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Biomedical subjects

T Söderström

Publications and source records attributed to T Söderström.

At least 19 recordsLinked to original sources
PubMed2005

High prevalence of IgE antibodies among blood donors in Sweden and Norway.

BACKGROUND: Reactions after a blood transfusion could be allergic because of passive transfer of immunoglobulin E (IgE) antibodies from allergic donors. AIMS OF THE STUDY: To compare spectrum and prevalence of IgE antibodies in blood donors from Sweden and Norway. METHODS: Using the ImmunoCAP method, serum samples from 1002 blood donors from Sweden and 500 from Norway were analysed for IgE antibodies to common inhalant and food allergens and allergens common in a hospital environment, such as penicilloyl G and latex. RESULTS: As many as 23.6-27.3% of the donors had IgE antibodies to at least one of the 14 allergens tested. Of these 6.8-16.7% had extremely high concentrations, i.e. >35 kU(A)/l corresponding to 100 times the cut-off for a positive allergy test. Most donors were sensitized to pollens, dander and mite but several had very high levels of IgE antibodies to penicilloyl G, latex and peanut. The pattern of sensitizing allergens differed between Sweden and Norway. CONCLUSIONS: High serum levels of IgE antibodies to various allergens are common among blood donors and the degree of sensitization and spectrum of involved allergen varies between geographical regions. Present routines to identify IgE sensitized, potential risk, donors are not satisfactory; the sensitivity of selection procedures is about 25%.

Allergens↗
PubMed2005

Occurrence of cold activation of transfusion plasma during storage at +4 degrees C.

BACKGROUND AND OBJECTIVES: The storage of transfusion plasma at +4 degrees C sometimes leads to the activation of several proteolytic systems. In this study the frequency of cold activation was investigated, as well as whether cold activation of plasma is an individually recurrent property of the donor. MATERIALS AND METHODS: Plasma units prepared from whole blood obtained from 100 male donors were stored at +2 degrees to +5 degrees C, in bags for 28 days and in cryotubes for up to 42 days. Samples from plasma units, collected by apheresis from 100 male donors, were stored in cryotubes for up to 42 days. Cold activation was measured weekly as kallikrein-like activity of plasma. Samples from repeat apheresis plasma units from 32 donors were measured 12-20 months later. The effects of storage on the contact, coagulation and fibrinolytic systems were determined. RESULTS: The cumulative frequency of cold-activated plasma units stored in bags was 5% on day 7 and 18% on day 28. After 42 days in cryotubes, 49% of the plasma units were cold activated. Large intraindividual differences in the onset-day of cold activation were observed in plasma samples of some donors. During cold activation, an increase in kallikrein-like activity was accompanied by a decrease in C1 esterase inhibitor activity and an increase in the concentrations of activated factor VII and fibrinopeptide A. The functional plasminogen level was unchanged, while a minor decrease in plasmin inhibitor activity was combined with a corresponding increase in the concentration of plasmin-plasmin inhibitor complex. CONCLUSIONS: The cumulative frequency of cold-activated plasma units increased in a time-dependent manner during storage at +2 degrees to +5 degrees C for 42 days. The intraindividual onset-day of cold activation varied widely between plasma samples of some donors. Cold activation was associated with a high degree of activation of the contact and coagulation systems. The fibrinolytic system was scarcely affected.

Blood Coagulation Factors↗
PubMed2003

Nicotinamide is a potent inhibitor of proinflammatory cytokines.

The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1 beta, IL-6 and TNF alpha responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4-40 mmol/l nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFalpha, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease.

Adjuvants, Immunologic↗
PubMed2003

Nicotinamide inhibits endotoxin-induced monocyte tissue factor expression.

