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Biomedical subjects

Anders Larsson

Publications and source records attributed to Anders Larsson.

At least 19 recordsLinked to original sources
PubMed2007

Inflation lung mechanics deteriorates markedly after saline instillation and open endotracheal suctioning in mechanically ventilated healthy piglets.

INTRODUCTION: Non-bronchoscopic bronchoalveolar lavage is an alternative to diagnostic bronchoscopy in pediatric patients, as fiberoptic bronchoscopes with aspiration channels are too large for small infants. There are many variations of the method in clinical practice, and saline instillation followed by open endotracheal suctioning is still commonly used. Lung function can deteriorate with these procedures, and we have investigated the effects on lung mechanics and oxygenation in healthy piglets. METHODS: The lungs of anesthetized and mechanically ventilated piglets were recruited with CPAP 35 cmH2O. Thereafter we instilled 5 ml of saline into the endotracheal tube, followed by three breaths from the ventilator. Saline was retrieved through a suction catheter wedged far distally in the airway. The procedure was followed by a new recruitment maneuver. Complete inspiratory/expiratory pressure - volume loops (PV-loops) were obtained just before and 5 min after saline instillation. Arterial blood gases were collected at equivalent times in 14 similar piglets submitted to exactly the same procedure. RESULTS: The inspiratory limb of the PV-loops changed markedly, as the lower inflection point was displaced towards higher pressures (P=0.004), and hysteresis measured at 15 and 30 cmH2O increased (P=0.004 and P=0.012, respectively). Although PaO2 decreased significantly (P=0.001), values after saline instillation/suctioning were still in the high normal range, that is, 22.2 +/- 2.6 kPa. CONCLUSIONS: Opening pressures of the lungs increase markedly after saline instillation/suctioning in healthy piglets. In this situation, adequate recruitment maneuvers and PEEP might prevent lung collapse and deteriorations in arterial oxygenation.

Animals↗
PubMed2006

Identification of the brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane as an androgen agonist.

To investigate androgen receptor (AR) activation by exogenous compounds, we used a combination of experimental analysis and theoretical modeling to compare a set of brominated flame retardants (BFRs) to dihydrotestosterone (DHT) with regard to ligand docking, AR binding, and AR activation in human hepatocellular liver carcinoma cells, as well as interacting energy analysis. Modeling of receptor docking was found to be a useful first step in predicting the potential to translocate to the ligand pocket of the receptor, and the computed interaction energy was found to correlate with the observed binding affinity. Flexible alignment studies of the BFR compounds demonstrated that 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (BCH) closely overlap DHT. Combining the theoretical modeling with in vitro ligand-binding and receptor-activation assays, we show that BCH binds to and activates the human AR. The remaining BFRs did not successfully interact with the ligand pocket, were not able to replace a synthetic androgen from the receptor, and failed to activate the receptor.

Androgens↗
PubMed2006

Antioxidant intake, oxidative stress and inflammation among immigrant women from the Middle East living in Sweden: associations with cardiovascular risk factors.

BACKGROUND AND AIMS: Immigrant women from the Middle East have higher cardiovascular risk compared to native women. Whether low antioxidant intake, oxidative stress or inflammation contributes to risk is unknown. In a cross-sectional study of 157 randomly selected foreign-born women (Iranian and Turkish) and native women living in Sweden, we investigated antioxidant status, oxidative stress (F(2)-isoprostanes) and systemic inflammation (plasma high sensitive C-reactive protein; CRP) markers. We also investigated relationships between F(2)-isoprostanes, CRP and cardiovascular risk factors. METHODS AND RESULT: Dietary intake was assessed using 24-h dietary recalls repeated four times. Micronutrient intake was not consistently different between groups. Serum alpha-tocopherol, but not gamma-tocopherol levels, was lower in Turkish vs. Swedish women (P<0.05). Turkish women had the highest F(2)-isoprostane levels (P<0.05 vs. Iranian women) and CRP levels (P<0.01 vs. Swedish women and P=0.05 vs. Iranian women). In immigrants (n=97), F(2)-isoprostanes correlated positively to insulin levels (r=0.31, P<0.01), and CRP was correlated to obesity and several cardiovascular risk factors (r-values >0.21, P values <0.05). CONCLUSION: The role of antioxidant status is unclear, whereas signs of oxidative stress and inflammation are evident in immigrant women from Middle East, especially Turkish women. Oxidative stress and low-grade inflammation might contribute to the higher cardiovascular risk previously observed in immigrant women. Further larger studies adjusting for more potential confounders are motivated to confirm these results.

