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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cyclooxygenase-mediated prostaglandin F2alpha is decreased in an elderly population treated with low-dose aspirin.

Low-dose aspirin (acetylsalicylic acid) is used as prophylaxis against cardiovascular diseases. The effect of aspirin on inflammation and oxidative stress, processes known to be involved in cardiovascular diseases, are not fully known. The cyclooxygenase(COX)-mediated inflammatory indicator prostaglandin F2alpha (PGF2alpha) (15-keto-dihydro-PGF2alpha), cytokine-mediated inflammatory indicators (interleukin-6, high-sensitivity C-reactive protein, serum amyloid A protein), and oxidative stress indicators (8-iso-PGF2alpha, tocopherols) were quantified in men with daily 75 mg of aspirin (n=175) and control men (n=464), all of age 77, in a cross-sectional study. Men treated with aspirin had decreased levels of urinary 15-keto-dihydro-PGF2alpha than controls (P<0.01), independent of possible cardiovascular risk factors. Aspirin-treated men had increased levels of alpha-tocopherol than controls (P<0.05). This is the first study to indicate that low-dose aspirin treatment is associated with decreased levels of PGF2alpha. This observation suggests a possible COX-mediated anti-inflammatory effect of low-dose aspirin, which should be further confirmed by intervention studies.

Aged↗
PubMed2005

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects.

OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA < 4 (insulin sensitive) and HOMA>9 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulin-resistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

Adult↗
PubMed2005

Increased serum cystatin C is associated with increased mortality in elderly men.

Renal dysfunction measured by serum creatinine is associated with increased cardiovascular morbidity and mortality. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of glomerular filtration rate (GFR). The aim of the present study was to investigate the relationship between cystatin C and mortality in elderly men. Serum cystatin C was analyzed by nephelometry in a group of 77-year-old men (n=792) and correlated cystatin C levels with mortality during a follow-up period of 1-4 years. The cystatin C values were significantly correlated with overall mortality (p=0.013). Mortality was three times higher in the highest cystatin C quintile in relation to the lowest quintile.

Aged↗
PubMed2005

Oral lichenoid contact reactions may occasionally transform into malignancy.

The purpose was to identify cases of squamous cell carcinoma (SCC) of the tongue, in which a biopsy taken at the site preceding the cancer could be verified to show a lichenoid contact type of reaction (LCR). We retrieved all 724 SCC of the tongue from the Swedish Cancer Registry in the period 1995-2000. These cases were cross-searched with our own oral biopsy data files from 1988 to 1994, in order to identify biopsies with LCR-type lesions preceding the cancer. We found four verified and some additional tentative cases. The study demonstrated that there is a low incidence of malignant transformation in LCR-type oral lesions, not much different from what has been previously reported in oral lichen planus.

Aged↗
PubMed2005

Immunohistochemistry of the B-cell component in lower lip salivary glands of Sjögren's syndrome and healthy subjects.

Serial sections of lower lip salivary gland (LSG) biopsies were examined by immunohistochemistry, using a battery of B- and partly T-related antibodies (CD5, CD20, CD21, CD27, CD38, CD45RO, CD79a, Bcl-2 and Bcl-6) in different groups of subjects: healthy controls and clinically verified smoking or nonsmoking cases of primary Sjögren's syndrome (SS). The purpose was to characterize the B-cell pattern of the lymphocytic foci and of the tiny perivascular infiltrates preceding the development of foci. Hyperplastic tonsil was used as stain control. In normal LSG, widely dispersed CD38+ and CD79a+ as well as some CD5+ cells are a normal constituent, with lack of staining with the other antibodies. In SS/LSG, the lymphocytic foci showed staining with all the antibodies, with variable degrees of overlapping or nonoverlapping. In SS/LSG of nonsmokers, CD20+ B cells make up a prominent part of the fully developed periductal lymphocytic foci, not overlapping with CD45RO. Also, CD20+ B cells did not overlap in the infiltrates with colocalized CD27+/CD38+ cells. CD20+ B cells and CD45RO+ T cells also occur as minute infiltrates perivascularly in areas of no foci in SS/LSG as well as in SS smokers lacking the typical foci. Smokers lack foci, but tiny infiltrates express CD20 as well CD45R0. Our findings suggest that CD20+ B cells and CD45RO+ T cells are early immigrants in the LSG of SS of smokers as well as nonsmokers and that another subgroup of CD27+/CD38+ B cells gradually mix with the first two to form the characteristic foci in SS/LSG. The simultaneous demonstration of CD20+ and CD27+ B cells in SS/LSG may constitute a significant diagnostic tool. Further, the findings suggest that the early immigrating lymphocytes may have been primed at a site remote from the glands before arriving via the blood to the gland tissue.

