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Biomedical subjects

S Larsson

Publications and source records attributed to S Larsson.

At least 109 records · Page 6Linked to original sources

Effects of a corticosteroid, budesonide, on production of bioactive IL-12 by human monocytes.

Interleukin 12 (IL-12) has a key role during the initial phase of the immune response, favouring development of T helper class 1 (Th1) cells. IL-12 is composed of two subunits, p35 and p40, which are both needed for bioactivity. The level of p35 expression determines the level of bioactive IL-12 (p70), while the p40 subunit is produced in excess. In the present study we examined the sensitivity of bioactive IL-12 production by human monocytes to a corticosteroid, budesonide. We also compared the corticosteroid sensitivity of IL-12 and two other cytokines, interleukin 1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocytes obtained from peripheral blood of healthy donors (n=12) were stimulated with lipopolysaccharide (LPS; 10 microg/ml; 20 h) in the presence or absence of budesonide (10(-11)-10(-7) M). The supernatants were assayed for IL-12 (p70), IL-1beta and GM-CSF concentrations using specific immunoassays. Budesonide potently inhibited the production of bioactive IL-12. A significant suppression was obtained by treatment with even very low budesonide concentrations; even 10(-11) M budesonide significantly inhibited IL-12 to 81.6+/-7.6% of the control level (P<0.05). The maximal inhibitory effect of budesonide was seen at 10(-8) M. The inhibition of IL-12 production was significantly higher than the inhibition of GM-CSF (P<0.01) or IL-1beta (P<0.001). Whereas IL-12 production was totally inhibited, GM-CSF production was inhibited to 16.4+/-3.7 and IL-1beta production to 43.1+/-7.3% of control, respectively. The dramatic capacity of corticosteroids to modulate production of IL-12 as well as other cytokines may be a major mechanism underlying the effectiveness of these drugs in a broad spectrum of inflammatory diseases.

Administration, Topical↗

Joint fluid enhancement at MRI of the glenohumeral joint with intravenous injection of gadodiamide in standard and triple dose: a prospective comparative study of stable and unstable shoulders.

OBJECTIVE: To investigate the joint fluid enhancement at MRI of unstable and stable glenohumeral joints after intravenous administration of different doses of gadodiamide. DESIGN AND PATIENTS: Fourteen patients with unilateral anterior shoulder instability and six healthy controls had both shoulders examined on two occasions using either a standard dose (0.1 mmol/kg) or a triple dose (0.3 mmol/kg) of gadodiamide in an open MRI magnet (0.2 T). RESULTS AND CONCLUSIONS: The joint fluid enhancement in the unstable shoulders was on average 134% following the lower dose and 182% for the triple dose, whereas corresponding values in the stable shoulder in the same individuals were 69% and 142%, and (65% and 159%) in the healthy controls. Enhancement of the joint fluid was higher after the triple dose than after the standard dose in both the unstable shoulders (P < 0.0001) and the controls (P < 0.0005). Compared with the stable controls enhancement in the unstable shoulders was higher for the lower dose (P < 0.0001) while there was no significant difference between the groups following the higher dose. The improved enhancement following the higher dose was especially evident in stable shoulders, while the lower dose was found satisfactory for unstable shoulders.

Adolescent↗

Indirect MR arthrography of anterior shoulder instability in the ABER and the apprehension test positions: a prospective comparative study of two different shoulder positions during MRI using intravenous gadodiamide contrast for enhancement of the joint fluid.

OBJECTIVE: The value of MRI for the evaluation of anterior shoulder instability can be enhanced by shoulder positions that stress the stabilising structures. The ABER position is one that has been described in combination with intra-articular gadopentetate dimeglumine arthrography. We believe that MRI in the Apprehension test position with 90 degrees abduction and maximal tolerable external rotation provides maximum tension on the anterior stabilising structures and with this technique it is sufficient to use indirect gadodiamide arthrography following intravenous injection of the contrast medium. The purpose of this study was to make a prospective comparative evaluation of the ABER and Apprehension test positions when using indirect arthrography with intravenous gadodiamide administration in shoulders with anterior instability. DESIGN AND PATIENTS: Sixteen patients with persistent anterior instability after recurrent shoulder dislocations were examined in an open MRI unit (0.2 T) following 0.1 mmol/kg of intravenous gadodiamide. Oblique axial T1-weighted imaging was used for analysis. Operative findings were used for correlation. RESULTS: Both the ABER and the Apprehension test position were useful techniques in detecting capsulolabral pathology and Hill-Sachs lesions. The Apprehension test position produced significantly better gadodiamide-enhanced joint fluid in the region of pathology in both the capsulolabral lesion and the Hill-Sachs lesion. It also visualised the size of the Hill-Sachs lesion significantly better than did the ABER position. CONCLUSION: MRI examination of anterior shoulder instability in the Apprehension test position was more beneficial than examination in the ABER position in visualising capsulolabral and Hill-Sachs lesions when using indirect arthrography.