Adult↗
PubMed2006

Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients.

AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxidase (MPO), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC). METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum. RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective well-being at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant. CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.

Adult↗
PubMed2006

Prostasome-derived proteins capable of eliciting an immune response in prostate cancer patients.

Prostate cancer consistently remains a difficult clinical enigma. Therefore, the development of novel strategies for diagnosis and treatment (e.g. immunotherapy) of prostate cancer is essential. We tried to identify the prostasome-derived proteins that were immunogenic in prostate cancer patients. Prostate cancer patients' sera (n = 44) with high enzyme-linked immunosorbent assay (ELISA) titers against prostasomes were selected for immunoblotting against purified seminal prostasomes. The SDS-PAGE and immunoblotting experiments were performed with Bio-Rad systems. Twenty-five of the recognized proteins were isolated and analyzed by means of mass spectrometry. Out of 44 patients' sera, 31 (70%) demonstrated in immunoblotting experiments reactivity against several prostasomal protein bands in the molecular weight range of 10-200 kDa. Some of the bands (55, 70 and 170 kDa) were more frequently recognized by the patients' sera. Concomitantly run control sera generated only very weak or no bands at all. The most frequently occurring prostasomal proteins were identified as heat shock proteins (HSP 70, 71) and clusterin. This study identified the most important molecular targets of autoantibodies against prostasomes generated in connection with the development of prostate cancer in man. These immunogenic prostasomal proteins could be appropriate target molecules for specific immunotherapy of prostate cancer patients.

Blotting, Western↗
PubMed2006

Central hemodynamics during lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia. A study by echocardiography and continuous pulmonary artery flow measurements in lung-injured pigs.

OBJECTIVE: The impact of lung-recruitment maneuvers on heart function at different volemic levels has not been studied in detail. We therefore investigated the effect on central hemodynamics of lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia in experimental lung injury. DESIGN: Randomized, controlled, cross-over experimental study. SETTING: Animal laboratory at a university hospital. PARTICIPANTS: Eleven anesthetized and lung-lavaged pigs. INTERVENTION: The animals were randomized to 10-s lung recruitment maneuvers followed by 30-s maneuvers (40 cm H(2)O airway pressure) or vice versa, performed under hypovolemia, normovolemia and hypervolemia. MEASUREMENTS AND MAIN RESULTS: Left-ventricular end-diastolic diameter and cardiac output were measured before, during, and 1 min and 5 min after the lung recruitment maneuver and left-ventricular eccentricity index was calculated for before and during the maneuver. Cardiac output and left-ventricular end-diastolic diameter (within parentheses) decreased significantly during both the 10-s and 30-s lung recruitment maneuvers at hypovolemia, by a mean of 89% (35) and 92% (33), at normovolemia by 75% (33) and 86% (32), and at hypervolemia by 56% (32) and 64% (43), respectively. At hypovolemia, cardiac output was increased above baseline 1-5 min following the 30-s maneuver. Left-ventricular eccentricity index increased significantly during the maneuver, indicating right ventricular dysfunction. CONCLUSIONS: In this animal lung injury model, lung recruitment maneuvers significantly decreased left-ventricular end-diastolic volume and cardiac output at hypovolemia. Hypervolemia did partly counteract this compromise. In addition, a marked right-ventricular dysfunction during the maneuver was found.

Animals↗
PubMed2006

Elevated levels of fibroblast growth factor-2 in serum from women with endometriosis.

