| 1. |
- Sjölin, Jan-Gunnar, et al.
(författare)
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Bildens retorik: Exemplet Endre Nemes
- 1994
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Ingår i: Konst och bildning. Studier tillägnade Sven Sandström den 1 juli 1993. - 9177988132 ; , s. 222-240
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Sjölin, Jan-Gunnar, et al.
(författare)
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Inledning
- 1993
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Ingår i: Att tolka bilder. Bildtolkningens teori och praktik med exempel på tolkningar av bilder från 1850 till i dag. - 9144347316
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Sjölin, Jan-Gunnar, et al.
(författare)
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Inledning
- 2003
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Ingår i: Om konstkritik: Studier av konstkritik i svensk dagspress 1990-2000. - 9189638026 ; , s. 11-33
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Sjölin, Jan-Gunnar, et al.
(författare)
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Inledning
- 1998
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Ingår i: Att tolka bilder. Bildtolkningens teori och praktik med exempel på tolkningar av bilder från 1850 till i dag. - 9144008856 ; , s. 11-194
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Sjölin, Jan-Gunnar, et al.
(författare)
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Måleri – det utvidgade fältet. En studie av 20 kritikers respons på en programutställning
- 2003
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Ingår i: Om konstkritik: Studier av konstkritik i svensk dagspress 1990-2000. - 9189638026 ; , s. 64-141
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Jan-Gunnar Sjölin's study deals with the response of 20 critics to the exhibition "Painting – the Extended Field" 1996-1997. The study concentrates primarily on the way the critics describe, contextualise, interpret and value the works that lie outside the traditional sphere of painting.
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| 6. |
- Floros, Lefteris, et al.
(författare)
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Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden
- 2019
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Ingår i: BMC Infectious Diseases. - : BMC. - 1471-2334. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden.Methods: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs.Results: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%.Conclusions: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.
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| 7. |
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| 8. |
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| 9. |
- Mellhammar, Lisa, et al.
(författare)
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Sepsis - vår tids okända folksjukdom
- 2015
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112:47
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Pauksen, Karlis, et al.
(författare)
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Granulocyte-macrophage colony-stimulating factor as immunomodulating factor together with influenza vaccination in stem cell transplant patients
- 2000
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 30:2, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation (SCT). The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition (HAI) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination, compared with the 53 who did not. In the subgroup of allogeneic SCT patients, HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group (P<.05). ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A (P<.05) and B (P<.01). At early vaccination, 4-12 months after stem cell transplantation, these responses were more pronounced. GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients, but only to a limited extent.
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| 11. |
- Wernerman, Jan, et al.
(författare)
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[Septic shock--a condition with great potential for improvement. Management and therapy].
- 2003
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 100:26-27, s. 2288-91
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Tidskriftsartikel (refereegranskat)abstract
- There is a recent focus upon treatment of septic shock, related to the publication of a number of interesting studies during the last two years. These studies indicate that patient outcome can be improved, provided care is organized so as to optimize and expedite initial treatment of the patient in septic shock. In parallel, new drugs have been launched using rather aggressive marketing, which calls for recommendations and advice from professional experts who are independent of the pharmaceutical industry. This article reviews the studies that have engendered a new optimism in the treatment of septic shock. These "new" therapies are presented in a total context with a temporal perspective. It is suggested that emergency sepsis teams be instituted at hospitals.
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| 12. |
- Angelin, Martin, et al.
(författare)
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Qdenga® - A promising dengue fever vaccine; can it be recommended to non-immune travelers?
- 2023
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Ingår i: Travel Medicine and Infectious Disease. - : Elsevier. - 1477-8939 .- 1873-0442. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows high efficacy against virologically confirmed dengue and severe dengue in clinical studies on 4–16-year old's living in endemic areas. For individuals 16–60 years old only serological data exists and there is no data for individuals > 60 years. Its use as a travel vaccine is still unclear. We present the studies behind the approval and the recommendations for travelers as issued by the Swedish Society for Infectious Diseases Physicians.
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| 13. |
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| 14. |
- Arnell, Kai, et al.