BACKGROUND: Tissue factor (TF) is the main initiator of blood coagulation in vivo. Its increased expression on activated monocytes is associated with thrombotic complications and mortality in conditions such as sepsis, disseminated intravascular coagulation and coronary artery disease. OBJECTIVE: The effect of the vitamin B derivative nicotinamide on endotoxin-induced monocyte TF and CD11b expression, soluble interleukin(IL)-6, and clotting onset time (COT) was studied. METHODS: Experiments were conducted in human peripheral blood leukocyte suspensions and in whole blood from eight healthy volunteers. Free oscillating rheometry (measuring COT) and flow cytometry were applied to evaluate the effect of endotoxin on TF, CD11b, IL-6 and the overall coagulation response of plasma supplemented with activated autologous leukocytes. RESULTS: In response to endotoxin, there was an increase in IL-6, TF and CD11b expression and a procoagulant shift of COT. At 4 mmol L-1 nicotinamide, inhibition of TF expression and IL-6 and a normalization of COT were seen. At 16 mmol L-1 nicotinamide, CD11b decreased also. The level of monocyte TF expression correlated with the COT readings, and the endotoxin-induced procoagulant shift of COT could be totally inhibited by blocking TF with an inhibitory antibody. CONCLUSIONS: These results demonstrate the ability of nicotinamide to inhibit the activation of coagulation associated with endotoxemia. We have previously shown that nicotinamide exerts strong anti-inflammatory effects. Evidence is accumulating for nicotinamide to have a therapeutic potential in modulating disease states in which there is a profound activation of coagulation and inflammation, such as in sepsis and disseminated intravascular coagulation.

Adult↗
PubMed2001

Active site-inactivated factor VIIa prevents thrombosis without increased surgical bleeding: topical and intravenous administration in a rat model of deep arterial injury.

PURPOSE: The primary event in the procoagulant response after vascular interventions is the tissue factor (TF)-factor VIIa complex formation, which occurs when TF is exposed to the circulating blood by the inflicted trauma. Human recombinant active site-inhibited coagulation factor VIIa (FFR-rFVIIa) binds well to TF but cannot initiate blood coagulation, and should thereby block thrombus formation. This hypothesis was tested with a rat model of arterial thrombosis. METHODS: In a blinded randomized study, the antithrombotic and antihemostatic effects of FFR-rFVIIa and heparin were evaluated in a rat model of mechanical deep arterial injury. In one arm of the study, FFR-rFVIIa (0.2 mg in 150 microL) or vehicle alone was applied topically at the site of vascular injury. In the other arm, FFR-rFVIIa (4 mg/kg), heparin (1 mg/kg), or vehicle alone was injected intravenously. RESULTS: FFR-rFVIIa produced a powerful antithrombotic effect after both topical and intravenous administrations (P =.02 and P =.005, respectively) without increasing the surgical bleeding. Heparin prevented thrombosis equally well as FFR-rFVIIa (P =.0007), but doubled the surgical bleeding compared with FFR-rFVIIa (P =.03) and controls (P =.008). In the topical study, the antithrombotic effect was achieved without altering parameters of plasma anticoagulation (prothrombin time and activated partial thromboplastin time) or producing detectable levels of FFR-rFVIIa in plasma. CONCLUSION: In this model FFR-rFVIIa effectively inhibits thrombus formation without the expense of increased surgical bleeding, which indicates the potential of FFR-rFVIIa as an effective and safe strategy for prevention of thrombosis in reconstructive vascular surgery and various forms of percutaneous revascularization.

Administration, Topical↗
PubMed2000

Effect of locally-applied active site-blocked activated factor VII (ASIS) on experimental arterial thrombosis.

The starting point of blood coagulation in vivo is the formation of a complex between tissue factor (TF), which is exposed following vascular disease or trauma, and activated blood coagulation factor VII (FVIIa). This blinded, random, paired study evaluates whether active site-blocked activated FVII (FVIIai, ASIS), which binds avidly to TF but is unable to initiate the coagulation processes, inhibits experimental thrombosis. Arteriotomy and deep vessel wall trauma were performed in the central arteries of rabbits' ears. The topical administration of ASIS (0.5 mg in 200 microl vehicle) resulted in a distinct antithrombotic effect compared to vehicle alone. Patency rates at 30 and 120 min after reperfusion were 85% and 75% in the ASIS group and 45% and 30% in the vehicle group, respectively (P = 0.008 and P = 0.004). In contrast, intravenous administration of ASIS (4 mg/kg) produced no antithrombotic effect. Arteriotomy bleeding times were 1.5 min in the ASIS group and 2.0 min in the vehicle group (medians, P = 1). Local application of ASIS produces a pronounced antithrombotic effect in rabbits without giving rise to antihaemostatic side-effects. This mode of treatment may have a potential for a variety of clinical interventions in injured or diseased vessels.