OBJECTIVE: The purpose of this study was to determine whether serum and peritoneal fluid levels of fibroblast growth factor-2 (FGF-2) differ between women with and without endometriosis and to examine the relationship between proliferative activity in the endometriotic lesions and the levels of FGF-2 in serum and peritoneal fluid. STUDY DESIGN: Biopsy specimens of peritoneal endometriotic lesions (n = 25) were analyzed immunohistochemically regarding proliferative activity in stroma, glands, and blood vessels. The FGF-2 concentration was measured in peritoneal fluid and serum from 25 women with endometriosis and 14 healthy controls. RESULTS: Patients with endometriosis had higher serum concentrations of FGF-2 during both the proliferative and secretory menstrual phases than healthy women. Peritoneal fluid levels of FGF-2 differed significantly between women with high and low proliferative activity in their endometriotic lesions. CONCLUSION: Women with endometriosis have a higher serum level of FGF-2 than healthy controls.

Adult↗
PubMed2006

Effects on blood compatibility in vitro by combining a direct P2Y12 receptor inhibitor and heparin coating of stents.

The effect of the direct platelet P2Y12 receptor inhibitor, AR-C69931MX, on activation of blood induced by stents with and without heparin coating was investigated using a whole blood Chandler loop model in vitro. Stents were deployed in Chandler loops. Fresh human blood with heparin and AR-C69931MX was rotated for 1 h at 37 degrees C and used for measurements of platelets, microparticles, thrombin-antithrombin complex (TAT), fibrinogen binding to platelets, P-selectin expression by platelets, CD11b, Prothrombin Fragment F1+2, FXIa-AT, FXIIa-AT, C3a, sC5b-9 and stent score. In the first experiment there were four study groups with unmodified stents: 1a, no AR-C69931MX; 1b, 250 nmol/L; 1c, 750 nmol/L; 1d, 2250 nmol/L of AR-C69931MX. In the second experiment the concentration of AR-C69931MX was 500 nmol/L: 2a; tubings without stent; 2b; tubings with heparin-coated stent; 2c; tubings with unmodified stents. Heparin-coated stents were used in the third experiment: 3a; no AR-C69931MX; 3b; 500 nmol/L of AR-C69931MX. In the first experiment there were significant differences in all parameters analysed except for C3a, and stent score when the group with no AR-C69931MX was compared to all the groups with AR-C69931MX. In the second experiment there were significant differences in platelet count, TAT, FXIa-AT, FXIIa-AT and stent score when unmodified stents were compared to loops with no stents and partly to loops with heparin-coated stents. In the third experiment there was a significant reduction in generation of TAT, stent score and better preservation of platelet number by combining the platelet inhibitor and heparin-coated stents as compared to heparin-coated stents alone. The conclusion is that the direct P2Y12 receptor inhibitor AR-C69931MX reduced the different aspects of activation of blood induced by both unmodified and heparin-coated stents.

Adenosine Monophosphate↗
PubMed2006

Plasma protein fractions in healthy blood donors quantitated by an automated multicapillary electrophoresis system.

During the last decade, capillary electrophoresis (CE) has emerged as an important alternative to traditional analysis of serum and plasma proteins by agarose or celluloseacetate electrophoresis. CE analysis of plasma proteins can now be fully automated and also includes bar-code identification of samples, preseparation steps, and direct post-separation quantitation of individual peaks, which permits short assay times and high throughput. For laboratory work, it is important to have reference values from healthy individuals. Therefore, plasma samples from 156 healthy blood donors (79 females and 77 males) have been analyzed with the Capillarys instrument and the new high resolution buffer, which yields higher resolution than the beta1-beta2+ buffer. Albumin concentrations in samples are measured using nephelometry in order to assign protein concentrations to each peak. The 2.5 and 97.5 percentiles for both the percentages of different peaks and the protein concentrations in the peaks are calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. The Capillarys instrument is a reliable system for plasma protein analysis, combining advantages of full automation with high analytical performances and throughput.