(författare)
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Cerebrospinal fluid shunt infections in children over a 13-year period : anaerobic cultures and comparison of clinical signs of infection with Propionibacterium acnes and with other bacteria
- 2008
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Ingår i: Journal of neurosurgery. Pediatrics. - 1933-0707. ; 1:5, s. 366-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: Shunt infections represent a major problem with risk for sequelae and even death. The aim in this retrospective study was to analyze the incidence, origin, and clinical presentation of shunt infections, with special reference to the results of cultures for anaerobic organisms performed in addition to the usual tests, to prolonged incubation times, and to infections caused by Propionibacterium acnes. METHODS: The medical records of 237 hydrocephalic children (age range 0-15 years) in whom operations were performed by a pediatric surgeon at Uppsala University Hospital during a 13-year period were reviewed. RESULTS: Thirty-four verified or suspected intraventricular shunt infections and 5 distal catheter infections occurred after 474 operations. Skin bacteria, such as coagulase-negative staphylococci ([CoNS], 19 patients), Staphylococcus aureus (7 patients), and P. acnes (6 patients) predominated. The addition of anaerobic cultures and prolonged incubation times increased the verification of shunt infection by more than one third. Children with P. acnes infection were significantly older, had a lower body temperature, fewer cerebrospinal fluid (CSF) leukocytes, a higher CSF/blood glucose ratio, more distal catheter infections, and other sources of infection. Four had an abdominal pseudocyst. Children < 1 year of age and infected with CoNS were more affected than older children with systemic and local symptoms. In children with distal catheter infection and growth of propionibacteria at the time of the distal catheter and valve replacement, no follow-up antibiotic treatment was necessary. CONCLUSIONS: Addition of anaerobic cultures and prolonged incubation times led to an increase in the detection of shunt infections. Infections caused by propionibacteria often result in mild symptoms that may be overlooked if adequate anaerobic cultures are not obtained.
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| 15. |
- Arnell, Kai, 1945-
(författare)
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Cerebrospinal Fluid Shunts in Children : Technical Considerations and Treatment of Certain Complications
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ventriculo-peritoneal shunting is the most commonly used method for the treatment of paediatric hydrocephalus. Despite improved shunts and surgical techniques there are still complications. This retrospective study focuses on diagnoses and treatment of shunt malfunction and infections. Cost/benefit of using an adjustable shunt was assessed. Two adjustable cerebrospinal fluid shunts and their compatible antisiphon devices were compared in-vitro. In 21 of 46 children the standard shunt was changed to an adjustable one due to over-drainage. Adjustment of the shunt was performed in 73% of the children thereby avoiding surgery in several cases. This was a financial advantage. Ascites or an abdominal pseudocyst without infection was detected in eight children due to resorption difficulties. A ventriculo-atrial shunt was inserted for a period of time. In three children it could successfully be reverted to a ventriculo-peritoneal. In six children papilloedema was the only sign of shunt dysfunction. At revision the intracranial pressure ranged from 25 to 52 cm H2O. Fundoscopic examination in children older than 8 years may detect symptomless shunt malfunction. During a 13-year period 39 shunt infections were diagnosed. Skin bacteria were found in 80%. Prolonged and anaerobic cultures increased the detection rate by more than one third. The intraventricular infections were treated with intraventricular and systemic antibiotics resulting in quick sterilisation. No relapses were encountered. In five older children with distal catheter infection Propionibacterium acne was found. These were treated with intravenous antibiotics and exchanging of the shunt system. Strata NSCTM and Codman HakimTM worked according to the manufacturers except at the lowest setting. The resistance was below and in the lower range of the physiological one respectively. The antisiphon device of Strata shunt had to be placed in line with shunt to function properly.
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| 16. |
- Arnell, Kai, et al.
