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Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients : a prospective study
- 2001
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 47:1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CdAD) was prospectively determined in a population of 2462 patients recruited from five Swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. AAD developed in 4.9% of the treated patients. Faecal samples were obtained from 69% of patients with AAD and 55.4% were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9% at the participating centres (P < 0.001). The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units (6.7 and 7.1%, respectively). There was no difference in frequency of AAD when analysed with respect to gender or age. Medical interventions (laxative treatment, endoscopy and abdominal surgery) or presence of one concomitant disease (diabetes, malignancy, chronic renal disease and inflammatory bowel disease) did not significantly affect the frequency of AAD, whereas patients suffering from two or more of these illnesses had significantly (P = 0.001) higher frequencies of AAD. Patients treated with antibiotics for 3 days had a significantly (P = 0.009) lower frequency of AAD than those treated for longer periods. Treatment with cephalosporins, clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD. With specimens from one centre, 62.5% of tested patients with AAD and 33.8% of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool samples was significantly associated with AAD IP = 0.003), the causal relationship with diarrhoea is not always evident.
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| 10. |
- Sunesson, Ylva, et al.
(författare)
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Role of the Base in Buchwald-Hartwig Amination
- 2014
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 79:24, s. 11961-11969
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Tidskriftsartikel (refereegranskat)abstract
- The BuchwaldHartwig amination has been investigated theoretically and experimentally to examine the scope of possible bases under different reaction conditions. Nonpolar solvents resist the formation of new charges. Therefore, the base should be anionic to be able to deprotonate the neutral palladiumamine complex and/or expel the anionic leaving group (bromide). The calculated barrier for the organic base DBU was found to be prohibitively high. In polar solvent, dissociation of bromide becomes possible, but here the base will instead form a complex with palladium, creating an overly stable resting state. The conclusions for both solvent classes hold for both a hindered monodentate phosphine and the labile bidentate ligand BINAP. The computational studies were supported by experimental testing of a range of bases using BINAP in two different solvents, toluene and DMF.
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| 11. |
- Thanert, R, et al.
(författare)
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Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3846-
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Tidskriftsartikel (refereegranskat)abstract
- Necrotizing soft tissue infections (NSTIs) are devastating infections caused by either a single pathogen, predominantly Streptococcus pyogenes, or by multiple bacterial species. A better understanding of the pathogenic mechanisms underlying these different NSTI types could facilitate faster diagnostic and more effective therapeutic strategies. Here, we integrate microbial community profiling with host and pathogen(s) transcriptional analysis in patient biopsies to dissect the pathophysiology of streptococcal and polymicrobial NSTIs. We observe that the pathogenicity of polymicrobial communities is mediated by synergistic interactions between community members, fueling a cycle of bacterial colonization and inflammatory tissue destruction. In S. pyogenes NSTIs, expression of specialized virulence factors underlies infection pathophysiology. Furthermore, we identify a strong interferon-related response specific to S. pyogenes NSTIs that could be exploited as a potential diagnostic biomarker. Our study provides insights into the pathophysiology of mono- and polymicrobial NSTIs and highlights the potential of host-derived signatures for microbial diagnosis of NSTIs.
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| 13. |
- Ahlquist, Mårten, et al.
(författare)
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An experimental and theoretical study of the mechanism of stannylcupration of alpha, beta-acetylenic ketones and esters
- 2006
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 12:10, s. 2866-2873
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Tidskriftsartikel (refereegranskat)abstract
- The title reaction has been investigated by experimental and computational (DFT) techniques, and subsequently compared to the corresponding carbocupration reaction, with particular emphasis oil the stereoselectivity. For stannylcupration of an ynone substrate, only the anti-addition product is observed, whereas for the corresponding ynoate substrate, the stereoselectivity can be affected by the reaction conditions: in the presence of methanol as proton donor, the initial syn-addition product can be trapped, whereas a syn/anti mixture is obtained in a non-protic solvent. This is in sharp contrast to the carbocupration of the same ynone substrate with a cyanocuprate (RCu(CN)Li), which is highly selective for syn-addition. The product selectivities can be understood from a detailed computational characterization of the reaction paths, and in particular from the relative stabilities of the vinyl cuprate and allenolate intermediates. It is suggested that the stereodetermining step is protonation of vinyl cuprate intermediates.
