (MCV) was seen in painters. The mode in size distribution of the erythrocytes (MAXRBC) was shifted towards larger cell volumes for both painters and mechanics. When data from painters and mechanics were combined, the exposed group showed a significantly reduced erythrocyte count (RBC), an increased mean erythrocyte volume (MVC), and an increased mean platelet volume (MPV) compared with the controls. Exposure measurements in combination with analysis of haematological parameters may be a tool for early detection of cellular changes in the blood caused by exposure to solvents, before the appearance of clinical symptoms.

Adult↗

Veno-venous extracorporeal membrane oxygenation with a heparin-coated system in adult respiratory distress syndrome.

Three patients with adult respiratory distress syndrome were treated with veno-venous extracorporeal membrane oxygenation, ECMO, using a heparin-coated system for 8, 12 and 34 days, respectively. Despite extracorporeal blood flow of 4-5 l/min, the patients were ventilator-dependent in the initial period of ECMO. Two of the three patients showed bleeding diatheses despite only slightly elevated activated partial thromboplastin time (APTT). Blood platelet count followed a variable course and serum fibrinogen was normal. Acute pulmonary hypertensive crises, fatal systemic infection, recurrent pneumothorax and plasma leakage from the oxygenators were other main complications during ECMO. Two of the three patients survived, and follow-up showed that severely damaged lungs, if supported in the acute phase, can recover sufficiently to permit normal living.

Adult↗

Binding of antithrombin to immobilized heparin under varying flow conditions.

Rheologic factors are likely to influence the balance between thrombotic and antithrombotic forces at the level of the vascular wall. In this study, the effects of flow-velocity/wall shear stress on the interaction of antithrombin (AT) with surface-immobilized heparin were investigated. The binding of AT to low-affinity and high-affinity heparin could be discriminated by measurements at physiological of elevated ionic strength. Under low shear stress conditions, substantial binding of AT to both high- and low-affinity heparin was observed, in relative quantities largely reflecting the proportion of these polysaccharide populations on the surface. With increasing shear stress, the binding to high-affinity sites was relatively constant, while total low-affinity binding decreased. Furthermore, under the highest shear stress (greater than 1,000 N/m2), the binding of AT to low-affinity heparin completely disappeared while binding to the high-affinity fraction persisted. These results were related to values obtained in a mathematical model, describing the theoretical maximum transport of AT from the liquid phase to the surface under the conditions used in the experimental system.

Animals↗

Effects on cyclo-oxygenase of low and high dose aspirin.

The study was undertaken to develop clinically applicable methods to detect the influence of low dose treatment with acetylsalicylic acid (ASA) on the platelet function. The cyclooxygenase activity of the platelets was measured by determination of the metabolite 12-HHT after challenge with arachidonic acid. Two healthy subjects received 600 mg ASA in a single dose. Two hours after intake the salicylate concentration level in plasma was 600 nmol/ml, with a 90 per cent reduction after 24 hours. The platelet cyclooxygenase activity (12-HHT) was completely and irreversibly inhibited within two hours after ASA intake. Five subjects received 75 mg ASA for eight consecutive days. The salicylate concentrations two hours after the intake of the first and last tablet were within 65 and 71 nmol/ml plasma, indicating that no accumulation of salicylate occurred during the treatment period. The decrease in cyclooxygenase activity during low dose treatment varied in the different subjects between 60 and 90 per cent. The rate of recovery of cyclooxygenase activity after termination of the low dose ASA treatment was faster than after the large single dose.

Adult↗

The use of a commercial ELISA for assay of thrombin-antithrombin complexes in purified systems.

Inhibition of thrombin by antithrombin III (AT) results in the formation of stable thrombin-AT complexes (TAT). An enzyme-linked immunosorbent assay (ELISA) following the sandwich principle is available for the determination of TAT complexes in human plasma, however, this ELISA method could not be used in purified systems containing thrombin and AT. It has therefore been modified for use in purified systems and an excellent correlation was found between the disappearance of thrombin and AT and the recovery of TAT complexes. Addition of thrombin inhibitor hirudin and heparin inhibitor polybrene into the reacting thrombin-AT mixture did not interfere with the assay of TAT. It was found that the use of siliconised tubes was necessary for the conservation of the TAT complexes.

Antithrombin III↗

[Distress].

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Adult↗

Blood flow in histamine- and allergen-induced weal and flare responses, effects of an H1 antagonist, alpha-adrenoceptor agonist and a topical glucocorticoid.

Allergen has previously been shown to induce a continuous increase in local dermal blood flow after a prick test in allergic subjects, whereas histamine induced, initially, similar peak increases in blood flow of much shorter duration. Blood flow changes induced by histamine and allergen have now been evaluated (i) after pretreatment with a local corticosteroid cream, clobetasole-17-propionate; (ii) after oral administration of the H1-antihistamine loratadine; and (iii) after oral pretreatment with the alpha 1-adrenoceptor agonist pseudoephedrine. Blinded placebo-controlled designs were used in the substudies. Laser doppler flowmetry was used for non-invasive recording of changes in local blood flow intermittently for 24 h after the topical corticosteroid, 6 h for the substudies on loratadine and pseudoephedrine. The size of the immediate weal and flare reactions, as well as late phase reactions, were also determined. Pretreatment with clobetasole-17-propionate cream on the skin for 1 week prior to prick tests did not affect the blood flow response elicited by histamine or allergen, in either the initial part (up to 1 h) or the protracted 24 h determinations. The size of the weal and flare reactions decreased. Loratadine and pseudoephedrine did not reduce the initial allergen-induced increase in blood flow, while lower blood flow compared with placebo pretreatment was noted for the protracted (1-6 h) determinations. Blood flow changes after histamine were unaffected. The histamine-induced weal and flare was inhibited by loratadine more effectively than the corresponding allergen-induced reaction. The weal and flare reactions after histamine and allergen were not changed after pseudoephedrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

[Welcome].