(författare)
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Treatment of cerebrospinal fluid shunt infections in children using systemic and intraventricular antibiotic therapy in combination with externalization of the ventricular catheter : efficacy in 34 consecutively treated infections
- 2007
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Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 107:3, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: There are no randomized studies comparing the efficacy of different antibiotic regimens for the treatment of cerebrospinal fluid (CSF) shunt infections, and in the studies that have been reported, efficacy data are limited. The aim of this study was therefore to report the authors' experience using a specific protocol for the management of shunt infections in children. Standard treatment included a two-stage procedure involving externalization of the ventricular catheter in combination with intraventricular and systemic administration of antibiotic medication followed by shunt replacement. Intraventricular treatment consisted of daily instillations of vancomycin or gentamicin with trough concentrations held at high levels of 7 to 17 mg/L for both antibiotic agents. METHODS: During a 13-year study period, the authors treated 34 consecutive intraventricular shunt infections in 30 children. Infections with coagulase-negative staphylococci predominated, and Gram-negative bacterial infection occurred in five children. Ten of the children were initially treated with intravenous antibiotic therapy for at least 3 days, but this treatment did not sterilize the CSF. After externalization of the ventricular catheter, high-dose intraventricular treatment was given for a median of 8 days (range 3-17 days) before shunt replacement. RESULTS: The CSF was found to be sterile (cultures were negative for bacteria) in one of three, seven of eight, 20 of 20, and six of six cases after 1, 2, 3, and more than 3 days' treatment, respectively. In no case was any subsequent culture positive after a negative result had been obtained. Clinical symptoms resolved in parallel with the sterilization of the CSF. There were no relapses or deaths during the 6-month follow-up period, and there have been none as of April 2007. CONCLUSIONS: Despite the ventricular catheter being left in place and the short duration of therapy, the treatment regimen described by the authors resulted in quick sterilization of the CSF, a low relapse rate, and survival of all patients in this series.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Brink, Magnus, 1960, et al.
(författare)
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Meropenem versus cefotaxime and ampicillin as empirical antibiotic treatment in adult bacterial meningitis: A quality registry study, 2008 to 2016
- 2019
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Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:11
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 American Society for Microbiology. All Rights Reserved. Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December 2016. Propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30 days was the primary outcome. The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. Using propensity score matching, the 30-day mortality rates were 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases, the odds ratio (OR) for 30-day mortality for meropenem versus cefotaxime plus ampicillin was 1.15 (confidence interval [CI], 0.41 to 3.22; P = 0.79). The OR for 90-day mortality was 1.47 (CI, 0.62 to 3.52; P = 0.38) and for unfavorable outcome was 1.10 (CI, 0.75 to 1.63; P = 0.62). The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as an empirical treatment for the majority of patients with ABM.
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| 21. |
- Calissendorff, Jan, et al.
(författare)
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Long-Term Outcome of Graves' Disease : A Gender Perspective
- 2023
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Ingår i: Women's Health Reports. - : Mary Ann Liebert. - 2688-4844. ; 4:1, s. 487-496
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective.Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided.Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05).Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms.
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| 22. |
- Carlsson, Markus, et al.
(författare)
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Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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| 23. |
- Castegren, Markus, et al.
(författare)
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Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin
- 2012
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Ingår i: Shock. - 1073-2322 .- 1540-0514. ; 37:5, s. 501-510
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Tidskriftsartikel (refereegranskat)abstract
- Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.
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| 24. |
- Castegren, Markus, 1976-, et al.
(författare)
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Endotoxin tolerance variation over 24 h during porcine endotoxemia : association to changes in circulation and organ dysfunction
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e53221-
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Tidskriftsartikel (refereegranskat)abstract
- Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known about the temporal development of ET. Further, in acute respiratory distress syndrome ET correlates to the severity of the disease, suggesting a complicated relation between ET and organ dysfunction. Eighteen pigs were subjected to intensive care and a continuous endotoxin infusion for 24 h with the aim to study the time course of early ET and to relate ET to outcome in organ dysfunction. Three animals served as non-endotoxemic controls. Blood samples for cytokine analyses were taken and physiological variables registered every third hour. Production of TNF-α, IL-6, and IL-10 before and after endotoxin stimulation ex vivo was measured. The difference between cytokine values after and before ex vivo LPS stimulation (Δ-values) was calculated for all time points. ΔTNF-α was employed as the principal marker of ET and lower ΔTNF-α values were interpreted as higher levels of ET. During endotoxin infusion, there was suppression of ex vivo productions of TNF-α and IL-6 but not of IL-10 in comparison with that at 0 h. The ex vivo TNF-α values followed another time concentration curve than those in vivo. ΔTNF-α was at the lowest already at 6 h, followed by an increase during the ensuing hours. ΔTNF-α at 6 h correlated positively to blood pressure and systemic vascular resistance and negatively to cardiac index at 24 h. In this study a temporal variation of ET was demonstrated that did not follow changes in plasma TNF-α concentrations. Maximal ET occurred early in the course and the higher the ET, the more hyperdynamic the circulation 18 h later.
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| 25. |
- Castegren, Markus, et al.
