| 1. |
- Sorelius, Karl, et al.
(författare)
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The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
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| 2. |
- Krarup, Anne L., et al.
(författare)
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Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.
- 2011
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 33:10, s. 1113-22
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Tidskriftsartikel (refereegranskat)abstract
- Background Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor ‘transient receptor potential vanilloid 1’(TRPV1) are a potential drug class for GERD treatment. Aim To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Methods Twenty-two healthy men (20–31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat. Results A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10–38%] and 28%, respectively (CI: 14–43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1–3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0–5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported ‘feeling cold’ and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 ± 0.3 °C and 0.7 ± 0.3 °C, respectively, P < 0.05). Conclusions AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).
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| 3. |
- Albrektsson, Tomas, 1945, et al.
(författare)
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Histologic investigations on 33 retrieved Nobelpharma implants.
- 1993
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Ingår i: Clinical materials. - 0267-6605. ; 12:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Thirty Nobelpharma implants were retrieved from 17 patients despite a remaining clinical stability, after between 1 and 16 years of clinical function. The reasons for implant removal were bone resorption in combination with soft tissue disorders, psychological causes, implant fracture and post mortem cases. When measured at the cortical passage, there was an average of 84.9% direct bone-to-implant contact and 81.8% average surface bone area in individual threads as evaluated in a computerized morphometric system at the light microscopic level.
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| 6. |
- Astrand, H., et al.
(författare)
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In vivo estimation of the contribution of elastin and collagen to the mechanical properties in the human abdominal aorta: effect of age and sex
- 2011
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 110:1, s. 176-187
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Tidskriftsartikel (refereegranskat)abstract
- Astrand H, Stalhand J, Karlsson J, Karlsson M, Sonesson B, Lanne T. In vivo estimation of the contribution of elastin and collagen to the mechanical properties in the human abdominal aorta: effect of age and sex. J Appl Physiol 110: 176-187, 2011. First published November 11, 2010; doi:10.1152/japplphysiol.00579.2010.-The mechanical properties of the aorta affect cardiac function and are related to cardiovascular morbidity/mortality. This study was designed to evaluate the isotropic (mainly elastin, elastin(iso)) and anisotropic (mainly collagen, collagen(ani)) material parameters within the human aorta in vivo. Thirty healthy men and women in three different age categories (23-30, 41-54, and 67-72 yr) were included. A novel mechanical model was used to identify the mechanical properties and the strain field with aid of simultaneously recorded pressure and radius in the abdominal aorta. The magnitudes of the material parameters relating to both the stiffness of elastin(iso) and collagen(ani) were in agreement with earlier in vitro studies. The load-bearing fraction attributed to collagen(ani) oscillated from 10 to 30% between diastolic and systolic pressures during the cardiac cycle. With age, stiffness of elastin(iso) increased in men, despite the decrease in elastin content that has been found due to elastolysis. Furthermore, an increase in stiffness of collagen(ani) at high physiological pressure was found. This might be due to increased glycation, as well as changed isoforms of collagen in the aortic wall with age. A marked sex difference was observed, with a much less age-related effect, both on elastin(iso) and collagen(ani) stiffness in women. Possible factors of importance could be the effect of sex hormones, as well as differing collagen isoforms, between the sexes.
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| 7. |
- Fakih, Dalia, et al.
(författare)
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Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs
- 2018
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:17
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), bacteria and mucus accumulates instead. To address the mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages from COPD patients and mucus collected in an elastase-induced mouse model of COPD was analyzed, revealing similarities with each other and with the protein content in colonic mucus. Moreover, stratified laminated sheets of mucus were observed in airways from patients with CF and COPD and in elastase-exposed mice. On the other hand, the mucus accumulation in the elastase model was reduced in Muc5b-KO mice. While mucus plugs were removed from airways by washing with hypertonic saline in the elastase model, mucus remained adherent to epithelial cells. Bacteria were trapped on this mucus, whereas, in non-elastase-treated mice, bacteria were found on the epithelial cells. We propose that the adherence of mucus to epithelial cells observed in CF, COPD, and the elastase-induced mouse model of COPD separates bacteria from the surface cells and, thus, protects the respiratory epithelium.
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| 9. |
- Gavali, Hamid, et al.
(författare)
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Semi-Conservative Treatment Versus Surgery in Abdominal Aortic Graft and Endograft Infections
- 2023
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 66:3, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft-preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort.METHODS: Patients with abdominal AGI-related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for definition of AGI. Multivariable regression was performed to identify factors associated with mortality.RESULTS: A total of 169 patients with surgically treated abdominal AGI were identified, comprising 43 SC [14 endografts; 53% with a graft-enteric fistula (GEF) in total] and 126 RS [26 endografts; 50% with a GEF in total]. The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated 5-year survival for SC versus RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated 5-year survival for SC patients with a GEF versus without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC versus RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in 5-year survival comparing SC versus RS (HR 1.0, 95% CI 0.6 - 1.5).CONCLUSION: In this national AGI cohort, we could not identify any mortality difference comparing SC versus RS for AGI when adjusting for comorbidities. Presence of GEF likely negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC-treated patients.
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| 10. |
- Giorgetti, Melania, et al.
(författare)
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New generation ENaC inhibitors detach cystic fibrosis airway mucus bundles via sodium/hydrogen exchanger inhibition
- 2021
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 904
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is a recessive inherited disease caused by mutations affecting anion transport by the epithelial ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The disease is characterized by mucus accumulation in the airways and intestine, but the major cause of mortality in CF is airway mucus accumulation, leading to bacterial colonization, inflammation and respiratory failure. Several drug targets are under evaluation to alleviate airway mucus obstruction in CF and one of these targets is the epithelial sodium channel ENaC. To explore effects of ENaC inhibitors on mucus properties, we used two model systems to investigate mucus characteristics, mucus attachment in mouse ileum and mucus bundle transport in piglet airways. We quantified mucus attachment in explants from CFTR null (CF) mice and tracheobronchial explants from newborn CFTR null (CF) piglets to evaluate effects of ENaC or sodium/hydrogen exchanger (NHE) inhibitors on mucus attachment. ENaC inhibitors detached mucus in the CF mouse ileum, although the ileum lacks ENaC expression. This effect was mimicked by two NHE inhibitors. Airway mucus bundles were immobile in untreated newborn CF piglets but were detached by the therapeutic drug candidate AZD5634 (patent WO, 2015140527). These results suggest that the ENaC inhibitor AZD5634 causes detachment of CF mucus in the ileum and airway via NHE inhibition and that drug design should focus on NHE instead of ENaC inhibition.
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