Adolescent↗

Long-term Doppler echocardiographic results of aortic or mitral valve replacement with Biocor porcine bioprosthesis.

OBJECTIVES: Our objectives were to evaluate the long-term bioprosthetic and cardiac functional outcome after insertion (over a 10-year period) of a new-generation porcine zero pressure-fixed Biocor bioprosthesis, as well as to determine the echocardiographic accuracy for selection of patients requiring reoperation. The long-term systematic Doppler echocardiographic assessment after valve replacement with this bioprosthesis is lacking. METHODS: Between January 1983 and January 1993, we inserted 756 Biocor prostheses in the aortic (619) or mitral (137) positions. All 51 patients who had a reoperation during the follow-up time were evaluated echocardiographically before reoperation. Additionally, 263 of 446 patients (59%) with aortic bioprostheses and 42 of 74 patients (57%) with mitral bioprostheses who were alive in January 1993 had long-term echocardiographic follow-up. RESULTS: Group A: Normally functioning bioprostheses were found in the aortic position in 242 of 263 patients and in the mitral position in 33 of 42 patients. Group B: Thirty patients had abnormal bioprosthetic function. Eleven patients had regurgitation, 3 had a combined lesion, and signs of calcification appeared in 16 patients with aortic valves, all with a peak gradient of above 60 mm Hg. Group C: Patients who had a reoperation (41 aortic and 10 mitral) within the follow-up period were followed up echocardiographically from the detection of a possible valve dysfunction until reoperation, and the findings accorded well with those at operation in 49 of 51 patients. CONCLUSIONS: These findings suggest that, during a long-term follow-up, most bioprostheses function normally, facilitating improved heart function. Abnormalities in a bioprosthesis usually develop gradually, enabling their detection by Doppler echocardiographic evaluations performed regularly or in case of any symptomatic deterioration.

Adult↗

IL-6 antisense oligonucleotides inhibit IgE production in IL-4 and anti-CD40-stimulated human B-lymphocytes.

Stimulation of tonsillar B-lymphocytes with CD40 antibodies and IL-4 leads to homotypic adhesion, proliferation, and differentiation into Ig-producing cells. It also leads to the production of IL-6, a pleiotropic cytokine involved in B-cell maturation and differentiation. To assess the importance of IL-6 in the differentiation process, an antisense oligonucleotide to IL-6 was added to tonsillar B-cells together with CD40 antibodies and IL-4. This led to clearly reduced levels of IL-6 as well as to a specific inhibition of IgE production. Also, IgG secretion was somewhat reduced while IgM appeared to be unaffected. The effects were not due to toxicity of the oligonucleotide since proliferation proceeded normally or was slightly enhanced in the presence of the antisense. The findings show that endogenous IL-6 is an important co-factor for the generation of B-cells secreting IgE and IgG but that it is not required for IgM production. They further indicate that IL-6 may not be necessary as a co-factor in CD40/IL-4 induced proliferation.

Antibodies↗

Reference Doppler echocardiographic values for St. Jude Medical, Omnicarbon, and Biocor prosthetic valves in the aortic position.

The objectives of the present investigation were (1) to describe Doppler echocardiographic findings for mechanical and biologic aortic valves at an early stage after operation and later in a stable phase and (2) to study the changes occurring between these investigations. Patients (n = 213) who received a mechanical (St. Jude Medical, Omnicarbon) or a biologic (Biocor) valve were studied by Doppler echocardiography within the first week (baseline, n = 203) and after 2 years (late, n = 172). The comparison of baseline with late investigation (mean +/- SD) showed an increase in systolic blood pressure (137 +/- 18.5 to 154 +/- 20.6 mm Hg, p = 0.0001, n = 112), reduction of heart rate (85 +/- 15.3 to 74 +/- 12.0 beats/min, p = 0.0001, n = 141) and increase in stroke volume (59 +/- 20.6 to 77 +/- 19.8 ml, p = 0.0001, n = 132). Prosthetic Doppler echocardiographic findings demonstrated a reduction in blood flow velocity in the left ventricular outflow tract (VLVOT, 1.10 +/- 0.25 to 0.96 +/- 0.23 m/sec, p = 0.0001, n = 146) reduction in peak velocity (Vmax 2.72 +/- 0.53 to 2.59 +/- 0.54 m/sec, p = 0.02, n = 150), reduction in mean pressure gradient (deltaPmean, 18.4 +/- 7.2 to 16.3 +/- 7.3 mm Hg, p = 0.004) and an increase in velocity index (Vmax/VLVOT, 2.56 +/- 0.62 to 2.67 +/- 0.60, p = 0.003, n = 144). The standard deviations of difference between baseline and late investigation expressed as percentage of mean were 25% for VLVOT, 20% for Vmax, 44% for deltaPmean, and 25% for velocity index. In conclusion, this large reference base provides data that should be useful for the clinician evaluating patients with prosthetic valves early after valve replacement as well as at a later stage. When valve dysfunction is suspected a previous investigation for comparison is helpful, and our data describe the changes that normally may be seen between an early baseline and a late investigation.