(författare)
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Initial levels of organ failure, microbial findings and mortality in intensive care-treated primary, secondary and tertiary sepsis
- 2015
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Ingår i: Critical Care and Resuscitation. - 1441-2772. ; 17:3, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Analysis of whether patients with primary, secondary and tertiary sepsis, defined by the presence or absence of recent systemic inflammation-inducing events before the onset of sepsis, differ in clinical presentation, microbiological test results, treatment received and outcome. Design, setting and participants: A retrospective observational study in a single, general intensive care unit, of all patients treated for severe sepsis or septic shock from 2006 to 2011. Patients with haematological malignancies, with immunosuppressive diseases or being treated with immunosuppressive drugs were excluded. Interventions: None. Main outcome measures: Sequential Organ Failure Assessment score, incidence of organ failure, microbiological results of blood cultures and mortality. Results: We included 213 patients, who were classified as having primary (n = 121), secondary (n = 65) or tertiary sepsis (n = 27). The groups differed significantly in SOFA score, the incidence of kidney failure and coagulation failure at onset of sepsis in the ICU, as well as in blood culture findings. No differences in 7-day or 28-day mortality were seen, but the time of death occurred earlier among non-survivors in the primary sepsis group. Conclusions: Inflammatory insults before the onset of sepsis affect the clinical picture, blood microbial findings, and in non-survivors, the time of death. These results could, if validated in a prospective study, form a basis for a novel and simple strategy for stratifying patients in clinical studies for immunomodulation therapies in sepsis.
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| 26. |
- Castegren, Markus, 1976-
(författare)
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Modulating Organ Dysfunction in Experimental Septic Shock : Effects of Aminoglycosides, Antiendotoxin Measures and Endotoxin Tolerance
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis is a common diagnose in the intensive care population, burdened with a high mortality. The systemic inflammatory reaction underlying the development of septic organ dysfunction can be modeled using Gram-negative bacterial lipopolysaccharide, endotoxin. This thesis used a porcine endotoxemic experimental sepsis model to address clinical questions difficult to answer in clinical trials; furthermore a model of secondary sepsis was developed. No additional effect on the development of renal dysfunction by tobramycin was found, indicating that a single dose of tobramycin does not further compromise renal function in inflammatory-induced acute kidney injury. Antiendotoxin treatment had no measurable effect on TNF-α-mediated toxicity once the inflammatory cascade was activated. There was an effect on the leukocyte response that was associated with improvements in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure. The lungs stood out compared to the other organ systems as having a threshold endotoxin dose for the protective effect of endotoxin tolerance. As to the development of circulatory and renal dysfunction, tolerance to endotoxin was evident regardless of the endotoxin pre-exposure and challenge dose. There was a temporal variation of endotoxin tolerance that did not follow changes in plasma TNF-α concentrations and maximal tolerance was seen very early in the course. More pronounced endotoxin tolerance at the time of maximum tolerance was associated with a more marked hyperdynamic circulation, reduced oxygen consumption and thrombocytopenia eighteen hours later. It might be of interest to use the experimental model of long-term endotoxemia followed by a second hit, which has been designed to resemble an intensive care setting, for the study of treatment effects of immunomodulating therapies in secondary sepsis.
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| 27. |
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| 28. |
- Chryssanthou, Erja, et al.
(författare)
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Post-antifungal effect of amphotericin B and voriconazole against germinated Aspergillus fumigatus conidia
- 2008
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 61:6, s. 1309-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The post-antifungal effect (PAFE) of amphotericin B and voriconazole on germinated Aspergillus fumigatus conidia was studied using the BacT/Alert detection system based on fungal CO(2) production. METHODS: Germinated conidia of A. fumigatus were exposed to 1-10x MIC of amphotericin B for 1 and 4 h and to 2.5-40x MIC of voriconazole for 4 and 24 h. After removal of the drug by washing, similar numbers of exposed and control germlings were inoculated into Pedi-BacT culture bottles. CO(2) production was automatically monitored until the bottles signalled positive. The difference in time for positive signals in drug-exposed and control bottles was used to calculate the PAFE. RESULTS: The killing rate of amphotericin B against germlings was both concentration- and time-dependent, as has been previously found for actively growing hyphae. Similarly, voriconazole showed fungicidal effect after 24 h of exposure, but not after 4 h. Amphotericin B induced a long concentration- and time-dependent PAFE, whereas voriconazole resulted in a short and dose-independent PAFE that was significantly longer after 24 h than after 4 h of exposure. CONCLUSIONS: An automated method is presented for the determination of PAFE on filamentous fungi using quantifiable numbers of germinated conidia. In contrast to previous results obtained from conidia, this method could demonstrate a PAFE of amphotericin B on Aspergillus that shared characteristics similar to that on Candida spp.