ADP-ribosyl Cyclase↗
PubMed2005

Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs.

BACKGROUND: During euglycemia acute hyperinsulinemia diminishes the cytokine response to endotoxin [Lipopolysaccharide (LPS)] exposure. In this study we elucidated whether acute hyperglycemia and hyperinsulinemia modify the cytokine content in several organs during LPS challenge in a porcine model. METHODS: Pigs (35-40 kg) were randomized to either normoglycemia (group 1, n = 8) or hyperglycemia and hyperinsulinemia (group 2, n = 8), anesthetized and mechanically ventilated. Both groups received a 180-min intravenous infusion of LPS (total 10 microg kg(-1)). Groups 1 and 2 were clamped at plasma glucose concentrations of 5 mM and 15 mM, respectively. Group 1 maintained a baseline insulin level while the hyperglycemic group exhibited increased insulin levels. RESULTS: Circulating cytokines, cytokine mRNA and cytokine protein content were examined in the heart, liver, kidneys, lungs, spleen, adipose and muscle tissue. After LPS exposure, in both groups vast and equal plasma cytokines were elicited by approximately 70-5000-fold. A 10-fold higher level of IL-10, IL-6 and TNF-alpha protein was found in kidney tissue compared to the other organs together with a 3-10-fold increase of TNF-alpha in adipose tissue. However, cytokine mRNAs as well as organ function were without statistical difference between the groups. CONCLUSION: Endotoxemia elicited a pronounced cytokine response in both plasma and at organ level. The kidneys and adipose tissue showed the highest cytokine protein content. Acute hyperglycemia apparently counteracts the well-established anti-inflammatory effects of insulin on the inflammatory response in a LPS challenged porcine model. Whether the observation can be extrapolated to more long-term stress-exposure remains to be clarified.

Animals↗
PubMed2005

Evidence that acute hyperinsulinaemia increases the cytokine content in essential organs after an endotoxin challenge in a porcine model.

BACKGROUND: Insulin has anti-inflammatory effects, as evaluated by its ability to reduce the plasma concentrations of cytokines. However, the inflammatory processing at the organ level is far less well established. The cytokine content in several organs after endotoxin (lipopolysaccharide, LPS) exposure and the effect of hyperinsulinaemia was examined. METHODS: Pigs (35-40 kg) were randomized into four groups, anaesthetized and mechanically ventilated for 570 min: group 1 (anaesthesia only; n = 10), group 2 (hyperinsulinaemic euglycaemic clamp, HEC; n = 9), group 3 (LPS; n = 10) and group 4 (LPS + HEC; n = 9). LPS was infused intravenously for 180 min (total dosage, 10 microg/kg). At the end of the study, i.e. 330 min after the termination of LPS or equivalent, cytokine mRNA and cytokine protein contents in the lungs, heart, liver, adipose tissue and spleen were measured. RESULTS: Hyperinsulinaemia led to increased interleukin-10 (IL-10) protein content in the heart and liver (by 40% and 28%, respectively) in comparison with normoinsulinaemic animals (P < 0.01 and P = 0.02, respectively), and increased tumour necrosis factor-alpha (TNF-alpha) protein content in the heart (P = 0.02). Animals exposed to LPS exhibited reduced TNF-alpha, IL-6 and IL-8 protein content in the heart (P = 0.02, P < 0.001 and P = 0.01, respectively). In the kidneys and adipose tissue, a particularly large cytokine protein content was observed. CONCLUSION: The findings strongly substantiate the role of insulin as an immune-modifying hormone at organ level during baseline and after an endotoxin challenge. Moreover, the kidneys and adipose tissue appear to be pivotal organs in terms of cytokine content shortly after endotoxin exposure, but the complexity remains to be clarified.

Animals↗
PubMed2005

Clonal populations of chondrocytes with progenitor properties identified within human articular cartilage.