Aged↗

Evaluation and metabolite studies of 125I- and 123I-labelled E-(R,R)-IQNP: potential radioligands for visualization of M1 muscarinic acetylcholine receptors in brain.

A new ligand for the M1 muscarinic receptor subtype, E-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (E-IQNP), was labelled with 125I and 123I for autoradiographic studies on human whole-brain cryosections and SPET studies, respectively, in Cynomolgus monkey. Autoradiography demonstrated E-[125I]IQNP binding in M1 receptor-rich regions such as the neocortex and the striatum. The binding was displaceable by the selective M1 antagonist biperiden. In vivo single photon emission tomography (SPET) studies with E-[123I]IQNP demonstrated a high accumulation of radioactivity in the monkey neocortex. Rapid hydrolysis of the quinuclidinyl ester to the free acid was found to be a major biotransformation route for E-[123I]IQNP. The free acid of E-[123I]IQNP does not pass the blood-brain barrier, but the plasma concentration was high as compared to the total radioactivity in brain. It is thus necessary to correct for the high concentration of radioactive metabolites in parenchymal blood (CBV) to obtain accurate values for E-[123I]IQNP binding in brain.

Animals↗

Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time.

BACKGROUND: A poor correlation between cytomegalovirus (CMV) seroreactivity and the risk of CMV transmission prompted an investigation of the presence of CMV DNA in peripheral blood mononuclear cells (PBMNCs) from seropositive and seronegative blood donors. Because latent CMV exists in monocytes, monocyte-enriched cells were analyzed separately. STUDY DESIGN AND METHODS: Samples from 270 blood donors were tested with a sensitive polymerase chain reaction (PCR) test that detects two CMV genes, and the results were correlated to CMV serology. Cross-reactivity with other herpesvirus genes was not recorded. RESULTS: PCR testing demonstrated that 71 percent of seropositive donors harbor CMV in PBMNCs. Thus, not all seropositive donors were CMV DNA positive when individual samples were tested. Tests repeated over a period of time showed that all seropositive individuals were positive. Increased sensitivity was obtained with enriched monocytes. Among seronegative donors, 55 percent harbored CMV DNA in monocyte-enriched PBMNCs, while 14 percent had CMV DNA in PBMNCs. CONCLUSION: All seropositive donors harbored latently infected PBMNCs, as demonstrated by the testing of samples collected over time. In addition, a substantial proportion of seronegative individuals are CMV carriers and might transfer infection. The findings concur with clinical evidence of CMV transmission by blood components from seronegative individuals and with in vitro reactivation of CMV in PBMNCs from seronegative donors.

Antibodies, Viral↗

Insect performance on experimentally stressed woody plants: a meta-analysis.

In this review, we test the hypothesis that abiotic stress increases the suitability of plants as food for herbivores. We conducted a meta-analysis that included 70 experimental studies in which insect performance was measured on woody plants subjected to water stress, pollution, and/or shading. Overall, plant stress had no significant effect on insect growth rate, fecundity, survival, or colonization density. We found great variation, however, in the magnitude and direction of insect responses among studies, most of which was related to insect feeding guild. In general, boring and sucking insects performed better on stressed plants, whereas plant stress adversely affected gall-makers and chewing insects. Reduction in performance of chewers was greater on stressed slow-growing plants than on stressed fast growers. Reproductive potential of sucking insects was increased by pollution but reduced by water stress. In some cases where sample sizes were small or the treatment periods short, apparent differences in insect responses to stress were probably artifacts due to inappropriate experimental design.

Journal Article↗

Immunological findings in blood and bronchoalveolar lavage fluid in chronic bronchitis patients with recurrent infectious exacerbations.