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| 29. |
- Dahlman, I, et al.
(författare)
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Adipose tissue pathways involved in weight loss of cancer cachexia
- 2010
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 102:10, s. 1541-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. METHODS: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n=13) or without (n=14) cachexia. RESULTS: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia. CONCLUSIONS: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin.
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| 30. |
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| 31. |
- Edberg, M, et al.
(författare)
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Neurointensive care of patients with severe community-acquired meningitis
- 2011
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 55:6, s. 732-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Reports about neurointensive care of severe community-acquired meningitis are few. The aims of this retrospective study were to review the acute clinical course, management and outcome in a series of bacterial meningitis patients receiving neurointensive care.METHODS:Thirty patients (median age 51, range 1-81) admitted from a population of 2 million people during 7 years were studied. The neurointensive care protocol included escalated stepwise treatment with mild hyperventilation, cerebrospinal fluid (CSF) drainage, continuous thiopentotal infusion and decompressive craniectomy. Clinical outcome was assessed using the Glasgow outcome scale.RESULTS:Twenty-eight patients did not respond to commands on arrival, five were non-reacting and five had dilated pupils. Twenty-two patients had positive CSF cultures: Streptococcus pneumoniae (n=18), Neisseria meningitidis (n=2), β-streptococcus group A (n=1) and Staphylococcus aureus (n=1). Thirty-five patients were mechanically ventilated. Intracranial pressure (ICP) was monitored in 28 patients (intraventricular catheter=26, intracerebral transducers=2). CSF was drained in 15 patients. Three patients received thiopentothal. Increased ICP (>20 mmHg) was observed in 7/26 patients with available ICP data. Six patients died during neurointensive care: total brain infarction (n=4), cardiac arrest (n=1) and treatment withdrawal (n=1). Seven patients died after discharge, three due to meningitis complications. At follow-up, 14 patients showed good recovery, six moderate disability, two severe disability and 13 were dead.CONCLUSION:Patients judged to have severe meningitis should be admitted to neurointensive care units without delay for ICP monitoring and management according to modern neurointensive care principles.
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| 32. |
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| 33. |
- Eriksson, Britt-Marie, et al.
(författare)
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Circulating soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in immunocompetent and renal transplant patients:correlation with cytomegalovirus disease and renal function
- 2001
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 33:5, s. 350-354
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Tidskriftsartikel (refereegranskat)abstract
- The plasma levels of the soluble adhesion molecules, soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1), were measured before and after transplantation in 26 renal transplant recipients, and in 173 longitudinally collected samples in 17 of the patients. The patients were carefully monitored for the presence of cytomegalovirus (CMV) infection and rejection. Forty healthy blood donors and 12 otherwise healthy subjects with symptomatic primary CMV infections served as controls. During CMV disease, plasma levels of sVCAM-1 and sICAM-1 were elevated in both renal transplant patients and otherwise healthy subjects with CMV disease. The sVCAM-1 levels were strongly elevated before transplantation in renal transplant recipients and correlated with creatinine levels. Increased sVCAM-1 levels were also registered during rejection episodes. CMV disease, per se, is associated with markedly increased levels of sVCAM-1 and sICAM-1. There is also a correlation of sVCAM-1 levels with serum creatinine levels. Thus, the presence of CMV infection and renal function are factors that must be considered in further studies of soluble adhesion molecules.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Furebring, Mia, 1962-
(författare)
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C5a Receptor Expression in Severe Sepsis and Septic Shock
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In patients with sepsis, the activation of the cascade systems, for example the complement system with the generation of C5a, is followed by a state of immunosuppression with impaired bactericidal capacity caused by suppression of the neutrophil granulocytes. To inhibit the C5a-induced systemic inflammatory and the following anti-inflammatory responses, different anti-C5a strategies have been successful in experimental models of sepsis. In animals and in healthy volunteers after injection of lipopolysaccharide (LPS), an up-regulation of the C5a receptor (C5aR) has been reported. Before designing clinical studies, it was of importance to increase the knowledge of C5a and C5aR regulation in humans. At the time when the diagnosis of severe sepsis or septic shock can be established clinically, granulocyte C5aR expression, analysed by flow cytometer, was shown to be reduced, whereas monocyte C5aR expression was unchanged. There was a correlation between granulocyte C5aR expression and the severity of disease, as measured by the APACHE II score. Ex vivo incubation of whole blood with LPS resulted in a reduction in granulocyte C5aR expression. Such a reduction was not found in isolated cells, indicating that the effect was mediated via plasma factors, such as C5a, IL-8 and TNF-α which all were shown to reduce C5aR expression ex vivo.Although there was a trend between chemotaxis, as measured by migration in a modified Boyden chamber, and C5aR expression on granulocytes from patients with severe sepsis or septic shock or from healthy individuals, the correlation failed to reach statistical significance.It is concluded that granulocyte C5aR expression is affected by several plasma factors and that a reduction is clinically evident at the time of the sepsis diagnosis. Reduced granulocyte C5aR expression is associated with an impaired chemotaxis but does not alone limit the chemotactic response.
