| 1. |
- Johansson, Inger, 1953, et al.
(författare)
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Lower incidence of CMV infection and acute rejections with valganciclovir
- 2013
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS).Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.
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| 2. |
- Inghammar, Malin, et al.
(författare)
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COPD and the risk of tuberculosis--a population-based cohort study.
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality. METHODS AND FINDINGS: All individuals > or = 40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987-2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989-2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1). CONCLUSIONS: This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies.
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| 3. |
- Karlsson, Michael, et al.
(författare)
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Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO.
- 2013
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 45:1, s. 5-151
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting cellular respiration of mitochondria. Recombinant human erythropoietin (rhEPO) is a promising new therapy that has been shown to reduce mortality in a mouse model of CM. In order to further elucidate the metabolic dysfunction in CM the objective of the present study was to assess brain mitochondrial respiratory function in CM with and without rhEPO treatment. The P. berghei ANKA - C57BL/6 murine model of CM was used. Mitochondrial respiration was analyzed in brain homogenates using high-resolution respirometry and a multiple substrate and inhibitor protocol. The animals were divided into four groups; infected injected with saline or with rhEPO, non-infected injected with saline or with rhEPO. Infected mice developed CM and treatment with rhEPO attenuated clinical signs of disease. There were no differences in respiratory parameters of brain mitochondria between infected and non-infected mice and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex vivo. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
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| 4. |
- Leander, Mai, et al.
(författare)
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Impact of anxiety and depression on respiratory symptoms
- 2014
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 108:11, s. 1594-1600
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Tidskriftsartikel (refereegranskat)abstract
- Psychological factors such as anxiety and depression are prevalent in patients with asthma. The purpose of this study was to investigate the relationship between respiratory symptoms and psychological status and to estimate the importance of psychological status in comparison with other factors that are known to be associated with respiratory symptoms. This study included 2270 subjects aged 20-44 (52% female) from Sweden, Iceland, and Norway. Each participant underwent a clinical interview including questions on respiratory symptoms. Spirometry and methacholine challenge were performed. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Eighty-two percent of the subjects reported no anxiety or depression whatsoever, 11% reported anxiety, 2.5% depression and 4% reported both anxiety and depression. All respiratory symptoms, such as wheezing, breathlessness and nightly symptoms, were more common, at a statistically significant level, in participants who had depression and anxiety, even after adjusting for confounders (ORs 1.33-1.94). The HADS score was the most important determinant for nightly symptoms and attacks of breathlessness when at rest whereas bronchial responsiveness was the most important determinant for wheezing, and breathlessness when wheezing. The probability of respiratory symptoms related to HADS score increased with increasing HADS score for all respiratory symptoms. In conclusion, there is a strong association between respiratory symptoms and psychological status. There is therefore a need for interventional studies designed to improve depression and anxiety in patients with respiratory symptoms. (C) 2014 Elsevier Ltd. All rights reserved.
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| 5. |
- Morota, Saori, et al.
(författare)
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Respiratory uncoupling by increased H+ or K+ flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition
- 2013
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Ingår i: BMC Cell Biology. - : Springer Science and Business Media LLC. - 1471-2121. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ischemic preconditioning has been proposed to involve changes in mitochondrial H+ and K+ fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K+ channels (MitoK(ATP)). The objectives of the present study were to explore how increased H+ and K+ fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Results: Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H+ and K+ conductance, respectively. Simultaneous monitoring of mitochondrial respiration and calcium retention capacity (CRC) demonstrated that the relative increase in respiration caused by valinomycin or CCCP correlated with a decrease in CRC, and that no level of respiratory uncoupling was associated with enhanced resistance to mPT. Mitochondria suspended in hyperosmolar buffer demonstrated a dose-dependent reduction in CRC with increasing osmolarity. However, mitochondria in hypoosmolar buffer to increase matrix volume did not display increased CRC. ROS generation was reduced by both K+- and H+-mediated respiratory uncoupling. The ability of heart mitochondria to detoxify H2O2 was substantially greater than the production rate. The H2O2 detoxification was dependent on respiratory substrates and was dramatically decreased following calcium-induced mPT, but was unaffected by uncoupling via increased K+ and H+ conductance. Conclusion: It is concluded that respiratory uncoupling is not directly beneficial to rat heart mitochondrial resistance to calcium overload irrespective of whether H+ or K+ conductance is increased. The negative effects of respiratory uncoupling thus probably outweigh the reduction in ROS generation and a potential positive effect by increased matrix volume, resulting in a net sensitization of heart mitochondria to mPT activation.
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| 6. |
- Rusanen, Minna, et al.
(författare)
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Chronic Obstructive Pulmonary Disease and Asthma and the Risk of Mild Cognitive Impairment and Dementia : A Population Based CAIDE Study
- 2013
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Ingår i: CURRENT ALZHEIMER RESEARCH. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 10:5, s. 549-555
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research indicates that persons with chronic obstructive pulmonary disease (COPD) and asthma may have more cognitive impairment compared to persons without these diseases. However, there are no previous studies regarding long-term effects of these diseases on the risk of clinically diagnosed mild cognitive impairment (MCI) and dementia. We examined the association between midlife and late-life self-reported COPD and asthma and the lifelong risk of cognitive impairment (MCI/dementia) in a population-based study with a follow-up of over 25 years. Methods: Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982 or 1988). Re-examinations were carried out in 1998 and 2005-8 (N=1511, 75.6 %) during which 172 persons were diagnosed with MCI and 117 with dementia. Results: Midlife COPD (HR 1.85, 95% CI 1.05 - 3.28), asthma (HR 1.88, 95% CI 0.77 - 4.63) and both pulmonary diseases combined (HR 1.94, 95% CI 1.16 - 3.27) increased the later risk of cognitive impairment even after full adjustments. However, pulmonary diseases diagnosed later in life seemed to be inversely related to cognitive impairment (fully adjusted model for both pulmonary diseases combined HR 0.42, 95% CI 0.19 - 0.93). Conclusions: In this population-based study, with more than 25 years of follow-up, midlife COPD and asthma were associated with an almost two-fold risk of MCI and dementia later in life. Pulmonary diseases diagnosed later in life seemed to have an inverse relationship with cognitive impairment probably reflecting survival bias.
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| 7. |
- Sjövall, Fredrik, et al.
(författare)
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Cytokine and nitric oxide levels in patients with sepsis - temporal evolvement and relation to platelet mitochondrial respiratory function.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- The levels of nitric oxide (NO) and various cytokines are known to be increased during sepsis. These signaling molecules could potentially act as regulators and underlie the enhancement of mitochondrial function described in the later phase of sepsis. Therefore, we investigated the correlation between observed changes in platelet mitochondrial respiration and a set of pro- and anti-inflammatory cytokines as well as NO plasma levels in patients with sepsis.
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| 8. |
- Sörenson, Sverre, et al.
(författare)
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Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:1, s. 115-120
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Tidskriftsartikel (refereegranskat)abstract
- Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.
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| 9. |
- Hoffner, S, et al.
(författare)
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Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience
- 2013
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Ingår i: The International Journal of Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 17:11, s. 1486-1490
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organizations yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. less thanbrgreater than less thanbrgreater thanOBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. less thanbrgreater than less thanbrgreater thanMETHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. less thanbrgreater than less thanbrgreater thanRESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.
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| 10. |
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