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| 2. |
- Cervin, Anders, et al.
(författare)
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Effects of long-term clarithromycin treatment on lavage-fluid markers of inflammation in chronic rhinosinusitis
- 2009
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 29:2, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- Macrolides can be clinically effective in chronic rhinosinusitis (CRS). However, little is known about how these drugs affect pathophysiological features of CRS in vivo. In the present study, patients with CRS were subjected to long-term treatment with clarithromycin. Nasal lavages with and without histamine (40 and 400 mu g ml(-1)) were carried out prior to and late into the treatment period. Histamine was included as a tool to produce plasma exudation, a process known to move free cellular products from the mucosal tissue into the airway lumen thereby enriching nasal surface liquids with such products. Interleukin-8 (IL-8), myeloperoxidase (MPO), eosinophil cationic protein (ECP), alpha(2)-macroglobulin and fucose were monitored as indices of pro-inflammatory cytokine production, neutrophil and eosinophil granulocyte activities, plasma exudation and mucinous secretion, respectively. Clarithromycin reduced the lavage fluid levels of IL-8 at the low-dose histamine observation (P < 0.001). There was a trend towards reduced MPO by the treatment, whereas ECP was significantly reduced at the low-dose histamine observation (P < 0.05). alpha(2)-Macroglobulin was reduced by clarithromycin (saline lavages) (P = 0.05), whereas fucose was unaffected. The exudative responsiveness to high-dose histamine was significantly reduced by the treatment (P < 0.05). Furthermore, significantly lower levels of fucose were observed at the low-dose histamine observation (P < 0.01). We conclude that long-term clarithromycin treatment likely exerts an anti-inflammatory effect in CRS.
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| 3. |
- Cervin, Anders, et al.
(författare)
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Macrolide therapy of chronic rhinosinusitis
- 2007
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Ingår i: Rhinology. - 0300-0729. ; 45:4, s. 259-267
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Forskningsöversikt (refereegranskat)abstract
- There is growing evidence that several antibiotics exert their beneficial effect not only by inhibiting or killing bacterial pathogens but also by down-regulating pro-inflammatory mechanisms. This review aims to give an overview of the immunomodulatory properties of macrolide antibiotics in chronic rhinosinusitis and to present a treatment algorithm for managing the difficult CRS patient with long-term, low-dose macrolide antibiotics. The most prominent effect of macrolides noted in vitro is the inhibition of pro-inflammatory cytokines such as interleukin-8. This effect is probably secondary to inhibition of the activation of transcription factor NF-kappa B. As a result an attenuation of neutrophilic inflammation takes place. Moreover, macrolides inhibit bacterial virulence and biofilm formation. In vivo, a reduction of pro-inflammatory cytokines is evident in nasal lavage as well as a reduction in nasal secretions. The clinical effect is shown in less facial pain, less headache, less post nasal drip, fewer exacerbations of sinusitis and improved quality of life The treatment should be targeted towards the non-atopic patients with bilateral disease whereas in unilateral disease, surgery is the first option. Macrolide resistant bacterial strains have to be monitored, but to date they have not been of clinical importance.
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- Greiff, Lennart, et al.
(författare)
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Challenge-induced plasma exudation and mucinous secretion in human airways
- 2005
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 25:4, s. 241-245
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Tidskriftsartikel (refereegranskat)abstract
- Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 microg ml(-1)), methacholine (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a global marker of mucinous secretion and alpha(2)-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level (P<0.01-0.05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of alpha(2)-macroglobulin (P<0.01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways.
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| 5. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 6. |
- Wallwork, Ben, et al.
(författare)
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Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis
- 2004
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Ingår i: Laryngoscope. - 1531-4995. ; 114:2, s. 286-290
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. It is believed that macrolide antibiotics produce this benefit through an anti-inflammatory effect. In this study, the effect of clarithromycin treatment on the expression of transforming growth factor (TGF)-beta and the key pro-inflammatory nuclear transcription factor, NF-kappa B, was examined in vitro and in vivo. STUDY DESIGN AND METHODS: In vitro: nasal mucosa was obtained from 10 patients with chronic sinusitis and was cultured for 24 hours in the presence of clarithromycin or control. Cellular expression of TGF-beta and NF-kappa B was determined by immunohistochemistry. In vivo: 10 patients with chronic rhinosinusitis were treated for 3 months with clarithromycin. Nasal mucosal biopsies were taken pre- and posttreatment. Cellular expression of TGF-beta and NF-kappa B was again determined by immunohistochemistry. RESULTS: Clarithromycin, when applied to nasal biopsies in vitro, reduced cellular expression of TGF-beta and NF-kappa B. Nasal biopsies taken before and after clarithromycin treatment showed no differences in cellular expression of NF-kappa B or TGF-beta. CONCLUSION: Clarithromycin can reduce cellular expression of TGF-beta and NF-kappa B when applied in vitro, but its action during clinical therapy is less clear. Clarithromycin is capable of inhibiting pro-inflammatory cytokines in vitro, and reductions of TGF-beta and NF-kappa B may represent additional mechanisms by which macrolides reduce inflammation in chronic airway disease. Discrepancies between the actions of clarithromycin on nasal biopsies in vitro and after clinical therapy warrant further investigation.
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