Bronchial infections are common in smokers and seem to be related to the presence of chronic bronchitis (CB). Why only some smokers develop repeated bronchial infections is not known. The aim of this study was to screen for immunological changes associated with disease in patients with CB and recurrent infectious exacerbations compared to asymptomatic smokers. Sixteen smokers with stable CB and recurrent infectious exacerbations, and 18 asymptomatic smokers, all without any immunomodulating treatment, underwent bronchoscopy and bronchoalveolar lavage (BAL). Smoking history and current smoking status were comparable. Serum levels of immunoglobulin (Ig)A, IgM, IgG and IgG subclasses were measured. Blood and BAL lymphocyte phenotypes and proliferative responses of peripheral blood mononuclear cells (PBMCs) to various stimulators were analysed. Unstimulated and tetanus toxoid-stimulated production of cytokines in PBMC cultures was measured. Natural killer (NK-) cell activity was analysed. A significantly (p<0.05) lower level of IgG3 was found in the CB group, and a significantly (p<0.01) higher proliferative response of PBMCs was found in the CB group after stimulation with diphtheria toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma, but not of IL-2, IL-4 or transforming growth factor-beta2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-alpha production was significantly (p<0.05) higher in the CB group. NK-cell activity did not differ significantly between the study groups. There were no major differences between the groups in lymphocyte subpopulations in blood or BAL. In conclusion, no major alterations in the analysed indices of cell-mediated and humoral immunity were found in patients with chronic bronchitis prone to recurrent infectious exacerbations when compared with asymptomatic smoking controls.

Adult↗

Reliability and validity of a Swedish version of the St George's Respiratory Questionnaire.

The St George's Respiratory Questionnaire (SGRQ) was designed to measure quality of life (QoL) in obstructive pulmonary disease. Its reliability, validity and sensitivity have been demonstrated. The aim was to develop a Swedish version of the SGRQ and to confirm its scaling and clinical properties. The SGRQ was adapted for Swedish conditions following a translation-backtranslation procedure. The psychometric and clinical evaluation included 68 patients with chronic obstructive pulmonary disease (COPD). Supplementary QoL, clinical and physiological data were collected. A follow-up study was performed 1 yr later. Correlation analysis used a multitrait-multimethod model. Internal consistency reliability and discriminant validity were documented by performing a multitrait analysis. The results confirmed expected levels of associations. Correlation coefficients between the SGRQ total score and the Sickness Impact Profile Total score (a generic health measure), forced expiratory volume in one second (FEV1) and 6 min walking distance were 0.69, -0.42 and -0.61 respectively. The pattern of correlations in the Swedish data set was very similar to that of the original. The stability of the SGRQ scores was confirmed at follow-up after 1 yr. The reliability was satisfactory, with Cronbach's alpha coefficients >0.80 for the SGRQ and its subdimensions. In conclusion, the Swedish version of the St George's Respiratory Questionnaire is reliable, valid and compares well with the corresponding tests of the original version.

Aged↗

Intramedullary versus extramedullary fixation of subtrochanteric fractures. A biomechanical study.

We compared two different subtrochanteric fracture fixation techniques, an intramedullary hip screw system (IMHS) and an extramedullary, dual sliding screw-plate system (MSP), to determine relative fixation stability. 6 matched pairs of osteosynthesized osteopenic cadaver femurs were axially loaded to 1000 N with concurrent, simulated abductor forces of 0%, 50%, or 86% of the applied head force. The initial loading sequence was made with uniaxial dynamization--the lag screw of the MSP locked and distal locking of the IMHS nail. Femoral head displacement and medial femoral strain were measured for intact femur controls, after fixation of a 2-part reverse oblique subtrochanteric fracture and finally a 3-part reverse oblique subtrochanteric fracture with a lateral wedge defect. The samples were then loaded at 750 N for 10(4) cycles with both devices uniaxially locked, followed by 10(4) cycles with both devices fully biaxially dynamized (unlocked). For the 2-part subtrochanteric fracture pattern, both devices exhibited similar inferior displacements of the femoral head (average 2.0 mm) and medial femoral strain (approximately 70% of intact). Increasing abductor forces decreased medial compressive strain but did not significantly affect head displacement. For the 3-part fracture model, the MSP demonstrated significantly less inferior displacement of the head (1.6 mm vs. 2.1 mm) and both devices demonstrated significantly decreased medial strain. After cycling, head displacement increased approximately 50% in both devices and medial strain increased slightly. After unlocking and cycling, the MSP group showed significant lateral displacement of the proximal fragment. The IMHS and MSP devices provide similar stability for fixation of 2-part and 3-part reverse oblique subtrochanteric fractures. In a biaxially dynamized, 3-part reverse oblique fracture, displacement of the proximal fragment can occur with the MSP.