Automation↗
PubMed2006

A population pharmacokinetic model for cefuroxime using cystatin C as a marker of renal function.

AIMS: Since cefuroxime mainly is excreted by renal filtration, dosing is currently based on serum creatinine (Scr) or creatinine clearance (CLcr). However, it has been suggested that cystatin C (CysC) is superior to Scr as a marker of renal function. The aim of this prospective study was to develop a population model that describes the pharmacokinetics of cefuroxime and to investigate the usefulness of CysC as a covariate of the model parameters. METHODS: Ninety-seven patients were studied (CLcr range 6.5-115 ml min(-1)). Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry. The population analysis was performed in NONMEM. RESULTS: A two-compartment model described the data well. The biomarkers Scr, CLcr and CysC were evaluated as covariates on clearance (CL). The model that included CysC generated the best fit. In the final population model CL was a function of CysC and body weight, whereas V(1) was only a function of body weight. Final parameter estimates (relative standard errors) were 6.00 (3.2%) l h(-1), 11.4 (5.3%) l and 5.11 (11%) l for CL, V(1) and V(2), respectively. CONCLUSIONS: Based on the results of the present study, and because CysC is practical to use in the clinic, it is suggested that individual dosing of cefuroxime may be based on CysC rather than on Scr or CLcr. Furthermore, our final population model may be useful as a tool when designing new dosing schedules for cefuroxime.

Anti-Bacterial Agents↗
PubMed2006

Flow cytometric technique for determination of prostasomal quantity, size and expression of CD10, CD13, CD26 and CD59 in human seminal plasma.

Summary Prostasomes are prostate-derived organelles in seminal plasma exhibiting pluripotent properties to facilitate the fertilization process. Seminal prostasome concentration, size distribution and expression of the prostasomal surface antigens CD10, CD13, CD26 and CD59 were examined by flow cytometry. The study group consisted of 79 men with involuntary infertility. Very strong correlations existed between the prostasome expressions of the different CD markers. Significant correlations between prostasome concentration and CD molecules were weak or lacking. Further, no or weak relationships were observed between the prostasomal CD markers and sperm morphology, seminal fructose, neutral alpha-glucosidase activity, zinc and tumour necrosis factor alpha concentrations. Flow cytometry is a practical way to study prostasomes in seminal fluid without prior separation. This is a new technique for evaluation of the role of prostasomes and their functions in male reproductive physiology.

CD13 Antigens↗
PubMed2006

Inflammatory, coagulatory and circulatory responses to logarithmic increases in the endotoxin dose in the anaesthetised pig.

Although porcine intravenous endotoxin shock models are widely employed in experimental sepsis, endotoxin dose-effect studies are scarce. Our primary aim was to establish the dose response to increasing endotoxin doses in inflammatory, coagulatory and haemodynamic effect variables, as well as to determine the optimal time point for assessment in a pig model. A secondary aim was to study pathophysiological covariations between the different responses. Twenty anaesthetised piglets received endotoxin intravenously in doses of 0.063 (n = 3), 0.25 (n = 3), 1.0 (n = 3), 4.0 (n = 3), 8 (n = 3) and 16 microg/kg/h (n = 2). In addition, non-endotoxin piglets constituted a control group (n = 3). Physiological variables were registered and blood samples analysed for TNF-alpha, IL-6, leukocyte, platelet and haemoglobin concentrations hourly for 6 h. Increases in the endotoxin dose induced significant log-log cytokine responses as well as log-linear leukocyte and platelet responses. Significant log-linear responses were observed for circulatory parameters, plasma leakage, hypoperfusion and pulmonary compliance. Significant covariations in the responses were noted. In conclusion, there were log-log or log-linear responses to endotoxin suggesting a greater effect of a given dose at lower pre-existing endotoxin concentrations and lower doses of < or = 1 microg/kg/h may be of advantage in experiments designed to study potential anti-endotoxin effects of experimental drugs or measures.

Anesthesia↗
PubMed2006

Selective recruitment maneuvers for lobar atelectasis: effects on lung function and central hemodynamics: an experimental study in pigs.

