| 451. |
- Kvarnström, Andreas, 1978, et al.
(författare)
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Complement activation and interleukin response in major abdominal surgery
- 2012
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 75:5, s. 510-516
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Tidskriftsartikel (refereegranskat)abstract
- Study Objective: The objective of this study was to evaluate whether major abdominal surgery leads to complement activation and interleukin response and whether the kind of anaesthesia influence complement activation and the release of inflammatory interleukins. Design: Prospective and randomised trial. Setting: Operating room and in the postoperative recovery area. Patients: Fifty patients undergoing open major colo-rectal surgery due to cancer disease or inflammatory bowel disease were studied. Interventions: Twenty-five patients were given total intravenous anaesthesia (TIVA) with propofol and remifentanil and 25 were given inhalational anaesthesia with sevoflurane and fentanyl. Measurements: In order to determine complement activation (C3a and SC5b-9) and the release of pro- and anti-inflammatory interleukins (tumour necrosis factor-α (TNF-α)), interleukin-1β (IL-1β), IL-6, IL-8, IL-4 and IL-10) blood samples were drawn pre-operatively, 60 minutes after start of surgery, 30 minutes after end of surgery and 24 hours postoperatively. Main Results: Complement was activated and pro-inflammatory interleukins (IL-6 and IL-8) and anti-inflammatory interleukins (IL-10) were released during major colorectal surgery. There was no significant difference between TIVA and inhalational anaesthesia regarding complement activation and cytokine release. Conclusion: Major colorectal surgery leads to activation of the complement cascade and the release of both pro-inflammatory and anti-inflammatory cytokines. There are no significant differences between total intravenous anaesthesia (TIVA) with propofol and remifentanil and inhalational anaesthesia with sevoflurane and fentanyl regarding complement activation and the release of pro- and anti-inflammatory interleukins.
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| 452. |
- Källmark, H., et al.
(författare)
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Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors
- 2023
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Ingår i: Rheumatology. - 1462-0324.
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Tidskriftsartikel (refereegranskat)abstract
- Objective Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known.Methods RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skane University Hospital, Lund and Malmo, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed.Results Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a >= 4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination.Conclusion The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population.Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.
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| 453. |
- Köhler, Per, et al.
(författare)
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Flexible multi electrode brain-machine interface for recording in the cerebellum.
- 2009
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Ingår i: IEEE Engineering in Medicine and Biology Society. Conference Proceedings. - 1557-170X. ; 1, s. 536-538
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Tidskriftsartikel (refereegranskat)abstract
- A new type of chip based microelectrode for acute electrophysiological recordings in the CNS has been developed. It's designed to be adaptable to a multitude of specific neuronal environments, in this study the cerebellar cortex of rat and cat. Photolithographically patternened SU-8 is used to yield flexible and biocompatible penetrating shanks with gold leads. Electrodes with an impedance of about 300 kOmega at 1kHz have excellent signal to noise ratio in acute recordings in cat cerebellum.
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| 454. |
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| 455. |
- Lang, Eric J., et al.
(författare)
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The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper
- 2017
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Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222. ; 16:1, s. 230-252
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Tidskriftsartikel (refereegranskat)abstract
- For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system’s primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less suitable for one or the other of these functions, and why having multiple functions makes sense from an evolutionary perspective. We did not attempt to reach a consensus on the specific role(s) the olivocerebellar system plays in different types of movements, as that will ultimately be determined experimentally; however, collectively, the various contributions highlight the flexibility of the olivocerebellar system, and thereby suggest that it has the potential to act in both the motor learning and motor control functions of the cerebellum.
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| 456. |
- Leffler, Jonatan, et al.
(författare)
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Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus
- 2013
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist of chromatin covered with antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which is known to have reduced activity in SLE. Decreased ability to degrade NETs is associated with disease activity. In the current study we investigated how the ability of serum from SLE patients to degrade NETs varies during the course of SLE as well as what impact this may have for the clinical phenotype of SLE.Methods: Serum from 69 patients with SLE, included in a prospective study, was taken every 60 days for a median of 784 days. The ability of serum to degrade NETs was determined and associated with clinical parameters occurring before and at the time of sampling, as well as after sampling by using conditional logistic regression.Results: As many as 41% of all patients in the study showed decreased ability to degrade NETs at least once, but with a median of 20% of all time points. Decreased degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA. Furthermore, the odds ratio for the patient to develop alopecia and fever after an episode of decreased NETs degradation was increased by four to five times compared to normal.Conclusions: Decreased degradation of NETs is associated with clinical manifestations in SLE and may contribute to disease pathogenesis. Potential therapeutics restoring the ability to degrade NETs could be beneficial for certain patients with SLE.