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| 16. |
- Ankerst, J., et al.
(författare)
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Induction of mammary fibroadenomas in rats by adenovirus type 9
- 1974
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 13:3, s. 286-290
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Tidskriftsartikel (refereegranskat)abstract
- After inoculation of adenovirus type 9 into newborn Wistar/Furth rats, seven out of seven females developed one or several mammary fibroadenomas within 14–25 weeks after virus inoculation. No tumours were observed in male rats inoculated with the same virus or in untreated controls. Neonatal inoculations of adenovirus type 5, produced on the same HeLa cells, gave negative results in both sexes. The results indicate that benign mammary tumours can be induced in rats by a virus and that mammary fibroadenomas are induced by adenovirus type 9, previously known to be capable of transforming cells in vitro but not of inducing tumours in vivo.
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| 17. |
- Backman, L., et al.
(författare)
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Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial
- 2006
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:8, s. 2654-6
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Tidskriftsartikel (refereegranskat)abstract
- This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.
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| 20. |
- Darenberg, J, et al.
(författare)
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Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome : A European randomized, double-blind, placebo-controlled trial
- 2003
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 37, s. 333-
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P = .02) and 3 (P = .04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P = .03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.
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| 21. |
- Dupont, Chris L., et al.
(författare)
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Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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| 26. |
- Gundersen, IM, et al.
(författare)
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Necrotising soft tissue infections
- 2024
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Ingår i: Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. - 0807-7096. ; 144:3
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Tidskriftsartikel (refereegranskat)
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| 27. |
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| 28. |
- Horst, SA, et al.
(författare)
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Prognostic value and therapeutic potential of TREM-1 in Streptococcus pyogenes- induced sepsis
- 2013
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 5:6, s. 581-590
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Tidskriftsartikel (refereegranskat)abstract
- TREM-1 (triggering receptor expressed on myeloid cells) is a surface molecule expressed on neutrophils and macrophages which has been implicated in the amplification of inflammatory responses triggered during infection. In the present study, we have investigated the clinical significance of TREM-1 in <i>Streptococcus pyogenes</i>-induced severe sepsis in both experimentally infected mice as well as in patients with streptococcal toxic shock. We found that <i>S. pyogenes</i> induced a dose-dependent upregulation of TREM-1 in in vitro cultured phagocytic cells and in the organs of <i>S. pyogenes-</i>infected mice. Furthermore, we reported a positive correlation between serum levels of soluble TREM-1 (sTREM-1) and disease severity in infected patients as well as in experimentally infected mice. Hence, sTREM-1 may represent a useful surrogate marker for streptococcal sepsis. We found that modulation of TREM-1 by administration of the TREM-1 decoy receptor rTREM-1/Fc substantially attenuated the synthesis of inflammatory cytokines. More importantly, treatment of <i>S. pyogenes</i>-infected septic mice with rTREM-1/Fc or the synthetically produced conserved extracellular domain LP17 significantly improved disease outcome. In summary, our data suggest that TREM-1 may not only represent a valuable marker for <i>S. pyogenes</i> infection severity but it may also be an attractive target for the treatment of streptococcal sepsis.
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| 33. |
- Johansson, Adam Johannes, 1976-
(författare)
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Biomimetic Transition Metal Catalysts : Insights from Theoretical Modeling
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The scientific interest in the chemistry of synthetic transition metal complexes is motivated by at least two arguments:1.These can be regarded as models of biological transition metal complexes, e.g. metalloenzymes, whose functions can be difficult to reveal in detail due to their complexity.2.Transition metal complexes are used for catalytic purposes in the industrial synthesis of chemicals. There is a large potential for further development of this technology, which can be motivated both by economic and environmental arguments.In the present thesis, density functional theory (a quantum mechanical method) has been applied to model reactions involving synthetic iron and copper complexes in solution. The complexity of the solvent environment is a challenging problem for theoretical investigations and a significant part of the theses has been to investigate the mechanistic effects of metal-coordinating solvent molecules, Lewis bases and counter ions. For example, it is explained why the cleavage of the O-O bond in heme-diiron-peroxides is faster in the presence of a coordinating Lewis base. Furthermore, the experimentally observed structure-activity relationship between the Fe(III)(µ-O)2Fe(IV) and (H2O)Fe(III)(µ-O)Fe(IV)O motifs is given an explanation. In addition, the present thesis presents a systematic investigation of how the self-interaction error in density functional theory (DFT) affects the modeling of transition metal catalysis.
