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Biomedical subjects

S Antonsen

Publications and source records attributed to S Antonsen.

At least 19 recordsLinked to original sources

[A randomized controlled trial of the use of CRP rapid test as a guide to treatment of respiratory infections in general practice].

INTRODUCTION: The aim was to assess whether the frequency of antibiotic prescriptions to patients with respiratory infections is reduced when general practitioners (GPs) use a CRP rapid test to support their clinical assessment, and to examine whether the use of the test would have any effect on the course of disease. MATERIAL AND METHOD: A randomised controlled trial was carried out by 35 general practices in the County of Funen, Denmark, with 812 patients with respiratory infection. The main outcome measures were frequency of antibiotic prescriptions and morbidity one week after the consultation, as stated by the patients. RESULTS: The frequency of antibiotic prescriptions was 43% (179/414) in the CRP group and 46% (184/398) in the control group (NS, OR = 0.9). At one week, increased or unchanged morbidity was stated more frequently in the CRP group (12%) than in the control group (8%) (OR = 1.6, p = 0.05). In the control group, the variable having the greatest influence on whether the GP prescribed antibiotics was the patient's general well-being (OR = 2.9, p < 0.0001), whereas in the CRP group the CRP value had the greatest influence (OR = 1.1 per unit increase [mg/l], p < 0.0001). CONCLUSION: From on the present study, the use of a single CRP rapid test to support possible antibiotic treatment of respiratory infections in general practice cannot be recommended.

Anti-Bacterial Agents↗

[Anticoagulant treatment].

In 1998, the sale of vitamin K antagonists (VKA) in Denmark corresponded to the amount used for treatment of more than 20,000 patients for one year. This is more than three times more than ten years earlier. The reasons for the increasing use of VKA are new indications for permanent anticoagulant treatment, especially chronic atrial fibrillation and venous thromboembolism associated with permanent thromboembolic risk factors. The risk of bleeding is higher in the introductory phase of anticoagulant treatment than later on. It is now recommended to commence anticoagulant therapy without a loading dose. This seems to hasten a good estimate of the maintenance dose. The metabolism of VKA depends on a number of genetic and acquired factors. Knowledge of these factors is crucial for optimal regulation of the treatment, and it is important that patients at start of treatment are thoroughly informed about these factors in order to minimize the risk of complications.

Anticoagulants↗

Randomised controlled trial of CRP rapid test as a guide to treatment of respiratory infections in general practice.

OBJECTIVE: To assess whether the frequency of antibiotic prescriptions to patients with respiratory infections is reduced when general practitioners (GPs) use a C-reactive protein (CRP) rapid test in support of their clinical assessment, and to study whether using the test will have any effect on the course of disease DESIGN: Randomised controlled trial. SETTING: 35 general practices, County of Funen, Denmark. PATIENTS: 812 patients with respiratory infection. MAIN OUTCOME MEASURES: Frequency of antibiotic prescriptions and morbidity 1 week after the consultation, as stated by the patients. RESULTS: In the CRP group the frequency of antibiotic prescriptions was 43% (179/414) compared with 46% (184/398) in the control group (odds ratio (OR) = 0.9, NS). After 1 week, increased or unchanged morbidity was stated more frequently in the CRP group (12%) than in the control group (8%) (OR = 1.6, p = 0.05). In the control group, the variable having the greatest influence on whether the GP prescribed antibiotics was the patients' general well-being (OR = 2.9, p < 0.0001), whereas in the CRP group the CRP value had the greatest influence (OR = 1.1 per unit increase (mg/l), p < 0.0001). CONCLUSION: Based on the present study, the use of the CRP rapid test in support of a possible antibiotic treatment for respiratory infections in general practice cannot be recommended.

Adolescent↗

[Natural history of abdominal aortic aneurysm with and without concomitant chronic obstructive pulmonary disease].