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| 457. |
- Leonsson, M, et al.
(författare)
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Growth hormone (GH) therapy in GH-deficient adults influences the response to a dietary load of cholesterol and saturated fat in terms of cholesterol synthesis, but not serum low density lipoprotein cholesterol levels.
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:4, s. 1296-303
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Tidskriftsartikel (refereegranskat)abstract
- An increased dietary load of cholesterol (ch) and saturated fat increases serum low density lipoprotein ch (LDL-ch) levels. GH therapy in GH-deficient adults decreases serum LDL-ch levels. In the rat, GH is important for resistance to dietary cholesterol in terms of serum cholesterol levels. The aim of this study was to investigate the influence of GH on the effects of an increase in the intake of cholesterol and saturated fat on serum lipoproteins and markers for cholesterol synthesis in man. Six GH-deficient adults were given an isocaloric diet enriched in cholesterol and saturated fat for 17 days with and without GH therapy (1-1.5 U/day). Serum cholesterol, LDL-ch, apolipoprotein B (apoB), and apoA1 levels increased during the diet period with GH therapy and tended to increase during the diet period without GH. However, GH therapy did not influence the dietary effect on serum cholesterol, LDL-ch, apoA1, or apoB levels. Serum levels of triglycerides, very low density lipoprotein ch, high density lipoprotein ch, and apoE were not affected by diet or GH therapy. GH therapy increased serum lipoprotein(a) levels, but did not affect the response to diet. The serum total delta7-lathosterol/cholesterol ratio increased less during the diet period with GH therapy than during the diet period without GH. Serum 7alpha-hydroxy-4-cholesten-3-one levels tended to increase during both diet periods, but were not influenced by GH treatment. Serum plant sterol levels did not change. These results indicate that GH counteracts an increase in cholesterol synthesis induced by a high fat diet without affecting bile acid synthesis or sterol absorption. GH therapy did not have any major influence on the dietary effects on serum lipoprotein levels.
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| 458. |
- Leonsson, M, et al.
(författare)
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Increased Interleukin-6 levels in pituitary-deficient patients are independently related to their carotid intima-media thickness.
- 2003
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Ingår i: Clinical endocrinology. - 0300-0664. ; 59:2, s. 242-50
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Tidskriftsartikel (refereegranskat)abstract
- Increased cardiovascular morbidity and mortality has been observed in patients with pituitary deficiency and untreated growth hormone deficiency (GHD). We investigated peripheral inflammatory and fibrinolytic markers and their associations with arterial intima-media thickness (IMT) in GHD.Cross-sectional study.Thirty-four patients with GHD, but without cardiovascular disease, were compared to healthy controls matched for age, sex, body mass index (BMI) and smoking habits.IMT of the common carotid artery, C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator antigen (tPA-ag) were measured.Median IL-6 concentrations were increased by 208% and 248% in GHD patients compared to BMI-matched and nonobese controls, respectively. Median CRP and tPA-ag levels were increased by 237% and 167% in patients compared to nonobese controls, but not significantly different compared to BMI-matched controls. Plasma levels of fibrinogen and PAI-1 activity did not differ between groups. Age, low-density lipoprotein (LDL) cholesterol, tPA-ag and IL-6 were positively correlated, and IGF-I was negatively correlated to IMT in the patient group, but only age and IL-6 were independently related to IMT.IL-6 concentrations were increased in GHD patients compared to controls and independently related to IMT in patients. This finding may help to explain the variance in IMT and the increased vascular morbidity and mortality in hypopituitary patients with GHD.
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| 459. |
- Leske, M. Cristina, et al.