The aim of the present study was to identify and characterize progenitor properties of human articular chondrocytes selected by using agarose suspension culture. In this chondrogenic selective culture condition, about 3.6% of seeded surplus chondrocytes from patients undergoing articular chondrocyte transplantation proliferated and formed cell clusters after 6 weeks. Phase-contrast microscopy and transmission electron microscopy revealed four different types of cell clusters differing in cellular content and matrix production. Based on their morphological features, they were named the homogenous (H), the homogenous matrix (HM), the differentiated matrix (DM) and the differentiated (D) cell clusters. All cell clusters showed positive safranin O staining, and matrix was positive for antibodies detecting type II collagen and aggrecan. The clusters were further demonstrated to express the genes for fibroblast growth factor receptor 3, type IIA collagen and type IIB collagen, while type X collagen was not expressed. After subcloning, the H and HM clusters demonstrated the best proliferative capacity. Chondrocytes from these two cell clusters also showed phenotypic plasticity in chondrogenic, adipogenic as well as osteogenic assays. This study demonstrates that existing subpopulations of cells with chondroprogenitor properties can be isolated from human adult articular cartilage using agarose suspension cultures.

Adolescent↗
PubMed2005

Fungus covered insulator materials studied with laser-induced fluorescence and principal component analysis.

A method combining laser-induced fluorescence and principal component analysis to detect and discriminate between algal and fungal growth on insulator materials has been studied. Eight fungal cultures and four insulator materials have been analyzed. Multivariate classifications were utilized to characterize the insulator material, and fungal growth could readily be distinguished from a clean surface. The results of the principal component analyses make it possible to distinguish between algae infected, fungi infected, and clean silicone rubber materials. The experiments were performed in the laboratory using a fiber-optic fluorosensor that consisted of a nitrogen laser and an optical multi-channel analyzer system.

Equipment Contamination↗
PubMed2004

Enhanced DNA-dependent protein kinase activity in Sjögren's syndrome B cells.

OBJECTIVE: To examine the stress response, including the role of DNA-dependent protein kinase (DNA-PK), in B cells from Sjögren's syndrome (SS) patients. METHODS: B-cell lines were exposed to gamma radiation and then postincubated to allow inducible stress functions to develop. The magnitude of the DNA damage response was monitored with respect to DNA-PK phosphorylation of a p53 peptide, defence protein levels (Ku, DNA-PK catalytic subunit, ATM, p21 and p53) and flow cytometric determination of cell cycle phases and apoptosis. RESULTS: B cells from SS patients, compared with healthy controls, displayed enhancement of two stress functions in undamaged cells: DNA-PK kinase activity and apoptosis. In addition, SS showed enhanced cell cycle arrest in gamma-irradiated cells. CONCLUSIONS: Strong kinase activity of DNA-PK, functioning not only in a DNA damage response but also in immunoglobulin gene rearrangement, may be an important component of the heightened stress response displayed by SS cells. In combination with recent reports, our data indicate that constitutional hyper-reactivity to danger signals is a basic pathogenetic factor in SS.

Antigens, Nuclear↗
PubMed2004

Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP.

OBJECTIVE: To examine if changes in serum cartilage oligomeric matrix protein (COMP) correlate with the development of cartilage damage, as measured by histological grading, in corticosteroid-treated animals with collagen-induced arthritis (CIA). METHODS: DA rats with established CIA were treated with corticosteroids (betamethasone, 0.1 mg/kg body weight) or placebo (saline) intraperitoneally once daily after reaching an arthritis score exceeding 1. The treatment continued throughout the study. Arthritis progression was monitored by clinical scoring of paws, serial measurements of serum COMP and fibrinogen, and histological grading of paws. RESULTS: Corticosteroid treatment reduced clinical signs of arthritis compared with placebo (arthritis score reduced, P < 0.01 at day 25). Corticosteroid treatment also reduced fibrinogen levels compared with placebo (P < 0.01). The morphological changes in the joint were less severe in the corticosteroid-treated animals (median cartilage score 4 in the placebo group, 0 in the corticosteroid-treated group; P < 0.01). The levels of COMP remained unchanged during treatment in the corticosteroid-treated arthritic animals, whereas an increase in levels of COMP was observed in rats treated with placebo (P < 0.01). There was a correlation between serum COMP and the extent of cartilage destruction at day 25 after immunization (r = 0.77, P < 0.001). CONCLUSIONS: Corticosteroids given therapeutically to arthritic rats diminish joint destruction histologically, and stable serum COMP levels reflect this effect.

Animals↗
PubMed2004

Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer.

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.

Adult↗
PubMed2004

Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre-eclampsia.