The relationship between abdominal aortic aneurysms (AAA) and chronical obstructive pulmonary disease (COPD), and in particular the suggested common elastin degradation caused by elastase and smoking was analysed by a cross sectional population mass screening study for AAA, and a prospective cohort study of small AAA. All previous computer-hospital-recorded diagnoses were received concerning 4,404 men invited to screening for AAA. One hundred and forty-one had AAA (4.2%). They were asked for an interview, a clinical examination, and a blood sample. Men with an AAA of 3-5 cm were offered annual control-scans to check for expansion. Of COPD-patients, 7.7% had AAA (crude OR = 2.05), however the adjusted OR was only 1.53 after adjusting for other co-existing diseases (p = 0.13). The mean annual expansion was 2.74 mm per year in COPD patients and 2.72 in non-COPD patients, and 4.7 mm in oral steroid-users compared to 2.6 in non-steroid-users (p < 0.05). S-elastin-peptides (SEP) and P-elastase-alpha1-antitrypsin-complexes (PEAC) were negatively correlated to FEV1 in COPD-patients. However, SEP, beta-agonist-treatment, and FEV1 was positively correlated to expansion by multivariate regression analysis, while PEAC and S-alpha1-antitrypsin did not influence expansion, suggesting elastase plays a major role in the pathogenesis of COPD but not in AAA. The high prevalence of AAA among patients with COPD is more likely to be caused by medication and coexisting diseases rather than a common pathway of pathogenesis.

Aortic Aneurysm, Abdominal↗

Natural history of abdominal aortic aneurysm with and without coexisting chronic obstructive pulmonary disease.

PURPOSE: To study the relation between abdominal aortic aneurysms and chronical obstructive pulmonary disease (COPD), in particular the suggested common elastin degradation caused by elastase and smoking. METHODS: A cross-sectional population study and a prospective cohort study of small abdominal aortic aneurysms was performed in a community setting. All previous diagnoses recorded in a hospital computer database were received for 4404 men 65 to 73 years of age who had been invited to a population screening for abdominal aortic aneurysm. One hundred forty-one men had AAA (4.2%). They were asked to participate in an interview, a clinical examination, and collection of blood sample. Men with an abdominal aortic aneurysm 3 to 5 cm in diameter were offered annual ultrasound scans to check for expansion. RESULTS: Among patients with COPD 7.7% had abdominal aortic aneurysms (crude odds ratio=2.05). The adjusted odds ratio, however, was only 1.59 after adjustment for coexisting diseases associated with abdominal aortic aneurysm (P=.13). The mean annual expansion was 2.74 mm per year among patients with COPD, 2.72 among patients without COPD, and 4.7 mm among patients who used oral steroids compared with 2.6 among patients who did not use steroids (P < .05). Concentration of serum elastin peptide and plasma elastase-alpha1-antitrypsin complexes correlated negatively with forced expiratory volume in the first second (FEV1) among patients with COPD. However, multivariate regression analysis showed that concentration of serum elastin peptide, therapy with beta-agonists, and FEV1 correlated positively with degree of expansion but that concentration of plasma elastase-alpha1-antitrypsin complexes and serum alpha1-antitrypsin did not influence expansion, suggesting that elastase plays an important role in the pathogenesis of COPD but not of abdominal aortic aneurysm. CONCLUSION: The high prevalence of abdominal aortic aneurysm among patients with COPD is more likely to be caused by medication and coexisting diseases rather than a common pathway of pathogenesis.

Aged↗

The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood.

The binding of immune complexes (IC) to polymorphonuclear leukocytes (PMN) and the consequent respiratory burst (RB) were investigated in whole blood cell preparations suspended in 75% human serum, using flow cytometry. Blockade of the complement receptor (CR)1 receptor sites for C3b on whole blood cells using the monoclonal antibody (mAb) 3D9 resulted in a 1.9-fold increase in the IC-elicited PMN RB after 5 min of incubation, rising to 3.1-fold after 40 min. This enhancement was not due to increased IC deposition on PMN. Blockade of CR3 abrogated the mAb 3D9-induced rise in RB activity and inhibited the IC binding to PMN in a whole blood cell preparation, with or without mAb 3D9, by approximately 40% from 15-40 min while reducing their RB over 40 min to approximately one third. Blockade of CR1 on either erythrocytes (E) or leukocytes, before mixing the populations, revealed that the potentiation of the RB by mAb 3D9 was associated with abrogation of E-CR1 function, whereas blockade of leukocyte-CR1 had a diminishing effect. Exposure to IC at high concentrations induced release of both specific and azurophilic granule contents from PMN. The latter was CR3 dependent in that blockade of the receptor inhibited the lactoferrin release by one third during 40 min of incubation. In conclusion, CR3 plays a significant role in the IC-mediated generation of an RB and release of specific granules by PMN, while CR1 on whole blood cells, primarily E CR1, restricts the IC-elicited RB in PMN. We propose that CR1 in whole blood promotes the degradation of IC-bound iC3b to C3dg, thereby rendering the IC inaccessible for binding to CR3.