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| 38. |
- Furebring, Mia, et al.
(författare)
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Differential expression of the C5a receptor and complement receptors 1 and 3 after LPS stimulation of neutrophils and monocytes
- 2004
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 60:5, s. 494-499
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Tidskriftsartikel (refereegranskat)abstract
- Animal experiments recently suggested that administration of anti-C5a, anti-C5a receptor or soluble complement receptor type-1 may be of value in the treatment of septic shock. Because results regarding C5a receptor expression (C5a-R, CD-88) have been found to differ between septic animals and patients, the aim of this study was to investigate the neutrophil and monocyte receptor expression of CD-88 and complement receptor-1 (CR-1, CD-35) after stimulation with lipopolysaccharide (LPS) ex vivo. Whole blood or isolated neutrophils and monocytes from healthy people were incubated with LPS in a dose range of 0.1-1000 ng/ml. The expressions of CD-88 and CD-35 were analysed by means of flow cytometry. For comparison, the expressions of complement receptor-3 (CR-3, CD-11b/CD-18), Fc-gamma receptor type-I (CD-64) and CEACAM-8 (CD-66b) were also investigated. In whole blood, CD-88 expression on neutrophils was reduced (P < 0.05). The expressions of CD-35 and CD-11b were increased both on neutrophils (P < 0.001; P < 0.05) and on monocytes (P < 0.001; P < 0.001). No effect was observed on isolated cells. In agreement with the findings in septic patients, LPS reduced the neutrophil C5a-R expression, whereas the expressions of CR-1 and CR-3 were increased. The effects of LPS were indirect and were mediated via factors in the blood. The clinical significance of this is not known, but may be associated with decreased chemotaxis.
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| 39. |
- Furebring, Mia, et al.
(författare)
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Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis
- 2002
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Ingår i: Critical Care. - 1364-8535 .- 1466-609X. ; 6:4, s. 363-370
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Treatment of patients with severe sepsis with agents antagonising the effects of C5a has been proposed based on beneficial effects in animal experiments and in vitro studies demonstrating upregulation of the C5a receptor (CD88) on granulocytes by endotoxin. MATERIALS AND METHODS: CD88 expression on leukocytes from 12 patients with severe sepsis or septic shock was analysed by flow cytometer, and serum complement factors C3a and C5b-9 were measured by enzyme immunoassay techniques. RESULTS: The granulocyte CD88 expression on day 1 was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P < 0.001), despite complement activation, while the monocyte CD88 expression was unchanged. The receptor reduction correlated significantly to the APACHE II score (r2 = 0.35, P < 0.05). The recovery of CD88 expression was slow. DISCUSSION: In contrast to the findings in animals, it is concluded that granulocyte CD88 expression is reduced at the time when the diagnosis of severe sepsis or septic shock can clinically be made. The reason for this needs further investigation but it may be due to a previous complement activation or to cytokine effects.
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| 40. |
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| 41. |
- Glimaker, Martin, et al.
