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Biomedical subjects

Anders Larsson

Publications and source records attributed to Anders Larsson.

84 records · Page 5Linked to original sources

Coagulation, fibrinolysis, and cell activation in patients and shed mediastinal blood during coronary artery bypass grafting with a new heparin-coated surface.

OBJECTIVES: Heparin coating of the cardiopulmonary bypass circuit is shown to improve the biocompatibility of the surface. We have studied a new heparin surface, the Corline Heparin Surface, applied to a complete set of an extracorporeal device used during coronary artery bypass grafting in terms of activation of inflammation, coagulation, and fibrinolysis in patients and in shed mediastinal blood. METHODS: Sixty patients scheduled for coronary artery bypass grafting were randomized to one of 3 groups with heparin-coated devices receiving either a standard, high, or low dose of systemic heparin or to an uncoated but otherwise identical circuit receiving a standard dose of systemic heparin. Samples were drawn before, during, and after the operation from the pericardial cavity and in shed mediastinal blood. No autotransfusion of shed mediastinal blood was performed. RESULTS: The Corline Heparin Surface significantly reduced the activation of coagulation, fibrinolysis, platelets, and inflammation compared with that seen with the uncoated surface in combination with a standard dose of systemic heparin during cardiac surgery with cardiopulmonary bypass. Both a decrease and an increase of systemic heparin in combination with the coated heparin surface resulted in higher activation of these processes. A significantly higher expression of all studied parameters was found in the shed mediastinal blood compared with in systemic blood at the same time. CONCLUSIONS: The Corline Heparin Surface used in cardiopulmonary bypass proved to be more biocompatible than an uncoated surface when using a standard systemic heparin dose. The low dose of systemic heparin might not be sufficient to maintain the antithrombotic activity, and the high dose resulted in direct cell activation rather than a further anti-inflammatory and anticoagulatory effect.

Aged↗

Studies of fibrinogen binding to porcine platelets by flow cytometry: a method for studies of porcine platelet activation.

Platelets have a central function in haemostasis. They also participate in arterial thrombus formation in vascular disorders. Platelets have an important role in initiating and mediating ischaemia and related complications of ischemic heart disease. Several research groups are thus studying platelet activation and developing new platelet inhibitors. Platelet function is dependent upon membrane receptors and their interaction with other proteins. Binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptor is a prerequisite for platelet aggregation and thrombus formation. Thus, several GPIIb/IIIa inhibitors have been developed of which abciximab is the clinically most widely used. Pigs are often used for experimental studies. We have developed a flow cytometry assay for measuring porcine platelet activation utilising an FITC-labelled chicken anti-fibrinogen antibody. ADP, ristocetin and thrombin induce fibrinogen binding to porcine platelets similarly to human platelets. Ristocetin induces platelet aggregation and microvesicle formation from porcine platelets as well as from human platelets.

Adenosine Diphosphate↗

Mild hypothermia has minimal effects on the tolerance to severe progressive normovolemic anemia in Swine.

BACKGROUND: The benefits of hypothermia during acute severe anemia are not entirely settled. The authors hypothesized that cooling would improve tolerance to anemia. METHODS: Eight normothermic (38.0 +/- 0.5 degrees C) and eight hypothermic (32.0 +/- 0.5 degrees C) pigs anesthetized with midazolam-fentanyl-vecuronium-isoflurane (0.5% inspired concentration) were subjected to stepwise normovolemic hemodilution (hematocrit, 15%, 10%, 7%, 5%, 3%). Critical hemoglobin concentration (Hgb(CRIT)) and critical oxygen delivery (DO(2CRIT)), i.e., the hemoglobin concentration (Hgb) and oxygen delivery (DO2) at which oxygen consumption (VO2, independently measured by indirect calorimetry) was no longer sustained, and Hgb at the moment of death, defined prospectively as the point when VO2, decreased below 40 ml/min, were used to assess the tolerance of the two groups to progressive isovolemic anemia. RESULTS: At hematocrits of 15% and 10% (Hgb, 47 and 31 g/l), VO2 was maintained in both groups by an increase (P < 0.001) in cardiac output (CO) and extraction ratio (ER; P< 0.001) with unchanged mean arterial lactate concentration (L(art)). At hematocrit of 7% (Hgb, 22 g/l), all normothermic but no hypothermic animals had DO2-dependent VO2. No normothermic and three hypothermic animals survived to 5% hematocrit (Hgb, 15 g/l), and none survived to 3%. Hgb(CRIT) was 23 +/- 2 g/l and 19 +/- 6 g/l (mean +/- SD) in normothermic and hypothermic animals, respectively (P = 0.053). Hgb at death was 19 +/- 3 g/l versus 14 +/- 4 g/l (P = 0.015), and DO(2CRIT) was 8.7 +/- 1.7 versus 4.6 +/- 0.8 ml x kg(-1) x min(-1) (P < 0.001). CONCLUSION: During progressive normovolemic hemodilution in pigs, hypothermia did not significantly change Hgb(CRIT), but it decreased the Hgb at death, i.e., short-term survival was prolonged.

Anemia↗

Pharmaceutical thrombosis prevention in cardiovascular disease.