Antigen-Antibody Complex↗

Interpretation of serial measurements of international normalized ratio for prothrombin times in monitoring oral anticoagulant therapy.

Despite careful monitoring of oral anticoagulant treatment (OAT), some international normalized ratio (INR) for prothrombin time values will fall outside the therapeutic range. Considerable changes in serial INR results from OAT patients may be caused by random fluctuation alone, and, for statistical reasons, a fraction of the INR values will fall outside therapeutic range and interfere with dose adjustments. On the basis of therapeutic intervals and statistical evaluation of reference changes, we suggest and discuss an alternative method for interpretation of serial INR measurements. Retrospective evaluation of serial measurements of INR from OAT patients revealed an "overshooting" phenomenon. When a dose was adjusted on the basis of insignificant change in INR value, the subsequent INR value generally fell in the opposite direction. If a further change of dose was initiated because of the new INR value, a similar course in the opposite direction was observed. This "ping-pong" effect renders patients in a fluctuating state of anticoagulation and may introduce increased risk of complications. The suggested method provides an objective criterion for dose adjustments in OAT, which should reduce patients' risk.

Anticoagulants↗

International normalized ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements.

To determine when a change in serial measurements of prothrombin time in patients receiving oral anticoagulant therapy (ACT) is a statistically significant biological change necessitating dose adjustment, one must know the size of the "critical difference" in statistical terms (i.e., probabilities). In a cohort of 32 ACT patients at pharmacological steady-state, we studied the within-subject total variation of prothrombin time, expressed as International Normalized Ratio (INR), over 6 months. The total within-subject variation (CV) of INR was 10.1%. The corresponding critical differences required for significance of change in serial INR results was 0.7 at a therapeutic target of 2.5 INR and 1.0 at a therapeutic target of 3.5 INR. The data presented allow generation of objective criteria for monitoring ACT patients and deciding dose adjustments. We recommend that estimations of critical differences for significant change of INR in ACT patients should be based on results obtained in the specific clinic investigated to mirror the routine total variation of INR measurements they obtain.

Aged↗

Aspects of preanalytical variation of lactoferrin and elastase/alpha 1-protease inhibitor complexes.

A number of interesting applications of plasma elastase/alpha 1-protease inhibitor complexes (ELA-PI) and lactoferrin (LAC) have recently been suggested. However, the clinical utility of these components often seems to be low. This might be improved by minimizing the preanalytical variation, if possible. Therefore, we have evaluated the influence of various aspects of sampling and handling conditions on the results obtained when measuring ELA-PI and LAC. Blood samples from both healthy persons as well as patients, who had undergone laparotomy the day before, were investigated. We confirmed the previous observations of higher concentrations of ELA-PI and LAC in serum compared to plasma. This was more pronounced in patients than in healthy adults. In EDTA-blood the most important change was seen in samples from patients when stored at room temperature. In this situation increases of LAC concentrations of 50% and 100% following 2 and 5 h, respectively were found. This in vitro release of LAC was abolished when samples were stored on ice until centrifugation within 5 h. In contrast, a statistically significant increase in ELA-PI of 10% was observed following storage on ice for 2 h of blood specimens drawn from healthy persons. EDTA-plasma obtained by venous puncture following minimal stasis contained 10% higher concentrations of LAC compared to samples drawn from intravenous catheters, while no difference was observed in the case of ELA-PI. However, in one individual prolonged venous stasis resulted in larger differences of both LAC and ELA-PI. Different centrifugation conditions (1500 vs. 3000 x g; room temperature vs. 4 degrees C) did not influence concentrations of LAC or ELA-PI measured, neither did eating a normal meal nor moderate physical activity (30 min walk). In conclusion, ELA-PI and LAC should be measured in EDTA-plasma. Blood must be drawn by venous puncture applying minimal stasis or from indwelling venous catheters. Samples for measuring LAC must be stored on ice until centrifugation. Separation of plasma from cells should be performed as fast as possible, but storage for up to 5 h can be accepted.

Blood Preservation↗

Increase in lactoferrin and elastase alpha-1-proteinase inhibitor complexes but lack of complement activation and IL-6 response following thoracic surgery.