(författare)
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Adult Bacterial Meningitis : Earlier Treatment and Improved Outcome Following Guideline Revision Promoting Prompt Lumbar Puncture
- 2015
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 60:8, s. 1162-1169
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Tidskriftsartikel (refereegranskat)abstract
- Background. In suspected acute bacterial meningitis (ABM), cerebral computerized tomography (CT) is recommended before lumbar puncture (LP) if mental impairment. Despite guideline emphasis on early treatment, performing CT prior to LP implies a risk of delayed treatment and unfavorable outcome. Therefore, Swedish guidelines were revised in 2009, deleting impaired mental status as a contraindication for LP without prior CT scan. The aim of the present study was to evaluate the guideline revision. Methods. The Swedish quality registry for community-acquired ABM was analyzed retrospectively. Door-to-antibiotic time and outcome were compared among patients treated 2005-2009 (n = 394) and 2010-2012 (n = 318). The effect of different LP-CT sequences was analyzed during 2008-2012. Results. Adequate treatment was started 1.2 hours earlier, and significantly more patients were treated <2 hours from admission 2010-2012 than 2005-2009. Compared with CT before LP, immediate LP resulted in 1.6 hours earlier treatment, significant increase in door-to-antibiotic times of <1 and <2 hours, and a favorable outcome. In 2010-2012, mortality was lower (6.9% vs 11.7%) and the risk of sequelae at follow-up decreased (38% vs 49%) in comparison with 2005-2009. Treatment delay resulted in a significantly increased risk for fatal outcome, with a relative increase in mortality of 12.6% per hour of delay. Conclusions. The deletion of impaired mental status as contraindication for prompt LP and LP without prior CT scan are associated with significantly earlier treatment and a favorable outcome. A revision of current international guidelines should be considered.
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| 42. |
- Glimaker, M., et al.
(författare)
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Early lumbar puncture in adult bacterial meningitis-rationale for revised guidelines
- 2013
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:9, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- Current international guidelines recommend cerebral computerized tomography (CT) before lumbar puncture (LP) in many adults with suspected acute bacterial meningitis (ABM), due to concern about LP-induced cerebral herniation. Despite guideline emphasis on early treatment based on symptoms, performing CT prior to LP implies a risk of delayed ABM treatment, which may be associated with a fatal outcome. Firm evidence for LP-induced herniation in adult ABM is absent and brain CT cannot discard herniation. Thus, the recommendation to perform CT before LP may contribute to an avoidable delay of LP and ABM treatment. The inappropriate use of the diagnostic treatment sequence of brain CT scan, followed by LP, followed by antibiotics and corticosteroids should be avoided in adults with suspected ABM by omitting needless contraindications for LP, thus eliminating an unnecessary fear of immediate LP. Revised Swedish guidelines regarding early LP are presented, and the background documentation and reasons for omitting impaired consciousness, new onset seizures, and immunocompromised state as contraindications to LP are discussed.
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| 43. |
- Glimaker, Martin, et al.
(författare)
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Etiology, clinical presentation, outcome and the effect of initial management in immunocompromised patients with community acquired bacterial meningitis
- 2020
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Ingår i: Journal of Infection. - : W B SAUNDERS CO LTD. - 0163-4453 .- 1532-2742. ; 80:3, s. 291-297
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim was to analyze differences in clinical presentation, etiology, management, and outcome between immunocompromised and immunocompetent patients with acute bacterial meningitis (ABM). Methods: Data were extracted from 1056 adult ABM patients prospectively registered in the national Swedish quality register for ABM during 2008-2017. Primary endpoint was 30-day mortality and secondary endpoints 90-day mortality and unfavorable outcome. Results: An immunocompromised state was observed in 352 (33%) of the 1056 patients. Streptococcus pneumoniae dominated in both immunocompromised and immunocompetent patients (53% in both groups), whereas L monocytogenes occurred in 11% and 2%, respectively. The unadjusted odds ratio (OR) for 30-day mortality in immunocompromised compared to immunocompetent patients was 1.68 (95% confidence interval (CI): 1.07-2.63). Adjusted for age, sex, and mental status on admission the OR was 1.34 (CI: 0.82-2.21). Adjusted also for time to antibiotic treatment and corticosteroids the OR was 1.10 (CI: 0.59-2.05), and in patients without Listeria meningitis 0.98 (CI: 0.50-1.90). Although, the ORs were higher for 90-day mortality and unfavorable outcome the effects of adjustments were similar. Conclusion: Mortality in immunocompromised patients with ABM is only moderately increased unless caused by Listeria. This difference is further reduced in patients given early antibiotic treatment and adjunctive corticosteroids. Funding: This work was supported by Stockholm County Council.