Cardiovascular diseases are a leading cause of morbidity and mortality in modern society. As a result of this, great efforts have been made to establish regimens for prophylaxis and treatment of such disorders. Pharmacological intervention is also a prerequisite for the success of other therapeutic approaches, e.g. coronary angioplasty. Prevention of platelet aggregation is a goal that can be achieved by counteracting various receptors on the platelet surface. The main attentions for such interventions are focused on inhibiting the glycoprotein IIb/IIIa receptor. So far, they are limited to intravenous usage. Adenosine diphosphate receptor inhibitors are available for intravenous and oral usage. Their effect is, at least partly, also exerted via the counteraction of adenosine diphosphate-mediated activation of the glycoprotein IIb/IIIa complex. An oral direct thrombin inhibitor is under clinical evaluation. This review focuses on atherothrombotic disorders, but recent advances within new fields of anticoagulation (i.e., treatment of severe septic shock and a novel approach to prevent thromboembolic disorder during surgery) should not be overlooked.

Cardiovascular Diseases↗

Retention of specific yolk IgY in the human oral cavity.

INTRODUCTION: The increasing prevalence of antibiotic-resistant bacteria emphasises the need for new treatments that can replace traditional antibiotics. Oral immunotherapy with yolk antibodies from hyperimmunised hens is a new promising treatment strategy, primarily for infections in the mouth and gastrointestinal tract. Several studies show that bacterial and viral infections can be prevented with egg yolk immunoglobulin (IgY) in a dose-dependent manner. Oral treatment could potentially be used against many frequently encountered diseases (e.g. common cold, tonsillitis and caries). GROUP STUDIED: Healthy volunteers. STUDY DESIGN: We studied the presence of yolk anti-Pseudomonas aeruginosa antibodies in saliva from healthy volunteers over time after 1 or 2 minutes' mouth rinse, performed in the evening, with an aqueous IgY antibody preparation. The test persons rinsed the mouth with 8.0ml phosphate buffered saline before gargling with the antibody preparation 8 and 24 hours later. Statistical analysis was performed with the Mann-Whitney U test. METHODS: The antibody titres in the mouth rinses were tested for their specific activity against P. aeruginosa by ELISA. RESULTS AND CONCLUSION: The next morning there were still active antibodies detected in the saliva from 18 of 19 subjects. After 24 hours, active antibodies could be detected in saliva from only a few of the subjects. A 2-minute mouth rinse resulted in higher mean ELISA absorbance values than a 1-minute rinse.

Administration, Oral↗

Simple function tests, but not the modified HAQ, correlate with radiological joint damage in rheumatoid arthritis.

OBJECTIVE: To test the validity of the Modified Stanford Health Assessment Questionnaire (MHAQ) for assessment of physical disability in rheumatoid arthritis (RA). METHODS: Sixty-one RA patients with mean age of 61 years and median disease duration of four years were included in this cross sectional study. The patients completed the MHAQ. Four simple function tests were performed (walk test, chair test, upper extremity mobility test, and grip strength) and a modified Larsen score was established. Pain score (VAS) and laboratory variables for inflammation were recorded. RESULTS: MHAQ, function tests, pain, and C reactive protein (CRP) showed highly significant mutual correlations (p < 0.01). However, MHAQ did not correlate with Larsen score (R = 0.06; NS), while most function tests did (walk test, R = 0.29; p < 0.05; chair test, R = 0.21; NS; mobility test, R = 0.36; p < 0.01 and grip strength, R = -0.35 p < 0.01). The superiority of function tests was even more pronounced after four years (walk test, R = 0.31; p < 0.05; chair test, R = 0.50; p < 0.01; mobility test, R = 0.49; p < 0.01; grip strength, R = -0.52; p < 0.01; MHAQ, R = 0.34; NS). CONCLUSION: Objective function tests are preferable to MHAQ in the assessment of physical disability in RA.

Adult↗

Dominant prostasome immunogens for sperm-agglutinating autoantibodies of infertile men.

The presence of naturally occurring anti-sperm antibodies (ASA) is a well-known cause of infertility in men and women, but the antigens for these antibodies are poorly characterized. We have previously shown that prostasomes adhere to sperm cells and that prostasomes are major targets for ASA associated with infertility. These autoantigens have not been characterized. We used 2-dimensional electrophoresis, immunoblotting, and mass-spectrometry to identify the prostasome antigens for these autoantibodies. By these techniques, we revealed that prolactin-inducible protein (PIP) and clusterin were dominant prostasome immunogens for sperm-agglutinating autoantibodies of 20 patients with immunological infertility. PIP was identified by 19 of 20 (95%) patient sera and clusterin by 17 of 20 (85%). In addition, 10 sporadically occurring prostasomal antigens were identified in this context, viz alcohol dehydrogenase [NADP+], annexin I, annexin III, BRCA1-associated ring domain protein 1, heat shock 27-kd protein, isocitrate dehydrogenase, lactoylglutathione lyase, NG,NG-dimethylarginine dimethylaminohydrolase 1, peroxiredoxin 2, and syntenin 1.