Animals↗
PubMed2000

Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden: variable frequencies found in a multicenter serological study.

Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.

Adolescent↗
PubMed2000

Gemini (dimeric) surfactant perturbation of the human erythrocyte.

We studied the ability of di-cationic gemini surfactantsdi (amphiphiles), i.e. 1,4-butanediammonium-N,N-dialkyl-N,N,N',N'-tetramethyl bromides (Di-Cm-di-QAS (s = 4), where m = 8, 11, 13, 16 and s = the number of alkyl groups in the spacer) to induce shape alteration, vesiculation, haemolysis and phosphatidylserine exposure in human erythrocytes, and to protect erythrocytes against hypotonic haemolysis. At high sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles rapidly induced echinocytic (spiculated) shapes and a release of exovesicles, mainly in the form of tubes, from the cell surface. Following 60 min incubation erythrocytes were sphero-echinocytic and a few cells with invaginations/endovesicles were observed. No phosphatidylserine exposure was detected. The haemolytic potency increased with an increase of the alkyl chain length. At sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles protected erythrocytes against hypotonic haemolysis. It is suggested that the Di-Cm-di-QAS (s = 4) amphiphiles perturb the membrane in a similar way as single-chain cationic amphiphiles, but that they do not easily translocate to the inner membrane leaflet.

Cell Size↗
PubMed1999

Processing of laser-Doppler signals from free flaps.

As conventional graphical laser-Doppler flowmetric (LDF) registrations from free flaps are difficult to interpret we explored the use of refined computerized signal processing to enhance the reliability of the blood flow supervision postoperatively. From eleven free flaps LDF data were collected using a software programme and a personal computer for analysis. Findings were compared with the clinical outcome. Nine flaps healed whereas one had wound problems and one suffered a partial necrosis. From the nine uneventful flaps, a peak within the range of frequencies from 0.04 to 0.23 Hz was seen. In the remaining two, such a low frequency peak could hardly be observed. Frequency analysis using computerized processing of LDF signals thus has the capacity to demonstrate the status of the flap perfusion. The slow wave vasomotion component seems to be of particular importance. Other frequency components warrant further investigation. A custom made monitoring device would be of great clinical value.

Algorithms↗
PubMed1998

Finger skin blood flow in response to indirect cooling in normal subjects and in patients before and after sympathectomy.

Finger skin blood flow was measured in 80 healthy subjects, using laser Doppler imaging during basal vasodilatation at a local temperature of 40 degrees C. The response to cooling of the contralateral hand at 15 degrees C was studied. A vasoconstriction index was calculated in all subjects and a nomogram was constructed, taking age into consideration. Compared with these normal subjects, four patients operated on with transthoracic endoscopic sympathectomy due to hand hyperhidrosis showed clearly attenuated responses. The results indicate that the test can be used to assess disturbances in the sympathetic regulation of the peripheral blood flow.

Adult↗
PubMed1998

Treatment of non-healing ulcers of the lower extremity with free muscle flaps. Case reports.

The surgical management of ulcers in the lower extremity is traditionally conservative, and includes debridement and split thickness skin grafting. In the most intractable cases, however, this management is often not enough. In this report of three patients with non-healing ulcers of the lower extremity successfully treated with free muscle flaps, we advocate a more active surgical approach to the treatment of such conditions. This is also appropriate in patients for whom a microsurgical approach might not be considered because of advanced age, peripheral arterio-occlusive disease, or the presence of other risk factors.

Aged↗
PubMed1998

No correlation between activated protein C resistance and free flap failures in 100 consecutive patients.