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| 44. |
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| 45. |
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| 46. |
- Glimåker, M., et al.
(författare)
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Betamethasone and dexamethasone in adult community-acquired bacterial meningitis : a quality registry study from 1995 to 2014
- 2016
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 22:9, s. 814.e1-814.e7
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Tidskriftsartikel (refereegranskat)abstract
- Acute bacterial meningitis (ABM) is a highly lethal disease. Available data support the use of corticosteroids in high-income countries, but the effect on mortality is still controversial. The effects of corticosteroids on mortality and sequelae were evaluated in the national Swedish quality registry. In total, during 1995-2014 1746 adults with ABM were included, of whom 989 were treated with corticosteroids (betamethasone, n = 766; dexamethasone, n = 248; methylprednisolone, n = 2), 498 were not given corticosteroids and in 259 patients data for corticosteroids were missing. Fatal outcome was observed in 8.9% of the patients in the corticosteroid-treated group vs. 17.9% in the non-corticosteroid-treated group (p < 0.001), resulting in an odds ratio (OR) of 0.57 with a 95% confidence interval (CI) of 0.40-0.81 adjusted for age, sex, mental status, and door-to-antibiotic time. In patients with meningitis caused by S. pneumoniae, mortality was 10.2% in the corticosteroid-treated group and 21.3% in the noncorticosteroid-treated group (p < 0.001) with an adjusted OR of 0.50 (95% CI 0.31-0.80). In ABM patients with non-pneumococcal aetiology the adjusted OR was 0.71 (95% CI 0.40-1.26). Lower mortality was observed in the corticosteroid-treated group with impaired mental status, whereas no significant difference was found in patients with unaffected mental status. The adjusted ORs for betamethasone and dexamethasone were 0.49 (95% CI 0.28-0.84) and 0.61 (95% CI 0.37-1.01), respectively. Corticosteroid treatment decreases mortality in ABM and should be administered initially with antibiotics in adult ABM patients with impaired mental status regardless of presumed aetiology. Betamethasone seems to be at least as effective as dexamethasone.
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| 47. |
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| 48. |
- Glimåker, Martin, et al.
(författare)
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Lumbar Puncture Performed Promptly or After Neuroimaging in Acute Bacterial Meningitis in Adults : A Prospective National Cohort Study Evaluating Different Guidelines.
- 2018
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 66:3, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early treatment is pivotal for favorable outcome in acute bacterial meningitis (ABM). Lumbar puncture (LP) is the diagnostic key. The aim was to evaluate the effect on outcome of adherence to European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), and Swedish guidelines regarding neuroimaging before LP.Methods: The cohort comprised 815 adult ABM patients in Sweden registered prospectively between 2008 and 2015. Primary endpoint was in-hospital mortality and secondary endpoint was favorable outcome at 2-6 months of follow-up.Results: Indications for neuroimaging before LP existed in 7%, 32%, and 65% according to Swedish, ESCMID, and IDSA guidelines, respectively. The adjusted odds ratio (aOR) was 0.48 (95% confidence interval [CI], .26-.89) for mortality and 1.52 (95% CI, 1.08-2.12) for favorable outcome if Swedish guidelines were followed. ESCMID guideline adherence resulted in aOR of 0.68 (95% CI, .38-1.23) for mortality and 1.05 (95% CI, .75-1.47) for favorable outcome. Following IDSA recommendations resulted in aOR of 1.09 (95% CI, .61-1.95) for mortality and 0.59 (95% CI, .42-.82) for favorable outcome. Performing prompt vs neuroimaging-preceded LP was associated with aOR of 0.38 (95% CI, .18-.77) for mortality and 2.11 (95% CI, 1.47-3.00) for favorable outcome. The beneficial effect of prompt LP was observed regardless of mental status and immunosuppression.Conclusions: Adherence to Swedish guidelines in ABM is associated with decreased mortality and increased favorable outcome in contrast to adherence to ESCMID or IDSA recommendations. Our findings support that impaired mental status and immunocompromised state should not be considered indications for neuroimaging before LP in patients with suspected ABM.
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| 49. |
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| 50. |
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