UNLABELLED: Polymorphonuclear neutrophil (PMN) stimulation and degranulation can be mediated by the cytokines and by complement activation. The aim of the present study was to measure TNF alpha, IL-1 alpha, IL-6 and C3d in relation to postoperative increase in lactoferrin and elastase alpha-1-proteinase inhibitor (E alpha-1-PI) levels. Eleven patients undergoing thoracic surgery took part in the study. Blood leucocytes, E alpha-1-PI, lactoferrin and C3d were measured preoperatively, at the end of surgery and postoperatively, at 4 h and on day 1, 2, 3 and 5. TNF alpha, IL-1 alpha and IL-6 were measured preoperatively, at the end of surgery and postoperatively, at 4 h, and on days 1 and 5. The leucocyte count, lactoferrin and E alpha-1-PI levels increased significantly postoperatively (P < 0.01). There was no significant change in C3d values. Plasma IL-6 levels were unchanged in the postoperative period. Plasma TNF alpha and IL-1 alpha were detectable at low levels in only two and four patients, respectively. CONCLUSION: The postoperative increase in blood levels of PMN lactoferrin and E alpha-1-PI complexes observed in the present study was not accompanied by complement activation, or increased blood levels of IL-6.

Aged↗

An enzyme-linked immunosorbent assay for plasma-lactoferrin. Concentrations in 362 healthy, adult blood donors.

Very different concentrations of plasma-lactoferrin in healthy adults have been reported in the literature. We compared three commercially available lactoferrins and lactoferrin purified in our laboratory as calibrators in an ELISA. No statistical differences among these preparations of lactoferrin were detected. The concentration of purified lactoferrin was measured by dry weight, and efforts were made in order to minimize loss of purified lactoferrin by adhesion to tubes etc. and thus, secure accuracy of the method. Dilutions were made in PBS 0.01 mol l-1 with NaCl 0.436 mol l-1, (NH4)2SO4 0.5 mol l-1, BSA 5 gl-1 and normal rabbit IgG 10 mg l-1, which was shown to give parallel dilution curves of primary calibrator, secondary calibrator and plasma samples. No significant difference in the content of lactoferrin in neutrophils (median; range) among men (1.78; 0.83-4.48 micrograms 10(-6) neutrophils; n = 20) and women (2.12; 1.16-9.30 micrograms 10(-6) neutrophils; n = 14) was found. Lactoferrin was analysed in EDTA-plasma obtained from 135 female and 227 male blood donors. Median concentrations were 84.7 and 97.8 micrograms l-1 respectively, while 2.5% and 97.5% reference limits (with 90% confidence intervals) were estimated to 42.9 (38.7-47.4) micrograms l-1 and 166.9 (151.0-186.3) micrograms l-1 for women and 52.3 (49.1-55.6) micrograms l-1 and 189.9 (175.9-206.4) micrograms l-1 for men, respectively.

Adult↗

An ELISA for elastase alpha 1-protease inhibitor complexes in human plasma and serum.

An ELISA for neutrophil elastase (ELA) in complex with alpha 1-protease inhibitor (PI) (alpha 1-antitrypsin) was developed in microtitre plates and compared to the ELISA kit from MERCK (2-h version). Recovery of ELA-PI was good in both assays. The detection limits were 4.4 micrograms l-1 and 7.7 micrograms l-1 of the in-house and MERCK assay, respectively, while limits of quantitation were estimated to 7.7 micrograms l-1 (5.5-9.9 micrograms l-1) and 28.9 micrograms l-1 (14.6-44.3 micrograms l-1) for the two assays. Furthermore, as dilution curves of normal plasma were parallel with the calibration curve in the in-house assay over a wide range of dilutions, it is feasible to assay plasma in dilutions of only 1:6, resulting in a limit of quantitation of only 1.1 micrograms l-1. The total analytical coefficient of variation for samples measured in double determinations was 10.5%-12.5% in the in-house assay and 13.9%-14.6% in the MERCK assay. One-hundred-and-eight plasma samples covering a wide range of ELA-PI concentrations were analysed in both assays. A proportional difference between the two methods was detected, the mean ratio (in-house/MERCK) with 95% confidence limits was 1.115 (1.070-1.160). The cause of the difference was probably due to difference calibration of the assays. Until this problem is solved, method specific reference intervals are needed. A reference interval for the in-house method based on plasma samples from 123 healthy adults; median age 36 years (range: 19-65 years) was estimated to 16.5-48.5 micrograms l-1.