Aged↗

The Medoff sliding plate and a standard sliding hip screw for unstable intertrochanteric fractures: a mechanical comparison in cadaver femurs.

The Medoff sliding plate has a dual side capability along both the femoral shaft and neck to increase theoretically interfragmentary compression and load-sharing in hip fractures. We studied intertrochanteric fracture fixation in cadaveric bone to determine whether this device has a mechanical advantage over a standard sliding hip screw. 2-part and 4-part fractures were created in 12 cadaver femurs. The fractures were fixated and sequentially destabilized; bone and plate strains and fragment displacements were determined during testing, as a function of applied physiological loads before and after short-term cycling. The Medoff sliding plate imposed a higher mean medial cortex strain than the sliding hip screw in all fracture models and at all loading levels, and the difference was statistically significant in the 2-part and in the unstable 4-part fracture models. The loading of the medial cortex region after cycling was approximately 50% higher in the Medoff samples than in the sliding hip screw samples. There were no significant differences in plate strains, fracture displacements or load to failure between the 2 devices. These observations favor the dual sliding principle as regards providing fracture compression and load-sharing, which may explain low failure rates in clinical series of unstable intertrochanteric fractures, treated with the Medoff sliding plate.

Aged↗

Norian SRS cement augmentation in hip fracture treatment. Laboratory and initial clinical results.

Bone quality, initial fracture displacement, severity of fracture comminution, accuracy of fracture reduction, and the placement of the internal fixation device are important factors that affect fixation stability. New high strength cements that are susceptible to remodeling and replacement for fracture fixation may lead to improved clinical outcome in the treatment of hip fractures. Norian SRS is an injectable, fast setting cement that cures in vivo to form an osteoconductive carbonated apatite of high compressive strength (55 MPa) with chemical and physical characteristics similar to the mineral phase of bone. It can be used as a space filling internal fixation device to facilitate the geometric reconstruction, load transfer, and healing of bone with defects and/or fractures in regions of cancellous bone. Furthermore, this cement can improve the mechanical holding strength of conventional fixation devices. Use of this material potentially could improve fracture stability, retain anatomy during fracture healing and improve hip function, thus achieving better clinical outcomes. In vivo animal studies have shown the material's biocompatibility, and cadaveric studies have shown the biomechanical advantage of its use in hip fractures. Initial clinical experience (in 52 femoral neck fractures and 39 intertrochanteric fractures) showed the potential clinical use of this innovative cement in the treatment of hip fractures.

Aged↗

A comparative study of fixation techniques in the open Bankart operation using either a cannulated screw or suture-anchors.

The purpose of this study was to compare fixation using either Mitek suture-anchors or a cannulated screw technique, both applied extracapsularly, for an open Bankart reconstruction. Fifty-five consecutive patients with recurrent anterior dislocation of the shoulder were operated in two consecutive series. The same surgical technique was applied regardless of group, except for the reattachment method of the capsulolabral complex to the glenoid rim. Patients operated with suture-anchor fixation had better anterior stability, external rotation and functional outcome after a 24-month minimum follow-up. There were no differences between the groups regarding redislocation or subluxation rate.

Adult↗

Interleukin-2 and -4 induce resistance of granulocyte-macrophage colony-stimulating factor to corticosteroids.

In vitro pretreatment of human mononuclear blood cells with a combination of interleukin-2 and interleukin-4 decreases corticosteroid receptor affinity and reduces the anti-proliferative effects of corticosteroids. Similar abnormalities have been observed in mononuclear blood cells of steroid-resistant asthmatics. In vitro steroid resistance was induced by 48 h pretreatment of mononuclear blood cells from healthy individuals (n = 10) with interleukin-2 and interleukin-4 (500 Units (U)/ml). The effects of three structurally different corticosteroids (10(-7)-10(-11) M) on lipopolysaccharide-stimulated (10 ng/ml; 20 h) production of granulocyte-macrophage colony-stimulating factor (GM-CSF) were examined. GM-CSF production was efficiently inhibited by all three corticosteroids in the control cultures. Cortivazol was significantly more potent (IC50 = 3 x 10(-11) M) than budesonide and tipredane (IC50 = 2.5 x 10(-10) M and IC50 = 2 x 10(-10) M, respectively). However. interleukin-2 and interleukin-4 pretreatment counteracted the inhibitory effects of all three corticosteroids to a similar degree. The results highlight the importance of interleukin-2 and interleukin-4 in the induction of steroid resistance, since pretreatment of mononuclear blood cells with these cytokines impaired corticosteroid inhibition of GM-CSF production.

Androstadienes↗