(författare)
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Predictors of long-term progression in the early manifest glaucoma trial
- 2007
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Ingår i: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 114:11, s. 1965-1972
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine progression factors at the end of the Early Manifest Glaucoma Trial (EMGT) based on all EMGT patients and evaluate separately patients with higher and lower baseline intraocular pressure (IOP; median split). Design: Cohort of clinical trial participants. Participants: Patients with early open-angle glaucoma randomized to argon laser trabeculoplasty plus betaxolol (n = 129) or no immediate treatment (n = 126), examined every 3 months for up to 11 years. Methods: Cox proportional hazard analyses, expressed by hazard ratios (HRs) and 95% confidence intervals (Cls). Main Outcome Measure: Time to progression, defined by perimetric and photographic disc criteria. Results: Overall progression was 67% when follow-up ended (median, 8 years). Treatment approximately halved progression risk (HR, 0.53; 95% Cl, 0.39-0.72); results were similar for patients with higher and lower baseline IOP (HRs, 0.41 and 0.55). Baseline progression factors (HRs, 1.51-2.12; P<0.01) were higher IOP, exfoliation, bilateral disease, and older age, as previously reported. New baseline predictors were lower ocular systolic perfusion pressure in all patients (<= 160 mmHg; HR, 1.42; 95% Cl, 1.04-1.94), cardiovascular disease history (HR, 2.75; 95% Cl, 1.44-5.26) in patients with higher baseline IOP, and lower systolic blood pressure (BP) (<= 125 mmHg; HR, 0.46; 95% Cl, 0.21-1.02) in patients with lower baseline IOP. Postbaseline progression factors were IOP levels at follow-up, with 12% to 13% average increase per millimeter of mercury in all patients (HRs, 1.12-1.13 per mmHg higher) and similar results in patients with higher and lower baseline IOP (HRs, 1.15 and 1.13 per mmHg higher). Disc hemorrhages (HR, 1.02; 95% Cl, 1.01-1.03 per percent higher frequency) also predicted progression. Thinner central corneal thickness (CCT) (HR, 1.25; 95% Cl, 1.01-1.55 per 40 mu m lower) was a new significant factor, a result observed in patients with higher baseline IOP (HR, 1.42; 95% Cl, 1.05-1.92 per 40 mu m lower) but not lower baseline IOP, with significant IOP-CCT interaction. Conclusions: Treatment and follow-up IOP continued to have a marked influence on progression, regardless of baseline IOP. Other significant factors were age, bilaterality, exfoliation, and disc hemorrhages, as previously determined. Lower systolic perfusion pressure, lower systolic BP, and cardiovascular disease history emerged as new predictors, suggesting a vascular role in glaucoma progression. Another new factor was thinner CCT, with results possibly indicating a preferential CCT effect with higher IOP. Ophthalmology 2007,114: 1965-1972 (C) 2007 by the American Academy of Ophthalmology.
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| 460. |
- Leske, MC, et al.
(författare)
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Factors for glaucoma progression and the effect of treatment - The Early Manifest Glaucoma Trial
- 2003
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Ingår i: Archives of Ophthalmology. - : American Medical Association (AMA). - 0003-9950. ; 121:1, s. 48-56
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of EMGT treatment. Setting/Participants: Two hundred fifty-five open-angle glaucoma patients randomized to argon laser trabeculoplasty plus topical betaxolol or no immediate treatment (129 treated; 126 controls) and followed up every 3 months. Methods: Progression was determined by perimetric and photographic optic disc criteria. Patient-based risk of progression was evaluated using Cox proportional hazard regression models and was expressed as hazard ratios (HR) with 95% confidence intervals (95% CI). Results: After 6 years, 53% of patients progressed. In multivariate analyses, progression risk was halved by treatment (HR=0.50; 95% CI, 0.35-0.71). Predictive baseline factors were higher intraocular pressure (IOP) (ie, the higher the baseline IOP, the higher the risk), exfoliation, and having both eyes eligible (each of the latter 2 factors doubled the risk), as well as worse mean deviation and older age. Progression risk decreased by about 10% with each millimeter of mercury of IOP reduction from baseline to the first follow-up visit (HR=0.90 per millimeter of mercury decrease; 95% CI, 0.86-0.94). The first IOP at that visit (3 months' follow-up) was also related to progression (HR=1.11 per millimeter of mercury higher; 95% CI, 1.06-1.17), as was the mean IOP at follow-up (HR=1.13 per millimeter of mercury higher; 95% CI, 1.07-1.19). The percent of patient follow-up visits with disc hemorrhages was also related to progression (HR=1.02 per percent higher; 95% CI, 1.01-1.03). No other factors were identified. Conclusions: Patients treated in the EMGT had half of the progression risk of control patients. The magnitude of initial IOP reduction was a major factor influencing outcome. Progression was also increased with higher baseline IOP, exfoliation, bilateral disease, worse mean deviation, and older age, as well as frequent disc hemorrhages during follow-up. Each higher (or lower) millimeter of mercury of IOP on follow-up was associated with an approximate 10% increased (or decreased) risk of progression.
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