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Aged↗

Blood flow in dermal allergen-induced immediate and late-phase reactions.

Changes in local skin blood flow after prick-tests with histamine and allergen challenge were evaluated using laser doppler flowmetry. Two series of measurements were performed; each included 11 subjects with seasonal allergic rhinitis. In the first series vascular reactions were registered intermittently for a period of 6 hr. This was then repeated with additional registrations after 14 and 24 hr. Registrations were made in the skin close to where the test substances were applied which was in the area of the initial weal reaction. Pre-loaded skin-prick test needles were used for the histamine and allergen tests. Controls using 'blank' needles were also set on the same occasion. The control induced a transient increase in blood flow which had disappeared after 1 hr. After histamine challenge, the initial rapid increase in blood flow was followed by a slow return to baseline within 1 hr, and no further changes were noticed during the registration period. A different blood flow response was seen after the application of allergen. After an initial increase, the blood flow remained at this higher level for more than 6 hr. Thereafter a slow decrease towards baseline was seen within 24 hr. The pronounced difference between the histamine- and allergen-induced responses in the later part of the registrations after similar initial peak responses indicates that actions other than an initial burst of released histamine are responsible for the changes in dermal blood flow observed after allergen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of high and low wall shear rates on the inhibition of factor Xa and thrombin at surfaces coated with immobilized heparin.

The thromboresistant function of a surface with end-point attached heparin is based upon interaction among the immobilized heparin, antithrombin, and at least factor Xa or thrombin. Heparinized arteriovenous shunts were implanted in dogs. By compressing a segment of the shunt, high and low wall shear rate regions were obtained in each shunt. After removal, the tubings were tested for their factor Xa and thrombin inhibitory capacity. It was found that on a molar basis, the factor Xa and thrombin inhibitory capacity were similar in low wall shear rate segments. In high wall shear rate segments, the thrombin inhibitory capacity was decreased, thus indicating that the AT-mediated inhibition of the serine protease is dependent on the wall shear rate.

Animals↗

Influence of blood flow and the effect of protamine on the thromboresistant properties of a covalently bonded heparin surface.

Polyethylene tubings, 2-mm inner diameter and the length of 1 m, untreated or furnished with a covalently bonded heparin surface layer, were inserted as arteriovenous shunts bilaterally in dogs. By compressing the middle part, the initial blood flow was adjusted to 10 or 40 mL/min. The thrombogenicity of the tubings was assessed by the patency of the shunts and by assaying the generation of fibrinopeptide A (FPA) in arterial blood and in blood after its passage through the shunts. In untreated shunts clotting rapidly occurred preceded by high FPA generation in blood passing through the shunts. The blood flow in heparinized shunts remained unchanged throughout the test period. At the low flow rate a certain degree of FPA generation in the shunts occurred. At the high flow rate no changes in FPA levels occurred. The function of the heparin surface is thus flow rate dependent. Systematic heparinization and subsequent neutralization with protamine or administration of protamine alone did not interfere with the function of the heparin surface.

Animals↗

Extracorporeal CO2-removal with a heparin coated artificial lung.

Treatment of severe acute respiratory failure with extracorporeal gas exchange necessitating near complete systemic anticoagulation requires a delicate balance to be maintained between disseminated intravascular coagulation and hemorrhagic complications. The present study describes our first experience using a heparin coated extracorporeal artificial lung and circuitry during clinical extracorporeal CO2 removal. In spite of a partial thromboplastin time and activated clotting time within or close to the normal range, neither laboratory evidence for disseminated intravascular coagulation induced by the extracorporeal circuit nor thrombi in the pulmonary vasculature were found. Scanning electron microscopy of the heparin coated hollow fiber gas exchanger demonstrated only minor deposits on the surface. Use of a heparin coated artificial lung may enhance the margin of safety of extracorporeal gas exchange and ultimately broaden its indications.

Acute Disease↗

Wheal-and-flare reactions induced by allergen and histamine: evaluation of blood flow with laser Doppler flowmetry.

Dermal blood flow was evaluated after skin prick test with histamine and allergen in six patients with seasonal allergic rhinitis. Blood flow was registered continuously for 60 minutes after the test procedure with laser doppler flowmetry, which allows noninvasive measurements. Blood flow was measured close to the skin test in the wheal obtained, and at a greater distance from the prick in the flare reaction. Tests were performed with preloaded skin test needles with histamine and the appropriate allergen freeze-dried on the point of the lancet, as well as with the appropriate negative control. The prick test procedure, by itself, induced a transient increase in blood flow that was normalized again after 9 minutes for the closest measurement. Histamine induced a rapid increase in blood flow in both the flare and wheal reaction that was normalized after about 45 minutes. The increase was significantly higher in the flare compared to the wheal for the time points from 6 1/2 to 13 minutes. Allergen induced a similar increase in blood flow. However, the increase was not noticeable until 2 1/2 minutes after the allergen application and was not completely abolished within 60 minutes. Furthermore, the difference between the flare and wheal reaction, with the higher values for the flare reaction, was present for a longer period of time than for the equivalent histamine measurements. In conclusion, laser doppler flowmetry appears useful for continuous evaluation of vascular changes induced at skin prick tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