Adult↗

Within-subject variation of elastase/alpha 1-protease inhibitor complexes and lactoferrin in plasma.

Several studies have shown increased plasma concentrations of neutrophil elastase in complex with alpha 1-protease inhibitor and/or lactoferrin in inflammatory conditions, and serial measurements have been advocated in order to follow disease activity. However, data on the magnitude of the within-subject variation are necessary for evaluation of the significance of changes in results obtained on analysis of serial samples. Within-subject variation of elastase/alpha 1-protease inhibitor complexes and lactoferrin over a short time was studied in six young men who had blood samples drawn every 4 h over 2 days. Within-subject variation over a longer time was investigated in 12 healthy adults, 6 females and 6 males, who had blood samples drawn in the morning once a week for 10 weeks. From five of the females and five of the males, blood samples were also drawn every morning on 5 consecutive days during 1 week. Within-subject variations over hours, days, and weeks were estimated as 0.050, 0.124, and 0.148 for elastase/alpha 1-protease inhibitor complexes and as 0.101, 0.119, and 0.143 for lactoferrin. A tendency towards variation of LAC with menstrual cycle in fertile females was noticed. From within-subject variation, between-subject variation and analytical variation, indices of individuality were calculated as 1.1 and 1.8 for elastase/alpha 1-protease inhibitor complexes and lactoferrin, respectively. This means that within-subject variation for lactoferrin is quite small compared to between-subject variation, and the usefulness of reference limits is very limited, when interpreting results from individual patients. For elastase/alpha 1-protease inhibitor complexes, the use of reference limits might be more appropriate, although still not optimal.

Adult↗

Specific opsonic activity for staphylococci in peritoneal dialysis effluent during continuous ambulatory peritoneal dialysis.

In a prospective study of intraperitoneal opsonins in 30 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the IgG concentration, the fibronectin concentration, the specific antistaphylococcal antibody level, and the opsonic activity against Staphylococcus epidermidis were measured in peritoneal dialysis effluent from the initiation of CAPD and monthly for 6 months. Significant correlation was found between the four assays, but the interindividual and intraindividual variations were considerable. No statistically significant correlation was observed between susceptibility of the patients to CAPD-related infectious peritonitis and any of the above-mentioned parameters of humoral defense. We conclude that at the present time it is not feasible to use these assays for the establishment of prognosis with regard to peritonitis in CAPD.

Adult↗

Granulocyte adherence after intravenous and intraarterial injection of ioxaglate or iohexol.

The effect of iohexol and ioxaglate on granulocyte adherence to nylon fibers was investigated with blood from 15 patients undergoing angiography, and from 24 patients undergoing excretory urography. Decreased adherence and increased numbers of granulocytes in the circulation were observed soon after injection of iohexol or ioxaglate in the aorta, or injection of ioxaglate i.v. Increased adherence and decreased numbers of granulocytes in the circulation were observed soon after injection of iohexol i.v. The differences were small soon after the injection of contrast media (CM). More pronounced decreased adherence and increased numbers of granulocytes were detected 2 and 5 hours after injection in the aorta for both CM.

Aorta↗

Radiographic contrast media and release of neutrophil specific proteins in vitro and after intravenous injection.

The neutrophil granulocytes contain granules in which different proteins are present. When activated the neutrophils degranulate and thereby release some of these proteins to the surroundings. Some of these proteins are specific for this type of cell, e.g., lactoferrin and elastase. To investigate the influence of contrast media (CM) on this release, blood was incubated with diatrizoate, ioxaglate, iohexol, iodixanol, hyperosmolar saline, and hyperosmolar mannitol at different concentrations, and the amount of the neutrophil specific proteins lactoferrin and elastase were measured. Decreasing protein concentrations were observed for increased medium concentrations, suggesting that the degranulation process of the neutrophils was inhibited by the CM. The protein concentrations were lowest after incubation with the two ionic media diatrizoate and ioxaglate. Significantly decreased values of plasma lactoferrin were observed one min after i.v. injection of iohexol or ioxaglate in 82 patients undergoing urography. There was no significant difference between the two CM.

Contrast Media↗