Pre-eclampsia is a serious complication of pregnancy and it is important to detect the condition as early as possible. Albuminuria is an important symptom of pre-eclampsia and repeated urine analyses to screen for the condition are part of the standard antenatal care. The purpose of this study was to investigate whether measurement of the urine albumin/creatinine ratio in spot samples could be a complement to the dipstick method and could reduce the need for 24-h urine collections. Urine samples were collected for 24 h in weeks 12, 24 and 36 of pregnancy from both normotensive women and women who developed hypertension or who had pregnancy-induced hypertension (PIH) when they entered the study. The 24-h albumin excretion was significantly correlated to the albumin/creatinine ratio in all measurements (Pearson correlation coefficient). In week 12, the values were: n = 44, r = 0.964, p < 0.001 (normotensive group) and in the PIH group: n = 8, r = 0.789, p < 0.05. In week 24, the correlation values were r = 1.0 and p < 0.001 in both the normotensive group (n = 41) and in the PIH group (n = 11). In week 36 the correlation values were r = 0.791 and p < 0.001 in the normotensive group (n = 39) and r = 1.0 and p < 0.001 in the PIH group (n = 16). Microalbuminuria was defined as urine albumin excretion higher than 30 mg/24 h and this corresponded to an albumin/creatinine ratio of 2.9. Microalbuminuria was found in three persons in the PIH group and in two persons in the normotensive group. Overt albuminuria (> 300 mg/24 h) was found in one of the 46 normotensive women (2%) and in 3 of the 19 PIH women (16%). In all these women the high albumin values had been detected by using the albumin/creatinine ratio method. In conclusion, it has been found that the albumin excretion in urine correlates significantly to the albumin/creatinine ratio during pregnancy. The urinary albumin/creatinine ratio appears to be a good alternative to the dipstick method and to 24-h urine collections.

Adult↗
PubMed2004

Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L.

The Cockcroft Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p < 0.0001) was found between cystatin C and iohexol clearance (r2 = 0.91) than between creatinine and iohexol clearance (r2 = 0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y = 77.24x(-1.2623) (Dade Behring cystatin C calibration) or y = 99.43x(-1.5837) (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations.

Adolescent↗
PubMed2004

Synovial concentrations of the angiogenic peptides bFGF and VEGF do not discriminate rheumatoid arthritis from other forms of inflammatory arthritis.

OBJECTIVES: To investigate whether concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in aspirated synovial fluid can be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis. METHODS: bFGF and VEGF concentrations were measured in aspirated synovial fluid and serum samples from 66 patients with active arthritis (clinical diagnoses: rheumatoid arthritis (35 patients), psoriatic arthritis (9), reactive arthritis (11) and arthritis UNS (11)) utilizing commercial ELISA kits. RESULTS: In comparison with controls, elevated concentrations of VEGF were found in synovial fluid compared with in serum in all forms of arthritis. There were no significant differences in synovial fluid bFGF or VEGF concentrations between rheumatoid arthritis and the other forms of inflammatory arthritis. CONCLUSION: Both serum bFGF and VEGF concentrations were increased in patients with rheumatoid arthritis. Patients treated with steroids had lower synovial fluid bFGF concentrations. Synovial fluid levels of bFGF and VEGF were elevated but could not be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis.

Adult↗
PubMed2004

Both lung recruitment maneuver and PEEP are needed to increase oxygenation and lung volume after cardiac surgery.

BACKGROUND: Patients ventilated after cardiac surgery commonly have impaired oxygenation, mainly due to lung collapse. We have previously found that PaO2 and end-expiratory lung volume (EELV) were increased by a lung recruitment maneuver (LRM) followed by positive end-expiratory pressure (PEEP). The aim of this study was to evaluate whether only PEEP or only a LRM could give similar effects. METHODS: Thirty circulatory stable patients (aged 55-79 years) mechanically ventilated after cardiac surgery were randomized to receive LRM (four 10-s insufflations to an airway pressure of 45 cmH2O) and zero end-expiratory pressure (LRM-group), PEEP 12 cmH2O (PEEP-group) or LRM in combination with PEEP 12 cmH2O (LRM + PEEP-group). The set end-expiratory pressure was kept for 75 min. Before, during and after the intervention, EELV (SF6 washout technique) and blood gases were measured. RESULTS: Initial EELV and PaO2 were similar in all groups. In the LRM-group, PaO2 and EELV increased transiently (P < 0.0001), but returned at 5 min to the initial values. In the PEEP-group, PaO2 did not change but EELV increased to 155 +/- 27% of the initial value (P < 0.0001). In the LRM+PEEP-group, PaO2 and EELV increased to 212 +/- 66% and 178 +/- 31% of the initial values (P < 0.0001), respectively, and were maintained during PEEP application. CONCLUSION: In patients ventilated after cardiac surgery: (1) PEEP increased lung volume but not PaO2, (2) a lung recruitment maneuver without subsequent PEEP had no sustained effect, and (3) both a lung recruitment maneuver and PEEP were needed to increase and maintain the increased lung volume and PaO2.

Aged↗