We investigated whether selective lung recruitment of a lobar collapse would improve oxygenation and lung volume as well as a general (global) lung recruitment maneuver, with fewer circulatory side effects. In 10 ventilated, anesthetized pigs, a bronchial blocker was inserted in the right lower lobe, which was selectively lavaged to create a dense lobar collapse. The pigs were randomized into two orders of lung recruitment maneuvers (40 cm H2O airway pressure for 30 s): either a selective lung recruitment maneuver (using the inner lumen of the bronchial blocker) followed by a general lung recruitment maneuver, or vice versa. Median end-expiratory lung volume and median Pao2 increased significantly by approximately 100 mL and 16 kPa, respectively, with no significant differences between the two recruitment methods. There were no circulatory changes during the selective lung recruitment maneuver, but during the general lung recruitment maneuver, mean arterial blood pressure decreased significantly by 36 (21, 41) mm Hg (median, 25th and 75th percentiles), cardiac output by 2.1 (1.6, 2.5) L/min and left ventricular end-diastolic area by 4.4 (3.5, 4.5) cm2. In conclusion, a selective recruitment maneuver improved lung function similar to a general lung recruitment maneuver but without any circulatory side effects.

Animals↗
PubMed2006

Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls.

BACKGROUND: Cystatin C is increasingly used as a glomerular filtration marker, but so far only a few companies produce most of the cystatin C reagents suited for turbidimetry or nephelometry use in clinical laboratories. METHODS: We studied different protocols for measuring cystatin C on an Architect ci8200 system using cystatin C reagents from Dako (Glostrup, Denmark). The results were compared with those obtained with Dade Behring reagents (Deerfield, IL, USA) on a BN ProSpec system. RESULTS: Differences in assay protocol on the same instrument with the Dako reagent yielded an up to 50% difference in glomerular filtration rate calculated from the cystatin C results when analyzing patient samples, but had no effect on the results for controls. There were also significant differences regarding linearity and kinetics between samples and controls/calibrators. CONCLUSIONS: The results indicate different reactivity of the Dako antibodies against calibrators and controls in comparison with patient samples, highlighting the importance of using controls and calibrators that do not differ from patient samples.

Calibration↗
PubMed2006

External quality assessment of HbA(1c) for point of care testing.

OBJECTIVES: To evaluate the long term total imprecision of HbA(1c) testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) < 3% for HbA(1c) and to study the cost of an external quality assurance program for point-of-care HbA(1c) The county uses Bayer DCA 2000 for point-of-care HbA(1c) testing currently having 23 of these instruments. METHODS: Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA(1c) testing. The samples were first analysed on a Bayer DCA 2000 and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II, Biorad). The testing was performed approximately 8 times per year with each instrument. RESULTS: The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%. CONCLUSION: The DCA 2000 systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.

Calibration↗
PubMed2006

Evaluation of Dade Behring N Latex Cystatin C reagent on Abbott ci8200.

Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for estimation of glomerular filtration rate (GFR). Reporting cystatin C results in mL/min using conversion formulas for transforming cystatin C expressed as mg/L to GFR expressed as mL/min has greatly facilitated the clinical use of the marker. At our hospital we have an increasing demand for cystatin C and at present we perform over 1400 cystatin C analyses a month. The test is available at all hours. This in combination with the volume emphasises the need to have the assay close to the routine chemistry instrument to reduce handling time per test and time to report test results. We have thus evaluated the Dade Behring N Latex Cystatin C assay (Dade Behring, Deerfield, IL, USA) on Architect ci8200 (Abbott Laboratories, Abbott Park, IL, USA). The nephelometric method on the ProSpec (Dade Behring) and the turbidimetric method on Architect ci8200 showed very good agreement (y = 1.0072x + 0.0042; R2 = 0.987). Accordingly, running the cystatin C analyses on a chemistry instrument (Architect ci8200) would be proper to increase the availability of the analysis and reduce turnaround times.

Cystatin C↗