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| 34. |
- Johansson, Linda, et al.
(författare)
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Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans
- 2008
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Ingår i: Infection and Immunity. - 1098-5522. ; 76:8, s. 3399-3404
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Tidskriftsartikel (refereegranskat)abstract
- Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococcus (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial load in the tissue even late after onset of infection. Antimicrobial peptides are important components of the innate host defence and cathelicidins have been shown to protect against murine necrotic skin infection caused by GAS. However, the streptococcal cysteine protease SpeB has been demonstrated to proteolytically inactivate the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsies. The results showed high amounts of LL-37, both the proform (hCAP18) and the mature peptide, present in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct co-localization between the bacteria and LL-37 could be noted, and bacterial load showed a positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with high amounts of SpeB. Confocal microscopy confirmed a strong co-localization of GAS, SpeB and LL-37 at the bacterial surface. Taken together the findings of this study provides in vivo support that SpeB-mediated inactivation of LL-37 at the streptococcal surface represent a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.
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| 41. |
- Mecklenburg, M., et al.
(författare)
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Differentiation of human serum samples by surface plasmon resonance monitoring of the integral glycoprotein interaction with a lectin panel
- 2002
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Ingår i: Analytica Chimica Acta. - 0003-2670 .- 1873-4324. ; 459:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial infection and inflammation result in massive changes in serum glycoproteins. These changes were investigated by the interaction of the saccharide glycoprotein moiety with lectins. A panel of eight lectins (Canavalia ensiformis, Bandeiraea simplicifolia BS-I, Arachis hypogaea, Phytolacca americana, Phaseolus vulgaris, Artocarpus integrifolia, Triticum vulgaris and Pisum sativum) was used to differentiate human serum glycoproteins obtained from patients with various bacterial infections. Lectin functionalised sensing layers were created on gold-coated wafers and lectin-glycoprotein interactions were monitored by surface plasmon resonance. The interaction of the lectin panel with serum glycoproteins produces unique patterns. Principal component analysis (PCA) was used to analyse the patterns. The actual panel of eight lectins enabled discrimination between sera obtained from patients sick with bacterial infection and healthy patients. Extended lectin panels have the potential to distinguish between types of bacterial infection and identify specific disease state. © 2002 Elsevier Science B.V. All rights reserved.
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| 45. |
- Norrby, E, et al.
(författare)
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Measles virus in the brain
- 1997
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Ingår i: Brain research bulletin. - 0361-9230. ; 44:3, s. 213-220
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Tidskriftsartikel (refereegranskat)
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| 46. |
- NORRBY, E
(författare)
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The paradigms of measles vaccinology
- 1995
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Ingår i: Current topics in microbiology and immunology. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0070-217X. ; 191, s. 167-180
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Tidskriftsartikel (refereegranskat)
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| 47. |
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| 48. |
- Palma Medina, LM, et al.
(författare)
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Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
- 2023
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Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 24:1, s. 62-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
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| 50. |
- Paterson, Andrew, 1988, et al.
(författare)
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Palladium Catalyzed Stereoselective Arylation of Biocatalytically Derived Cyclic 1,3-Dienes: Chirality Transfer via a Heck-Type Mechanism
- 2020
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7052 .- 1523-7060. ; 22:6, s. 2464-2469
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Tidskriftsartikel (refereegranskat)abstract
- Microbial arene oxidation of benzoic acid with Ralstonia eutropha B9 provides a chiral highly functionalized cyclohexadiene, suitable for further structural diversification. Subjecting this scaffold to a Pd-catalyzed Heck reaction effects a regio- and stereoselective arylation of the cyclohexadiene ring, with 1,3-chirality transfer of stereogenic information installed in the microbial arene oxidation. Quantum chemical calculations explain the selectivity both by a kinetic preference for the observed arylation position and by reversible carbopalladation in competing positions. Further product transformation allowed the formation of a tricyclic ketone possessing four stereogenic centers. This demonstrates the capability of the method to introduce stereochemical complexity from planar nonchiral benzoic acid in just a few steps.
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