This study evaluates whether thrombophilic disorders contribute to failures in microvascular surgery. A recently discovered condition is focused on, i.e., activated protein C resistance, which is a highly prevalent functional defect of a crucial endogenous anticoagulant system--the protein C anticoagulant pathway (up to 15 percent of Caucasians affected). One hundred consecutive patients were operated on with 103 free tissue transfers during a 2.5-year period, all of which received perioperative intravenous anticoagulation, principally based on dextran (1 liter) and a heparin bolus at vascular reperfusion (80 to 100 IU/kg). The patients underwent extensive laboratory analysis with respect to conditions predisposing for thrombosis. Eleven patients were found to be activated protein C resistant, and one patient had congenital protein S deficiency. There were six total and five partial flap losses, which, however, in only one case coincided with the presence of a thrombophilic disorder (activated protein C resistance). By contrast, a substantial portion of flap necroses could be related to nonconstitutional factors (for example, pedicle kinking). It is concluded that routine screening for hypercoagulable states such as activated protein C resistance is not necessary in microvascular surgery.

Enzyme Activation↗
PubMed1998

Kinetics of bradykinin levels during and after leucocyte filtration of platelet concentrates.

OBJECTIVE: To measure bradykinin levels in platelet concentrates during and after leucocyte filtration. METHODS: Platelet concentrates were leukocyte depleted using three different leucocyte-depletion filters selected to represent filters with negative, positive or neutral charge, respectively. Bradykinin levels were analysed before, during and up to 90 min post-filtration. RESULTS: Significant levels of bradykinin were generated when negatively charged leucocyte depletion filters were used. However, we found a high variation between platelet concentrates prepared from different donors as well as within the same concentrate when this was divided into three aliquots. Generated bradykinin was rapidly degraded in the collection bag and no bradykinin was detectable 60 min post-filtration. CONCLUSION: Bradykinin generation is more pronounced when negatively charged leucocyte removal filters are used. Due to a rapid degradation of bradykinin in the storage bag, pre-storage filtration should minimise the risk of bradykinin related adverse reactions during transfusion with some filters.

Adolescent↗
PubMed1997

Stress and sensitization in children: a controlled prospective psychophysiological study of children exposed to international relocation.

This controlled prospective study investigated the development of sensitization as a result of international relocation in children, using the analyzing system Phadiatop. The effects of climate and predisposition to allergy were also measured. Children were examined prior to and during their first year of living abroad. A control group living at home was also examined during the same period. Participants answered a questionnaire before and after 1 year abroad, and blood samples were collected to determine sensitization. Before going abroad, there were no significant differences in atopic sensitization between groups nor in other key variables. After 1 year abroad, the proportion of children showing sensitization had increased significantly as compared with the control group at home. The exposed group reported an increase in skin symptoms during the year abroad. This study suggests that unidentified factors associated with foreign relocation increase the risk of sensitization in predisposed children. Stress might be one factor.

Acclimatization↗
PubMed1995

Frequent patient-to-patient transmission of hepatitis C virus in a haematology ward.

Blood transfusion is a well-documented route of transmission of hepatitis C virus (HCV). However, a persisting high frequency of HCV infections was recorded in our haematology ward even after screening of blood donors had been introduced. We investigated the viral strains in 37 patients with haematological malignant diseases who had developed hepatitis C when treated in the ward during 1990-93. 17 of the patients acquired hepatitis C despite being transfused only with blood components screened by second-generation anti-HCV tests. The viral strains were characterised by PCR genotyping and nucleotide sequencing of the hypervariable region of the E2 gene. Five clusters of closely related or identical viruses were found involving 2, 3, 4, 6, and 15 patients, respectively. Blood components could be ruled out as the common source of infection because no donor had given blood to all patients sharing a specific strain, and even donors whose blood had been given to several patients were negative for HCV RNA. All patients in each cluster had been treated in the ward during overlapping periods. These findings suggest that despite strict hygienic control, HCV transmission occurred between patients treated in the same hospital setting, as has previously been reported in a smaller group of haemodialysis patients.

Adult↗