Agglutination↗

Antiprostasome antibodies: possible serum markers for prostate cancer metastasizing liability.

Prostasomes are secretory granules synthesized, stored, and secreted by normal and neoplastic human prostate epithelial cells. In prostate cancer, they are anticipated to be released into the blood circulation where they may be immunogenic. The aim of our study was to examine whether prostasome antibody presence in serum bears any prognostic significance for men with prostate cancer. We developed a sensitive and specific immunoassay (enzyme-linked immunosorbent assay) to establish the presence of antiprostasome antibodies in serum. The antiprostasome antibody titer in serum, sampled before any kind of therapy for prostate cancer, was examined together with clinicopathologic variables and outcome over a median follow-up of 350 days in 218 patients with verified prostate cancer. We detected these antibodies in 191 (88%) of these patients. This antibody titer did not correlate to serum values of prostate-specific antigen. Significant, inverse relationships were registered for antiprostasome antibody titer, and metastases to bone and/or lymph nodes (P = 0.035) and pT (P = 0.025). These results indicate that the antiprostasome antibody titer in serum may be a novel marker for prostate cancer liability to metastasize.

Adult↗

The presence of anti-p53 antibodies in sera prior to thoracic surgery in non small cell lung cancer patients: its implications on tumor volume, nodal involvement, and survival.

BACKGROUND: During recent years, a correlation between the presence of antibodies in sera against p53 and survival has been reported. The aim of the present study was to analyze anti-p53 antibodies in sera from patients with non small cell lung cancer (NSCLC) prior to thoracic surgery and their correlation to survival, nodal involvement, and tumor volume. PATIENTS AND METHODS: Serum samples from 58 patients with NSCLC admitted to the Department of Pulmonary Medicine in Uppsala were collected between 1993 and 1995 and analyzed for the expression of anti-p53 antibodies. RESULTS: Antibodies against p53 were detected in 12 patients (21%). No association was found between increased levels of anti-p53 antibodies and tumor volume (P =.84). There was a numerical trend towards higher levels of anti-p53 antibodies in patients without nodal disease, when compared with patients with nodal involvement, although not statistically significant (P =.136). However, when patients with metastatic disease were included, statistically significantly lower levels of anti-p53 antibodies were demonstrated, in comparison to patients without any sign of nodal engagement or metastatic disease (P =.038). Anti-p53 antibodies and survival showed no correlation between increasing index levels of anti-p53 antibodies and survival (P =.18). Neither was a correlation found between using the cutoff (>1.1) described by the manufacturer and survival. CONCLUSION: The presence of anti-p53 antibodies was correlated neither to survival nor to tumor volume in the present study. However, patients with either nodal or metastatic disease had lower levels of anti-p53 antibodies in comparison to patients without signs of either nodal or metastatic disease. These issues are discussed.

Antibodies↗

The presence of anti-p53 antibodies in sera from patients with oesophageal carcinoma: correlation to treatment, tumour volume and survival.

BACKGROUND: A correlation between mutations in the p53 gene and the presence of anti-p53 antibodies in sera has been reported. The aim of the present study was to analyse anti-p53 antibodies in sera from patients with oesophageal carcinoma and their implications for clinical outcome and survival PATIENTS AND METHODS: Between 1996 and 2002, patients treated for oesophageal carcinoma at the Department of Oncology, Uppsala University Hospital, Sweden, were asked to donate serum samples during treatment and follow-up. A total of 42 patients, with serum samples collected prior to therapy, were analysed for expressions of anti-p53 antibodies using a commercially available sandwich ELISA (Dianova, Hamburg, Germany). RESULTS: Anti-p53 antibodies did not correlate with investigated laboratory parameters. No correlation between anti-p53 antibodies and tumour volume was found (n=31; r=0.08;p=0.66). Anti-p53 antibodies as a continuous variable was not associated with survival (p = 0.42). Neither was the presence of anti-p53 antibodies (according to defined cut-off of 1.1, provided by the manufacturer) associated with survival (p = 0.99). CONCLUSION: The presence of anti-p53 antibodies correlated neither to tumour volume nor to clinical parameters.

Adenocarcinoma↗

Antiprostasome antibody titres in benign and malignant prostate disease.

BACKGROUND: Prostasomes are secretory granules synthesized, stored and secreted by normal and neoplastic human prostate epithelial cells and by prostate cancer metastasis. Prostasomes are postulated to be shed into the blood circulation in prostate cancer patients, where they may cause an immune response. MATERIALS AND METHODS: An antiprostasome antibody ELISA was developed and used to measure serum antibody titres in 81 males with prostate cancer or benign prostate hyperplasia. RESULTS: Patients with biopsy-verified prostate cancer had significantly higher antibody titres [p = 0.019 for the dominant tumour expression (first Gleason parameter) and p = 0.022 for the dominant and non-dominant form (first and second Gleason parameters)] than individuals with benign prostate hyperplasia or other benign prostate disorders. No correlation existed between antibody titres and PSA values. CONCLUSION: These results indicate that the antiprostasome antibody titre in serum may be a novel prostate cancer marker not replacing, but rather supplementing, PSA.

Aged↗